Hypothalamic-pituitary-thyroid axis

Explain the major components of the hypothalamic-pituitary-thyroid axis and the interaction among these components. 

FIGURE 41-1. Hypothalamic-pituitary-thyroid axis. Thyrotropinreleasing hormone (TRH) is synthesized in the neurons within the paraventricular nucleus of the hypothalamus. TRH is released into the hypothalamic-pituitary portal circulation and carried to the pituitary, where it activates the pituitary to synthesize and release thyrotropin (TSH). TSH activates the thyroid to stimulate the synthesis and secretion of thyroxine (T4) and triiodothyronine (T3). T4 and T3 inhibit TRH and TSH secretion, closing the feedback loop. 

Nemeroff CB, Bissette G, Martin JB, et al Effect of chronic treatment with thyrotropin-releasing hormone (TRH) or an analog of TRH (hnear-beta-alanine TRH) on the hypothalamic-pituitary-thyroid axis. Neuroendocrinology 30 193-199, 1980... 

Dysregulation of the hypothalamic-pituitary-thyroid axis causes a reduction in thyroid function. There may be a relationship between an abnormal TSH response to TRH and depressive symptoms. Thus, unipolar patients undergoing the TRH-TSH test (which measures the difference between baseline TSH and peak postinfusion TSH after they are given synthetic TRH) reportedly have a blunted response, whereas bipolar, depressed patients have an elevated response (see also Chapter 1,... 

The hypothalamic-pituitary-thyroid axis. Acute psychosis or prolonged exposure to cold may activate the axis. Hypothalamic thyroidreleasing hormone (TRH) stimulates pituitary thyroid-stimulating hormone (TSH) release, while somatostatin and dopamine inhibit it. TSH stimulates T4 and T3 synthesis and release from the thyroid, and they in turn inhibit both TRH and TSH synthesis and release. 

The many effects of lithium on thyroid physiology and on the hypothalamic-pituitary axis and their clinical impact (goiter, hypothyroidism, and hyperthyroidism) have been reviewed (620). Lithium has a variety of effects on the hypothalamic-pituitary-thyroid axis, but it predominantly inhibits the release of thyroid hormone. It can also block the action of thyroid stimulating hormone (TSH) and enhance the peripheral degradation of thyroxine (620). Most patients have enough thyroid reserve to remain euthyroid during treatment, although some initially have modest rises in serum TSH that normalize over time. 

Nikrodhanond AA, Ortiga-Carvalho TM, Shibusawa N, et al. Dominant role of thyrotropin-releasing hormone in the hypothalamic-pituitary-thyroid axis. J Biol Chem. 2006 281 5000-5007. 

When the serum free thyroxine concentration (FT4) or ultrasensitive TSH result is normal, the hypothalamic-pituitary-thyroid axis is assumed to be intact. If primary hypothyroidism is suspected clinically, however, a single measurement of a basal TSH concentration may be sufficient to confirm the diagnosis. In patients with a history of pituitary disease and secondary hypothyroidism, the serum TSH concentration is frequently normal thus in this situation, an FT4 concentration is tlie better test to gauge normality of the hypothalamic-pituitary-thyroid axis. On occasion a TRH stimulation test is used to distinguish hypothalamic... 

Figure 52-2 Hypothalamic-pituitary-thyroid axis—hormone synthesis dependent on dietary intake of ISO pg of iodine per day.T4 major thyronine secreted from thyroid gland with T3 coming predominantly from peripheral deiodination.

Hypothalamic-pituitary-thyroid axis dysregulation Hyperthyroidism may precipitate a mania. 

Uy HL, Reasner CA, Samuels MH. Pattern of recovery of the hypothalamic-pituitary-thyroid axis following radioactive iodine therapy in patients with Graves disease. Am J Med 1995 99 173-179. 

Pintar JE. 2000. Normal development of the hypothalamic-pituitary-thyroid axis. In Braverman LE, Utiger RD, ed. Werner and Ingbar s the thyroid A fundamental and clinical text. Philadelphia, PA Lippincott-Raven, 7-19. 

Three- to four-day old northern bobwhite were used to evaluate the influence of ammonium perchlorate (AP) on thyroid function, as well as thyroidal hormone level systemic effects on the hypothalamic-pituitary-thyroid axis [46], The perchlorate ion competitively inhibits iodide uptake, thus with time AP has the potential to reduce... 

Hypothyroidism is caused by a deficiency of thyroid hormones. Primary hypothyroidism is failure of the thyroid gland itself and is one of the mo.st commonly encountered endocrine problems. The demonstration of an elevated T.SH concentration is usually diagnostic. Secondary hypothyroidism, failure of the pituitary to secrete TSH, is much less common. Isolated pituitary deficiency of TSH is rare, but impairment of the hypothalamic-pituitary-thyroid axis may happen as a result of any pituittu y disca.se or damage. 

Thyroid hormone production is governed by the actions of the hypothalamic-pituitary-thyroid axis (HPT axis). Thyrotropin releasing hormone (TRH) synthesized by the hypothalamus is transported to the anterior pituitary, where TRF stimulates thyrotrophic cells to produce thyrotrophin (TSH). TSH is a glycoprotein with a short half-life of less than 20 min it is one of three pituitary glycoprotein hormones with alpha- and beta-subunits. These three pituitary glycoproteins (luteotrophin, fol-liotrophin, and TSH) share the same alpha-subunit. 

TSH test. Measuring the serum TSH has become the screen test of choice for thyroid disease. Primary hypothyroidism produces elevated TSH levels, whereas patients with primary hyperthyroidism (i.e., Graves disease) should have undetectable TSH values. This relationship is true only in individuals with an intact hypothalamic-pituitary-thyroid axis. Patients who present with a normal or detectable TSH level and elevated thyroid hormone concentrations require further evaluation to exclude central causes of hyperthyroidism. 

Thyroid dysfunction continues to be an infrequent and unpredictable complication found in only 3% of patients according to one review (47 ) and occurring more often in women. A study of the mechanism of action (50 ) in 17 patients on lithium maintenance therapy involved exploration of the hypothalamic-pituitary-thyroid axis. Fourteen subjects showed an exaggerated thyrotropin response to intravenous thyrotropinreleasing hormone that persisted during lithium therapy. However, only 2 of these patients showed any clinical or biochemical evidence of hypothyroidism both showed a delayed recovery of normal TRH response after discontinuing lithium. 

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