Basic Pharmacology And Physiology Of Thyroid Disorder

The thyroid gland synthesizes the hormones thyroxine (T4) and triiodothyronine (T3), iodine-containing amino acids that regulate the body’s metabolic rate. Adequate levels of thyroid hormone are necessary in infants for normal development of the CNS, in children for normal skeletal growth and maturation, and in adults for normal function of multiple organ systems. Thyroid dysfunction is one of the most common endocrine disorders encountered in clinical practice. Although abnormally high or low levels of thyroid hormones may be tolerated for long periods of time, usually there are symptoms and signs of overt thyroid dysfunction. Thyroid hormones are extremely important and have diverse actions. They act on virtually every cell in the body to alter gene transcription: under- or over-production of these hormones has potent effects. Disorders associated with altered thyroid hormone secretion are common and affect about 5% women and 0.5% men.

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The thyroid gland consists of two lobes lying on either side of the ventral aspect of the trachea. Each lobe is about 4 cm in length and 2 cm thickness connected together by a thin band of connective tissue called the isthmus. Weighing approximately 20 g, it is one of the largest classical endocrine glands in the body and receives a high blood flow from the superior thyroid arteries (arising from the external carotids) and the inferior thyroid arteries (arising from the subclavian arteries). The gland is so important that it takes more blood per unit weight than the kidney and sometimes, when there is a goiter, blood flow in the gland may be heard with a stethoscope. The sound is termed a bruit. the thyroid gland consists of many closely packed acini, called follicles, each surrounded by capillaries and stroma. Each follicle is roughly spherical, lined by a single layer of cuboidal epithelial cells and filled with colloid, a proteinaceous material composed mainly of thyroglobulin and stored thyroid hormones. When the gland is inactive, the follicles are large, the lining cells are flat, and the colloid is abundant. When the gland is active, the follicles are small, the lining cells are cuboidal or columnar, the colloid is scanty, and its edges are scalloped, forming reabsorption lacunae. Scattered between follicles are the parafollicular cells (C cells), which secrete calcitonin, a hormone that inhibits bone resorption and lowers the plasma calcium level

Approximately 100 μg of thyroid hormones are secreted from the gland each day, mostly in the form of T4 with about 10% as T3. Eighty percent of the T4 undergoes peripheral conversion to the more active T3 in the liver and kidney (T3 is ten times more active than T4) or to reverse T3 (rT3) that has little or no biological activity. Very small quantities of other iodinated molecules, such as MIT and DIT as well as thyroglobulin, are also measurable in the circulation.

The diagnosis of Hashimoto’s disease is usually easy, based on the presence of goiter, circulating thyroid autoantibodies and low circulating concentrations of thyroid hormones with high TSH concentrations. Use of the prohormone thyroxine in the treatment of primary hypothyroidism is cheap and easy to monitor. The conversion of T4 to T3 is physiologically regulated and the dose can be altered according to serum TSH concentrations. Thyroid hormone resistance does exist but, compared to the millions of people exhibiting insulin resistance, the number of people showing resistance to thyroid hormones is minute. The key clinical features of thyroid hormone resistance are attention deficit hyperactivity disorder, developmental delay, learning disability, deafness and impaired growth in children with goiters. Patients with a generalized resistance and with signs and symptoms of hypothyroidism are treated with doses of thyroxine that facilitate normal growth and development.

Tumors of the thyroid gland may be primary (arising from cells within the thyroid gland) or secondary due to malignant cells which have spread from other tissues. Those arising from parafollicular cells which secrete calcitonin (giving rise to medullary cell carcinomas) are discussed. Lymphomas may arise from infiltrating lymphocytes and, though they are much more common in Hashimoto’s disease, they are still very rare. Other tumors such as sarcomas from smooth muscle cells within the gland are also exceedingly rare.

The majority of primary tumors arise from epithelial cells of the thyroid gland and are, therefore, termed adenomas if benign and carcinomas if malignant. The epithelial cell tumors are sub-classified as either papillary or follicular according to their histological appearance. These tumors are found more often in women (2 to 4 fold more often than men), aged 45–50 years.

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