Thyroid Hormone Replacement Therapy for Primary and Secondary Hypothyroidism

Abstract

Primary hypothyroidism is defined as a deficiency of thyroid hormone as a result of intrinsic failure of the thyroid gland. This leads to low levels of circulating thyroxine, insufficient levels of thyroid hormone in target tissues, and typical symptoms, signs, and laboratory abnormalities. When severe or long standing, the clinical diagnosis is straightforward, confirmed by the finding of elevated serum levels of thyrotropin (TSH) and depressed serum concentrations of free-thyroxine (fT4) or the free-T4 estimate (free-T4 index or FTI). Circulating serum tri-iodothyronine (T3) concentrations are generally low or low normal. It is a relatively common disorder, affecting 1–3% of the population. The annual incidence is approx 1–2 per 1000 women and 1 per 10,000 men, with higher rates in older individuals (1). Autoimmune (Hashimoto’s) thyroiditis is the cause of spontaneous primary hypothyroidism in the vast majority of cases. Postablative hypothyroidism after therapy for hyperthyroidism or thyroid surgery is the second most common cause. Drugs may also precipitate primary hypothyroidism, especially in people with underlying autoimmune thyroid disease (i.e., positive antithyroid antibodies). Lithium and iodine-containing drugs such as the antiarrhythmic amiodarone frequently lead to hypothyroidism in such individuals. Rare congenital causes of primary hypothyroidism include thyroid agenesis or maldevelopment and a variety of hereditary intrathyroidal enzyme deficiencies or thyroglobulin biosynthetic abnormalities probably the result of specific genetic mutations.