A Significant Proportion of Thalassemia Major Patients Have Adrenal Insufficiency Detectable on Provocative Testing

Abstract

Advances in chelation therapy and noninvasive monitoring of iron overload have resulted in substantial improvements in the survival of transfusion dependent patients with thalassemia major. Myocardial decompensation and sepsis remain the major causes of death. While endocrine abnormalities are a well-recognized problem in these iron-overloaded patients, adrenal insufficiency and its consequences are under-appreciated by the hematology community. The aims of this study were to determine the prevalence of adrenal insufficiency in thalassemia major subjects, to identify risk factors for adrenal insufficiency, and to localize the origin of the adrenal insufficiency within the hypothalamic-pituitary-adrenal axis. Eighteen subjects with thalassemia major (18.9 ± 9.3 years old, 7 female) were tested for adrenal insufficiency using a glucagon stimulation test (GST). Those found to have adrenal insufficiency (stimulated cortisol < 18 μg/dL) subsequently underwent an ovine corticotrophin-releasing hormone (oCRH) stimulation test to define the physiological basis for the adrenal insufficiency. The prevalence of adrenal insufficiency was 61%, with an increased prevalence in males over females (92% vs. 29%, p=0.049). Ten of 11 subjects who failed the GST subsequently demonstrated normal ACTH and cortisol responses to oCRH, indicating a possible hypothalamic origin to their adrenal insufficiency.

Adrenal insufficiency in non‐transfusion‐dependent α‐thalassemia

“…Unfortunately, liver iron assessment was not performed in the present study. There was no clear explanation for the present high proportion of secondary AI, but a previous study in TDT reported smaller pituitary volume in patients with AI . We also found that patients with AI tended to be older and had lower serum hemoglobin than patients with normal adrenal function, but the difference was not statistically significant.…”

Evaluation of Iron Deposition in the Adrenal Glands of β Thalassemia Major Patients Using 3-Tesla MRI

“…Studies performed on β-TM patients have shown that the prevalance of biochemical adrenal insufficiency depends on the clinical course of the disease, age of the patient, transfusion load, degree of iron accumulation, and chelation therapy. The prevalence has been reported as 13% - 61% although there are variations among diagnostic tests and cut-off values (16-18). In β-TM patients, most of the time, the biochemical adrenal insufficiency is not evident clinically with adrenal crisis.…”

“…Diagnosis of adrenal insufficiency is critical because in stress conditions including surgery or sepsis, adrenal crisis may ensue. In addition, for β-TM patients with adrenal insufficiency, glucocorticoids are needed in the treatment of hypotenion accompanying cardiac insufficiency (16-18). …”

Multiple Endocrinologic Complications in Thalassemia Major

“…Adrenal glands might also be directly affected by iron toxicity producing primary adrenal insufficiency [9][10][11].…”