title: 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. Although endocrine abnormalities are a well-recognized problem in these iron-overloaded patients, adrenal insufficiency and its consequences are underappreciated 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 y old, 7 female) were tested for adrenal insufficiency using a glucagon stimulation test. Those found to have adrenal insufficiency (stimulated cortisol <18 µg/dL) subsequently underwent an ovine corticotropin-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 glucagon stimulation test subsequently demonstrated normal ACTH and cortisol responses to oCRH, indicating a possible hypothalamic origin to their adrenal insufficiency.
authors.affiliation: *Department of Pediatrics, The Center for Pediatric Endocrinology, Diabetes, and Metabolism, Keck School of Medicine of USC †Children's Hospital Los Angeles §Department of Pediatrics, Division of Hematology-Oncology ‡Saban Research Institute of Children's Hospital Los Angeles ∥Department of Pediatrics, Division of Cardiology, Children's Hospital Los Angeles, Los Angeles, CA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Huang
authors.forename: Steven D
authors.initials: SD
authors.lastname: Mittelman
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Coates
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Geffner
authors.forename: John C
authors.initials: JC
authors.lastname: Wood
mesh_terms: D000293:Adolescent; D000309:Adrenal Insufficiency / Q000453:epidemiology* / Q000209:etiology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D002648:Child; D005260:Female; D005934:Glucagon / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D015995:Prevalence; D011446:Prospective Studies; D012727:Sex Characteristics; D017086:beta-Thalassemia / Q000150:complications*
chemical_list: D000324:Adrenocorticotropic Hormone; D005934:Glucagon; D006854:Hydrocortisone