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INTRODUCTION

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  • Thyroid disorders involve thyroid hormone production or secretion and result in alterations in metabolic stability.

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THYROID HORMONE PHYSIOLOGY

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  • Thyroid hormones: thyroxine (T4) and triiodothyronine (T3) are formed on thyroglobulin, a large glycoprotein synthesized within the thyroid cell. Inorganic iodide enters the thyroid follicular cell and is oxidized by thyroid peroxidase and covalently bound (organified) to tyrosine residues of thyroglobulin.

  • Iodinated tyrosine residues monoiodotyrosine (MIT) and diiodotyrosine (DIT) combine (couple) to form iodothyronines in reactions catalyzed by thyroid peroxidase. Thus, two molecules of DIT combine to form T4, and MIT and DIT join to form T3.

  • Proteolysis within thyroid cells releases thyroid hormone into the bloodstream. T4 and T3 are transported by thyroid-binding globulin (TBG), transthyretin, and albumin. Only the unbound (free) thyroid hormone can diffuse into cells, elicit biologic effects, and regulate thyroid-stimulating hormone (TSH) secretion from the pituitary.

  • T4 is secreted solely from the thyroid, but less than 20% of T3 is produced there; most T3 is formed from breakdown of T4 catalyzed by the enzyme 5′-monodeiodinase in peripheral tissues. T3 is five times more active than T4. T4 may also be acted on by 5′-monodeiodinase to form reverse T3, which has no significant biologic activity.

  • Thyroid hormone production is regulated by TSH secreted by the anterior pituitary, which in turn is under negative feedback control by the circulating level of free thyroid hormone and the positive influence of hypothalamic thyrotropin-releasing hormone (TRH). Thyroid hormone production is also regulated by extrathyroidal deiodination of T4 to T3, which can be affected by nutrition, nonthyroidal hormones, drugs, and illness.

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THYROTOXICOSIS (HYPERTHYROIDISM)

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PATHOPHYSIOLOGY

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  • Thyrotoxicosis results when tissues are exposed to excessive levels of T4, T3, or both. Hyperthyroidism, which is one cause of thyrotoxicosis, refers to overproduction of thyroid hormone by the thyroid gland.

  • TSH-secreting pituitary tumors occur sporadically and release biologically active hormone that is unresponsive to normal feedback control. The tumors may cosecrete prolactin or growth hormone; therefore, patients may present with amenorrhea, galactorrhea, or signs of acromegaly.

  • Resistance to thyroid hormone occurs rarely and can be due to various molecular defects, including mutations in the TRβ gene. Pituitary resistance to thyroid hormone (PRTH) refers to selective resistance of the pituitary thyrotrophs to thyroid hormone.

  • Graves’ disease is the most common cause of hyperthyroidism, which results from the action of thyroid-stimulating antibodies (TSAb) directed against the thyrotropin receptor on the surface of thyroid cell. These immunoglobulins bind to the receptor and activate the enzyme adenylate cyclase in the same manner as TSH.

  • An autonomous thyroid nodule (toxic adenoma) is a thyroid mass whose function is independent of pituitary control. Hyperthyroidism usually occurs with larger nodules (>3 cm in diameter).

  • In multinodular goiter, follicles with autonomous function coexist ...

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