Chapter 39

INTRODUCTION

Thyroid hormone is essential for normal development, especially of the central nervous system (CNS). In the adult, thyroid hormone maintains metabolic homeostasis and influences the function of virtually all organ systems. Thyroid hormone contains iodine that must be supplied by nutritional intake. The thyroid gland contains large stores of thyroid hormone in the form of thyroglobulin. These stores maintain systemic concentrations of thyroid hormone despite variations in iodine availability and nutritional intake. The thyroidal secretion is predominantly the prohormone thyroxine, which is converted in the liver and other tissues to the active form, triiodothyronine. Local activation of thyroxine also occurs in target tissues (e.g., brain and pituitary) and is increasingly recognized as an important regulatory step in thyroid hormone action. Serum concentrations of thyroid hormones are precisely regulated by the pituitary hormone, thyrotropin (TSH), in a classic negative-feedback system. The predominant actions of thyroid hormone are mediated through binding to nuclear thyroid hormone receptors (TRs) and modulating transcription of specific genes. Thyroid hormones share a common mechanism of action with steroid and steroid-like hormones, such as vitamin D and the retinoids, whose receptors are members of a superfamily of nuclear receptors (Chapter 3). Although the predominant actions of thyroid hormone are nuclear, actions of thyroid hormone outside the nucleus have been reported.

Disorders of the thyroid are common. Thyroid nodules and goiter, thyroid enlargement, are the most common abnormalities and can be either benign or malignant processes. In most of these patients, circulating thyroid hormone levels are normal. Overt hyperthyroidism and hypothyroidism, thyroid hormone excess or deficiency, are usually associated with dramatic clinical manifestations. Milder disease often has a more subtle clinical presentation and is identified based on abnormal biochemical tests of thyroid function. Screening of the newborn population for congenital hypothyroidism occurs in all developed countries, and when followed by the prompt institution of appropriate thyroid hormone replacement therapy, has dramatically decreased the incidence of mental retardation and cretinism. Maternal and neonatal hypothyroidism, due to iodine deficiency, remains the major preventable cause of mental retardation worldwide, although much progress has been made in eradicating iodine deficiency.

Effective treatment of most thyroid disorders is readily available. Treatment of the hypothyroid patient consists of thyroid hormone replacement. Treatment options for the hyperthyroid patient include anti-thyroid drugs to decrease hormone synthesis and secretion, destruction of the gland by the administration of radioactive iodine, or surgical removal. In most patients, disorders of thyroid function can be either cured or have their diseases controlled. Likewise, thyroid malignancies are most often localized and resectable. Metastatic disease often responds to radioiodide treatment but may become highly aggressive and unresponsive to conventional treatment. Newer therapies that target specific genetic mutations in malignancies have shown significant activity in both medullary and papillary thyroid cancers.

THYROID

The thyroid gland is the source of two fundamentally different types of hormones. The thyroid follicle produces the iodothyronine hormones ...

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