Circadian and Pulsatile Thyrotropin Secretion in Euthyroid Man Under the Influence of Thyroid Hormone and Glucocorticoid Administration*

Abstract

The inhibitory action of thyroid hormones (TH) and glucocorticoids on circadian and pulsatile TSH secretion was investigated in groups of five normal men by sampling blood every 10 min for 24 h (start, 1750 h). Serum TSH was measured by a sensitive immunoradiometric assay. Continuous infusion of 50 micrograms T3 or 250 micrograms T4 for 8 h (1900-0300 h) significantly suppressed serum TSH levels (T3, P less than 0.025; T4, P less than 0.05; by paired t test). Administration of 3 g sodium ipodate 7 h before TH infusion did not alter the TSH response to T3, but T4-dependent suppression was abolished. Pulsatile TSH secretion [basally, 5.8 +/- 1.3 (+/- SD) pulses/24 h, as analyzed by the PULSAR program; 6.8 +/- 1.9 by the Cluster program] was not significantly altered by any of the experimental conditions. The additional finding of blunting of the TSH response to TRH after TH alone or ipodate and T3 suggests a predominantly pituitary feedback action of TH exerted via conversion of T4 to T3. In contrast, bolus injections of 4 mg dexamethasone (dex) at 1900 and 2200 h abolished TSH pulses for at least 6 h (PULSAR, 6.6 +/- 1.6 pulses/24 h basally vs. 3.6 +/- 3.0 under dex; Cluster, 7.0 +/- 2.7 pulses/24 h basally vs. 1.6 +/- 1.6 under dex). Dex administration also resulted in a prompt, sustained, and significant suppression of basal TSH (P less than 0.0005). Together with a normal serum TSH response to TRH (in separate experiments 1, 9, and 19 h after dex administration), these data suggest that glucocorticoid feedback occurs at a suprapituitary level.

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

“…Our findings are also in keeping with previous reports documenting decreased efficacy of TRH in inducing TSH release in patients with hypercortisolism and in healthy subjects after glucocorticoid administration, and suggesting a relationship between the degree of glucocorticoid excess and impairment in the TSH response (10)(11)(12). Indeed, a single dose of glucocorticoids (1-2 mg dexamethasone) causes an acute decrease in pulsatile TSH production in healthy men (9). Even a mild elevation of serum cortisol concentrations (about 32%) induced by timed cortisol infusions decreases pulsatile TSH secretion by 50% (20).…”

“…One of the important metabolic signals modulating the activity of the hypothalamus-pituitary-thyroid (HPT) axis is leptin, which exerts a stimulating effect on TRH synthesis and release, both directly and indirectly via the proopiomelanocortin/cocaine-and amphetaminerelated transcript expressing neurons of the arcuate nucleus (8). Glucocorticoid administration to healthy subjects diminishes the TSH increase to TRH and decreases spontaneous TSH secretion (9,10). In Cushing's disease, the TSH response to TRH administration is decreased (11,12).…”

Opposing Crosstalk between Leptin and Glucocorticoids Rapidly Modulates Synaptic Excitation via Endocannabinoid Release

“…Whereas GCs (Brabant et al, 1987) and exogenous cannabinoids (Hillard et al, 1984) were shown to suppress the HPT axis, leptin prevents the fasting-induced suppression of the HPT axis (Ahima, 2000). We previously demonstrated GSE in PVN TRH neurons (Di et al, 2003), and our current results suggest that the drop in leptin levels in combination with the increase in GC levels during fasting is likely to favor GSE in PVN TRHreleasing neurons, contributing to the fasting-induced inhibition of the HPT axis.…”

Free T3 to free T4 ratio less than 2.0 suggests low T3 syndrome rather than central hypothyroidism from the age of two to eighteen years

“…The obesity index was calculated using height and standard body weight values (see Supplementary Tables 1 and 2) published in the List of School Health Statistical Survey Conducted by the Ministry of Education, Science and Culture in 2000 in Japan [9,10]. With regard to BMI values, for a male or a female child above 6 years of age whose obesity index was -20%, the BMI was14.9-20.8 and 14.9-20.36, respectively.…”

“…As is shown in Fig. 2, the following patients were further excluded: 1) those with fT3 and fT4 values under the sensitivity of the measurements (n = 21); 2) those presenting complications or receiving drugs which may have influenced thyroid function (n = 157) [8][9][10] such as artificial dialysis, high dose corticosteroids (above 20 mg of predonisolone), amiodarone, antiepileptic agents such as carbamazepine, levothyroxine; and 3) those presenting a complication of a primary thyroid disease. Among the final 229 patients of this second set of participants, group L ( Fig.…”