Effects of exogenous growth hormone pretreatment on the pituitary growth hormone response to growth hormone-releasing hormone alone or in combination with pyridostigmine in Type I diabetic patients

• Published in: Acta endocrinologica (Copenhagen) Vol. 125; no. 5; pp. 510 - 517
• Main Authors: Giustina, A, Bossoni, S, Bodini, C, Cimino, A, Pizzocolo, G, Schettino, M, Wehrenberg, W B
• Format: Journal Article
• Language: English
• Published: Denmark 01.11.1991
• Subjects: Administration, Oral; Adolescent; Adult; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Double-Blind Method; Drug Therapy, Combination; Female; Growth Hormone - administration & dosage; Growth Hormone - blood; Growth Hormone - therapeutic use; Growth Hormone-Releasing Hormone - administration & dosage; Growth Hormone-Releasing Hormone - therapeutic use; Humans; Injections, Intravenous; Male; Middle Aged; Pyridostigmine Bromide - administration & dosage; Pyridostigmine Bromide - therapeutic use
• ISSN: 0804-4643; 0001-5598; 1479-683X
• DOI: 10.1530/acta.0.1250510

We evaluated the effects of iv pretreatment with exogenous GH on the GH response to GHRH either alone or in combination with pyridostigmine in 14 Type I diabetic patients and 6 normal subjects. All the subjects received an iv bolus injection of biosynthetic human GH, 2 IU; 2 h later they received either a. pyridostigmine, 120 mg orally, or b. placebo, 2 tablets orally, followed 1 h later by iv injection of GHRH(1-29) NH2, 100 μg. In normal subjects the median GH peak after GH+GHRH was 1.8, range 1.2-6.9 μg/l. Pyridostigmine enhanced the GH response to GHRH in all subjects. The median GH peak after pyridostigmine+ GH+GHRH was 32.7, range 19.8-42.1 μg/l (p<0.001 vs GHRH alone). Seven diabetic subjects had median GH peaks after GH+GHRH >6.9 μg/l (the maximum GH peak after GH+GHRH in normal subjects) (group A: median GH peak 35.7, range 21.7-55 μg/l). The other diabetic subjects had GH peak lower than 6.9 μg/l (group B: median GH peak 4.4, range 2.1-6.5 μg/l). Pyridostigmine significantly increased the GH response to GHRH in group B patients (median GH peak 29.3, range 15.7-93.4 μg/l, p<0.001 vs GH+GHRH alone), but not in group A patients (median GH peak 39.9, range 21.9-64.9 μg/l). Group A diabetic patients were younger and had higher HbA1c and blood glucose levels than group B patients. In those diabetic patients with an exaggerated GH response to GH+GHRH, pyridostigmine failed to cause the increase in GH secretion observed in diabetic and control subjects with no responses to GH+GHRH. It can be suggested that elevated 24-h GH levels in some Type I diabetic patients may be due to decreased somatostatinergic tone which in turn causes altered autoregulation of GH secretion. We hypothesize that this finding is a consequence of a reset of the hypothalamic control of GH secretion caused by a chronically elevated blood glucose level in this subpopulation.