The diagnosis of GH deficiency in adult β-thalassemic patients: are two different stimulation tests necessary to improve specificity?

Purpose: β-thalassemia major (βTM) frequently leads to endocrinological complications of chronic transfusion-induced iron overload, including growth hormone deficiency (GHD). With contrasting data on GHD in adult βTM populations, our study aimed to reevaluate the diagnosis of GHD using multiple tests and its progression over time.

Methods: Two experimental studies were conducted in adult βTM patients to assess GH secretory status. The first study reevaluated GH secretion after two years using a GHRH plus arginine test performed initially and during follow-up. The second study applied a glucagon stimulation test to those initially diagnosed with severe GHD, comparing the results with those of a GHRH plus arginine test.

Results: The first study involved 80 patients: 67 patients had normal GH secretion at the first test, confirmed in 57 of them. Of the 13 initially diagnosed with GHD, only 3 were confirmed at the second test. The second study included 91 patients: 18 of the initially identified as having severe GHD, were tested with another challenge, but only 6 confirmed severe GHD, suggesting a possible risk of overdiagnosis in initial evaluations.

Conclusions: The marked variability in GHD diagnoses among adult patients with βTM highlights the need for multiple diagnostic tests to improve accuracy and avoid unnecessary interventions. Our findings highlight the importance of reassessing GH secretory reserves with multiple tests at multiple time points, supporting a cautious approach to hormone replacement therapy, suggesting to start it only when clearly indicated.