The clinical manifestations of hypothyroidism emerge insidiously, are nonspecific, and often are attributed to aging. They include a general slowing down, mental depression, modest weight gain, intolerance of cold, constipation, vague aches and pains, dryness of the skin, and brittleness of the scalp hair. As the disorder becomes more fully established, the classic features of nonpitting edema (myxedema) of the skin, periorbital edema, hoarseness, sinus bradycardia, decrease in body temperature, and delayed relaxation of the deep tendon reflexes appear. Laboratory investigation may reveal a mild anemia, increased creatine phosphokinase concentrations, and an abnormal lipid profile with increased total and low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol concentrations. In the United States, primary thyroid failure is most often caused by chronic autoimmune thyroiditis, with or without goiter, or by prior surgical or 131I ablative therapy.