Adrenal Insufficiency for USMLE Step 2

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Adrenal Insufficiency for the USMLE Step 2 Exam

Primary Adrenal Insufficiency (Addison's Disease): Results from damage to the adrenal cortex, causing reduced production of cortisol, aldosterone, and adrenal androgens. Both cortisol and aldosterone deficiencies lead to hypotension, hyponatremia, and hyperkalemia.
Secondary Adrenal Insufficiency: Due to inadequate adrenocorticotropic hormone (ACTH) secretion from the pituitary, which decreases cortisol but usually spares aldosterone since aldosterone is regulated by the renin-angiotensin system.
Tertiary Adrenal Insufficiency: Caused by decreased hypothalamic secretion of corticotropin-releasing hormone (CRH), most commonly seen after chronic glucocorticoid therapy.

Primary Adrenal Insufficiency:
Autoimmune Adrenalitis: The most common cause in developed countries, where the immune system destroys the adrenal cortex.
Infections: Tuberculosis, fungal infections (histoplasmosis), and cytomegalovirus (CMV) can damage the adrenal glands.
Metastatic Cancer: Lung or breast cancer may metastasize to the adrenal glands.
Adrenal Hemorrhage: Waterhouse-Friderichsen syndrome, often secondary to meningococcemia, causes acute adrenal hemorrhage.
Secondary Adrenal Insufficiency:
Chronic Glucocorticoid Therapy: Suppresses ACTH production, leading to adrenal atrophy.
Pituitary Tumors or Surgery: Can impair ACTH secretion.
Tertiary Adrenal Insufficiency:
Caused by hypothalamic dysfunction, often related to chronic exogenous steroid use.

Primary Adrenal Insufficiency (Addison’s Disease):
Fatigue, Weakness, and Anorexia: Caused by cortisol deficiency.
Hypotension: Results from both cortisol and aldosterone deficiency.
Hyperpigmentation: Due to elevated ACTH, which shares a precursor with melanocyte-stimulating hormone (MSH).
Hyponatremia and Hyperkalemia: Due to aldosterone deficiency, causing sodium loss and potassium retention.
Hypoglycemia: From impaired gluconeogenesis due to cortisol deficiency.
Secondary and Tertiary Adrenal Insufficiency:
Similar symptoms but without hyperpigmentation or hyperkalemia. Aldosterone is typically preserved, so sodium and potassium balance is less affected.

Morning Serum Cortisol: Low morning cortisol (<5 µg/dL) suggests adrenal insufficiency.
ACTH Levels:
Elevated ACTH in primary adrenal insufficiency.
Low ACTH in secondary and tertiary adrenal insufficiency.
ACTH Stimulation Test (Cosyntropin Test): Synthetic ACTH is administered, and cortisol levels are measured:
Primary Adrenal Insufficiency: Cortisol remains low after stimulation.
Secondary/Tertiary Adrenal Insufficiency: A blunted cortisol response or delayed rise indicates pituitary or hypothalamic dysfunction.
Electrolytes: Hyponatremia and hyperkalemia suggest primary adrenal insufficiency.

Primary Adrenal Insufficiency:
Glucocorticoid Replacement: Hydrocortisone or prednisone replaces cortisol.
Mineralocorticoid Replacement: Fludrocortisone replaces aldosterone in patients with Addison's disease.
Secondary and Tertiary Adrenal Insufficiency:
Glucocorticoid Replacement: Hydrocortisone or prednisone is given, but mineralocorticoid replacement is usually not needed.
Acute Adrenal Crisis:
Emergency Treatment: High-dose IV hydrocortisone and fluid resuscitation with normal saline are required to treat hypotension, hyponatremia, and hyperkalemia.

Adrenal Crisis: A life-threatening emergency precipitated by infection, surgery, or trauma in patients with adrenal insufficiency, characterized by shock, severe hypotension, and electrolyte imbalances.
Chronic Fatigue: Untreated or undertreated adrenal insufficiency leads to chronic fatigue, weakness, and hypotension, significantly affecting the patient’s quality of life.

Key Points

Pathophysiology: Primary adrenal insufficiency involves cortisol and aldosterone deficiency, while secondary and tertiary forms affect cortisol only, sparing aldosterone.
Etiology: Primary causes include autoimmune destruction, infections, and adrenal metastases. Secondary causes are mainly due to chronic glucocorticoid therapy or pituitary disorders.
Clinical Features: Primary adrenal insufficiency presents with fatigue, hyperpigmentation, hypotension, hyponatremia, and hyperkalemia. Secondary/tertiary forms lack hyperpigmentation and typically do not cause significant electrolyte disturbances.
Diagnosis: Low morning cortisol and an abnormal ACTH stimulation test are key diagnostic tools. Electrolyte imbalances support the diagnosis in primary adrenal insufficiency.
Treatment: Glucocorticoid replacement for all forms, with mineralocorticoid replacement only required in primary adrenal insufficiency.