Adrenocortical Hyperfunction: Hyperadrenalism785 medulla. Intervening is the broad zona fasciculata, which makes up about 75% of the total cortex.
The adrenal cortex synthesizes three different types of steroids:
Glucocorticoids (principally cortisol), synthesized primarily in the zona fasciculata, with a small contribution from the zona reticularis
Mineralocorticoids, the most important being aldosterone, generated in the zona glomerulosa
Sex steroids (estrogens and androgens), produced largely in the zona reticularis
The adrenal medulla is composed of chromaffin cells, which synthesize and secrete catecholamines, mainly epinephrine. This section deals first with disorders of the adrenal cortex and then of the medulla. Diseases of the adrenal cortex can be conveniently divided into those associated with cortical hyperfunction or hypofunction.
ADRENOCORTICAL HYPERFUNCTION: HYPERADRENALISM
There are three distinctive hyperadrenal clinical syndromes, each caused by abnormal production of one or more of the hormones produced by the three layers of the cortex:
Cushing syndrome, characterized by an excess of cortisol
Hyperaldosteronism, caused by an excess of mineralocorticoid
Adrenogenital or virilizing syndromes, caused by an excess of androgens
The clinical features of some of these syndromes show some similarities because of the shared functions of adrenal steroids.
Hypercortisolism: Cushing Syndrome
Hypercortisolism (Cushing syndrome) is caused by elevated glucocorticoid levels. In clinical practice, the vast majority of cases of Cushing syndrome are the result of administration of exogenous glucocorticoids (iatrogenic). The remaining cases are endogenous, and the three most common disorders are as follows (
Fig. 20.34
Primary hypothalamic-pituitary diseases associated with hypersecretion of ACTH
Secretion of ectopic ACTH by nonpituitary neoplasms
Primary adrenocortical neoplasms (adenoma or carcinoma) and, rarely, primary cortical hyperplasia
Primary hypothalamic-pituitary disease associated with hypersecretion of ACTH, also known as Cushing disease,
Fig. 20.34 Schematic representation of the various forms of Cushing syndrome: The three endogenous forms, as well as the more common exogenous (iatrogenic) form. ACTH, Adrenocorticotropic hormone.
accounts for approximately 70% of cases of spontaneous, endogenous Cushing syndrome. The prevalence of this disorder is about four times higher among women than among men, and it occurs most frequently during young adulthood (the twenties and thirties). In the vast majority of cases, the pituitary gland contains an ACTH-producing microadenoma that does not produce mass effects in the brain. In some cases there is a microadenoma and rarely, the anterior pituitary contains areas of corticotroph cell hyperplasia without a discrete adenoma. Corticotroph cell hyperplasia may be primary or, much less commonly, secondary to excessive ACTH release by a hypothalamic corticotropinreleasing hormone (CRH)–producing tumor. The adrenal glands in patients with Cushing disease show variable degrees of bilateral nodular cortical hyperplasia (discussed later), secondary to the elevated levels of ACTH (“ACTHdependent” Cushing syndrome). The cortical hyperplasia is, in turn, responsible for the hypercortisolism.