Hypothyroidism hypothalamic

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. 

In patients with hypothyroidism caused by hypothalamic or pituitary failure, alleviation of the clinical syndrome and restoration of serum T4 to the normal range are the only criteria available for estimating the appropriate replacement dose of levothyroxine. 

Weight gain can be caused by medical conditions (e.g., hypothyroidism, Cushing s syndrome, hypothalamic lesion) or genetic syndromes (e.g., Prader-Willi s syndrome), but these are unusual to rare causes of obesity. 

Tertiary hypothyroidism, or hypothalamic hypothyroidism, 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 hypothyroidism is also characterized by inappropriately low levels of serum TSH. 

Antagonists of TRH have also been synthesized. For example, cyclopentylcarbonyl-thienylalanyl-pyrrolidine amide inhibits TSH release at high doses. Thyroliberin is used diagnostically only, to distinguish between hypothalamic and pituitary hypothyroidism. 

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. 

Peak serum thyrotropin levels occur 20-30 seconds after intravenous TRH injection in healthy individuals. In hyperthyroidism, the serum thyrotropin level is suppressed. In primary hypothyroidism, thyrotropin levels are high and the thyrotropin response to TRH may be accentuated. In secondary (pituitary) hypothyroidism, serum thyrotropin levels are "inappropriately" normal or low (using a sensitive TSH assay) TSH often fails to rise after TRH administration. In tertiary (hypothalamic) hypothyroidism, the baseline serum thyrotropin level may be normal or low and the thyrotropin response to TRH may be normal or blunted. 

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... 

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. 

Secondary hypothyroidism (central thyroid disease) occurs as a result of pituitary or hypothalamic diseases that produce a deficiency in either TSH, TRH, or both. Isolated TSH defi-... 

TRH deficiency also causes hypothyroidism. In both adults and children it may occur as a result of cranial irradiation, trauma, infiltrative diseases, or neoplastic diseases. Hypothalamic hypothyroidism... 

In patients with hypothyroidism caused by hypothalamic or pituitary failure, alleviation of the chnical syndrome and restoration of serum T4 to the normal range are the only criteria available for estimating the appropriate replacement dose of levothyroxine. Concurrent use of dopamine, dopaminergic agents (bromocriptine), somatostatin or somatostatin analogs (octreotide), and corticosteroids suppresses TSH concentrations and may confound the interpretation of this monitoring parameter. ... 

---