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The Glucagon Test in the Diagnosis of Growth Hormone Deficiency in Children With Short Stature Younger than 6 Years

Department of Pediatrics (A.S., N.d.I., F.N., E.C., M.G., C.F., R.L., M.M.) and Epidemiology and Biostatistics Section, Scientific Directorate (S.P.), Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini Institute, University of Genova, 16147 Genova, Italy; and Servizio di Endocrinologia Pediatrica (M.R.C., S.L.), Ospedale Regionale per le Microcitemie, 09121 Cagliari, Italy

Address all correspondence and requests for reprints to: Mohamad Maghnie, M.D., Ph.D., Associate Professor of Pediatrics, Department of Pediatrics Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, University of Genova, Largo Gerolamo Gaslini, 5, 16147 Genova, Italy. E-mail: mohamadmaghnie{at}ospedale-gaslini.ge.it.

Context: Few studies have addressed the diagnostic role of the glucagon test in children with suspected GH deficiency (GHD).

Objective: The objective of the study was to investigate the diagnostic value of the glucagon test as an alternative test to insulin tolerance test (ITT) and arginine in GHD children younger than 6 yr.

Design and Setting: This study was conducted in two pediatric endocrinology centers.

Patients and Methods: Forty-eight children (median age 4.2 yr, median height –3.0 SD score) with GHD confirmed by a peak GH to ITT and arginine less than 10 µg/liter (median 4.7 and 3.4 µg/liter, respectively) underwent a glucagon stimulation test. Magnetic resonance imaging showed normal hypothalamic-pituitary anatomy in 24 children, isolated anterior pituitary hypoplasia in seven, and structural hypothalamic-pituitary abnormalities in 17.

Results: Median GH peak response to glucagon (13.5 µg/liter) was significantly higher than that observed after ITT and arginine (P < 0.0001). GH peak after glucagon was less than 10 µg/liter in 20 subjects (group 1) and greater than 10 µg/liter in 28 subjects (group 2) without significant clinical or biochemical differences between the two groups. Median GH peak after glucagon was similar between patients with multiple pituitary hormone deficiency and those with isolated GHD and between subjects with and without structural hypothalamic-pituitary abnormalities. The magnitude of the GH peak after glucagon was negatively correlated to age at diagnosis ( = –0.636, P < 0.0001).

Conclusions: This study shows that glucagon has an effective GH-releasing activity and can be used to evaluate somatotroph function in young children with short stature. Normative data for this test in young children need to be established before its use in clinical practice.