Adrenal gland

The adrenal glands, also known as suprarenal glands, are paired endocrine organs situated above the kidneys. They produce a wide range of hormones that are essential for maintaining physiological stability, including steroid hormones from the adrenal cortex and catecholamines from the adrenal medulla. These hormones regulate metabolism, stress responses, immune modulation, fluid and electrolyte balance, and aspects of sexual development. Because of their wide-ranging influence, diseases of the adrenal glands can lead to significant endocrine disorders. Their structure, blood supply, hormone synthesis, and functional specialisation make them among the most complex endocrine glands in the human body.

Anatomy and Structural Organisation

Each adrenal gland lies in the retroperitoneum on the superior pole of each kidney, enclosed within the renal fascia and cushioned by perirenal fat. The right adrenal gland is typically pyramidal in shape, while the left is semilunar and slightly larger. Both glands are small—approximately 5 cm long, 3 cm wide, and up to 1 cm thick—with a combined adult weight of about 7–10 grams. Their yellowish colour reflects their high lipid content, essential for steroid hormone synthesis.
A weak connective-tissue septum separates each gland from its respective kidney. The adrenal glands are closely related to the crura of the diaphragm, to which they are anchored by fascial connections. Despite their small size, they possess a remarkably rich vascular supply.
Structurally, each gland is composed of two distinct regions:

• Adrenal cortex – the outer, thicker portion responsible for steroid hormone synthesis.
• Adrenal medulla – the central region producing catecholamines.

These two regions differ embryologically, functionally, and histologically, but their hormonal output interacts to support whole-body homeostasis.

Adrenal Cortex: Zones and Hormonal Output

The adrenal cortex is organised into three concentric zones, each of which synthesises different steroid hormones from cholesterol precursors. Histological examination reveals distinct cellular characteristics in each layer, corresponding to specialised functions.

Zona glomerulosa

The outermost layer, immediately beneath the fibrous capsule, consists of cells arranged in small arched clusters. This zone is the principal site for aldosterone synthesis, a mineralocorticoid crucial for long-term regulation of blood pressure and electrolyte balance. Aldosterone production relies on the enzyme aldosterone synthase and is regulated primarily by angiotensin II and extracellular potassium. Its action on the distal convoluted tubules and collecting ducts of the kidneys promotes sodium reabsorption and potassium and hydrogen-ion excretion, thereby influencing extracellular fluid volume and arterial pressure.

Zona fasciculata

Situated between the other two zones, the zona fasciculata accounts for nearly 80 per cent of the adrenal cortex volume. Its cells, arranged in radial cords, contain abundant lipid droplets, smooth endoplasmic reticulum, and mitochondria—hallmarks of steroidogenic activity. This zone primarily produces glucocorticoids, notably cortisol, which regulate carbohydrate, protein, and fat metabolism, support stress adaptation, and suppress immune responses. Cortisol secretion follows a circadian rhythm and is tightly controlled by the hypothalamic–pituitary–adrenal (HPA) axis.

Zona reticularis

The innermost cortical layer forms irregular clusters of smaller cells containing modest cytoplasm and occasional lipofuscin pigment. This zone produces adrenal androgens, such as dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and androstenedione. Although weak in androgenic potency, these hormones serve as precursors for more potent sex steroids produced in the gonads and peripheral tissues, contributing to pubertal development and secondary sexual characteristics.

Adrenal Medulla and Catecholamine Secretion

The adrenal medulla is composed primarily of chromaffin cells, modified postganglionic sympathetic neurons derived from neural crest tissue. It lacks distinct synapses and instead releases hormones directly into the bloodstream. Stimulated by preganglionic sympathetic fibres originating from spinal cord segments T5–T11, these cells secrete approximately 80 per cent adrenaline and 20 per cent noradrenaline.
Catecholamines facilitate the fight-or-flight response by increasing heart rate, blood pressure, glucose availability, and blood flow to skeletal muscles. As a specialised sympathetic ganglion, the medulla integrates neural and endocrine components of the stress response.

Blood Supply and Venous Drainage

The adrenal glands have one of the highest blood-flow rates per gram of tissue in the body. Each gland is typically supplied by three arterial sources:

• Superior suprarenal arteries, branches of the inferior phrenic arteries.
• Middle suprarenal artery, a direct branch of the abdominal aorta.
• Inferior suprarenal artery, originating from the renal artery.

Within the capsule, these arteries form a branching network that delivers blood to both cortical and medullary tissues. Venous drainage is via a single suprarenal vein on each side: the right drains directly into the inferior vena cava, whereas the left drains into the left renal or inferior phrenic vein. The central adrenomedullary vein possesses distinctive longitudinal smooth muscle bundles, contributing to rapid catecholamine release.

Variations and Developmental Anomalies

The adrenal glands may occasionally be absent, malformed, or fused. Fusion behind the aorta can occur and is often associated with anomalies of renal development, including agenesis or fusion of the kidneys. Partial or complete cortical absence may also occur, as can ectopic adrenal tissue, which may be found in unusual anatomical locations due to embryological migration patterns.

Functions and Hormonal Regulation

The adrenal glands secrete multiple hormone classes essential for physiological regulation. These hormones undergo metabolism either within the gland or in peripheral tissues.

Corticosteroids

Corticosteroids include:

• Mineralocorticoids (primarily aldosterone) – regulate sodium and potassium balance, extracellular fluid volume, and blood pressure.
• Glucocorticoids (predominantly cortisol) – modulate metabolism, stress responses, and immune activity.
• Adrenal androgens – contribute to the synthesis of sex hormones.

Mineralocorticoids

Aldosterone enhances sodium retention in the kidneys, colon, and sweat glands while promoting potassium and hydrogen-ion excretion. These effects help maintain extracellular volume and normal blood pressure. The renin–angiotensin–aldosterone system and plasma potassium concentration are the primary regulators of aldosterone release.

Glucocorticoids

Cortisol influences metabolic pathways by increasing glucose production, mobilising amino acids, and modulating lipid metabolism. It ensures adequate energy availability during stress and plays a critical role in maintaining vascular tone and immune balance.

Clinical Significance and Associated Diseases

Dysfunction of the adrenal glands leads to several endocrinopathies. Overproduction of cortisol causes Cushing’s syndrome, while insufficient glucocorticoid and mineralocorticoid production results in Addison’s disease. Congenital adrenal hyperplasia represents a group of genetic disorders characterised by impaired steroid biosynthesis and consequent hormonal imbalance. Tumours of the adrenal cortex or medulla, both benign and malignant, are often discovered incidentally through imaging conducted for unrelated conditions.