Abstract
Hypogonadism is the most common morbidity in patients with transfusionβdependent anemias such as thalassemia major. We used magnetic resonance imaging (MRI) to measure pituitary __R__2 (iron) and volume to determine at what age these patients develop pituitary iron overload and volume loss. We recruited 56 patients (47 with thalassemia major, five with chronically transfused thalassemia intermedia and four with BlackfanβDiamond syndrome) to have pituitary MRIs to measure pituitary __R__2 and volume. Hypogonadism was defined clinically based on the timing of secondary sexual characteristics or the need for sex hormone replacement therapy. Patients with transfusional iron overload begin to develop pituitary iron overload in the first decade of life; however, clinically significant volume loss was not observed until the second decade of life. Severe pituitary iron deposition (Z > 5) and volume loss (Z < β2.5) were independently predictive of hypogonadism. Pituitary __R__2 correlated significantly with serum ferritin as well as liver, pancreatic, and cardiac iron deposition by MRI. Log pancreas __R__2* was the best single predictor for pituitary iron, with an area under the receiving operator characteristic curve of 0.88, but log cardiac __R__2* and ferritin were retained on multivariate regression with a combined r^2^ of 0.71. Pituitary iron overload and volume loss were independently predictive of hypogonadism. Many patients with moderateβtoβsevere pituitary iron overload retained normal gland volume and function, representing a potential therapeutic window. The subset of hypogonadal patients having preserved gland volumes may also explain improvements in pituitary function observed following intensive chelation therapy. Am. J. Hematol. 2011. Β© 2011 Wiley Periodicals, Inc.