“Non-classical” indication for provocative testing of growth hormone: a retrospective cohort study in adult patients under replacement therapy

Background: Adult growth hormone deficiency (GHD) is considered a rare condition. Current guidelines state that GH provocative test is indicated in patients affected by organic hypothalamic/pituitary disease or with history of head injury, irradiation, hemorrhage or hypothalamic disease with multiple pituitary deficiencies. Nevertheless, clinical picture related to GHD may be subtle. Objective: We have retrospectively evaluated the indication to GHRH+arginine test in our monocentric cohort of patients treated with hrGH in order to assess whether other conditions had been considered as a rationale for provocative testing. Methods: 96 patients (51 females and 45 males), aged 19-67 years were included. The GHRH+arginine test had been performed in 29 patients with organic hypothalamic/pituitary disease and in 4 patients for Childhood onset-GHD (Co-GHD). In other patients the diagnosis was suspected for “non classical” reasons in clinical picture suspected for GHD. Results: Classical indications included previously known primary empty sella (n=15), pituitary surgery (n=14), pituitary cyst (n=1), non-secreting pituitary tumors (n=3) but more than half patients (57.3%) had been studied for “non classical” indications: metabolic syndrome (n=25), asthenia (n=13), heart failure (n=4), osteoporosis (n=6), unexplained hypoglycaemia (n=1) and infertility (n=6). The latter represented a significant percentage in the male subgroup under 45 ys. IGF-1 levels were lower than 50th percentile in 63% of patients. Finally, among non-classical reasons organic pituitary disease was discovered in 22 patients. Conclusions: Idiopathic GHD may be unrecognized due to its subtle manifestations and that an extended use of dynamic GH test may reveal such condition. A potential field of investigation could be to identify subsets of patients with clinical conditions caused or worsened by underlying unrecognized GHD.