Clinical and pharmacological characterization of anomalous metoclopramide-induced growth hormone secretion in insulin-dependent diabetes mellitus.
An abnormal growth hormone (GH) increase after non-specific stimuli (such as TRH, LHRH and, in a few cases, metoclopramide), has been described in insulin-dependent diabetes. Sixty-nine non-hypogonadic male insulin-dependent diabetic patients (mean age 38.6 years, range 18-54; mean duration of diabetes 11.1 years, range 1.3-28, in different degree of metabolic control, some of them with retinopathy, nephropathy and peripheral and/or autonomic neuropathy) were tested twice with 10 mg i.v. metoclopramide (MCP), an antidopaminergic agent with weak serotoninergic activity. Anomalous GH response (i.e. GH increment equal to or higher than 5 ng/ml from basal level) occurred in 33 patients (47.8%). Mean (+/- SE) MCP-induced GH release in these 'responder' patients peaked up to 17.2 +/- 1.7 ng/ml in comparison with no variation found in 'non-responders' and in 25 healthy control men. Abnormal GH secretion appeared to be unrelated to age, metabolic control, basal GH values and duration of diabetes. Moreover, it remained unmodified by pretreatments with placebo, cimetidine, meclastine, propranolol, acetylsalicylic acid and naloxone, while it was enhanced by metergoline, significantly reduced by bromocriptine and almost completely blunted by pirenzepine, a cholinergic muscarinic receptor antagonist. Neuropathy and nephropathy were equally distributed in the two groups, while retinopathy was more frequent in 'responders'. In conclusion, the exact mechanism(s) by which MCP may induce a paradoxical GH release in many insulin-dependent diabetic patients, is still unclear; it might be dependent, at least in part, on the activation of cholinergic pathways. Indeed, it seems to indicate the presence, in diabetes, of a rather complex derangement in the regulatory mechanisms of GH secretion.
Cattedra di Endocrinologia e Medicina Costituzionale, Istituto di Scienze Medico-Chirurgiche S. Donato, Italy.
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D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000209:etiology; D003929:Diabetic Neuropathies / Q000209:etiology; D003930:Diabetic Retinopathy / Q000209:etiology; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D006441:Hemoglobin A / Q000032:analysis; D006801:Humans; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D008875:Middle Aged; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D001786:Blood Glucose; D013739:Testosterone; D013006:Growth Hormone; D006441:Hemoglobin A; D008787:Metoclopramide