Biomedical subjects
Publications and source records attributed to F Darendeliler.
Long-term diazoxide and somatostatin analogue have been used in the treatment of persistent hyperinsulinemic hypoglycemia of infancy albeit with some side effects. We report a case with persistent hyperinsulinemic hypoglycemia who has been on diazoxide therapy for 4.5 years. Diazoxide treatment maintained normoglycemia without causing any side effects, including hypertrichosis.
Explore the source record for details and available documents.
The appropriate management of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) still remains controversial. Some patients show a response to treatment with diazoxide or somatostatin, but a number of children require total or near-total pancreatectomy to control hyperinsulinism. Recent studies suggest a dysfunction in the adenosine triphosphate-sensitive potassium channel present in the plasma membrane of pancreatic beta-cells in PHHI. The closure of these channels initiating the depolarization of the beta-cell membrane and opening of calcium channels results in an increase in intracellular calcium which triggers insulin secretion. A calcium channel blocking agent has been shown to block this process and decrease insulin secretion of the nesidioblastotic beta-cells in vitro and to control the hyperinsulinemic hypoglycemia of the patient in vivo. To examine the efficacy of calcium channel blocker therapy, three patients with PHHI were treated with nifedipine. PHHI was diagnosed by inappropriately high insulin levels for low blood glucose levels at 8-10 days of age. Normoglycemia was maintained by a high dose of glucose infusion at a rate of 14-16 mg/kg/min. Therapy using diazoxide and/or somatostatin analogue failed to restore euglycemia in these three patients. The first patient underwent near-total pancreatectomy; however, hyperinsulinism recurred 30 days after surgery. All patients were started on short acting nifedipine at a dose of 0.3 mg/kg/day per os in four doses. To maintain blood glucose levels in normal ranges, the dose of nifedipine was progressively increased to 0.7-0.8 mg/kg/day. Glucose infusion rate to restore euglycemia decreased and was discontinued on the 4th to 10th day of nifedipine treatment. The patients, who have now been followed on nifedipine therapy for over 12 months, are normoglycemic with normal insulin levels. The growth and neuromotor development of the patients are unremarkable except for mild developmental delay of the patient who underwent near-total pancreatectomy. No side effects were encountered at the doses used. In conclusion, calcium channel blocking agents can be used with efficacy and safety in PHHI to control the hyperinsulinemia.
To determine the glucocorticoid receptor (GC-R) status in congenital adrenal hyperplasia (CAH) we examined 11 patients (5 female, 6 male) with 21-hydroxylase deficiency and 3 patients (2 female, 1 male) with 11beta-hydroxylase deficiency. The mean age at investigation was 8.9+/-3.5 yr. Age of diagnosis was 4.4+/-3.2 yr and all patients were being treated with hydrocortisone. The control group included 10 (5 female, 5 male) age-matched healthy children. Blood samples were drawn at 0800 a.m. after an overnight fast in all subjects and after 5 days off treatment in patients with CAH. Serum cortisol (in all children), and serum 17-hydroxyprogesterone and androstenedione (in the patient group) were measured by radioimmunoassay. Mononuclear leukocytes were isolated from peripheral blood and the binding of [3H]dexamethasone to GC-R was examined. GC-R number and the dissociation constant (Kd), which is inversely proportional to its binding affinity, were determined. Mean GC-R numbers were 5814+/-1574 and 6816+/-1647; mean Kd values were 3.6+/-1.5 nM and 4.2+/-0.7 nM in patient and control groups, respectively. There were no significant differences in these parameters between the two groups. Neither receptor number nor binding affinity correlated with basal serum cortisol levels in either group. In the patient group, no correlation was observed between replacement hydrocortisone doses and either morning serum cortisol levels or GC-R number. The higher binding affinity and requirement of higher hydrocortisone dose might have been due to a compensatory response to increased clearance of glucocorticoids. In conclusion, GC-R parameters are not changed in patients with CAH and the variability of glucocorticoid replacement doses may be related to other functional defects of GC-R and glucocorticoid pharmacokinetics.