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 (nZ16) or primary-adrenal origin (nZ11) and after remission by pituitary surgery (nZ7) in order to delineate aberrations in the hypothalamus-pituitary-thyroid system. Intervention: Patients and controls (nZ27) 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 (PZ0.003). Total 24-h TSH correlated negatively and linearly with logtransformed cortisol secretion (RZ0.43, PZ0.001). 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.

Thyroid hormone regulation by stress and behavioral differences in adult male rats

“…Glucocorticoids (corticosterone), which were certainly elevated by the stress paradigm (Helmreich et al, 1999), have been suggested to inhibit TSH release at the level of the pituitary (Wilber and Utiger, 1969) both in vivo (Hangaard et al, 1996, Roelfsema et al, 2009) and in vitro (Taylor et al, 1995). However, studies also suggest that glucocorticoid effects on the HPT axis are mediated at the level of the hypothalamus (Wilber and Utiger, 1969, Kondo et al, 1997, Haugen, 2009, Roelfsema et al, 2009). Conducting the current experiment in adrenalectomized/corticosterone replaced animals would help clarify the role of corticosterone in stress-induced decreases in TH levels.…”

Effects of forced swimming stress on thyroid function, pituitary thyroid-stimulating hormone and hypothalamus thyrotropin releasing hormone expression in adrenalectomy Wistar rats

“…In the classical model of stress, cortisol hormone levels exhibit significant increases, and a number of studies have revealed that increased cortisol can influence pituitary TSH release (20,21). However, there are studies suggesting that cortisol exerts effects on the hypothalamus (1,20).…”

“…However, there are studies suggesting that cortisol exerts effects on the hypothalamus (1,20). Furthermore, glucocorticoid receptors are discovered in the TRH neurons of the PVN, and glucocorticoid response elements have been identified on the TRH gene (22).…”

Network Identification of Hormonal Regulation

“…Well-established associations were found for ACTH and cortisol [26]–[29], and between cortisol and TSH [30], [31]. The latter serves as a partial validation of the method.…”