Endocrine abnormalities in hemodialysis patients with iron overload: reversal with iron depletion

Abstract

The endocrine function was studied in 9 hemodialysis patients with iron overload (IO) before and after iron depletion. Diagnosis of IO was established by high serum ferritin (> 1100 micrograms/L), high hepatic CT density (> 70 Hounsfield units), and excessive iron stores in bone marrow aspirate (grade 6). At the start of the study, 8 patients had gonadal failure, 6 of whom had hypothalamopituitary disease, and 4 manifested thyroid abnormalities. At the end of the study, the hypothalamopituitary function and thyroid abnormalities improved in all patients except one who manifested hypothalamic disease. Primary gonadal failure persisted in the 8 patients. ACTH stimulation produced adequate increments in plasma cortisol at the start and end of the study. Pancreatic (beta cell) function was adequate at the end of the study as shown by normal oral glucose tolerance test and free insulin increments during the test. The CT scan and follow-up indicated significant iron mobilization from the liver, pancreas, and the adrenal glands. Hormonal studies were repeated in 4 of the 5 patients who manifested endocrine abnormalities and had received recombinant human erythropoietin (rHuEPO), 3 mo after discontinuation of the drug. Improvement in the endocrine function persisted in those patients. Our results indicated that dialysis patients exposed to iron overload are at risk for development of multiple endocrine defects. Fortunately, aggressive iron depletion can mobilize iron from these organs and reverse some of the defects.