Context: Similar to patients with severe GHD, those with a more moderate impairment of GH secretion (GH insufficiency, GHI) have abnormal body composition, dyslipidaemia, 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: 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: 31 patients with GHD, 23 with GHI (peak GH 3-7µg/l [9-21mU/l]), and 30 age and sex-matched controls.

Main Outcome Measures: Demographic and biochemical markers of GH status.

Results: Nineteen (83%) of the patients with GHI 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 ITT, four the AST, 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 2.4-2.9µg/l. IGF-I values for the GHI adults were significantly lower than the control subjects (121+/-48 vs 162+/-75 µg/l; P<0.05), however, only six (26%) had values below the 10^th percentile of levels seen in the control group. IGFBP-3 and ALS levels of the GHI adults were not significantly different from the controls.

Conclusion: The diagnosis of GHI in an individual is extremely difficult as 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.