Erythropoiesis and Erythropoietin in Hypo- and Hyperthyroidism*

Abstract

Qualitative and quantitative studies of erythropoiesis in 23 patients with hypothyroidism and 21 patients with hyperthryoidism included routine hematologic evaluation, bone marrow morphology, status of serum iron, B12 and folate red blood cell mass and plasma volume by radioisotope methods, erythrokinetics and radiobioassay of plasma erythropoietin. A majority of patients with the hypothyroid state had significant reduction in red blood cell mas per kg of body weight. The presence of anemia in many of these patients was not evident from hemoglobin and hematocrit values due to concomitant reduction of plasma volume. The erythrokinetic data in hypothyroid patients provided evidence of significant decline of the erythropoietic activity of the bone marrow. Erythroid cells in the marrow were depleted and also showed reduced proliferative activity as indicated by lower 3H-thymidine labeling index. Plasma erythropoietin levels were reduced, often being immeasurable by the polycythemic mouse bioassay technique. These changes in erythropoiesis in the hypothyroid state appear to be a part of physiological adjustment to the reduced oxygen requirement of the tissues due to diminished basal metabolic rate. Similar investigations revealed mild erythrocytosis in a significant proportion of patients with hyperthyroidism. Failure of erythrocytosis to occur in other patients of this group was associated with impaired erythropoiesis due to a deficiency of hemopoietic nutrients such as iron, vitamin B12 and folate. The mean plasma erythropoietin level of these patients was significantly elevated; in 4 patients the levels were in the upper normal range whereas in the rest, the values were above the normal range. The bone marrow showed erythyroid hyperplasia in all patients with hyperthyroidism. The mean 3H-thymidine labeling index of the erythroblasts was also significantly higher than normal in hyperthyroidism; in 8 patients the index was within the normal range whereas in the remaining 13 it was above the normal range. Erythrokinetic studies also provided evidences of increased erythropoietic activity in the bone marrow. It is postulated that thyroid hormones stimulate erythropoiesis, sometimes leading to erythrocytosis provided there is no deficiency of hemopoietic nutrients. Stimulation of erythropoiesis by thryoid hormones appears to be mediated through erythropoietin.

A study of prevalence and pattern of anemia in primary hypothyroidism

“…[5] Similar to the pattern observed by us, normocytic, normochromic anemia was the most common type of anemia and was present in 31 patients (51.6%) followed by microcytic anemia in 26 patients (43.3%). Six patients (10%) had megaloblastic anemia with Vitamin B12 deficiency including 3 cases of pernicious anemia.…”

Characteristics of anemia in subclinical and overt hypothyroid patients

“…Folic acid deficiency, one of the reasons of anemia, occurs as a result of intestinal malabsorption. Again hypothyroidism ruins folate mechanism by decreasing hepatic level of dihydrofolate reductase such as methylene-tetrahydrofolate reductase [22]. Folic acid deficiency almost always occurs as secondary to an underlying disease.…”

“…Erythrocyte life cycle in hypothyroidism is normal, and there is hypoproliferative erythropoiesis. Thyroid hormones also increase 2-3 DPG (diphosphoglycerate) levels assisting in the transmission of oxygen into the tissues [4][5][6].…”

A Case of Sheehan's Syndrome Associated with Severe Anemia and Empty Sella Proved 48 Years After Postpartum Hemorrhage.

“…Thyroid hormones stimulate not only EPO production [2] but also the proliferation of erythroid progenitor cells [9,10]. Steroid hormones also stimulate erythropoiesis [3,.…”

“…Hypothyroidism, adrenocortical insufficiency and panhypopituitarism are known to be often complicated with mild anemia, which is corrected by appropriate replacement with glucocorticoids and thyroxine [1][2][3]. There have been a few cases of hypopituitarism associated with severe anemia, in which circulating hemoglobin (Hb) levels were less than 9.0 g/dl [4].…”