28-08: Hypothyroidism & Myxedema

ESSENTIALS OF DIAGNOSIS

GENERAL CONSIDERATIONS

Hypothyroidism is common, with 0.3% of the population having overt disease. 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.

Autoimmune thyroiditis is the most common cause of hypothyroidism (see Thyroiditis). Hypothyroidism also may be due to failure or resection of the thyroid gland itself (primary hypothyroidism) or deficiency of pituitary TSH (secondary hypothyroidism; see Hypopituitarism). A hypothyroid phase also occurs in subacute (de Quervain) viral thyroiditis following initial hyperthyroidism.

Goiter (thyroid enlargement) 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. Total thyroidectomy causes hypothyroidism; after hemithyroidectomy, hypothyroidism develops in 22% of patients.

Amiodarone, because of its high iodine content, causes clinically significant hypothyroidism in 15–20% of patients as well as thyrotoxicosis (see Amiodarone-induced thyrotoxicosis, below). Hypothyroidism occurs most often in patients with preexisting autoimmune thyroiditis. The T₄ level is low or low-normal, and the TSH is elevated, usually over 20 mIU/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 CAD 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 if they have underlying lymphocytic thyroiditis. Some malignancies overexpress thyroid hormone inactivating enzyme (type 3 deiodinase) and cause “consumptive hypothyroidism.” This has occurred with large hemangiomas or ...