Hypothalamic-pituitary-thyroid

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. 

FIGURE 52-1 Schematic representation of possible and known reciprocal interactions among hypothalamic, pituitary, thyroid, adrenal and gonadal hormones. 

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. 

A large number of ubiquitous environmental pollutants are very toxic to the hypothalamic-pituitary-thyroid (HPT) axis when administered at high (greater than environmental) levels. To study low level effects on the HPT axis, laboratory animals were administered a mixture of 16 organochlorine pesticides and other chlorinated hydrocarbons and heavy metals, all at levels similar to those found environmentally, so as to simulate environmental exposure. The chemicals included DDT (6.91), HCB (5.73), TCDD (6.80), PCBs (6.29), methoxychlor (5.08), endosulfan (3.83), heptachlor (6.10), hexachlorocyclohexane (3.80), dieldrin (5.40), aldrin (6.50), mirex (7.18), several chlorinated benzenes (2.84-3.44), cadmium (-1.65), and lead (1.35). Effects were measured by monitoring thyroid activity. The study found that this mixture of environmental pollutants was toxic and can alter HPT physiology in sexually mature malesJ50 ... 

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.

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