Diagnosis of growth hormone (GH) deficiency in adults with hypothalamic-pituitary disorders: Comparison of test results using pyridostigmine plus GH-releasing hormone (GHRH), clonidine plus GHRH, and insulin-induced hypoglycemia as GH secretagogues

The insulin tolerance test (ITT) is widely accepted as the method of choice to evaluate GH secretion capacity in adults with hypothalamic-pituitary di sorders. However, the test is not suitable in the elderly or in patients wi th cardiovascular disease or seizure disorders. In recent years alternative s to the ITT have been introduced. The purpose of the present study was to investigate the diagnostic outcome with the ITT, the pyridostigmine plus GH RH (PD + GHRH) test, the clonidine plus GHRH (CLO + GHRH) test, and insulin -like growth factor I (IGF-I) in an unselected group of patients with hypot halamic-pituitary disease. An evaluation of the reproducibility of the diff erent stimulation tests was included in the study. Based on repeated testin g with the various GH stimulation tests in healthy adult males and females, the lower limits of normality for the ITT, the PD+GHRH test, and the CLO+G HRH test were 3.92, 12.8, and 19.0 mu g/L, respectively. A consecutive grou p of 26 unselected patients with hypothalamic-pituitary disorders, 13 males and 13 females (median age, 44 ys), were tested twice with all stimulation tests, except that only 10 patients were tested once with the CLO+GHRH tes t due to side-effects related to clonidine. The peak GH responses between t est 1 and test 2 correlated significantly in both the ITT and the PD+GHRH t est (P < 0.02), and no significant difference was observed in the median pe ak response to repeated testing. In addition, no sex difference was observe d. The coefficients of variation (CV) were 96% (ITT) and 45% (PD + GHRH), b ut in the majority of patients low values were repeatedly low. The peak GH response was significantly higher during the PD+GHRH test than during the I TT (P = 0.008). In the 10 patients tested with the PD+GHRH and CLO+GHRH tes ts there was no significant difference in the peak GH response (P = 0.398). When the test specific cut-off values were used, no significant difference in diagnostic outcome was observed between the various tests (P > 0.3). In contrast, the diagnosis obtained with IGF-I differed significantly from al l GH stimulation tests (P < 0.03). Twenty (77%) and 22 (85%) patients were diagnosed to be GH deficient with the ITT and the PD+GHRH test, respectivel y. Of the 14 patients with multiple pituitary failure (>2 hormones affected ), GH deficiency was present in more than 90% regardless of the type of sti mulation test used. The IGF-I levels were only subnormal in 42% of the pati ents and did not correlate viith the peak GH responses in any of the stimul ation tests (P > 0.05). Except for 1 patient all patients with subnormal IG F-I were GH deficient in all stimulation tests. It is concluded that in pat ients with hypothalamic-pituitary disease and a normal IGF-I level 2 stimul ation tests should be performed to establish a diagnosis of GH deficiency. In patients with a subnormal IGF-I Value a single GH stimulation test shoul d be sufficient to confirm the presence of GH deficiency.