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Effects of Metyrapone Administration on Thyrotropin Secretion in Healthy Subjects–A Clinical Research Center Study¹

Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health Sciences University, Portland, Oregon 97201

Address all correspondence and requests for reprints to: Dr. M. H. Samuels, Division of Endocrinology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201. E-mail: samuelsm{at}ohsu.edu

Although pharmacological doses of glucocorticoids suppress TSH secretion, less is known regarding the effects of physiological variations in cortisol levels on TSH. To study this issue, 12 healthy subjects each underwent 2 studies, in random order: 1) each subject received an infusion of saline for 48 h; and 2) each subject received an infusion of saline and oral administration of metyrapone (500 mg every 4 h) for 48 h. Cortisol and TSH levels were measured every 15 min during the final 24 h of each study, and resulting mean hormone levels during the 24-h periods were compared between the two studies. Metyrapone administration reduced serum cortisol levels by 39% between 0800 and 1345 h and by 47% between 0200 and 0745 h, with no significant changes during other time periods. Metyrapone increased daytime (0800–1945 h) mean TSH levels by 35%, with no change in nocturnal (2000–0745 h) TSH levels. This led to equalization of daytime and nocturnal TSH levels and abolition of the usual circadian variation in TSH. TSH pulse frequency was no different between the two studies, whereas daytime TSH pulse amplitude increased 33% during metyrapone administration. There were no changes in TSH responses to TRH, or in serum T₃ or free T₄ levels, at the end of the studies. These results suggest that the early morning increase in endogenous cortisol levels in healthy subjects causes the daytime decrease in TSH levels. In addition, these results show that very mild changes in cortisol levels within the physiological range are sufficient to affect TSH secretion.

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