Adrenal cortex treatment

Historically the only melanocortin peptide to be used clinically is the parent hormone from which all these peptides are derived from namely ACTH (see above). It has also been used in the treatment infantile spasms for epilepsy, where it is administered as an intramuscular injection only over a 2-12 weeks period. Obvious side effects include weight gain, puffy face, high blood pressure and an increased risk of infection and should never be administered to patients with diabetics, renal or heart failure. ACTH is also used as a stimulation test to measure adrenal cortex activity, i.e. production of cortisol and is used to ascertain whether someone has Addison s disease. 

Corticosteroids are hormones secreted from the adrenal cortex. These hormones arise from the cortex of the adrenal gland and are made from the crystalline steroid alcohol cholesterol. Synthetic forms of the natural adrenal cortical hormones are available The potent antiinflammatory action of the corticosteroids makes these drugs useful in the treatment of many types of musculoskeletal disorders. The corticosteroids are discussed in Chapter 50. 

The male and female gonads, as well as the placenta of pregnant females and, to a lesser extent, the adrenal cortex, produce a range of steroid hormones which regulate the development and maintenance of reproductive and related functions. As such, these steroid sex hormones have found medical application in the treatment of various reproductive dysfunctions. 

Mitotane, or o,p -DDD, is an oral medication used in the treatment of adrenocortical carcinoma. Chemically it is an isomere of DDT. Following its metabolism in the adrenal cortex to a reactive acyl chloride intermediate, mitotane covalently binds to adrenal proteins, specitically inhibiting adrenal cortical hormone production. The drug accumulates in fat tissue. It is eliminated mainly by the kidneys with a half-life of 18-159 days. Common side effects include anorexia, nausea, lethargy, sleepiness and skin problems. 

Metyrapone is a competitive inhibitor of 11 beta hydroxylation in the adrenal cortex, and effectively inhibits cortisol production. It is used in low doses, titrated to achieve plasma cortisol levels as close as possible to normal day-time values. Occasionally it is used in higher doses combined with replacement corticosteroid treatment. Its main side effects relate to overdosage and resulting hypoadrenalism, but it can also cause hirsutism and hypertension, due to accumulation of precursor steroids. Ketoconazole is also sometimes used to suppress adrenal steroid production, but its potential for hepatotoxicity limits its... 

The natural adrenocortical hormones are steroid molecules produced and released by the adrenal cortex. Both natural and synthetic corticosteroids are used for the diagnosis and treatment of disorders of adrenal function. They are also used—more often and in much larger doses—for treatment of a variety of inflammatory and immunologic disorders. 

Metyrapone is commonly used in tests of adrenal function. The blood levels of 11-deoxycortisol and the urinary excretion of 17-hydroxycorticoids are measured before and after administration of the compound. Normally, there is a twofold or greater increase in the urinary 17-hydroxycorticoid excretion. A dose of 300-500 mg every 4 hours for six doses is often used, and urine collections are made on the day before and the day after treatment. In patients with Cushing s syndrome, a normal response to metyrapone indicates that the cortisol excess is not the result of a cortisol-secreting adrenal carcinoma or adenoma, since secretion by such tumors produces suppression of ACTH and atrophy of normal adrenal cortex. 

Byme JJ, Carbone JP, Pepe MG. 1988. Suppression of serum adrenal cortex hormones by chronic low-dose polychlorobiphenyl or polybromobiphenyl treatments. Arch Environ Contam Toxicol 17 47-53. 

Withdrawal symptoms disappear if the glucocorticoid is resumed, but as a rule they will in any case vanish spontaneously within a few days. More serious consequences can ensue, however, in certain types of cases and if adrenal cortical atrophy is severe. In patients treated with corticoids for the nephrotic syndrome and apparently cured, the syndrome is particularly likely to relapse on withdrawal of therapy if the adrenal cortex is atrophic (SEDA-3,305). In some cases, acute adrenocortical insufficiency after glucocorticoid treatment has actually proved fatal. It is advisable to withdraw long-term glucocorticoid therapy gradually so that the cortex has sufficient opportunity to recover. Table 5 lists methods of... 

Ostrowska Z, Buntner B, Rosciszewska D, Guz I. Adrenal cortex hormones in male epileptic patients before and during a 2-year phenytoin treatment. J Neurol Neurosurg Psychiatry 1988 51(3) 374-8. 

Some of the most important physiological steroids are the adrenocortical hormones, synthesized by the adrenal cortex. Most of these hormones have either a carbonyl group or a hydroxyl group at Cl 1 of the steroid skeleton. The principal adrenocortical hormone is cortisol, used for the treatment of inflammatory diseases of the skin (psoriasis), the joints (rheumatoid arthritis), and the lungs (asthma). Figure 25-10 compares the structure of natural cortisol with two synthetic corticoids fluocinolone acetonide, a fluori-nated synthetic hormone that is more potent than cortisol for treating skin inflammation and beclomethasone, a chlorinated synthetic hormone that is more potent than cortisol for treating asthma. 

Haack D, Engel R, Vecsei P (1978) The effect of chronic ACTH treatment on blood pressure and urinary excretion of steroids in the rat. Klin-Wochenschr 56(Suppl 1) 183—186 Harvey PW, Everett DJ (2003) The adrenal cortex and steroidogenesis as cellular and molecular targets for toxicity criti-... 

The adrenal cortex secretes steroid hormones, primarily glucocorticoids and mineralocorticoids. Deficiency of these steroids results in Addison s disease, characterized by hypoglycaemia, lethargy and weight loss, anorexia and nausea and hypotension, which can be severe and may result in cardiovascular collapse. Treatment includes replacement of the missing steroids. 

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