HPA Axis and Adrenal Gland Function
📌 The Hypothalamic-Pituitary-Adrenal (HPA) axis is a crucial and sensitive system involving the hypothalamus releasing CRH, which stimulates the pituitary to release ACTH, which then acts on the adrenal cortex to produce hormones, primarily cortisol.
⏱️ Normal cortisol and ACTH levels fluctuate daily, typically being lowest around 4 AM and peaking around 8 AM.
🔗 This axis maintains a negative feedback loop where rising cortisol levels regulate ACTH release from the pituitary.

Adrenal Cortex Hormones and Effects
🔥 The adrenal cortex secretes key hormones: Corticoids (like cortisol), Aldosterone (crucial for electrolyte balance via the Renin-Angiotensin-Aldosterone system), and Sex Hormones (Androgens).
💥 Chronic high ACTH (e.g., from primary pituitary issues) leads to adrenal gland hypertrophy and hyperplasia.
📉 Conversely, chronic reduction of ACTH (due to external glucocorticoid use or pituitary damage) causes adrenal cortex atrophy and reduced endogenous cortisol production.

Causes of Adrenal Insufficiency (Adrenal Failure)
🦠 Primary Adrenal Insufficiency (Addison's Disease): Often caused by autoimmune destruction, leading to the cortex failing to produce sufficient cortisol (even with 90% destruction).
🩺 Secondary Causes: Inhibition of the HPA axis due to prolonged glucocorticoid use (medical treatment or abuse), which suppresses ACTH secretion, leading to adrenal atrophy.
🩸 Acute Adrenal Crisis Triggers: Include adrenal hemorrhage/infection (e.g., Waterhouse-Friderichsen syndrome), adrenalectomy, or insufficient glucocorticoid replacement during stress (like infection).

Clinical Manifestations and Diagnosis
😔 Chronic Symptoms: Include fatigue/weakness (100% of cases), anorexia (100%), nausea/vomiting (86% and 75% respectively), and weight loss (93%).
🎨 Hyperpigmentation: Seen in primary insufficiency due to high ACTH stimulating melanocytes, causing darkening in sun-exposed areas, scars, and mucous membranes.
🧪 Diagnosis: Involves measuring baseline ACTH and performing a Rapid ACTH Stimulation Test; high ACTH with low cortisol indicates primary failure, while low/normal ACTH with low cortisol suggests secondary failure.

Management and Treatment Principles
💊 Primary Treatment: Lifelong glucocorticoid replacement, typically with hydrocortisone (e.g., 20 mg morning, 10 mg evening).
💧 Mineralocorticoid Replacement: Fludrocortisone is often added (0.05 to 0.2 mg/day) to manage salt/water retention, monitored by blood pressure and potassium levels.
⚠️ Stress Dosing: Patients must be instructed to increase glucocorticoid dosage 2 to 5 times during periods of mild stress (like minor infections) and return to baseline after the stress resolves.

Key Points & Insights
➡️ HPA Axis Sensitivity: Stressors like hypoglycemia directly activate the HPA axis, making it a key diagnostic tool (e.g., the older insulin-induced hypoglycemia test).
➡️ Diagnostic Differentiation: If cortisol is low, checking ACTH levels is critical: high ACTH points to Primary Adrenal Failure (adrenal gland issue), while low/normal ACTH points to Secondary Failure (pituitary/hypothalamic issue).
➡️ Treatment Adherence: Patient education is vital; they must understand the necessity of lifelong glucocorticoid replacement and the critical need to adjust doses during stress to prevent acute adrenal crisis.
➡️ Prognosis Improvement: With proper glucocorticoid and mineralocorticoid replacement, patients with adrenal insufficiency can now expect a nearly normal lifespan, mortality being primarily linked to delayed diagnosis or the underlying cause (e.g., metastatic cancer).

📸 Video summarized with SummaryTube.com on Jan 12, 2026, 02:30 UTC