Endocrine Abstracts

Background: The Insulin Tolerance Test (ITT) is the gold standard for assessing pituitary function in adults, but used variably in paediatrics due to concerns of serious adverse events. Our aim was to assess the safety of ITT and identify factors associated with the hypoglycaemic response.

Methods: We retrospectively collected the following data from patients who underwent ITT (n=122) under Paediatric Endocrinology from 2019-2021: demography, anthropometry, indication for ITT, pituitary deficiencies, insulin dose, blood glucose (BG) values, IGF1, peak growth hormone (GH) and cortisol levels, features and treatment of hypoglycaemia, and adverse outcomes. Severe biochemical hypoglycaemia (SBH) was defined as nadir BG (NBG) ≤2.0 mmol/l and poor response to treatment (PRT) as further decrease in BG despite glucose administration.

Results: 90 patients were evaluated for GH deficiency diagnosis (age=12.0±3.0yrs) and 32 underwent re-evaluation at final height (age=17.4±1.5yrs), with mainly standard insulin dose of 0.1units/kg (2 received 0.05units/kg and 0.15units/kg each). The mean basal BG (BBG) was 4.91±0.52 mmol/l, NBG 1.83±0.53 mmol/l and duration of hypoglycaemia 14.1±8.7 minutes. 112 (92.6%) patients achieved adequate hypoglycaemia (BG <2.6 mmol/l). 81 (66.9%) patients developed SBH and 65 (53.3%) PRT. None developed seizure, unconsciousness or other serious hypoglycaemia-related adverse effects. 3 (2.7%) patients received IV glucose and one IV hydrocortisone for poor oral intake/prolonged hypoglycaemia. Duration of hypoglycaemia was longer in patients assessed for re-evaluation than for diagnosis (19.0±12.4 vs 12.5±6.4 minutes, P=0.001), but NBG were similar. NBG was associated with BBG (r=0.42, p<0.0001) and peak cortisol levels (r=0.21, P=0.022), but not peak GH levels or BMI. PRT was associated with lower BBG (r=-0.29, PPPP=0.002) and peak cortisol levels (r=-0.20, P=0.027). BBG of ≤4.0 mmol/l (approximately <--2SD of BBG) was associated with higher proportion of SBH (83.3% vs 66.4%) and PRT (100% vs 53.0%). Duration of hypoglycaemia was associated positively with age (r=0.25, P=0.009) and number of pituitary deficiencies (r=0.22, P=0.020), and negatively with BBG (r=-0.23, P=0.015).

Conclusions: Despite the high incidence of SBH, there were no significant hypoglycaemia-related adverse events. Reducing insulin dose to 0.05units/kg when cortisol deficiency is likely or BBG ≤4.0 mmol/l and using a higher hypoglycaemia threshold may reduce the frequency of SBH and duration of hypoglycaemia.