{"paper_id":"02fa1b8b-4ebc-4e4a-8de0-85b429e8441e","body_text":"Structural MRI Biomarkers of Intracranial Pressure in IIH: Linking Optic Nerve Sheath, Pituitary Morphology, and Hormonal Changes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Structural MRI Biomarkers of Intracranial Pressure in IIH: Linking Optic Nerve Sheath, Pituitary Morphology, and Hormonal Changes Zeynep Bendella, Barbara Daria Wichtmann, Ralf Clauberg, Wiebke Fenske, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7177945/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Jan, 2026 Read the published version in Clinical Neuroradiology → Version 1 posted You are reading this latest preprint version Abstract Purpose: To investigate the relationship between intracranial pressure (ICP), anterior pituitary hormones, and structural brain changes in women with idiopathic intracranial hypertension (IIH). Methods: Eighteen women with therapy-refractory IIH underwent lumbar puncture, endocrine assessment, and high-resolution brain MRI. Serum levels of pituitary hormones were correlated with ICP and radiological parameters including pituitary volume, flattening, and optic nerve sheath (ONS) volume. Group comparisons, partial correlations, and regression models were used to evaluate associations. Results: ICP was significantly associated with higher thyroid-stimulating hormone (TSH) levels ( r = 0.628, p = 0.0163), which emerged as a robust predictor of ICP in both linear (β = 4.8348, p = 0.017) and Huber regression models (coefficient = 0.070817, p < 0.001). Growth hormone (GH) was negatively associated with ICP ( r = -0.602, p = 0.023) and reached significance in robust modeling (coefficient = -0.023842, p = 0.041). Insulin-like Growth Factor 1 (IGF-19 and testosterone levels were significantly lower in patients with elevated ICP (IGF-1: p = 0.039; testosterone: p = 0.027). Volumetric MRI revealed no group difference in pituitary volume, but flattening and complete empty sella were more frequent in patients with elevated ICP. ONS volumes correlated with ICP only in the normal ICP group (left: r = 0.804, p = 0.054; right: r = 0.797, p = 0.058), suggesting a ceiling effect at higher pressures. Conclusion: Elevated ICP in IIH is linked to functional changes in the thyroid and somatotropic axes, as well as structural alterations in the pituitary gland and ONS. Combining quantitative MRI with endocrine profiling may improve diagnostic accuracy, help identify patients at risk, and support individualized treatment strategies. Idiopathic intracranial hypertension optic nerve sheath hormone axes growth hormone thyroid stimulating hormone intracranial pressure Figures Figure 1 Figure 2 Figure 3 1. Introduction Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure (ICP) without a detectable structural lesion or hydrocephalus. IIH primarily affects obese women of childbearing age and carries a risk for severe symptoms, including vision loss [ 1 , 2 ]. The underlying mechanisms of IIH remain incompletely understood, although multifactorial contributions have been proposed, including alterations in cerebrospinal fluid (CSF) dynamics, venous outflow obstruction, and hormonal dysregulation [ 3 , 4 ]. While the association between IIH and obesity is well-established, accumulating evidence suggests that endocrine abnormalities may also contribute to its pathophysiology. Several case reports and small cohort studies [ 5 – 8 ], as well as more recent observational work, have described associations between IIH and hormonal imbalances involving the thyroid, adrenal, gonadal, and somatotropic axes [ 3 , 9 – 12 ]. In particular, thyroid dysfunction has been disproportionately reported in IIH, and recent evidence suggests normalization of thyroid-stimulating hormone (TSH) levels following ICP reduction [ 12 ]. Nevertheless, systematic endocrine investigations in relation to ICP remain scarce, particularly in adults. In parallel, structural MRI findings such as an empty sella, pituitary flattening, and optic nerve sheath (ONS) distension are frequently observed in IIH and are commonly attributed to mechanical effects of elevated ICP [ 13 , 14 ]. However, it remains unclear whether these changes reflect true endocrine dysfunction or merely passive compression. Prior studies have reported hypopituitarism in patients with empty sella in up to 52% of cases, with growth hormone (GH) deficiency particularly prevalent [ 15 ]. Given the bidirectional interactions between hormonal function and CSF physiology-including evidence for the expression of hormone receptors and transporters in the choroid plexus and arachnoid granulations [ 16 – 18 ], an integrated analysis of structural and endocrine markers may offer new insights into IIH. In this study, we investigated the relationship between anterior pituitary hormone levels and quantitative MRI measures in women with IIH. We hypothesized that elevated ICP is associated with alterations in the thyroid and somatotropic axes and that these endocrine changes are paralleled by structural brain alterations detectable on MRI. By integrating hormonal data with volumetric imaging markers such as pituitary gland volume, pituitary flattening, and ONS volume, we aim to refine the understanding of neuroendocrine regulation in IIH and to evaluate potential non-invasive markers of disease burden. To test these hypotheses, we conducted a cross-sectional study in a well-defined cohort of women with therapy-resistant IIH. We systematically assessed anterior pituitary hormone levels and performed high-resolution brain MRI to quantify structural changes. We statistically examined associations between hormone levels, imaging features, and ICP measured via lumbar puncture. 2. Materials and Methods 2.1 Study Design and Participants In this cross-sectional study, we consecutively enrolled 18 female patients with therapy-refractory IIH who were hospitalized due to recurrent symptoms requiring lumbar puncture between May 2018 and October 2019. The diagnosis of IIH was confirmed according to the modified Dandy criteria [ 19 ] by reviewing external medical reports for individual diagnostic components. Exclusion criteria included age under 18 years, neurological disorders other than IIH, contraindications to MRI (e.g., history of seizures, severe psychiatric or systemic illness, metallic implants, claustrophobia, pregnancy), and substance abuse. Sample size was based on data availability; no power calculation was performed. All subjects provided written informed consent, and the study was approved by the local ethics committee (No. 383/17), conducted in accordance with the Declaration of Helsinki. Demographic and clinical variables included age, body mass index (BMI), waist-to-hip ratio, medication use, and detailed neurological, gynecological, and ophthalmological history. Polycystic ovary syndrome (PCOS) was diagnosed using the Rotterdam criteria [ 20 ], requiring at least two of the following: oligo- or amenorrhea, clinical or biochemical hyperandrogenism, or polycystic ovaries on ultrasound. 2.2 Endocrinological Assessment Venous blood samples were collected from all subjects after overnight fasting at 7:00 am. Each blood sample was processed according to the standard protocols of our clinical laboratory. Post hoc serum concentrations of thyroid hormones, including TSH, free thyroxine (fT4), and triiodothyronine (fT3), gonadotropins, including follicle stimulating hormone (FSH) and luteinising hormone (LH), as well as reproductive hormones, such as prolactin, estradiol, testosterone, androstenedione, and dehydroepiandrosterone sulphate (DHEAS), were analysed. Glucocorticoids adrenocorticotropic hormone (ACTH) and cortisol, as well as GH, were measured using an electrochemiluminescence immunoassay (ECLIA) (Roche Diagnostics). Serum concentrations of insulin-like growth factor 1 (IGF-1) were determined using an Immunodiagnostic Systems (IDS ® ) immunoassay. Levothyroxine intake was considered indicative of hypothalamic-pituitary-thyroid-axis dysregulation regardless of TSH levels. Values below detection thresholds were set to half the detection limit. 2.3 Lumbar Puncture Lumbar puncture was performed in lateral decubitus position on the same day as the endocrine evaluation. ICP was measured in cmH2O. If ICP was ≥ 25 cmH2O, 20–30 mL of CSF were drained for therapeutic relief. Based on ICP measurements, patients were categorized into a normal (< 25 cmH2O) and elevated (≥ 25 cmH2O) group. 2.4 Ophthalmological examination Ophthalmological examination included assessments of the optic disc, visual field, visual acuity, and bulbar motility. Papilledema was assessed using fundus examination and the Frisén scale [ 21 ], graded from 0 to 5. Visual acuity was measured with the revised Snellen chart, with reduction defined as < 20/25. Visual fields were assessed using the OCULUS Twinfield perimeter with automated kinetic (stimulus III/4) and static perimetry (program 30 − 2, stimulus size III, fast threshold strategy). The mean deviation (MD), indicating total field loss, was automatically generated. Field restriction was defined as < 40° nasal or < 75° temporal. Enlarged blind spots were also assessed. Visual fields with unacceptable reliability indices (loss of fixation > 30%, false-positive errors > 15%) were excluded. Optic disc volume was measured using optical coherence tomography (OCT) with Spectralis® (Heidelberg Engineering, Heidelberg, Germany). 2.5 Imaging Protocol and Morphometric Analysis High-resolution structural brain MRI was performed before lumbar puncture to exclude secondary causes of raised ICP. For morphometric analysis, volumetric T1-weighted images were used to segment and quantify pituitary gland volume, sella turcica volume, pituitary gland flattening (defined as percentage of sella filled), left and right ONS and optic nerve (ON) volumes each. Segmentations were performed manually using 3D Slicer (version 5.8.0) by an experienced neuroradiologist blinded to ICP group. Incomplete empty sella was defined as 0–50% CSF-filling, and complete empty sella as > 50%. Intra-rater reliability was confirmed by duplicate measurement across all participants. Representative segmentations are shown in Fig. 1 . 2.6 Statistical Analyses The statistical analyses and visualizations were performed using Python (v3.11.8) and appropriate statistical packages. Descriptive statistics were reported as means ± standard deviation (SD) for normally distributed variables and as medians with interquartile ranges (IQR) for non-normally distributed data. Depending on data distribution and measurement scale, group comparisons were performed using Student’s t-test, Mann–Whitney U-test, chi-squared test, or Fisher’s exact test. Effect sizes were calculated using Cohen’s d, rank-biserial correlations, Cramer's V, and Phi coefficients. Statistical significance was set at p < 0.05 (two-tailed). To explore relationships between radiological findings, endocrine parameters, and ICP, we followed a structured analytic framework. First, demographic, clinical, imaging, and endocrine characteristics were compared between groups with normal (< 25 cmH2O in lateral position) and increased (≥ 25 cmH2O) ICP. Missing values were excluded pairwise, and reduced group sizes are indicated in the tables. Subsequently, imaging parameters (pituitary gland volume, flattening percentage, sella volume, and bilateral ONS and ON volumes) were correlated with ICP using partial correlation analyses adjusted for age and BMI. These analyses were also stratified by ICP status to identify pressure-specific associations. To examine structural-endocrine relationships, partial correlations were calculated between pituitary hormone levels (TSH, LH, FSH, ACTH, GH) and pituitary gland volume, separately within ICP subgroups and adjusted for age and BMI. Next, serum hormone concentrations were evaluated in relation to ICP. First, frequencies of values outside reference ranges were examined. Second, group differences in raw hormone concentrations were analyzed using either analysis of covariance (ANCOVA) for normally distributed variables or generalized linear models (GLM) for non-normally distributed variables. All models were adjusted for age, BMI, and pituitary volume. The ANCOVA was based on ordinary least squares (OLS) regression; the GLM used a Gamma distribution with log-link function. For each model, corresponding effect sizes (R² for ANCOVA, McFadden’s pseudo R² for GLM) were reported. Model assumptions, including homogeneity of regression slopes (ANCOVA) and distributional fit (GLM), were verified using graphical and statistical diagnostics. Significant variables from group comparisons were further examined using partial correlation analyses. To evaluate predictors of ICP, linear regression models were constructed with hormone levels as predictors. ICP values were Box-Cox transformed to approximate normality, and TSH and GH were z-standardized. Because the OLS model violated normality and homoscedasticity assumptions, Huber regression was used to improve robustness against outliers. Model performance was assessed using 10-fold cross-validation with mean squared error (MSE) as the evaluation metric. Model assumptions were verified using residual plots, histograms, and Q-Q plots. This multi-level approach enabled the assessment of group-level, correlational, and predictive relationships between endocrine and structural MRI parameters in the context of ICP. 3. Results 3.1. Demographic and Clinical Profile Eighteen women with therapy-refractory IIH were enrolled between May 2018 and October 2019 (Table 1 ). Ten patients showed elevated ICP (≥ 25 cmH₂O; median 26.5 cmH₂O, IQR 25.3–31.0), while eight had normal pressures (mean 19.0 ± 2.4 cmH₂O). Patients with elevated ICP tended to be older (37.5 ± 8.4 vs 31.9 ± 7.2 years) and more obese (BMI 37.0 ± 6.2 vs 33.1 ± 5.3 kg/m²), but these differences were not statistically significant (p > 0.15). Waist-to-hip ratios were identical (0.8 ± 0.1). No between-group differences emerged in the prevalence of PCOS, neuropsychiatric or neurological comorbidities, or use of IIH-related medication (all p > 0.47; Table 1 , Supplementary Table S1 ). Ophthalmologic metrics including papilledema grade, visual acuity, visual-field indices, and OCT-derived optic-disc volume were likewise comparable, and no cranial nerve palsies were detected (Supplementary Table S2 ). Table 1 Demographic and clinical group characteristics for the total group and for normal and increased ICP Whole Group ICP < 25 cmH 2 O ICP ≥ 25 cmH 2 O P Value Test Statistics Cohen's d/Rank-Biserial/Phi coefficient (φ)/ Cramer's V Age [years] a 35.0 ± 8.2 (n = 18) 31.9 ± 7.2 (n = 8) 37.5 ± 8.4 (n = 10) 0.152 t(16) = -1.505 -0.714 BMI [kg/m2] a 35.3 ± 6 (n = 18) 33.1 ± 5.3 (n = 8) 37.0 ± 6.2 (n = 10) 0.180 t(16) = -1.401 -0.665 Waist to Hip ratio a 0.8 ± 0.1 (n = 18) 0.8 ± 0.1 (n = 8) 0.8 ± 0.1 (n = 10) 0.549 t(16) = 0.612 0.626 ICP [cmH 2 O] b 24.3 ± 6.0 (n = 18) 19.0 ± 2.4 (n = 8) 26.5 [25.3, 31.0] (n = 10) p < 0.001* U = 0.000 1 Flattening of the Pituitary Gland [%] a 49.4 ± 41.1 (n = 17) 56.3 ± 13.0 (n = 8) 43.3 ± 25.5 (n = 9) 0.217 t(15) = 1.288 0.626 No/Incomplete/Complete Empty Sella [%] d 0/47/53 (n = 0/8/9 / 17) 0/38/63 (n = 0/3/5 / 8) 0/56/44 (n = 0/5/4 / 9) 0.797 χ2(1) = 0.066 0.063 Pituitary Gland Volume [mm 3 ] a 852.5 ± 149.9 (n = 17) 889.5 ± 174.5 (n = 8) 819.6 ± 125.3 (n = 9) 0.353 t(15) = 0.958 0.465 Sella Volume [mm 3 ] a 1516.5 ± 364.1 (n = 17) 1570.9 ± 491.36 (n = 8) 1468.2 ± 219.7 (n = 9) 0.578 t(15) = 0.568 0.276 Left ONS Volume [mm 3 ] a 854.0 ± 155.5 (n = 17) 791.7 ± 124.3 (n = 8) 909.5 ± 165.7 (n = 9) 0.122 t(15) = -1.639 -0.797 Right ONS Volume [mm 3 ] a 901.6 ± 131.8 (n = 17) 855.3 ± 129.2 (n = 8) 942.7 ± 126.9 (n = 9) 0.181 t(15) = -1.406 -0.683 Left ON Volume [mm 3 ] a 145.2 ± 28.8 (n = 17) 135.0 ± 25.2 (n = 8) 154.2 ± 30.1 (n = 9) 0.179 t(15) = -1.409 -0.685 Right ON Volume [mm 3 ] b 155.4 ± 37.7 (n = 17) 143.0 ± 30.8 (n = 8) 144.4 [135.7, 176.0] (n = 9) 0.20 U = 22.000 0.389 PCOS [%] c 11 (n = 2/18) 0 (n = 0/8) 20 (n = 2/10) 0.477 χ 2 (1) = 0.345 0.138 History of neurological/ psychatric disorder [%] c 56 (n = 10/18) 63 (n = 5/8) 50 (n = 5/10) 0.664 χ 2 (1) = 0.003 0.013 Neurological impairments detected in examination [%] c 22 (n = 4/18) 25 (n = 2/8) 20 (n = 2/10) 1.000 χ 2 (1) = 0.000 0.000 IIH associated medication [%] c 72 (n = 13/18) 75 (n = 6/8) 70 (n = 7/10) 1.000 χ 2 (1) = 0.000 0.000 Reported headache [%] c 100 (n = 18/18) 100 (n = 8/8) 100 (n = 10/10) NA NA NA Group characteristics are presented as mean ± standard deviation (SD) for normally distributed data, as median [interquartile range (IQR)] for non-normally distributed data, or as percentage and number in parentheses for dichotomous variables. Depending on distribution, either the independent Student's t-test (a), the Mann-Whitney U test (b), Fisher's exact test (c) or Chi-squared test (d) was performed, with the corresponding effect sizes Cohen's d, Rank-Biserial, Phi coefficient (φ) or Cramer's V respectively and each with p < 0.05 two-sided. BMI = Body Mass Index; cmH 2 O = centimeter water column; ICP = intracranial pressure; NA = not applicable; PCOS = polycystic ovary syndrome 3.2. Structural MRI Findings and ICP Group-level metrics showed no difference in pituitary gland volume or percentage flattening between normal and elevated ICP cohorts (Table 2 ). Optic-nerve-sheath and optic-nerve volumes were numerically larger under raised pressure but did not reach statistical significance. Correlation analyses revealed pressure-specific patterns. In the elevated ICP subgroup, right optic-nerve volume increased linearly with ICP (r = 0.90, p = 0.005), whereas optic-nerve-sheath volumes no longer tracked pressure, suggesting a structural ceiling. Conversely, in the normal-pressure subgroup, ICP correlated strongly with bilateral sheath volumes (r ≈ 0.80, p ≈ 0.05), but not with optic-nerve size (Table 2 ). Table 2 Relationships between ICP and Imaging Parameters Partial Correlation Adjusted for Age & BMI Whole Group ICP < 25 cmH2O ICP ≥ 25 cmH2O N R P Value N R P Value N R P Value Flattening of the Pituitary Gland [%] 17 -0.214 0.4436 8 0.593 0.2149 9 -0.119 0.7997 Pituitary Gland Volume [mm 3 ] 17 0.008 0.9762 8 0.169 0.7482 9 -0.363 0.4241 Sella Volume [mm 3 ] 17 -0.171 0.5423 8 0.003 0.9954 9 0.026 0.9553 Left ONS Volume [mm 3 ] 17 0.367 0.1788 8 0.804 0.0536* 9 -0.329 0.4716 Right ONS Volume [mm 3 ] 17 0.429 0.1104 8 0.797 0.0578* 9 -0.169 0.7167 Left ON Volume [mm 3 ] 17 0.34 0.2154 8 0.591 0.2169 9 -0.574 0.1774 Right ON Volume [mm 3 ] a 17 0.34 0.2153 8 0.124 0.8148 9 0.903 0.0053* Partial correlation analyses were performed using either Pearson rank correlation or Spearman rank correlation (a) depending on value distribution and adjusted for the potential confounder age and BMI. Each test was performed with p < 0.05 two-sided. 3.3. Endocrine Correlates of Pituitary Morphology After adjustment for age and BMI, pituitary size correlated positively with TSH only in the normal ICP group (r = 0.88, p = 0.020; Fig. 2 a), an association that disappeared and reversed under elevated pressure (Fig. 2 b). No meaningful relationships emerged for LH, FSH, ACTH, or GH (Table 3 ). Table 3 Relationships between Pituitary Gland associated hormones and Pituitary Gland Volume [mm 3 ] Laboratory Parameter Partial Correlation Adjusted for Age & BMI ICP < 25 cmH2O ICP ≥ 25 cmH2O N R P Value N R P Value TSH [µU/ml] 8 0.882 0.02* 9 -0.478 0.2784 LH [U/l] a 8 -0.218 0.6782 a 9 -0.292 0.5246 a FSH [mIU/ml] 8 -0.69 0.1296 9 0.594 0.1597 a ACTH [pg/ml] 8 -0.037 0.945 a 8 -0.123 0.8163 GH [ng/ml] 8 -0.148 0.7792 a 9 -0.056 0.9052 a Partial correlation analyses were performed using either Pearson rank correlation or Spearman rank correlation (a) depending on value distribution and adjusted for the potential confounder age and BMI. Each test was performed with p < 0.05 two-sided. 3.4. Hormonal Alterations and Association with ICP While hormone levels outside reference ranges were common, group differences were limited (Supplementary Table S3). ANCOVA and GLM analyses revealed significantly lower serum IGF-1 and testosterone concentrations in participants with elevated ICP (IGF-1: p = 0.039; testosterone: p = 0.027; Table S4). Partial correlation analyses adjusted for age, BMI, and pituitary volume demonstrated that ICP correlated positively with TSH (r = 0.628, p = 0.016) and negatively with GH (r = -0.602, p = 0.023; Table 4, Figure 3). No other hormone showed significant associations. These findings suggest pressure-related alterations in the thyroid and somatotropic axes in IIH. Table 4 Relationships between ICP and Serum Levels of Laboratory Parameters Laboratory Parameter Descriptive Statistics Whole Group Partial Correlation Adjusted for Age, BMI & Pituitary Gland Volume N R P Value TSH [μU/ml] 1.6 ± 0.7 (n = 18) 17 0.628 0.016* fT3 [pg/ml] 2.8 ± 0.4 (n = 17) 16 -0.056 0.856 fT4 [ng/dl] 1.2 ± 0.2 (n = 18) 17 -0.505 0.065 LH [U/l] 6.8 [5.3, 14.4] (n = 18) 17 -0.133 0.652 a FSH [mIU/ml] 5.8 [4.4, 7.3] (n = 18) 17 0.125 0.671 a DHEAS [μg/ml] 1.5 [0.8, 1.9] (n = 18) 17 -0.417 0.138a Testosterone [ng/ml] 0.2 [0.2, 0.4] (n = 18) 17 -0.3 0.298 a Estradiol [pg/ml] 75.8 ± 56.0 (n = 18) 17 0.181 0.535 Androstenedione [ng/ml] 1.5 [0.8, 2.3] (n = 18) 17 -0.277 0.338 a Prolactin [ng/ml] 18.4 [16.2, 26.6] (n = 18) 17 0.193 0.508 a ACTH [pg/ml] 19.2 [13.9, 44.3] (n = 17) 16 0.373 0.209 a Cortisol [μg/dl] 13.7 ± 4.7 (n = 18) 17 -0.317 0.270 GH [ng/ml] 0.1 [0.1, 0.3] (n = 18) 17 -0.602 0.023 a * IGF1 [ng/ml] 161.0 ± 61.7 (n = 16) 15 -0.372 0.234 All results are displayed as mean ± standard deviation (SD) or median [interquartile range (IQR)] in case of non-normal distribution. Partial correlation analyses were performed using either Pearson rank correlation or Spearman rank correlation (a) depending on value distribution and adjusted for the potential confounders age, BMI, and pituitary gland volume. Each test was performed with p < 0.05 two-sided. ACTH = adrenocorticotropic hormone; cmH 2 O = centimeter water column; DHEAS = dehydroepiandrosterone sulphate; FSH = follicle stimulating hormone; fT3 = free triiodothyronine; fT4 = free thyroxine; GH = growth hormone; ICP = intracranial pressure; IGF-1 = insulin-like growth factor 1; LH = luteinising hormone; TSH = thyroid stimulating hormone; 95% CI. 3.5 Predictive Modeling of ICP Univariate linear regression model revealed serum TSH as a significant positive predictor of ICP (β = 4.83 ± 1.81, t(16) = 2.68, p = 0.017, R² = 0.31), whereas GH showed a non-significant inverse trend (β = -1.02 ± 0.62, t(16) = 2.68, p = 0.122, R² = 0.14). Residual diagnostics exposed non-normality, heteroscedasticity and non-linear patterns (Supplementary figures S1-S4), prompting a Box–Cox transformation of ICP and z-standardisation of predictors. Robust Huber regression then confirmed TSH (β = 0.071 ± 0.02, p < 0.001) and GH (β = -0.024 ± 0.01, p = 0.041) as independent, oppositely directed determinants, explaining approximately 31% of ICP variance with consistent 10-fold cross-validation performance (mean squared error = 0.012). These findings suggest that TSH and GH provide complementary, biologically plausible markers for non-invasive ICP estimation in IIH. 4. Discussion This study demonstrates a multimodal link between elevated ICP, anterior pituitary hormone alterations, and structural brain changes in women with IIH. By combining endocrine profiling and quantitative MRI, we demonstrated that elevated ICP is significantly associated with alterations in thyroid and somatotropic axes, and that these changes are accompanied by morphological adaptations of the pituitary gland and surrounding structures. Our findings highlight the thyroid axis as a key hormonal system affected by increased ICP. TSH levels showed a significant positive correlation with ICP (r = 0.628, p = 0.0163) and emerged as a robust predictor in both standard (β = 4.8348, SE = 1.808, p = 0.017, R² = 0.309) and robust regression models (coefficient = 0.070817, SE = 0.020, p < 0.001). These observations build upon earlier case reports suggesting a relationship between IIH and thyroid disorders, including hypo- and hyperthyroidism as well as subacute thyroiditis [5-8, 22-24]. The elevated rate of thyroxine supplementation in our sample (13% in normal ICP vs. 30% in elevated ICP) exceeds rates reported in population studies (5-12%) [25-27], potentially reflecting female predominance and elevated BMI [28, 29]. Prior cohort studies yielded inconsistent findings regarding thyroid involvement in IIH. Giuseffi et al. (1991) [2] reported equal prevalence of thyroid disease in IIH patients and controls (2%), whereas KesKin et al. (2020) [30] reported a combined diabetes and thyroid disease rate of 19% in IIH. Recent work by Prabhat et al. (2024) [12] demonstrated normalization of elevated TSH following ICP reduction, further supporting the association between ICP and thyroid regulation. Mechanistically, TSH receptors and thyroid hormone transporters are expressed in the choroid plexus, the main site of CSF production, where aquaporins and transthyretin mediate hormone and fluid transport [16,18,31,32]. These mechanisms may partly explain the observed link between thyroid dysfunction and structural MRI findings in IIH. The somatotropic axis was also implicated. Serum GH levels correlated negatively with ICP (r = -0.602, p = 0.023), and became a significant predictor in the Huber regression model (coefficient = -0.023842, SE = 0.011, p = 0.041). While GH did not reach significance in the initial model, our findings align with prior reports linking GH deficiency to primary empty sella, present in over half of our cohort, and frequently observed in IIH [15]. While true GH deficiency was unlikely in our cohort-given normal IGF-1 levels in all patients with elevated ICP, IGF-1 concentrations were significantly lower in the elevated ICP group (137.7 ± 46.4 ng/mL vs. 205.8 ± 62.4 ng/mL; p = 0.039, R² = 0.604), and testosterone was also reduced (0.2 ± 0.1 ng/mL vs. 0.4 ± 0.2 ng/mL; p = 0.027, R² = 0.572). These findings may reflect functional suppression of the somatotropic and gonadal axes under mechanical compression or metabolic stress. Previous literature supports a role for GH/IGF-1 in CSF regulation. GH treatment has been associated with secondary IIH [33], while octreotide, a somatostatin analogue, has improved IIH symptoms [34]. GH/IGF-1 and somatostatin receptor expression in choroid plexus and arachnoid granulations suggest direct endocrine modulation of CSF dynamics [17, 35]. Our volumetric MRI findings parallel these hormonal alterations. Although pituitary volumes were not significantly different (normal ICP: 889.5 ± 174.5 mm³ vs. increased ICP: 819.6 ± 125.3 mm³; p = 0.353), pituitary flattening and empty sella were more frequent in elevated ICP (complete empty sella in 44% vs. 63%, p = 0.797; mean flattening 43.3 ± 25.5% vs. 56.3 ± 13.0%, p = 0.217), suggesting mechanical distortion rather than atrophy. A subgroup correlation analysis identified a strong positive association between TSH and pituitary volume in the normal ICP group (r = 0.882, p = 0.020), but not in the elevated ICP group (r = -0.478, p = 0.278), suggesting impaired glandular adaptation under sustained pressure. ONS distension is a well-established marker of elevated ICP. In our study, ONS volumes correlated with ICP only in the normal ICP group (left: r = 0.804, p = 0.054; right: r = 0.797, p = 0.058), but not in the elevated group ((right ONS: r = -0.169, p = 0.717), where a ceiling effect may limit further distension. This phenomenon may contribute to decoupling between ICP and imaging parameters, and potentially affect surrounding structures such as the pituitary. Additional findings included mild hyperprolactinemia (50% in normal ICP, 30% in elevated ICP), consistent with prior reports of stalk compression and altered dopaminergic inhibition in IIH [36, 37]. Although group differences were not significant, 20% of patients with elevated ICP had concurrent PCOS, and one exhibited elevated prolactin. Gonadotropic and adrenal hormone levels (e.g., ACTH: r = 0.373, p = 0.209; DHEAS: r = -0.417, p = 0.138) showed moderate but non-significant associations with ICP. Taken together, our findings suggest that IIH may involve a pressure-induced neuroendocrine dysregulation, primarily affecting the thyroid and somatotropic axes. Quantitative MRI provides structural correlates that reflect this dysfunction, particularly in the pituitary and ONS. Our data support the integration of endocrine profiling and neuroimaging in the diagnostic and monitoring process of IIH. This study has limitations. ICP was measured at a single time point, and the sample size was small. GH status was not assessed via stimulation testing. Obesity, which can independently affect hormone levels, was present in nearly all participants. Due to ethical constraints, a matched control group could not be included. Future studies should validate these results in larger cohorts, using longitudinal designs, dynamic endocrine testing, and multimodal imaging. The predictive role of ONS and pituitary morphology in treatment outcomes warrants further investigation. Clinically, our findings emphasize the need to evaluate endocrine status, particularly thyroid and somatotropic function, in patients with IIH, especially in the presence of empty sella. In conclusion, sustained ICP elevation in IIH appears to induce measurable endocrine and structural brain changes. Hormonal markers particularly TSH and GH together with MRI-based indicators such as pituitary flattening and ONS distension, may serve as complementary tools for improving diagnostic precision and disease monitoring. Clinical Implications In conclusion , sustained ICP elevation in women with IIH is associated with measurable endocrine dysfunction, particularly involving TSH and GH, as well as with distinct structural brain changes visible on MRI. Combining quantitative neuroimaging with focused endocrine assessment may enhance diagnostic precision, help identify individuals at risk for persistent disease activity, and support more individualized treatment strategies. Declarations Ethics Approval The study was approved by the local ethics committee (Approval No. 383/17) and conducted in accordance with the Declaration of Helsinki. All subjects provided written informed consent prior to inclusion in the study, and any identifying details have been omitted to protect their privacy. Author Contribution Conceptualization: Z.B.,R.C., A.R., U.W., C.K. Methodology: Z.B., B.D.W., R.C., W.F., B. W., U.W., C.K. Formal analysis and investigation: Z.B., B.D.W., R.C., W.F., C.F., M.J., M.M., A.H.S., F.M.S., B.W., C.S., M.W., B.K., A.R., J.L., U.W., C.K.Writing - original draft preparation: Z.B., B.D.W., R.C., M.M., A.H.S., B.W., C.S., M.W., B.K., J.L., C.K. Z.B., C.K., R.C., B.W., B.D.W., M.M., A.H.S. wrote the main manuscript text and Z.B., C.K., C.S., M.W., R.C., B.K., J.L. prepared figures and tables. Writing - review and editing: Z.B., B.D.W., W.F., R.C., C.F., M.J., M.M., A.H.S., F.M.S., B.W., C.S., M.W., B.K., A.R., J.L., U.W., C.K. Resources: Z.B., B.W., A.R., U.W., C.K.Supervision: Z.B., B.W., A.R., U.W., C.K.All authors reviewed the manuscript. Acknowledgement I thank the German Society of Intracranial Hypertension for their support in conducting the study. References Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology 2013;81(13):1159–65. https://doi.org/10.1212/WNL.0b013e3182a55f17. PMID: 23966248. 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Idiopathic intracranial hypertension following levothyroxine replacement therapy: systematic review and a case report. Indian J Endocrinol Metab. 2023;27(1):17-24. https://doi.org/10.4103/ijem.ijem_439_22. PMID: 37215264; PMCID: PMC10198199. Khattak RM, Ittermann T, Nauck M, Below H, Völzke H. Monitoring the prevalence of thyroid disorders in the adult population of Northeast Germany. Popul Health Metr. 2016;14:39. https://doi.org/10.1186/s12963-016-0111-3. PMID: 27833458; PMCID: PMC5101821. Kiel S, Ittermann T, Völzke H, Chenot JF, Angelow A. Frequency of thyroid function tests and examinations in subjects of a population-based study. BMC Health Serv Res. 2020;20(1):70. https://doi.org/10.1186/s12913-020-4910-7. PMID: 32000765; PMCID: PMC6993310. Viniol A, Bösner S, Baum E, Donner-Banzhoff N. Forgotten drugs: long-term prescriptions of thyroid hormones-a cross-sectional study. Int J Gen Med. 2013;6:32934. https://doi.org/10.2147/IJGM.S43187. PMID: 23641158; PMCID: PMC3639717. Ruhla S, Arafat AM, Osterhoff M, Weickert MO, Mai K, Spranger J, Schöfl C, Pfeiffer AF, Möhlig M. Levothyroxine medication is associated with adiposity independent of TSH. Exp Clin Endocrinol Diabetes 2012;120(6):351-4. https://doi.org/10.1055/s-0032-1312599. PMID: 22639395. Wouters HJCM, Slagter SN, Muller Kobold AC, van der Klauw MM, Wolffenbuttel BHR. Epidemiology of thyroid disorders in the Lifelines Cohort Study (the Netherlands). PLoS One 2020;15(11):e0242795. https://doi.org/10.1371/journal.pone.0242795. PMID: 33237973; PMCID: PMC7688129. KesKın AO, İdıman F, Kaya D, Bırcan B. Idiopathic intracranial hypertension: etiological factors, clinical features, and prognosis. Noro Psikiyatr Ars. 2018;57(1):23-6. https://doi.org/10.5152/npa.2017.12558. PMID: 32110146; PMCID: PMC7024819. Mariani LH, Berns JS. The renal manifestations of thyroid disease. J Am Soc Nephrol. 2012;23(1):22-6. https://doi.org/10.1681/ASN.2010070766. PMID: 22021708. Richardson SJ, Wijayagunaratne RC, D'Souza DG, Darras VM, Van Herck SL. Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and thyroid hormone transmembrane transporters. Front Neurosci. 2015;9:66. https://doi.org/10.3389/fnins.2015.00066. PMID: 25784853; PMCID: PMC4347424. Loukianou E, Tasiopoulou A, Demosthenous C, Brouzas D. Pseudotumor cerebri in a child with idiopathic growth hormone insufficiency two months after initiation of recombinant human growth hormone treatment. Case Rep Ophthalmol Med. 2016;2016:4756894. https://doi.org/10.1155/2016/4756894. PMID: 26966604; PMCID: PMC4757697. Panagopoulos GN, Deftereos SN, Tagaris GA, Gryllia M, Kounadi T, Karamani O, Panagiotidis D, Koutiola-Pappa E, Karageorgiou CE, Piadites G. Octreotide: a therapeutic option for idiopathic intracranial hypertension. Neurol Neurophysiol Neurosci. 2007;10:1. PMID: 17700925. Deijen JB, Arwert LI. Impaired quality of life in hypopituitary adults with growth hormone deficiency: can somatropin replacement therapy help? Treat Endocrinol. 2006;5(4):243-50. https://doi.org/10.2165/00024677-200605040-00005. PMID: 16879003. De Marinis L, Bonadonna S, Bianchi A, Maira G, Giustina A. Primary empty sella. J Clin Endocrinol Metab. 2005;90(9):5471-7. https://doi.org/10.1210/jc.2005-0288. PMID: 15972577. Aruna P, Sowjanya B, Reddy PA, Krishnamma M, Naidu JN. Partial empty sella syndrome: a case report and review. Indian J Clin Biochem. 2014;29(2):253-6. https://doi.org/10.1007/s12291-013-0369-1. PMID: 24757313; PMCID: PMC3990803. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-7177945\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":495254217,\"identity\":\"94b02f0b-d3ea-43a9-93c2-f5057d2d2a2d\",\"order_by\":0,\"name\":\"Zeynep Bendella\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCklEQVRIiWNgGAWjYBCDBCA2YHhQwCDHwMMDFmFsIEpLggGDMelaEhsIaZFv7zF78HEHQx6/dPPGBwkGdukbzpw9+LhwB4NsPw4tjD1nzA1nnmEolpxzrNggwSA5d8PZvmRjoIjxTBzWMEvkmEnztjEkbriRYyaRYMCcu+E8D1TkAHYtbPJvzKT/AhXsv5Fj/iPBoD7dAKZlPw4tPBJABYwgM4HWAb1/OMHgbA/UFhx+keBJK5PsPSNRLHEjrRjosONAj51LNuZtkzCegcMW+fbD2yR+7rDJ45+RvPHDh4pqeb4zuQcf87bZyPbj8D4DA4cBMAokMK3HpR4I2B8QjuhRMApGwSgY2QAAmV5aBbZtR7QAAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"University of Bonn\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Zeynep\",\"middleName\":\"\",\"lastName\":\"Bendella\",\"suffix\":\"\"},{\"id\":495254219,\"identity\":\"cc7903a1-d6eb-4fa9-b7ac-27708395c240\",\"order_by\":1,\"name\":\"Barbara Daria Wichtmann\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Bonn\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Barbara\",\"middleName\":\"Daria\",\"lastName\":\"Wichtmann\",\"suffix\":\"\"},{\"id\":495254220,\"identity\":\"44af03ba-f0b9-4bad-9c6d-572466b5f7ff\",\"order_by\":2,\"name\":\"Ralf Clauberg\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Bonn\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ralf\",\"middleName\":\"\",\"lastName\":\"Clauberg\",\"suffix\":\"\"},{\"id\":495254221,\"identity\":\"3bdaef3a-9958-4be1-9fca-7e7f3dad1775\",\"order_by\":3,\"name\":\"Wiebke Fenske\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"BG University Hospital Bergmannsheil Bochum\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Wiebke\",\"middleName\":\"\",\"lastName\":\"Fenske\",\"suffix\":\"\"},{\"id\":495254222,\"identity\":\"c59faccd-33c3-48cd-9e52-3746e8daf6ab\",\"order_by\":4,\"name\":\"Charlotte Fries\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Bonn\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Charlotte\",\"middleName\":\"\",\"lastName\":\"Fries\",\"suffix\":\"\"},{\"id\":495254223,\"identity\":\"e2eb38db-a835-4aae-b4d5-ce3cba1bb398\",\"order_by\":5,\"name\":\"Monika Jeub\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Bonn\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Monika\",\"middleName\":\"\",\"lastName\":\"Jeub\",\"suffix\":\"\"},{\"id\":495254224,\"identity\":\"83ade9c4-f21d-4756-a24c-2a285184ebe6\",\"order_by\":6,\"name\":\"Martina Minnerop\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Research Center Juelich\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Martina\",\"middleName\":\"\",\"lastName\":\"Minnerop\",\"suffix\":\"\"},{\"id\":495254225,\"identity\":\"46e4d2a9-ca7d-4ccf-8f30-2b740c5726ba\",\"order_by\":7,\"name\":\"Arndt-Hendrik Schievelkamp\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University Hospital Cologne\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Arndt-Hendrik\",\"middleName\":\"\",\"lastName\":\"Schievelkamp\",\"suffix\":\"\"},{\"id\":495254227,\"identity\":\"471e05cf-3e08-4eb7-9660-4bd372efc043\",\"order_by\":8,\"name\":\"Franziskus M. 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(A) Midsagittal T1-weighted MRI scan showing the segmented pituitary gland (green). (B) Coronal T1-weighted scan illustrating pituitary segmentation (green) in the frontal plane. (C) Axial T1-weighted scan with bilateral segmentation of the ONS (blue: left; red: right). (D) Coronal T1-weighted scan showing ONS segmentation (blue and red) in the transverse plane. These images illustrate typical morphological changes in IIH and the applied voxel-based approach to structural quantification\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7177945/v1/6b03c224e3898df2c3b0d739.png\"},{\"id\":88491804,\"identity\":\"4312904c-04b7-442c-a546-8e79bb94a6f3\",\"added_by\":\"auto\",\"created_at\":\"2025-08-07 04:24:54\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":41639,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eScatterplots with regression lines and kernel density estimates illustrating the relationship between ICP [cmH₂O] and serum hormone levels in IIH, adjusted for age, BMI, and pituitary gland volume. (A) Higher TSH [μU/mL] levels are positively associated with ICP.\\u003cbr\\u003e\\n(B) GH [ng/mL] levels show a negative association with ICP. Shaded areas represent 95% confidence intervals around the regression lines.\\u003cbr\\u003e\\nAbbreviations: cmH₂O = centimeter water column; GH = growth hormone; ICP = intracranial pressure; TSH = thyroid-stimulating hormone\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7177945/v1/c835203f95860f888f6e1d5c.png\"},{\"id\":88490989,\"identity\":\"b644a13d-c672-48a7-88d1-4ca8058c60b6\",\"added_by\":\"auto\",\"created_at\":\"2025-08-07 04:16:54\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":41656,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eScatterplots with regression lines and kernel density estimates illustrating the relationship between serum TSH levels (μU/mL) and pituitary gland volume (mm³) in IIH, stratified by ICP. (A) Patients with normal ICP (\\u0026lt; 25 cmH₂O) show a significant positive association between TSH and pituitary volume (\\u003cem\\u003er\\u003c/em\\u003e = 0.882, \\u003cem\\u003ep\\u003c/em\\u003e = 0.020). (B) In patients with elevated ICP (≥ 25 cmH₂O), this relationship is no longer evident (\\u003cem\\u003er\\u003c/em\\u003e = –0.478, \\u003cem\\u003ep\\u003c/em\\u003e = 0.278), suggesting a pressure-dependent dissociation.\\u003cbr\\u003e\\nShaded areas indicate 95% confidence intervals around the regression line.\\u003cbr\\u003e\\nAbbreviations: cmH₂O = centimeter water column; ICP = intracranial pressure; mm³ = cubic millimeter; TSH = thyroid-stimulating hormone\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7177945/v1/0c078c6d520ef2f35185ff03.png\"},{\"id\":101690550,\"identity\":\"1e57ecb6-d2f2-4782-8650-3e4fbd8e9591\",\"added_by\":\"auto\",\"created_at\":\"2026-02-02 16:05:27\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1878853,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7177945/v1/0db5efd1-9a40-4b8e-bf04-37d3aecec27c.pdf\"},{\"id\":88492467,\"identity\":\"e4db0a59-dfe4-408b-9053-446ba02729fa\",\"added_by\":\"auto\",\"created_at\":\"2025-08-07 04:32:54\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":19988,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"supplementarymaterialtableS1.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7177945/v1/2c690057347e28c3e5ab300f.docx\"},{\"id\":88491805,\"identity\":\"c3916b93-a91a-4746-b188-a0ed37cb7b21\",\"added_by\":\"auto\",\"created_at\":\"2025-08-07 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04:16:54\",\"extension\":\"docx\",\"order_by\":4,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":23640,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"supplementarymaterialtableS4.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7177945/v1/9a14707ee9cffd9cd7f24940.docx\"},{\"id\":88492469,\"identity\":\"fda7d719-0876-4ac7-bbc7-7c9488a2caf3\",\"added_by\":\"auto\",\"created_at\":\"2025-08-07 04:32:54\",\"extension\":\"docx\",\"order_by\":5,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":66423,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"supplementarymaterialfigureS1.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7177945/v1/a9f36768d905b0ad498f347f.docx\"},{\"id\":88491003,\"identity\":\"7dd60ad9-326c-45b1-87e3-9a40267ad2a6\",\"added_by\":\"auto\",\"created_at\":\"2025-08-07 04:16:54\",\"extension\":\"docx\",\"order_by\":6,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":2261375,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"supplementarymaterialfigureS2.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7177945/v1/7881cd916536c654ced29496.docx\"},{\"id\":88491012,\"identity\":\"a512b5b7-2f8d-485c-8e0b-a356545b1d55\",\"added_by\":\"auto\",\"created_at\":\"2025-08-07 04:16:55\",\"extension\":\"docx\",\"order_by\":7,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":5249427,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"supplementarymaterialfigureS3.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7177945/v1/2d52f3f6d38e1b9a07d51de6.docx\"},{\"id\":88491810,\"identity\":\"22097cfc-58da-4fae-8a3e-1171c3632786\",\"added_by\":\"auto\",\"created_at\":\"2025-08-07 04:24:54\",\"extension\":\"docx\",\"order_by\":8,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":5249378,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"supplementarymaterialfigureS4.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7177945/v1/8967cb9e3dd54d6eddcf8c1e.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Structural MRI Biomarkers of Intracranial Pressure in IIH: Linking Optic Nerve Sheath, Pituitary Morphology, and Hormonal Changes\",\"fulltext\":[{\"header\":\"1. Introduction\",\"content\":\"\\u003cp\\u003eIdiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure (ICP) without a detectable structural lesion or hydrocephalus. IIH primarily affects obese women of childbearing age and carries a risk for severe symptoms, including vision loss [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. The underlying mechanisms of IIH remain incompletely understood, although multifactorial contributions have been proposed, including alterations in cerebrospinal fluid (CSF) dynamics, venous outflow obstruction, and hormonal dysregulation [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003eWhile the association between IIH and obesity is well-established, accumulating evidence suggests that endocrine abnormalities may also contribute to its pathophysiology.\\u003c/p\\u003e\\u003cp\\u003eSeveral case reports and small cohort studies [\\u003cspan additionalcitationids=\\\"CR6 CR7\\\" citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e], as well as more recent observational work, have described associations between IIH and hormonal imbalances involving the thyroid, adrenal, gonadal, and somatotropic axes [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan additionalcitationids=\\\"CR10 CR11\\\" citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. In particular, thyroid dysfunction has been disproportionately reported in IIH, and recent evidence suggests normalization of thyroid-stimulating hormone (TSH) levels following ICP reduction [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. Nevertheless, systematic endocrine investigations in relation to ICP remain scarce, particularly in adults.\\u003c/p\\u003e\\u003cp\\u003eIn parallel, structural MRI findings such as an empty sella, pituitary flattening, and optic nerve sheath (ONS) distension are frequently observed in IIH and are commonly attributed to mechanical effects of elevated ICP [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. However, it remains unclear whether these changes reflect true endocrine dysfunction or merely passive compression. Prior studies have reported hypopituitarism in patients with empty sella in up to 52% of cases, with growth hormone (GH) deficiency particularly prevalent [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003eGiven the bidirectional interactions between hormonal function and CSF physiology-including evidence for the expression of hormone receptors and transporters in the choroid plexus and arachnoid granulations [\\u003cspan additionalcitationids=\\\"CR17\\\" citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e], an integrated analysis of structural and endocrine markers may offer new insights into IIH.\\u003c/p\\u003e\\u003cp\\u003eIn this study, we investigated the relationship between anterior pituitary hormone levels and quantitative MRI measures in women with IIH. We hypothesized that elevated ICP is associated with alterations in the thyroid and somatotropic axes and that these endocrine changes are paralleled by structural brain alterations detectable on MRI. By integrating hormonal data with volumetric imaging markers such as pituitary gland volume, pituitary flattening, and ONS volume, we aim to refine the understanding of neuroendocrine regulation in IIH and to evaluate potential non-invasive markers of disease burden.\\u003c/p\\u003e\\u003cp\\u003eTo test these hypotheses, we conducted a cross-sectional study in a well-defined cohort of women with therapy-resistant IIH. We systematically assessed anterior pituitary hormone levels and performed high-resolution brain MRI to quantify structural changes. We statistically examined associations between hormone levels, imaging features, and ICP measured via lumbar puncture.\\u003c/p\\u003e\"},{\"header\":\"2. Materials and Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e2.1 Study Design and Participants\\u003c/h2\\u003e\\u003cp\\u003eIn this cross-sectional study, we consecutively enrolled 18 female patients with therapy-refractory IIH who were hospitalized due to recurrent symptoms requiring lumbar puncture between May 2018 and October 2019. The diagnosis of IIH was confirmed according to the modified Dandy criteria [\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e] by reviewing external medical reports for individual diagnostic components. Exclusion criteria included age under 18 years, neurological disorders other than IIH, contraindications to MRI (e.g., history of seizures, severe psychiatric or systemic illness, metallic implants, claustrophobia, pregnancy), and substance abuse. Sample size was based on data availability; no power calculation was performed. All subjects provided written informed consent, and the study was approved by the local ethics committee (No. 383/17), conducted in accordance with the Declaration of Helsinki.\\u003c/p\\u003e\\u003cp\\u003eDemographic and clinical variables included age, body mass index (BMI), waist-to-hip ratio, medication use, and detailed neurological, gynecological, and ophthalmological history. Polycystic ovary syndrome (PCOS) was diagnosed using the Rotterdam criteria [\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e], requiring at least two of the following: oligo- or amenorrhea, clinical or biochemical hyperandrogenism, or polycystic ovaries on ultrasound.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e2.2 Endocrinological Assessment\\u003c/h2\\u003e\\u003cp\\u003eVenous blood samples were collected from all subjects after overnight fasting at 7:00 am. Each blood sample was processed according to the standard protocols of our clinical laboratory.\\u003c/p\\u003e\\u003cp\\u003ePost hoc serum concentrations of thyroid hormones, including TSH, free thyroxine (fT4), and triiodothyronine (fT3), gonadotropins, including follicle stimulating hormone (FSH) and luteinising hormone (LH), as well as reproductive hormones, such as prolactin, estradiol, testosterone, androstenedione, and dehydroepiandrosterone sulphate (DHEAS), were analysed. Glucocorticoids adrenocorticotropic hormone (ACTH) and cortisol, as well as GH, were measured using an electrochemiluminescence immunoassay (ECLIA) (Roche Diagnostics). Serum concentrations of insulin-like growth factor 1 (IGF-1) were determined using an Immunodiagnostic Systems (IDS\\u003csup\\u003e\\u0026reg;\\u003c/sup\\u003e) immunoassay. Levothyroxine intake was considered indicative of hypothalamic-pituitary-thyroid-axis dysregulation regardless of TSH levels. Values below detection thresholds were set to half the detection limit.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e2.3 Lumbar Puncture\\u003c/h2\\u003e\\u003cp\\u003eLumbar puncture was performed in lateral decubitus position on the same day as the endocrine evaluation. ICP was measured in cmH2O. If ICP was \\u0026ge;\\u0026thinsp;25 cmH2O, 20\\u0026ndash;30 mL of CSF were drained for therapeutic relief. Based on ICP measurements, patients were categorized into a normal (\\u0026lt;\\u0026thinsp;25 cmH2O) and elevated (\\u0026ge;\\u0026thinsp;25 cmH2O) group.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e2.4 Ophthalmological examination\\u003c/h2\\u003e\\u003cp\\u003eOphthalmological examination included assessments of the optic disc, visual field, visual acuity, and bulbar motility. Papilledema was assessed using fundus examination and the Fris\\u0026eacute;n scale [\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e], graded from 0 to 5. Visual acuity was measured with the revised Snellen chart, with reduction defined as \\u0026lt;\\u0026thinsp;20/25. Visual fields were assessed using the OCULUS Twinfield perimeter with automated kinetic (stimulus III/4) and static perimetry (program 30\\u0026thinsp;\\u0026minus;\\u0026thinsp;2, stimulus size III, fast threshold strategy). The mean deviation (MD), indicating total field loss, was automatically generated. Field restriction was defined as \\u0026lt;\\u0026thinsp;40\\u0026deg; nasal or \\u0026lt;\\u0026thinsp;75\\u0026deg; temporal. Enlarged blind spots were also assessed. Visual fields with unacceptable reliability indices (loss of fixation\\u0026thinsp;\\u0026gt;\\u0026thinsp;30%, false-positive errors\\u0026thinsp;\\u0026gt;\\u0026thinsp;15%) were excluded. Optic disc volume was measured using optical coherence tomography (OCT) with Spectralis\\u0026reg; (Heidelberg Engineering, Heidelberg, Germany).\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e2.5 Imaging Protocol and Morphometric Analysis\\u003c/h2\\u003e\\u003cp\\u003eHigh-resolution structural brain MRI was performed before lumbar puncture to exclude secondary causes of raised ICP. For morphometric analysis, volumetric T1-weighted images were used to segment and quantify pituitary gland volume, sella turcica volume, pituitary gland flattening (defined as percentage of sella filled), left and right ONS and optic nerve (ON) volumes each.\\u003c/p\\u003e\\u003cp\\u003eSegmentations were performed manually using 3D Slicer (version 5.8.0) by an experienced neuroradiologist blinded to ICP group. Incomplete empty sella was defined as 0\\u0026ndash;50% CSF-filling, and complete empty sella as \\u0026gt;\\u0026thinsp;50%. Intra-rater reliability was confirmed by duplicate measurement across all participants. Representative segmentations are shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e.\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003e2.6 Statistical Analyses\\u003c/h2\\u003e\\u003cp\\u003eThe statistical analyses and visualizations were performed using Python (v3.11.8) and appropriate statistical packages. Descriptive statistics were reported as means\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;standard deviation (SD) for normally distributed variables and as medians with interquartile ranges (IQR) for non-normally distributed data. Depending on data distribution and measurement scale, group comparisons were performed using Student\\u0026rsquo;s t-test, Mann\\u0026ndash;Whitney U-test, chi-squared test, or Fisher\\u0026rsquo;s exact test. Effect sizes were calculated using Cohen\\u0026rsquo;s d, rank-biserial correlations, Cramer's V, and Phi coefficients. Statistical significance was set at p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 (two-tailed).\\u003c/p\\u003e\\u003cp\\u003e To explore relationships between radiological findings, endocrine parameters, and ICP, we followed a structured analytic framework. First, demographic, clinical, imaging, and endocrine characteristics were compared between groups with normal (\\u0026lt;\\u0026thinsp;25 cmH2O in lateral position) and increased (\\u0026ge;\\u0026thinsp;25 cmH2O) ICP. Missing values were excluded pairwise, and reduced group sizes are indicated in the tables.\\u003c/p\\u003e\\u003cp\\u003eSubsequently, imaging parameters (pituitary gland volume, flattening percentage, sella volume, and bilateral ONS and ON volumes) were correlated with ICP using partial correlation analyses adjusted for age and BMI. These analyses were also stratified by ICP status to identify pressure-specific associations.\\u003c/p\\u003e\\u003cp\\u003eTo examine structural-endocrine relationships, partial correlations were calculated between pituitary hormone levels (TSH, LH, FSH, ACTH, GH) and pituitary gland volume, separately within ICP subgroups and adjusted for age and BMI.\\u003c/p\\u003e\\u003cp\\u003eNext, serum hormone concentrations were evaluated in relation to ICP. First, frequencies of values outside reference ranges were examined. Second, group differences in raw hormone concentrations were analyzed using either analysis of covariance (ANCOVA) for normally distributed variables or generalized linear models (GLM) for non-normally distributed variables. All models were adjusted for age, BMI, and pituitary volume. The ANCOVA was based on ordinary least squares (OLS) regression; the GLM used a Gamma distribution with log-link function. For each model, corresponding effect sizes (R\\u0026sup2; for ANCOVA, McFadden\\u0026rsquo;s pseudo R\\u0026sup2; for GLM) were reported. Model assumptions, including homogeneity of regression slopes (ANCOVA) and distributional fit (GLM), were verified using graphical and statistical diagnostics.\\u003c/p\\u003e\\u003cp\\u003eSignificant variables from group comparisons were further examined using partial correlation analyses. To evaluate predictors of ICP, linear regression models were constructed with hormone levels as predictors. ICP values were Box-Cox transformed to approximate normality, and TSH and GH were z-standardized. Because the OLS model violated normality and homoscedasticity assumptions, Huber regression was used to improve robustness against outliers. Model performance was assessed using 10-fold cross-validation with mean squared error (MSE) as the evaluation metric. Model assumptions were verified using residual plots, histograms, and Q-Q plots.\\u003c/p\\u003e\\u003cp\\u003eThis multi-level approach enabled the assessment of group-level, correlational, and predictive relationships between endocrine and structural MRI parameters in the context of ICP.\\u003c/p\\u003e\\u003c/div\\u003e\"},{\"header\":\"3. Results\",\"content\":\"\\u003cdiv id=\\\"Sec10\\\" class=\\\"Section2\\\"\\u003e\\n \\u003ch2\\u003e3.1. Demographic and Clinical Profile\\u003c/h2\\u003e\\n \\u003cp\\u003eEighteen women with therapy-refractory IIH were enrolled between May 2018 and October 2019 (Table \\u003cspan class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Ten patients showed elevated ICP (\\u0026ge;\\u0026thinsp;25 cmH₂O; median 26.5 cmH₂O, IQR 25.3\\u0026ndash;31.0), while eight had normal pressures (mean 19.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.4 cmH₂O). Patients with elevated ICP tended to be older (37.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.4 vs 31.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.2 years) and more obese (BMI 37.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;6.2 vs 33.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.3 kg/m\\u0026sup2;), but these differences were not statistically significant (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.15). Waist-to-hip ratios were identical (0.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.1).\\u003c/p\\u003e\\n \\u003cp\\u003eNo between-group differences emerged in the prevalence of PCOS, neuropsychiatric or neurological comorbidities, or use of IIH-related medication (all p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.47; Table \\u003cspan class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e, Supplementary Table \\u003cspan class=\\\"InternalRef\\\"\\u003eS1\\u003c/span\\u003e). Ophthalmologic metrics including papilledema grade, visual acuity, visual-field indices, and OCT-derived optic-disc volume were likewise comparable, and no cranial nerve palsies were detected (Supplementary Table \\u003cspan class=\\\"InternalRef\\\"\\u003eS2\\u003c/span\\u003e).\\u003c/p\\u003e\\n \\u003cdiv class=\\\"gridtable\\\"\\u003e\\n \\u003ctable id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e\\n \\u003ccaption language=\\\"En\\\"\\u003e\\n \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e\\n \\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\n \\u003cp\\u003eDemographic and clinical group characteristics for the total group and for normal and increased ICP\\u003c/p\\u003e\\n \\u003c/div\\u003e\\n \\u003c/caption\\u003e\\n \\u003cthead\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eWhole Group\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eICP\\u0026thinsp;\\u0026lt;\\u0026thinsp;25 cmH\\u003csub\\u003e2\\u003c/sub\\u003eO\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eICP\\u0026thinsp;\\u0026ge;\\u0026thinsp;25 cmH\\u003csub\\u003e2\\u003c/sub\\u003eO\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e Value\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eTest Statistics\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eCohen\\u0026apos;s d/Rank-Biserial/Phi coefficient (\\u0026phi;)/ Cramer\\u0026apos;s V\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/thead\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAge [years]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ea\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e35.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.2 (n\\u0026thinsp;=\\u0026thinsp;18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e31.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.2 (n\\u0026thinsp;=\\u0026thinsp;8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e37.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.4 (n\\u0026thinsp;=\\u0026thinsp;10)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.152\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003et(16) = -1.505\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-0.714\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eBMI [kg/m2]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ea\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e35.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;6 (n\\u0026thinsp;=\\u0026thinsp;18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e33.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.3 (n\\u0026thinsp;=\\u0026thinsp;8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e37.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;6.2 (n\\u0026thinsp;=\\u0026thinsp;10)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.180\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003et(16) = -1.401\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-0.665\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eWaist to Hip ratio\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ea\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.1 (n\\u0026thinsp;=\\u0026thinsp;18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.1 (n\\u0026thinsp;=\\u0026thinsp;8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.1 (n\\u0026thinsp;=\\u0026thinsp;10)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.549\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003et(16)\\u0026thinsp;=\\u0026thinsp;0.612\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.626\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eICP [cmH\\u003c/strong\\u003e\\u003csub\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sub\\u003e\\u003cstrong\\u003eO]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003eb\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e24.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;6.0 (n\\u0026thinsp;=\\u0026thinsp;18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e19.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.4 (n\\u0026thinsp;=\\u0026thinsp;8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e26.5 [25.3, 31.0] (n\\u0026thinsp;=\\u0026thinsp;10)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eU\\u0026thinsp;=\\u0026thinsp;0.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eFlattening of the Pituitary Gland [%]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ea\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e49.4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;41.1 (n\\u0026thinsp;=\\u0026thinsp;17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e56.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;13.0 (n\\u0026thinsp;=\\u0026thinsp;8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e43.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;25.5 (n\\u0026thinsp;=\\u0026thinsp;9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.217\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003et(15)\\u0026thinsp;=\\u0026thinsp;1.288\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.626\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eNo/Incomplete/Complete Empty Sella [%]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ed\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0/47/53 (n\\u0026thinsp;=\\u0026thinsp;0/8/9 / 17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0/38/63 (n\\u0026thinsp;=\\u0026thinsp;0/3/5 / 8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0/56/44 (n\\u0026thinsp;=\\u0026thinsp;0/5/4 / 9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.797\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026chi;2(1)\\u0026thinsp;=\\u0026thinsp;0.066\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.063\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePituitary Gland Volume [mm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e3\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ea\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e852.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;149.9 (n\\u0026thinsp;=\\u0026thinsp;17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e889.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;174.5 (n\\u0026thinsp;=\\u0026thinsp;8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e819.6\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;125.3 (n\\u0026thinsp;=\\u0026thinsp;9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.353\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003et(15)\\u0026thinsp;=\\u0026thinsp;0.958\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.465\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSella Volume [mm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e3\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ea\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1516.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;364.1 (n\\u0026thinsp;=\\u0026thinsp;17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1570.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;491.36 (n\\u0026thinsp;=\\u0026thinsp;8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1468.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;219.7 (n\\u0026thinsp;=\\u0026thinsp;9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.578\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003et(15)\\u0026thinsp;=\\u0026thinsp;0.568\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.276\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eLeft ONS Volume [mm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e3\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ea\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e854.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;155.5 (n\\u0026thinsp;=\\u0026thinsp;17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e791.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;124.3 (n\\u0026thinsp;=\\u0026thinsp;8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e909.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;165.7 (n\\u0026thinsp;=\\u0026thinsp;9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.122\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003et(15) = -1.639\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-0.797\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eRight ONS Volume [mm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e3\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ea\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e901.6\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;131.8 (n\\u0026thinsp;=\\u0026thinsp;17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e855.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;129.2 (n\\u0026thinsp;=\\u0026thinsp;8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e942.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;126.9 (n\\u0026thinsp;=\\u0026thinsp;9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.181\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003et(15) = -1.406\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-0.683\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eLeft ON Volume [mm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e3\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ea\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e145.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;28.8 (n\\u0026thinsp;=\\u0026thinsp;17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e135.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;25.2 (n\\u0026thinsp;=\\u0026thinsp;8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e154.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;30.1 (n\\u0026thinsp;=\\u0026thinsp;9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.179\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003et(15) = -1.409\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-0.685\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eRight ON Volume [mm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e3\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003eb\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e155.4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;37.7 (n\\u0026thinsp;=\\u0026thinsp;17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e143.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;30.8 (n\\u0026thinsp;=\\u0026thinsp;8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e144.4 [135.7, 176.0] (n\\u0026thinsp;=\\u0026thinsp;9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.20\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eU\\u0026thinsp;=\\u0026thinsp;22.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.389\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePCOS [%]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ec\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e11 (n\\u0026thinsp;=\\u0026thinsp;2/18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0 (n\\u0026thinsp;=\\u0026thinsp;0/8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e20 (n\\u0026thinsp;=\\u0026thinsp;2/10)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.477\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026chi;\\u003csup\\u003e2\\u003c/sup\\u003e(1)\\u0026thinsp;=\\u0026thinsp;0.345\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.138\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eHistory of neurological/ psychatric disorder [%]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ec\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e56 (n\\u0026thinsp;=\\u0026thinsp;10/18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e63 (n\\u0026thinsp;=\\u0026thinsp;5/8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e50 (n\\u0026thinsp;=\\u0026thinsp;5/10)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.664\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026chi;\\u003csup\\u003e2\\u003c/sup\\u003e(1)\\u0026thinsp;=\\u0026thinsp;0.003\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.013\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eNeurological impairments detected in examination [%]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ec\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e22 (n\\u0026thinsp;=\\u0026thinsp;4/18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e25 (n\\u0026thinsp;=\\u0026thinsp;2/8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e20 (n\\u0026thinsp;=\\u0026thinsp;2/10)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026chi;\\u003csup\\u003e2\\u003c/sup\\u003e(1)\\u0026thinsp;=\\u0026thinsp;0.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eIIH associated medication [%]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ec\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e72 (n\\u0026thinsp;=\\u0026thinsp;13/18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e75 (n\\u0026thinsp;=\\u0026thinsp;6/8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e70 (n\\u0026thinsp;=\\u0026thinsp;7/10)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026chi;\\u003csup\\u003e2\\u003c/sup\\u003e(1)\\u0026thinsp;=\\u0026thinsp;0.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eReported headache [%]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ec\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e100 (n\\u0026thinsp;=\\u0026thinsp;18/18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e100 (n\\u0026thinsp;=\\u0026thinsp;8/8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e100 (n\\u0026thinsp;=\\u0026thinsp;10/10)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNA\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNA\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNA\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003c/table\\u003e\\n \\u003c/div\\u003e\\n\\u003c/div\\u003e\\n\\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e\\n \\u003cp\\u003eGroup characteristics are presented as mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;standard deviation (SD) for normally distributed data, as median [interquartile range (IQR)] for non-normally distributed data, or as percentage and number in parentheses for dichotomous variables. Depending on distribution, either the independent Student\\u0026apos;s t-test (a), the Mann-Whitney U test (b), Fisher\\u0026apos;s exact test (c) or Chi-squared test (d) was performed, with the corresponding effect sizes Cohen\\u0026apos;s d, Rank-Biserial, Phi coefficient (\\u0026phi;) or Cramer\\u0026apos;s V respectively and each with p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 two-sided. BMI\\u0026thinsp;=\\u0026thinsp;Body Mass Index; cmH\\u003csub\\u003e2\\u003c/sub\\u003eO\\u0026thinsp;=\\u0026thinsp;centimeter water column; ICP\\u0026thinsp;=\\u0026thinsp;intracranial pressure; NA\\u0026thinsp;=\\u0026thinsp;not applicable; PCOS\\u0026thinsp;=\\u0026thinsp;polycystic ovary syndrome\\u003c/p\\u003e\\n \\u003ch2\\u003e3.2. Structural MRI Findings and ICP\\u003c/h2\\u003e\\n \\u003cp\\u003eGroup-level metrics showed no difference in pituitary gland volume or percentage flattening between normal and elevated ICP cohorts (Table \\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). Optic-nerve-sheath and optic-nerve volumes were numerically larger under raised pressure but did not reach statistical significance.\\u003c/p\\u003e\\n \\u003cp\\u003eCorrelation analyses revealed pressure-specific patterns. In the elevated ICP subgroup, right optic-nerve volume increased linearly with ICP (r\\u0026thinsp;=\\u0026thinsp;0.90, p\\u0026thinsp;=\\u0026thinsp;0.005), whereas optic-nerve-sheath volumes no longer tracked pressure, suggesting a structural ceiling. Conversely, in the normal-pressure subgroup, ICP correlated strongly with bilateral sheath volumes (r\\u0026thinsp;\\u0026asymp;\\u0026thinsp;0.80, p\\u0026thinsp;\\u0026asymp;\\u0026thinsp;0.05), but not with optic-nerve size (Table \\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e\\n \\u003cdiv class=\\\"gridtable\\\"\\u003e\\n \\u003ctable id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e\\n \\u003ccaption language=\\\"En\\\"\\u003e\\n \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e\\n \\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\n \\u003cp\\u003eRelationships between ICP and Imaging Parameters\\u003c/p\\u003e\\n \\u003c/div\\u003e\\n \\u003c/caption\\u003e\\n \\u003cthead\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\" colspan=\\\"9\\\"\\u003e\\n \\u003cp\\u003ePartial Correlation\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\" colspan=\\\"9\\\"\\u003e\\n \\u003cp\\u003eAdjusted for Age \\u0026amp; BMI\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\" colspan=\\\"3\\\"\\u003e\\n \\u003cp\\u003eWhole Group\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\" colspan=\\\"3\\\"\\u003e\\n \\u003cp\\u003eICP\\u0026thinsp;\\u0026lt;\\u0026thinsp;25 cmH2O\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\" colspan=\\\"3\\\"\\u003e\\n \\u003cp\\u003eICP\\u0026thinsp;\\u0026ge;\\u0026thinsp;25 cmH2O\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/thead\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eN\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eR\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eP\\u003c/strong\\u003e \\u003cstrong\\u003eValue\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eN\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eR\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eP\\u003c/strong\\u003e \\u003cstrong\\u003eValue\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eN\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eR\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eP\\u003c/strong\\u003e \\u003cstrong\\u003eValue\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eFlattening of the Pituitary Gland [%]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-0.214\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.4436\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.593\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.2149\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-0.119\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.7997\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePituitary Gland Volume [mm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e3\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.008\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.9762\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.169\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.7482\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-0.363\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.4241\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSella Volume [mm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e3\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-0.171\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.5423\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.003\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.9954\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.026\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.9553\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eLeft ONS Volume [mm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e3\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.367\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.1788\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.804\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0.0536*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-0.329\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.4716\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eRight ONS Volume [mm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e3\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.429\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.1104\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.797\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0.0578*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-0.169\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.7167\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eLeft ON Volume [mm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e3\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.34\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.2154\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.591\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.2169\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-0.574\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.1774\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eRight ON Volume [mm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e3\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ea\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.34\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.2153\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.124\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.8148\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.903\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0.0053*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003c/table\\u003e\\n \\u003c/div\\u003e\\n \\u003cp\\u003ePartial correlation analyses were performed using either Pearson rank correlation or Spearman rank correlation (a) depending on value distribution and adjusted for the potential confounder age and BMI. Each test was performed with p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 two-sided.\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003cdiv id=\\\"Sec12\\\" class=\\\"Section2\\\"\\u003e\\n \\u003ch2\\u003e3.3. Endocrine Correlates of Pituitary Morphology\\u003c/h2\\u003e\\n \\u003cp\\u003eAfter adjustment for age and BMI, pituitary size correlated positively with TSH only in the normal ICP group (r\\u0026thinsp;=\\u0026thinsp;0.88, p\\u0026thinsp;=\\u0026thinsp;0.020; Fig. \\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003ea), an association that disappeared and reversed under elevated pressure (Fig. \\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eb). No meaningful relationships emerged for LH, FSH, ACTH, or GH (Table \\u003cspan class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e).\\u003c/p\\u003e\\n \\u003cdiv class=\\\"gridtable\\\"\\u003e\\n \\u003ctable id=\\\"Tab3\\\" border=\\\"1\\\"\\u003e\\n \\u003ccaption language=\\\"En\\\"\\u003e\\n \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 3\\u003c/div\\u003e\\n \\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\n \\u003cp\\u003eRelationships between Pituitary Gland associated hormones and Pituitary Gland Volume [mm\\u003csup\\u003e3\\u003c/sup\\u003e]\\u003c/p\\u003e\\n \\u003c/div\\u003e\\n \\u003c/caption\\u003e\\n \\u003cthead\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\" rowspan=\\\"4\\\"\\u003e\\n \\u003cp\\u003eLaboratory Parameter\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\" colspan=\\\"6\\\"\\u003e\\n \\u003cp\\u003ePartial Correlation\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\" colspan=\\\"6\\\"\\u003e\\n \\u003cp\\u003eAdjusted for Age \\u0026amp; BMI\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\" colspan=\\\"3\\\"\\u003e\\n \\u003cp\\u003eICP\\u0026thinsp;\\u0026lt;\\u0026thinsp;25 cmH2O\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\" colspan=\\\"3\\\"\\u003e\\n \\u003cp\\u003eICP\\u0026thinsp;\\u0026ge;\\u0026thinsp;25 cmH2O\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eN\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eR\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eP\\u003c/strong\\u003e \\u003cstrong\\u003eValue\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eN\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eR\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eP\\u003c/strong\\u003e \\u003cstrong\\u003eValue\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/thead\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eTSH [\\u0026micro;U/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.882\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0.02*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.478\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.2784\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eLH [U/l]\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003ea\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.218\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.6782\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.292\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.5246\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eFSH [mIU/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.69\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.1296\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.594\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.1597\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eACTH [pg/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.037\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.945\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.123\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.8163\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eGH [ng/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.148\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.7792\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.056\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.9052\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003ctfoot\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"7\\\"\\u003ePartial correlation analyses were performed using either Pearson rank correlation or Spearman rank correlation (a) depending on value distribution and adjusted for the potential confounder age and BMI. Each test was performed with p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 two-sided.\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tfoot\\u003e\\n \\u003c/table\\u003e\\n \\u003c/div\\u003e\\n \\u003cp\\u003e\\u003cem\\u003e3.4. Hormonal Alterations and Association with ICP\\u003c/em\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003eWhile hormone levels outside reference ranges were common, group differences were limited (Supplementary Table S3). ANCOVA and GLM analyses revealed significantly lower serum IGF-1 and testosterone concentrations in participants with elevated ICP (IGF-1: p = 0.039; testosterone: p = 0.027; Table S4).\\u003c/p\\u003e\\n \\u003cp\\u003ePartial correlation analyses adjusted for age, BMI, and pituitary volume demonstrated that ICP correlated positively with TSH (r = 0.628, p = 0.016) and negatively with GH (r = -0.602, p = 0.023; Table 4, Figure 3). No other hormone showed significant associations.\\u003c/p\\u003e\\n \\u003cp\\u003eThese findings suggest pressure-related alterations in the thyroid and somatotropic axes in IIH.\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eTable 4\\u003c/strong\\u003e Relationships between ICP and Serum Levels of Laboratory Parameters\\u003c/p\\u003e\\n \\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"638\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eLaboratory Parameter\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eDescriptive Statistics\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eWhole Group\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"3\\\" style=\\\"width: 265px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePartial Correlation\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAdjusted for Age, BMI \\u0026amp; Pituitary Gland Volume\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eN\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eR\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eP\\u003c/em\\u003e\\u003c/strong\\u003e\\u003cstrong\\u003e\\u0026nbsp;Value\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eTSH [\\u0026mu;U/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e1.6 \\u0026plusmn; 0.7 (n = 18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e0.628\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0.016*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003efT3 [pg/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e2.8 \\u0026plusmn; 0.4 (n = 17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e16\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e-0.056\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e0.856\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003efT4 [ng/dl]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e1.2 \\u0026plusmn; 0.2 (n = 18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e-0.505\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e0.065\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eLH [U/l]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e6.8 [5.3, 14.4]\\u0026nbsp;(n = 18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e-0.133\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e0.652\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eFSH [mIU/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e5.8 [4.4, 7.3] (n = 18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e0.125\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e0.671\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eDHEAS [\\u0026mu;g/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e1.5 [0.8, 1.9] (n = 18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e-0.417\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e0.138a\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eTestosterone [ng/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e0.2 [0.2, 0.4]\\u0026nbsp;(n = 18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e-0.3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e0.298\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eEstradiol [pg/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e75.8 \\u0026plusmn; 56.0 (n = 18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e0.181\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e0.535\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAndrostenedione [ng/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e1.5 [0.8, 2.3] (n = 18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e-0.277\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e0.338\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eProlactin [ng/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e18.4 [16.2, 26.6]\\u0026nbsp;(n = 18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e0.193\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e0.508\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eACTH [pg/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e19.2 [13.9, 44.3] (n = 17)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e16\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e0.373\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e0.209\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eCortisol [\\u0026mu;g/dl]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e13.7 \\u0026plusmn; 4.7 (n = 18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e-0.317\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e0.270\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eGH [ng/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e0.1 [0.1, 0.3] (n = 18)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e-0.602\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e0.023\\u003csup\\u003ea\\u003c/sup\\u003e*\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 170px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eIGF1 [ng/ml]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 203px;\\\"\\u003e\\n \\u003cp\\u003e161.0 \\u0026plusmn; 61.7 (n = 16)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 76px;\\\"\\u003e\\n \\u003cp\\u003e15\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 85px;\\\"\\u003e\\n \\u003cp\\u003e-0.372\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e0.234\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003c/table\\u003e\\n \\u003cp\\u003eAll results are displayed as mean \\u0026plusmn; standard deviation (SD) or median [interquartile range (IQR)] in case of non-normal distribution. Partial correlation analyses were performed using either Pearson rank correlation or Spearman rank correlation (a) depending on value distribution and adjusted for the potential confounders age, BMI, and pituitary gland volume. Each test was performed with p \\u0026lt; 0.05 two-sided. ACTH = adrenocorticotropic hormone; cmH\\u003csub\\u003e2\\u003c/sub\\u003eO = centimeter water column; DHEAS = dehydroepiandrosterone sulphate; FSH = follicle stimulating hormone; fT3 = free triiodothyronine; fT4 = free thyroxine; GH = growth hormone; ICP = intracranial pressure; IGF-1 = insulin-like growth factor 1; LH = luteinising hormone; TSH = thyroid stimulating hormone; 95% CI.\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cem\\u003e3.5 Predictive Modeling of ICP\\u003c/em\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003eUnivariate linear regression model revealed serum TSH as a significant positive predictor of ICP (\\u0026beta; = 4.83 \\u0026plusmn; 1.81, t(16) = 2.68, p = 0.017, R\\u0026sup2; = 0.31), whereas GH showed a non-significant inverse trend (\\u0026beta; = -1.02 \\u0026plusmn; 0.62, t(16) = 2.68, p = 0.122, R\\u0026sup2; = 0.14). Residual diagnostics exposed non-normality, heteroscedasticity and non-linear patterns (Supplementary figures S1-S4), prompting a Box\\u0026ndash;Cox transformation of ICP and z-standardisation of predictors. Robust Huber regression then confirmed TSH (\\u0026beta; = 0.071 \\u0026plusmn; 0.02, p \\u0026lt; 0.001) and GH (\\u0026beta; = -0.024 \\u0026plusmn; 0.01, p = 0.041) as independent, oppositely directed determinants, explaining approximately 31% of ICP variance with consistent 10-fold cross-validation performance (mean squared error = 0.012). These findings suggest that TSH and GH provide complementary, biologically plausible markers for non-invasive ICP estimation in IIH.\\u003c/p\\u003e\\n\\u003c/div\\u003e\"},{\"header\":\"4. Discussion\",\"content\":\"\\u003cp\\u003eThis study demonstrates a multimodal link between elevated ICP, anterior pituitary hormone alterations, and structural brain changes in women with IIH. By combining endocrine profiling and quantitative MRI, we demonstrated that elevated ICP is significantly associated with alterations in thyroid and somatotropic axes, and that these changes are accompanied by morphological adaptations of the pituitary gland and surrounding structures.\\u003c/p\\u003e\\n\\u003cp\\u003eOur findings highlight the thyroid axis as a key hormonal system affected by increased ICP. TSH levels showed a significant positive correlation with ICP (r = 0.628, p = 0.0163) and emerged as a robust predictor in both standard (β\\u0026nbsp;= 4.8348, SE = 1.808, p = 0.017,\\u0026nbsp;R² = 0.309) and robust regression models (coefficient = 0.070817, SE = 0.020, p \\u0026lt; 0.001). These observations build upon earlier case reports suggesting a relationship between IIH and thyroid disorders, including hypo- and hyperthyroidism as well as subacute thyroiditis [5-8, 22-24]. The elevated rate of thyroxine supplementation in our sample (13% in normal ICP vs. 30% in elevated ICP) exceeds rates reported in population studies (5-12%) [25-27], potentially reflecting female predominance and elevated BMI [28, 29].\\u003c/p\\u003e\\n\\u003cp\\u003ePrior cohort studies yielded inconsistent findings regarding thyroid involvement in IIH. Giuseffi et al. (1991) [2] reported equal prevalence of thyroid disease in IIH patients and controls (2%), whereas KesKin et al. (2020) [30] reported a combined diabetes and thyroid disease rate of 19% in IIH. Recent work by Prabhat et al. (2024) [12] demonstrated normalization of elevated TSH following ICP reduction, further supporting the association between ICP and thyroid regulation.\\u003c/p\\u003e\\n\\u003cp\\u003eMechanistically, TSH receptors and thyroid hormone transporters are expressed in the choroid plexus, the main site of CSF production, where aquaporins and transthyretin mediate hormone and fluid transport [16,18,31,32]. These mechanisms may partly explain the observed link between thyroid dysfunction and structural MRI findings in IIH.\\u003c/p\\u003e\\n\\u003cp\\u003eThe somatotropic axis was also implicated. Serum GH levels correlated negatively with ICP (r = -0.602, p = 0.023), and became a significant predictor in the Huber regression model (coefficient = -0.023842, SE = 0.011, p = 0.041). While GH did not reach significance in the initial model, our findings align with prior reports linking GH deficiency to primary empty sella, present in over half of our cohort, and frequently observed in IIH [15].\\u003c/p\\u003e\\n\\u003cp\\u003eWhile true GH deficiency was unlikely in our cohort-given normal IGF-1 levels in all patients with elevated ICP, IGF-1 concentrations were significantly lower in the elevated ICP group (137.7\\u0026nbsp;±\\u0026nbsp;46.4 ng/mL vs. 205.8\\u0026nbsp;±\\u0026nbsp;62.4 ng/mL; p = 0.039,\\u0026nbsp;R² = 0.604), and testosterone was also reduced (0.2 ±\\u0026nbsp;0.1 ng/mL vs. 0.4\\u0026nbsp;±\\u0026nbsp;0.2 ng/mL; p = 0.027,\\u0026nbsp;R² = 0.572). These findings may reflect functional suppression of the somatotropic and gonadal axes under mechanical compression or metabolic stress.\\u003c/p\\u003e\\n\\u003cp\\u003ePrevious literature supports a role for GH/IGF-1 in CSF regulation. GH treatment has been associated with secondary IIH [33], while octreotide, a somatostatin analogue, has improved IIH symptoms [34]. GH/IGF-1 and somatostatin receptor expression in choroid plexus and arachnoid granulations suggest direct endocrine modulation of CSF dynamics [17, 35].\\u003c/p\\u003e\\n\\u003cp\\u003eOur volumetric MRI findings parallel these hormonal alterations. Although pituitary volumes were not significantly different\\u0026nbsp;(normal ICP: 889.5 ± 174.5 mm³ vs. increased ICP: 819.6 ± 125.3 mm³; p = 0.353), pituitary flattening and empty sella were more frequent in elevated ICP (complete empty sella in 44% vs. 63%, p = 0.797; mean flattening 43.3 ± 25.5% vs. 56.3 ± 13.0%, p = 0.217), suggesting mechanical distortion rather than atrophy. A subgroup correlation analysis identified a strong positive association between TSH and pituitary volume in the normal ICP group (r = 0.882, p = 0.020), but not in the elevated ICP group (r = -0.478, p = 0.278), suggesting impaired glandular adaptation under sustained pressure.\\u003c/p\\u003e\\n\\u003cp\\u003eONS distension is a well-established marker of elevated ICP. In our study, ONS volumes correlated with ICP only in the normal ICP group (left: r = 0.804, p = 0.054; right: r = 0.797, p = 0.058), but not in the elevated group ((right ONS: r = -0.169, p = 0.717), where a ceiling effect may limit further distension. This phenomenon may contribute to decoupling between ICP and imaging parameters, and potentially affect surrounding structures such as the pituitary.\\u003c/p\\u003e\\n\\u003cp\\u003eAdditional findings included mild hyperprolactinemia (50% in normal ICP, 30% in elevated ICP), consistent with prior reports of stalk compression and altered dopaminergic inhibition in IIH [36, 37]. Although group differences were not significant, 20% of patients with elevated ICP had concurrent PCOS, and one exhibited elevated prolactin. Gonadotropic and adrenal hormone levels (e.g., ACTH: r = 0.373, p = 0.209; DHEAS: r = -0.417, p = 0.138) showed moderate but non-significant associations with ICP.\\u003c/p\\u003e\\n\\u003cp\\u003eTaken together, our findings suggest that IIH may involve a pressure-induced neuroendocrine dysregulation, primarily affecting the thyroid and somatotropic axes. Quantitative MRI provides structural correlates that reflect this dysfunction, particularly in the pituitary and ONS. Our data support the integration of endocrine profiling and neuroimaging in the diagnostic and monitoring process of IIH.\\u003c/p\\u003e\\n\\u003cp\\u003eThis study has limitations. ICP was measured at a single time point, and the sample size was small. GH status was not assessed via stimulation testing. Obesity, which can independently affect hormone levels, was present in nearly all participants. Due to ethical constraints, a matched control group could not be included. Future studies should validate these results in larger cohorts, using longitudinal designs, dynamic endocrine testing, and multimodal imaging. The predictive role of ONS and pituitary morphology in treatment outcomes warrants further investigation. Clinically, our findings emphasize the need to evaluate endocrine status, particularly thyroid and somatotropic function, in patients with IIH, especially in the presence of empty sella.\\u003c/p\\u003e\\n\\u003cp\\u003eIn conclusion, sustained ICP elevation in IIH appears to induce measurable endocrine and structural brain changes. Hormonal markers particularly TSH and GH together with MRI-based indicators such as pituitary flattening and ONS distension, may serve as complementary tools for improving diagnostic precision and disease monitoring.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eClinical Implications\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eIn conclusion\\u003c/strong\\u003e, sustained ICP elevation in women with IIH is associated with measurable endocrine dysfunction, particularly involving TSH and GH, as well as with distinct structural brain changes visible on MRI. Combining quantitative neuroimaging with focused endocrine assessment may enhance diagnostic precision, help identify individuals at risk for persistent disease activity, and support more individualized treatment strategies.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003ch2\\u003eEthics Approval\\u003c/h2\\u003e\\u003cp\\u003e The study was approved by the local ethics committee (Approval No. 383/17) and conducted in accordance with the Declaration of Helsinki. All subjects provided written informed consent prior to inclusion in the study, and any identifying details have been omitted to protect their privacy.\\u003c/p\\u003e\\u003c/p\\u003e\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\u003cp\\u003eConceptualization: Z.B.,R.C., A.R., U.W., C.K. Methodology: Z.B., B.D.W., R.C., W.F., B. W., U.W., C.K. Formal analysis and investigation: Z.B., B.D.W., R.C., W.F., C.F., M.J., M.M., A.H.S., F.M.S., B.W., C.S., M.W., B.K., A.R., J.L., U.W., C.K.Writing - original draft preparation: Z.B., B.D.W., R.C., M.M., A.H.S., B.W., C.S., M.W., B.K., J.L., C.K. Z.B., C.K., R.C., B.W., B.D.W., M.M., A.H.S. wrote the main manuscript text and Z.B., C.K., C.S., M.W., R.C., B.K., J.L. prepared figures and tables. Writing - review and editing: Z.B., B.D.W., W.F., R.C., C.F., M.J., M.M., A.H.S., F.M.S., B.W., C.S., M.W., B.K., A.R., J.L., U.W., C.K. Resources: Z.B., B.W., A.R., U.W., C.K.Supervision: Z.B., B.W., A.R., U.W., C.K.All authors reviewed the manuscript.\\u003c/p\\u003e\\u003ch2\\u003eAcknowledgement\\u003c/h2\\u003e\\u003cp\\u003eI thank the German Society of Intracranial Hypertension for their support in conducting the study.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eFriedman DI, Liu GT, Digre KB. 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PMID: 26966604; PMCID: PMC4757697\\u003c/li\\u003e\\n\\u003cli\\u003eBoonyatarp K, Samintharapanya K, Vongchaiudomchoke T, Wachiraphansakul N. Subacute thyroiditis presenting as idiopathic intracranial hypertension. Case Rep Endocrinol. 2021:9203319. https://doi.org/10.1155/2021/9203319. PMID: 34966564; PMCID: PMC8712176\\u003c/li\\u003e\\n\\u003cli\\u003ePrabhat N, Kaur K, Takkar A, Ahuja C, Katoch D, Goyal M, Dutta P, Bhansali A, Lal V. Pituitary dysfunction in idiopathic intracranial hypertension: an analysis of 80 patients. Can J Neurol Sci. 2024;51(2):265-71. https://doi.org/10.1017/cjn.2023.42. PMID: 37014102.\\u003c/li\\u003e\\n\\u003cli\\u003eYuh WT, Zhu M, Taoka T, Quets JP, Maley JE, Muhonen MG, Schuster ME, Kardon RH. MR imaging of pituitary morphology in idiopathic intracranial hypertension. J Magn Reson Imaging 2000;12(6):808-13. https://doi.org/10.1002/1522-2586(200012)12:6\\u0026lt;808::aid-jmri3\\u0026gt;3.0.co;2-n. PMID: 11105018.\\u003c/li\\u003e\\n\\u003cli\\u003eBidot S, Saindane AM, Peragallo JH, Bruce BB, Newman NJ, Biousse V. Brain Imaging in Idiopathic Intracranial Hypertension\\u003cem\\u003e. \\u003c/em\\u003e\\u003cem\\u003eJournal of Neuro-Ophthalmology\\u003c/em\\u003e 2015;35(4):400\\u0026ndash;411. https://doi.org/10.1097/WNO.0000000000000255. PMID: 26324201.\\u003c/li\\u003e\\n\\u003cli\\u003eAuer MK, Stieg MR, Crispin A, Sievers C, Stalla GK, Kopczak A. Primary empty sella syndrome and the prevalence of hormonal dysregulation. Dtsch Arztebl Int. 2018;115(7):99-105. https://doi.org/10.3238/arztebl.2018.0099. PMID: 29510819; PMCID: PMC5842341.\\u003c/li\\u003e\\n\\u003cli\\u003eBoedtkjer E, Praetorius J, F\\u0026uuml;chtbauer EM, Aalkjaer C. Antibody-independent localization of the electroneutral Na+-HCO3- cotransporter NBCn1 (slc4a7) in mice. Am J Physiol Cell Physiol. 2008;294(2):C591-603. https://doi.org/10.1152/ajpcell.00281.2007. PMID: 18077606.\\u003c/li\\u003e\\n\\u003cli\\u003eKatz SE, Klisovic DD, O\\u0026apos;Dorisio MS, Lynch R, Lubow M. Expression of somatostatin receptors 1 and 2 in human choroid plexus and arachnoid granulations: implications for idiopathic intracranial hypertension. Arch Ophthalmol. 2002;120(11):1540-3. https://doi.org/10.1001/archopht.120.11.1540. PMID: 12427069.\\u003c/li\\u003e\\n\\u003cli\\u003eCrisanti P, Omri B, Hughes E, Meduri G, Hery C, Clauser E, Jacquemin C, Saunier B. The expression of thyrotropin receptor in the brain. Endocrinology 2001;142(2):812-22. https://doi.org/10.1210/endo.142.2.7943. PMID: 11159854.\\u003c/li\\u003e\\n\\u003cli\\u003eFriedman DI, Jacobson DM. Diagnostic criteria for idiopathic intracranial hypertension. Neurology 2002;59(10):1492-5. https://doi.org/10.1212/01.wnl.0000029570.69134.1b. PMID: 12455560.\\u003c/li\\u003e\\n\\u003cli\\u003eThe Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2003;81(1):19-25. https://doi.org/10.1016/j.fertnstert.2003.10.004.\\u003c/li\\u003e\\n\\u003cli\\u003eFris\\u0026eacute;n L. Swelling of the optic nerve head: a staging scheme. J Neurol Neurosurg Psychiatry 1982;45(1):13-8. https://doi.org/10.1136/jnnp.45.1.13. PMID: 7062066; PMCID: PMC491259.\\u003c/li\\u003e\\n\\u003cli\\u003eBoonyatarp K, Samintharapanya K, Vongchaiudomchoke T, Wachiraphansakul N.Subacute thyroiditis presenting as idiopathic intracranial hypertension. Case Rep Endocrinol. 2021;2021:9203319. https://doi.org/10.1155/2021/9203319. PMID: 34966564; PMCID: PMC8712176.\\u003c/li\\u003e\\n\\u003cli\\u003eCoutinho E, Silva AM, Freitas C, Santos E. Graves\\u0026apos; disease presenting as pseudotumor cerebri: a case report. J Med Case Rep. 2011;5:68. https://doi.org/10.1186/1752-1947-5-68. PMID: 21324147; PMCID: PMC3049746.\\u003c/li\\u003e\\n\\u003cli\\u003eDatta SG, S L SR, Dhananjaya MS, Tamminedi N, Nayak V, Kodapala S, Sarathi V. Idiopathic intracranial hypertension following levothyroxine replacement therapy: systematic review and a case report. Indian J Endocrinol Metab. 2023;27(1):17-24. https://doi.org/10.4103/ijem.ijem_439_22. PMID: 37215264; PMCID: PMC10198199.\\u003c/li\\u003e\\n\\u003cli\\u003eKhattak RM, Ittermann T, Nauck M, Below H, V\\u0026ouml;lzke H. Monitoring the prevalence of thyroid disorders in the adult population of Northeast Germany. Popul Health Metr. 2016;14:39. https://doi.org/10.1186/s12963-016-0111-3. PMID: 27833458; PMCID: PMC5101821.\\u003c/li\\u003e\\n\\u003cli\\u003eKiel S, Ittermann T, V\\u0026ouml;lzke H, Chenot JF, Angelow A. Frequency of thyroid function tests and examinations in subjects of a population-based study. BMC Health Serv Res. 2020;20(1):70. https://doi.org/10.1186/s12913-020-4910-7. PMID: 32000765; PMCID: PMC6993310.\\u003c/li\\u003e\\n\\u003cli\\u003eViniol A, B\\u0026ouml;sner S, Baum E, Donner-Banzhoff N. Forgotten drugs: long-term prescriptions of thyroid hormones-a cross-sectional study. Int J Gen Med. 2013;6:32934. https://doi.org/10.2147/IJGM.S43187. PMID: 23641158; PMCID: PMC3639717.\\u003c/li\\u003e\\n\\u003cli\\u003eRuhla S, Arafat AM, Osterhoff M, Weickert MO, Mai K, Spranger J, Sch\\u0026ouml;fl C, Pfeiffer AF, M\\u0026ouml;hlig M. Levothyroxine medication is associated with adiposity independent of TSH. Exp Clin Endocrinol Diabetes 2012;120(6):351-4. https://doi.org/10.1055/s-0032-1312599. PMID: 22639395.\\u003c/li\\u003e\\n\\u003cli\\u003eWouters HJCM, Slagter SN, Muller Kobold AC, van der Klauw MM, Wolffenbuttel BHR. Epidemiology of thyroid disorders in the Lifelines Cohort Study (the Netherlands). PLoS One 2020;15(11):e0242795. https://doi.org/10.1371/journal.pone.0242795. PMID: 33237973; PMCID: PMC7688129.\\u003c/li\\u003e\\n\\u003cli\\u003eKesKın AO, İdıman F, Kaya D, Bırcan B. Idiopathic intracranial hypertension: etiological factors, clinical features, and prognosis. Noro Psikiyatr Ars. 2018;57(1):23-6. https://doi.org/10.5152/npa.2017.12558. PMID: 32110146; PMCID: PMC7024819.\\u003c/li\\u003e\\n\\u003cli\\u003eMariani LH, Berns JS. The renal manifestations of thyroid disease. J Am Soc Nephrol. 2012;23(1):22-6. https://doi.org/10.1681/ASN.2010070766. PMID: 22021708.\\u003c/li\\u003e\\n\\u003cli\\u003eRichardson SJ, Wijayagunaratne RC, D\\u0026apos;Souza DG, Darras VM, Van Herck SL. Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and thyroid hormone transmembrane transporters. Front Neurosci. 2015;9:66. https://doi.org/10.3389/fnins.2015.00066. PMID: 25784853; PMCID: PMC4347424.\\u003c/li\\u003e\\n\\u003cli\\u003eLoukianou E, Tasiopoulou A, Demosthenous C, Brouzas D. Pseudotumor cerebri in a child with idiopathic growth hormone insufficiency two months after initiation of recombinant human growth hormone treatment. Case Rep Ophthalmol Med. 2016;2016:4756894. https://doi.org/10.1155/2016/4756894. PMID: 26966604; PMCID: PMC4757697.\\u003c/li\\u003e\\n\\u003cli\\u003ePanagopoulos GN, Deftereos SN, Tagaris GA, Gryllia M, Kounadi T, Karamani O, Panagiotidis D, Koutiola-Pappa E, Karageorgiou CE, Piadites G. Octreotide: a therapeutic option for idiopathic intracranial hypertension. Neurol Neurophysiol Neurosci. 2007;10:1. PMID: 17700925.\\u003c/li\\u003e\\n\\u003cli\\u003eDeijen JB, Arwert LI. Impaired quality of life in hypopituitary adults with growth hormone deficiency: can somatropin replacement therapy help? Treat Endocrinol. 2006;5(4):243-50. https://doi.org/10.2165/00024677-200605040-00005. PMID: 16879003.\\u003c/li\\u003e\\n\\u003cli\\u003eDe Marinis L, Bonadonna S, Bianchi A, Maira G, Giustina A. Primary empty sella. J Clin Endocrinol Metab. 2005;90(9):5471-7. https://doi.org/10.1210/jc.2005-0288. PMID: 15972577.\\u003c/li\\u003e\\n\\u003cli\\u003eAruna P, Sowjanya B, Reddy PA, Krishnamma M, Naidu JN. Partial empty sella syndrome: a case report and review. Indian J Clin Biochem. 2014;29(2):253-6. https://doi.org/10.1007/s12291-013-0369-1. PMID: 24757313; PMCID: PMC3990803.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Idiopathic intracranial hypertension, optic nerve sheath, hormone axes, growth hormone, thyroid stimulating hormone, intracranial pressure\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-7177945/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-7177945/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003ePurpose:\\u003c/strong\\u003e To investigate the relationship between intracranial pressure (ICP), anterior pituitary hormones, and structural brain changes in women with idiopathic intracranial hypertension (IIH).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods:\\u003c/strong\\u003eEighteen women with therapy-refractory IIH underwent lumbar puncture, endocrine assessment, and high-resolution brain MRI. Serum levels of pituitary hormones were correlated with ICP and radiological parameters including pituitary volume, flattening, and optic nerve sheath (ONS) volume. Group comparisons, partial correlations, and regression models were used to evaluate associations.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults:\\u003c/strong\\u003e ICP was significantly associated with higher thyroid-stimulating hormone (TSH) levels (\\u003cem\\u003er\\u003c/em\\u003e = 0.628, \\u003cem\\u003ep\\u003c/em\\u003e = 0.0163), which emerged as a robust predictor of ICP in both linear (β = 4.8348, \\u003cem\\u003ep\\u003c/em\\u003e = 0.017) and Huber regression models (coefficient = 0.070817, \\u003cem\\u003ep\\u003c/em\\u003e \\u0026lt; 0.001). Growth hormone (GH) was negatively associated with ICP (\\u003cem\\u003er \\u003c/em\\u003e= -0.602, \\u003cem\\u003ep\\u003c/em\\u003e = 0.023) and reached significance in robust modeling (coefficient = -0.023842, \\u003cem\\u003ep\\u003c/em\\u003e = 0.041). Insulin-like Growth Factor 1 (IGF-19 and testosterone levels were significantly lower in patients with elevated ICP (IGF-1: \\u003cem\\u003ep \\u003c/em\\u003e= 0.039; testosterone: \\u003cem\\u003ep\\u003c/em\\u003e = 0.027). Volumetric MRI revealed no group difference in pituitary volume, but flattening and complete empty sella were more frequent in patients with elevated ICP. ONS volumes correlated with ICP only in the normal ICP group (left: \\u003cem\\u003er\\u003c/em\\u003e = 0.804, \\u003cem\\u003ep\\u003c/em\\u003e = 0.054; right: \\u003cem\\u003er\\u003c/em\\u003e = 0.797, \\u003cem\\u003ep \\u003c/em\\u003e= 0.058), suggesting a ceiling effect at higher pressures.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion:\\u003c/strong\\u003e Elevated ICP in IIH is linked to functional changes in the thyroid and somatotropic axes, as well as structural alterations in the pituitary gland and ONS. Combining quantitative MRI with endocrine profiling may improve diagnostic accuracy, help identify patients at risk, and support individualized treatment strategies.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Structural MRI Biomarkers of Intracranial Pressure in IIH: Linking Optic Nerve Sheath, Pituitary Morphology, and Hormonal Changes\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-08-07 04:16:49\",\"doi\":\"10.21203/rs.3.rs-7177945/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"ff200b92-2305-4a32-b250-5f24dce5221c\",\"owner\":[],\"postedDate\":\"August 7th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-02-02T16:02:12+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-7177945\",\"link\":\"https://doi.org/10.1007/s00062-026-01618-8\",\"journal\":{\"identity\":\"clinical-neuroradiology\",\"isVorOnly\":false,\"title\":\"Clinical Neuroradiology\"},\"publishedOn\":\"2026-01-27 15:58:31\",\"publishedOnDateReadable\":\"January 27th, 2026\"},\"versionCreatedAt\":\"2025-08-07 04:16:49\",\"video\":\"\",\"vorDoi\":\"10.1007/s00062-026-01618-8\",\"vorDoiUrl\":\"https://doi.org/10.1007/s00062-026-01618-8\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-7177945\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-7177945\",\"identity\":\"rs-7177945\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}