14 PERSISTENT HYPERINSULINENIC HYPOGLYCEMIA OF INFANCY – LONG-TERM EXPERIENCE WITH 28 PATIENTS

Abstract

We studied 28 patients with Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI). Twenty-two developed symptomatic hypoglycemia within 2 days of life (15 of these required surgery) while 5 developed first symptoms at age 2-7 months (1 required surgery). Twelve patients belonged to 5 families indicating a genetic basis for the disease (autosomal recessive). Non-pancreatectomized patients received frequent high carbohydrate feedings, raw cornstarch, diazoxide and/or somatostatin analogue (Sandostatin™, Sandoz, Switzerland, n=5). All 85-90% pancreatectomized patients (n=15) required some medical treatment for hypoglycemia post-operatively. Three patients died (2 of sepsis and 1 of acute gastric perforation). Diabetes developed only in the 1 patient who had a total pancreatecomy. Of 25 living patients, 16 entered remission between 0.3 & 8 years of age (follow-up 0.3-12 years, mean 5.5 years). Of the 22 living patients who were not retarded at diagnosis, 21 developed normally while 1 is retarded (IQ 65). Pathologic examination of 16 pancreata showed focal findings in 3, the rest being histologically normal for age. Beta-cells from 3 histologicaly normal pancreata were cultured on extra-cellular matrix and showed significant & unchanged insulin secretion at all levels of glucose tested (0-16.7 mmol), which suppressed with epinephrine or somatostatin and stimulated with IBMX or forskolin. In conclusion: PHHI appears to be caused by a functional β-cell defect, presumably genetic in origin, manifested by a lack of suppression of insulin secretion by low glucose, and which may resolve spontaneously with time. Intensive conservative treatment, with 85-90% pancreatectomy only when absolutely necessary, resulted in a good long-term prognosis in 95% of our patients in whom the diagnosis was made before the onset of neurologic damage.