Effect of Altered Thyroid Function Upon Adrenocortical ACTH and Methopyrapone (Su-4885) Responsiveness in Man

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Abstract
The effect of abnormal thyroid function on the adrenocortical response to ACTH and methopyrapone (Metopirone, Su-4885) infused at different times in the 24 hours has been studied and compared to the response in normal subjects. Hyperthyroidism advanced and exaggerated the normal circadian variation in the adrenocortical response to exogenous ACTH and potentiated adrenocortical activation following Su-4885 when the drug was infused in the early morning. Hypothyroidism produced the opposite effects. Infusion of Su-4885 later in the day demonstrated persistence at both extremes of thyroid function of the circadian variation in the sensitivity of the central nervous system mechanism regulating ACTH release to changes in cortisol concentration. The data are interpreted to suggest 2 independent effects of thyroid hormone upon pituitary ACTH activity: 1) an indirect effect through its influence on the peripheral metabolism of cortisol mediated by the negative feed-back mechanism on the magnitude of ACTH secretion, and 2) a direct effect on the central nervous system centers regulating ACTH release. The findings also offer an explanation for the contradictory assessments of pituitary ACTH reserve in patients with altered thyroid function previously reported in the literature.