Adrenal Glands: Structure, Hormones, and Disorders

Adrenal Glands

Overview and Anatomy

The adrenal glands are paired endocrine organs located on top of each kidney. They play a crucial role in regulating metabolism, stress response, and electrolyte balance through hormone secretion.

• Location: Superior to the kidneys.

• Structure: Each gland is divided into two distinct regions: cortex (outer layer) and medulla (inner core).

• Functional Independence: The cortex and medulla function almost as separate endocrine organs, each producing different hormones.

Adrenal Cortex: Zones and Hormones

The adrenal cortex is responsible for synthesizing steroid hormones, all derived from cholesterol. It consists of three layers, each producing specific hormones:

• Zona Glomerulosa: Produces aldosterone (a mineralocorticoid).

• Zona Fasciculata: Produces glucocorticoids (mainly cortisol and corticosterone).

• Zona Reticularis: Produces androgens (e.g., dehydroepiandrosterone, DHEA) and small amounts of estrogen.

All cortical hormones are regulated by adrenocorticotropic hormone (ACTH) from the anterior pituitary, which itself is controlled by corticotropin-releasing hormone (CRH) from the hypothalamus.

Adrenal Medulla: Hormones

The adrenal medulla produces catecholamines:

• Epinephrine (adrenaline)

• Norepinephrine (noradrenaline)

These hormones are involved in the body's acute stress response ("fight or flight").

Adrenal Cortex Hormones

Glucocorticoids (Cortisol)

Glucocorticoids are primarily produced in the zona fasciculata. Cortisol is the most important glucocorticoid, essential for survival and stress adaptation.

• Metabolic Effects:

  • Increase blood glucose via gluconeogenesis in the liver

  • Antagonize insulin action

  • Decrease glucose uptake in muscle, fat, and lymph tissue

  • Stimulate protein breakdown and decrease protein synthesis

• Immune and Anti-inflammatory Effects:

  • Suppress immune cell activity (NK cells, T cells, macrophages)

  • Decrease inflammatory cytokines, increase anti-inflammatory cytokines

  • Inhibit bone formation

  • Inhibit ADH and ACTH secretion

  • Stimulate gastric secretions

  • Potentiate catecholamines, thyroid, and growth hormones

  • Affect mood and sleep

• Regulation:

  • ACTH stimulates cortisol release

  • Cortisol secretion follows a diurnal rhythm, peaking 3-5 hours after waking

  • Excess cortisol inhibits further ACTH release (negative feedback)

Mineralocorticoids (Aldosterone)

Aldosterone is produced in the zona glomerulosa and is the principal mineralocorticoid.

• Function:

  • Promotes sodium retention and potassium excretion in the distal nephron

  • Helps regulate blood pressure and fluid balance

  • Increases myocardial contraction and vascular tone

  • Decreases fibrinolysis

• Regulation:

  • Mainly controlled by the renin-angiotensin-aldosterone system (RAAS)

  • Angiotensin II is the primary stimulant

  • Short half-life (~15 minutes), metabolized by the liver and excreted by the kidneys

Androgens and Estrogens

The zona reticularis produces weak androgens (e.g., DHEA), which can be converted to more potent androgens (testosterone) or estrogens in peripheral tissues.

• Function:

  • Contribute to secondary sexual characteristics

  • Peripheral conversion is increased in obesity, hypothyroidism, or liver dysfunction

Adrenal Gland Disorders

Addison's Disease (Primary Adrenal Insufficiency)

Addison's disease is a condition where the adrenal cortex fails to produce adequate amounts of corticosteroids and mineralocorticoids.

• Causes:

  • Autoimmune destruction (most common, 60-70%)

  • Infections (AIDS, TB, fungal, cytomegalovirus)

  • Metastatic cancer

  • Surgery or trauma causing hemorrhage

• Symptoms:

  • Hyperpigmentation (if ACTH is elevated)

  • Vitiligo (autoimmune destruction of melanocytes)

  • Hyponatremia (low aldosterone)

  • Hypoglycemia (low glucocorticoids)

  • Poor immune, injury, and stress response

  • Symptoms worsen throughout the day

• Treatment:

  • Address underlying cause

  • Hormone replacement (hydrocortisone, DHEAS for XX genotype, salt tablets)

Secondary Adrenal Insufficiency

Secondary adrenal insufficiency results from decreased ACTH due to pituitary or hypothalamic dysfunction, or withdrawal of corticosteroid medications.

• Symptoms:

  • Similar to Addison's but without renin-angiotensin pathway involvement

  • Aldosterone and potassium levels remain normal

  • No hyperpigmentation (no excess ACTH)

Acute Adrenal Crisis

An acute adrenal crisis is a life-threatening emergency due to sudden deficiency of adrenal hormones.

• Symptoms:

  • Dizziness, sudden onset of weakness

  • Low blood sugar, low blood pressure

  • Vascular collapse, shock-like symptoms

Cushing's Disease/Syndrome

Cushing's disease is caused by excess cortisol, often due to increased ACTH (pituitary tumor) or adrenal tumor, or long-term corticosteroid use (iatrogenic).

• Symptoms:

  • Muscle wasting, protein breakdown

  • Moon face, buffalo hump, central obesity

  • Striae, easy bruising, osteoporosis

  • Acne, menstrual irregularities (XX genotype)

  • Hypertension (increased aldosterone)

  • Impaired immune and inflammatory responses

  • Gastric ulceration, mood disturbances

Primary Aldosteronism (Conn's Syndrome)

Primary aldosteronism is characterized by excess aldosterone production, usually due to adrenal hyperplasia or adenoma.

• Symptoms:

  • Hypervolemia, hypertension

  • Hypokalemia (low potassium), leading to alkalosis

  • Hypocalcemia, paresthesia, tetany, muscle weakness, paralysis

• Diagnosis:

  • High sodium, low potassium

  • High aldosterone, low renin (primary)

  • Imaging (CT abdomen)

Secondary Hyperaldosteronism

Secondary hyperaldosteronism is due to increased renin production, often from decreased renal blood flow (renal artery stenosis, heart failure, pregnancy, or overuse of oral contraceptives).

• Symptoms: Similar to primary, but both renin and aldosterone are elevated.

Regulation of Adrenal Hormones

Hypothalamic-Pituitary-Adrenal (HPA) Axis

The HPA axis is the central stress response system:

• Hypothalamus: Releases CRH

• Anterior Pituitary: Releases ACTH in response to CRH

• Adrenal Cortex: Releases cortisol in response to ACTH

Negative Feedback: High cortisol inhibits CRH and ACTH release.

Table: Adrenal Cortex Zones and Their Hormones

Zone	Main Hormone(s)	Function
Zona Glomerulosa	Aldosterone	Regulates sodium and potassium balance
Zona Fasciculata	Cortisol, Corticosterone	Regulates metabolism, stress response, immune function
Zona Reticularis	Androgens (DHEA), Estrogen	Contributes to secondary sexual characteristics

Key Equations

• Cortisol Negative Feedback: $\text{High Cortisol} \rightarrow \text{Inhibition of CRH and ACTH}$

• Renin-Angiotensin-Aldosterone System: $\text{Low Blood Pressure} \rightarrow \text{Renin Release} \rightarrow \text{Angiotensin II} \rightarrow \text{Aldosterone Release}$

Factors Affecting Adrenal Function

• Stress: Physical, emotional, or chronic stress increases cortisol production.

• Infections: Can impair adrenal function.

• Drugs: Prescription corticosteroids suppress endogenous hormone production.

• Wound Healing: Cortisol affects tissue repair.

Additional info:

• Peripheral conversion of adrenal androgens to estrogens is especially significant in postmenopausal women and individuals with certain metabolic conditions.

• Adrenal fatigue is not a recognized medical diagnosis but refers to a group of symptoms attributed to prolonged stress and suboptimal adrenal function.