HYPERINSULINISM DURING THERAPEUTIC ADMINI STRATION OF GROWTH-HORMONE (GH) IN PATIENTS WITH GH DEFICIENCY OR TURNER-SYNDROME

Background: An increased incidence of diabetes mellitus in patients wi th hypersecretion of growth hormone (acromegaly, pituitary gigantism) is well known. In the present study, the effect of long-term growth ho rmone (GH) therapy on basal as well as stimulated blood glucose and in sulin concentrations was studied in pediatric patients. Methods: Durin g an oral glucose tolerance test, plasma glucose and insulin were meas ured every 30 minutes. 2 groups patients were studied before during GH therapy: 9 patients with complete or partial GH deficiency (mean age at initiation of therapy: 9.1 +/- 1.0 years) as well as 11 girls with Turner syndrome (mean age: 10.8 +/- 0.9 years). Results: A weekly dose of growth hormone of 12.8 +/- 0.9 units/m(2) did not increase blood g lucose in patients with GH deficiency, all patients displayed normal g lucose tolerance. In contrast, the integrated secretion of insulin dur ing the OGT-test increased from 3.7 +/- 0.8 U/l x min before therapy t o 5.9 +/- 0.6 after 1 year (p < 0.005; Wilcoxon). Hyperinsulinism was still present after 2 years of GH therapy (n = 7). In Ullrich-Turner p atients, a significantly higher dose of growth hormone was used (mean: 22.4 +/- 2.0 Units/m(2) x week). After 1 year of GH therapy, blood gl ucose 30 min after the ingestion of oral glucose had increased to 167 +/- 6 mg/dl compared to 147 +/- 7 mg/dl before GH administration (p = 0.05). One girl developed impaired glucose tolerance. Insulin secretio n rose by more than 100 % (AUG for insulin before therapy: 4.1 +/- 0.3 U/l x min, after 1 year of therapy: 9.5 +/- 1.4). In 8 Ullrich-Turner girls, the OGT-test was repeated again after 3 years of GH therapy, i nsulin secretion continued to be clearly elevated (AUG: 10.8 +/- 2.1 U /l x min). Conclusions: GH therapy for 1 year increases insulin releas e during the OGT-test by 59 % in patients with GH deficiency and by 13 1 % in Ullrich-Turner syndrome. This difference may be due to a higher dose, or due to a specific tendency for insulin resistance in girls w ith gonadal dysgenesis. The long-term consequences of hyperinsulinism (hypertension, cardiovascular risk) cannot be predicted in these patie nts and should be followed in prospective studies.