TRH: Pathophysiologic and clinical implications

Abstract

SummaryThyrotropin releasing hormone is thought to be a tonic stimulator of the pituitary TSH secretion regulating the setpoint of the thyrotrophs to the suppressive effect of thyroid hormones. The peptide stimulates the release of normal and elevated prolactin. ACTH and GH may increase in response to exogenous TRH in pituitary ACTH and GH hypersecretion syndromes and in some extrapituitary diseases.The pathophysiological implications of extrahypothalamic TRH in humans are essentially unknown.The TSH response to TRH is nowadays widely used as a diganostic amplifier in thyroid diseases being suppressed in borderline and overt hyperthyroid states and increased in primary thyroid failure. In hypothyroid states of hypothalamic origin, TSH increases in response to exogenous TRH often with a delayed and/or exaggerated time course.But in patients with pituitary tumors and suprasellar extension TSH may also respond to TRH despite secondary hypothyroidism. This TSH increase may indicate a suprasellar cause for the secondary hypothyroidism, probably due to portal vessel occlusion. The TSH released in these cases is shown to be biologically inactive.Keywords: TRH; diagnostic significance; hypothalamic diseases; pituitary failure. TRH, initially detected and synthesized as the hypothalamic hormone that controls the thyrotrophic activity was found to stimulate the prolactin release in vivo and in vitro 43, 45, 63, 72, 77 Moreover, TRH has been shown to be widely distributed over the central nervous system36, 3v, 44, 71, where it is believed to have neurotransmitter functions besides the hypophysiotropic effects.TRH has been detected in the upper gastrointestinal tract 14, where its endogenous functions are unknown. Exogenous TRH inhibits the pentagastrin stimulated gastric secretion 12 and by some degree the glucagon and pancreatic polypeptide release after insulin induced hypoglycemia 13. TRH and Thyrotropie ActivityExperimental and pathological disruption of the hypothalamic supply of the pituitary with TRH results in decreased thyroid function 47, called secondary hypothyroidism. TRH antibodies induce impairment of thyroid function with some effects on the prolactin secretion as well 28, 32, 39, 76. But until now, there are no consistent data on the physiological hypothalamopituitary relationship in humans. This is due to the fact that serum and urinary TRH is mainly derived from extrahypothalamic sources 46. In experimental hypoand hyperthyroidism the hypothalamic content of TRH does not change 52 arguing against a feedback inhibition between TRH and TSH. There are few studies reporting a decrease of TRH in hyper-and an increase in hypothyroidism with marked differences in the reported normal levels 29, 50. Most authors postulate today that TRH is a tonic stimulator of the TSH secretion, modulating the set point of the thyrotrophs to the suppressive effect of thyroid hormones 47.TSH responses to TRH are modulated by estrogens in females and in males 2o. This modulation is due to increasing binding sites of pituitary cell...

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“…Circulating TSH has multiple molecular forms or isoforms due to variations in oligosaccharide structures [25][26][27] . Furthermore, TSH isoforms have been shown to possess different biological activities, and both increased and decreased TSH bioactivities have been reported in various thyroid disorders 28,29 .…”