Autoimmune thyroid disease - is high prolactin a risk factor?

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SEHER ÇETİNKAYA ALTUNTAŞ, Gamze Kocaman, Ali Erol, Emre Dökmetaş, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8523918/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background In addition to its classic effect of lactation, prolactin (PRL) has begun to attract attention for its non-classic effects, particularly on the immune system. Objective This study aimed to compare the prevalence of autoimmune thyroid disease (AITD), thyroid autoantibodies and thyroid function tests (TFTs) in patients with hyperprolactinemia (HPRL) of at least 25 ng/ml and in healthy controls with PRL of less than 25 ng/ml.We conducted a retrospective case-control study at a single tertiary referral centre. All study participants underwent measurement of antibodies to thyroglobulin (anti-Tg), thyroid peroxidase (anti-TPO), TSH and fT4 levels, as well as ultrasonographic thyroid pattern assessment. Results The AITD rate was found to be 33.5% in those with PRL ≥ 25. In the healthy control group, this rate was 23.5%, and this difference was statistically significant (p = 0.006). Among those with PRL ≥ 25, Anti-TPO and Anti-Tg levels, as well as TSH levels, were significantly higher and sT4 levels were significantly lower compared to the control group (p < 0.001).. There was a positive relationship between PRL levels and TSH, Anti-Tg, and Anti-TPO levels, while there was a negative relationship with sT4 levels, all of which were statistically significant but relatively weak .The ROC analysis revealed that the PRL level was 21.77 ng/mL for detecting Anti-TPO positivity and Anti-Tg positivity, the cut-off value was determined to be 21.92 ng/mL Conclusions There is an increase in the frequency of AITD and thyroid autoantibodies in HPRL patients. We can conclude that exceeding the PRL threshold value increases the risk. Autoimmune thyroid disease prolactin antibodies to thyroglobulin thyroid peroxidase (anti-TPO) Figures Figure 1 Introduction Prolactin (PRL) is a polypeptide hormone that is secreted by the anterior pituitary gland. It is synthesised not only in the pituitary gland, but also by neurons, adipocytes, endothelial cells, immune cells, thymocytes and peripheral blood cells, especially lymphocytes. The primary function of PRL is well known: breast growth and lactation. In addition to these classical effects, PRL also affects calcium-bone metabolism, insulin resistance, atherogenicity and the immune system. 1 , 2 Recently, the effects of PRL on the immune system have attracted significant attention. The effects of PRL on the immune system have recently attracted considerable interest. PRL receptors are expressed in monocytes, macrophages, T- and B-lymphocytes, natural killer cells, granulocytes, natural killer cells, granulocytes and thymic epithelial cells . 3 Although the mechanism is not fully understood, PRL can trigger some autoimmune diseases and play a role in their pathogenesis and the clinical course of these diseases. 4 It is thought that it achieves this by inducing B-cell tolerance at a genetic level, increasing the presentation of antigens and antibodies, and the production of cytokines, while also inhibiting apoptosis. 5 The PRL gene HLA-DRB1 is located on the short arm of chromosome 6. This region is also associated with immune-mediated diseases. 6 The relationship between PRL and autoimmunity has been studied more extensively in diseases such as rheumatoid arthritis, antiphospholipid syndrome, systemic lupus erythematosus (SLE) and multiple sclerosis. However, the number of studies related to autoimmune thyroid disease (AITD) is limited and the results are inconsistent. 7, 8, 9, 10, 11 In this study, we aimed to compare the levels of thyroid autoantibodies and the frequency of thyroid autoimmunity in patients with PRL ≥ 25 with a healthy control group with PRL < 25 and to determine the relationship between PRL levels and these autoantibodies and thyroid function tests (TFT). MATERIALS AND METHODS Study sample Our study is a retrospective, single-centre, case-control study. Between 2021 and 2024, we examined patients diagnosed with hyperprolactinemia (HPRL) who had test results for PRL, TSH, free thyroxine (fT4), thyroid peroxidase antibody (anti-TPO) and thyroglobulin antibody (anti-Tg) from the Endocrinology and Metabolism outpatient clinic at Bursa Yüksek İhtisas Hospital, which is part of the University of Health Sciences. Patients aged 18–70 with a PRL level of 25 or above, regardless of the aetiology of HPRL, who had not received treatment, were included in the study. The healthy control group consisted of individuals with a PRL level below 25 and no additional diseases who were referred from occupational health clinics or attended for check-ups. A total of 835 patients were recorded. We excluded 134 patients who had missing data or did not meet the specified criteria. patients with missing data or who did not meet the specified criteria were excluded. A total of 701 patients were included in the study. All patient information was obtained from our hospital's computer database. The following were excluded from the study as they could affect the results: 1) History of pregnancy and breastfeeding 2) Patients with TFT levels outside the reference range 3) Diagnosis of diabetes mellitus 4) Diagnosis of acute or chronic liver and kidney disease 5) History of thyroid surgery 6) History of receiving radioactive iodine/radiotherapy 7) History of using dopamine agonists (DA) were excluded from the study as this could affect the results. TSH, fT4, Anti-TPO and Anti-Tg values were recorded in the patient and control groups. Thyroid ultrasonography (USG) was used to evaluate the presence of hypoechoic, diffusely heterogeneous echogenicity or pseudonodules in favour of autoimmunity. In patients with pituitary adenoma detected by magnetic resonance imaging, the adenoma size was recorded in millimetres (mm). In our hospital laboratory, the normal reference ranges for TSH and fT4 are 0.35–4.94 µIU/mL and 0.7–2.77 ng/dL, respectively. The normal reference ranges for anti-Tg and anti-TPO are 0–4.11 IU/mL and 0–5.61 IU/mL, respectively. As antibody positivity can also occur in healthy individuals, an antibody titer of ≥ 45 IU/mL was considered positive. Patients with at least one positive antibody and/or an autoimmune pattern on thyroid ultrasound were defined as having AITD. All data were compared with those of the healthy control group. Prior to the study, necessary permission was obtained from the Ethics Committee of SBÜ Bursa Yüksek İhtisas Training and Research Hospital (Approval No. 2024-TBEK-2025/03–08, Approval Date. 12/03/2025). Due to the retrospective design of the study, written informed consent was waived. All procedures performed in this study were conducted in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments, or comparable ethical standards. Statistical analysis Data analysis was performed using the SPSS v.25 statistical program. For the descriptive findings, variables specified by count are presented as numbers and percentages, while variables measured are indicated by the median (minimum – maximum), bearing in mind that the data does not conform to a normal distribution. The distribution characteristic of the measured variables was evaluated using the Kolmogorov–Smirnov test. For binary analyses, the chi-square test was used for categorical variables indicated by counts and the Mann–Whitney U test for variables indicated by measurements. For comparisons involving more than two measurements, Kruskal–Wallis variance analysis was used. The Spearman test was used to calculate the correlation coefficients and determine the statistical significance of relationships between non-normally distributed variables. The most appropriate cut-off value for predicting antibody positivity according to PRL levels was calculated using ROC analysis. The significance level was accepted as p < 0.05 Results The median age of the 701 individuals in the study group is 37 years (range 18–69 years), and 91.9% (n = 644) are women. The median PRL level in the study group is 16 (minimum 4.05, maximum 201), with 30.2% (n = 212) having PRL ≥ 25. Of the patients with HPRL, 49 have a tumoral origin (non-tumoral n = 163), and the diameter of the pituitary adenoma ranges from a minimum of 1.5 mm to a maximum of 45 mm. The hormonal and demographic data of the HPRL and healthy control groups are provided in Table 1 . Table 1 The study group had specific demographic and hormonal parameters. PRL ≥ 25 (n = 212) PRL < 25 (n = 489) p Age (year) 35.5 (18–69) 37 (18–68) 0.331 Gender (female ) n (%) 92.9 (197) 91.4 (447) 0.501 PRL 41.1 (26.0-201.0) 11.9 (4.1–24.8) 0.000 TSH (µIU/mL) 1.97 (0.35–4.93) 1.50 (0.35–4.88) 0.000 fT4 (ng/dL) 0.98 (0.40–1.66) 1.0 (0.45–2.65) 0.038 Anti-TPO positivity n (%) 62 (29.2) 75 (15.3) 0.000 Anti-Tg positivity n (%) 34 (16.0) 32 (6.5) 0.000 Anti-TPO Titer (min/max) 2.96 (0.18–1000.0) 0.61 (0.01–1000.0) 0.000 Anti-Tg Titer (min /max) 1.41 (0.54–1000.0) 1.20 (0.24–1000.0) 0.000 Thyroid ultrasound: Presence of hypoechoic pattern n (%) 38.7 (24) 30.5 (36) 0.267 Autoimmune thyroid disease diagnosis n (%) 71 (33.5) 115 (23.5) 0.006 Abbreviations: TSH: Thyroid-stimulating hormone. fT4 : Free Thyroxine. Anti-Tg: Anti-Thyroglobulin Anti -Tpo: Anti-Thyroid Peroxidase USG: U ltrasonograph Table 2: Thyroid function tests based on prolactin levels and thyroid autoantibodies. PRL≥25-<50 (n=134) PRL ≥ 50 -<100 (n=56) PRL ≥ 100 (n=22) p TSH (μIU/mL) 1.91 (0.35-4.92) 2.05 (0.35-4.85) 2.64 (0.40-4.93) 0.076 fT4 (ng/dL) 0.99 (0.40-1.66) 0.97 (0.56-1.43) 0.97 (0.40-1.16) 0.705 Anti-Tg positivity n (%) 16 (11.9) 13 (23.2) 5 (22.7) 0.668 Anti-TPO positivity n (%) 37 (27.6) 19 (33.9) 6 (27.3) 0.103 Anti-TgTiter (min /max) 1.30 (0.54-1000.0) 1.76 (0.60-1000.0) 6.60 (1.70-1000.0)* 0.020 Anti-Tpo Titer (min/max) 1.70 (0.18-1000.0) 4.98 (0.40-1000.0) 6.81 (0.34-1000) 0.083 *Kruskal Wallis varyans analizi kullanılmıştır Abbreviations: TSH: Thyroid-stimulating hormone. fT4 : Free Thyroxine. Anti-Tg: Anti-Thyroglobulin Anti -Tpo: Anti-Thyroid Peroxidase In patients with PRL ≥ 25, the AITD rate is 33.5% (n = 71), while in healthy controls with PRL < 25, this rate drops to 23.5% (n = 115). The difference between the two groups is significant (p = 0.006). In patients with PRL ≥ 25, both the presence of and the titer for anti-Tg and anti-TPO are significantly higher (p < 0.001). TSH levels are significantly high-normal in individuals with PRL ≥ 25, while free T4 levels are significantly low-normal. There is a positive correlation between PRL levels and TSH, Anti-Tg and Anti-TPO levels, and a weak negative correlation between sT4 levels and these parameters (r = 0.200, p < 0.001 for TSH; r = 0.244, p < 0.001 for Anti-TPO; r = 0.182, p < 0.001 for Anti-Tg). (r = 0.182, p < 0.001; r = 0.244, p < 0.001; r = 0.200, p < 0.001; r = 0.098, p = 0.016). When the PRL levels were categorised into three groups: PRL ≥ 25–<50, PRL ≥ 50–<100 and PRL ≥ 100, we found that the Anti-Tg titer in the group with PRL ≥ 100 was higher than in the other two groups. These data are presented in Table 2. ROC analysis was used to predict antibody positivity based on PRL levels in a cut-off analysis performed in Fig. 1 . The PRL level that discriminated best between anti-TPO positivity and negativity was determined to be 21.77 ng/mL. At this cut-off value, the sensitivity was found to be 53.3%, with a specificity of 69.7%. For anti-Tg positivity, the most suitable cut-off value was found to be 21.92 ng/mL, with a calculated sensitivity of 59.4% and a specificity of 68.4%. These data are provided in Table 3 . Table 3 The relationship between anti-TPO and anti-Tg positivity, as well as the prolactin cut-off value Anti-TPO positivity Anti-Tg positivity PRL Cut-off 21.77 ng/mL 21.92 ng/mL Sensitivity (%) 53.3% 59.4% Specificity (%) 69.7% 68.4% AUC (ROC) 0.63 0.65 Abbreviations: Anti-Tg : Anti-Thyroglobulin Anti -Tpo : Anti-Thyroid Peroxidase Discussion In this study, we investigated the relationship between elevated PRL and AITD The results showed that 33.5% of patients with PRL ≥ 25 had AITD, with Anti-TPO and Anti-Tg positivity rates of 29.2% and 16.0%, respectively. The titres of these antibodies were higher compared to those of healthy controls with PRL < 25. Additionally, despite being euthyroid, TSH levels in the HPRL group were higher and sT4 levels were lower compared to the control group. In the literature, there are few studies on HPRL and thyroid autoimmunity, and the results are variable. Önal et al. found that thyroid autoimmunity in patients with HPRL was similar to that in the control group. 7 Ferrari et al. found significantly higher levels of thyroid autoantibodies in patients with HPRL compared to control groups: anti-microsomal Ab (12%), anti-Tg (20%), Kramer thyroid antibodies (57.1%), Giusti (29.6%), Saykı anti-TPO antibodies (63%) and anti-Tg antibodies (13%). 12, 11, 13, 10 Elenkova et al. found an AITD frequency of 21% in one of their studies on HPRL 8 and 29.9% in another study where thyroid ultrasound was added 9 . Despite some studies suggesting the opposite, our study supports the idea that high PRL levels may increase thyroid autoimmunity. As can be seen, the frequency of antibody levels varies considerably. The frequency of AITD varies depending on factors such as the addition of imaging methods, the predominance of females in the study population, and the thyroid antibodies measured. As is known, in prolactinomas, there is generally a relation between the PRL level and the adenoma diameter. The PRL level provides an indication of the adenoma diameter. However, PRL values between 25 and 100 are more often associated with reasons such as medication, stalk compression and idiopathic causes. It is thought that PRL at these levels serves other purposes. Therefore, the term 'Homeo FIT-PRL' has emerged in the literatüre. 14 It has been suggested that very high (> 100 ng/mL) and very low (< 7 ng/mL) PRL levels have negative effects, while moderate and mild levels have a protective effect on metabolic functions. 15 Similarly, it is not yet known whether PRL levels have a similar effect on thyroid autoimmunity and TFT levels. In our study, antibody positivity appears to begin at a PRL level of 22 ng/mL and above, with the PRL level correlated with the presence of both Anti-TPO and Anti-Tg. Studies that found otherwise 8 , 10 only exist for cases in which a weak correlation was detected between anti-TPO and PRL. 9 Ultimately, PRL indicates that the risk of AITD begins at moderately high levels. However, since the highest PRL level in our study remained at 200, we cannot comment clearly on whether there is a linear correlation between PRL level and the presence of autoantibodies. Further studies should be conducted with patients who have higher PRL levels (such as > 500 ng/mL). Additionally, the finding of higher anti-Tg titres in the group with PRL ≥ 100 compared to those with lower PRL levels suggests that there may be a correlation between high PRL levels and progression to hypothyroidism. The pathophysiology of AITD has not been fully elucidated. Various factors are being blamed, including genetic background, geographical factors, endocrine disruptors, gender, iodine status, environmental factors and hormones. Among these, the non-classical effects of PRL, such as its impact on calcium metabolism, insulin resistance, atherogenicity and the immune system, have begun to attract attention alongside its classical effects. 1, 2 It has been suggested that PRL plays an important role in modulating the immune system, particularly in cases of elevated PRL levels. This is thought to be achieved by PRL inducing B-cell tolerance, enhancing antigen presentation and antibody production, increasing cytokine production and inhibiting apoptosis. 5 , 16 , 19 , 20 , 21 .Due to these effects on the immune system, PRL may be responsible for the development of autoimmune diseases. Indeed, in addition to its role in the onset of autoimmune diseases, PRL has also been found to affect the course, prognosis and complications of these diseases. For instance, the level of anti-ds-DNA in SLE patients has been found to be positively correlated with thyroid antibodies and associated with disease complications such as kidney involvement, serositis, and anaemia. Furthermore, SLE activation has been found to decrease after DA treatment. 17 Similarly, studies have shown that patients receiving DA treatment have reduced thyroid autoimmunity compared to untreated patients. 9,11 New research studies could explore the option of DA treatment as a way to reduce thyroid antibodies and halt the progression to hypothyroidism. The results of studies evaluating TFT in patients with HPRL vary considerably . 7, 8, 9, 10, 18 In our study, individuals with TFT disorders were excluded due to the impact of hypo- and hyperthyroidism on PRL levels. Interestingly, despite being euthyroid, participants had higher TSH levels and lower sT4 levels than the healthy control group. Two studies conducted in our country observed a similar decrease in sT4 levels. 7 , 10 This similarity can be explained by iodine deficiency due to shared geographical characteristics. The elevation of TSH can be explained by two mechanisms. Firstly, in patients with HPRL, TSH may escape dopamine inhibition. Secondly, elevated PRL levels are associated with the activation of humoral immune pathways and the formation of blocking antibodies, which leads to a tendency towards hypothyroidism. The strengths of the study are its sufficient sample size, the fact that the participants were euthyroid and the inclusion of untreated HPRL patients. The limitations are that the study design is retrospective, PRL levels do not exceed 200, iodine status could not be determined and data such as participants' body mass index is missing. In conclusion, it is difficult to establish a direct relationship between HPRL and AITD. While our study supports this, it indicates that, in addition to its classical effects, PRL contributes to autoimmunity by affecting the immune system. Alongside studies on high PRL levels, research into thyroid autoimmunity at very low PRL levels should also be conducted. In patients with HPRL, routine TFT, Anti-TPO, and Anti-Tg testing for the diagnosis of AITD is recommended. This testing has not yet been included in the guidelines. In this area, well-designed multicentre case-control studies are needed. Declarations **“All data generated or analyzed during this study are available and can be shared upon reasonable request.” **‘The authors declare that they have no conflict of interest.” ** The authors declare that this study received no funding and no sponsorship from any public, commercial, ” References Reuwer AQ, van Eijk M, Houttuijn-Bloemendaal FM, van der Loos CM, Claessen N, Teeling P, et al. The prolactin receptor is expressed in macrophages within human carotid atherosclerotic plaques: a role for prolactin in atherogenesis? J Endocrinol 2011;208:107–17 Hietala M, Olsson H, Jernstrom H. Prolactin levels, breast-feeding and milk production in a cohort of young healthy women from high-risk breast cancer families: implications for breast cancer risk. Fam Cancer 2008;7:221–8 Shelly S, Boaz M, Orbach H. Prolactin and autoimmunity. Autoimmun Rev. 2012; May;11(6-7):A465-70 Tang MW, Garcia S, Gerlag DM, Tak PP, Reedquist KA. Insight into the endocrine system and the immune system: a review of the inflammatory role of prolactin in rheumatoid arthritis and psoriatic arthritis. Front Immunol. 2017; 8:720. De Bellis A, Bizzarro A, Pivonello R, Lombardi G, Bellastella A. Prolactin and autoimmunity. Pituitary. 2005;8(1):25-30. doi: 10.1007/s11102-005-5082-5 Arango MT, Perricone C, Kivity S, Cipriano E, Ceccarelli F, Valesini G, et al. HLA-DRB1 the notorious gene in the mosaic of autoimmunity. Immunol Res 2017; 65(1):82–98. Onal ED, Saglam F, Sacikara M, Ersoy R, Cakir B. Thyroid autoimmunity in patients with hyperprolactinemia: an observational study. Arq Bras Endocrinol Metabol. 2014; Feb;58(1):48-52 Elenkova A, Petrossians P, Zacharieva S, Beckers A. High prevalence of autoimmune thyroid diseases in patients with prolactinomas: A cross-sectional retrospective study in a single tertiary referral centre. Ann Endocrinol. 2016 Feb;77(1):37-42. doi: 10.1016/j.ando.2015.10.008 Elenkova A, Аtanasova I, Кirilov G, Natchev Е, Ivanova R, Кovatcheva R, Vandeva S, Tcharaktchiev D, Zacharieva S. Autoimmune hypothyroidism is three times more frequent in female prolactinoma patients compared to healthy women: data from a cross-sectional case-control study. Endocrine. 2017 Sep;57(3):486-493. doi: 10.1007/s12020-017-1372-8. Sayki Arslan M, Sahin M, Topaloglu O, Tutal E, Karakose M, Gungunes A, Cakal E, Ozbek M, Delibasi T. Hyperprolactinaemia associated with increased thyroid volume and autoimmune thyroiditis in patients with prolactinoma. Clin Endocrinol. 2013; Dec;79(6):882-6. Kramer, C.K., Tourinho, T.F., de Castro, W.P. et al. Association between systemic lupus erythematosus, rheumatoid arthritis, hyperprolactinemia and thyroid autoantibodies. Archives of Medical Research. 2005; 36, 54–58 Ferrari, C., Boghen, M., Paracchi, A. et al. Thyroid autoimmunity in hyperprolactinaemic disorders. Acta Endocrinologica. 1983; 104, 35–41 Giusti M, Foppiani L, Fazzuoli L, Molinari E, Guido R, Valenti S, Giordano G. An increased prevalence of thyroid echographic and autoimmune changes in hyperprolactinemic women on therapy with dopaminergic drugs Recenti Prog Med. 1999 Mar;90(3):147-51. Italian. Pirchio R, Graziadio C, Colao A, Pivonello R, Auriemma RS. Metabolic effects of prolactin. Front Endocrinol.2022 Sep27;13:1015520. doi: 10.3389/fendo.2022.1015520. Macotela Y, Ruiz-Herrera X, Vázquez-Carrillo DI, Ramírez-Hernandez G, Martínez de la Escalera G, Clapp C. The beneficial metabolic actions of prolactin. Front Endocrinol. 2022 Sep 23;13:1001703. doi: 10.3389/fendo.2022.1001703. Ishibashi, M., Kuzuya, N., Sawada, S. et al. Anti-thyroid antibodies in patients with hyperprolactinemia. Endocrinologia Japonica.1991; 38, 517–522. 15 Rezaieyazdi Z, Hesamifard A. Correlation between serum prolactin levels and lupus activity. Rheumatol Int. 2006 Sep;26(11):1036-9. doi: 10.1007/s00296-006-0129-0. Dieguez, C., Peters, J.R., Page, M.D. et al. (1986) Thyroid function in patients with hyperprolactinaemia: relationship to dopaminergic inhibition of TSH release. Clinical Endocrinology, 25, 435–440 Borba VV, Zandman-Goddard G and Shoenfeld Y Prolactin and Autoimmunity. Front. Immunol. 2018; 9:73. Dong YH, Fu DG. Autoimmune thyroid disease: mechanism, genetics and current knowledge. Eur Rev Med Pharmacol Sci 2014; 18(23):3611–8. 114. Yamamoto M, Iguchi G, Takeno R, Okimura Y, Sano T, Takahashi M, et al. Adult combined GH, prolactin, and TSH deficiency associated with circulating PIT-1 antibody in humans. J Clin Invest. 2011; 121(1):113–9. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 26 Feb, 2026 Reviews received at journal 11 Feb, 2026 Reviews received at journal 31 Jan, 2026 Reviewers agreed at journal 24 Jan, 2026 Reviewers agreed at journal 23 Jan, 2026 Reviewers invited by journal 19 Jan, 2026 Editor invited by journal 09 Jan, 2026 Editor assigned by journal 09 Jan, 2026 Submission checks completed at journal 09 Jan, 2026 First submitted to journal 05 Jan, 2026 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-8523918","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":577118847,"identity":"5ce0385c-af82-476c-956c-06c72c11fabb","order_by":0,"name":"SEHER ÇETİNKAYA 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07:15:18","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":81158,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8523918/v1/6b9cfdbe1077314d91457cf9.html"},{"id":100949258,"identity":"c7ecf375-c8ba-4a5d-a29e-2cd6293d6582","added_by":"auto","created_at":"2026-01-23 06:56:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":56698,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe relationship between anti-TPO and anti-Tg positivity. It also shows the prolactin cut-off value.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e \u003cstrong\u003eAnti-Tg: \u003c/strong\u003eAnti-Thyroglobulin \u003cstrong\u003eAnti -Tpo: \u003c/strong\u003eAnti-Thyroid Peroxidase\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8523918/v1/286e51d62995b0aa9c2cceaa.png"},{"id":101397575,"identity":"94f84a38-f770-4fd0-9c56-a07bd8120096","added_by":"auto","created_at":"2026-01-29 09:29:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":794195,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8523918/v1/db43e81f-28b6-4c81-895d-0a10ed17d2b9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eAutoimmune thyroid disease - is high prolactin a risk factor?\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eProlactin (PRL) is a polypeptide hormone that is secreted by the anterior pituitary gland. It is synthesised not only in the pituitary gland, but also by neurons, adipocytes, endothelial cells, immune cells, thymocytes and peripheral blood cells, especially lymphocytes. The primary function of PRL is well known: breast growth and lactation. In addition to these classical effects, PRL also affects calcium-bone metabolism, insulin resistance, atherogenicity and the immune system.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Recently, the effects of PRL on the immune system have attracted significant attention. The effects of PRL on the immune system have recently attracted considerable interest. PRL receptors are expressed in monocytes, macrophages, T- and B-lymphocytes, natural killer cells, granulocytes, natural killer cells, granulocytes and thymic epithelial cells .\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Although the mechanism is not fully understood, PRL can trigger some autoimmune diseases and play a role in their pathogenesis and the clinical course of these diseases. \u003csup\u003e4\u003c/sup\u003e It is thought that it achieves this by inducing B-cell tolerance at a genetic level, increasing the presentation of antigens and antibodies, and the production of cytokines, while also inhibiting apoptosis. \u003csup\u003e5\u003c/sup\u003e The PRL gene HLA-DRB1 is located on the short arm of chromosome 6. This region is also associated with immune-mediated diseases. \u003csup\u003e6\u003c/sup\u003e The relationship between PRL and autoimmunity has been studied more extensively in diseases such as rheumatoid arthritis, antiphospholipid syndrome, systemic lupus erythematosus (SLE) and multiple sclerosis. However, the number of studies related to autoimmune thyroid disease (AITD) is limited and the results are inconsistent. \u003csup\u003e7, 8, 9, 10, 11\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn this study, we aimed to compare the levels of thyroid autoantibodies and the frequency of thyroid autoimmunity in patients with PRL\u0026thinsp;\u0026ge;\u0026thinsp;25 with a healthy control group with PRL\u0026thinsp;\u0026lt;\u0026thinsp;25 and to determine the relationship between PRL levels and these autoantibodies and thyroid function tests (TFT).\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy sample\u003c/h2\u003e \u003cp\u003eOur study is a retrospective, single-centre, case-control study. Between 2021 and 2024, we examined patients diagnosed with hyperprolactinemia (HPRL) who had test results for PRL, TSH, free thyroxine (fT4), thyroid peroxidase antibody (anti-TPO) and thyroglobulin antibody (anti-Tg) from the Endocrinology and Metabolism outpatient clinic at Bursa Y\u0026uuml;ksek İhtisas Hospital, which is part of the University of Health Sciences.\u003c/p\u003e \u003cp\u003ePatients aged 18\u0026ndash;70 with a PRL level of 25 or above, regardless of the aetiology of HPRL, who had not received treatment, were included in the study. The healthy control group consisted of individuals with a PRL level below 25 and no additional diseases who were referred from occupational health clinics or attended for check-ups. A total of 835 patients were recorded. We excluded 134 patients who had missing data or did not meet the specified criteria. patients with missing data or who did not meet the specified criteria were excluded. A total of 701 patients were included in the study. All patient information was obtained from our hospital's computer database. The following were excluded from the study as they could affect the results:\u003c/p\u003e \u003cp\u003e1) History of pregnancy and breastfeeding 2) Patients with TFT levels outside the reference range 3) Diagnosis of diabetes mellitus 4) Diagnosis of acute or chronic liver and kidney disease 5) History of thyroid surgery 6) History of receiving radioactive iodine/radiotherapy 7) History of using dopamine agonists (DA) were excluded from the study as this could affect the results. TSH, fT4, Anti-TPO and Anti-Tg values were recorded in the patient and control groups. Thyroid ultrasonography (USG) was used to evaluate the presence of hypoechoic, diffusely heterogeneous echogenicity or pseudonodules in favour of autoimmunity. In patients with pituitary adenoma detected by magnetic resonance imaging, the adenoma size was recorded in millimetres (mm).\u003c/p\u003e \u003cp\u003eIn our hospital laboratory, the normal reference ranges for TSH and fT4 are 0.35\u0026ndash;4.94 \u0026micro;IU/mL and 0.7\u0026ndash;2.77 ng/dL, respectively. The normal reference ranges for anti-Tg and anti-TPO are 0\u0026ndash;4.11 IU/mL and 0\u0026ndash;5.61 IU/mL, respectively. As antibody positivity can also occur in healthy individuals, an antibody titer of \u0026ge;\u0026thinsp;45 IU/mL was considered positive. Patients with at least one positive antibody and/or an autoimmune pattern on thyroid ultrasound were defined as having AITD. All data were compared with those of the healthy control group.\u003c/p\u003e \u003cp\u003ePrior to the study, necessary permission was obtained from the Ethics Committee of SB\u0026Uuml; Bursa Y\u0026uuml;ksek İhtisas Training and Research Hospital (Approval No. 2024-TBEK-2025/03\u0026ndash;08, Approval Date. 12/03/2025). Due to the retrospective design of the study, written informed consent was waived. All procedures performed in this study were conducted in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments, or comparable ethical standards.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData analysis was performed using the SPSS v.25 statistical program. For the descriptive findings, variables specified by count are presented as numbers and percentages, while variables measured are indicated by the median (minimum \u0026ndash; maximum), bearing in mind that the data does not conform to a normal distribution. The distribution characteristic of the measured variables was evaluated using the Kolmogorov\u0026ndash;Smirnov test. For binary analyses, the chi-square test was used for categorical variables indicated by counts and the Mann\u0026ndash;Whitney U test for variables indicated by measurements. For comparisons involving more than two measurements, Kruskal\u0026ndash;Wallis variance analysis was used. The Spearman test was used to calculate the correlation coefficients and determine the statistical significance of relationships between non-normally distributed variables. The most appropriate cut-off value for predicting antibody positivity according to PRL levels was calculated using ROC analysis. The significance level was accepted as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe median age of the 701 individuals in the study group is 37 years (range 18\u0026ndash;69 years), and 91.9% (n\u0026thinsp;=\u0026thinsp;644) are women. The median PRL level in the study group is 16 (minimum 4.05, maximum 201), with 30.2% (n\u0026thinsp;=\u0026thinsp;212) having PRL\u0026thinsp;\u0026ge;\u0026thinsp;25. Of the patients with HPRL, 49 have a tumoral origin (non-tumoral n\u0026thinsp;=\u0026thinsp;163), and the diameter of the pituitary adenoma ranges from a minimum of 1.5 mm to a maximum of 45 mm. The hormonal and demographic data of the HPRL and healthy control groups are provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe study group had specific demographic and hormonal parameters.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePRL\u0026thinsp;\u0026ge;\u0026thinsp;25 (n\u0026thinsp;=\u0026thinsp;212)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePRL\u0026thinsp;\u0026lt;\u0026thinsp;25\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;489)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (year)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35.5 (18\u0026ndash;69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (18\u0026ndash;68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.331\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender (female ) n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e92.9 (197)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91.4 (447)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.501\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePRL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e41.1 (26.0-201.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.9 (4.1\u0026ndash;24.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTSH (\u0026micro;IU/mL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.97 (0.35\u0026ndash;4.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.50 (0.35\u0026ndash;4.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003efT4 (ng/dL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.98 (0.40\u0026ndash;1.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0 (0.45\u0026ndash;2.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.038\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti-TPO positivity\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e62 (29.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti-Tg positivity\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34 (16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti-TPO\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eTiter (min/max)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.96 (0.18\u0026ndash;1000.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.61 (0.01\u0026ndash;1000.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti-Tg Titer (min /max)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.41 (0.54\u0026ndash;1000.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.20 (0.24\u0026ndash;1000.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThyroid ultrasound: Presence of hypoechoic pattern n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e38.7 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.5 (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.267\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAutoimmune thyroid disease diagnosis\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e71 (33.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e115 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e \u003cstrong\u003eTSH:\u003c/strong\u003e Thyroid-stimulating hormone.\u003cstrong\u003e\u0026nbsp;fT4\u003c/strong\u003e: Free Thyroxine. \u003cstrong\u003eAnti-Tg:\u0026nbsp;\u003c/strong\u003eAnti-Thyroglobulin \u003cstrong\u003eAnti -Tpo:\u0026nbsp;\u003c/strong\u003eAnti-Thyroid Peroxidase \u0026nbsp; \u0026nbsp;\u003cstrong\u003eUSG: U\u003c/strong\u003eltrasonograph\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 2:\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eThyroid function tests based on prolactin levels and thyroid autoantibodies.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"680\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9118%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.4118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;PRL\u0026ge;25-\u0026lt;50 (n=134)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2647%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePRL \u0026ge; 50\u0026nbsp;-\u0026lt;100\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=56)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.4118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePRL \u0026ge; 100\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=22)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15%;\"\u003e\n \u003cp\u003ep\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSH (\u0026mu;IU/mL)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.4118%;\"\u003e\n \u003cp\u003e1.91 (0.35-4.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2647%;\"\u003e\n \u003cp\u003e2.05 (0.35-4.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.4118%;\"\u003e\n \u003cp\u003e2.64 (0.40-4.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15%;\"\u003e\n \u003cp\u003e0.076\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003efT4 (ng/dL)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.4118%;\"\u003e\n \u003cp\u003e0.99 (0.40-1.66)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2647%;\"\u003e\n \u003cp\u003e\u0026nbsp;0.97 (0.56-1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.4118%;\"\u003e\n \u003cp\u003e0.97 (0.40-1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15%;\"\u003e\n \u003cp\u003e\u0026nbsp;0.705\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnti-Tg\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003epositivity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.4118%;\"\u003e\n \u003cp\u003e16 (11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2647%;\"\u003e\n \u003cp\u003e13 (23.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.4118%;\"\u003e\n \u003cp\u003e5 (22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15%;\"\u003e\n \u003cp\u003e0.668\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnti-TPO\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003epositivity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.4118%;\"\u003e\n \u003cp\u003e37 (27.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2647%;\"\u003e\n \u003cp\u003e19 (33.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.4118%;\"\u003e\n \u003cp\u003e6 (27.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15%;\"\u003e\n \u003cp\u003e0.103\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnti-TgTiter (min /max)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.4118%;\"\u003e\n \u003cp\u003e1.30 (0.54-1000.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2647%;\"\u003e\n \u003cp\u003e\u0026nbsp;1.76 (0.60-1000.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.4118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.60 (1.70-1000.0)*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;0.020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnti-Tpo Titer (min/max)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.4118%;\"\u003e\n \u003cp\u003e1.70 (0.18-1000.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.2647%;\"\u003e\n \u003cp\u003e\u0026nbsp;4.98 (0.40-1000.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.4118%;\"\u003e\n \u003cp\u003e6.81 (0.34-1000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15%;\"\u003e\n \u003cp\u003e\u0026nbsp;0.083\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Kruskal Wallis varyans analizi kullanılmıştır \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e \u003cstrong\u003eTSH:\u003c/strong\u003e Thyroid-stimulating hormone.\u003cstrong\u003e\u0026nbsp;fT4\u003c/strong\u003e: Free Thyroxine. \u003cstrong\u003eAnti-Tg:\u0026nbsp;\u003c/strong\u003eAnti-Thyroglobulin \u003cstrong\u003eAnti -Tpo:\u0026nbsp;\u003c/strong\u003eAnti-Thyroid Peroxidase\u003c/p\u003e\u003cp\u003eIn patients with PRL\u0026thinsp;\u0026ge;\u0026thinsp;25, the AITD rate is 33.5% (n\u0026thinsp;=\u0026thinsp;71), while in healthy controls with PRL\u0026thinsp;\u0026lt;\u0026thinsp;25, this rate drops to 23.5% (n\u0026thinsp;=\u0026thinsp;115). The difference between the two groups is significant (p\u0026thinsp;=\u0026thinsp;0.006). In patients with PRL\u0026thinsp;\u0026ge;\u0026thinsp;25, both the presence of and the titer for anti-Tg and anti-TPO are significantly higher (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). TSH levels are significantly high-normal in individuals with PRL\u0026thinsp;\u0026ge;\u0026thinsp;25, while free T4 levels are significantly low-normal. There is a positive correlation between PRL levels and TSH, Anti-Tg and Anti-TPO levels, and a weak negative correlation between sT4 levels and these parameters (r\u0026thinsp;=\u0026thinsp;0.200, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for TSH; r\u0026thinsp;=\u0026thinsp;0.244, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for Anti-TPO; r\u0026thinsp;=\u0026thinsp;0.182, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for Anti-Tg). (r\u0026thinsp;=\u0026thinsp;0.182, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; r\u0026thinsp;=\u0026thinsp;0.244, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; r\u0026thinsp;=\u0026thinsp;0.200, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; r\u0026thinsp;=\u0026thinsp;0.098, p\u0026thinsp;=\u0026thinsp;0.016).\u003c/p\u003e \u003cp\u003eWhen the PRL levels were categorised into three groups: PRL\u0026thinsp;\u0026ge;\u0026thinsp;25\u0026ndash;\u0026lt;50, PRL\u0026thinsp;\u0026ge;\u0026thinsp;50\u0026ndash;\u0026lt;100 and PRL\u0026thinsp;\u0026ge;\u0026thinsp;100, we found that the Anti-Tg titer in the group with PRL\u0026thinsp;\u0026ge;\u0026thinsp;100 was higher than in the other two groups. These data are presented in Table\u0026nbsp;2.\u003c/p\u003e \u003cp\u003eROC analysis was used to predict antibody positivity based on PRL levels in a cut-off analysis performed in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The PRL level that discriminated best between anti-TPO positivity and negativity was determined to be 21.77 ng/mL. At this cut-off value, the sensitivity was found to be 53.3%, with a specificity of 69.7%. For anti-Tg positivity, the most suitable cut-off value was found to be 21.92 ng/mL, with a calculated sensitivity of 59.4% and a specificity of 68.4%. These data are provided in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe relationship between anti-TPO and anti-Tg positivity, as well as the prolactin cut-off value\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnti-TPO positivity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-Tg positivity\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePRL Cut-off\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.77 ng/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.92 ng/mL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSensitivity (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSpecificity (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAUC (ROC)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cb\u003eAbbreviations: Anti-Tg\u003c/b\u003e: Anti-Thyroglobulin \u003cb\u003eAnti -Tpo\u003c/b\u003e: Anti-Thyroid Peroxidase\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we investigated the relationship between elevated PRL and AITD The results showed that 33.5% of patients with PRL\u0026thinsp;\u0026ge;\u0026thinsp;25 had AITD, with Anti-TPO and Anti-Tg positivity rates of 29.2% and 16.0%, respectively. The titres of these antibodies were higher compared to those of healthy controls with PRL\u0026thinsp;\u0026lt;\u0026thinsp;25. Additionally, despite being euthyroid, TSH levels in the HPRL group were higher and sT4 levels were lower compared to the control group.\u003c/p\u003e \u003cp\u003eIn the literature, there are few studies on HPRL and thyroid autoimmunity, and the results are variable. \u0026Ouml;nal et al. found that thyroid autoimmunity in patients with HPRL was similar to that in the control group. \u003csup\u003e7\u003c/sup\u003e Ferrari et al. found significantly higher levels of thyroid autoantibodies in patients with HPRL compared to control groups: anti-microsomal Ab (12%), anti-Tg (20%), Kramer thyroid antibodies (57.1%), Giusti (29.6%), Saykı anti-TPO antibodies (63%) and anti-Tg antibodies (13%).\u003csup\u003e12, 11, 13, 10\u003c/sup\u003e Elenkova et al. found an AITD frequency of 21% in one of their studies on HPRL \u003csup\u003e8\u003c/sup\u003e and 29.9% in another study where thyroid ultrasound was added \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Despite some studies suggesting the opposite, our study supports the idea that high PRL levels may increase thyroid autoimmunity. As can be seen, the frequency of antibody levels varies considerably. The frequency of AITD varies depending on factors such as the addition of imaging methods, the predominance of females in the study population, and the thyroid antibodies measured.\u003c/p\u003e \u003cp\u003eAs is known, in prolactinomas, there is generally a relation between the PRL level and the adenoma diameter. The PRL level provides an indication of the adenoma diameter. However, PRL values between 25 and 100 are more often associated with reasons such as medication, stalk compression and idiopathic causes. It is thought that PRL at these levels serves other purposes. Therefore, the term 'Homeo FIT-PRL' has emerged in the literat\u0026uuml;re. \u003csup\u003e14\u003c/sup\u003e It has been suggested that very high (\u0026gt;\u0026thinsp;100 ng/mL) and very low (\u0026lt;\u0026thinsp;7 ng/mL) PRL levels have negative effects, while moderate and mild levels have a protective effect on metabolic functions. \u003csup\u003e15\u003c/sup\u003e Similarly, it is not yet known whether PRL levels have a similar effect on thyroid autoimmunity and TFT levels. In our study, antibody positivity appears to begin at a PRL level of 22 ng/mL and above, with the PRL level correlated with the presence of both Anti-TPO and Anti-Tg. Studies that found otherwise \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e only exist for cases in which a weak correlation was detected between anti-TPO and PRL. \u003csup\u003e9\u003c/sup\u003e Ultimately, PRL indicates that the risk of AITD begins at moderately high levels. However, since the highest PRL level in our study remained at 200, we cannot comment clearly on whether there is a linear correlation between PRL level and the presence of autoantibodies. Further studies should be conducted with patients who have higher PRL levels (such as \u0026gt;\u0026thinsp;500 ng/mL). Additionally, the finding of higher anti-Tg titres in the group with PRL\u0026thinsp;\u0026ge;\u0026thinsp;100 compared to those with lower PRL levels suggests that there may be a correlation between high PRL levels and progression to hypothyroidism.\u003c/p\u003e \u003cp\u003eThe pathophysiology of AITD has not been fully elucidated. Various factors are being blamed, including genetic background, geographical factors, endocrine disruptors, gender, iodine status, environmental factors and hormones. Among these, the non-classical effects of PRL, such as its impact on calcium metabolism, insulin resistance, atherogenicity and the immune system, have begun to attract attention alongside its classical effects. \u003csup\u003e1, 2\u003c/sup\u003e It has been suggested that PRL plays an important role in modulating the immune system, particularly in cases of elevated PRL levels. This is thought to be achieved by PRL inducing B-cell tolerance, enhancing antigen presentation and antibody production, increasing cytokine production and inhibiting apoptosis. \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.Due to these effects on the immune system, PRL may be responsible for the development of autoimmune diseases. Indeed, in addition to its role in the onset of autoimmune diseases, PRL has also been found to affect the course, prognosis and complications of these diseases. For instance, the level of anti-ds-DNA in SLE patients has been found to be positively correlated with thyroid antibodies and associated with disease complications such as kidney involvement, serositis, and anaemia. Furthermore, SLE activation has been found to decrease after DA treatment. \u003csup\u003e17\u003c/sup\u003e Similarly, studies have shown that patients receiving DA treatment have reduced thyroid autoimmunity compared to untreated patients. \u003csup\u003e9,11\u003c/sup\u003e New research studies could explore the option of DA treatment as a way to reduce thyroid antibodies and halt the progression to hypothyroidism.\u003c/p\u003e \u003cp\u003eThe results of studies evaluating TFT in patients with HPRL vary considerably .\u003csup\u003e7, 8, 9, 10, 18\u003c/sup\u003e In our study, individuals with TFT disorders were excluded due to the impact of hypo- and hyperthyroidism on PRL levels. Interestingly, despite being euthyroid, participants had higher TSH levels and lower sT4 levels than the healthy control group. Two studies conducted in our country observed a similar decrease in sT4 levels. \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e This similarity can be explained by iodine deficiency due to shared geographical characteristics. The elevation of TSH can be explained by two mechanisms. Firstly, in patients with HPRL, TSH may escape dopamine inhibition. Secondly, elevated PRL levels are associated with the activation of humoral immune pathways and the formation of blocking antibodies, which leads to a tendency towards hypothyroidism.\u003c/p\u003e \u003cp\u003eThe strengths of the study are its sufficient sample size, the fact that the participants were euthyroid and the inclusion of untreated HPRL patients. The limitations are that the study design is retrospective, PRL levels do not exceed 200, iodine status could not be determined and data such as participants' body mass index is missing.\u003c/p\u003e \u003cp\u003eIn conclusion, it is difficult to establish a direct relationship between HPRL and AITD. While our study supports this, it indicates that, in addition to its classical effects, PRL contributes to autoimmunity by affecting the immune system. Alongside studies on high PRL levels, research into thyroid autoimmunity at very low PRL levels should also be conducted. In patients with HPRL, routine TFT, Anti-TPO, and Anti-Tg testing for the diagnosis of AITD is recommended. This testing has not yet been included in the guidelines. In this area, well-designed multicentre case-control studies are needed.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e**\u0026ldquo;All data generated or analyzed during this study are available and can be shared upon reasonable request.\u0026rdquo;\u003c/p\u003e \u003cp\u003e**\u0026lsquo;The authors declare that they have no conflict of interest.\u0026rdquo;\u003c/p\u003e \u003cp\u003e** The authors declare that this study received no funding and no sponsorship from any public, commercial, \u0026rdquo;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eReuwer AQ, van Eijk M, Houttuijn-Bloemendaal FM, van der Loos CM, Claessen N, Teeling P, et al. The prolactin receptor is expressed in macrophages within human carotid atherosclerotic plaques: a role for prolactin in atherogenesis? J Endocrinol 2011;208:107–17\u003c/li\u003e\n \u003cli\u003eHietala M, Olsson H, Jernstrom H. Prolactin levels, breast-feeding and milk production in a cohort of young healthy women from high-risk breast cancer families: implications for breast cancer risk. Fam Cancer 2008;7:221–8\u003c/li\u003e\n \u003cli\u003eShelly S, Boaz M, Orbach H. Prolactin and autoimmunity. Autoimmun Rev. 2012; May;11(6-7):A465-70\u003c/li\u003e\n \u003cli\u003eTang MW, Garcia S, Gerlag DM, Tak PP, Reedquist KA. Insight into the endocrine system and the immune system: a review of the inflammatory role of prolactin in rheumatoid arthritis and psoriatic arthritis. Front Immunol. 2017; 8:720.\u003c/li\u003e\n \u003cli\u003eDe Bellis A, Bizzarro A, Pivonello R, Lombardi G, Bellastella A. Prolactin and autoimmunity. Pituitary. 2005;8(1):25-30. doi: 10.1007/s11102-005-5082-5\u003c/li\u003e\n \u003cli\u003eArango MT, Perricone C, Kivity S, Cipriano E, Ceccarelli F, Valesini G, et al. HLA-DRB1 the notorious gene in the mosaic of autoimmunity. Immunol Res 2017; 65(1):82–98.\u003c/li\u003e\n \u003cli\u003eOnal ED, Saglam F, Sacikara M, Ersoy R, Cakir B. Thyroid autoimmunity in patients with hyperprolactinemia: an observational study. Arq Bras Endocrinol Metabol. 2014; Feb;58(1):48-52\u003c/li\u003e\n \u003cli\u003eElenkova A, Petrossians P, Zacharieva S, Beckers A. High prevalence of autoimmune thyroid diseases in patients with prolactinomas: A cross-sectional retrospective study in a single tertiary referral centre. Ann Endocrinol. 2016 Feb;77(1):37-42. doi: 10.1016/j.ando.2015.10.008\u003c/li\u003e\n \u003cli\u003eElenkova A, Аtanasova I, Кirilov G, Natchev Е, Ivanova R, Кovatcheva R, Vandeva S, Tcharaktchiev D, Zacharieva S. Autoimmune hypothyroidism is three times more frequent in female prolactinoma patients compared to healthy women: data from a cross-sectional case-control study. Endocrine. 2017 Sep;57(3):486-493. doi: 10.1007/s12020-017-1372-8.\u003c/li\u003e\n \u003cli\u003eSayki Arslan M, Sahin M, Topaloglu O, Tutal E, Karakose M, Gungunes A, Cakal E, Ozbek M, Delibasi T. Hyperprolactinaemia associated with increased thyroid volume and autoimmune thyroiditis in patients with prolactinoma. Clin Endocrinol. 2013; Dec;79(6):882-6.\u003c/li\u003e\n \u003cli\u003eKramer, C.K., Tourinho, T.F., de Castro, W.P. et al. Association between systemic lupus erythematosus, rheumatoid arthritis, hyperprolactinemia and thyroid autoantibodies. Archives of Medical Research. 2005; 36, 54–58\u003c/li\u003e\n \u003cli\u003eFerrari, C., Boghen, M., Paracchi, A. et al. Thyroid autoimmunity in hyperprolactinaemic disorders. Acta Endocrinologica. 1983; 104, 35–41\u003c/li\u003e\n \u003cli\u003eGiusti M, Foppiani L, Fazzuoli L, Molinari E, Guido R, Valenti S, Giordano G. An increased prevalence of thyroid echographic and autoimmune changes in hyperprolactinemic women on therapy with dopaminergic drugs Recenti Prog Med. 1999 Mar;90(3):147-51. Italian.\u003c/li\u003e\n \u003cli\u003ePirchio R, Graziadio C, Colao A, Pivonello R, Auriemma RS. Metabolic effects of prolactin. Front Endocrinol.2022 Sep27;13:1015520. doi: 10.3389/fendo.2022.1015520.\u003c/li\u003e\n \u003cli\u003eMacotela Y, Ruiz-Herrera X, Vázquez-Carrillo DI, Ramírez-Hernandez G, Martínez de la Escalera G, Clapp C. The beneficial metabolic actions of prolactin. Front Endocrinol. 2022 Sep 23;13:1001703. doi: 10.3389/fendo.2022.1001703.\u003c/li\u003e\n \u003cli\u003eIshibashi, M., Kuzuya, N., Sawada, S. et al. Anti-thyroid antibodies in patients with hyperprolactinemia. Endocrinologia Japonica.1991; 38, 517–522. 15\u003c/li\u003e\n \u003cli\u003eRezaieyazdi Z, Hesamifard A. Correlation between serum prolactin levels and lupus activity. Rheumatol Int. 2006 Sep;26(11):1036-9. doi: 10.1007/s00296-006-0129-0.\u003c/li\u003e\n \u003cli\u003eDieguez, C., Peters, J.R., Page, M.D. et al. (1986) Thyroid function in patients with hyperprolactinaemia: relationship to dopaminergic inhibition of TSH release. Clinical Endocrinology, 25, 435–440\u003c/li\u003e\n \u003cli\u003eBorba VV, Zandman-Goddard G and Shoenfeld Y Prolactin and Autoimmunity. Front. Immunol. 2018; 9:73. \u003c/li\u003e\n \u003cli\u003eDong YH, Fu DG. Autoimmune thyroid disease: mechanism, genetics and current knowledge. Eur Rev Med Pharmacol Sci 2014; 18(23):3611–8. 114. \u003c/li\u003e\n \u003cli\u003eYamamoto M, Iguchi G, Takeno R, Okimura Y, Sano T, Takahashi M, et al. Adult combined GH, prolactin, and TSH deficiency associated with circulating PIT-1 antibody in humans. J Clin Invest. 2011; 121(1):113–9. \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":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Autoimmune thyroid disease, prolactin, antibodies to thyroglobulin, thyroid peroxidase (anti-TPO)","lastPublishedDoi":"10.21203/rs.3.rs-8523918/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8523918/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn addition to its classic effect of lactation, prolactin (PRL) has begun to attract attention for its non-classic effects, particularly on the immune system.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study aimed to compare the prevalence of autoimmune thyroid disease (AITD), thyroid autoantibodies and thyroid function tests (TFTs) in patients with hyperprolactinemia (HPRL) of at least 25 ng/ml and in healthy controls with PRL of less than 25 ng/ml.We conducted a retrospective case-control study at a single tertiary referral centre. All study participants underwent measurement of antibodies to thyroglobulin (anti-Tg), thyroid peroxidase (anti-TPO), TSH and fT4 levels, as well as ultrasonographic thyroid pattern assessment.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe AITD rate was found to be 33.5% in those with PRL\u0026thinsp;\u0026ge;\u0026thinsp;25. In the healthy control group, this rate was 23.5%, and this difference was statistically significant (p\u0026thinsp;=\u0026thinsp;0.006). Among those with PRL\u0026thinsp;\u0026ge;\u0026thinsp;25, Anti-TPO and Anti-Tg levels, as well as TSH levels, were significantly higher and sT4 levels were significantly lower compared to the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).. There was a positive relationship between PRL levels and TSH, Anti-Tg, and Anti-TPO levels, while there was a negative relationship with sT4 levels, all of which were statistically significant but relatively weak .The ROC analysis revealed that the PRL level was 21.77 ng/mL for detecting Anti-TPO positivity and Anti-Tg positivity, the cut-off value was determined to be 21.92 ng/mL\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThere is an increase in the frequency of AITD and thyroid autoantibodies in HPRL patients. We can conclude that exceeding the PRL threshold value increases the risk.\u003c/p\u003e","manuscriptTitle":"Autoimmune thyroid disease - is high prolactin a risk factor?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-22 07:15:12","doi":"10.21203/rs.3.rs-8523918/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-26T07:42:35+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-11T07:00:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-31T05:42:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"103947102503923185798133255274062316442","date":"2026-01-24T16:13:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"332485553895882287491658597542190960934","date":"2026-01-23T05:11:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-19T14:29:22+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-09T09:38:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-09T08:29:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-09T08:26:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Endocrine Disorders","date":"2026-01-05T17:44:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9a0d6121-9ecb-493d-96c3-3029237619c8","owner":[],"postedDate":"January 22nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T14:11:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-22 07:15:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8523918","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8523918","identity":"rs-8523918","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}