ESPE Abstracts

Background: Several studies in adults have provided evidence for opioid-induced hypofunction of the hypothalamo-pituitary–adrenal and GH–IGF1 axis after chronic (oral and intrathecal) administration. This so-called opioid endocrinopathy has not been reported in children.

Objective and hypotheses: We report the occurrence of delayed growth with low serum IGF1 levels and recurrent hypoglycemia due to central hypocorticism in a toddler after a presumably intentional chronic codeine administration by her parents.

Method: In a healthy 12 months old girl, admitted for coma related to a benzodiazepine and codeine intoxication, a symptomatic hypoglycemia (glucose <45 mg/dl), responding to glucose administration, was documented when excessive sleepiness reoccurred at the third day of hospitalization. Subsequent glucose monitoring showed several asymptomatic hypoglycemic episodes during the next day. Poor growth and previous episodes of excessive sleepiness were evidenced during the 4 months preceding the hospitalization.

Results: A critical sample analysis documented a ACTH level of 10 pg/ml and a cortisol of 1.7 μg/dl, which increased up to 13.9 μg/dl after a low dose ACTH test. Basal serum PRL and TSH were normal, but IGF1 was low (25 μg/l) and DHEAS not measurable. A normal pituitary and hypothalamus were seen on MR imaging of the brain. After the instauration of hydrocortisone therapy, glucose levels remained normal and hydrocortisone was stopped after 6 weeks. Four weeks after stopping therapy, a normal basal cortisol, but a weak response to ACTH was documented. A normal GH and cortisol response at glucagon testing was found after 6 weeks.

Conclusion: In contrast with hyperglycemia seen in toddlers with acute codeine intoxication, recurrent hypoglycemia due to a transient central hypocorticism can be observed in chronic codeine ingestion. Genetic differences in opioid receptor binding and metabolizing properties might be responsible for the induction and recovery of the endocrine dysfunction after opioid administration in children.