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 recombinant 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 (8 females, aged 29-68 years) with active acromegaly and 12 control subjects (7 females, 24-65 years). All participants were tested with TRH (400 microg 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 injection) 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 determinations. Hormone responses were studied by a time-averaged (area under the secretory curve (AUC)) and time-independent (peak values) analysis. RESULTS: Twelve patients exhibited a paradoxical GH reaction after TRH administration with great interindividual variability in GH levels. When patients were stimulated with rhEPO plus TRH there were no changes in the variability 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 subjects. Baseline and TRH-stimulated PRL concentrations in patients did not differ 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 PRL peak and the AUC for PRL secretion were significantly increased in patients. Infusion 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 TRH, were significantly lower in patients than in controls. Infusion with rhEPO modified neither the peak TSH reached nor the AUC for TSH secretion after TRH injection in acromegalic patients and in healthy volunteers. CONCLUSION: Results in patients with acromegaly suggest that (i) the paradoxical 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.