Steroids of the Adrenal Cortex (Physiology)

The steroids of the adrenal cortex include glucocorticoids (principally cortisol), mineralocorticoids (aldosterone), and androgens.

The principal glucocorticoid produced by the adrenal cortex in mammals is cortisol.

The main mineralocorticoid produced by the adrenal cortex is aldosterone.

Excess cortisol production leads to a condition called Cushing’s syndrome.

Adrenal insufficiency, specifically primary adrenal insufficiency, is associated with Addison’s disease.

Blood flows from the outer cortex to the inner medulla in the adrenal gland.

The adrenal cortex exhibits functional zonation due to layer-specific enzymes and the inhibition of different enzymes in subsequent layers during steroid synthesis.

Functional zonation in the adrenal cortex leads to the production of different hormones in each layer.

Mineralocorticoids regulate salt and water balance in the body.

Glucocorticoids regulate metabolism and immune function.

Stress increases the release of adrenal steroids, but minimal levels are essential for normal function.

Androgens produced by the adrenal cortex, often called "weak androgens," contribute to various physiological processes in the body.

Yes, cortisol and aldosterone have similar affinity for the aldosterone receptor.

Cortisol doesn't stimulate salt and water retention like aldosterone because it is rapidly metabolized to inactive cortisone in the kidney.

The enzyme required for the metabolism of cortisol to cortisone in the kidney is 11beta-hydroxysteroid dehydrogenase type 2 (11B-HSD2).

A rare inactivating mutation of 11B-HSD2 leads to a syndrome called apparent mineralocorticoid excess (AME).

Liquorice contains a compound called glycyrrhizinic acid that blocks the enzyme 11B-HSD2, leading to increased cortisol activity and potential mineralocorticoid effects.

Glucocorticoids decrease glucose utilization, a process known as glucose sparing.

Glucocorticoids promote lipolysis, gluconeogenesis (to maintain plasma glucose concentration), and proteolysis (to supply amino acid substrates for gluconeogenesis).

Glucocorticoids play a vital role in the maintenance of blood glucose levels, which is essential for survival during fasting.

Glucocorticoids are required for vascular integrity.

Hypocortisolism leads to inappropriate vasodilation and hypotension.

Hypercortisolism leads to hypertension.

Glucocorticoids have anti-inflammatory and immunosuppressive effects.

Glucocorticoids have been used in therapy for over 60 years.

Glucocorticoid therapy is highly profitable and extremely effective, but it can have unintended side effects, making it a double-edged sword.

ACTH is synthesized from pro-opiomelanocortin (POMC) prohormone.

The ACTH receptor belongs to the melanocortin group of receptors.

Different forms of melanocyte-stimulating hormones can bind to melanocortin receptors, including alpha-, beta-, and gamma-melanocyte-stimulating hormones.

Besides the ACTH receptor, ACTH can also bind to other melanocortin receptors.

Excess circulating ACTH may cause skin pigmentation due to its effects on melanocytes.

Clinical features of primary adrenal insufficiency include low circulating adrenal steroids, high ACTH levels, normal to low plasma sodium (Na+), normal to high plasma potassium (K+), and elevated plasma renin. It may be unmasked by significant stress or illness, leading to adrenal crisis.

Adrenal insufficiency can be caused by Addison's disease (primary adrenal insufficiency), hypopituitarism (secondary hypocortisolism), failure in the renin-angiotensin-aldosterone system (secondary hypoaldosteronism), or enzyme defects in steroid synthesis pathways.

Cushing's syndrome is characterized by excess glucocorticoid levels.

Cushing's syndrome can be ACTH-dependent, such as in Cushing's disease due to increased ACTH secretion (typically due to a pituitary adenoma), or ACTH-independent, such as adrenal adenoma or carcinoma, ectopic ACTH-secreting tumors, or iatrogenic causes (exogenous glucocorticoid therapy).

Clinical features of hypercortisolism include hypertension, hyperglycemia, truncal obesity, fatigue, muscle weakness, virilization (hirsutism in females), and mood or psychiatric disturbances.

The first step is to confirm hypersecretion of cortisol through tests such as 24-hour urinary cortisol measurement or cortisol measurement at the nadir of secretion (around midnight).

The cause of Cushing's syndrome is determined by assessing plasma ACTH levels and performing the dexamethasone suppression test.

Failure of cortisol suppression in response to both low and high doses of dexamethasone suggests an ectopic source of ACTH secretion, such as an ACTH-secreting tumor elsewhere in the body.

The most common cause of Cushing's syndrome is iatrogenic, which is typically due to the administration of exogenous glucocorticoids.

Exogenous glucocorticoids activate the cortisol receptor. At high doses, they can suppress the hypothalamic-pituitary-adrenal (HPA) axis, leading to adrenal cortex atrophy due to lack of adrenocorticotropic hormone (ACTH) stimulation.

Adrenal cortex atrophy reduces the responsiveness of the adrenal glands to ACTH. After cessation of exogenous glucocorticoid therapy, it may take several days for the adrenal glands to become responsive to ACTH again.