Tuesday, August 18, 2009

Diminished and irregular thyrotropin secretion with delayed acrophase in patients with Cushing’s syndrome

F Roelfsema, A Pereira, N Biermasz, Marijke Frölich, Daniel Keenan, Johannes Veldhuis and J Romijn

F Roelfsema, Endocrinology and Metabolism, Leiden University Medical Center, Leiden, 2333ZA, Netherlands
A Pereira, Endocrinology and Metabolism, Leiden University Medical Center, Leiden, Netherlands
N Biermasz, Endocrinology and Metabolism, Leiden University Medical Center, Leiden, Netherlands
M Frölich, Endocrinology and Metabolism, Leiden University Medical Center, Leiden, Netherlands
D Keenan, Statistics, University of Virginia, Charlottesville, United States
J Veldhuis, Endocrine Research Unit, Mayo Clinic, Rochester, United States
J Romijn, Department of Endocrinology, C4-R, Leiden University Medical Center, Leiden, 2300 RC, Netherlands

Correspondence: F Roelfsema, Email: f.roelfsema@lumc.nl

Abstract

Context. The hypothalamo-pituitary-thyroid axis in Cushing’ syndrome may be altered.

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 hypothalamo-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 (P<0.001). TSH secretion was increased in patients in remission only during day-time due to increased basal secretion (P<0.01). Pulse frequency and half life of TSH were similar in patients and controls. TSH ApEn (irregularity) was increased in patients with hypercortisolism (P<0.01), but was normal in cured patients. Cross-ApEn between TSH and cortisol, a measure of pattern-synchrony loss, was increased in active disease, indicating (partial) loss of secretory synchrony. The TSH rhythm was phase-delayed in hypercortisolemic patients, but normal in cured patients (P<0.01). Free thyroxine levels were decreased only in pituitary-dependent hypercortisolism compared with controls (P=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 non-pulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic / annexin-1 control.

From http://www.eje.org/cgi/content/abstract/EJE-09-0580v1