Adrenocortical Mineralocorticoid

Adrenocortical hormone (Section 27.6) A steroid hormone secreted by the adrenal glands. There are two types of adrenocortical hormones mineralocorticoids and glucocorticoids. 

This section of the chapter discusses the hormones produced by the adrenal cortex or the adrenocortical hormones, which are the glucocorticoids and mineralocorticoids. These hormones are essential to life and influence many organs and structures of the body. The glucocorticoids and mineralocorticoids are collectively called corticosteroids. 

Fludrocortisone is used for replacement therapy for primary and secondary adrenocortical deficiency. Even though this drug lias both mineralocorticoid and glucocorticoid activity, it is used only for its mineralocorticoid effects. 

Mitotane (o,p-DDD) -adrenocortical cytotoxin -nausea and vomiting -CNS toxicity—lethargy, vertigo, sedation, dizziness -adrenal insufficiency—must use replacement doses of mineralocorticoids and glucocorticoids -diarrhea -fever -wheezing -flushing... 

Pharmacology The naturally occurring adrenal cortical steroids have both anti-inflammatory (glucocorticoid) and salt-retaining (mineralocorticoid) properties. These compounds are used as replacement therapy in adrenocortical deficiency states and may be used for their anti-inflammatory effects. 

Deoxycortone acetate Modified form of natural corticosteroid (deoxycortone). Is a mineralocorticoid, displays no significant glucocorticoid action Used to treat Addison s disease and other adrenocortical deficiency states... 

The steroidal nature of adrenocortical hormones was established in 1937, when Reichstein synthesized desoxycorticosterone. Eventually it was clearly established that the adrenal cortex elaborated a number of hormones and that these compounds differed in their amount of inherent metabolic (glucocorticoid) and electrolyte regulating (mineralocorticoid) activity. The actions of these hormones extend to almost every cell in the body. In humans, hydrocortisone (cortisol) is the main carbohydrate-regulating steroid, and aldosterone is the main electrolyte-regulating steroid. 

The remaining steroid lipids constitute two main classes of steroid hormones sex hormones and adrenocortical hormones. The sex hormones include androgens (testosterone, androsterone), estrogens (estrone, estradiol), and progestins (progesterone). The adrenocortical hormones include mineralocorticoids (aldosterone) and glucocorticoids (hydrocortisone). 

This compound, a potent steroid with both glucocorticoid and mineralocorticoid activity, is the most widely used mineralocorticoid. Oral doses of 0.1 mg two to seven times weekly have potent salt-retaining activity and are used in the treatment of adrenocortical insufficiency associated with mineralocorticoid deficiency. These dosages are too small to have important anti-inflammatory or antigrowth effects. 

Substitution therapy is used in cases of primary and secondary adrenocortical insufficiency the aim is to provide glucocorticoids and mineralocorticoids in physiological amounts, and the better the dosage regimen is adapted to the individual s needs, the less the chance of adverse effects (1). 

Drugs with mineralocorticoidlike activity (aldosterone agonists) are frequently administered as replacement therapy whenever the natural production of mineralo-corticoids is impaired. Mineralocorticoid replacement is usually required in patients with chronic adrenocortical insufficiency (Addison disease), following adrenalectomy, and in other forms of adrenal cortex hypofunction. These conditions usually require both mineralocorticoid and glucocorticoid replacement. 

Replacement therapy for secondary or tertiary adrenocortical insufficiency These deficiencies are caused by a defect either in CRF production by the hypothalamus or corticotropin production by the pituitary (see p. 247). [Note Under these conditions, the adrenal cortex synthesis of mineralocorticoids is less impaired than that of glucocorticoids.] The adrenal cortex responds to corticotropin administration by synthesizing and releasing the adrenal corticosteroids. Hydrocortisone is also used for these deficiencies. 

The short-term action of ACTH on the adrenocortical cell is the stimulation of the conversion of cholesterol to glucocorticoid, mineralocorticoid or androgen-precursor steroids (Fig. 2). The conversion of cholesterol to the end-product steroids involves two mitochondrial cytochrome P-450 enzymes, cytochrome P-450scc (cho-... 

The adrenal cortex (AC) produces the glucocorticoid cortisol (hydrocortisone) in the zona fasciculata and the mineralocorticoid aldosterone in the zona glomerulosa. Both steroid hormones are vitally important in adaptation responses to stress situations, such as disease, trauma, or surgery. Cortisol secretion is stimulated by hypophyseal ACTH aldosterone secretion by angiotensin II in particular (p. 128). In AC failure (primary adrenocortical insuf ciency, Addison disease), both cortisol and aldosterone must be replaced when ACTH production is deficient (secondary adrenocortical insuf ciency), cortisol alone needs to be replaced. Cortisol is effective when given orally (30 mg/day, 2/3 a.m 1 /3 p.m.). In stress situations, the dose is raised 5- to 10-fold. Aldosterone is poorly effective via the oral route instead, the mineralocorticoid fludrocortisone (0.1 mg/day) is given. 

Adrenocortical steroids are used for their action on specific cancers and also to treat some of the complications of cancer, e.g. hypercalcaemia, raised intracranial pressure. Their principal use is in cancer of the lymphoid tissues and blood. In leukaemias they may also reduce the incidence of complications such as haemolytic anaemia and thrombocytopenia. A glucocorticoid is preferred, e.g. prednisolone, as high doses are used and mineralocorticoid actions are not needed and cause fluid retention. 

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