Adrenal Cortex

1. Overview

The adrenal cortex is the outer portion of the adrenal gland and plays a central role in maintaining homeostasis by producing essential steroid hormones. These hormones regulate metabolism, fluid balance, immune response, and secondary sexual characteristics. The adrenal cortex operates independently from the adrenal medulla and responds primarily to signals from the hypothalamic-pituitary-adrenal (HPA) axis and the renin-angiotensin-aldosterone system (RAAS).

2. Location

The adrenal cortex is located as the outer shell of the adrenal glands, which sit atop each kidney. Each adrenal gland lies in the retroperitoneal space above the renal cortex, enclosed in a connective tissue capsule. The cortex surrounds the inner adrenal medulla and accounts for nearly 90% of the gland's mass.

3. Structure

The adrenal cortex is divided into three concentric histological zones, each responsible for the production of different hormones:

• Zona glomerulosa: The outermost layer, arranged in rounded clusters. It secretes mineralocorticoids, primarily aldosterone.

• Zona fasciculata: The thickest middle layer, with cells arranged in long columns. It produces glucocorticoids, chiefly cortisol.

• Zona reticularis: The innermost layer, with a network-like cellular arrangement. It synthesizes androgens, especially dehydroepiandrosterone (DHEA).

4. Function

Each zone of the adrenal cortex has a specific hormonal output:

• Aldosterone (zona glomerulosa): Regulates sodium and potassium levels, and helps control blood pressure by promoting sodium retention in the kidneys.

• Cortisol (zona fasciculata): Modulates glucose metabolism, suppresses immune responses, and facilitates stress adaptation.

• DHEA and other androgens (zona reticularis): Contribute to the development of secondary sexual characteristics, particularly in females, and serve as precursors for sex hormones in peripheral tissues.

5. Physiological role(s)

The adrenal cortex plays a foundational role in multiple body systems through its steroid hormone production:

• Fluid and Electrolyte Regulation: Aldosterone conserves sodium and excretes potassium, essential for blood pressure and fluid balance.

• Glucose Metabolism: Cortisol promotes gluconeogenesis, increases blood sugar levels, and inhibits insulin sensitivity during stress or fasting.

• Immune Response Modulation: Cortisol has anti-inflammatory effects, helping prevent excessive immune activation and tissue damage.

• Sexual Maturation: Adrenal androgens supplement gonadal hormones and are especially important in women for libido and axillary/pubic hair development.

• Stress Response: Cortisol mobilizes energy and suppresses non-essential functions during physical or emotional stress, forming a key part of the HPA axis response.

6. Clinical Significance

Dysfunction of the adrenal cortex can lead to a variety of endocrine disorders:

• Addison’s Disease (Primary Adrenal Insufficiency): Caused by autoimmune destruction, infections (e.g., TB), or metastatic disease. Leads to decreased cortisol and aldosterone. Symptoms include fatigue, weight loss, low blood pressure, hyperpigmentation, and electrolyte imbalances.

• Secondary Adrenal Insufficiency: Due to decreased ACTH from the pituitary. Cortisol is low, but aldosterone is often preserved. May result from chronic steroid use or pituitary disease.

• Cushing’s Syndrome: Characterized by excess cortisol production (endogenous or exogenous). Symptoms include central obesity, muscle wasting, osteoporosis, hypertension, and moon face.

• Congenital Adrenal Hyperplasia (CAH): A group of genetic disorders (most commonly 21-hydroxylase deficiency) that impair cortisol synthesis and lead to excess androgen production. Manifestations may include ambiguous genitalia in females and early virilization in males.

• Conn’s Syndrome (Primary Hyperaldosteronism): Caused by an aldosterone-producing adenoma or adrenal hyperplasia. Results in hypertension, hypokalemia, and metabolic alkalosis.

• Adrenal Cortical Carcinoma: A rare malignancy that can produce excessive corticosteroids and androgens. Often presents with rapidly progressing symptoms and poor prognosis.