The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Jan 1990
Dynamics of 24-hour endogenous cortisol secretion and clearance in primary hypothyroidism assessed before and after partial thyroid hormone replacement.
Although various abnormalities of hypothalamic pituitary adrenal function have been reported in primary hypothyroidism, neither 24-h patterns of pulsatile cortisol release nor estimation of its endogenous secretion and clearance rates have been fully investigated in this clinical setting. We studied pulsatile and circadian patterns of cortisol secretion in six hypothyroid men [mean free T4 index, 0.59 +/- 0.22 (+/- SE); mean TSH, greater than 50 mU/L] by sampling blood at 20-min intervals for 24 h before (unreplaced) and then after 5-7 months of partial replacement treatment with levo-T4. Compared to a normal group, hypothyroid men had significantly elevated 24-h mean serum concentrations of cortisol (419 vs. 254 nmol/L; P less than 0.001), with no change in serum cortisol-binding globulin concentrations. ⋯ Partial replacement therapy with levo-T4 caused significant decreases in 1) mean 24-h serum cortisol concentrations (419 vs. 323 nmol/L; P less than 0.05); 2) mean cortisol peak amplitudes (527 vs. 375 nmol/L; P less than 0.05); 3) mean prepeak nadir concentrations (298 vs. 221 nmol/L; P less than 0.05); and 4) mean half-life of cortisol disappearance (155 vs. 112 min; P less than 0.0019). In summary, the present study of cortisol secretory dynamics in hypothyroid men has shown elevated mean 24-h serum concentrations of cortisol with preserved circadian rhymicity and normal endogenous production rates, but prolonged half-lives of cortisol disappearance. In conjunction with normal serum cortisol-binding globulin concentrations, these largely reversible findings suggest that significant hypercortisolemia in primary hypothyroidism is primarily due to decreased metabolic clearance of cortisol and a presumptive decrease in the negative feedback effect of cortisol on the hypothalamo-pituitary axis.
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J. Clin. Endocrinol. Metab. · Jan 1990
Randomized Controlled Trial Clinical TrialEffects of chronic testosterone administration in normal men: safety and efficacy of high dosage testosterone and parallel dose-dependent suppression of luteinizing hormone, follicle-stimulating hormone, and sperm production.
In normal men, chronic testosterone (T) administration results in negative feedback suppression of gonadotropin and sperm production. However, azoospermia is achieved in only 50-70% of men treated with high dosages of T. Furthermore, the relative sensitivity of LH and FSH secretion to chronic administration of more physiological dosages of T is unclear. ⋯ We conclude that 1) LH and FSH secretion are equally sensitive to the long term negative feedback effects of T administration; 2) sperm production is suppressed in parallel with the LH and FSH reductions induced by chronic T administration; and 3) even at the clearly supraphysiological dosage of 300 mg/week, T enanthate does not reliably induce azoospermia in normal men. However, there was also no evidence of a stimulatory effect of this T dosage on spermatogenesis. Furthermore, we found no evidence of major adverse health effects of T administered chronically even at the highest dosage.