CC BY
28
□dû* International Journal of Endocrinology
OpuriHOAbHi AOOAÏA^eHHq
/Original Researches/
UDC 613.25:616-056:616.441006.6 DOI: https://doi.Org/10.22141/2224-0721.16.6.2020.215386
Eyyup Murat Efendioglu1 G, Duygu Kavuncuoglu2 D
1 Gaziantep University, Department of Geriatrics, Gaziantep, Turkey
2 Hatay Health Directorate, Turkey
The association between obesity and thyroid stimulating hormone in adults
For citation: Miznarodnij endokrinologicnij zurnal. 2020;16(6):478-482. doi: 10.22141/2224-0721.16.6.2020.215386
Abstract. Background. Obesity is the most important social epidemic of the 21st century. The combination of increased thyroid pathology and obesity is particularly noteworthy. Obesity is associated with numerous endocrine abnormalities, including thyroid dysfunction and central obesity. However, it is unclear whether thyroid disorder in obese individuals is a cause of that condition or an effect. Obesity is the most important social epidemic of the 21st century. The combination of increased thyroid pathology and obesity is particularly noteworthy. Aim of the study was to elucidate the relationship between obesity and serum plasma thyroid stimulating hormone (TSH) level. Materials and methods. The records of 73 obese patients with BMI > 30 kg/m2 among individuals aged 18-65 and a 27-member non-obese group with normal BMI were scanned retrospectively. Age, sex, anthropometric measurements, TSH, fasting plasma glucose (FPG), insulin, total cholesterol, triglyceride, and HDL results were recorded. The t test, Mann Whitney U test, chi square test, and Pearson and Spearman correlation tests were employed for data analysis. A p value < 0.05 was considered statistically significant. Results. Seventy-three patients with BMI > 30 kg/m2 and 27 non-obese controls were included in the study. Fifty-nine of the individuals enrolled were women and 41 were men, with an average age of 36.4 ± 10.4 years. Significant differences were observed in BMI, FPG, insulin, HbA1c, HDL, and TSH values between the groups (p < 0.05). TSH was significantly positively correlated with TSH and BMI, HbA1c, insulin and FPG (p < 0.001, r = 0.360; p = 0.031, r = 0.231; p = 0.021, r = 0.231 andp = 0.017, r = 0.237, respectively). Negative correlation was present between TSH and HDL (p = 0.006, r = -0.272). Conclusions. TSH, fasting blood glucose, HbA1c and insulin values were higher in the obese group compared with the normal weight healthy group, while HDL values were lower. Significant positive correlation was determined between TSH and BMI. These findings support the idea that a slight increase in TSH levels may occur in obese individuals. Keywords: obesity; body mass index; thyroid stimulating hormone
Introduction
Obesity is an important public health problem widely seen across the world and affecting both developing and developed nations. Figures published by the World Health Organization show that the global prevalence of obesity has risen approximately three-fold in the 45-year-period since 1975 [1]. The condition has been linked to complications such as insulin resistance, hypertension, systemic inflammation, type 2 diabetes mellitus, cardiovascular diseases, and cancer [2]. Obesity is also associated with numerous endocrine abnormalities, including thyroid dysfunction and central obesity. However, it is unclear whether thyroid disorder in obese individuals is a cause of that condition or an effect. Thyroid dysfunction is associated with changes in body temperature, basal energy
expenditure independently of total and physical activity, body weight, and body composition [3]. Although thyroid functions are generally normal in obese individuals, body mass index (BMI) and thyroid stimulating hormone (TSH) are positively related, and a mild increase in TSH levels has been shown compared with normal weight individuals [4, 5]. Although the reason for high TSH values in obese individuals is uncertain, thyroid hormone resistance, autoimmune thyroiditis, iodine deficiency, TSH gene mutation, functional disorders in the hypothalamus-pituitary-thyroid axis, impaired mitochondrial function, and leptin-mediated pro-thyroid releasing hormone (pro-TRH) production have all been implicated [6, 7]. The hormone leptin also occupies an important place in the relationship between obesity and TSH levels. Adipocyte
© 2020. The Authors. This is an open access article under the terms of the Creative Commons Attribution 4.0 International License, CC BY, which allows others to freely distribute the published article, with the obligatory reference to the authors of original works and original publication in this journal.
For correspondence: Duygu Kavuncuoglu, MD, Hatay Health Directorate, Department of Public Health, Hatay, Turkey; e-mail: [email protected]; phone: 0530 885 02 60. Full list of author information is available at the end of the article.
iEI_
hypertrophy in obese individuals causes hyperleptinemia, and increased leptin results in increased TSH, or hypothyroidism [8]. Several studies have shown that leptin can also affect hypothalamic TRH production [9, 10].
The aim of this study was to elucidate the relationship between obesity and serum plasma TSH levels.
Material and methods
The records of 73 obese patients with BMI > 30 kg/m2 among individuals aged 18—65 presenting to the internal diseases clinic in our center over a one-year period (1 December, 2014, to 1 December, 2015) and a 27-member non-obese group with normal BMI were scanned retrospectively. Individuals with BMI values less than 25 kg/m2 were regarded as non-obese, while participants with BMI exceeding 30 kg/m2 were defined as obese.
The patients were divided into two groups:
Group 1 — Obese patients (BMI > 30 kg/m2, n = 73).
Group 2 — Non-obese control group (BMI < 25 kg/m2, n = 27).
Individuals with acute infectious conditions, malignancies, inflammatory rheumatic diseases, chronic kidney failure, or acute or chronic liver disease, and pregnant women were excluded.
Parameters Used During Evaluation and Follow-Up
Age, sex, anthropometric measurements, TSH, fasting plasma glucose (FPG), insulin, total cholesterol, triglyceride, and HDL results were collected from the patient files in this retrospective study. The files of 73 obese patients with BMI > 30 kg/m2 and 27 individuals with normal BMI were examined retrospectively. All cases' biochemical parameters (TSH, FPG, insulin, HbA1c, and lipid profile) were recorded. Insulin resistance (IR) was calculated with the Homeostasis Model Assessment (HOMA) index.
HOMA was determined by applying the formula fasting insulin value (^IU/mL) x fasting glucose value (mg/dL)/405.
Cases' demographic characteristics, height, and body weight were recorded.
BMI was calculated using the formula body weight (kg)/ height2 (m2).
Statistical analysis
Data analysis was performed on IBM SPSS software version 22.0 for Windows (Statistical Package for the Social Sciences Inc., Chicago, IL, USA). Continuous variables were expressed as mean plus standard deviation (SD), and categorical variables as frequency (%). The distributions of the continuous variables were examined by Kolmogorov Smirnov test. The t test, Mann Whitney U test, and Pearson and Spearman correlation tests were applied for data analysis, and the chi square test was used to compare categorical data. P values < 0.05 were considered statistically significant.
Ethical considerations
Ethical approval for the study was obtained from the Ga-ziantep University Faculty of Medicine Ethics Committee, Turkey (no. 29.11.2015/330). All participants were briefed about the study and gave informed written consent to participate.
OpuriHOAbHi AOCAiAweHHfl /Original Researches/
Results
Seventy-three patients with BMI values exceeding > 30 kg/m2 and 27 non-obese controls were enrolled in this research. All patients' demographic and laboratory characteristics are shown in Table 1. There was no difference between the groups in terms of mean age (p = 0.188). The groups were also similar in terms of gender distributions (p = 0/580). However, significant variations were observed between the groups in terms of TSH, BMI, FPG, insulin, HbA1c and HDL levels (p < 0.05). Obese group TSH, FPG, HbA1c and insulin were higher than those of the normal weight group, while HDL values were lower. No significant difference was observed in total cholesterol or triglyceride values between the study groups (p = 0.652 and p = 0.051, respectively).
Comparison of TSH values in the obese and non-obese groups revealed significant positive correlation between TSH and BMI, HbA1c, insulin and FPG in both groups (p < 0.001, r = 0.360, p = 0.031, r = 0.231, p = 0.021, r = 0.231, and p = 0.017, r = 0.237). Significant negative correlation was observed between TSH and HDL (p = 0.006 r = —0.272). Correlation of TSH levels with other variables are shown in Table 2.
Discussion
This study investigated the relationships between TSH, BMI, FPG, HbA1c, total cholesterol, triglyceride, and HDL in obese patients and a non-obese control group. BMI, a practical, inexpensive and easily applied parameter with a high level of accuracy generally recognized in the measurement of obesity, and known to exhibit good correlation with body fat percentage, was employed in this study [11]. A significant difference was observed in TSH levels between the obese patients and the non-obese control group. Additionally, significant positive correlation was determined between TSH and BMI. A similar study evaluated TSH levels in 87 metabolically stable euthyroid women divided into two groups, with BMI above or below 40 kg/m2 at physical examination. TSH levels were higher in the morbidly obese group, and positive correlation was determined between BMI and TSH [12]. In another study involving 165 obese and 116 normal weight patients, TSH levels were again higher in the obese group [13]. Knudsen et al. also determined positive correlation between TSH and BMI, and suggested that a high prevalence of obesity in a population might be associated with increased serum TSH levels [14].
Thyroid hormones represent a particular factor of interest in the development and treatment of obesity. The fact that thyroid hormones play a regulatory role in thermoge-nesis constitutes a potential factor in the development of obesity. Although the reason for TSH elevation in the obese is unclear, it has been suggested that, similarly to insulin resistance, this may be associated with TSH resistance [6]. In addition, parallel weight gain has been observed if elevation in TSH in obese patients persists over a five-year period. Mild TSH elevation is observed in approximately 25 % of obese individuals (generally below 10 IU/l) [15]. There is a pituitary adaptation mechanism that leads to high TSH levels, particularly in morbid obesity, characterized by rapid weight gain [16]. Studies investigating the association be-
OpMNHOAbHi AOCAiA^eHHfl /Original Researches/
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Table 1. Demographic and laboratory features of the study groups
Indicator Obese, n = 73 Non-obese, n = 27 P value
Gender, Female/Male, n (%) 43/30 (58.9/41.1) 16/11 (59.3/40.7) 0.580
Age, year* 37.26 ± 11.35 34.14 ± 7.26 0.188
BMI, kg/m2* 35.56 ± 5.51 23.97 ± 2.67 < 0.001
FPG, mg/dl** 98.71 ± 22.37 86.44 ± 8.41 0.007
Insulin, |jIU/ml** 13.91 ± 10.08 7.96 ± 5.67 0.005
HbAlc, %** 5.73 ± 0.79 5.38 ± 0.32 0.032
Homa IR, mmol/l** 4.40 ± 0.84 1.73 ± 1.29 0.059
Total Cholesterol, mg/dl** 205.35 ± 43.81 200.51 ± 47.86 0.652
Triglyceride, mg/dl** 181.36 ± 97.07 139.85 ± 81.72 0.051
HDL, mg/dl** 47.45 ± 10.42 54.59 ± 11.77 0.004
TSH, uIU/ml** 2.39 ± 0.91 1.61 ± 0.92 < 0.001
Notes: * — t-test; ** — Mann-Whitney U-test.
tween metabolic syndrome parameters and TSH have determined that metabolic syndrome parameters, and particularly obesity, are more common in patients with TSH levels greater than 2.5 IU/l than in those with low TSH [17]. A relationship has also been found between a high BMI and obesity and overt and even subclinical hypothyroidism [18]. Thyroid dysfunction was frequently seen in obese patients in Alkag et al.'s study, with Hashimoto's thyroiditis and hypothyroidism being more common [19]. Significantly lower HDL values were observed in the obese group compared with the non-obese controls. TSH also exhibited significant negative correlation with HDL. Similarly to the present study, Ekinci et al. reported significantly low HDL in their obese group compared with non-obese controls, and observed significant negative correlation between HDL and TSH [20]. Significant differences were also determined between these two groups in terms of FPG, insulin, and HbA1c levels, but no difference was found in terms of total cholesterol and triglyceride values.
The principal limitations of our study are its retrospective design and single-center nature. However, it yields important findings concerning the relationship between obesity and TSH levels, a very widespread health problem. We think that further more extensive studies are now needed to elucidate the relationship between TSH level and obesity. Patients must be screened in terms of obesity and thyroid pathology, and the requisite therapy and follow-ups must be initiated as a matter of urgency in terms of public health.
Information on funding. List funding sources — all people and organizations provided financial support for the study (grants, donation, instruments, agents, materials, drugs, etc.) as well as other subjects with another financial or personal participation that can cause the conflict of interest. Do not specify the volume of funding.
Acknowledgment
The authors have carefully considered ethical issues (including plagiarism, informed consent, misconduct, data fabrication and/or falsification, double publication and/or submission, redundancy, etc.).
Table 2. Correlation of TSH levels with other variables
Indicator TSH, uIU/ml
R P
BMI, kg/m2* 0.360 < 0.001
HbA1c, %** 0.216 0.031
Insulin, |IU/ml** 0.231 0.021
FPG, mg/dl** 0.237 0.017
Total Cholesterol, mg/dl** 0.138 0.171
Triglyceride, mg/dl** 0.126 0.211
HDL, mg/dl** -0.272 0.006
HOMA-IR, mmol/l** -0.064 0.525
Notes: * — Pearson's correlation test; ** — Spearman's correlation test.
Efendioglu E.M. Concept and design of study, collection and processing of the material, literature search, text writing; Kavuncuoglu D. Analysis of the data, literature search, text writing.
Conflicts of interests. Authors declare the absence of any conflicts of interests and their own financial interest that might be construed to influence the results or interpretation of their manuscript.
References
1. World Health Organization (WHO). Obesity and overweight: key facts. Available from: http://www.who.int/mediacentre/factsheets/fs311/ en/. Accessed: April 1, 2020.
2. Nie X, Ma X, Xu Y, Shen Y, Wang Y, Bao Y. Characteristics of Serum Thyroid Hormones in Different Metabolic Phenotypes of Obesity. Front Endocrinol (Lausanne). 2020 Feb 28; 11:68. doi:10.3389/ fendo.2020.00068.
3. Biondi B. Thyroid and obesity: an intriguing relationship. J Clin EndocrinolMetab. 2010Aug;95(8):3614-7. doi:10.1210/jc.2010-1245.
4. Biondi B, Cappola AR, Cooper DS. Subclinical Hypothyroidism: A Review. JAMA. 2019 Jul 9;322(2):153-160. doi:10.1001/jama.2019.9052.
5. Nyrnes A, Jorde R, Sundsfjord J. Serum TSH is positively associ-
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Оригiнальнi дослiдження /Original Researches/
ated with BMI. Int J Obes (Lond). 2006 Jan;30(1):100-5. doi:10.1038/ sj.ijo.0803112.
6. Krotkiewski M. Thyroid hormones in the pathogenesis and treatment of obesity. Eur J Pharmacol. 2002 Apr 12;440(2-3):85-98. doi:10.1016/s0014-2999(02)01420-6.
7. Oh JY, Sung YA, Lee HJ. Elevated thyroid stimulating hormone levels are associated with metabolic syndrome in euthyroid young women. Korean J Intern Med. 2013 Mar;28(2): 180-6. doi:10.3904/ kjim.2013.28.2.180.
8. Fontenelle LC, Feitosa MM, Severo JS, et al. Thyroid Function in Human Obesity: Underlying Mechanisms. Horm Metab Res. 2016 Dec;48(12):787-794. doi:10.1055/s-0042-121421.
9. Lloyd RV, Jin L, Tsumanuma I, et al. Leptin and leptin receptor in anterior pituitary function. Pituitary. 2001 Jan-Apr;4(1-2):33-47. doi:10.1023/a:1012982626401.
10. Ortiga-Carvalho TM, Oliveira KJ, Soares BA, Pazos-Moura CC. The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies. J Endocrinol. 2002 Jul;174(1):121-5. doi:10.1677/ joe.0.1740121.
11. World Health Organisation (WHO). Obesity: preventing and managing the global epidemic: report of a WHO Consultation on Obesity, Geneva, 3-5 June 1997. Geneva: WHO-Press; 1998. 276p.
12. Iacobellis G, RibaudoMC, ZappaterrenoA, Iannucci CV, Leonet-ti F. Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women. Clin Endocrinol (Oxf). 2005Apr;62(4):487-91. doi:10.1111/j.1365-2265.2005.02247.x.
13. Marzullo P, Minocci A, Tagliaferri MA, et al. Investigations of thyroid hormones and antibodies in obesity: leptin levels are associated with thyroid autoimmunity independent of bioanthropometric, hormonal, and weight-related determinants. J Clin Endocrinol Metab. 2010 Aug;95(8):3965-72. doi:10.1210/jc.2009-2798.
14. Knudsen N, Laurberg P, Rasmussen LB, et al. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab. 2005 Jul;90(7):4019-24. doi:10.1210/jc.2004-2225.
15. Douyon L, Schteingart DE. Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol secretion. Endocrinol Metab Clin North Am. 2002 Mar;31(1):173-89. doi:10.1016/s0889-8529(01)00023-8.
16. Zhang X, Li Y Zhou X, Han X, Gao Y Ji L. Association between serum thyrotropin within the euthyroid range and obesity. Endocr J. 2019 May 28;66(5):451-457. doi:10.1507/endocrj.EJ18-0140.
17. Topsakal S, Yerlikaya E, Akin F, Kaptanoglu B, Erurker T. Relation with HOMA-IR and thyroid hormones in obese Turkish women with metabolic syndrome. Eat Weight Disord. 2012 Mar; 17(1):e57-61. doi:10.1007/BF03325329.
18. Garin MC, Arnold AM, Lee JS, Tracy RP, Cappola AR. Subclinical hypothyroidism, weight change, and body composition in the elderly: the Cardiovascular Health Study. J Clin Endocrinol Metab. 2014 Apr;99(4):1220-6. doi:10.1210/jc.2013-3591.
19. Alkaf Q, Akba§ F, Alkag B, Atmaca HU. Obesity and thyroid functions. JAREM. 2014;(2):74-76. doi: 10.5152/ jarem.2014.466. (in Turkish).
20. Ekinci F, Merder-Coskun D, Tungel B, Uzuner A. Obesity and thyroid function in adults. Marmara Medical Journal. 2018;31(2):20-24. doi:10.5472/marumj.430795.
Received 03.08.2020 Revised 11.09.2020 Accepted 01.10.2020 ■
Information about authors
Eyyüp Murat Efendioglu, MD, Gaziantep University, Department of Geriatrics, Gaziantep, Turkey; e-mail: [email protected], ORCID: http://orcid.org/0000-0002-3257-7352. Duygu Kavuncuoglu, MD, Hatay Health Directorate, Department of Public Health, Hatay, Turkey; e-mail: [email protected], ORCID: http://orcid.org/ 0000-0002-0546-5478.
Eyyüp Murat Efendioglu1, Duygu Kavuncuoglu2
1 Gaziantep University, Department of Geriatrics, Gaziantep, Turkey
2 Hatay Health Directorate, Turkey
Резюме. Актуальтсть. Ожиршня — найважливта сощаль-на епщемш XXI столитя. Особливо заслуговуе на увагу часте поеднання патологи щитоподiбноl залози (ЩЗ) та ожиршня. Ожиршня пов'язане з численними ендокринними патологш-ми, включаючи порушення функци ЩЗ та центральне ожиршня. Однак не встановлено, чи е розлад функци ЩЗ в ошб з ожиршням причиною цього стану чи його наслвдком. Метою дослвдження було з'ясувати взаемозв'язок м1ж ожиршням та рiвнем тиреотропного гормона (ТТГ) у плазмi кровi. Мате-рiали таметоди. Пд спостереженням перебувало 73 пащенти з ожиршням (шдекс маси тша (1МТ) > 30 кг/м2) вшом 18—65 роив та 27 оаб, яю не страждають вщ ожиршня, з нормаль-ним 1МТ. Реестрували вгк, стать, антропометричш вимiрю-вання, рiвень ТТГ, глюкози в плазмi натще (ГПН), шсулшу, загального холестерину, триглщеридш та холестерину лшо-протещш високо! щшьносп (ХС ЛПВЩ). Для аналiзу даних використовували 1-тест, и-тест Манна — У!тш, критерш хь квадрат та кореляцшш тести Прсона та Стрмена. Значення р < 0,05 вважали статистично значущим. Результати. У досль
Зв'язок мiж ожиршням та рiвнем тиреотропного гормона в дорослих
дження були включеш 73 пащенти з 1МТ > 30 кг/м2 та 27 оаб, яю не страждають вщ ожиршня. З числа обстежених було 59 жшок i 41 чоловш, середнш вгк яких становив 36,4 ± 10,4 року. Суттевi вщмшносп спостертались у показниках 1МТ, ГПН, шсулшу, ИЪЛ1с, ХС ЛПВЩ та ТТГ мiж трупами (р < 0,05). ТТГ вiрогiдно позитивно корелював iз показниками ТТГ та 1МТ, ИЪЛ1с, шсулшу та ГПН у контрольны груш (р < 0,001, г = 0,360; р = 0,031, г = 0,231; р = 0,021, г = 0,231 i р = 0,017, г = 0,237 вщповщно). Негативна кореляцш вщзначалася мiж ТТГ та ХС ЛПВЩ (р = 0,006, г = -0,272). Висновки. Значення ТТГ, глюкози в кровi натще, ИЪЛ1с та шсулшу були ви-щими в груш з ожиршням порiвняно зi здоровою групою з нормальною масою тша, у той же час показники ХС ЛПВЩ були нижчими. Визначена вiроriдна позитивна кореляцш мiж ТТГ та 1МТ. Щ висновки пщтверджують думку про те, що в ошб з ожиршням може спостертатися незначне пщвищення рiвня ТТГ.
Ключовi слова: ожиршня; шдекс маси тша; тиреотропний гормон
Орипнальш дослiдження /Original Researches/
Eyyüp Murat Efendioglu1, Duygu Kavuncuoglu2
1Gaziantep University, Department of Geriatrics, Gaziantep, Turkey
2Hatay Health Directorate, Turkey
Взаимосвязь между ожирением и уровнем тиреотропного гормона у взрослых
Резюме. Актуальность. Ожирение — серьезная социальная эпидемия XXI века. Особого внимания заслуживает частое сочетание патологии щитовидной железы (ЩЖ) и ожирения. Ожирение связано с многочисленными эндокринными нарушениями, включая дисфункцию ЩЖ и центральное ожирение. Однако неясно, является ли заболевание ЩЖ у людей с ожирением причиной или следствием этого состояния. Целью исследования было выяснить взаимосвязь между ожирением и уровнем тиреотропного гормона (ТТГ) в плазме крови. Материалы и методы. Под наблюдением находились 73 пациента с ожирением (индекс массы тела (ИМТ) > 30 кг/м2) в возрасте 18—65 лет и группа из 27 человек без ожирения с нормальным ИМТ. Ретроспективно регистрировали возраст, пол, антропометрические измерения, уровень ТТГ, глюкозы в плазме натощак (ГПН), инсулина, общего холестерина, триглицеридов и холестерина липопротеидов высокой плотности (ХС ЛПВП). Для анализа данных использовались 1-критерий, и-критерий Манна — Уитни, критерий хи-квадрат и корреляционные тесты Пирсона и Спирмена. Значение р < 0,05 считалось статистически значимым. Резуль-
таты. В исследование были включены 73 пациента с ИМТ > 30 кг/м2 и 27 лиц, которые не страдают от ожирения. Среди обследованных было 59 женщин и 41 мужчина, средний возраст которых составил 36,4 ± 10,4 года. Значительные различия наблюдались в значениях ИМТ, ГПН, инсулина, НЬА1с, ХС ЛПВП и ТТГ между группами (р < 0,05). ТТГ достоверно положительно коррелировал с ТТГ и ИМТ, НЬА1с, инсулином и ГПН (р < 0,001, г = 0,360; р = 0,031, г = 0,231; р = 0,021, г = 0,231 и р = 0,017, г = 0,237 соответственно). Отрицательная корреляция наблюдалась между ТТГ и ХС ЛПВП (р = 0,006, г = —0,272). Выводы. Значения ТТГ, глюкозы в крови натощак, НЬА1с и инсулина были выше в группе с ожирением по сравнению с группой здоровых людей с нормальным весом, в то время как значения ХС ЛПВП были ниже. Определена достоверная положительная корреляция между ТТГ и ИМТ. Эти данные подтверждают мнение о том, что у людей с ожирением может наблюдаться небольшое повышение уровня ТТГ.
Ключевые слова: ожирение; индекс массы тела; тиреотроп-ный гормон
