Chapter 6: Anemia of Endocrine Disorders

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 not fully understood.

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. Many cases of hypothyroidism and all cases of pernicious anemia are autoimmune states and the concurrence may reflect a type of autoimmune polyendocrine state.

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.

A normocytic normochromic anemia may be seen in primary adrenal insufficiency (Addison disease) but the anemia (decrease in red cell mass) is not 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).

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

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.

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; in some patients, polycythemia can ensue and promptly subsides with discontinuation of androgen therapy.

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.

Hypopituitarism results in a moderately severe normochromic normocytic anemia, with an average hemoglobin of 10 g/dL.

Anemia of hypopituitarism results from the absence of the anterior lobe hormones, adrenocorticotropic hormone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, growth hormone, and prolactin; the resulting deficiencies of thyroid hormones, adrenal hormones and androgens are likely the major contributors to anemia.

Red cell survival is normal in hypopituitarism, but the marrow is hypoplastic.

In addition to anemia, leukopenia or pancytopenia can occur.

Replacement therapy with a combination of thyroid, adrenal, and gonadal hormones usually corrects the anemia and other cytopenias.

Erythropoietin therapy may be effective in postoperative hypopituitarism refractory to hormone replacement therapy.

A normochromic and normocytic anemia not attributable to other causes is present in 3 to 5 percent of patients with primary hyperparathyroidism.

The cause of the anemia is unknown, but marrow fibrosis has been described in a few patients.

Secondary hyperparathyroidism in patients with renal failure may contribute to refractoriness to erythropoietin therapy.