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Reassessment of the Growth Hormone Status in Young Adults with Childhood-Onset Growth Hormone Deficiency: Reappraisal of Insulin Tolerance Testing

Department of Pediatrics (A.S., N.d.I., F.N., E.C., A.C., M.G., C.F., N.F., R.G., R.L., M.M.) and Epidemiology and Biostatistics Section, Scientific Directorate (S.P.), Instituto di Ricovero e Cura a Carattere Scientifico, Giannina Gaslini Institute, University of Genova, 16147 Genova, Italy; and Department of Pediatrics (M.B., Y.L., G.R.), Regional Hospital of Bolzano, 39100 Bolzano, Italy

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

Context: The 2007 Consensus Statement suggested a peak GH cutoff to insulin tolerance test (ITT) of less than 6 µg/liter in the diagnosis of permanent GH deficiency (GHD) in young adults with childhood-onset GHD (COGHD), although further validation was recommended.

Objective: The aim of the study was to evaluate the accuracy of ITT, mean 12-h spontaneous nocturnal GH (SNGH), and IGF-I in the definition of permanent GHD.

Design and Setting: The study was conducted in two Pediatric Endocrinology Centers.

Patients and Methods: ITT, 12-h SNGH, and IGF-I were evaluated as single or combined tests in 79 subjects with COGHD (median age, 18.0 yr). The cohort consisted of 48 subjects with isolated GHD or one additional pituitary defect and normal MRI or anterior pituitary hypoplasia (group LLGHD, low likelihood GHD), and 31 subjects with structural hypothalamic-pituitary abnormalities or multiple pituitary hormone deficiencies (group HLGHD, high likelihood GHD).

Results: Receiver operating characteristic analysis showed the best diagnostic accuracy for peak GH cutoffs to ITT of 5.62 µg/liter or less [sensitivity, 77.4%; specificity, 93.8%; area under the curve (AUC) = 0.92], mean 12-h SNGH of 1.20 µg/liter or less (sensitivity, 90.3%; specificity, 89.6%; AUC = 0.93), and IGF-I of –2.83 SD score or less (sensitivity, 80.7%; specificity, 95.7%; AUC = 0.93). Seven patients in group HLGHD showed a peak GH to ITT above 5.62 µg/liter, but a median IGF-I that was significantly lower than that of group LLGHD (–3.30 vs. –0.73 SD score; P = 0.0001). Peak GH to ITT of 3.6 µg/liter or less and arginine of 3.1 µg/liter or less at childhood diagnosis can predict a future permanent GHD condition.

Conclusions: The adopted peak GH to ITT below 5.62 µg/liter is an accurate diagnostic cutoff point for HLGHD in young adults with COGHD. In addition, IGF-I is a reliable marker providing information about the severity of GHD. Careful follow-up is required for subjects with discordant ITT and IGF-I results.