How many tests are required to diagnose growth hormone (GH) deficiency in adults?

Abstract

Objective: The diagnosis of GH deficiency in adults relies on the results of GH provocative testing. Whilst in some patients the testing strategy is clear, this is not the case in all patients. The objective of this study was to further examine the concordance between the GH responses to two different provocative stimuli, to correlate this with the number of additional pituitary hormone deficits, and to produce guidelines as to which patients require two GH provocative tests and which require only one.

Study design and patients: The results of GH provocative tests were reviewed in 103 patients (mean age 28 years, 48 male), with documented or potential hypothalamic-pituitary disease and 35 normal volunteers (mean age 21 years, 18 male). All patients and normal volunteers underwent an insulin tolerance test (ITT) and an arginine stimulation test (AST). Severe GH deficiency was defined as a GH response to an ITT of < 5 mU/l and a GH response to an AST of < 2 mU/l, utilizing data from previous studies in this unit. Patients were divided into four groups according to the number of anterior pituitary hormone deficits present other than possible GH deficiency: no other pituitary hormone deficits (GHD0) or one, two or three other hormone deficits (GHD1, GHD2 or GHD3).

Results: The 103 patients were divided between the four groups as follows: 69 (67%) in GHD0, 15 (14. 6%) in GHD1, six (5.8%) in GHD2, and 13 (12.6%) in GHD3. There was a significant decline in the median GH peak to both the ITT and the AST with increasing numbers of other pituitary hormone deficits (P < 0.0001). If the magnitude of the difference between each individual's GH response to the ITT and AST is plotted against the mean GH value a clear trend is seen (Spearmans rank correlation = 0. 88, P < 0.0001) indicating that the magnitude of the difference between the GH responses to an ITT and AST increases with the underlying mean GH value. These data allow the estimation of the median ITT/AST ratio as 1.17 (CI 0.98, 1.39). None of the control subjects and 14.1% (10), 26.7% (four), 83% (five) and 92.3% (12) of groups GHD0, 1, 2 and 3, respectively, had severe GHD. The concordance between the AST and ITT (percent of patients in whom both tests confirmed or refuted the biochemical diagnosis of severe GHD) was 100%, 76.8%, 66.6%, 83.3%, and 92.3% in the controls, GHD0, 1, 2, and 3, respectively. Thus, 16/69 GHD0, 5/15 GHD1, 1/6 GHD2 and 1/13 GHD3 patients were misclassified by one or other test.

Conclusion: We have demonstrated that a constant ratio links the GH response to an ITT and AST in an individual, rather than a constant difference, and that the difference between the GH responses to two provocative stimuli is greater in those patients with milder degrees of GH deficiency or insufficiency. These patients tend to have one or no additional pituitary hormone deficits and may be misclassified if a single GH provocative test is performed. We suggest that whilst a single GH provocative test can be used with confidence in patients with two or three additional pituitary hormone deficits, in patients with suspected isolated GH deficiency or with only one additional pituitary hormone deficit, two GH provocative tests should be performed.