Endocrine Abstracts

Background: Adult beta-thalassemia patients experience various endocrine complications associated with iron deposition. However, data regarding adrenal insufficiency (AI) are limited.

Subjects and Methods: A total of 104 beta-thalassemia patients examined between 2015 and 2024 in our outpatient clinic had at least one measurement of morning serum ACTH and cortisol levels. At the time of presentation, two male patients had already been diagnosed with primary AI. Twenty-two additional patients opted for screening with a 250 mg-tetracosactid stimulation test. Among them, 20 tests were performed on 18 patients who agreed to be tested in a median follow-up period of 3 years.

Results: The mean age in the test group was 30.6±6.7 years. Sixteen patients had beta-thalassemia major (5 F, 11 M), while the remaining three had beta-thalassemia intermedia (all F). All patients were transfusion-dependent except the patients with beta-thalassemia intermedia. Three patients showed maximum cortisol responses of less than 18 mg/dl (16.6%). Two of the three patients with inadequate cortisol responses had thalassemia intermedia. Four additional patients had less than 20 mg/dl peak cortisol responses. Only two patients in the test group had ACTH levels higher than twice the upper normal limit at baseline, with peak cortisol responses of 14.8 mg/dl and 20.6 mg/dl, respectively. None of the patients had baseline morning cortisol levels of less than 5 mg/dl, and none exhibited typical symptoms or signs of AI except for mild fatigue. All patients remained asymptomatic during a median of 3-years’ follow-up, with no glucocorticoid requirement. The mineralocorticoid axis was evaluated in ten patients: none had low aldosterone levels; however, seven revealed high renin levels. Among these seven, three had peak cortisol responses <18 mg/dl, while the remaining four had responses >20 mg/dl. All patients but one had additional beta-thalassemia-related endocrinopathies, bone metabolism disorders being the most common (84.2%), followed by hypogonadism (73.7%).

Conclusions: Subclinical AI may be more common than overt AI in beta-thalassemia patients. Our findings highlight the difficulty of detecting AI in beta-thalassemia patients, indicating that standard symptoms, signs, and laboratory parameters might be unreliable. The discordance between the pituitary and adrenal glands may further complicate the diagnostic process. Moreover, iron accumulation in the adrenal gland might not involve all regions, but only the glomerulosa region in some patients. Our study proposes the utilization of the 250 mg-tetracosactid stimulation test, as a more accurate method to diagnose adrenal insufficiency in patients with beta-thalassemia, regardless of transfusion dependence and disease severity.