Mastering Medical
USMLE Step 1 · Endocrine

Addison disease vs Waterhouse-Friderichsen syndrome

How to tell Addison disease and Waterhouse-Friderichsen syndrome apart when a board question makes them look alike.

Fastest separator

Addison is chronic primary adrenal failure with hyperpigmentation; Waterhouse-Friderichsen is acute septic adrenal hemorrhage with purpura and shock.

Side by side

Addison diseaseWaterhouse-Friderichsen syndrome
Key clue

Chronic primary adrenal insufficiency with fatigue, weight loss, hypotension, hyperpigmentation, hyponatremia, hyperkalemia, and low cortisol with high ACTH.

Acute adrenal hemorrhage and shock classically from meningococcemia with fever, purpura, DIC, hypotension, and rapidly fatal adrenal crisis.

Mechanism

Autoimmune or infectious destruction of adrenal cortex reduces cortisol and often aldosterone, raising ACTH through loss of feedback.

Septic DIC causes bilateral adrenal hemorrhage, abruptly destroying adrenal function during overwhelming infection.

Labs and tests

Low cortisol, high ACTH, hyperkalemia, hyponatremia, and positive adrenal autoantibodies support chronic Addison disease.

Meningococcemia, purpuric rash, DIC labs, shock, and bilateral adrenal hemorrhage support Waterhouse-Friderichsen syndrome.

The trap

Both are primary adrenal insufficiency, but tempo and infection/DIC clues separate them.

The repair move

For adrenal insufficiency, decide chronic autoimmune cortex loss versus acute hemorrhagic septic collapse.

Try a free question

Core

A patient has months of fatigue, weight loss, orthostatic hypotension, hyperpigmentation, hyponatremia, hyperkalemia, low cortisol, and high ACTH. Which diagnosis best fits?

Show answer and explanation

Answer: A. Addison disease. Chronic primary adrenal insufficiency with high ACTH and hyperpigmentation points to Addison disease.

Why the other choices are tempting

  • B. Waterhouse-Friderichsen is acute adrenal hemorrhage during sepsis with purpura and shock.
  • C. Cushing disease causes cortisol excess from pituitary ACTH.
  • D. Conn syndrome causes aldosterone excess with hypertension and hypokalemia.
  • E. Secondary adrenal insufficiency has low ACTH and usually lacks hyperpigmentation or hyperkalemia.

Flashcards

Tap a card to flip it.

What chronic clue points to Addison disease?

Hyperpigmentation with chronic fatigue, hypotension, hyponatremia, hyperkalemia, low cortisol, and high ACTH points to Addison disease.

What acute clue points to Waterhouse-Friderichsen syndrome?

Meningococcemia with purpura, DIC, shock, and bilateral adrenal hemorrhage points to Waterhouse-Friderichsen syndrome.

Quick answers

What is the fastest way to tell Addison disease from Waterhouse-Friderichsen syndrome?

Addison is chronic primary adrenal failure with hyperpigmentation; Waterhouse-Friderichsen is acute septic adrenal hemorrhage with purpura and shock.

What is the key clue for Addison disease?

Chronic primary adrenal insufficiency with fatigue, weight loss, hypotension, hyperpigmentation, hyponatremia, hyperkalemia, and low cortisol with high ACTH.

What is the key clue for Waterhouse-Friderichsen syndrome?

Acute adrenal hemorrhage and shock classically from meningococcemia with fever, purpura, DIC, hypotension, and rapidly fatal adrenal crisis.

What is the common trap with Addison disease vs Waterhouse-Friderichsen syndrome?

Both are primary adrenal insufficiency, but tempo and infection/DIC clues separate them.