Adrenocorticotropic hormone production

See Table 15-6. Potassium-sparing diuretics are most useful in states of mineralocorticoid excess or hyperaldosteronism (also called aldosteronism), due either to primary hypersecretion (Conn s syndrome, ectopic adrenocorticotropic hormone production) or secondary hyperaldosteronism (evoked by heart failure, hepatic cirrhosis, nephrotic syndrome, or other conditions associated with diminished effective intravascular volume). Use of diuretics such as thiazides or loop agents can cause or exacerbate volume contraction and may cause secondary hyperaldosteronism. In the setting of enhanced mineralocorticoid secretion and excessive delivery of Na+ to distal nephron sites, renal K+ wasting occurs. Potassium-sparing diuretics of either type may be used in this setting to blunt the K+ secretory response. 

Adrenal hormone production is controlled by the hypothalamus and pituitary gland. Corticotropin-releasing hormone (CRH) is secreted by the hypothalamus and stimulates secretion of adrenocorticotropic hormone (ACTH), also known as corticotropin from the anterior pituitary. ACTH, in turn, stimulates the adrenal cortex to produce cortisol. When sufficient or excessive cortisol levels are reached, a negative feedback is exerted on the secretion of CRH and ACTH, thereby decreasing overall cortisol production. The control of adrenal androgen synthesis also follows a similar negative-feedback mechanism. 

FIGURE 1 8-5 Tissue-specific processing of the pro-opiomelanocortin (POMC) precursor yields a wide array of bioactive peptide products. Processing of the POMC precursor varies in various tissues. In anterior pituitary, adrenocorticotropic hormone (ACTH (1-39)) and P-1 ipo tropin (P-LPH) are the primary products of post-translational processing. Arcuate neurons produce the potent opiate P-endorphin (P-endo (1-31)) as well as ACTIK1 -13) NIT,. Intermediate pituitary produces a-melanocyte-stimulating hormone (aMSH), acetylated P endof 1 31) and P-endo(l-27). NTS, nucleus tractus solitarius. 

Adrenocorticotropic hormone (Fig. 4) stimulates the cells of the adrenal cortex into the secretion and production of steroid hormones. Conversely, the pituitary secretion of ACTH is inhibited by the adrenal hormones via a feedback mechanism. 

Melanocortins. This is a generic name for the peptide hormones, melanotropin and corticotropin, (ACTH, adrenocorticotropic hormone), because both hormones are formed in the anterior pituitary gland from the same melanocortin precursor. Melanotropin controls melanocyte growth and pigmentation. Corticotropin stimulates the production of glucocorticoids and mineralocorticoids, such as aldosteron, in the adrenal cortex. The Melanocortin-pathway is somehow involved in the control of appetite and body weight. 

With the introduction and use of monoclonal antibodies, the measurement of hormones is now accurate and precise. The production of hormones in cancer involves two separate routes. First, the endocrine tissue that normally produces it can produce excess amounts of a hormone. Second, a hormone may be produced at a distant site by a non-endocrine tissue that normally does not produce the hormone. The latter condition is called ectopic syndrome. For example, the production of adrenocorticotropic hormone (ACTH) is norraotopic by the pituitary and is ectopic by the small cell of the lung. Consequently, elevation of a given hormone is not diagnostic of a specific tumor, because a hormone may be produced by a variety of cancers. 

Corticotropin is a peptide hormone secreted by the adenohypophysis, one of the derivatives of pro-opiomelanocortin (POMC) it acts primarily on the adrenal cortex, stimulating its grovrth and the secretion of corticosteroids. Its production is increased during times of stress. It is also known as adrenocorticotropic hormone, ACTH, corticotrophin, adrenocorticotrophin, and adrenocorticotropin. 

Figure 54-1 Schematic representation of steroid and protein hormone production by the placenta. DHEA-S, Dehydro-epiandrosterone sulfate CG, chorionic gonadotropin PL, placental lactogen ACTH, adrenocorticotropic hormone TRH, thyroid-stimulating hormone CT, chorionic thyrotropin GnRH, gonadotropin-releasing hormone CRH, corticotropin-releasing hormone PAPP-A, pregnancy associated plasma protein-A.

Corticosteroids and adrenocorticotropic hormone have been widely used for the treatment of ulcerative cohtis and Crohn s disease, given parenterally, orally, or rectally. Corticosteroids are believed to modulate the immune system and inhibit production of cytokines and mediators. It is not clear whether the most important steroid effects are systemic or local (mucosal). Budesonide is a corticosteroid that is administered orally in a controlled-release formulation. The drug undergoes extensive first-pass metabolism, so systemic exposure is thought to be minimized. Immunosuppressive agents such as azathioprine, mercaptopurine (a metabolite of azathioprine), methotrexate, or cyclosporine are sometimes used for the treatment of IBD. ... 

ACTH (adrenocorticotropic hormone or corticotropin) Hormone produced in the anterior pimitary, which stimulates adrenal production of cortisol. 

FIGURE 10.46 Distribution of markers in large cell NE carcinoma. CEA(m), monoclonal carcinoembryonic antigen PGP, protein gene product 9.5 CK, cytokeratin NSE, neuron-specific enoiase CgA, chromogranin A SYN, synaptophysin GRP, gastrin-reieasing peptide ACTH (b), big adrenocorticotropic hormone CT, calcitonin. 

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