Bicytopenia - a rare hematological manifestation secondary to hypothalamic dysfunction in a case of craniopharyngioma: A case report

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These complications often require long-term follow-up and periodic reassessment. Case Presentation: We present the case of an 11-year-old girl with craniopharyngioma who, following surgical resection and radiotherapy, developed multiple pituitary hormone deficiencies, adipsic diabetes insipidus, hyperphagia, cognitive disturbances, and delayed puberty. Unique to this case was the occurrence of cyclic bicytopenia mirroring thermal dysregulation episodes, in the absence of an identifiable hematological cause. As body temperature normalized, hematological parameters improved, suggesting a potential link between thermal dysregulation and cytopenia. Management involved hormone replacement, fluid and sodium balance monitoring, topical estrogen therapy, and lifestyle interventions. We address and review the mechanisms proposed for cytopenias related to thermoregulation and propose possible mechanisms for the other findings while discussing the therapeutic challenges in managing such complex cases. Conclusion: Postoperative management of craniopharyngioma is often complicated by involvement of multiple hypothalamic domains. This case emphasizes the importance of recognizing uncommon and underreported manifestations, such as thermoregulation-associated cytopenia and adipic diabetes insipidus. Early diagnosis and multidisciplinary management are essential for improving outcomes and long-term quality of life in affected children. craniopharyngioma adipsic diabetes insipidus bicytopenia thermal dysregulation hypothalamic dysfunction Figures Figure 1 Figure 2 Background Hypothalamus plays a central role in regulation of pituitary hormones, thirst - water balance, feeding- energy expenditure, autonomic system, somatic behavior, body temperature and sleep wake cycle [ 1 ]. So, abnormalities of the same should be expected in patients with tumors within or encroaching on the hypothalamus or operative damage to hypothalamus. However, clinicians usually emphasize on the secondary effect of these tumors on pituitary hormone secretion. Disturbances in water and energy balance and disordered thermoregulation are uncommonly reported. Disturbances in water and energy balance can lead to disorders such as electrolyte imbalance and hypothalamic obesity [ 2 , 3 ]. Abnormal thermoregulation can have potentially life-threatening consequences. Hypothermia may present with muscle dysfunction, impaired mental function, respiratory depression, arrhythmias, and hypotension, which can progress to coma or cardiac arrest. Hyperthermia may present with flushing, sweating, tachycardia, fatigue and headache, which can progress to muscle weakness and cramps, hypotension, confusion, agitation, delirium, seizures, and coma [ 4 ]. Additionally, disordered thermal regulation can rarely be associated with hematological abnormalities. Both therapeutic and accidental hypothermia have been associated with thrombocytopenia which may resolve with rewarming [ 5 ]. We wish to report a child of craniopharyngioma who presented postoperatively with various endocrine and non-endocrine abnormalities in the form of multiple hormonal deficiencies, adipsic diabetes insipidus (DI), hyperphagia, obesity and hematological abnormalities. Case report A 11-year girl child developed headache for 1 month and impaired vision of both eyes. There was no history of head injury, vomiting or seizures. There was no history of excess weight gain, increased thirst or frequency of urination, change in behavior or drop in scholastic performance. She had not attained menarche. On examination, she weighed 46 kilograms, and height was 150 cm (body mass index – 20.44 kg/m 2 ). Axillary temperature measured at various visits to hospital ranged between 35.5 and 36.2º C. Her tanner staging for breast and pubic hair were 4 and 1 respectively. There was no axillary hair. Magnetic resonance imaging of brain showed a well-defined thick walled multicystic lesion with internal proteinaceous contents arising from sellar-suprasellar area measuring 3.9×4.5 cm with obstructive hydrocephalus. Preoperative complete blood counts were within normal limits (Hemoglobin − 11.3 g/dL, total count – 11,980/µL and platelets – 2.25 lakh/µL). She underwent craniotomy with excision of lesion and post operatively, received radiotherapy. Vision had improved postoperatively. Histopathology was consistent with adamantinomatous craniopharyngioma. Upon post operative follow up she was detected to have multiple pituitary hormone deficiencies (central hypothyroidism, adrenal insufficiency, central DI) for which she was started on specific hormonal replacement therapy. 7 months post-surgery she developed severe anemia with mild thrombocytopenia (Table 1 ) which improved with blood transfusion but recurred. Further in the follow up, 1 year later, she developed severe anemia and thrombocytopenia. Initial evaluation revealed no identifiable cause of anemia (Table 2 ). Hence diagnosis of thermal dysregulation leading to anemia was considered. She was asked to strictly avoid extremes of temperature and monitor her fluid balance. After 2–3 weeks, her counts normalized suggestive of response to strict thermal regulation and fluid balance. Post operatively, she was also found to have polyuria, and recurrent episodes of hypernatremia (serum sodium values ranging from 154 mmol/L to 170 mmol/L) with limited thirst sensation. Hence a diagnosis of adipsic central DI was considered. She was managed with oral desmopressin with doses ranging from 200 to 300 µg/day divided in 2–3 doses per day. She was advised to avoid dehydration and adjust total daily fluid intake to match the urinary output. Serial monitoring of serum sodium, body weight monitoring and titration of oral desmopressin at each follow up visit was done to maintain serum sodium within normal limits and she responded (serum sodium values ranging from 142 mmol/L to 149 mmol/L). 1 ½ years post-surgery she developed right sided hemiparesis and computed tomography of brain showed left middle cerebral artery territory infarct. Magnetic resonance angiography of neck vessels was normal. She was continued on desmopressin with serial serum sodium and input-output monitoring. On follow up visits it was also noticed that there was non progression of puberty. Upon evaluation her serum follicle stimulating hormone was 2.1mIU/ml, Luteinizing hormone 0.78 mIU/ml and estradiol < 10 pg/ml. In view of prior episode of stroke, topical preparation in the form of 17 beta Estradiol 0.06% gel application in gradually increasing doses was preferred. She also had a rapid gain in body weight which peaked at 63 kg (body mass index 27.6 kg/m 2 and > 97th percentile). It was evident from the mother’s statement that her appetite was increased. She was advised to restrict her calorie intake and screen time, and she responded subsequently with a weight loss of 4 kg. She was also noted to have short term memory loss (including forgetting common words while speaking) and exhibiting apathy. She was followed up on regular basis with monitoring of temperature and other vital parameters, anthropometric measures, pubertal progression, hydration status, input output, serum sodium and hormonal levels. Postoperative imaging is presented in Figs. 1 and 2. Table 1 Complete Blood Count Parameters noted at various visits during follow up 12/1 1/20 19 15/0 8/20 20 13/1 1/20 20 17/0 3/20 21 25/0 8/20 21 06/0 9/20 21 24/0 2/20 22 06/0 4/20 22 11/0 6/20 22 10/1 1/20 22 09/0 2/20 23 Hemoglobin (g/dl) 6 5.4 7.7 8.4 5.1 8.9 8.9 10.4 5.7 9.4 9.8 Total leukocyte count (cells/µL) 3200 5200 6400 9760 8200 7470 1926 0 9730 9010 9100 Platelet count (lakh cells/µL) 1.17 1.79 1.4 1.5 1.32 1.25 1.56 0.75 1.65 1.2 Mean corpuscular volume (MCV) (fL) 82.9 93.8 82 102 102. 5 93 94.1 Mean corpuscular hemoglobin (MCH) (pg) 24 24 25 Mean corpuscular hemoglobin concentration (MCHC) (g/dL) 30 23 27 Table 2 Laboratory tests performed during evaluation of cause of anemia Iron (µg/dl) 120 TIBC (µg/dl) 236 Ferritin (ng/ml) 954 Vitamin B12 (pg/ml) 1500 Peripheral Blood Smear Red blood cells- dimorphic, marked anisopoikilocytosis White blood cells- leukopenia, lymphocytic predominance Platelets- reduced Bone Marrow Aspiration cellular marrow particles with erythroid hyperplasia with predominant normoblastic maturation, megaloblastosis & sideroblastic changes, normal myelopoiesis & megakarocyte Bone Marrow Biopsy hypocellular with trilineage hematopoiesis Reticulocyte count (%) 1.5 Direct Coombs Test Negative Antinuclearantibody (ANA) Negative Anti-doublestranded DNA (anti-dsDNA) Negative Homocysteine (µmol/L) 6.64 Antiphospholipid antibodies (APLA) Profile Lupus anticoagulant- Absent Antiphospholipid antibody- <1 U/mL Serum cardiolipin antibody- 0.5 U/mL Dilute Russell's Viper Venom Time screen ratio 1.14 MRI Brain with contrast Post surgical sagittal T2 weighted and post contrast sagittal T1 weighted images show no evidence of residual or recurrent lesion in the sellar or suprasellar region. Pituitary stalk appear normal in calibre. No focal lesion in hypothalamus. Discussion This case describes findings from a pediatric patient in whom craniopharyngioma was diagnosed which upon excision resulted in various endocrine and non-endocrine manifestations including rare manifestations of hematological abnormality, adipsic DI, hyperphagia, and obesity. This case provides insight into varied manifestations of hypothalamic dysfunction and their management. The interesting and rare finding in this child was the occurrence of hematological abnormality. An extensive evaluation failed to reveal any causes of bicytopenia (nutritional/pathological) other than hypothermia. The specific association between hypothermia and pancytopenia has been reported in the literature in few cases, while in other cases, thrombocytopenia and leukopenia were consistent findings but the degrees of anemia varied [ 6 , 7 ]. However, we describe a case in which hematological changes in the form of anemia and thrombocytopenia were seen. In this case, anemia was consistent finding, but thrombocytopenia and leukopenia were variable. Normal body temperature is maintained by a delicate balance between heat production and heat loss, which is required for numerous chemical and biological reactions essential to survival. Hypothalamus acts as a major integrating centre involved in regulation of body temperature. Inputs from various parts like surface thermoreceptors in the skin, spinal cord, and deep structures of abdominal cavity are relayed to the preoptic area of the hypothalamus [ 8 – 10 ]. The posterior hypothalamus initiates thermogenesis through shivering and increased basal metabolic rate. Thermoregulation may happen (through the brainstem and cervical cord) if a portion of its synapse is damaged, but it will be less precise and integrated. Thyroid hormones (via brown adipose tissue) and sex steroids also play a role in maintaining thermogenesis, which too may be disrupted in lesions of hypothalamus [ 6 ]. Multiple mechanisms have been found to play a role in hematologic abnormalities noted in patients with accidental or therapeutic hypothermia (i) transient bone marrow suppression, (ii) splenic or hepatic sequestration (iii) leukocyte depletion and impaired neutrophil migration, margination and bacterial phagocytosis- predisposing to infection [ 11 ], (iv) bone marrow suppression and progressive bone marrow failure- could be the cause for erythroid hypoplasia and normocytic normochromic anemia. The reason why hypothermia should lead to bone marrow failure is still unknown, and more research is required to determine how prolonged hypothermia affects levels of cytokines, bone marrow function and blood cell survival. In this case, at admission, the reticulocyte index was inappropriately low for the degree of anemia, reflecting bone marrow suppression. The hematological features of thrombocytopenia, erythroid hypoplasia and ringed sideroblasts in bone marrow, might be caused by hypothermia [ 12 ]. Absence of any other identifiable cause together with strong circumstantial evidence of the patient's history, i.e. presence of evidence of hypothalamic dysfunction, documentation of hypothermia during hospital visits suggest that the hypothermia produced these hematological changes. The child also developed adipsic DI which is an uncommon presentation of DI. DI is characterized by the biochemical presentation of hypernatremia with increased serum osmolality in the presence of inappropriately dilute urine in large volumes. The supraoptic and paraventricular nuclei control secretion of vasopressin and any damage in this region will result in central DI. Majority of these patients have an intact thirst mechanism which increases fluid intake to offset the increased renal water loss. However, a subset of patients suffering from damage to the thirst centre (osmoreceptors signaling pathway connecting subfornical-organ, organum vasculosum of the lamina terminalis, and median preoptic nucleus) have reduced thirst, and are unable to compensate, which leads to hypernatremia [ 13 ]. Despite hypernatremia, these adipsic DI patients report little to no thirst when using a thirst scale to measure their level of thirst. Two mechanisms can lead to the development of adipsic DI. (i) Damage to both neurohypophysis and central anteriorly placed osmostat will result in absence of release of vasopressin in response to either osmotic or baroreceptor stimulation. (ii) Adipsic DI can also result from isolated damage to the hypothalamic osmoreceptors, with intact baroreceptors, such that there is adequate synthesis of vasopressin and normal release in response to baroreceptor stimulation but attenuated release in response to osmotic stimulation [ 14 – 16 ]. A preferred therapeutic practice is to administer a fixed dose of desmopressin to maintain chronic antidiuresis together with a prescribed volume of fluid intake with close monitoring. Patient and family education on the principles of water balance and management plays a crucial part. Daily weight tracking is useful to detect dehydration or water intoxication. It is recommended to do regular serum sodium measurements to monitor any fluctuations. However, even with stringent monitoring, it is difficult to achieve round the clock control of serum sodium concentrations that resembles physiological osmoregulation. It is advisable to maintain sodium levels near the higher reference range due to the risk of rapid swings in sodium levels and the symptoms of hyponatremia observed at the low reference range. [ 17 , 18 ]. Increased rates of cerebrovascular disease have been reported in a number of studies after pituitary radiotherapy. 14% rate of cerebrovascular events has been reported by Regine et al. [ 19 ], all in patients with craniopharyngioma who received irradiation doses > 61 Gy. Cerebral infarct can also occur in craniopharngioma even without radiotherapy. Wijnen et al. reported on an increased risk for cerebral infarct after craniopharyngioma. The excess risk for cerebral infarct was higher in female patients with childhood-onset craniopharyngioma, and in patients with hydrocephalus and craniopharyngioma recurrence [ 20 ]. Severe dehydration with hypernatremia can also be associated with thrombotic complication and leading to stroke event. Thus, stroke in such patients may be due to (i) craniopharyngioma per se [ 21 ] (ii) radiotherapy (iii) severe dehydration. In this patient, the event occurred 1½ years post-surgery indicating the possibility of radiotherapy or hypernatremia induced stroke. Similarly, anterior pituitary hormonal deficiencies were present in this child evident by low serum hormonal levels (thyroxine, cortisol, leutinizing hormone, follicle stimulating hormone, and estradiol) for which she received appropriate hormone replacement therapy. Hypopituitarism is commonly observed in post-operative patients with craniopharyngioma. In a retrospective study, 51 out of 54 (95%) patients with craniopharyngioma had at least 1 pituitary hormone insufficiency postoperatively [ 22 , 23 ]. In another retrospective study, 75% of children with craniopharyngioma had panhypopituitarism postoperatively [ 24 ]. One interesting finding in this child was the development of stroke 1 ½ years post-surgery. Oral estrogens can adversely affect serum levels of fibrinogen, factor VII and plasminogen activator inhibitor- 1. A meta-analysis of clinical trials suggested a higher risk of venous thromboembolic events among oral estrogen users compared with transdermal estrogen users [ 25 ]. Hence topical therapy of estradiol was preferred for management of gonadotropin deficiency to avoid systemic effects. Social and emotional impairment, school dysfunction and neurobehavioral impairment were present in this child negatively affecting quality of life. Since surgical resection of craniopharyngioma is often followed by impaired hypothalamic-pituitary function, it has been postulated that social and emotional impairment may be caused by oxytocin deficiency following surgery. However, no studies have been done to assess the efficacy of oxytocin therapy in improving social interaction in individuals with known hypothalamic dysfunction resulting from structural abnormalities or surgery [ 26 ]. The child also developed obesity post-surgery. The arcuate nucleus contains two neuronal populations- one expressing proopiomelanocortin (POMC) that inhibits food intake and stimulates energy expenditure, and the other co-expressing agouti-related peptide and neuropeptide-Y, which both stimulate food intake and reduce energy expenditure. Insults to the medial hypothalamic nuclei resulting from tumor, surgery or radiation can lead to unopposed action of orexigens released from lateral hypothalamus or disruption of signals such as POMC from medial hypothalamus or adiposity signals such as leptin. This disruption of feeding cycle can result in hyperphagia. [ 27 ]. Iatrogenic Cushing can also explain the cause of obesity in such patients on glucocorticoid replacement. Therefore, a patient on glucocorticoid replacement should be closely monitored for development of clinical evidence of overdosage, and the dose of glucocorticoid adjusted based on clinical features, body weight and serial monitoring of serum electrolytes. In this child, clinical features were not suggestive of Cushing’s syndrome. Conclusion We reported a case of craniopharyngioma in a child who presented post operatively and post radiotherapy with various endocrine and non-endocrine manifestations including multiple pituitary hormone deficiency, adipsic DI, altered behavior, energy imbalances, uncommon hematological picture of cyclic bicytopenia mirroring thermal dysregulation episodes, and stroke. Post operative management of craniopharyngioma is quite challenging particularly when the patient presents with affection of various domains of hypothalamus. A strong clinical suspicion is warranted to look out for the rare manifestations of hypothalamic dysfunction for improvement of patient’s overall survival and quality of life. Patient perspective After my daughter underwent surgery for her brain tumor and completed radiation therapy, I believed she would recover like she had in the past. But this time, her journey was different. She started experiencing problems like low hemoglobin and blood counts, fluctuating sodium levels, and low hormone levels that we couldn’t understand. However, with regular follow-up, the doctors were able to identify the underlying condition. Now, she is improving, and we are feeling hopeful again. Declarations Funding: Nil Conflicts of interest: The authors declare no conflicts of interest Ethics approval: not applicable Consent to participate: Not applicable Consent for publication: The parent (mother) signed the consent for publication Data availability: Not applicable Code availability: Not applicable Author’s contribution: Amritava Ghosh, Saroj Bala and Nikhil Sanjeev K wrote the main manuscript text and Amritava Ghosh and Nikhil Sanjeev K prepared Tables 1,2. All authors reviewed the manuscript. References Lechan RM. Neuroendocrinology. In: Melmed M, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ, editors. Williams textbook of endocrinology. 14th edition. Philadelphia, PA: Elsevier, Inc; 2020:117. Roth CL, McCormack SE. Acquired hypothalamic obesity: A clinical overview and update. Diabetes Obes Metab. 2024 Apr;26 Suppl 2:34-45. doi: 10.1111/dom.15530. Hannon MJ, Finucane FM, Sherlock M, Agha A, Thompson CJ. 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J Pediatr Endocrinol Metab. 2016 Aug 1;29(8):995-1000. doi: 10.1515/jpem- 2015-0445. Roth CL. Hypothalamic Obesity in Craniopharyngioma Patients: Disturbed Energy Homeostasis Related to Extent of Hypothalamic Damage and Its Implication for Obesity Intervention. J Clin Med. 2015 Sep 9;4(9):1774-97. doi: 10.3390/jcm4091774. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 10 Dec, 2025 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted Editorial decision: Revision requested 14 Aug, 2025 Editor assigned by journal 12 Aug, 2025 Submission checks completed at journal 12 Aug, 2025 First submitted to journal 31 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-7264794","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":500361661,"identity":"8fa7be02-db38-4180-b7b1-0355246bfd30","order_by":0,"name":"Amritava Ghosh","email":"","orcid":"","institution":"All India Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Amritava","middleName":"","lastName":"Ghosh","suffix":""},{"id":500361662,"identity":"c399fc20-5bfd-489f-b8f6-142cfc900290","order_by":1,"name":"Nikhil Sanjeev K","email":"","orcid":"","institution":"All India Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Nikhil","middleName":"Sanjeev","lastName":"K","suffix":""},{"id":500361663,"identity":"788d9ed8-6d6c-4ce2-a9af-ef2e68a801e5","order_by":2,"name":"Saroj Bala","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIiWNgGAWjYHCCBAbeBgYGCQkgU+KHjRxI6MADorVY9qQZg7UkELIHrqWC7XBiA8QY3EB+NtARb3fY5UnObn724QZPWvr8sMMPgbbYyek2YNdicC4hgXHumeRiaZljxjNnWNjkbrydZgDUkmxsdgCHFh6GBGbeNubEeRIJxswSPGm5G2cngLQcSNyGQ4t8D1hLPVBL+mfmP2yH0w1np3/Aq4XhDFjL4cTZEjnGDBJshxPkpXPw22IA1HJwbtvxxJkzcooZJHvSDDdI5xQcSDDA7Rf5Hp7EB2/bqhNn3EjfDIpKefnZ6Zs/fKiwk8OlhYGBJwFVygDMNcClHATY0QyTb8CnehSMglEwCkYiAACfXGLqbkjqGwAAAABJRU5ErkJggg==","orcid":"","institution":"All India Institute of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Saroj","middleName":"","lastName":"Bala","suffix":""}],"badges":[],"createdAt":"2025-07-31 17:53:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7264794/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7264794/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s42399-025-02216-4","type":"published","date":"2025-12-10T15:58:08+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":91086446,"identity":"2eadd5de-10de-4a30-a22f-c8940eb32777","added_by":"auto","created_at":"2025-09-11 12:25:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1069396,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7264794/v1/83cf1e49b28d36820f1ceb36.png"},{"id":91086411,"identity":"59a733ed-5971-4b97-9eae-fc7d983bc50e","added_by":"auto","created_at":"2025-09-11 12:25:34","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1506317,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7264794/v1/f35d094c96ad0de0017a9ea8.png"},{"id":98244818,"identity":"b5ef7636-3e8e-48a1-929e-e7f55a3e042d","added_by":"auto","created_at":"2025-12-15 16:15:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5034940,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7264794/v1/f43424b2-5f78-4b95-8612-2ec0e9366bbf.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Bicytopenia - a rare hematological manifestation secondary to hypothalamic dysfunction in a case of craniopharyngioma: A case report","fulltext":[{"header":"Background","content":"\u003cp\u003eHypothalamus plays a central role in regulation of pituitary hormones, thirst - water balance, feeding- energy expenditure, autonomic system, somatic behavior, body temperature and sleep wake cycle [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. So, abnormalities of the same should be expected in patients with tumors within or encroaching on the hypothalamus or operative damage to hypothalamus. However, clinicians usually emphasize on the secondary effect of these tumors on pituitary hormone secretion. Disturbances in water and energy balance and disordered thermoregulation are uncommonly reported. Disturbances in water and energy balance can lead to disorders such as electrolyte imbalance and hypothalamic obesity [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Abnormal thermoregulation can have potentially life-threatening consequences. Hypothermia may present with muscle dysfunction, impaired mental function, respiratory depression, arrhythmias, and hypotension, which can progress to coma or cardiac arrest. Hyperthermia may present with flushing, sweating, tachycardia, fatigue and headache, which can progress to muscle weakness and cramps, hypotension, confusion, agitation, delirium, seizures, and coma [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Additionally, disordered thermal regulation can rarely be associated with hematological abnormalities. Both therapeutic and accidental hypothermia\u003c/p\u003e\u003cp\u003ehave been associated with thrombocytopenia which may resolve with rewarming [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. We wish to report a child of craniopharyngioma who presented postoperatively with various endocrine and non-endocrine abnormalities in the form of multiple hormonal deficiencies, adipsic diabetes insipidus (DI), hyperphagia, obesity and hematological abnormalities.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 11-year girl child developed headache for 1 month and impaired vision of both eyes. There was no history of head injury, vomiting or seizures. There was no history of excess weight gain, increased thirst or frequency of urination, change in behavior or drop in scholastic performance. She had not attained menarche. On examination, she weighed 46 kilograms, and height was 150 cm (body mass index \u0026ndash; 20.44 kg/m\u003csup\u003e2\u003c/sup\u003e). Axillary temperature measured at various visits to hospital ranged between 35.5 and 36.2\u0026ordm; C. Her tanner staging for breast and pubic hair were 4 and 1 respectively. There was no axillary hair. Magnetic resonance imaging of brain showed a well-defined thick walled multicystic lesion with internal proteinaceous contents arising from sellar-suprasellar area measuring 3.9\u0026times;4.5 cm with obstructive hydrocephalus. Preoperative complete blood counts were within normal limits (Hemoglobin \u0026minus;\u0026thinsp;11.3 g/dL, total count \u0026ndash; 11,980/\u0026micro;L and platelets \u0026ndash; 2.25 lakh/\u0026micro;L). She underwent craniotomy with excision of lesion and post operatively, received radiotherapy. Vision had improved postoperatively. Histopathology was consistent with adamantinomatous craniopharyngioma.\u003c/p\u003e\u003cp\u003eUpon post operative follow up she was detected to have multiple pituitary hormone deficiencies (central hypothyroidism, adrenal insufficiency, central DI) for which she was started on specific hormonal replacement therapy.\u003c/p\u003e\u003cp\u003e7 months post-surgery she developed severe anemia with mild thrombocytopenia (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) which improved with blood transfusion but recurred. Further in the follow up, 1 year later, she developed severe anemia and thrombocytopenia. Initial evaluation revealed no identifiable cause of anemia (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Hence diagnosis of thermal dysregulation leading to anemia was considered. She was asked to strictly avoid extremes of temperature and monitor her fluid balance. After 2\u0026ndash;3 weeks, her counts normalized suggestive of response to strict thermal regulation and fluid balance.\u003c/p\u003e\u003cp\u003ePost operatively, she was also found to have polyuria, and recurrent episodes of hypernatremia (serum sodium values ranging from 154 mmol/L to 170 mmol/L) with limited thirst sensation. Hence a diagnosis of adipsic central\u003c/p\u003e\u003cp\u003eDI was considered. She was managed with oral desmopressin with doses ranging from 200 to 300 \u0026micro;g/day divided in 2\u0026ndash;3 doses per day. She was advised to avoid dehydration and adjust total daily fluid intake to match the urinary output. Serial monitoring of serum sodium, body weight monitoring and titration of oral desmopressin at each follow up visit was done to maintain serum sodium within normal limits and she responded (serum sodium values ranging from 142 mmol/L to 149 mmol/L). 1 \u0026frac12; years post-surgery she developed right sided hemiparesis and computed tomography of brain showed left middle cerebral artery territory infarct. Magnetic resonance angiography of neck vessels was normal. She was continued on desmopressin with serial serum sodium and input-output monitoring.\u003c/p\u003e\u003cp\u003eOn follow up visits it was also noticed that there was non progression of puberty. Upon evaluation her serum follicle stimulating hormone was 2.1mIU/ml, Luteinizing hormone 0.78 mIU/ml and estradiol \u0026lt; 10 pg/ml. In view of prior episode of stroke, topical preparation in the form of 17 beta Estradiol 0.06% gel application in gradually increasing doses was preferred.\u003c/p\u003e\n\u003cp\u003eShe also had a rapid gain in body weight which peaked at 63 kg (body mass index 27.6 kg/m\u003csup\u003e2\u003c/sup\u003e and \u0026gt; 97th percentile). It was evident from the mother’s statement that her appetite was increased. She was advised to restrict her calorie intake and screen time, and she responded subsequently with a weight loss of 4 kg. She was also noted to have short term memory loss (including forgetting common words while speaking) and exhibiting apathy.\u003c/p\u003e\n\u003cp\u003eShe was followed up on regular basis with monitoring of temperature and other vital parameters, anthropometric measures, pubertal progression, hydration status, input output, serum sodium and hormonal levels. Postoperative imaging is presented in Figs.\u0026nbsp;1 and 2.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eComplete Blood Count Parameters noted at various visits during follow up\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\u003e12/1\u003c/p\u003e\n \u003cp\u003e1/20\u003c/p\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e15/0\u003c/p\u003e\n \u003cp\u003e8/20\u003c/p\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e13/1\u003c/p\u003e\n \u003cp\u003e1/20\u003c/p\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e17/0\u003c/p\u003e\n \u003cp\u003e3/20\u003c/p\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e25/0\u003c/p\u003e\n \u003cp\u003e8/20\u003c/p\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e06/0\u003c/p\u003e\n \u003cp\u003e9/20\u003c/p\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e24/0\u003c/p\u003e\n \u003cp\u003e2/20\u003c/p\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e06/0\u003c/p\u003e\n \u003cp\u003e4/20\u003c/p\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e11/0\u003c/p\u003e\n \u003cp\u003e6/20\u003c/p\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e10/1\u003c/p\u003e\n \u003cp\u003e1/20\u003c/p\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e09/0\u003c/p\u003e\n \u003cp\u003e2/20\u003c/p\u003e\n \u003cp\u003e23\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\u003eHemoglobin\u003c/p\u003e\n \u003cp\u003e(g/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal leukocyte count (cells/µL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7470\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1926\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9730\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlatelet count (lakh cells/µL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean corpuscular volume (MCV) (fL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e102.\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e94.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean corpuscular hemoglobin (MCH) (pg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean corpuscular hemoglobin concentration (MCHC)\u003c/p\u003e\n \u003cp\u003e(g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eLaboratory tests performed during evaluation of cause of anemia\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIron (µg/dl)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e120\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\u003eTIBC (µg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e236\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFerritin (ng/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e954\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVitamin B12 (pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1500\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeripheral Blood Smear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRed blood cells- dimorphic, marked anisopoikilocytosis\u003c/p\u003e\n \u003cp\u003eWhite blood cells- leukopenia, lymphocytic predominance\u003c/p\u003e\n \u003cp\u003ePlatelets- reduced\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBone Marrow Aspiration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecellular marrow particles with erythroid hyperplasia with predominant normoblastic maturation, megaloblastosis \u0026amp; sideroblastic changes, normal myelopoiesis \u0026amp; megakarocyte\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBone Marrow Biopsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ehypocellular with trilineage hematopoiesis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReticulocyte count (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDirect Coombs Test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntinuclearantibody\u003c/p\u003e\n \u003cp\u003e(ANA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnti-doublestranded\u003c/p\u003e\n \u003cp\u003eDNA (anti-dsDNA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHomocysteine (µmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntiphospholipid\u003c/p\u003e\n \u003cp\u003eantibodies (APLA) Profile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLupus anticoagulant- Absent Antiphospholipid antibody- \u0026lt;1 U/mL Serum cardiolipin antibody- 0.5 U/mL\u003c/p\u003e\n \u003cp\u003eDilute Russell's Viper Venom Time screen ratio 1.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\n\u003cp\u003eMRI Brain with contrast\u003c/p\u003e\n\u003cp\u003ePost surgical sagittal T2 weighted and post contrast sagittal T1 weighted images show no evidence of residual or recurrent lesion in the sellar or suprasellar region. Pituitary stalk appear normal in calibre. No focal lesion in hypothalamus.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case describes findings from a pediatric patient in whom craniopharyngioma was diagnosed which upon excision resulted in various endocrine and non-endocrine manifestations including rare manifestations of hematological abnormality, adipsic DI, hyperphagia, and obesity. This case provides insight into varied manifestations of hypothalamic dysfunction and their management.\u003c/p\u003e\u003cp\u003eThe interesting and rare finding in this child was the occurrence of hematological abnormality. An extensive evaluation failed to reveal any causes of bicytopenia (nutritional/pathological) other than hypothermia. The specific\u003c/p\u003e\u003cp\u003eassociation between hypothermia and pancytopenia has been reported in the literature in few cases, while in other cases, thrombocytopenia and leukopenia were consistent findings but the degrees of anemia varied [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, we describe a case in which hematological changes in the form of anemia and thrombocytopenia were seen. In this case, anemia was consistent finding, but thrombocytopenia and leukopenia were variable. Normal body temperature is maintained by a delicate balance between heat production and heat loss, which is required for numerous chemical and biological reactions essential to survival. Hypothalamus acts as a major integrating centre involved in regulation of body temperature. Inputs from various parts like surface thermoreceptors in the skin, spinal cord, and deep structures of abdominal cavity are relayed to the preoptic area of the hypothalamus [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The posterior hypothalamus initiates thermogenesis through shivering and increased basal metabolic rate. Thermoregulation may happen (through the brainstem and cervical cord) if a portion of its synapse is damaged, but it will be less precise and integrated. Thyroid hormones (via brown adipose tissue) and sex steroids also play a role in maintaining thermogenesis, which too may be disrupted in lesions of hypothalamus [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMultiple mechanisms have been found to play a role in hematologic abnormalities noted in patients with accidental or therapeutic hypothermia (i) transient bone marrow suppression, (ii) splenic or hepatic sequestration (iii) leukocyte depletion and impaired neutrophil migration, margination and bacterial phagocytosis- predisposing to infection [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], (iv) bone marrow suppression and progressive bone marrow failure- could be the cause for erythroid hypoplasia and normocytic normochromic anemia. The reason why hypothermia should lead to bone marrow failure is still unknown, and more research is required to determine how prolonged hypothermia affects levels of cytokines, bone marrow function and blood cell survival. In this case, at admission, the reticulocyte index was inappropriately low for the degree of anemia, reflecting bone marrow suppression. The hematological features of thrombocytopenia, erythroid hypoplasia and ringed sideroblasts in bone marrow, might be caused by hypothermia [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Absence of any other identifiable cause together with strong circumstantial evidence of the patient's history, i.e. presence of evidence of hypothalamic dysfunction, documentation of hypothermia during hospital visits suggest that the hypothermia produced these hematological changes.\u003c/p\u003e\u003cp\u003eThe child also developed adipsic DI which is an uncommon presentation of DI. DI is characterized by the biochemical presentation of hypernatremia with increased serum osmolality in the presence of inappropriately dilute urine in large volumes. The supraoptic and paraventricular nuclei control secretion of vasopressin and any damage in this region will result in central DI. Majority of these patients have an intact thirst mechanism which increases fluid intake to\u003c/p\u003e\u003cp\u003eoffset the increased renal water loss. However, a subset of patients suffering from damage to the thirst centre (osmoreceptors signaling pathway connecting subfornical-organ, organum vasculosum of the lamina terminalis, and median preoptic nucleus) have reduced thirst, and are unable to compensate, which leads to hypernatremia [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Despite hypernatremia, these adipsic DI patients report little to no thirst when using a thirst scale to measure their level of thirst. Two mechanisms can lead to the development of adipsic DI. (i) Damage to both neurohypophysis and central anteriorly placed osmostat will result in absence of release of vasopressin in response to either osmotic or baroreceptor stimulation.\u003c/p\u003e\u003cp\u003e(ii) Adipsic DI can also result from isolated damage to the hypothalamic osmoreceptors, with intact baroreceptors, such that there is adequate synthesis of vasopressin and normal release in response to baroreceptor stimulation but attenuated release in response to osmotic stimulation [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A preferred therapeutic practice is to administer a fixed dose of desmopressin to maintain chronic antidiuresis together with a prescribed volume of fluid intake with close monitoring. Patient and family education on the principles of water balance and management plays a crucial part. Daily weight tracking is useful to detect dehydration or water intoxication. It is recommended to do regular serum sodium measurements to monitor any fluctuations. However, even with stringent monitoring, it is difficult to achieve round the clock control of serum sodium concentrations that resembles physiological osmoregulation. It is advisable to maintain sodium levels near the higher reference range due to the risk of rapid swings in sodium levels and the symptoms of hyponatremia observed at the low reference range. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIncreased rates of cerebrovascular disease have been reported in a number of studies after pituitary radiotherapy. 14% rate of cerebrovascular events has been reported by Regine et al. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], all in patients with craniopharyngioma who received irradiation doses\u0026thinsp;\u0026gt;\u0026thinsp;61 Gy. Cerebral infarct can also occur in craniopharngioma even without radiotherapy. Wijnen et al. reported on an increased risk for cerebral infarct after craniopharyngioma. The excess risk for cerebral infarct was higher in female patients with childhood-onset craniopharyngioma, and in patients with hydrocephalus and craniopharyngioma recurrence [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Severe dehydration with hypernatremia can also be associated with thrombotic complication and leading to stroke event. Thus, stroke in such patients may be due to (i) craniopharyngioma per se [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] (ii) radiotherapy (iii) severe dehydration. In this patient, the event occurred 1\u0026frac12; years post-surgery indicating the possibility of radiotherapy or hypernatremia induced stroke.\u003c/p\u003e\u003cp\u003eSimilarly, anterior pituitary hormonal deficiencies were present in this child evident by low serum hormonal levels (thyroxine, cortisol, leutinizing hormone, follicle stimulating hormone, and estradiol) for which she received appropriate hormone replacement therapy. Hypopituitarism is commonly observed in post-operative patients with craniopharyngioma. In a retrospective study, 51 out of 54 (95%) patients with craniopharyngioma had at least 1 pituitary hormone insufficiency postoperatively [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In another retrospective study, 75% of children with craniopharyngioma had panhypopituitarism postoperatively [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. One interesting finding in this child was the development of stroke 1 \u0026frac12; years post-surgery. Oral estrogens can adversely affect serum levels of fibrinogen, factor VII and plasminogen activator inhibitor- 1. A meta-analysis of clinical trials suggested a higher risk of venous thromboembolic events among oral estrogen users compared with transdermal estrogen users [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Hence topical therapy of estradiol was preferred for management of gonadotropin deficiency to avoid systemic effects.\u003c/p\u003e\u003cp\u003eSocial and emotional impairment, school dysfunction and neurobehavioral impairment were present in this child negatively affecting quality of life. Since surgical resection of craniopharyngioma is often followed by impaired hypothalamic-pituitary function, it has been postulated that social and emotional impairment may be caused by oxytocin deficiency following surgery. However, no studies have been done to assess the efficacy of oxytocin therapy in improving social interaction in individuals with known hypothalamic dysfunction resulting from structural abnormalities or surgery [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe child also developed obesity post-surgery. The arcuate nucleus contains two neuronal populations- one expressing proopiomelanocortin (POMC) that inhibits food intake and stimulates energy expenditure, and the other co-expressing agouti-related peptide and neuropeptide-Y, which both stimulate food intake and reduce energy expenditure. Insults to the medial hypothalamic nuclei resulting from tumor, surgery or radiation can lead to unopposed action of orexigens released from lateral hypothalamus or disruption of signals such as POMC from medial hypothalamus or adiposity signals such as leptin. This disruption of feeding cycle can result in hyperphagia. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Iatrogenic Cushing can also explain the cause of obesity in such patients on glucocorticoid replacement. Therefore, a patient on glucocorticoid replacement should be closely monitored for development of clinical evidence of overdosage, and the dose of glucocorticoid adjusted based on clinical features, body weight and serial monitoring of serum electrolytes. In this child, clinical features were not suggestive of Cushing\u0026rsquo;s syndrome.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe reported a case of craniopharyngioma in a child who presented post operatively and post radiotherapy with various endocrine and non-endocrine manifestations including multiple pituitary hormone deficiency, adipsic DI, altered behavior, energy imbalances, uncommon hematological picture of cyclic bicytopenia mirroring thermal dysregulation episodes, and stroke. Post operative management of craniopharyngioma is quite challenging particularly when the patient presents with affection of various domains of hypothalamus. A strong clinical suspicion is warranted to look out for the rare manifestations of hypothalamic dysfunction for improvement of patient\u0026rsquo;s overall survival and quality of life.\u003c/p\u003e"},{"header":"Patient perspective","content":"\u003cp\u003eAfter my daughter underwent surgery for her brain tumor and completed radiation therapy, I believed she would recover like she had in the past. But this time, her journey was different. She started experiencing problems like low hemoglobin and blood counts, fluctuating sodium levels, and low hormone levels that we couldn\u0026rsquo;t understand. However, with regular follow-up, the doctors were able to identify the underlying condition. Now, she is improving, and we are feeling hopeful again.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding: Nil\u003c/p\u003e\n\u003cp\u003eConflicts of interest: The authors declare no conflicts of interest\u003c/p\u003e\n\u003cp\u003eEthics approval: not applicable\u003c/p\u003e\n\u003cp\u003eConsent to participate: Not applicable\u003c/p\u003e\n\u003cp\u003eConsent for publication: The parent (mother) signed the consent for publication\u003c/p\u003e\n\u003cp\u003eData availability: Not applicable\u003c/p\u003e\n\u003cp\u003eCode availability: Not applicable\u003c/p\u003e\n\u003cp\u003eAuthor\u0026rsquo;s contribution: Amritava Ghosh, Saroj Bala and Nikhil Sanjeev K wrote the main manuscript text and Amritava Ghosh and Nikhil Sanjeev K prepared Tables 1,2. All authors reviewed the manuscript.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLechan RM. Neuroendocrinology. In: Melmed M, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ, editors. Williams textbook of endocrinology. 14th edition. Philadelphia, PA: Elsevier, Inc; 2020:117.\u003c/li\u003e\n\u003cli\u003eRoth CL, McCormack SE. Acquired hypothalamic obesity: A clinical overview and update. Diabetes Obes Metab. 2024 Apr;26 Suppl 2:34-45. doi: 10.1111/dom.15530.\u003c/li\u003e\n\u003cli\u003eHannon MJ, Finucane FM, Sherlock M, Agha A, Thompson CJ. Clinical review: Disorders of water homeostasis in neurosurgical patients. J Clin Endocrinol Metab. 2012 May;97(5):1423-33. doi: 10.1210/jc.2011-3201.\u003c/li\u003e\n\u003cli\u003eCheshire WP Jr. Thermoregulatory disorders and illness related to heat and cold stress. Auton Neurosci. 2016 Apr;196:91-104. doi: 10.1016/j.autneu.2016.01.001.\u003c/li\u003e\n\u003cli\u003eVella MA, Jenner C, Betteridge DJ, Jowett NI. Hypothermia-induced thrombocytopenia. J R Soc Med. 1988 Apr;81(4):228-9. doi: 10.1177/014107688808100414.\u003c/li\u003e\n\u003cli\u003eDickinson O, Hanson B, Benditt DG, Duran-Nelson AM. Haematological, neurological and electrocardiographic findings in secondary hypothermia. BMJ Case Rep. 2012 Nov 15;2012:bcr2012007587. doi: 10.1136/bcr-2012-007587.\u003c/li\u003e\n\u003cli\u003eLo L, Singer ST, Vichinsky E. Pancytopenia induced by hypothermia. J Pediatr Hematol Oncol. 2002 Nov;24(8):681-4. doi: 10.1097/00043426-200211000- 00017.\u003c/li\u003e\n\u003cli\u003eBaddeley AD, Cuccaro WJ, Egstrom GH, Weltman G, Willis MA. Cognitive of divers working in cold water. Hum Factors. 1975 Oct;17(5):446-54. doi: 10.1177/001872087501700503.\u003c/li\u003e\n\u003cli\u003eDavis FM, Baddeley AD, Hancock TR. Diver performance: the effect of cold. Undersea Biomed Res. 1975 Sep;2(3):195-213.\u003c/li\u003e\n\u003cli\u003eColeshaw SR, Van Someren RN, Wolff AH, Davis HM, Keatinge WR. Impaired memory registration and speed of reasoning caused by low body temperature. J Appl Physiol Respir Environ Exerc Physiol. 1983 Jul;55(1 Pt 1):27 doi: 10.1152/jappl.1983.55.1.27.\u003c/li\u003e\n\u003cli\u003eAkriotis V, Biggar WD. The effects of hypothermia on neutrophil function in vitro. J Leukoc Biol. 1985 Jan;37(1):51-61. doi: 10.1002/jlb.37.1.51.\u003c/li\u003e\n\u003cli\u003eO\u0026apos;Brien H, Amess JA, Mollin DL. Recurrent thrombocytopenia, erythroid hypoplasia and sideroblastic anaemia associated with hypothermia. Br J Haematol. 1982 Jul;51(3):451-6. doi: 10.1111/j.1365-2141.1982.tb02802.x.\u003c/li\u003e\n\u003cli\u003eDalan R, Chin H, Hoe J, Chen A, Tan H, Boehm BO, Chua KS. Adipsic Diabetes Insipidus-The Challenging Combination of Polyuria and Adipsia: A Case Report and Review of Literature. Front Endocrinol (Lausanne). 2019 Sep 18;10:630. doi: 10.3389/fendo.2019.00630.\u003c/li\u003e\n\u003cli\u003eCrowley RK, Sherlock M, Agha A, Smith D, Thompson CJ. Clinical insights into adipsic diabetes insipidus: a large case series. Clin Endocrinol (Oxf). 2007 Apr;66(4):475-82. doi: 10.1111/j.1365-2265.2007.02754.x.\u003c/li\u003e\n\u003cli\u003eMcIver B, Connacher A, Whittle I, Baylis P, Thompson C. Adipsic hypothalamic diabetes insipidus after clipping of anterior communicating artery aneurysm. BMJ. 1991 Dec 7;303(6815):1465-7. doi: 10.1136/bmj.303.6815.1465.\u003c/li\u003e\n\u003cli\u003eSmith D, McKenna K, Moore K, Tormey W, Finucane J, Phillips J, Baylis P, Thompson CJ. Baroregulation of vasopressin release in adipsic diabetes insipidus. J Clin Endocrinol Metab. 2002 Oct;87(10):4564-8. doi: 10.1210/jc.2002-020090.\u003c/li\u003e\n\u003cli\u003eMavrakis AN, Tritos NA. Diabetes insipidus with deficient thirst: report of a patient and review of the literature. Am J Kidney Dis. 2008 May;51(5):851-9. doi: 10.1053/j.ajkd.2007.11.028.\u003c/li\u003e\n\u003cli\u003eBall SG, Vaidja B, Baylis PH. 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Front Oncol. 2021 Jul 14;11:698150. doi: 10.3389/fonc.2021.698150.\u003c/li\u003e\n\u003cli\u003eDeVile CJ, Grant DB, Hayward RD, Stanhope R. Growth and endocrine sequelae of craniopharyngioma. Arch Dis Child. 1996 Aug;75(2):108-14. doi: 10.1136/adc.75.2.108.\u003c/li\u003e\n\u003cli\u003eB\u0026uuml;low B, Attewell R, Hagmar L, Malmstr\u0026ouml;m P, Nordstr\u0026ouml;m CH, Erfurth EM. Postoperative prognosis in craniopharyngioma with respect to cardiovascular mortality, survival, and tumor recurrence. J Clin Endocrinol Metab. 1998 Nov;83(11):3897-904. doi: 10.1210/jcem.83.11.5240.\u003c/li\u003e\n\u003cli\u003eVinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019 Jan 9;364:k4810. doi: 10.1136/bmj.k4810.\u003c/li\u003e\n\u003cli\u003eMartin KA, Manson JE. Approach to the patient with menopausal symptoms. J Clin Endocrinol Metab. 2008 Dec;93(12):4567-75. doi: 10.1210/jc.2008-1272.\u003c/li\u003e\n\u003cli\u003eCook N, Miller J, Hart J. Parent observed neuro-behavioral and pro-social improvements with oxytocin following surgical resection of craniopharyngioma. J Pediatr Endocrinol Metab. 2016 Aug 1;29(8):995-1000. doi: 10.1515/jpem- 2015-0445.\u003c/li\u003e\n\u003cli\u003eRoth CL. Hypothalamic Obesity in Craniopharyngioma Patients: Disturbed Energy Homeostasis Related to Extent of Hypothalamic Damage and Its Implication for Obesity Intervention. J Clin Med. 2015 Sep 9;4(9):1774-97. doi: 10.3390/jcm4091774.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"craniopharyngioma, adipsic diabetes insipidus, bicytopenia, thermal dysregulation, hypothalamic dysfunction","lastPublishedDoi":"10.21203/rs.3.rs-7264794/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7264794/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e\u003cp\u003eHypothalamic dysfunction can result in a wide range of endocrine and non-endocrine manifestations, including pituitary hormone deficiencies, disorders of water balance, obesity, thermoregulatory disturbances, autonomic dysfunction, behavioral changes, and sleep abnormalities. These complications often require long-term follow-up and periodic reassessment.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e\u003cp\u003eWe present the case of an 11-year-old girl with craniopharyngioma who, following surgical resection and radiotherapy, developed multiple pituitary hormone deficiencies, adipsic diabetes insipidus, hyperphagia, cognitive disturbances, and delayed puberty. Unique to this case was the occurrence of cyclic bicytopenia mirroring thermal dysregulation episodes, in the absence of an identifiable hematological cause. As body temperature normalized, hematological parameters improved, suggesting a potential link between thermal dysregulation and cytopenia. Management involved hormone replacement, fluid and sodium balance monitoring, topical estrogen therapy, and lifestyle interventions. We address and review the mechanisms proposed for cytopenias related to thermoregulation and propose possible mechanisms for the other findings while discussing the therapeutic challenges in managing such complex cases.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003ePostoperative management of craniopharyngioma is often complicated by involvement of multiple hypothalamic domains. This case emphasizes the importance of recognizing uncommon and underreported manifestations, such as thermoregulation-associated cytopenia and adipic diabetes insipidus. Early diagnosis and multidisciplinary management are essential for improving outcomes and long-term quality of life in affected children.\u003c/p\u003e","manuscriptTitle":"Bicytopenia - a rare hematological manifestation secondary to hypothalamic dysfunction in a case of craniopharyngioma: A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-11 12:25:07","doi":"10.21203/rs.3.rs-7264794/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-14T07:28:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-13T02:16:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-13T00:28:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2025-07-31T17:46:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"141f8118-33ad-4223-99cc-2e03681c640a","owner":[],"postedDate":"September 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-15T16:10:32+00:00","versionOfRecord":{"articleIdentity":"rs-7264794","link":"https://doi.org/10.1007/s42399-025-02216-4","journal":{"identity":"sn-comprehensive-clinical-medicine","isVorOnly":false,"title":"SN Comprehensive Clinical Medicine"},"publishedOn":"2025-12-10 15:58:08","publishedOnDateReadable":"December 10th, 2025"},"versionCreatedAt":"2025-09-11 12:25:07","video":"","vorDoi":"10.1007/s42399-025-02216-4","vorDoiUrl":"https://doi.org/10.1007/s42399-025-02216-4","workflowStages":[]},"version":"v1","identity":"rs-7264794","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7264794","identity":"rs-7264794","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}