Disorders of thyroid hormone secretion are second only to diabetes mellitus as the most common endocrine disorders. Throughout the world, the most common thyroid disorders are iodine deficiency disorders. In the United States and Canada, the use of iodized salt has eliminated iodine deficiency disorders, and the most common thyroid disorders are the autoimmune diseases Graves disease and Hashimoto’s thyroiditis.
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 disorders due to 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. Endemic cretinism is a disorder of cognitive development with reduced physical growth that occurs if thyroid hormone is deficient during gestation and early post-natal life. “Endemic” means prevalent in a particular region. This disorder is entirely preventable by making sure that pregnant women have sufficient iodine in their diet to be euthyroid (having adequate thyroid hormone levels). The World Health Organization is actively working to reduce iodine deficiency by supplying iodized salt to communities, and developing effective monitoring programs.
Iodine deficient goiter,
(enlargement of the thyroid gland) 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 and T4 can be
synthesized. As diagrammed in the figure, when there is less T3
and T4, there is reduced negative feedback inhibition on 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 euthyroid, because the enlarged thyroid
gland is better able to use the limited amount of iodine
available. This is an example of hormonal homeostasis.
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 destroying the
receptor, these antibodies activate it, stimulating synthesis of
T3 and T4, and causing growth of the thyroid gland. 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.
The symptoms of hyperthyroidism in Graves disease are related to the effects of thyroid hormone on metabolism and cardiac function. Because thyroid hormone increases basal metabolic rate, 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 are similar to 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.
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 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 the 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).