Medical brain notes 47

  Thyroid and Antithyroid Drugs Three hormones, thyroxine (3,5,3’ ,5’ -tetraiodothy-ronine, or T 4 ), triiodothyronine (3,5,3’ -triiodothyronine, or T 3 ), and calcitonin  are secreted by the thyroid gland. The hormones T 4  and T 3  are iodine-containing amino acid derivatives and are unique in that they have no discrete target tissue. Every tissue in the body is affected in some way by thyroid hormones, and almost all cells appear to require constant optimal amounts for normal operation.   Thyroid hormones exert a wide variety of physio-logical actions through genomic and nongenomic mech-anisms and influence the metabolism of proteins, car-bohydrates, and lipids; cell morphology; membrane transport; ion homeostasis; oxygen consumption; heat production; and so on. Relatively constant circulating concentrations of T 4  and T 3  are required for normal growth and development and the proper functioning of the neural, reproductive, cardiovascular, gastroi...

  BIOSYNTHESIS, STORAGE, SECRETION, AND METABOLISM OF THYROID HORMONES   Thyroid epithelial cells synthesize and secrete T 4  and T 3  and make up the functional units of thyroid glandular tissue, the thyroid follicles. Thyroid follicles are hollow vesicles formed by a single layer of epithelial cells that are filled with  colloid.  T 4 ,T 3 , and iodine are stored in the follicular colloid. T 4  and T 3  are derived from tyrosyl residues of the protein  thyroglobulin  (Tg). Thyroid fol-licular cells synthesize and secrete Tg into the follicular lumen. Thyroid follicular cells also remove iodide (I ) from the blood and concentrate it within the follicular lumen. Within the follicles, some of the tyrosyl residues of Tg are iodinated, and a few specific pairs of iodoty-rosyl residues may be coupled to form T 4  and T 3 . Thus, T 4 , T 3 , and iodine (in the form of iodinated tyrosyl residues) are found within the peptide structure of ...

  MECHANISMS OF ACTION OF THYROID HORMONES   Thyroid hormone mechanisms of action can be classi-fied into two types: (1) genomic or nuclear and (2) nongenomic, including effects at the plasma mem-brane and mitochondria. Genomic effects involve modi-fication of gene transcription, are mediated only by T 3 , and require at least several hours to detect. Nongenomic actions are generally rapid in onset and occur in response to T 4  and some T 4  metabolites (e.g., rT 3 , T 3 , and T 2 ).   Genomic Actions of Thyroid Hormones   Thyroid hormone receptors  are members of a super-family of nuclear receptors that includes receptors for estrogen, glucocorticoid, mineralocorticoid, retinoic acid, 9-cis-retinoic acid (retinoid X), and vitamin D. Similar to the mechanism of action of lipophilic steroid hormones, the lipophilic T 3  binds to a protein receptor to form a complex and the hormone–receptor complex binds to an appropriate hormone response el-ement o...

  PHYSIOLOGICAL EFFECTS OF THYROID HORMONES   There is no discrete target tissue for thyroid hormones; virtually every cell in the body is affected by thyroid hormones in some way. These hormones are intimately involved in the maintenance of normal function in vir-tually every cell type, including cellular responsiveness to other hormones, to the availability of metabolic sub-strates, to growth factors, and so on. Thyroid dysfunc-tion can produce dramatic changes in the metabolism of proteins, carbohydrates, and lipids at the cellular level that can have repercussions for the operation of the cardiovascular, gastrointestinal, musculoskeletal, reproductive, and nervous systems. Some of the clinical manifestations of thyroid dysfunction are presented next in the discussions of hypothyroid and hyperthy-roid states.

  HYPOTHYROID STATES   Hypothyroidism  refers to the exposure of body tissues   to a subnormal amount of thyroid hormone. This can re-sult from a defect anywhere in the HPTA. As a conse-quence of the lack of thyroid hormone, a wide variety of physiological and clinical disturbances involving virtu-ally every organ system may result.   Primary hypothyroidism  results from an inability of   the thyroid gland itself to produce and secrete sufficient quantities of T 4  and T 3  and accounts for most cases of hypothyroidism. In iodine-sufficient areas of the world, the most common cause of primary hypothyroidism is  chronic autoimmune thyroiditis ( Hashimoto’s thyroidi-tis). Other causes of primary hypothyroidism include spontaneous degeneration of glandular tissue (idio-pathic hypothyroidism), thyroid ablation with radioac-tive iodine uptake ( 131 I), and total or subtotal surgical thyroidectomy. Primary hypothyroidism is accompa-nied by an ...

  DRUGS USED IN THE TREATMENT OF HYPOTHYROIDISM   Levothyroxine Sodium   Levothyroxine sodium ( Levothroid, Synthroid, Levoxine ) is the sodium salt of the naturally occurring levorota-tory isomer of T 4 . It is the preparation of choice for maintenance of plasma T 4  and T 3  concentrations for thyroid hormone replacement therapy in hypothyroid patients. It is absorbed intact from the gastrointestinal tract, and its long half-life allows for convenient once-daily administration. Since much of the T 4  is deiodi-nated to T 3 , it is usually unnecessary to use more ex-pensive preparations containing both T 4  and T 3 . The aim is to establish euthyroidism with measured serum con-centrations of T 4 , T 3 , and TSH within the normal range.   The TSH-suppressive effects of exogenous T 4  also prove useful in removing the stimulatory effects of TSH on the thyroid gland in the management of simple nonendemic goiter, chronic thyroiditis, and TSH-dep...