15.02.2 Hyperthroidism

Hyperthyroidism is elevated circulating thyroid hormone, and when the levels are very high the condition is known as thyrotoxicosis, a medical emergency. Graves’ disease, an autoimmune disease causing the excessive secretion of thyroid hormone, accounts for 60-90% cases of thyrotoxicosis.

The symptoms or hyperthyroidism are calorigenic with a high basal metabolic rate, increased body temperature, and weight loss. The central nervous system symptoms are irritability, restlessness, and insomnia. On the cardiovascular system there is increased activity of sympathetic nervous system leading to a rapid heart rate and possible palpitations, and high blood pressure. A unique feature is ophthalmopathy leading to exopthalmos, which is protrusion of the eyeballs

Treatment for hyperthyroidism is drugs or surgery, or drugs prior to surgery. The drugs used include propylthiouracil, methimazole, iodide and radioactive iodine. Adjuvant treatment of hyperthyroidism is to treat the consequences of hyperthyroidism on the heart and includes β-adrenoceptor antagonist and Ca²⁺ channel blockers, which are discussed as cardiac drugs.

Propylthiouracil or carbimazole are used in the treatment of hyperthyroidism, either to control Graves disease in anticipation of remission or to control the hyperthyroidism prior to surgery. Both of these drugs can be used in conjunction with radioactive iodine, to hasten recovery while awaiting the effects of radiation (discussed below). Propiothiouracil inhibits 2 enzymes involved in the synthesis of the thyroid hormones; thyroid gland peroxidase and peripheral tissues iodothyronine 5^/-deiodinase (Figure 15.1). Carbimazole only inhibits thyroid gland peroxidase (Figure 15.1). The incidence of side effects is relatively low with these drugs.

High concentrations of iodide (6 mg day) are used pre-operatively, and in conjunction with propylthiouracil and propranolol in the treatment of thyrotoxic crisis. High doses of iodide inhibit its own transport into thyroid gland, and therefore the synthesis of thyroxine. Iodide inhibits the synthesis of iodotyrosines and iodothryonines, which are the precursors for the thyroid hormones, and this inhibition last about 2 days. High dose iodide also inhibits the release of thyroid hormone.

Radioactive iodine, ¹³¹I, emits both g rays and b particles, which accumulate in the thyroid gland and are cytotoxic. Radioactive iodine and be used to selectively destroy some or all the thyroid gland, without affecting other tissues. This approach is used in hyperthyroidism.

Figure 15.1 Mechanism of action of propylthiouracil and carbimazole (Copyright QUT, Sheila Doggrell)