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CHAPTER 38 also causes macrocytosis that resolves with thyroxine treatment. The
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mean corpuscular volume of hypothyroid patients with low vitamin B
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ERYTHROPOIETIC EFFECTS levels is similar to those with uncomplicated hypothyroidism, so this is
not a sensitive means of identifying patients with hypothyroidism com-
5
OF ENDOCRINE DISORDERS plicated by B deficiency. Although there is an established association
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17,18
the underlying mecha-
of hypothyroidism and pernicious anemia,
nism is unclear. In one analysis of 116 hypothyroid patients, 40 percent
19
had low serum vitamin B levels. Although the mean hemoglobin was
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Xylina T. Gregg slightly lower in the vitamin B –deficient group (11.9 g/L vs. 12.4 g/L),
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the mean corpuscular volume and prevalence of antithyroid antibodies
did not differ between the two groups. 19
However, even when iron deficiency, vitamin B deficiency, and
SUMMARY other confounding causes of anemia have been excluded, anemia can
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be a direct consequence of thyroid hormone deficiency. Dogs sub-
5,16
Anemia is the most common hematopoietic abnormality in endocrine disor- jected to thyroidectomy have a normocytic, normochromic anemia that
ders and may be the first manifestation of an endocrine disorder. Polycythe- is associated with reticulocytopenia and marrow erythroid hypoplasia.
20
mia/erythrocytosis is less common, but occurs in certain endocrine disorders. In hypothyroid humans and thyroidectomized animals, the red cell life
The pathophysiologic basis of the anemia is often multifactorial, but a direct span is normal, and results of ferrokinetic studies are compatible with
influence of hormones on erythropoiesis in some instances may contribute to hypoproliferative erythropoiesis. 20,21 Administration of thyroid hor-
anemia. A decreased plasma volume in some of these disorders may mask the mones increases the rate of red cell production in experimental
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severity of anemia. It has been proposed that anemia in endocrine-deficiency animals, whereas thyroidectomy decreases red cell production.
states may be physiologic to adjust for decreased oxygen requirements. Some Because thyroid hormones affect the cellular needs for oxygen, these
responses are compatible with an appropriate physiologic adjustment.
endocrine disorders are associated with an impaired response to the therapeu- Evidence of a direct effect of thyroid hormones on erythropoiesis exists.
tic use of erythropoietin. Some in vitro studies show that triiodothyronine, thyroxine, and nonca-
lorigenic resin triiodothyronine all potentiate the effect of erythropoi-
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etin on erythroid colony formation. Thyroid hormones also increase
hypoxia-induced production of erythropoietin in the rat kidney and a
THYROID DYSFUNCTION human hepatoma cell line. However, other in vitro studies show an
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inhibitory effect of triiodothyronine on erythroid colony formation,
HYPOTHYROIDISM particularly in combination with all-trans retinoic acid. 26
Anemia is a well-recognized complication of thyroidectomy and other Hypothyroidism may also affect the response to erythropoietin
causes of hypothyroidism and may also occur in subclinical hypothy- therapy. After adjusting for other variables, the mean monthly erythro-
roidism. In a retrospective review, anemia defined as a hemoglobin less poietin dose required to maintain a target hemoglobin level in hemo-
1
than 13 g/dL in men and less than 12 g/dL in women was present in 57 dialysis patients was significantly higher in hypothyroid compared with
percent of patients with hypothyroidism. The anemia in hypothyroidism euthyroid patients. 27
2
has been described variably as normocytic, macrocytic, or microcytic Improvement in the hemoglobin concentration in response to
3
5
coexisting deficiencies of iron, vitamin B , and folate may explain some thyroid hormone therapy is seen over a several-month period. White
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of this heterogeneity. In a study of approximately 60 anemic patients with blood cell and platelet counts usually are unaffected in hypothyroidism.
untreated primary hypothyroidism, 10 percent had a macrocytic ane- However, pancytopenia in association with marrow hypoplasia has been
mia, all of whom had vitamin B deficiency, 43 percent had a microcytic reported in a patient with myxedema coma; the hematologic abnormali-
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anemia and iron deficiency, and the remainder had a normocytic ane- ties in this patient resolved with thyroid hormone replacement. 28
mia. However, even when these deficiencies have been excluded, some
4
hypothyroid patients have a macrocytic anemia. In addition, although HYPERTHYROIDISM
5
most hypothyroid patients have a significant reduction in their red cell Although thyroid hormone administration increases red cell production
mass, anemia is not always evident from hemoglobin and hematocrit in animals, humans with hyperthyroidism generally do not have ery-
29
values owing to a concomitant reduction of plasma volume. 6,7 throcytosis. Anemia is present in 10 to 25 percent of these patients. 30–32
Hypothyroidism may contribute to the development of iron defi- This finding may be the result of increased plasma volume ; however,
7
ciency (Chap. 43) due to associated menorrhagia, although this asso- decreased red cell survival and ineffective erythropoiesis also have
34
33
ciation is less common than previously thought. Because thyroid been described. Antithyroid treatment ameliorates the anemia. 31,32 A
8
hormone may augment iron absorption, iron deficiency in hypothy- patient with autoimmune hemolytic anemia and hyperthyroidism has
9,10
roidism may also be caused by impaired iron absorption, either directly been described; the hemolysis in this patient abated with treatment of
from a lack of thyroid hormone or an associated achlorhydria. 11,12 Con- the hyperthyroidism. Pancytopenia rarely occurs but also may respond
35
versely, iron deficiency impairs thyroid hormone synthesis by reducing to treatment of hyperthyroidism. 36,37
the activity of heme-dependent thyroid peroxidase. In patients with
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coexisting iron-deficiency anemia and subclinical hypothyroidism, the
anemia often does not adequately respond to oral iron therapy. Com- ADRENAL GLAND DISORDERS
bined treatment with oral iron and levothyroxine results in superior
improvement in hemoglobin and ferritin levels compared with levothy- ADRENOCORTICAL INSUFFICIENCY
roxine alone in these patients. 14,15 A normocytic normochromic anemia may be seen in primary adrenal
Although the macrocytosis seen in hypothyroid patients may be insufficiency (Addison disease), 12,38 but the anemia may also be masked
due to deficiencies of vitamin B 4,5 or folate (Chap. 41), hypothyroidism by the concomitant reduction in plasma volume that is common in
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Kaushansky_chapter 38_p0559-0562.indd 559 9/17/15 6:19 PM