An 82-year-old woman presents with 2 months of foul-smelling, greasy diarrhea. She says that she also has felt very tired recently and has had some associated bloating and flatus. She denies any recent abdominal pain, nausea, melena, hematochezia, or vomiting. She also denies any history of recent travel and states that her home has city water. Which of the following tests would be most appropriate to initially work up the most likely diagnosis in this patient?

Tissue transglutaminase antibody test

CT of the abdomen with oral contrast

A 49-year-old woman comes to the physician because of difficulty walking and dizziness for the past 2 weeks. She has also had fatigue, heartburn, and diarrhea for 4 months. The stools are foul-smelling and do not flush easily. Over the past 4 months, she has had a 2.2-kg (5-lb) weight loss. Her only medication is an over-the-counter antacid. Her mother has autoimmune thyroid disease and Crohn disease. She is 150 cm (4 ft 11 in) tall and weighs 43 kg (95 lb); BMI is 19.1 kg/m2. Vital signs are within normal limits. Examination shows a wide-based gait. Muscle strength and tone are normal in all extremities. Rapid alternating movement of the hands is impaired. The abdomen is soft and there is mild tenderness to palpation in the epigastric area. Her hemoglobin concentration is 11.1 mg/dL, and levels of vitamin E and vitamin D are decreased. Upper endoscopy shows several ulcers in the gastric antrum and the descending duodenum. Which of the following is the most likely underlying mechanism of this patient's symptoms?

Inactivation of pancreatic enzymes

Autoantibodies against the intestinal mucosa

Intestinal inflammatory reaction to gluten

T. whipplei infiltration of intestinal villi

Small intestine bacterial overgrowth

A 46-year-old man is brought to the emergency department because of severe epigastric pain and vomiting for the past 4 hours. The pain is constant, radiates to his back, and is worse on lying down. He has had 3–4 episodes of greenish-colored vomit. He was treated for H. pylori infection around 2 months ago with triple-regimen therapy. He has atrial fibrillation and hypertension. He owns a distillery on the outskirts of a town. The patient drinks 4–5 alcoholic beverages daily. Current medications include dabigatran and metoprolol. He appears uncomfortable. His temperature is 37.8°C (100°F), pulse is 102/min, and blood pressure is 138/86 mm Hg. Examination shows severe epigastric tenderness to palpation with guarding but no rebound. Bowel sounds are hypoactive. Rectal examination shows no abnormalities. Laboratory studies show: Hematocrit 53% Leukocyte count 11,300/mm3 Serum Na+ 133 mEq/L Cl- 98 mEq/L K+ 3.1 mEq/L Calcium 7.8 mg/dL Urea nitrogen 43 mg/dL Glucose 271 mg/dL Creatinine 2.0 mg/dL Total bilirubin 0.7 mg/dL Alkaline phosphatase 61 U/L AST 19 U/L ALT 17 U/L γ-glutamyl transferase (GGT) 88 u/L (N=5–50 U/L) Lipase 900 U/L (N=14–280 U/L) Which of the following is the most appropriate next step in management?

Endoscopic retrograde cholangio-pancreatography

A 2720-g (6-lb) female newborn delivered at 35 weeks’ gestation starts vomiting and becomes inconsolable 48 hours after birth. The newborn has not passed her first stool yet. Examination shows abdominal distention and high-pitched bowel sounds. A water-soluble contrast enema study shows microcolon. Serum studies show increased levels of immunoreactive trypsinogen. Which of the following is the most likely additional laboratory finding?

Increased sodium concentration in sweat

Decreased hydrogen ion concentration in renal collecting duct

Increased chloride concentration in alveolar fluid

Increased bicarbonate concentration in pancreatic secretions

Increased serum calcium concentration

Exocrine pancreatic insufficiency for USMLE Step 3: High-Yield Internal Medicine Lessons

Etiology & Pathophysiology - The Broken Factory

Primary Causes:
- Adults: Chronic pancreatitis (most common), pancreatic surgery, ductal obstruction (e.g., neoplasm).
- Children: Cystic fibrosis (most common), Shwachman-Diamond syndrome.
Pathophysiology: Progressive loss of acinar cells impairs digestive enzyme production. Fat and protein digestion are most affected due to reduced lipase and protease secretion.

⭐ Clinical symptoms of malabsorption, particularly steatorrhea, do not manifest until >90% of the pancreas's exocrine function is lost.

Etiologies of Exocrine Pancreatic Insufficiency

Clinical Features - The Greasy Truth

Steatorrhea: The hallmark symptom. Stools are greasy, foul-smelling, voluminous, and difficult to flush due to fat malabsorption (fecal fat >7 g/day).
Weight Loss & Malnutrition: Occurs despite a normal or even increased appetite (polyphagia).
Abdominal Discomfort: Bloating, cramping, and excessive flatulence are common.
Fat-Soluble Vitamin Deficiency:
- A: Night blindness
- D: Bone pain, fractures (osteomalacia/osteoporosis)
- E: Neuropathy, ataxia
- K: Easy bruising, bleeding (↑ PT/INR)

Steatorrhea: Yellow, greasy stools

⭐ Symptoms of malabsorption typically do not manifest until over 90% of the pancreas's exocrine function is lost. Chronic pancreatitis is the leading cause in adults.

Diagnosis - Catching the Culprit

Indirect Pancreatic Function Tests (PFTs):
- Fecal Elastase-1 (FE-1): Test of choice. Not affected by pancreatic enzyme replacement therapy (PERT).
  - Result < 200 µg/g confirms diagnosis.
- 72-hour Fecal Fat: Gold standard but cumbersome. Measures steatorrhea (> 7 g/day).
- Serum Trypsinogen: Low levels (< 20 ng/mL) suggest severe EPI.
Direct PFTs:
- Secretin/CCK Stimulation Test: Most sensitive & specific. Invasive (endoscopic), reserved for equivocal cases. Measures bicarbonate and enzyme output.

⭐ Fecal elastase-1 is the preferred initial test for EPI. Its measurement is not affected by concurrent pancreatic enzyme replacement therapy (PERT), unlike other fecal tests.

Management - Restoring the Flow

Pancreatic Enzyme Replacement Therapy (PERT) is the cornerstone.
- Contains lipase, amylase, and protease.
- Dosing is based on lipase component: start 500-2,500 lipase units/kg per meal.
- Administer with the first bite of meals and snacks; do not crush or chew capsules.
Adjunctive Acid Suppression
- PPIs or H2 blockers may be added to prevent the gastric acid degradation of lipase.
Dietary & Lifestyle Modification
- Small, frequent, moderate-fat meals.
- Supplement fat-soluble vitamins (A, D, E, K) as needed.
- Strict alcohol cessation.

⭐ The primary goal of PERT is not just to resolve steatorrhea, but to reverse the nutritional deficiencies, especially of fat-soluble vitamins.

High‑Yield Points - ⚡ Biggest Takeaways

Chronic pancreatitis is the most common cause of EPI in adults; cystic fibrosis is the primary cause in children.

Classic presentation includes steatorrhea (greasy, foul-smelling stools), weight loss, and deficiency of fat-soluble vitamins (A, D, E, K).

Fecal elastase-1 is the most sensitive and specific non-invasive diagnostic test; a level <200 µg/g is confirmatory.

Management is centered on pancreatic enzyme replacement therapy (PERT), administered with all meals and snacks.

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