Thyroid Disorders

Disorders of thyroid hormone secretion are second only to diabetes mellitus as the most common endocrine disorders in the United States. Throughout the world, the most common thyroid disorders are iodine deficiency disorders. In the United States and Canada, the use of iodized salt has largely eliminated iodine deficiency disorders, and the most common thyroid disorders are the autoimmune diseases Graves' disease and Hashimoto’s thyroiditis.

Iodine Deficiency

Iodine is a trace mineral that is high in seafood, and is found in variable amounts in fruits and vegetables, depending on the iodine content of the local soil. In many parts of the world, the soils are naturally deficient in iodine, and iodine deficiency and hypothyroidism will occur without iodine supplementation. Thyroid hormone has a crucial role in the development of the nervous system, being involved in the growth of synapses and the formation of myelin. Congenital hypothyroidism (hyppothyroidism from birth) may lead to a disorder of cognitive development with reduced physical growth that occurs if thyroid hormone is deficient during gestation and early post-natal life.  This disorder is entirely preventable by making sure that pregnant women have sufficient iodine in their diet and by newborn screening programs that identify infants who are hypothyroid. The World Health Organization is actively working to reduce iodine deficiency by supplying iodized salt to communities, and developing effective monitoring programs.

Goiter is the term that means enlargement of the thyroid gland.  Iodine deficient goiter results because iodine is a crucial component of active thyroid hormones. If there is a low level of iodine in the diet, then less active T3 (triiodothyronine) and T4 (thyroxine) can be synthesized. As diagrammed in the figure, when there is less T3 and T4, there is reduced negative feedback inhibition of secretion of the tropic hormones, TRH (thyrotropin releasing hormone; released by the hypothalamus) and TSH (thyroid stimulating hormone or thyrotropin; released by the anterior pituitary). TSH stimulates all aspects of thyroid hormone synthesis; it also stimulates proliferation of follicle cells. When iodine in the diet is low but not too low, individuals may have goiter and yet be have normal thyroid hormone levels, because the enlarged thyroid gland is better able to use the limited amount of iodine available. This is an example of how negative feedback regulation works to keep hormone secretion within the appropriate physiological range.

Graves Disease

Graves' disease is the most common cause of hyperthyroidism. Graves' disease is an autoimmune disorder in which antibodies are produced that bind to the TSH receptor. Instead of causing destruction of follicle cells, these antibodies act as receptor agonists, stimulating the receptor to cause synthesis of T3 and T4, and proliferation of follicle cells. Negative feedback inhibition is increased, so the levels of TRH and TSH decrease, but this does not decrease thyroid hormone production because the stimulation of the thyroid gland is independent of TSH. Measurement of low TSH levels is a key diagnostic test for hyperthyroidism.  (This is because hyperthyroidism caused by pituitary hypersecretion of TSH is very rare.)

The symptoms of hyperthyroidism in Graves' disease are related to the effects of thyroid hormone on metabolism and cardiac function. Because thyroid hormone increases resting energy expenditure, there is increased heat production and individuals will become heat intolerant. Individuals experience tachycardia (fast heart rate) because thyroid hormone affects expression of cardiac ion channels and contractile proteins so that the force and rate of the heart beat are both increased. Because thyroid hormone increases the responsiveness to epinephrine and norepinephrine, excess thyroid hormone can cause symptoms that occur due to increased sympathetic activation, such as nervousness, sweating and increased heart rate. For this reason, beta-adrenergic antagonists may be used to relieve symptoms.

Graves' disease can be treated by drugs that inhibit thyroid hormone synthesis. Other treatment approaches involve reduction of thyroid tissue. The thyroid gland may be removed surgically (thyroidectomy). Another approach is to administer radioactive iodine, which concentrates in the thyroid gland, where the radiation ablates thyroid tissue.

Hashimoto's Thyroiditis

The most common cause of hypothyroidism in the United States is due to autoimmune destruction of the thyroid gland that occurs in Hashimoto’s thyroiditis. In this case, antibodies to thyroid antigens, as well as infiltration by cytotoxic T cells, lead to destruction of thyroid tissue. Because the thyroid gland stores large amounts of thyroid hormone as thyroglobulin, a patient with Hashimoto’s thyroiditis may initially develop goiter, (which occurs due to inflammation), rather than symptoms due to hypothyroidism. As the store of thyroid hormone decreases, negative feedback inhibition decreases and TSH levels will rise.

As Hashimoto's thyroiditis progresses, it will eventually lead to overt hypothyroidism. The symptoms of hypothyroidism result from decreased metabolic rate, and are opposite to the symptoms of hyperthyroidism. Patients may gain weight, feel sluggish and cold, and have a slowed heart rate. Hypothyroidism is treated with replacement therapy with thyroxine (T4).