Euthyroid Hyperthyrotropinemia Secondary to Hyperestrogenemia in a Male With Congenital Adrenal Hyperplasia

A 10-year-old boy with congenital adrenal hyperplasia and associated hyperplastic testicular adrenal rests had high serum concentrations of 17-OH progesterone (17-OHP), estradiol (E₂), testosterone (T), and basal and TRH-stimulated TSH and PRL, but normal thyroid hormones (T₃, T₄, FT₃, FT₄) and thyroxine-binding globulin (TBG). Upon dexamethasone therapy, steroid hormones returned progressively toward normal as did both PRL and TSH; PRL declined faster than TSH. Serum E₂ correlated better with PRL than with TSH. Therefore, the responsiveness of the thyrotrophs to the ambient concentration of E₂ is lower and slower than that of the lactotrophs. In the context of the inconclusive data on the role of estrogens in controlling the secretion of TSH in humans, our case suggests that E₂ does stimulate the secretion of basal and TRH-elicited both TSH and PRL, and that this positive action is unopposed by T. In contrast, T antagonizes the estrogen-induced increase in serum TBG. We also postulate that E₂ might impair the bioactivity of TSH, in order to explain (i) the approximate 3-fold increase in serum TSH coexisting with a normally sized (rather than enlarged) thyroid and normal (rather than increased) serum thyroid hormones, and (ii) the inability of TRH-stimulated TSH to acutely raise FT₃ serum levels.

Key words

TRH - Prolactin - Estradiol - Testosterone - Steroid Hormones