The diagnosis of partial growth hormone deficiency in adults with a putative insult to the hypothalamo-pituitary axis

CONTEXT: Similar to patients with severe GH deficiency (GHD), those with a more moderate impairment of GH secretion [GH insufficiency (GHI)] have abnormal body composition, dyslipidemia, and insulin resistance. Given the inherent problems in the diagnosis of severe GHD, the situation is likely to be even more difficult in individuals with GHI. OBJECTIVE: The objective of the study was to examine the utility of GH stimulation tests and GH-dependent proteins in the diagnosis of GHI. DESIGN: The study was a cross-sectional, case-controlled study. PATIENTS: The study included 31 patients with GHD, 23 with GHI [peak GH 3-7 microg/liter (9-21 mU/liter)], and 30 age- and sex-matched controls. MAIN OUTCOME MEASURES: Demographic and biochemical markers of GH status were measured. RESULTS: Nineteen of the patients with GHI (83%) had no additional anterior pituitary hormone deficits. Ten GHI patients showed discordant GH status based on the two GH stimulation tests performed. GH status was defined by the highest peak GH value achieved; in four this was to the insulin tolerance test (ITT), four the arginine test, and two the GHRH-arginine test. In five of the six patients in whom GH status was not defined by the ITT, peak GH levels to the ITT were in the range 2.4-2.9 microg/liter. IGF-I values for the GHI adults were significantly lower than the control subjects (121 +/- 48 vs. 162 +/- 75 microg/liter; P < 0.05); however, only six (26%) had values below the 10th percentile of levels seen in the control group. IGF binding protein-3 and acid labile subunit levels of the GHI adults were not significantly different from the controls. CONCLUSION: The diagnosis of GHI in an individual is extremely difficult because the patients rarely exhibit additional pituitary hormone deficits, and levels of GH-dependent proteins are normal in the majority. Diagnosis relies heavily on GH stimulation tests and requires two tests in all patients to define GHI; obesity when present is potentially a major confounder.