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

OBJECTIVE The diagnosis of GH deficiency in adults relies on the results of GH provocative testing. Whilst in some patients the testing strategy is cl ear, 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 differen t provocative stimuli, to correlate this with the number of additional pitu itary hormone deficits, and to produce guidelines as to which patients requ ire 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 toleran ce test (ITT) and an arginine stimulation test (AST). Severe GH deficiency was defined as a GH response to an ITT of <5 mU/I and a GH response to an A ST of <2 mU/I, 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 pitui tary hormone deficits (GHDO) or one, two or three other hormone deficits (G HD1, GHD2 or GHD3). RESULTS The 103 patients were divided between the four groups as follows: 6 9 (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 t rend is seen (Spearmans rank correlation = 0.88, P < 0.0001) indicating tha t the magnitude of the difference between the GH responses to an ITT and AS T increases with the underlying mean GH value. These data allow the estimat ion of the median ITT/AST ratio as 1.17 (CI 0.98, 1.39). None of the contro l subjects and 14.1% (10), 26.7% (four), 83% (five) and 92.3% (12) of group s GHD0, 1, 2 and 3, respectively, had severe GHD. The concordance between t he 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%, an d 92.3% in the controls, GHDO, 1, 2, and 3, respectively. Thus, 16/69 GHDO, 5/15 GHD1, 1/6 GHDP and 1/13 GHD3 patients were misclassified by one or ot her 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 insuffic iency. These patients tend to have one or no additional pituitary hormone d eficits and may be misclassified if a single GH provocative test is perform ed. We suggest that whilst a single GH provocative test can be used with co nfidence in patients with two or three additional pituitary hormone deficit s, in patients with suspected isolated GH deficiency or with only one addit ional pituitary hormone deficit, two GH provocative tests should be perform ed.