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Modifications in Serum Growth Hormone Concentration Induced by Sulpiride in Acromegalic Patients Pretreated with Dopamine, Bromocriptine, and Metergoline

Second Medical Clinic, Endocrine Unit, University of Milan, 20122 Milan, Italy

Address requests for reprints to: Dr. Giovanni Faglia, Endocrine Unit, Second Medical Clinic, Via F. Sforza 35, 20122 Milano, Italy.

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 µ/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 µ 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.

Received October 24, 1979.