Elevated Serum Ferritin Levels Are Highly Associated with Diabetes Mellitus and Hypothyroidism in Thalassemia Patients

Endocrinopathiesare well recognized serious complications in thalassemia patients with iron overload. Elevated serum ferritin levels reflect severity of iron overload and are associated with relevant clinical outcomes.

Increased serum ferritin > 2, 500 μg/dl has been found to predict the development of cardiac function abnormalities but the predicting serum ferritin level for diabetes and hypothyroidism has not been determined.

This is a cross sectional and retrospective study to evaluate the correlation between ferritin levels and endocrinopathies (diabetes, hypothyroidism) in thalassemia patients. All thalassemia patients age > 18 years old, during August 2011 and June 2012 were enrolled. The diagnosis and type of thalassemia were reviewed and confirmed. Diabetes and hypothyroidism were diagnosed by fasting blood sugar and thyroid functions test. Serum ferritin was measured at the same period. The medical record was reviewed for age, sex, splenomegaly, history of splenectomy, transfusion requirement, maximum serum ferritin level, mean serum ferritin level and iron chelation history.

Among 92 thalassemia patients [35 male (38%) and 57 female (62%)] with a median age of 30. 6 years (range, 18–71). There were 28 (30. 4%) cases of Homozygous β-thalassemia, 45 cases (48. 9%) of β-thalassemia/Hemoglobin E and 18 cases (19. 5%) of Hemoglobin H or AE Bart's disease. Most patients (60. 9%) underwent splenectomy, while only one third of patients (34. 8%) were NTDT (non-transfusion dependent thalassemia) (Table 1). The mean value of random and maximum serum ferritin levels for the whole group were 2, 408 μg/dl (range279–9, 817) and 5, 101 μg/dl (range 279–37, 656), respectively.

The prevalence of diabetes mellitus and impaired fasting glucose (IFG) were 9. 8% (9 cases) and 10. 9% (10 cases), respectively. Patients with diabetes had significantly higher mean maximum serum ferritin levels than those with non-diabetes (11, 241 μg/dl vs. 4, 468 μg/dl, (p=0. 0001) (Table 2). The cut-off point of maximum serum ferritin levels > 2, 500 μg/dl was the major risk factor for the development of diabetes complication in this group of patients.

Six patients (6. 5%) and 21 patients (22. 8%) had hypothyroidism and subclinical hypothyroidism, respectively. Patients with hypothyroidism had significantly higher mean maximum serum ferritin levels than those with euthyroidism [(7, 638 vs. 4, 117 μg/dl, (p=0. 003)]. From univariate analysis, the cut-off point of maximum serum ferritin levels > 3, 500 μg/dl was the major risk factor associated with hypothyroidism (p=0. 007).

Elevated serum ferritin level is a predictor of the development of diabetes mellitus and hypothyroidism in thalassemia patients with iron overload. The maximum serum ferritin levels of greater than 2, 500 and 3, 500 μg/dl are associated with diabetes mellitus and hypothyroidism, respectively. These findings warrant the value of iron chelating therapy to maintain serum ferritin levels below 2, 500 μg/dl to avoid the development of endocrinopathies in patients with thalassemia.

No relevant conflicts of interest to declare.