THE DIAGNOSIS OF SEVERE GROWTH-HORMONE DEFICIENCY IN ELDERLY PATIENTSWITH HYPOTHALAMIC-PITUITARY DISEASE

OBJECTIVE Adults over the age of 60 years with organic disease of the hypothalamic-pituitary axis may be deficient in growth hormone (GH) to a degree that is distinct from the age-related decline in GH secretio n and sufficient to cause perturbations of body composition, serum lip id profile and bone metabolism. In order to determine the best method for detecting GH deficiency in this age group we have compared spontan eous GH secretion, a provocative test of GH secretion, the arginine st imulation test (AST), and basal estimates of circulating insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP). DESIGN Twenty-f our patients (16 male) with organic hypothalamic-pituitary disease and 24 controls (17 male) were studied. The groups were matched for BMI b ut the patients were slightly younger than the controls, 66.0 (61.0-85 .7) vs. 70.6 (60.8-87.5) years (P=0.04). All subjects underwent a 24-h GH profile (20-minute sampling), measurement of serum IGF-I, IGF-II, IGFBP3, IGFBP2 and growth hormone binding protein (GHBP) and, after an overnight fast, an AST (intravenous arginine 20g/m(2) over 30 minutes ). GH concentrations were measured using an ultrasensitive chemilumine scence assay (sensitivity 0.002 mu g/l). Normative data for serum IGF- I, IGF-II, IGFBP3 and IGFBP2 were obtained from 125 subjects aged 60-8 7 years. RESULTS None of the parameters studied was able to distinguis h between all the GH deficient patients and the healthy controls. The median (range) area under the GH profile (AUC(GH)) and peak GH respons e to arginine were lower in the patients than in the controls, 310.05 (18.90-2193.36) vs. 2518.20 (526.76-12024.97) min mU/I (P<0.00001), 1. 07 (0.08-17.90) vs. 23.06 (4.60-109.98) mU/I (P<0.00001), respectively . There was a significant relationship between AUC(GH) and peak GH res ponse to arginine in the patients (r=0.89, P<0.0001) and in the contro ls (r=0.56, P=0.005). Serum IGF-I, IGFBP2, and IGFBP3 levels were sign ificantly lower in the patients compared with the normal range, 102 (1 4-162) vs. 142 (59-298) mu g/l (P<0.0001), 415 (122-1868) vs. 640 (140 -2585) mu g/l (P=0.0007) and 2.29 (0.81-3.75) vs. 2.59 (1.00-3.52) mg/ l (P=0.009), respectively. The degree of overlap between the two group s, however, was too great to make these measurements useful diagnostic ally. Serum IGF-II and GHBP concentrations in the patients were not si gnificantly different from the normal range. The patients were divided into groups determined by the number of anterior pituitary hormone de ficits present. There was a significant downward trend in the peak GH response to arginine with increasing severity of hypopituitarism (J= - 3.04, P=0.0012). Ninety per cent of patients with two or three additio nal pituitary deficiencies had a peak GH response less than 2.0 mU/L. CONCLUSIONS Of the indices studied the arginine stimulation test is mo re effective than GH markers, such as IGF-I or IGFBP3, or measurement of spontaneous GH secretion for diagnosing GH deficiency in adults ove r the age of 60 years. By relating the peak GH response to the degree of hypopituitarism, a GH response less than 2.0 mU/I is suggestive of severe GH deficiency in this age group under the appropriate clinical circumstances.