Hemochromatosis and iron therapy of Restless Legs Syndrome.

Restless legs syndrome (RLS) occurs in some persons with iron deficiency, and some persons with RLS benefit from oral iron therapy. Approximately one in 200 persons of northern European ancestry have hemochromatosis attributable to inheritance of two common mutations of the hemochromatosis-associated HFE gene on chromosome 6. We evaluated and treated a 46-year-old man with RLS who was diagnosed as having hemochromatosis after he developed new symptoms associated with taking iron therapy for RLS. He had transferrin saturation 88%, serum ferritin 658 ng/ml, and C282Y homozygosity. Therapeutic phlebotomy of one unit of blood (450-500 ml) weekly (total 24 units) relieved his non-RLS symptoms, caused RLS symptoms to occur more frequently, and was associated with transient fatigue and mild dependent edema. His sister, who also has RLS, was subsequently diagnosed as having hemochromatosis. We conclude that serum transferrin saturation and ferritin levels should be measured before initiation of iron therapy of RLS. Patients with a history of iron deficiency or low serum iron parameters should undergo evaluation for iron deficiency; patients who have histories suggestive of hemochromatosis or iron overload or elevated pre-treatment transferrin saturation or serum ferritin levels should undergo evaluation to determine the cause of these abnormalities before they are treated with iron. In all persons with RLS treated with oral iron, serum iron parameters should be re-measured once or twice yearly during therapy.

Testicular leydig cell hyperplasia as a cause of familial sexual precocity.

Testicular Leydig cell hyperplasia was observed in two brothers presenting with progressive sexual precocity at 2 yr of age. Virilization was shown to result from increased secretion rather than decreased clearance of gonadal testosterone. Testosterone hypersecretion appeared to be gonadotropin independent, as basal and gonadotropin-releasing hormone-induced serum LH concentrations were low by both RIA and bioassay. Adrenal steroidogenesis was demonstrated to be normal by ACTH stimulation, dexamethasone suppression, and split adrenal venous function tests. Testicular histology revealed immature reproductive structures in the 2 yr old, but advanced spermatogenesis in the 3 yr-old brother. The etiology of both Leydig cell hyperplasia and reproductive testicular maturation in the absence of significant gonadotropin secretion remains to be established.