Chapter 228: Hypothyroidism and Myxedema Crisis

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

PATHOPHYSIOLOGY

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.

CLINICAL FEATURES OF ...