PITUITARY GLYCOPROTEIN HORMONES IN CHRONIC-RENAL-FAILURE - EVIDENCE FOR AN UNCONTROLLED ALPHA-SUBUNIT RELEASE

Chronic renal failure affects the secretion of pituitary glycoprotein hormones by mechanism(s) that are still unknown. In this study, we eva luated serum concentrations of TSH, free thyroid hormones (FT4, FT3), LH, FSH, testosterone (T), and alpha-subunit (alpha-SU) in 25 uremic p atients (19 males and 6 females), both in basal conditions and after s timulatory and inhibitory tests. Basal TSH levels were in the normal r ange, while FT4 and FT3 were significantly lower than in controls. Bas al LH and FSH levels were clearly elevated. The LH levels measured by RIA were significantly higher than those measured by a ''two-site'' IR MA (48.9+/-16.5 vs 18.0+/-8.6 U/L) due to alpha-SU cross-reactivity in RIA. FSH bioactivity was normal in all patients. Serum T was normal i n all but 3 males, without any correlation with LH and FSH levels. Ser um alpha-SU concentrations were significantly elevated (5.5+/-3.0 vs 0 .4+/-0.2 mug/L). Of 17 patients, the TSH response to TRH was normal in 9 and impaired in 8, whereas alpha-SU response was normal in 5 and im paired in 12. In 8 male patients, TRH plus GnRH caused a normal LH and FSH response in 4 patients, while the increase of alpha-SU was normal in only one patient and significantly lower than expected in subjects with comparable basal alpha-SU levels in the remaining 7. In 2 patien ts, the combined suppression test with T undecanoate and T3 completely blocked TSH secretion and reduced both LH and FSH release by 30%, whi le serum alpha-SU levels did not change. The present data 1) confirm t hat pituitary glycoprotein hormone secretion in patients with chronic renal failure is altered, 2) demonstrate the existence of an uncontrol led hypersecretion of alpha-SU and, finally, 3) show that circulating FSH molecules posses normal bioactivity.