Modifications in serum growth hormone concentration induced by sulpiride in acromegalic patients pretreated with dopamine, bromocriptine, and metergoline

The modifications in serum GH concentrations after the administration of a dopamine antagonist [sulpiride (Sip); 100 mg, im] during the infusion of either saline or dopamine (DA; 4 μg/kg-min) were studied in 5 normal volunteers and 19 acromegalic patients. Sip also was given 3 h after the oral administration of 4 mg metergoline (Mtg) and 5 h after 2.5 mg bromocriptine (Brc) to 8 and 5 patients, respectively, and to 5 normal controls. All acromegalic patients had their GH responsiveness to TRH evaluated. No significant variations in serum GH were recorded in normal controls after DA-Slp, except for a slight and transient increase in some individuals occurring at 30- 60 min during DA infusion. In acromegalics, no major GH variations were observed after Sip during saline administration, while during DA infusion there was a significant diminution in serum GH, from 27.6 ± 6.9 to 17.3 ± 5.0 (SE) ng/ml (P < 0.002). This was followed by a prompt and significant rise in 13 cases (68. 4%) after Sip injection (mean net increase over the mean basal value, 32.1 ± 9.6 ng/ml; P < 0.05). Serum GH increased after TRH in 8 acromegalic patients (42%); all responded to DASlp. Five DA-Slp responders were retested after selective adenomectomy; 4 patients whose serum GH levels fell below 2 ng/ml became DA-Slp unresponsive, and the fifth patient, whose serum GH level fell from 53 to 6.5 ng/ml, remained DA-Slp responsive. After Mtg administration, Sip increased serum GH in 3 DA-Slpresponsive acromegalic patients but had no effect in 2 other DASlp responders, in 3 nonresponders, and in normal controls. After Brc, Sip did not increase serum GH levels in either normal controls or acromegalics, although 4 patients were DA-Slp responders. These data suggest that Sip directly stimulates GH secretion from the tumoral cells in the presence of DA. In fact, DA does not cross the blood-brain barrier, and DA-Slp responses disappeared after successful adenomectomy. The Da-Sip test, which appears to be reproducible, might be a useful tool for the evaluation of GH secretion in acromegaly. Mtg seems to display some dopaminergic activity on the tumoral cells. The absence of Sip-induced GH release after Brc could be explained by a more stable binding to dopaminergic receptors than DA itself.