Endocrine Abstracts

Introduction: Glucagon stimulation test is one of the recommended growth hormone provocation tests for diagnosing growth hormone deficiency in children. In adult patients, recent data showed that glucagon administration is able to stimulate the release of copeptin, the stable C-terminal glycopeptide of the AVP prohormone whose evaluation during hypertonic saline infusion represents the gold standard for the differential diagnosis of polyuria/polydipsia. However, similar data on pediatric population are still lacking. Aim of this study was to evaluate copeptin levels during glucagon test in children with suspected GH deficiency and to correlate its secretion with that of glucose, GH and cortisol.

Methods: Twenty-one children (10 females, mean age 10.3±2.9 years) with suspected growth hormone deficiency were studied during glucagon stimulation test (30 μg/Kg, maximum 1 mg intramuscolarly). Of these, 20 patients had normal posterior pituitary function, and one patient had well-established central diabetes insipidus. Blood samples for measurement of glucose, GH, cortisol and copeptin were taken at baseline and 60, 90 120, 150 and 180 minutes after glucagon administration.

Results: Median basal copeptin levels in 20 patients without diabetes insipidus were 4.1 pmol/l (interquartile range: 3.3-6.7). During glucagon test, a significant increase of copeptin was recorded 120, 150 and 180 minutes after stimulation (median: 8.1, 10.6 and 8.9 pmol/l, respectively, for all P<0.01 vs basal) with a peak after 150 minutes (median: 10.6 pmol/l, interquartile range: 5.4-17.9).

Correlation study for repeated measures showed that copeptin was directly associated with cortisol (r=0.39, P<0.001) and GH (r=0.42, P<0.001), and inversely associated with glucose (r=-0.36, P<0.001). In a multilevel mixed-effects regression model, copeptin was associated with cortisol (β=0.375, P=0.01) and time (β=0.005, P<0.001) but not with GH and glucose. No difference in median copeptin levels at any time point between patients with negative and positive response to glucagon test was found. The only patient with central diabetes insipidus showed low basal and stimulated copeptin levels (basal: 1.5 pmol/l, peak: 2.0 pmol/l)

Conclusion: glucagon administration represents a nonosmotic stimulus of the posterior pituitary also in children, as indicated by increased copeptin levels during the test. Copeptin peak is reached after 150 minutes and its trend seems to be related to cortisol secretion. Further studies are needed in order to clarify the mechanism behind the copeptin stimulation and to confirm the usefulness of this test for the assessment of posterior pituitary function.