title: Effect of altered thyroid hormone levels on hypothalamic-pituitary-adrenal function.
abstract: To determine whether alterations in serum thyroid hormone levels affect hypothalamic-pituitary-adrenal function, we measured the plasma immunoreactive (IR) ACTH and IR-cortisol responses to 1 microgram/kg BW ovine CRH (oCRH) given iv in the late afternoon and the plasma IR-ACTH, IR-cortisol, and IR-11-deoxycortisol responses to 2 g metyrapone given orally at midnight in 10 athyreotic patients during T4 treatment and 1 month after stopping T4 when they were biochemically, but not clinically, hypothyroid. Mean serum TSH increased from 0.7 +/- 0.9 (+/- SD) mU/L (normal range 0.5-4.9 mU/L) during T4 therapy to 107 +/- 82 mU/L after stopping T4. The serum total T4 level and free T4 index fell from 165 +/- 37 nmol/L and 1.9 +/- 0.4, respectively (normal range, 59-154 nmol/L and 0.9-2.5, respectively), to 19 +/- 9 and 0.2 +/- 0.1, respectively, after stopping T4. Basal plasma IR-ACTH and IR-cortisol levels at 0800 and 1630 h were similar during and after stopping T4 therapy. Peak plasma IR-ACTH and IR-cortisol levels after oCRH were significantly greater after stopping T4 (20 +/- 9.2 pmol/L and 880 +/- 260 nmol/L, respectively) than during T4 therapy (9.7 +/- 4.7 pmol/L and 720 +/- 190 nmol/L; P less than 0.01 and P less than 0.05, respectively). The mean integrated plasma IR-ACTH and IR-cortisol responses to oCRH were also significantly greater P less than 0.01 and P less than 0.05, respectively) after stopping T4 than during T4 therapy. Plasma IR-ACTH the morning after metyrapone was slightly (1.6-fold) but not significantly greater during therapy than after stopping T4 therapy (100 +/- 86 vs. 65 +/- 54 pmol/L, respectively). The plasma IR-11-deoxycortisol responses to metyrapone during and after stopping T4 therapy were similar (720 +/- 250 and 750 +/- 330 nmol/L, respectively), presumably because plasma IR-ACTH concentrations were maximally stimulating in both instances. These results indicate that thyroid hormone deficiency of short duration 1) increases corticotroph sensitivity to oCRH, 2) may diminish the plasma ACTH response to metyrapone-induced hypocortisolemia, and 3) has no apparent effect on the acute adrenal response to ACTH. These data together with those of previous studies that have shown reduced responses of the hypothalamic-pituitary-adrenal axis to metyrapone and hypoglycemia in hypothyroid patients suggest that the release of hypothalamic CRH and/or other ACTH secretagogues may be decreased in hypothyroidism.
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008797:Metyrapone / Q000494:pharmacology; D008875:Middle Aged; D009994:Osmolar Concentration; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012756:Sheep; D013963:Thyroid Hormones / Q000097:blood*
chemical_list: D013963:Thyroid Hormones; D003346:Corticotropin-Releasing Hormone; D008797:Metyrapone