Chapter 6: Anemia 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.

• 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 because a deficit of thyroid hormone may decrease iron absorption.

• 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 erythroid colony formation.

• 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.

• 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.

• Polycythemia has been reported in Cushing syndrome, primary aldosteronism, Bartter syndrome, and congenital adrenal hyperplasia secondary to 21-hydroxylase deficiency.

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

• Some individuals with congenital polycythemia develop recurrent pheochromocytomas, paragangliomas, and somatostatinomas that are heterozygous for a gain-of-function mutation of hypoxia-inducible factor 2α. However, the association of these tumors with polycythemia is unknown.

GONADAL HORMONES

• Decrease in androgen production due to orchiectomy or medical androgen blockade causes anemia.

• Androgen therapy has been used for the treatment of various anemias, especially before the development of recombinant erythropoietin.

• The mechanism of androgen action appears to be complex, with evidence for stimulation of erythropoietin secretion and a direct effect on the marrow erythroid progenitors.

• Estrogens in large doses cause moderately severe anemia by a mechanism not clearly defined.