Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

Objective: Our aim has been to evaluate the effects of i.v. infusion of rec ombinant human erythropoietin (rhEPO) on the responses of growth hormone: ( GH), prolactin (PRL) and thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) stimulation in acromegalic patients. Methods: We studied 16 patients is females, aged 29-68 years) with active a cromegaly and 12 control subjects (7 females, 24-65 years). All participant s were tested with TRH (400 mu g i.v, as bolus) and with TRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before TRH in jection) on different days. Blood samples were obtained between -30 and 120 min for GH and PRL determinations, and between -30 and 90 min for TSH dete rminations. Hormone responses were studied by a time-averaged (area under t he secretory curve (AUC)) and time-independent (peak values) analysis, Results: Twelve patients exhibited a paradoxical GH reaction after TRH admi nistration with great interindividual variability in GH levels. When patien ts were stimulated with rhEPO plus TRH there were no changes in the variabi lity of GH responses or in the peak and AUC for GH secretion. Infusion with rhEPO did not induce any significant change in GH secretion in normal subj ects. Baseline and TRH-stimulated PRL concentrations in patients did not di ffer from those values found in controls. When TRH was injected during the rhEPO infusion, a significant (P < 0.05) increase in PRL concentrations at 15-120 min was found in acromegalic patients. Accordingly, the PRC peal; an d the AUC for PRL secretion were significantly increased in patients. Infus ion with rhEPO had no effect on TRH-induced PRL release in control subjects . Baseline TSH concentrations, as well as the TSH peak and the AUC after TR H, were significantly lower in patients than in controls, Infusion with rhE PO modified neither the peak TSH reached nor the AUC for TSH secretion afte r TRH injection in acromegalic patients and in healthy volunteers. Conclusion: Results in patients with acromegaly suggest that ii) the parado xical GH response to TRH is not modified by rhEPO infusion, (ii) rhEPO has no effect on TRH-induced TSH release, and (iii) acute rhEPO administration increases the TRH-induced PRL release in acromegalic patients.