adrenal glands

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Adrenal Glands

Overview

The paired adrenal (suprarenal) glands sit atop the superior pole of each kidney in the retroperitoneal space. Each weighs approximately 4 g. Despite their small size, they receive one of the highest rates of blood flow per gram of any organ in the body. Each gland is functionally two distinct organs - an outer cortex and an inner medulla - with different embryological origins, structures, and hormonal products.

Medical Physiology (Barrett), p. 50-1

Embryology

Region	Embryological Origin	Key Point
Cortex	Mesoderm (coelomic epithelium)	Differentiates by gestational week 8; fetal cortex involutes after birth
Medulla	Neural crest cells	Migrate into developing cortex; differentiate into chromaffin cells

The fetal adrenal cortex is distinct from the adult cortex and is responsible for steroid production throughout intrauterine life. It involutes soon after birth and is replaced by the three-layered adult cortex.

Langman's Medical Embryology; Costanzo Physiology 7e, p. 431

Gross Anatomy & Blood Supply

The adrenal gland has no hilum. Blood enters via three suprarenal arteries arising from larger abdominal vessels, which penetrate the capsule independently and immediately branch into a subcapsular arterial plexus. From there, separate arterioles supply the cortex and medulla. Notably, the medulla receives a dual blood supply:

Direct arterial blood from medullary arterioles
Venous blood draining from cortical capillaries (meaning medullary chromaffin cells are exposed to high concentrations of cortical steroids)

Venous drainage is via the suprarenal veins.

Junqueira's Basic Histology 17e, p. 1020

Adrenal Cortex (80% of gland mass)

The cortex has three concentric zones, each producing distinct hormones:

Adrenal gland zones and their secretions

The Three Zones (GFR mnemonic - outside to inside)

Zone	Location	Hormone	Class
Zona Glomerulosa	Outermost	Aldosterone	Mineralocorticoid
Zona Fasciculata	Middle (widest)	Cortisol	Glucocorticoid
Zona Reticularis	Innermost	DHEA, DHEAS, Androstenedione	Androgens

All cortical steroids are synthesized from cholesterol as the precursor.

Histology of Cortical Cells

Cortical cells (adrenocortical cells) share features typical of all steroid-secreting cells:

Acidophilic cytoplasm rich in lipid droplets (cholesterol esters)
Abundant smooth ER (SER) - contains enzymes for cholesterol synthesis and steroid conversion
Mitochondria with tubular/vesicular cristae (not the usual shelf-like cristae) - contain enzymes for cholesterol → pregnenolone conversion and other steroidogenic steps
Steroids are not stored in granules - as lipid-soluble molecules, they diffuse freely across the plasma membrane
Junqueira's Basic Histology 17e, p. 1021

Cortisol (Glucocorticoid)

Synthesis: Zona fasciculata and (to a lesser degree) zona reticularis.

Key actions across body tissues:

Liver: Activates gluconeogenesis; promotes glycogen synthesis
Muscle/adipose: Mobilizes amino acids and fatty acids (catabolic)
Immune system: Anti-inflammatory; suppresses lymphocyte and eosinophil activity; stabilizes mast cell membranes
Bone: Inhibits osteoblasts; chronic excess causes osteoporosis
CNS: Affects mood, cognition, appetite
Cardiovascular: Supports vascular responsiveness to catecholamines

Regulation - HPA Axis:

Hypothalamus → CRH (41-amino acid peptide, from paraventricular nuclei) → Anterior pituitary corticotrophs → ACTH → Adrenal cortex → Cortisol

Cortisol exerts negative feedback at three points: (1) directly inhibits hypothalamic CRH, (2) via hippocampal neurons that synapse on the hypothalamus, (3) inhibits CRH action on the anterior pituitary

Diurnal rhythm: Cortisol secretion is pulsatile (~10 bursts/day). Levels are lowest around midnight and peak just before awakening (~8 AM). The pre-awakening burst accounts for ~50% of total daily cortisol output. This pattern is driven by ACTH, which in turn is driven by CRH. The diurnal rhythm is abolished by coma, blindness, or constant light/dark exposure.

Costanzo Physiology 7e, pp. 435-436

Aldosterone (Mineralocorticoid)

Synthesis: Zona glomerulosa exclusively.

Actions: Promotes Na⁺ reabsorption and K⁺ excretion in the renal collecting tubule; increases water retention; raises blood pressure.

Regulation: Primarily by the renin-angiotensin-aldosterone system (RAAS) and plasma K⁺ levels. ACTH plays only a minor role (unlike with cortisol).

Structurally, aldosterone differs from cortisol by lacking the -OH at C17 and having an aldehyde group at C18 - a seemingly minor difference that completely eliminates glucocorticoid activity at physiological concentrations.

Adrenal Androgens

Synthesis: Zona reticularis.

Key hormones: Dehydroepiandrosterone (DHEA), DHEAS, and androstenedione - all weak androgens (far weaker than testosterone or DHT).

DHEAS circulates at the highest concentration of any adrenal steroid and shows no diurnal variation
Plasma DHEA follows the same diurnal pattern as cortisol
In women, adrenal androgens are a significant source of androgen activity

Adrenal Medulla (20% of gland mass)

Origin: Neuroectoderm (neural crest). The medulla is essentially a modified sympathetic ganglion.

Cell type: Chromaffin cells (named for their staining with chromium salts), innervated by preganglionic sympathetic neurons.

Hormones: Catecholamines

Epinephrine (adrenaline): ~80% of output; synthesized from norepinephrine via PNMT enzyme (induced by high local cortisol from cortical venous blood)
Norepinephrine: ~20% of output; also produced at sympathetic nerve terminals elsewhere

Catecholamines are stored in granular complexes with chromogranins (49 kDa proteins), Ca²⁺, and ATP, and released by exocytosis in response to preganglionic stimulation.

Fight-or-flight effects:

Epinephrine: increases heart rate, dilates bronchioles, dilates skeletal/cardiac muscle arteries, elevates blood glucose (glycogenolysis)
Norepinephrine: constricts splanchnic and skin vessels, redirects blood to heart, muscles, and brain
Both: promote glycogenolysis and lipolysis
Junqueira's Basic Histology 17e, p. 1027

Clinical Summary: Major Disorders

Disorder	Pathology	Key Features
Cushing's syndrome	Cortisol excess	Central obesity, moon face, striae, hypertension, hyperglycemia, osteoporosis
Addison's disease	Primary adrenocortical insufficiency	Fatigue, hypotension, hyponatremia, hyperkalemia, hyperpigmentation (↑ ACTH/MSH)
Primary hyperaldosteronism (Conn's)	Aldosterone excess	Hypertension, hypokalemia, metabolic alkalosis
Pheochromocytoma	Catecholamine-secreting medullary tumor	Paroxysmal hypertension, headache, sweating, palpitations; "10% tumor"
Congenital adrenal hyperplasia (CAH)	Enzyme defect in steroidogenesis (usually 21-hydroxylase)	Virilization, salt-wasting, ↑ ACTH driving adrenal hyperplasia

Summary Table

Feature	Cortex	Medulla
Origin	Mesoderm	Neural crest (neuroectoderm)
% of gland	~80%	~20%
Hormones	Cortisol, aldosterone, DHEA	Epinephrine, norepinephrine
Hormone class	Steroids	Catecholamines (amine)
Storage	Not stored; diffuse freely	Stored in chromaffin granules
Regulation	HPA axis (cortisol/androgens); RAAS + K⁺ (aldosterone)	Sympathetic innervation

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