Hypothalamic-Pituitary-Thyroid Function

White A (1987) Clinical evaluation of a two-site immunoradio-metric assay for adrenocorticotrophin in unextracted human plasma using monoclonal antibodies. Clin Endocrinol (Oxf) 26 41-51 

Zahradnik R (1989) Immunoradiometric assay of corticotropin with use of avidin-biotin separation. Clin Chem 35 804-807 

In the endocrine safety pharmacology for the hypothalamic pituitary adrenal system, the levels to be examined are  

CRH activity, by determination of the hypothalamic peptide content - the information obtained by this measurement is usually limited and and will be controlled by the feedback action of pituitary hormone release or inhibition and adrenal steroid secretion 

ACTH secretion and synthesis, which may be modified by compounds affecting pituitary gland - this information is valuable and reflects the level of secretion of glucocorticoids over several days of treatment, and 

---

Ontogenesis of hypothalamic pituitary thyroid function and metabolism in man, sheep and rat. Rec. Prog. Horm. Res. 33 ... 

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,... 

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... 

Control of thyroid function via thyroid-pituitary feedback is also discussed in Chapter 37. Briefly, hypothalamic cells secrete thyrotropin-releasing hormone (TRH) (Figure 38-3). TRH is secreted into capillaries of the pituitary portal venous system, and in the pituitary gland, TRH stimulates the synthesis and release of thyrotropin (thyroid-stimulating hormoneTSH). TSH in turn stimulates an adenylyl cyclase-mediated mechanism in the thyroid cell to increase the synthesis and release of T4 and T3. These thyroid hormones act in a negative feedback fashion in the pituitary to block the action of TRH and in the hypothalamus to inhibit the synthesis and secretion of TRH. Other hormones or drugs may also affect the release of TRH or TSH. 

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. 

Regulation of synthesis Thyroid function is controlled by a tropic hormone, thyroid-stimulating hormone (TSH, thyrotropin), a glycoprotein synthesized by the anterior pituitary (see Figure 25.2). TSH generation is governed by the hypothalamic thyrotropin-... 

The effect of various narcotic analgesics on th5nroid function have been assessed and it was concluded that they did not exert a direct action on the thyroid but depressed thyroid function through an effect on the hypothalamic-pituitary axis. This was further clarified in an elegant study by Lc aax and George whose results lead them to postulate that morphine acts on the thyroid by activating areas in the posterior hypothalamus which inhibit the release of TSH from the pituitary. 

Guillemin et al. (G9) reported that they had extracted and purified a substance from the hypothalamus of sheep which stimulated thyroid function in the rat. Others showed that crude hypothalamic extracts would stimulate thyroid function in mice and rabbits, and Schreiber (S6) reported that a crude extract of bovine hypothalamus would release TSH from rat pituitaries in vitro. Schally et al. (S3) obtained a more purified TRF factor from 100,000 porcine hypothalami. TRF is apparently a small molecular weight substance and, although originally thought to be a protein (G8, S2), more recent evidence suggests that... 

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. 

Results in Chronic Renal Failure. The TRH test provides unreliable information in patients with impaired renal function. An exaggerated response may be due to poor renal clearance of TRH (G12), and we have observed impaired, absent, or delayed TSH responses (G3) without any evidence of hypothalamic-pituitary or thyroid disease in a group of patients with chronic renal failure. 

---