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


METHODS
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).


CONCLUSIONS
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.
Roelfsema
Ferdinand
F
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. f.roelfsema@lumc.nl
Pereira
Alberto M
AM
Biermasz
Nienke R
NR
Frolich
Marijke
M
Keenan
Daniel M
DM
Veldhuis
Johannes D
JD
Romijn
Johannes A
JA
D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology; D003480:Cushing Syndrome / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D055815:Young Adult
D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine; D006854:Hydrocortisone