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The Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 2 477-485
Copyright © 2002 by The Endocrine Society

Special Features

Which Patients Do Not Require a GH Stimulation Test for the Diagnosis of Adult GH Deficiency?

Mark L. Hartman, Brenda J. Crowe, Beverly M. K. Biller, Ken K. Y. Ho, David R. Clemmons and John J. Chipman on behalf of the HypoCCS Advisory Board and the U.S. HypoCCS Study Group

Lilly Research Laboratories (M.L.H., B.J.C., J.J.C.), Eli Lilly \|[amp ]\| Co., Indianapolis, Indiana 46285; Massachusetts General Hospital (B.M.K.B.), Boston, Massachusetts 02114; Garvan Institute of Medical Research, St. Vincent’s Hospital of Sydney (K.K.Y.H.), Sydney, NSW 2064, Australia; and University of North Carolina (D.R.C.), Chapel Hill, North Carolina 27599

Address all correspondence and requests for reprints to: Mark L. Hartman, Eli Lilly \|[amp ]\| Co., Lilly Corporate Center, Drop Code 5015, Indianapolis, IN 46285. E-mail: hartman{at}lilly.com

Abstract

Adult GH deficiency (GHD) is currently diagnosed in patients with either a history of childhood-onset GHD or acquired hypothalamic-pituitary disease by GH stimulation testing. However, GH stimulation tests are invasive, time consuming, and associated with side effects. Based on preliminary analyses of patients enrolled in the U.S. Hypopituitary Control and Complications Study (HypoCCS), we proposed the presence of adult GHD could be predicted with 95% accuracy by the presence of three or more pituitary hormone deficiencies (PHDs) or a serum IGF-I concentration less than 84 µg/liter (11 nmol/liter). To validate the diagnostic utility of these criteria, we studied results obtained in 817 adult patients (mean [SD] age: 46.4 [15.7] yr, body mass index: 30.1 [7.2] kg/m2) enrolled in HypoCCS who had serum GH concentrations from stimulation tests (11 different tests used, excluding clonidine) and serum IGF-I (competitive binding RIA) measured at the central laboratory (Esoterix Endocrinology, Calabasas Hills, CA). When patients were stratified into subgroups on the basis of the presence of zero, one, two, three, and four additional PHDs, median (25th, 75th percentile) peak GH levels (micrograms per liter) were 3.5 (0.85, 7.1), 0.73 (0.18, 4.2), 0.29 (0.05, 1.4), 0.06 (0.025, 0.295), and 0.025 (0.025, 0.07), respectively. The mean log (peak GH) concentration was significantly different among the subgroups (P < 0.05). The proportion of patients in each group with severe GHD diagnosed by stimulation testing (peak GH < 2.5 µg/liter) was 41%, 67%, 83%, 96%, and 99% for patients with zero, one, two, three, and four PHDs, respectively. The positive predictive values (PPVs) for GHD of three PHDs, four PHDs, and serum IGF-I less than 84 µg/liter were 96%, 99%, and 96%, respectively. The PPV of these three diagnostic criteria was also 95% or more after excluding the data originally used to identify these potential predictors. Taken together, the presence of either three or four additional PHDs or IGF-I less than 84 µg/liter (55% of the patients met at least one of these criteria) reliably predicted GHD with a high PPV (95%), high specificity (89%), and moderate sensitivity (69%). We concluded that patients with an appropriate clinical history and either the presence of three or four additional PHDs or serum IGF-I less than 84 µg/liter (measured in the Esoterix assay) do not require GH stimulation testing for the diagnosis of adult GHD. In clinical practice, we suggest that other causes of low serum IGF-I should be excluded before applying these diagnostic criteria.




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