Adrenal Cortex

The adrenal cortex is the outer portion of the adrenal gland and is responsible for producing a wide range of vital steroid hormones involved in electrolyte balance, stress response, metabolism, and sexual development. It comprises approximately 80–90% of the adrenal gland’s volume and is subdivided into three distinct histological zones: the zona glomerulosa, zona fasciculata, and zona reticularis. Each zone produces specific classes of steroid hormones under the regulation of different endocrine signals.

Histological Structure

The adrenal cortex is organized into three concentric zones, each distinguishable under the microscope by the arrangement of cells and their staining characteristics:

Zone	Position	Primary Hormones	Stimulated By
Zona Glomerulosa	Outermost	Aldosterone (mineralocorticoid)	Renin–angiotensin–aldosterone system (RAAS)
Zona Fasciculata	Middle, largest zone	Cortisol (glucocorticoid)	Adrenocorticotropic hormone (ACTH)
Zona Reticularis	Innermost cortical zone	Androgens (e.g., DHEA, androstenedione)	ACTH and other poorly understood signals

The cortex is surrounded by a thin connective tissue capsule, and the cells within the cortex are arranged in radial cords surrounded by sinusoidal capillaries, allowing efficient hormonal release into the bloodstream.

Hormone Classes and Functions

1. Mineralocorticoids (Aldosterone)

• Produced in the zona glomerulosa
• Regulates sodium and potassium levels in the distal nephron of the kidney
• Promotes sodium reabsorption and potassium excretion
• Indirectly maintains blood pressure and extracellular fluid volume

2. Glucocorticoids (Cortisol)

• Produced in the zona fasciculata
• Regulates glucose metabolism, protein catabolism, and fat distribution
• Suppresses the immune system and inhibits inflammation
• Increases during stress, fasting, or infection

3. Adrenal Androgens (DHEA, Androstenedione)

• Produced in the zona reticularis
• Serve as precursors to sex steroids (testosterone, estrogen) in peripheral tissues
• Minor role in males but significant in females for pubic/axillary hair and libido

Regulation

Renin–Angiotensin–Aldosterone System (RAAS)

• Low blood pressure or sodium → renin release from juxtaglomerular cells in the kidney
• Renin converts angiotensinogen → angiotensin I → angiotensin II
• Angiotensin II stimulates aldosterone release from zona glomerulosa

Hypothalamic–Pituitary–Adrenal (HPA) Axis

• Stress or circadian signals stimulate the hypothalamus to release CRH (corticotropin-releasing hormone)
• CRH stimulates the anterior pituitary to release ACTH
• ACTH stimulates cortisol (and to a lesser extent androgen) production in the cortex
• Negative feedback: Cortisol inhibits CRH and ACTH secretion

Developmental Origin

• Adrenal cortex arises from mesoderm during fetal development
• The fetal adrenal cortex is initially large and produces precursor hormones for placental estrogen synthesis
• Postnatally, the adult cortical zones form progressively

Blood Supply

The adrenal cortex is richly vascularized:

• Arterial supply: Superior, middle, and inferior suprarenal arteries
• Blood flows from the capsule inward through sinusoids, bathing all three zones
• Venous drainage: Central adrenal vein (right → IVC; left → renal vein)

Histological Features

Zone	Cell Arrangement	Appearance
Zona Glomerulosa	Small, rounded clusters	Dense nuclei, fewer lipid droplets
Zona Fasciculata	Straight cords of cells	Lipid-rich, “foamy” cytoplasm
Zona Reticularis	Irregular, branching network	Smaller, darker cells with fewer lipids

Clinical Significance

Addison’s Disease (Primary Adrenal Insufficiency)

• Autoimmune destruction of adrenal cortex → ↓ cortisol and aldosterone
• Symptoms: fatigue, hypotension, weight loss, hyperpigmentation (↑ACTH)
• Treatment: corticosteroid and mineralocorticoid replacement

Cushing’s Syndrome

• Excess cortisol from adrenal tumor or prolonged steroid use
• Symptoms: moon face, central obesity, purple striae, hypertension, muscle wasting
• Diagnosis via dexamethasone suppression test or ACTH assays

Congenital Adrenal Hyperplasia (CAH)

• Genetic enzyme deficiency (commonly 21-hydroxylase) → ↓ cortisol, ↑ ACTH → adrenal hyperplasia
• Results in overproduction of androgens → virilization in females, early puberty in males
• Treatment: corticosteroids to suppress ACTH

Hyperaldosteronism (Conn’s Syndrome)

• Excess aldosterone → sodium retention, hypokalemia, hypertension
• Caused by adrenal adenoma or bilateral adrenal hyperplasia

Imaging and Surgical Considerations

• CT or MRI used to evaluate adrenal masses and hyperplasia
• Adrenal cortical tumors may be functional (hormone-secreting) or non-functional
• Adrenalectomy requires preservation of adrenal vein and careful distinction of cortex vs medulla