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Should Human Chorionic Gonadotropine Treatment Increase original article Should human chorionic gonadotropine treatment increase thyroid volume? Ayten Oguz1, Dilek Tuzun1, Murat Sahin1, Nese Bulbul1, Ahmet Celik2, Numan Guvenc3, Elif Inanc4, Kamile Gul1 ABSTRACT 1 Kahramanmaras Sutcu Objective: Our aim was to investigate the thyroid function tests and thyroid volume differences Imam University, Faculty of among males with isolated hypogonadotropic hypogonadism (IHH) who take androgen replacement Medicine, Department of treatment (ART). Materials and methods: Forty-four male with IHH with a mean age 33.2 (18-54), Endocrinology and Metabolism, Kahramanmaras, Turkey diagnosed in Endocrinology and Metabolism Department between September 2013 and September 2 Kahramanmaras Sutcu Imam 2014 and 40 healthy male control with a mean age 27.77 (18-55) were involved to study. Patient group University, Faculty of Medicine, was divided to testosterone-treated patients (n = 19) and human chorionic gonadotropine (hCG)- Department of Biochemistry, treated patients (n = 25). Patient group was compared in terms of total testosterone, thyroid func- Kahramanmaras, Turkey tion tests [thyroid stimulating hormone (TSH), free thyroxine (fT )] and thyroid volume, before and 3 4 Kahramanmaras Sutcu Imam 6 months after treatment. Patient group was compared with control group as well. Results: When University, Faculty of Medicine, Department of Family Medicine, we compared the patient group with the control group, there was no significant difference for age, Kahramanmaras, Turkey Body mass index, TSH, fT4 and thyroid volume between two groups before treatment. There was no 4 Kahramanmaras Sutcu Imam difference in terms of TSH, but fT4, testosterone levels and thyroid volume were significantly higher University, Faculty of Medicine, after treatment, when the patient group was compared before and after treatment (p < 0.05). When Department of Internal Medicine, we compared testosterone-treated patients and hCG-treated patients; thyroid volume was higher Kahramanmaras, Turkey among hCG-treated patients (p = 0.001) but there was no difference for thyroid volume before and Correspondence to: after testosterone treatment (p > 0.05). There was no statistically significant correlation between tes- Ayten Oguz tosterone levels with TSH, fT and thyroid volume (r = 0.09, p = 0.32; r = 0.14, p = 0.11; r = 0.15, Kayseri Yolu 10 km 4 AvsarÇ Kampüsü KahramanmarasÇ p = 0.09, respectively). Conclusion: Our study showed that ART increases the thyroid volume espe- Sütçü Imam- Üniversitesi cially in hCG-treated patients. Therefore, we suggest that thyroid volume changes should be followed 46100 – Kahramanmaras, Turkiye up in hCG-treated patients. Arch Endocrinol Metab. 2015;59(6):482-6 [email protected] Keywords Received on June/19/2015 Accepted on July/1/2015 Thyroid volume; thyroid stimulating hormone; human chorionic gonadotropin DOI: 10.1590/2359-3997000000096 INTRODUCTION ing hormone (FSH) and TSH (3). Human chorionic solated hypogonadotropic hypogonadism (IHH) gonadotropin has thyroid-stimulating activity in bio- I may present as an isolated hormonal deficiency assays in mice, rats, chicks and men (4-6). The thy- (low testosterone and low or normal levels of gonad- roid-stimulating activity of a commercial preparation otropins) secondary to hypothalamic or pituitary de- of hCG was first demonstrated by Burger in a mouse fects (1). The goals of therapy for IHH in adolescent bioassay (7). Subsequently, thyrotrophic activity has or young adult males include the induction of normal been found in several hCG preparations (4,5). These puberty and testicular development that allow future studies showed that hCG is the molar TSH and that 1 fertility. Androgen replacement treatment (ART) that Unite hCG has intrinsic thyrotrophic activity equiva- includes testosterone and gonadotropins are used in lent to approximately 0.5 µU TSH in the Mouse bio- these patients (2). assay (4). Additionally, hCG stimulates iodide uptake, Human chorionic gonadotropin (hCG) is a glyco- adenylate cyclase, and DNA synthesis in cultured rat protein hormone that has structural similarity to thy- thyroid cells (8). Many investigations have detected roid stimulating hormone (TSH). The beta subunit of that hCG and TSH share not only structural homol- AE&M all rights reserved. © hCG is unique to hCG but alpha-subunit is identical ogy but also their receptors show structural similar- Copyright to that luteinizing hormone (LH), follicle stimulat- ity as well, and this homology suggests the basis for 482 Arch Endocrinol Metab. 2015;59/6 HCG treatment and thyroid volume the reactivity of hCG with the TSH receptor (9,10). other anterior and/or posterior pituitary hypofunction Therefore, high hCG concentrations are associated and pathological findings on a pituitary magnetic reso- with thyroid stimulation, both functionally (lower se- nance image (1). rum TSH concentrations) and anatomically (increased thyroid volume) (11). Exclusion criteria There are several conflicting results about the effect Patients with previously known history of thyroid di- of ART on thyroid function tests among males with hy- sease or receiving any drugs affecting thyroid gland, pogonadism. Several studies also showed that androgen those with hyperthyroidism, primary or secondary administration may be associated with increased (12), hypothyroidism, euthyroid or hypothyroid Hashima- decreased (13) or unaltered (14) TSH response to thy- to’s disease, thyrotoxicosis (factitia, subacute thyroi- rotropin-releasing hormone (TRH). But most studies ditis), and those receiving L-thyroxin suppression the- evaluated only patients with primary hypogonadism. So rapy, bromocriptine, somatostatin, anti-thyroid drugs, we aimed to investigate whether both hypogonadism lithium, interferon, perchlorate, and sulfonamides were and ART (especially hCG) effect the thyroid function excluded. Moreover, patients who underwent radiolo- tests and thyroid volume in males with IHH. gical examination with an iodinated contrast medium within at least 3 days, those who last received drugs including iodine 7 days ago, and those who underwent MATERIALS AND METHODS thyroid operation or received radioactive iodine were Male patients with IHH and healthy male controls who not included in the study. Patients with systemic illnes- were admitted to Endocrinology and Metabolism Cli- ses were excluded, in addition to those who took exces- nic at Kahramanmaras Sutcu Imam University Hospital sive exercise, used certain medications or as these could were included in the study. The study was approved by affect the metabolism of testosterone and testosterone the ethics committee of Kahramanmaras Sutcu Imam levels. Secondary causes of hypogonadotropic hypogo- University. nadism, such as panhypopituitarism, hyperprolactinae- mia and intracranial masses, were excluded before ma- Subjects and study protocol king a diagnosis of IHH. Forty-four male with IHH (patient group) with a mean age 33.2 (18-54) that was diagnosed in Endocrinolo- Biochemical analyses gy and Metabolism Department in Kahramanmaras (a Blood samples was collected in the morning between mild iodine deficient city in Turkey) between Septem- 08.00–09.00 hours after an overnight fast to avoid dif- ber 2013 and September 2014 and 40 healthy male ferences because of diurnal variation, especially for hor- control (control group) with a mean age 27.77 (18-55) monal parameters. Normal reference values were as follow were involved to study. Patient group was divided into FSH (1.42–15.4 mIU/ml), LH (1.24–7.8 mIU/mL), two goups; treated with testosterone (n = 19) and HCG TT (280-1100 ng/dL), prolactin (3–14.7 ng/mL), group (n = 25). Patient group was compared in terms TSH (0.4-4.2 µIU/mL), fT4 (0.8-2.7 ng/dL) and of body mass index (BMI), total testosterone (TT), Cortisol (5-23 µg/dL). Hormone analyses were car- thyroid function tests [TSH, free thyroxine (fT4)] and ried out using chemiluminescence enzyme immunoas- thyroid volume, before and 6 months after treatment. say (Immulite 2000, Diagnostic Products Corporation, These parameters were evaluated between patient and Los Angeles, CA, USA, or UniCel DxI 800, Beckman control group as well. Coulter CA, USA) commercial kits. Inclusion criteria Conventional thyroid ultrasonography Isolated hypogonadotropic hypogonadism was defined Conventional thyroid ultrasonography (US) was per- as the presence of clinical symptoms related to hypogo- formed before and 6 month after the treatment. Each nadism (e.g. incomplete or delayed sexual development, participants underwent a preliminary ultrasonography reduced libido and erectile dysfunction/infertility) and and it was investigated whether there was any abnorma- AE&M all rights reserved. low serum TT levels (< 250 ng/dL), insufficient LH lity such as a nodule or parenchymal heterogeneity. All © (i.e. low or non-elevated levels), the absence of any grey scale measurements were performed by the same Copyright Arch Endocrinol Metab. 2015;59/6 483 HCG treatment and thyroid volume endocrinologist with the same US device (Logic P5 RESULTS System, GeneralElectric Medical Systems, Milwaukee, Forty-four male patients with IHH and 40 healthy WI, USA) using a linear transducer of 12 MHz width. male controls were involved to the study. The baseli- While the participant was lying in supine position with ne characteristics and thyroid function tests, TT levels, the neck in hyperextension, the skin was covered with thyroid volume of the male patient with IHH and con- acoustic material. The thyroid
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