INTRODUCTION AND EPIDEMIOLOGY
Hypothyroidism is a clinical syndrome caused by insufficient thyroid hormone production, which slows cell metabolism. The prevalence of overt hypothyroidism in the general population varies between 0.3% and 3.7% in the United States, and between 0.2% and 5.3% in Europe.1-4 The prevalence of hypothyroidism increases with age (>65 years) and is higher among white individuals and women.5 The disorder is nearly 10 times more common in females than in males. On the other hand, subclinical hypothyroidism is more prevalent than overt hypothyroidism in all age groups and can be seen in 4% to 15% of women, especially the elderly.6 Myxedema coma mortality rates with current treatments are between 30% and 60%.6
Thyroxine (T4) and triiodothyronine (T3) are the thyroid hormones. The ratio of thyroxine T4 to triiodothyronine T3 released in the blood is about 10:1. Peripherally, thyroxine T4 is converted to the active triiodothyronine T3, which is three to four times more potent than thyroxine T4. The half-life of thyroxine T4 is 7 days, and the half-life of triiodothyronine T3 is about 1 day.
Primary hypothyroidism is caused by the intrinsic dysfunction of the thyroid gland. The most common cause is Hashimoto’s thyroiditis. Primary hypothyroidism is also caused by surgical removal or radioactive ablation and can be a result of some drug effects.7 Drugs such as lithium, α-interferon, interleukin, and tyrosine kinase inhibitors (e.g., sunitinib) can cause hypothyroidism. Amiodarone can cause hypothyroidism in up to 14% of patients.8-10
Secondary hypothyroidism is caused by a deficiency of thyroid-stimulating hormone (TSH) from the pituitary gland or deficiency of thyrotropin-releasing hormone from the hypothalamus. Some literature specifically refers to hypothalamic causes as tertiary hypothyroidism.11,12 Nevertheless, both are central causes of hypothyroidism involving the hypothalamic-pituitary axis and shall be referred to as secondary hypothyroidism in this chapter.
Euthyroid sick syndrome is associated with low triiodothyronine T3 or thyroxine T4 levels and a normal or low TSH level in a patient who is clinically euthyroid. This condition is found in critically ill patients or those with severe systemic illness.
Table 228-1 lists common causes of hypothyroidism.
TABLE 228-1Common Causes Primary and Secondary of Hypothyroidism |Favorite Table|Download (.pdf) TABLE 228-1 Common Causes Primary and Secondary of Hypothyroidism
|Primary Hypothyroidism (disorders of thyroid gland) ||Secondary Hypothyroidism (disorders of hypothalamic-pituitary axis) |
Autoimmune disease (e.g., Hashimoto’s thyroiditis)
After ablation (surgery, radioiodine)
Infiltrative thyroid disease (lymphoma, sarcoid, tuberculosis)
Drugs directly affecting thyroid function
Pituitary adenoma, hypothalamic tumor
Infiltrative disorders (hemochromatosis, sarcoidosis)