Tsh Secretion In Cushing's Syndrome: Relation To Glucocorticoid Excess, Diabetes, Goitre, And The ‘Sick Euthyroid Syndrome’

Abstract

Thyrotrophin (TSH) secretion was studied in 63 patients with Cushing's syndrome (53 patients with pituitary dependent Cushing's disease, eight with adrenocortical tumours, and two with the ectopic ACTH syndrome). Prior to treatment, TSH response to 200 micrograms of TRH intravenously was significantly decreased compared to controls; TSH response was 'flat' (increment less than 2 mU/l) in 34 patients (54%). Patients with a flat response to TRH had significantly higher morning and midnight cortisol levels than patients with a TSH response of 2 mU/l and more; this was not due to differences in serum thyroid hormone levels. Basal TSH, TSH increment after TRH, and stimulated TSH value, but not serum triiodothyronine, were correlated with cortisol measurements (0800 h serum cortisol, midnight cortisol, and urinary free corticoid excretion). After exclusion of 40 patients with additional disease (severe systemic disease, diabetes mellitus, or goitre), cortisol-TSH correlations were even more pronounced (r = -0.73 for midnight cortisol and stimulated TSH levels), while in the patients with additional complications, these correlations were slight or absent. Successful treatment in 20 patients was associated with a rise in thyroid hormone levels and the TSH response to TRH. These results indicate that (1) the corticoid excess but not serum T3 is the principal factor regulating TSH secretion in Cushing's syndrome, (2) a totally flat response to TRH is rare, and (3) TSH suppression and lower than normal serum thyroid hormone levels are reversible after treatment. Since factors like severe systemic disease, diabetes mellitus and goitre also affect TSH secretion, they tend to obscure the statistically significant correlations between cortisol excess and TSH secretion.

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

“…Another TSH profile study in pituitary-dependent hypercortisolism, comprising three patients, reported decreased pulsatile TSH secretion with different analytical techniques (19). 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).…”

“…Indeed, levels were decreased in patients with hypercortisolism, although in all cases serum fT 4 concentration levels remained within normal limits as reported in other studies (11,12,19). A possible explanation for the relatively normal T 4 concentrations during hypercortisolism is that the biological activity of TSH was increased by altered posttranslational processing of the oligosaccharide chains of the TSH molecule (44).…”

“…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).…”

Nonthyroidal illness syndrome in patients with subarachnoid hemorrhage due to intracranial aneurysm

“…It has been described that most of the patients with NTIS have normal TSH responses in the TRH stimulation test 4 . A normal response in the presence of a low basal TSH can suggest an hypothalamic abnormality 10,27,28 . It has been shown that the reduction of the glycosylation process of the TSH molecule makes it immunologically active and biologically inactive and this process is dependent on the TRH levels 10,28 .…”

Organization and Integration of the Endocrine System: The Arousal and Sleep Perspective

“…Activation of the HPA axis is associated with decreased production of thyroidstimulating hormone and inhibition of conversion of the relatively inactive thyroxine to the more biologically active triiodothyronine in peripheral tissues (the "euthyroid sick" syndrome). [89][90] Although the exact mechanism for these phenomena is not known, both phenomena may be caused by the increased levels of glucocorticoids and may serve to conserve energy during stress. Inhibition of thyroid-stimulating hormone secretion by CRH-stimulated increases in somatostatin might also participate in the central component of thyroid axis suppression during stress.…”