Suppression of Testicular Androgenesis by &lt;i&gt;D&lt;/i&gt;-Tryptophan-6-Luteinizing Hormone-Releasing Hormone Does Not Affect TSH Secretion in Male Subjects

We have assessed the effect of androgen deprivation therapy (ADT) in the thyroid function test in prostate cancer patients. Serum levels of tri-iodothyronine (T3), thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were determined in a cross-sectional study that included 279 patients diagnosed with prostate cancer. A subset of 96 patients free of prostate-specific antigen relapse after radical prostatectomy became a control group and 183 patients under continuous ADT formed the study group. Sixty-four patients out of the study group were treated with luteinizing hormone-releasing hormone (LHRH) agonist and 119 with LHRH agonist plus bicalutamide. The average time of ADT was 42.5 months (3-218). Results were as follows. Mean T3 level was 122.7 ng/dl (72.6-213.0) in the control group and 123.8 ng/dl (64.4-228.2) in patients under ADT, p=0.472. Mean T4 level was 7.66 (1.81-4.30) and 7.66 microg/dl (3.60-13.30), respectively, p=0.884. Mean TSH level was 1.58 (0.44-11.70) and 1.81 mU/dl (0.15-6.58), respectively, p=0.007. Mean FT4 level was 1.24 (0.80-1.90) and 1.18 ng/dl (0.80-1.90), respectively, p=0.018. No statistically significant differences between the T3, T4, TSH and FT4 serum levels were detected according to the modality of ADT. The serum level of TSH was higher than 5 mU/l in six patients (2.1%); however, all cases had a normal FT4 serum level. This mild hypothyroidism was detected in two of the 96 patients of the control group (2.1%) and in four of the 183 under ADT (2.2%). Our data show that ADT seems to alter the thyroid function test. A statistically significant increase in TSH serum level and a decrease in FT4 serum level were detected in patients under ADT. However, only a mild hypothyroidism was detected in about 2% of the patients with prostate cancer, independently of ADT.

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Hypothalamic-Pituitary-Thyroid Axis Set Point Alterations Are Associated With Body Composition in Androgen-Deprived Men

Hoermann

Cheung

Milne

et al. 2017

Journal of the Endocrine Society

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Objective:Androgen deprivation therapy (ADT) given to men with prostate cancer is associated with metabolically adverse changes in body composition leading to insulin resistance, but the underlying mechanisms are not fully understood. We investigated prospectively whether androgen deprivation or its consequences may be associated with alterations in thyroid function in men.Design:We performed a prespecified secondary analysis of a prospective case control study.Methods:We prospectively followed men with nonmetastatic prostate cancer newly commencing ADT (n = 34) and age-matched controls (n = 29) for 12 months. We assessed secondary outcomes on thyrotropin (TSH) and thyroid hormones using a linear mixed model to determine mean adjusted differences (MADs) between groups.Results:After a 12-month follow-up period, TSH increased in cases compared with control subjects [MAD, 0.69 mIU/L; 95% confidence interval (CI), 0.58–0.82; P < 0.001]. This was accompanied by a rise in FT4 (MAD, 2.2 pmol/L; 95% CI, 1.1–3.2; P < 0.001), reduced FT3-FT4 conversion (MAD, −0.07; 95% CI, −0.10 to −0.4; P < 0.001), and stable FT3. TSH change correlated significantly with changes in weight, body mass index, and fat mass in cases but not with waist circumference, lean mass, visceral fat, insulin resistance, testosterone, sex hormone binding globulin, and estradiol. The rise in TSH after 12 months was strongly associated with changes in leptin.Conclusions:A profound rise in TSH in the absence of peripheral hypothyroidism under ADT suggests set point adaptations of the hypothalamic-pituitary-thyroid axis. This appears to be mediated by body composition changes and by the fat-associated hormone leptin rather than by androgen deficiency. Further studies are required to determine the causality and biological implications of these findings.

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Suppression of Testicular Androgenesis by <i>D</i>-Tryptophan-6-Luteinizing Hormone-Releasing Hormone Does Not Affect TSH Secretion in Male Subjects

Cited by 4 publications

References 15 publications

Effect of adjuvant androgen deprivation on thyroid function tests in prostate cancer patients

Effect of adjuvant androgen deprivation on thyroid function tests in prostate cancer patients

Effect of androgen deprivation therapy in the thyroid function test of patients with prostate cancer

Hypothalamic-Pituitary-Thyroid Axis Set Point Alterations Are Associated With Body Composition in Androgen-Deprived Men

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