Chapter 6: Erythropoietic Effects of Endocrine Disorders

INTRODUCTION

• Anemia due to endocrine disease is generally mild to moderate; however, a decreased plasma volume in some of these disorders may mask the severity of the decrease in red cell mass (Chap. 27).

• The pathophysiologic basis of the anemia seen in endocrine disorders is often multifactorial.

THYROID DYSFUNCTION

• Anemia in hypothyroidism may be normocytic, macrocytic, or microcytic; coexisting deficiencies of iron, B₁₂, and folate may explain some of this heterogeneity.

• Iron deficiency often occurs in hypothyroidism as a result of increased predisposition to menorrhagia, an associated achlorhydria, or a deficit of thyroid hormone that decreases iron absorption (Chap. 9).

• In patients with coexisting iron-deficiency anemia and subclinical hypothyroidism, the anemia often does not adequately respond to oral iron therapy.

• The mechanism underlying the association of hypothyroidism and pernicious anemia is unknown.

• The mean corpuscular volume cannot be used to differentiate hypothyroid patients with low vitamin B₁₂ levels from those with uncomplicated hypothyroidism.

• Anemia is also a direct consequence of thyroid hormone deficiency; thyroid hormones have been shown to potentiate the effect of erythropoietin on erythropoiesis.

• Patients with hyperthyroidism have increased red cell mass, but the hematocrit and hemoglobin concentration are usually not elevated because the plasma volume is also increased.

• Autoimmune hemolytic anemia and pancytopenia responsive to treatment of hyperthyroidism have also been reported.

ADRENAL GLAND DISORDERS

• The red cell mass is decreased in primary adrenal insufficiency (Addison disease), but it may not be reflected in the hematocrit or hemoglobin measurements because of a concomitant reduction in plasma volume (Chap. 27).

• The pathophysiologic basis of the anemia and any influence of adrenal cortical hormones on erythropoiesis are not well defined.

• Some patients with Addison disease develop a transient fall in hematocrit and hemoglobin concentration after initiation of hormone replacement therapy (presumably secondary to an increased plasma volume).

• Pernicious anemia occurs in patients with autoimmune adrenal insufficiency but is seen primarily in patients with type I polyglandular autoimmune syndrome, whose other manifestations include mucocutaneous candidiasis and hypoparathyroidism.

• Erythrocytosis has been reported in Cushing syndrome, primary aldosteronism, Bartter syndrome, and congenital adrenal hyperplasia secondary to 21-hydroxylase deficiency by activation of glucocorticoid receptors that enhances self-renewal of early erythroid progenitors and their differentiation.

• Conversely, some males with Cushing syndrome are anemic; this finding is correlated with a low testosterone level.

• HIF-2α (EPAS1) mosaicism: Several individuals with unexplained congenital erythrocytosis subsequently developed recurrent pheochromocytomas, paragangliomas, and somatistatinomas. Their tumors were heterozygous for various gain-of-function mutations of the gene encoding HIF-2α (EPAS1), and erythropoietin transcript was present not only in tumor tissue but also in the surrounding normal tissue. Consequently, resection of the tumor did not resolve the erythrocytosis. The disease is thought to arise from genomic mosaicism of the gain-of-function EPAS1 gene, so that adrenal cells with this mutation produce erythropoietin and likely predispose to further ...