26-08: Hypothyroidism & Myxedema

GENERAL CONSIDERATIONS

Hypothyroidism is common, affecting over 1% of the general population and about 5% of individuals over age 60 years. About 85% of affected individuals are women. Thyroid hormone deficiency affects almost all body functions. The degree of severity ranges from mild and unrecognized hypothyroid states to striking myxedema. The fluid retention seen in myxedema is caused by the interstitial accumulation of hydrophilic mucopolysaccharides, which leads to lymphedema. Hyponatremia is the result of impaired renal tubular sodium reabsorption due to reductions in Na⁺–K⁺-ATPase. Maternal hypothyroidism during pregnancy results in offspring with IQ scores that are an average 7 points lower than those of euthyroid mothers. Congenital hypothyroidism occurs in about 1:4000 births; untreated, it causes cretinism with permanent cognitive impairment.

Hypothyroidism may be due to failure or resection of the thyroid gland itself or deficiency of pituitary TSH (see Hypopituitarism). The condition must be distinguished from the functional hypothyroidism that occurs in severe nonthyroidal illness, which does not require treatment with levothyroxine (see Euthyroid Sick Syndrome). Autoimmune thyroiditis is the most common cause of hypothyroidism (see Thyroiditis). A hypothyroid phase also occurs in subacute (de Quervain) viral thyroiditis following initial hyperthyroidism.

Goiter may be present with thyroiditis, iodide deficiency, genetic thyroid enzyme defects, food goitrogens in iodide-deficient areas (eg, turnips, cassavas), or, rarely, peripheral resistance to thyroid hormone or infiltrating diseases (eg, cancer, sarcoidosis). Goitrogenic medications include iodide, propylthiouracil (PTU) or methimazole, sulfonamides, amiodarone, interferon-alpha, interferon-beta, interleukin-2, and lithium. About 50% of patients taking lithium long term have an ultrasound-detectable goiter. Goiter is often absent in patients with autoimmune thyroiditis. Goiter is also usually absent when hypothyroidism is due to destruction of the gland by head-neck or chest-shoulder radiation therapy or ¹³¹I therapy. Thyroidectomy causes hypothyroidism; after hemithyroidectomy, hypothyroidism develops in 22% of patients.

Amiodarone, because of its high iodine content, causes clinically significant hypothyroidism in about 15–20% of patients as well as thyrotoxicosis (see Amiodarone-induced thyrotoxicosis, below). Hypothyroidism occurs most often in patients with preexisting autoimmune thyroiditis and in patients who are not iodine-deficient. The T₄ level is low or low-normal, and the TSH is elevated, usually over 20 milli-international units/L. Another 17% of patients taking amiodarone are asymptomatic with normal serum T₄ levels despite elevations in serum TSH; they can be closely monitored without levothyroxine therapy. Low-dose amiodarone is less likely to cause hypothyroidism. Patients with coronary insufficiency who have amiodarone-induced symptomatic hypothyroidism are treated with just enough levothyroxine to relieve symptoms. Hypothyroidism usually resolves over several months if amiodarone is discontinued. Hypothyroidism may also develop in patients with a high iodine intake from other sources, especially ...