Endocrine Abstracts

Rationale: In the diagnosis of hypopituitarism, the glucagon stimulation test allows for the simultaneous and safe evaluation of the somatotropic and corticotropic axes; recent data have highlighted a stimulating action also on the neurohypophyseal secretion of arginine-vasopressin. This procedure involves the intramuscular or subcutaneous administration of 1-1.5 mg of glucagon based on the patient’s weight (respectively less or more than 90 kg). Nowadays no data are available regarding the new intranasal formulation (Baqsimi^®, 3 mg single-dose nasal powder). This considered, the primary outcome of this pilot proof-of-concept study was to evaluate the anterior and posterior pituitary response in healthy subjects, in terms of changes in ACTH and cortisol, GH and copeptin levels, after administration of 3 mg of glucagon nasal powder or placebo.

Design and methods: For this non-randomized cross-over study, we recruited 10 healthy subjects (50% women) aged ≥ 18 years and with a BMI between 18.5 and 25 kg/m². Exclusion criteria were any current ongoing treatment, pregnancy and breastfeeding. All participants underwent to 2 different days of testing, when glucagon or placebo were administered intranasally in a random order. At baseline (immediately before taking glucagon or placebo), every 15’ up to +90’, and then every 30’ up to +180’ a blood sample was taken for ACTH, cortisol, GH, copeptin, glucose, insulin, sodium, potassium, plasma osmolarity. At baseline and the end of the test urinary osmolarity was evaluated as well.

Results: After administration of both placebo and glucagon ACTH and cortisol values progressively decreased over time (P<0.001) but in the drug group the reduction in cortisol was blunted up to +90’ (P<0.05). GH values decreased after placebo administration (P<0.001) while after glucagon there was a non-significant trend towards its increase (P=0.096) with the difference between the two groups evident starting from +120’ onwards (P<0.005). The placebo administration led to a reduction of copeptin (P=0.008), while its stability was observed after glucagon administration. Six subjects developed hypokalemia (potassium <3.5 mmol/l) post-glucagon. The potassium nadir at 45’ was significantly correlated with the immediate post-glycemic rise insulin peak (Spearman’s rho -0.719; P=0.019). No significant differences were observed regarding the other analytes tested.

Conclusions: Nasal administration of glucagon, unlike the intramuscular or subcutaneous injection, does not constitute an effective stimulus for anterior and posterior pituitary secretion, at least at the dose typically used for severe hypoglycemia. Hypokalemia secondary to hyperinsulinemic rebound appears to be a frequent complication of acute glucagon administration.