Effects of Variations in Physiological Cortisol Levels on Thyrotropin Secretion in Subjects with Adrenal Insufficiency: A Clinical Research Center Study1

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, seven subjects with primary adrenal insufficiency each underwent four studies. In the first study subjects received infusions of saline for 48 h (baseline study). In the second study subjects received infusions of hydrocortisone for 48 h in a pulsatile and diurnal pattern that replicated serum cortisol levels in healthy subjects (physiological study). In most cases, the dose of hydrocortisone was 19 mg/24 h, but this was adjusted as necessary until the resulting serum cortisol levels reproduced those seen in healthy, nonstressed control subjects. In the third study subjects received the same total dose of hydrocortisone as in the physiological study, but with pulses of equal magnitude spaced evenly throughout the time period (constant study). In the fourth study subjects received the same total dose of hydrocortisone, but with the diurnal pattern shifted 12 h from the physiological infusion (reversed study). TSH levels were measured every 15 min during the final 24 h of each study. During the baseline study, the 24-h mean TSH level was 2.87 +/- 0.56 mU/L and did not exhibit any diurnal variation. During the physiological study, daytime TSH levels decreased 39% compared to those during the baseline study due to decreased TSH pulse amplitude, and the normal TSH diurnal rhythm was reestablished. The constant and reversed studies did not lead to significant changes in serum TSH levels compared to baseline. These results suggest that the normal circadian variation in endogenous cortisol levels may control TSH secretion, with maximal TSH suppression seen during the time when cortisol levels are highest. However, changing the diurnal pattern of hydrocortisone infusion did not lead to reciprocal changes in TSH levels, and the specific nature of the interactions between cortisol and TSH within the physiological range remains to be fully elucidated.