The impact of fasting and treatment omission on susceptibility to hypoglycaemia in children and adolescents with GH and cortisol insufficiency

Objective Hypoglycaemia may be a frequent occurrence in young GH deficient patients and so we studied the response to fasting in children and adolescents with GH and/or cortisol deficiency. Methods A total of 20 patients (2–18 years) fasted for 14 h (22·00–12·00 h) on two occasions as part of a randomized cross‐over study. Fourteen had pituitary hormone deficiency (PHD) including GH deficiency (GHD). Of the 14 patients, seven were ACTH sufficient (PHDC+) and seven ACTH deficient (PHDC–). Six had primary adrenal failure (PAF). Subjects administered or omitted their normal dose of evening GH and/or morning hydrocortisone. Glucose, insulin, GH, cortisol, ketones and catecholamines were measured at 04·00 h and regularly from 07·00 to 12·00 h. Insulin sensitivity was assessed by HOMA and hypoglycaemia defined as a blood glucose (BG) ≤ 3·3 mmol/l. Results BG was related to age and body mass index on treatment but no subject became hypoglycaemic on or off therapy prior to 07·00 h. Five children (aged 3, 4, 7, 8 and 11 years) were hypoglycaemic between 07·00 and 12·00 h off treatment. There was a positive relationship between GH AUC and minimum BG in patients with PHD on treatment (r² = 0·45, P = 0·012) with increased insulin sensitivity off treatment. Increased cortisol levels were seen in PHDC+ patients off GH (P < 0·001). A negative relationship was observed between minimum BG and adrenaline (r² = 0·37, P = 0·01), ketone bodies (r² = –0·20, P = 0·05) and NEFA (r² = –0·35, P = 0·02). Noradrenaline levels were reduced in patients with PHDC–. Low BMI (on treatment) and young age (off treatment) were determinants of low BG levels in a multiple regression model. Conclusions Unrecognized overnight hypoglycaemia in children and adolescents on pituitary hormone replacement is uncommon but BG levels quickly become abnormal when treatment and meals are omitted. The insulin antagonistic actions of GH are important in preventing hypoglycaemia. Patients with PHD have altered sympathetic nerve activity.