Adrenal Gland Disorders
Hypofunction or insufficiency of adrenal cortex results in Addison’s disease
Hyperfunction or tumors in
Zona glomerulosa → hyperaldosteronism
Zona fasciculata → hypercortisolism (Cushing’s syndrome)
Zona reticularis → adrenogenital syndrome
Medulla → pheochromocytoma
All steroids are generated from cholesterol
The types of steroids a cell makes depend upon the types and concentrations of
enzymes a cell has
Cholesterol → pregnenolone
Mutations affecting enzymes primarily responsible for the production of cortisol and
mineralocorticoids can have secondary effects on sex steroid production.
No glucocorticoids, mineralocorticoids, androgens, estrogens
Salt excretion in urine
Most common form of CAH
Usually a partial deficiency
ACTH elevated, causing an increased shift to sex hormones and
Decreased cortisol, aldosterone, corticosterone
Increased deoxycorticosterone leading to fluid retention and hypertension
Masculinization Adrenocortical Disorders: Zona Reticularis
21-hydroxylase deficiency impairs the synthesis of both cortisol and aldosterone. The
resultant decrease in feedback inhibition causes increased secretion of ACTH, resulting
ultimately in adrenal hyperplasia and increased synthesis of testosterone.
Congenital adrenal hyperplasia
Deficiency of 21- or 11β-hydroxylase in adrenals can have secondary effects on sex
Virilization (adrenogenital syndrome; female pseudohermaphorditism)
Virilization can be ameliorated by administering oral steroids to the mother
Multiple Actions of Cortisol
Cortisol has powerful anti-inflammatory effects.
Inhibits phospholipase A 2rom converting membrane phospholipids to
Inhibits cyclooxygenase from converting arachidonic acid to prostaglandins
Cortisol exerts catabolic actions on most tissues, with the exception of the liver, on which
it exerts anabolic effects.
Potentiates actions of epinephrine and glucagon
Glucose uptake ↓
Protein catabolism ↑
Glucose uptake ↓
Cortisol increases blood pressure in several ways. It facilitates activity of the sympathetic nervous system by increasing the
expression of α- and β-adrenergic receptors in multiple tissues.
At increased levels, cortisol exerts mineralocorticoid actions on the kidneys
because it is similar in structure to aldosterone. This stimulates renal sodium
reabsorption and causes plasma volume expansion.
At supraphysiologic levels, cortisol weakens bones by stimulating bone-degrading cells
In addition, cortisol reduces intestinal absorption of calcium, which can
precipitate a compensatory increased in parathyroid hormone secretion, causing
further bone breakdown.
Etiology and pathogenesis
Hyposecretion of adrenal cortex
Autoimmune, infections (e.g., TB), injury
Inadequate secretion of ACTH (anterior pituitary)
Iatrogenic; prolonged exogenous corticosteroid therapy
Lack of CRH secretion (hypothalamus)
Amenorrhea Fat loss
Muscle weakness and atrophy
↓ HCO 3
Signs and symptoms result from the deficiency of glucocorticoids and
mineralocorticoids. Adrenal androgens are also missing, but this deficiency is
less obvious clinically.
Autoimmune Polyendocrine Disorder, APS
Autoimmune adrenalitis, by far the most common cause of primary adrenal insufficiency
in developed countries, can occur in one of two clinical settings
Autoimmune polyendocrine syndrome type 1 (APS1) is also known as
autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy.
APS1 is characterized by chronic mucocutaneous candidiasis and
abnormalities of skin, dental enamel, and nails (ectodermal dystrophy)
occurring in association with a combination of organ-specific autoimmune
APS1 is caused by mutations in the autoimmune regulator (AIRE) gene
on chromosome 21q22 Autoimmune polyendocrine syndrome type 2 (APS2) usually starts in early
adulthood and presents as a combination of adrenal insufficiency and
autoimmune thyroiditis or type I diabetes.
Unlike in APS1, mucocutaneous candidiasis, ectodermal dysplasia, and
autoimmune hypoparathyroidism do not occur.
Most common form of the