Hypothyroidism refers to the exposure of body tissues to a subnormal amount of thyroid hormone. This can result from a defect anywhere in the HPTA. As a consequence of the lack of thyroid hormone, a wide variety of physiological and clinical disturbances involving virtually every organ system may result.
Primary hypothyroidism results from an inability of the thyroid gland itself to produce and secrete sufficient quantities of T4 and T3 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 thyroiditis). Other causes of primary hypothyroidism include spontaneous degeneration of glandular tissue (idiopathic hypothyroidism), thyroid ablation with radioactive iodine uptake (131I), and total or subtotal surgical thyroidectomy. Primary hypothyroidism is accompanied by an elevation in pituitary TSH secretion and circulating TSH levels. An enlargement of the thyroid, or goiter, usually develops with increasing duration of the primary hypothyroidism.
Biosynthetic defects in thyroid hormonogenesis may also result in an inability of the thyroid gland to produce sufficient hormone and may be due to inherited enzymatic deficiencies or the ingestion of natural or thera-peutically administered antithyroid agents. An example in the latter category is lithium, widely used to treat psychiatric disorders and associated with the development of hypothyroidism and goiter. It is concentrated by the thyroid, where it inhibits thyroidal uptake, incorpora-
tion of I" into Tg, coupling of iodotyrosine, and, eventually, thyroid hormone secretion.
Secondary hypothyroidism, or pituitary hypothyroidism, is the consequence of impaired thyroid-stimulating hormone (TSH) secretion and is less common than primary hypothyroidism. It may result from any of the causes of hypopituitarism (e.g., pituitary tumor, postpartum pituitary necrosis, trauma). Patients with secondary hypothyroidism exhibit undetectable or inappropriately low serum TSH concentrations. In secondary hypothyroidism, a normal thyroid gland lacks the normal level of TSH stimulation necessary to synthesize and secrete thyroid hormones. Such patients usually also have impaired secretion of TSH in response to exogenous thyrotropin-releasing hormone (TRH) administration.
Tertiary hypothyroidism, or hypothalamic hypothy-roidism, results from impaired TRH stimulation of pituitary TSH. This may be due to a disorder that damages the hypothalamus or interferes with hypothalamic-pituitary portal blood flow, thereby preventing delivery of TRH to the pituitary. Tumors, trauma, radiation therapy, or infiltrative disease of the hypothalamus can cause such damage. This relatively rare form of hy-pothyroidism is also characterized by inappropriately low levels of serum TSH.
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