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Am Fam Physician. 2002;66(11):2145-2146

A 38-year-old woman presents complaining of bilateral eye pulsations, leg swelling, palpitations, and heat intolerance for the past two years. She also states that she has noticed swelling and bluish discoloration of her toes and feet, extending up to the shins (see accompanying figure). During this period, she altered between bouts of elation, anxiety, periods of “lots of energy,” and depression. Serum electrolyte, glucose, and transaminase levels were all normal. A mild microcytic anemia was present.

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Based on the patient's history and physical examination, which one of the following is the most likely diagnosis?


The answer is B: Pretibial myxedema in a patient with thyroid acropachy secondary to Graves' disease. Thyroid acropachy comprises hyperthyroidism, pretibial myxedema (as in this patient), finger and toe clubbing, and exophthalmos. It is an extrathyroidal manifestation of Graves' disease, where immunologically mediated activation of fibroblasts at sites such as the extraocular muscles and skin leads to the accumulation of glycosaminoglycans, causing localized edema and fluid retention.1 The localized pretibial myxedema of hyper-thyroidism is often well demarcated and may be hyperpigmented, which is distinguished from the diffuse myxedema seen in hypothy-roidism where the skin becomes dry, pale, and feels rough or doughy to touch.

The patient's thyroid-stimulating hormone level was found to be virtually undetectable, 0.002 mU per L, while thyroxine was 17.6 mcg per dL, which confirmed that she was in a hyperthyroid state. A chest radiograph showed moderate cardiomegaly. Echocardiography revealed left ventricular ejection fraction 40 to 45 percent, and she also was diagnosed with cardiac failure secondary to hyperthyroidism. However, the skin changes in the legs were not caused by venous stasis.

Addison's disease leads to diffuse hyperpig-mentation, not just pretibial, and the patient's normal serum electrolyte and glucose levels, and history of occasional increased activity did not support the diagnosis of adrenal failure.

Diabetic necrobiosis typically causes discrete pretibial plaques, not the confluent skin changes seen in this patient.

In this patient, the areas of increased skin pigmentation were confined to the lower extremities, unlike the generalized hyperpig-mentation seen in hemochromatosis. The microcytic anemia and normal liver enzyme levels in this patient also make hemochro-matosis an unlikely diagnosis.

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