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This Article Full Text Full Text (PDF) All Versions of this Article: EJE-09-0580v1 161/5/695    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Roelfsema, F. Articles by Romijn, J. A PubMed PubMed Citation Articles by Roelfsema, F. Articles by Romijn, J. A

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

Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands¹ Department of Statistics, University of Virginia, Charlottesville, Virginia 22904, USA² Endocrine Research Unit, Mayo Medical and Graduate Schools, Clinical Translational Research Center, Mayo Clinic, Rochester, Minnesota 55901, USA

(Correspondence should be addressed to F Roelfsema; Email: f.roelfsema{at}lumc.nl)

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 (P<0.001). TSH secretion was increased in patients in remission only during daytime 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 nonpulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic/annexin-1 control.

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