Clinical NP Exam Prep: Differential
Diagnosis Question Bank
(150Q&A)2025/2026
1. A 45-year-old male presents with chest pain radiating to the left arm,
sweating, and nausea. What is the most likely diagnosis?
A. Gastroesophageal reflux
B. Pulmonary embolism
C. Myocardial infarction
D. Panic attack
Rationale: Classic symptoms of myocardial infarction include chest
pain radiating to the left arm, diaphoresis, and nausea. Other
conditions may mimic MI, but the combination of these features is
most indicative of MI.
2. A 30-year-old woman presents with fatigue, pallor, and pica. Labs
show microcytic anemia. What is the most likely cause?
A. Iron deficiency anemia
B. Vitamin B12 deficiency
C. Hemolytic anemia
D. Aplastic anemia
Rationale: Microcytic anemia with fatigue and pica is most commonly
due to iron deficiency, often from chronic blood loss or dietary
insufficiency.
3. A 25-year-old male presents with acute onset of fever, dysuria, and
penile discharge. The most likely causative agent is:
A. Escherichia coli
B. Neisseria gonorrhoeae
C. Chlamydia trachomatis
,D. Trichomonas vaginalis
Rationale: Acute urethritis with purulent discharge and dysuria in a
sexually active male is most commonly caused by Neisseria
gonorrhoeae.
4. A 65-year-old female presents with tremor at rest, bradykinesia, and
rigidity. The most likely diagnosis is:
A. Essential tremor
B. Huntington disease
C. Parkinson disease
D. Multiple sclerosis
Rationale: Parkinson’s disease is characterized by resting tremor,
bradykinesia, and muscle rigidity, typically in older adults.
5. A 40-year-old male presents with sudden severe headache described
as “the worst headache of my life.” The most likely diagnosis is:
A. Migraine
B. Subarachnoid hemorrhage
C. Tension headache
D. Cluster headache
Rationale: Sudden, severe “thunderclap” headache is classic for
subarachnoid hemorrhage, often from a ruptured aneurysm.
6. A 55-year-old female presents with jaundice, pruritus, and dark
urine. Labs show elevated alkaline phosphatase. What is the most likely
diagnosis?
A. Hepatitis A infection
B. Hemolytic anemia
C. Cholestatic liver disease (e.g., primary biliary cholangitis)
D. Wilson disease
Rationale: Cholestatic liver disease presents with jaundice, pruritus,
,dark urine, and elevated alkaline phosphatase. Hepatitis usually
elevates transaminases more than ALP.
7. A 35-year-old male presents with polyuria, polydipsia, and
hyperglycemia. What is the most likely diagnosis?
A. Type 2 diabetes mellitus
B. Type 1 diabetes mellitus
C. Diabetes insipidus
D. Hyperthyroidism
Rationale: Acute onset polyuria, polydipsia, and hyperglycemia in a
young adult suggest type 1 diabetes mellitus.
8. A 28-year-old female presents with fatigue, weight gain, cold
intolerance, and constipation. Labs show elevated TSH. Most likely
diagnosis:
A. Hypothyroidism
B. Hyperthyroidism
C. Addison disease
D. Cushing syndrome
Rationale: Hypothyroidism presents with fatigue, weight gain, cold
intolerance, constipation, and elevated TSH.
9. A 60-year-old male presents with sudden vision loss in one eye.
Fundoscopy shows a pale retina with a cherry-red spot. Most likely
diagnosis:
A. Retinal detachment
B. Central retinal artery occlusion
C. Central retinal vein occlusion
D. Optic neuritis
Rationale: Central retinal artery occlusion presents with sudden,
painless vision loss and a pale retina with a cherry-red macula.
, 10. A 70-year-old male presents with progressive shortness of breath
and bibasilar crackles. Chest X-ray shows bilateral interstitial infiltrates.
Most likely diagnosis:
A. COPD exacerbation
B. Pulmonary embolism
C. Idiopathic pulmonary fibrosis
D. Pneumothorax
Rationale: Progressive dyspnea in an older adult with interstitial
infiltrates suggests idiopathic pulmonary fibrosis.
11. A 22-year-old female presents with lower abdominal pain, dysuria,
and urinary frequency. Pregnancy test is negative. Most likely diagnosis:
A. Appendicitis
B. Urinary tract infection
C. Ovarian torsion
D. Pelvic inflammatory disease
Rationale: Dysuria, frequency, and suprapubic pain in a non-pregnant
female are classic for urinary tract infection.
12. A 50-year-old male with a history of smoking presents with chronic
cough, hemoptysis, and weight loss. Most likely diagnosis:
A. Pneumonia
B. Tuberculosis
C. Lung cancer
D. Chronic bronchitis
Rationale: Chronic cough, hemoptysis, weight loss, and smoking
history are classic features of lung cancer.
13. A 40-year-old male presents with severe epigastric pain radiating to
the back, nausea, and vomiting. Labs show elevated amylase and lipase.
Most likely diagnosis:
A. Cholecystitis
Diagnosis Question Bank
(150Q&A)2025/2026
1. A 45-year-old male presents with chest pain radiating to the left arm,
sweating, and nausea. What is the most likely diagnosis?
A. Gastroesophageal reflux
B. Pulmonary embolism
C. Myocardial infarction
D. Panic attack
Rationale: Classic symptoms of myocardial infarction include chest
pain radiating to the left arm, diaphoresis, and nausea. Other
conditions may mimic MI, but the combination of these features is
most indicative of MI.
2. A 30-year-old woman presents with fatigue, pallor, and pica. Labs
show microcytic anemia. What is the most likely cause?
A. Iron deficiency anemia
B. Vitamin B12 deficiency
C. Hemolytic anemia
D. Aplastic anemia
Rationale: Microcytic anemia with fatigue and pica is most commonly
due to iron deficiency, often from chronic blood loss or dietary
insufficiency.
3. A 25-year-old male presents with acute onset of fever, dysuria, and
penile discharge. The most likely causative agent is:
A. Escherichia coli
B. Neisseria gonorrhoeae
C. Chlamydia trachomatis
,D. Trichomonas vaginalis
Rationale: Acute urethritis with purulent discharge and dysuria in a
sexually active male is most commonly caused by Neisseria
gonorrhoeae.
4. A 65-year-old female presents with tremor at rest, bradykinesia, and
rigidity. The most likely diagnosis is:
A. Essential tremor
B. Huntington disease
C. Parkinson disease
D. Multiple sclerosis
Rationale: Parkinson’s disease is characterized by resting tremor,
bradykinesia, and muscle rigidity, typically in older adults.
5. A 40-year-old male presents with sudden severe headache described
as “the worst headache of my life.” The most likely diagnosis is:
A. Migraine
B. Subarachnoid hemorrhage
C. Tension headache
D. Cluster headache
Rationale: Sudden, severe “thunderclap” headache is classic for
subarachnoid hemorrhage, often from a ruptured aneurysm.
6. A 55-year-old female presents with jaundice, pruritus, and dark
urine. Labs show elevated alkaline phosphatase. What is the most likely
diagnosis?
A. Hepatitis A infection
B. Hemolytic anemia
C. Cholestatic liver disease (e.g., primary biliary cholangitis)
D. Wilson disease
Rationale: Cholestatic liver disease presents with jaundice, pruritus,
,dark urine, and elevated alkaline phosphatase. Hepatitis usually
elevates transaminases more than ALP.
7. A 35-year-old male presents with polyuria, polydipsia, and
hyperglycemia. What is the most likely diagnosis?
A. Type 2 diabetes mellitus
B. Type 1 diabetes mellitus
C. Diabetes insipidus
D. Hyperthyroidism
Rationale: Acute onset polyuria, polydipsia, and hyperglycemia in a
young adult suggest type 1 diabetes mellitus.
8. A 28-year-old female presents with fatigue, weight gain, cold
intolerance, and constipation. Labs show elevated TSH. Most likely
diagnosis:
A. Hypothyroidism
B. Hyperthyroidism
C. Addison disease
D. Cushing syndrome
Rationale: Hypothyroidism presents with fatigue, weight gain, cold
intolerance, constipation, and elevated TSH.
9. A 60-year-old male presents with sudden vision loss in one eye.
Fundoscopy shows a pale retina with a cherry-red spot. Most likely
diagnosis:
A. Retinal detachment
B. Central retinal artery occlusion
C. Central retinal vein occlusion
D. Optic neuritis
Rationale: Central retinal artery occlusion presents with sudden,
painless vision loss and a pale retina with a cherry-red macula.
, 10. A 70-year-old male presents with progressive shortness of breath
and bibasilar crackles. Chest X-ray shows bilateral interstitial infiltrates.
Most likely diagnosis:
A. COPD exacerbation
B. Pulmonary embolism
C. Idiopathic pulmonary fibrosis
D. Pneumothorax
Rationale: Progressive dyspnea in an older adult with interstitial
infiltrates suggests idiopathic pulmonary fibrosis.
11. A 22-year-old female presents with lower abdominal pain, dysuria,
and urinary frequency. Pregnancy test is negative. Most likely diagnosis:
A. Appendicitis
B. Urinary tract infection
C. Ovarian torsion
D. Pelvic inflammatory disease
Rationale: Dysuria, frequency, and suprapubic pain in a non-pregnant
female are classic for urinary tract infection.
12. A 50-year-old male with a history of smoking presents with chronic
cough, hemoptysis, and weight loss. Most likely diagnosis:
A. Pneumonia
B. Tuberculosis
C. Lung cancer
D. Chronic bronchitis
Rationale: Chronic cough, hemoptysis, weight loss, and smoking
history are classic features of lung cancer.
13. A 40-year-old male presents with severe epigastric pain radiating to
the back, nausea, and vomiting. Labs show elevated amylase and lipase.
Most likely diagnosis:
A. Cholecystitis
