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Anemia may be the first manifestation of an endocrine disorder. Anemia caused by endocrine disease is generally mild to moderate; however, a decreased plasma volume in some of these disorders may mask the severity of anemia. It has been proposed that anemia in endocrine-deficiency states may be physiologic because of decreased oxygen requirements, but a direct influence of hormones on erythropoiesis may also contribute to anemia. The pathophysiologic basis of the anemia seen in endocrine disorders may be multifactorial and, thus, not always clear-cut.

Acronyms and Abbreviations

Acronyms and abbreviations used in this chapter include: ACTH, adrenocorticotropic hormone; AZT, azidothymidine; T3, triiodothyronine; T4, thyroxine.

Hypothyroidism

Since the 1880s, anemia has been a recognized complication of thyroidectomy1 and other causes of hypothyroidism.2 The anemia is usually mild to moderate, with hemoglobin concentrations rarely below 8 to 9 g/dL (80–90 g/L). However, a concomitant decrease in the plasma volume3 makes the hemoglobin concentration an unreliable indicator of the red cell mass.4 Dogs subjected to thyroidectomy have a normocytic, normochromic anemia that is associated with reticulocytopenia and marrow erythroid hypoplasia.5 In humans with hypothyroidism, the associated anemia has been described variably as normocytic, macrocytic, or microcytic;6 coexisting deficiencies of iron, B12, and folate may explain some of this heterogeneity. Hypothyroidism may contribute to the development of iron deficiency (see Chap. 42) because of an increased predisposition to menorrhagia.7 Males with hypothyroidism may also be iron deficient, possibly as a result of an associated achlorhydria8 or because thyroid hormone may augment iron absorption.9,10 Conversely, iron deficiency impairs thyroid hormone synthesis by reducing the activity of heme-dependent thyroid peroxidase.11 In patients with coexisting iron-deficiency anemia and subclinical hypothyroidism, the anemia often does not adequately respond to oral iron therapy. In a study in which these patients were randomized to receive 240 mg per day of oral iron alone or 240 mg per day of oral iron plus 75 mcg per day of levothyroxine, the group that received the levothyroxine had statistically significant improvement in the hemoglobin, hematocrit, and ferritin levels.12

Although macrocytosis may be seen in uncomplicated anemia of hypothyroidism,13 significant elevations in the mean corpuscular volume are usually caused by accompanying B12 or folate deficiency (see Chap. 41). However, macrocytosis is not a sensitive means of identifying patients with hypothyroidism complicated by B12 deficiency.13 There is an established association of hypothyroidism and pernicious anemia,14,15 but the underlying mechanism is unknown. In an analysis of 116 hypothyroid patients, 40 percent had low serum vitamin B12 levels.16 Although the mean hemoglobin was slightly lower in the B12-deficient group (11.9 g/L vs. 12.4 g/L), the mean corpuscular volume and prevalence of antithyroid antibodies did not differ between the two groups.

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