The metabolism of aldosterone is similar to that of cortisol, about 50 mcg/24 h appearing in the urine as conjugated tetrahydroaldosterone. Approximately 5–15 mcg/24 h is excreted free or as the 3-oxo glucuronide.
DOC, which also serves as a precursor of aldosterone (Figure 39–1), is normally secreted in amounts of about 200 mcg/d. Its half-life when injected into the human circulation is about 70 minutes. Preliminary estimates of its concentration in plasma are approximately 0.03 mcg/dL. The control of its secretion differs from that of aldosterone in that the secretion of DOC is primarily under the control of ACTH. Although the response to ACTH is enhanced by dietary sodium restriction, due to adaptations, a low-salt diet does not increase DOC secretion. The secretion of DOC may be markedly increased in abnormal conditions such as adrenocortical carcinoma and congenital adrenal hyperplasia with reduced P450c11 or P450c17 activity.
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.
The adrenal cortex secretes large amounts of DHEA and smaller amounts of androstenedione and testosterone. Although these androgens are thought to contribute to the normal maturation process, they do not stimulate or support major androgen-dependent pubertal changes in humans. Studies suggest that DHEA and its sulfate may have other important physiologic actions. If that is correct, these results are probably due to the peripheral conversion of DHEA to more potent androgens or to estrogens and interaction with androgen and estrogen receptors, respectively. Additional effects may be exerted through an interaction with the GABAA and glutamate receptors in the brain or with a nuclear receptor in several central and peripheral sites. The therapeutic use of DHEA in humans has been explored, but the substance has already been adopted with uncritical enthusiasm by members of the sports drug culture and the vitamin and food supplement culture.
The results of a placebo-controlled trial of DHEA in patients with systemic lupus erythematosus have been reported as well as those of a study of DHEA replacement in women with adrenal insufficiency. In both studies a small beneficial effect was seen, with significant improvement of the disease in the former and a clearly added sense of well-being in the latter. The androgenic or estrogenic actions of DHEA could explain the effects of the compound in both situations. In contrast, there is no evidence to support DHEA use to increase muscle strength or improve memory.
Inhibitors of steroid synthesis act at several different steps and one glucocorticoid antagonist acts at the receptor level.