Hypothalamic hormones Hypothyroidism

So far no definite therapeutic applications have been described for TRH. It has been suggested that it has antidepressant effects, but further controlled studies (M15) did not substantiate the initial reports. The role of TRH as a tool in the treatment of thyroid carcinoma (by increasing uptake of the therapeutic dose of radioiodine by the tumor) (F4) is as yet not confirmed. TRH could be used in the treatment of hypothalamic (tertiary) hypothyroidism, but it does not offer any advantage over thyroid hormone replacement. We have not observed any beneficial effect of TRH in regenerating thyroid remnants after surgery. It has been reported that TRH administration to cows results in an elevation of PRL which increases milk production (K3). Further controlled studies of the applications of TRH in the dairy industry are required. 

Prolactin is an essential hormone for normal production of breast milk following childbirth. It also plays a pivotal role in a variety of reproductive functions. Prolactin is regulated primarily by the hypothalamus-pituitary axis and secreted solely by the lactotroph cells of the anterior pituitary gland. Under normal conditions, secretion of prolactin is predominantly under inhibitory control by dopamine and acts on the D2 receptors located on the lactotroph cells. Increase of hypothalamic thyrotropin-releasing hormone (TRH) in primary hypothyroidism can stimulate the release of prolactin. 

Thyroid function tests are often altered by somatropin because of increased conversion of T4 to T3, but this is clinically insignificant at low doses (SEDA-21, 453). One child with Prader-Willi syndrome had a fall in serum thyroxine concentration during somatropin therapy and needed thyroxine replacement (33). Hypothyroidism developed in 11 of 46 growth hormone-deficient children treated with somatropin (34). Prior abnormalities in hypothalamic-pituitary function and alterations in thyroid hormone metabolism, probably both, contributed to the high incidence of hypothyroidism, which was similar to that in previous studies. 

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. 

Many structural or functional abnormalities of the thyroid gland can lead to thyroid hormone deficiency (Box 52-2). Primary hypothyroidism is frequently caused by diseases or treatments that directly destroy thyroid tissue or interfere with thyroid hormone biosynthesis. Secondary hypothyroidism occurs as a result of pituitary or hypothalamic disease and/or disorders. 

Destruction of the pituitary gland may result in secondary hypothyroidism, hypogonadism, adrenal insufficiency, growth hormone deficiency, and hypoprolactinemia. The formation of certain types of pituitary tumors may result in pituitary hormone excess. Pituitary tumors may also physically compress the pituitary and prevent the release of the trophic hypothalamic factors that regulate pituitary hormones. In this chapter, the pathophysiology and role of pharmacotherapy in the treatment of acromegaly, short stature, hyperprolactinemia, and panhypopituitarism will be discussed. 

Less common etiologies include central nervous system lesions that physically compress the pituitary stalk and interrupt tonic hypothalamic dopamine secretion, resulting in hyperprolactinemia. Increased thyroid-releasing hormone (TRH) concentrations in hypothyroidism can stimulate prolactin secretion and cause hyperprolactinemia. During conditions of renal or liver compromise, the... 

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. 

Like other anterior pituitary hormones, prolactin is secreted in a pulsatile manner. Prolactin is unique among the anterior pituitary hormones in that hypothalamic regulation of its secretion is predominantly inhibitory. The major regulator of prolactin secretion is dopamine, which is released by tuberoinfundibular neurons and interacts with the Dj receptor on lactotropes to inhibit prolactin secretion. A number of putative prolactin-releasing factors have been described, but their physiological roles are unclear. Under certain pathophysiological conditions, such as severe primary hypothyroidism, persistently elevated levels of TRH can induce hyperprolactinemia and consequent galactorrhea. 

Thyroid Hypofunction Hypothyroidism is the most common disorder of thyroid function. It can be divided into patients who have a failure of the thyroid gland to produce sufficient thyroid hormone (primary hypothyroidism) and patients in which pituitary or hypothalamic disease is associated with impaired TSH stimulation (central or secondary hypothyroidism). Worldwide, primary hypothyroidism is caused most often by iodine deficiency. In areas where iodine is sufficient, chronic autoimmune thyroiditis (Hashimoto s thyroiditis) accounts for most cases. Other causes include postpartum thyroiditis, surgical removal, or radioactive iodine ablation of the gland. Hypothyroidism present at birth (cretinism) is the most common preventable cause of mental retardation in the world. 

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. 

If a patient suspected of developing clinical hypothyroidism is investigated only with routine tests, namely total T4, FTI, and the ETR or a similar estimation, there is no way of determining whether the patient has idiopathic myxedema or hypothyroidism secondary to hypothalamic or anterior pituitary disease. The distinction should be made, however, because it is dangerous to treat pituitary hypothyroidism with thyroid hormone without simultaneously treating with adrenocortical hormones. 

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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