Adrenal Insufficiency for USMLE Step 1

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Adrenal Insufficiency for the USMLE Step 1 Exam

Primary Adrenal Insufficiency (Addison’s Disease): Results from the destruction or dysfunction of the adrenal cortex, leading to reduced production of cortisol, aldosterone, and adrenal androgens. Cortisol deficiency impairs glucose metabolism and causes hypotension, while aldosterone deficiency leads to sodium loss and potassium retention.
Secondary Adrenal Insufficiency: Caused by decreased adrenocorticotropic hormone (ACTH) secretion from the pituitary, resulting in low cortisol production. Aldosterone production is usually preserved because it is regulated by the renin-angiotensin-aldosterone system.
Tertiary Adrenal Insufficiency: Results from dysfunction of the hypothalamus, often due to chronic glucocorticoid use, leading to decreased corticotropin-releasing hormone (CRH) and subsequent low ACTH and cortisol levels.

Primary Adrenal Insufficiency:
Autoimmune Adrenalitis: The most common cause in developed countries, where the body’s immune system attacks the adrenal cortex.
Infections: Tuberculosis, fungal infections (e.g., histoplasmosis), and HIV can damage the adrenal glands.
Metastasis: Cancer, especially from the lung or breast, can spread to the adrenal glands.
Adrenal Hemorrhage: Occurs in Waterhouse-Friderichsen syndrome, often associated with meningococcal sepsis, or with anticoagulation therapy.
Secondary Adrenal Insufficiency:
Chronic Glucocorticoid Use: Long-term use of exogenous steroids suppresses ACTH production, leading to adrenal atrophy.
Pituitary Disorders: Tumors, surgery, or radiation to the pituitary gland can impair ACTH secretion.

Primary Adrenal Insufficiency (Addison’s Disease):
Fatigue, Weakness, and Anorexia: Result from cortisol deficiency.
Hypotension: Due to both cortisol and aldosterone deficiencies.
Hyperpigmentation: Caused by increased ACTH, which stimulates melanocyte production.
Hyponatremia and Hyperkalemia: Due to aldosterone deficiency.
Hypoglycemia: Occurs because cortisol deficiency impairs gluconeogenesis.
Secondary and Tertiary Adrenal Insufficiency:
Symptoms include fatigue and hypotension but lack hyperpigmentation and significant electrolyte abnormalities, as aldosterone function is intact.

Morning Serum Cortisol: A cortisol level <5 µg/dL suggests adrenal insufficiency.
ACTH Levels: Elevated in primary adrenal insufficiency and low in secondary/tertiary forms.
ACTH Stimulation Test (Cosyntropin Test): Synthetic ACTH is administered, and cortisol levels are measured:
Primary Adrenal Insufficiency: Cortisol levels remain low after ACTH administration.
Secondary/Tertiary Adrenal Insufficiency: Cortisol may rise partially, depending on the extent of adrenal atrophy.
Electrolyte Abnormalities: Hyponatremia and hyperkalemia are common in primary adrenal insufficiency.

Primary Adrenal Insufficiency:
Glucocorticoid Replacement: Hydrocortisone or prednisone is given to replace cortisol. Dosing is adjusted to mimic the body's natural diurnal rhythm.
Mineralocorticoid Replacement: Fludrocortisone is used to replace aldosterone in cases of aldosterone deficiency.
Secondary/Tertiary Adrenal Insufficiency:
Glucocorticoid Replacement: Hydrocortisone or prednisone, as aldosterone replacement is not required.
Acute Adrenal Crisis: A life-threatening emergency managed with IV hydrocortisone and aggressive fluid resuscitation.

Adrenal Crisis: Triggered by infection, surgery, or trauma in untreated patients, characterized by severe hypotension, shock, and electrolyte imbalances. This requires immediate IV glucocorticoids and fluids.

Key Points

Pathophysiology: Primary adrenal insufficiency affects both cortisol and aldosterone production, while secondary and tertiary forms only affect cortisol.
Etiology: Primary adrenal insufficiency is often autoimmune; secondary is caused by chronic glucocorticoid use or pituitary dysfunction.
Clinical Features: Primary adrenal insufficiency presents with hyperpigmentation, hypotension, hyponatremia, and hyperkalemia, while secondary forms lack these findings.
Diagnosis: Low morning cortisol, elevated ACTH (in primary), and ACTH stimulation tests are key diagnostic tools.
Treatment: Glucocorticoid replacement is needed for all forms; mineralocorticoid replacement is required only for primary adrenal insufficiency. Acute adrenal crisis requires urgent intervention.