USMLE PRACTICE QUESTION #120
TOPIC: Endocrine/Pathology
USMLE practice question #120 will test your understanding of a commonly tested endocrine disorder.
I’m Paul Ciurysek, MD, founder of The USMLE Guys, and this is The USMLE Times. This daily newsletter aims to provide super high-yield USMLE concepts commonly tested on exam day. All content is FREE! If you’d like to work with me and my team, please see the options at the bottom of today’s newsletter. Please share the newsletter with a friend if you’d like to support our efforts!
A 35-year-old woman presents to her physician with a 6-month history of progressive fatigue, weight loss, and hyperpigmentation of her skin and mucous membranes. She also reports occasional episodes of dizziness, nausea, and abdominal pain. Laboratory studies reveal hyponatremia, hyperkalemia, and an elevated plasma adrenocorticotropic hormone (ACTH) level. A cosyntropin stimulation test fails to elicit a significant increase in serum cortisol levels. Which of the following laboratory findings, if present, would most strongly suggest autoimmune adrenalitis?
A) Presence of acid-fast bacilli on adrenal biopsy
B) Elevated levels of very-long-chain fatty acids
C) Presence of antibodies against 21-hydroxylase
D) Adrenal calcifications on CT imaging
E) Bilateral adrenal enlargement on magnetic resonance imaging
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
It’s important to adopt the correct MENTAL MODEL when answering USMLE questions; it saves time and increases accuracy. The mental model outlined below is a foundational component of our test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:
Step 1. Read the last line to get to the heart of the question: “Which of the following laboratory findings, if present, would most strongly suggest autoimmune adrenalitis?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 1st order. 1st: Identify the marker for autoimmune adrenalitis.
Step 3: Read the vignette carefully and ask yourself: “Which of the given options suggests autoimmune adrenalitis”
Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.
GENERAL ANALYSIS
The 35-year-old woman presents with progressive fatigue, weight loss, hyperpigmentation, and symptoms such as dizziness, nausea, and abdominal pain. Laboratory findings of hyponatremia, hyperkalemia, and elevated plasma ACTH levels, along with a failed cosyntropin stimulation test, confirm the diagnosis of primary adrenal insufficiency (PAI). The most common cause of PAI in Western countries is autoimmune adrenalitis (Addison's disease). To confirm autoimmune adrenalitis as the underlying cause, the presence of antibodies against 21-hydroxylase is highly specific.
ANSWER CHOICES:
CHOICE A: Presence of acid-fast bacilli on adrenal biopsy
Explanation: Acid-fast bacilli indicate tuberculosis (TB), which can cause adrenal insufficiency via destruction of the adrenal glands.
Why Incorrect: While TB was historically a common cause of PAI, it is now rare in Western countries. Additionally, there is no evidence of TB infection or systemic symptoms (e.g., fever, weight loss due to TB).
CHOICE B: Elevated levels of very-long-chain fatty acids
Explanation: Elevated very-long-chain fatty acids (VLCFA) are seen in adrenoleukodystrophy (ALD), an X-linked disorder that causes adrenal insufficiency due to accumulation of VLCFAs in the adrenal cortex.
Why Incorrect: ALD primarily affects males and often presents with neurological symptoms. This patient’s presentation is more consistent with autoimmune adrenalitis.
CHOICE C: Presence of antibodies against 21-hydroxylase
Explanation: The enzyme 21-hydroxylase, which is involved in cortisol and aldosterone synthesis, is the primary autoantigen in autoimmune adrenalitis.
Why Correct: Testing for 21-hydroxylase antibodies is a key diagnostic step after confirming PAI. These antibodies are present in up to 90% of cases of autoimmune adrenalitis and are highly specific for this condition.
CHOICE D: Adrenal calcifications on CT imaging
Explanation: Adrenal calcifications are characteristic of infectious causes of adrenal insufficiency, such as TB or histoplasmosis.
Why Incorrect: Autoimmune adrenalitis does not typically cause calcifications. Imaging findings would not confirm an autoimmune etiology.
CHOICE E: Bilateral adrenal enlargement on magnetic resonance imaging
Explanation: Bilateral adrenal enlargement may be seen in infiltrative diseases (e.g., lymphoma, metastases) or infections (e.g., TB).
Why Incorrect: Autoimmune adrenalitis usually results in atrophic or normal-sized adrenals rather than enlargement.
FINAL VERDICT…
CORRECT ANSWER: C) Presence of antibodies against 21-hydroxylase
The detection of antibodies against 21-hydroxylase strongly supports autoimmune adrenalitis as the underlying cause of this patient’s primary adrenal insufficiency. This test is both sensitive and specific for autoimmune Addison's disease and eliminates the need for further invasive testing or imaging to establish the etiology.
KEY CONCEPTS:
Autoimmune Adrenalitis:
Most common cause of primary adrenal insufficiency in Western countries.
Results from autoantibody-mediated destruction of the adrenal cortex.
21-Hydroxylase Antibodies:
Present in up to 90% of cases of autoimmune adrenalitis.
Highly specific for diagnosing autoimmune Addison's disease.
Primary Adrenal Insufficiency Features:
Clinical: Fatigue, weight loss, hyperpigmentation (due to elevated ACTH), dizziness, nausea.
Laboratory: Hyponatremia, hyperkalemia, elevated ACTH, low cortisol levels.
Diagnostic Testing:
Cosyntropin stimulation test confirms primary adrenal insufficiency.
Testing for 21-hydroxylase antibodies confirms autoimmune etiology.
Differential Diagnosis:
Infectious causes (e.g., TB): Associated with calcifications or acid-fast bacilli.
Infiltrative diseases (e.g., lymphoma): May show bilateral adrenal enlargement.
Adrenoleukodystrophy: Characterized by elevated VLCFAs and neurologic symptoms.
1) 1-ON-1 STRATEGY SESSION: CLICK HERE TO SET UP YOUR 1-ON-1 STRATEGY SESSION
2) TEST-TAKING SKILLS & RESIDENCY MASTERCLASSES: LEARN ABOUT THE MASTERCLASSES HERE
3) ASSESSMENT EXAMS: CLICK FOR USMLE STEP 1, STEP 2, & CLINICAL SHELF EXAMS
See ya tomorrow 👋