Hypothalams-pituitary-thyroid-peripheral

Thyroid disorders. Disturbances in thyroid metabolism can occur at any level of the hypothalams-pituitary-thyroid-peripheral tissue axis. Several of these disorders have been discussed previously. Hyperthyroidism is more prevalent in women than men. The three most common causes of hyperthyroidism are Graves hyperthyroidism, toxic multinodular goiter, and toxic adenoma. The clinical features of hyperthyroidism include hyperkinesis, weight loss, cardiac anomalies (e.g., atrial fibrillation), fatigue, weakness, sweating, palpitations, and nervousness. The typical biochemical laboratory parameters are increased serum free T4 and decreased serum TSH. 

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. 

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.

Thyroid hormone release is subject to the negative feedback strategy that is typical of endocrine systems controlled by the hypothalamic-pituitary axis. Increased circulating levels of the thyroid hormones (T4, T3) serve to limit their own production by inhibiting TRH release from the hypothalamus and TSH release from the anterior pituitary.30,35 This negative feedback control prevents peripheral levels of thyroid hormones from becoming excessively high. 

However, it is now known to exist in various nerve tracts and neuroendocrine tissues and it has general inhibitor actions. It can also inhibit release of other pituitary hormones (including thyroid-stimulating hormone (TSH) and prolactin). other endocrine hormones including pancreatic hormones (insulin and glucagon), peptide hormones from a variety of neuroendocrine tumours (e.g. VIPomas and glucagonomas) and also the release of most intestinal hormones. It is produced in the gut, the pancreas and in some peripheral nerves (see hypothalamic hormones PITUITARY hormones). Somatostatin is a cyclic peptide of 14 residues (SRIF-14) but is formed from a precursor of 28 residues (SRIF-28). 

One important neuronal TRH control center appears to be the paraventricular nucleus, but TRH Is widely distributed in the hypothalamus and highly concentrated in the median eminence (4). One important ipactor regulating TRH production is environmental temperature. Both peripheral thermal receptors and preoptic neuronal thermal receptors monitor environmental and central body temperature these receptors modulate preoptic neuronal outflow to the paraventricular nucleus and other TRH synthesizing neurons in the hypothalamus and median eminence which. In turn, modulate TRH secretion (4). Decreasing environmental and/or core body temperature Increase TRH output and increase the tonic level of TSH release. Somatostatin (SRIF) and dopamine can inhibit TSH release by actions at the pituitary level, and these inhibitory transmitters contribute to central nervous system modulation of TSH release (4). There is evidence that serotonin may be inhibitory in the adult rat, but this does not seem to be so in other species. Norepinephrine also may be inhibitory. Glucocorticoid can inhibit TSH release at the hypothalamic level, but the mechanism is not known. The exact roles of TRH and non-TRH regulatory factors in TSH control are not clear. Administration of somatostatin antiserum to adult rats increases basal TSH levels and potentiates the TSH response to cold (19). Inhibitory factors probably also play a role in the diurnal variation in TSH secretion, in the inhibitory reactions to stress, in the variation in thyroidal activity in psychosis, etc. 

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