Definition and incidence

Hypothyroidism is a state of thyroid gland hypofunction resulting in decreased circulating concentrations of thyroid hormones. Laboratory findings show decreased plasma T₃ and T₄ concentrations and increased TSH levels in patients with primary hypothyroid disease. The clinical spectrum of thyroid hormone deficiency can range from the asymptomatic patient with no overt physical findings to the classic myxedematous patient with profound symptoms. Hypothyroidism is the most common disorder of thyroid function, occurring in 5% to 10% of women and 0.5% to 2% of men.

Pathophysiology

Primary hypothyroidism accounts for 95% of all cases of hypothyroidism. An autoimmune-mediated destruction of the thyroid gland, known as Hashimoto’s thyroiditis, is the most common form of hypothyroidism in the United States. The disorder most often occurs in women of middle age and is associated with other autoimmune disorders such as myasthenia gravis and adrenal insufficiency.

Primary hypothyroidism may also be the result of severe iodine deficiency, previous thyroid surgery, neck irradiation, or treatment for hyperthyroidism (radioiodine therapy). The antiarrhythmic agent amiodarone is associated with hyper- and hypothyroidism. Lithium inhibits the release of thyroid hormone and causes hypothyroidism in some patients.

Rarely, secondary hypothyroidism is the result of pituitary or hypothalamic disorders. Secondary hypothyroidism is associated with decreased concentrations of both thyroid hormones and TSH. Regardless of the etiology, the clinical manifestations of hypothyroidism are similar.

Clinical manifestations

Most cases of hypothyroidism are subclinical, with laboratory findings of increased plasma TSH but no overt signs. Patients with more significant disease develop signs and symptoms that reflect a slowed metabolism and impaired cellular functions. The thyroid gland usually is enlarged, nontender, and firm. Patients may have dry skin, cold intolerance, paresthesias, slow mental functioning, ataxia, a puffy face, and constipation. Lack of thyroid hormones causes the muscles to become sluggish. Patients with severe hypothyroidism may be hypersomnolent with a decreased ventilatory response to hypoxia and hypercarbia. The hair and nails frequently are brittle.

The accumulation of proteinaceous fluid in serous body cavities is a well-recognized feature of hypothyroidism. The most common sites of effusions associated with hypothyroidism are the pleural, pericardial, and peritoneal cavities. Inappropriate ADH secretion and impaired free water clearance can lead to hyponatremia. Accumulation of mucopolysaccharides and fluid imparts the characteristic edematous appearance, called myxedema.

Cardiovascular complications include sinus bradycardia, dysrhythmias, cardiomegaly, impaired contractility, congestive heart failure, and labile blood pressure. Symptoms of low exercise tolerance and shortness of breath with exertion may be partially the result of decreased cardiac function. Chronic vasoconstriction produces diastolic hypertension and decreases the intravascular fluid volume. The autonomic nervous system response is blunted, and there is a decrease in the sensitivity and number of β-receptors.

Overt hypothyroidism is associated with a number of abnormalities in lipid metabolism that may predispose patients to accelerated coronary artery disease. Hypothyroidism is associated with anemia and decreased erythrocyte production of 2,3-diphosphoglycerate, leading to a leftward shift of the oxyhemoglobin dissociation curve and decreased oxygen delivery to the tissues.

These “classic” clinical features of hypothyroidism are often lacking in elderly hypothyroid patients. In older patients, thyroid status may not always be predicted from clinical signs and symptoms, and diagnosing hypothyroidism is more difficult.