Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing's syndrome

Abstract

Context: The hypothalamus–pituitary–thyroid axis in Cushing's syndrome may be altered. Previous reports have shown diminished serum TSH concentration and decreased response to TRH.Objective: We analyzed serum TSH profiles in relation to cortisol profiles in patients with hypercortisolism of pituitary (n=16) or primary-adrenal origin (n=11) and after remission by pituitary surgery (n=7) in order to delineate aberrations in the hypothalamus–pituitary–thyroid system.Intervention: Patients and controls (n=27) underwent a 24-h blood sampling study. Serum TSH and cortisol were measured with precise methods, and data were analyzed with a deconvolution program, approximate entropy (ApEn), and cosinor regression.Results: Pulsatile TSH secretion and mean TSH pulse mass were diminished during hypercortisolism, independently of etiology (PPPPP=0.003). Total 24-h TSH correlated negatively and linearly with log-transformed cortisol secretion (R=0.43, P=0.001).Conclusion: Cortisol excess decreases TSH secretion by diminishing pulsatile release, whereas surgically cured patients have elevated nonpulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic/annexin-1 control.