Steroids adrenal disorders

Adrenal disorders Glucocorticoids are essential to preserve life in patients with chronic adrenal cortical insufficiency (Addison s disea.se) and are necessary in acute adrenal insufficiency associated with life-threatening shock, infection, or trauma. Glucocorticoids are also used in certain types of congenital adrenal hyperplasia, in which synthesis of abnormal forms of corticosteroids are stimulated by ACTO. In these conditions, administration of a potent synthetic glucocorticoid suppresses ACTH secretion sufficiendy to reduce the synthesis of the abnormal steroids. 

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 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. 

Primary aldosteronism usually results from the excessive production of aldosterone by an adrenal adenoma. However, it may also result from abnormal secretion by hyperplastic glands or from a malignant tumor. The clinical findings of hypertension, weakness, and tetany are related to the continued renal loss of potassium, which leads to hypokalemia, alkalosis, and elevation of serum sodium concentrations. This syndrome can also be produced in disorders of adrenal steroid biosynthesis by excessive secretion of deoxycorticosterone, corticosterone, or 18-hydroxycorticosterone—all compounds with inherent mineralocorticoid activity. 

The THEiTHF + 5aTHF ratio is commonly greater than 15 in these disorders, the opposite to AME syndrome. While the ratio of saturated steroids demonstrates a high 11-oxo l 1/1-hydroxy ratio, this is not the case for steroids retaining a - -4-ene structure. The F E ratio is normal or elevated (i.e., > 1 Table 5.3.9). Steroid profile analysis also typically reveals an elevated excretion of DHEA and other androgen metabolites. Clearly the excessive ACTH production resultant from an apparent cortisol deficiency is responsible for the elevated adrenal androgen production, which in turn is responsible for female virilization and other manifestations of polycystic ovary syndrome. 

Infants with salt-losing crisis and adrenal insufficiency in infancy may have adrenal hypoplasia congenita. This can be of two types recessive, for which the cause has not been defined and which affects mostly the fetal zone, and X-linked, which is caused by mutations in the DAX-1 gene, which (with steroidogenic factor-1) controls definitive zone development and steroidogenesis [71]. GC-MS analysis of patients with the disorder show variant patterns from absence of neonatal A5 steroids, appropriate for the recessive form [81], to extremely low cortisol production and transient 11/Lhy-droxylase deficiency, as evidenced through increased THS excretion (Malunowicz, personal communication). 

We found normal levels of conventional urinary steroids in this disorder, but these patients can show blunted response to ACTH, and adrenal hyperplasia is often noted post-mortem in nonsurviving newborns. Many distinctive metabolites have been found in urine from patients with the disorder, major examples being 5/3-prcgn-... 

The adrenal cortex synthesizes corticosteroids (glucocorticoids and mineralocor-ticoids), which differ in activities. In humans, cortisol is the main glucocorticoid, and aldosterone is a main mineralocorticoid. Steroid therapy causes severe potential side effects, hence a careful consideration is always exercised before starting therapy. These are used in variety of disorders such as rheumatic disorder, renal disease, allergic manifestation, bronchial asthma, skin diseases, infectious diseases, malignancy, and hepatic diseases. 

Bondy PK Disorders of the adrenal cortex, in Wilson JD, Foster DW (eds) Textbook of Endocrinology. Saunders, New York, 1985, pp. 816-890. Carroll MC, Campbell RD, Porter RR Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man. Proc Natl AcadSci USA 82 521-525,1985. 

New MI, Wilson RC Steroid disorders in children congenital adrenal hyperplasia and apparent mineralocorticoid excess. Proc Natl Acad Sci USA 96 12790-12797,1999. 

Today, it is well known that the introduction of a chlorine or fluorine atom at the C-9 position of the natural adrenal substances cortisone and hydrocortisone (and of their dehydro-analogues) markedly enhances the anti-inflammatory activity of these agents, and is accompanied by a striking increase in both salt and water retention [14]. These undesirable side effects, which are manifested generally by 9-halo-steroids, preclude their use systemically in the management of disorders that are normally responsive to adrenocortical steroid therapy. 

Addison s disease an endocrine disorder associated with the adrenal gland, when low levels of steroid hormones are produced. 

There are three other recognised varieties of disorders leading to congenital adrenal hyperplasia, including 3/3-hydroxysteroid dehydrogenase deficiency. Patients with this defect have grossly elevated levels of 3/3-hydroxy-5-ene steroids in their plasma and urine. Complete lack of the enzyme is incompatible with life however, an incomplete deficiency has been reported [262,263] where GC-MS identification of saturated C19 and C21 steroids revealed that some enzyme activity was present in the liver. 

Uses. Adrenal steroids should be considered a symptomatic and sometimes curative, but not preventive, treatment. Ideally a potent steroid (see below) should be given only as a short course and reduced as soon as the response allows. Corticosteroids are most useful for eczematous disorders (atopic, discoid, contact) and other inflammatory conditions save those due to infection. Dilute corticosteroids are useful in psoriasis (see p. 309). 

Contraindications to the use of adrenal steroids for suppressing inflammation are all relative, depending on the advantage to be expected. They should be used only for serious reasons if the patient has diabetes, a history of mental disorder or peptic ulcer, epilepsy, tuberculosis, hypertension or heart failure. The presence of any infection demands that effective chemotherapy be begun before the steroid, but there are exceptions (some viral infections, see above). Topical corticosteroid applied to an inflamed eye (with the very best of intention) can be disastrous if the inflammation is due to herpes virus. 

The science of endocrinology was developing rapidly at this time. Outstanding was the isolation of insulin for treatment of diabetes by Banting in the early 1920s. Continuing research in this field led to the development of many hormones for treatment of a wide variety of disorders, especially the adrenal cortical steroid hormone (ACTH), cortisone, and thyroxine. 

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