Megaloblastic Anemia Secondary to Folate Deficiency Associated with Hypothyroidism

Megaloblastic anemia and hypothyroidism, coexisting in relapse simultaneously, were documented in eight women; five patients had primary myxedema; two had secondary myxedema; and one had pituitary insufficiency. The diagnosis of pernicious anemia was excluded by the demonstration of an acidic gastric juice after betazole (Histalog®) stimulation in all eight, quantitatively normal gastric intrinsic factor concentrations in seven, and normal Schilling tests in two. The serum vitamin B12 concentrations were normal (seven patients) or diagnostically indeterminate (one patient) effectively excluding vitamin B12 deficiency as a cause of the megaloblastic anemia. Serum folate levels were subnormal in seven patients and diagnostically indeterminate in one; red cell folate concentrations were subnormal in three and normal in five. Five patients treated with 100 µg/day of oral pteroylglutamic acid in addition to undergoing thyroid replacement achieved complete hematologic remissions within 2 months, two patients were lost to follow-up, and one patient who exhibited a suboptimal hematologic response to phamacologic amounts of pteroylglutamic acid required iron administration for complete hematologic remission. These data suggest that folate deficiency was the cause of the megaloblastic anemia observed in these patients. The anemias occurring with myxedema are reviewed with reference to morphologic aspects and possible causative factors.