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 multifactorial.

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.

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.

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.

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, which include 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. However, the marrow is hypoplastic, and leukopenia or pancytopenia can also occur.

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

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

Children with isolated growth hormone deficiency become anemic, which is improved with growth hormone replacement therapy.

Macroprolactinomas have been associated with anemia, likely due to a concomitant decrease in testosterone levels.

Pituitary adenomas that secrete gonadotropins are rare but have been associated with erythrocytosis, likely due to testosterone excess.

A normochromic and normocytic anemia not attributable to other causes is present in 3% to 5% 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.