What is the next best step in diagnosing a 50-year-old woman with dizziness, flushing, itchy skin, abdominal cramping, watery diarrhea, wheezing, and a systolic murmur?

Diagnostic Approach for a 50-Year-Old Woman with Flushing, Dizziness, and Gastrointestinal Symptoms

The next best diagnostic step for this patient is to measure 5-hydroxyindoleacetic acid (5-HIAA) in urine (option D) to evaluate for carcinoid syndrome.

Clinical Presentation Analysis

This patient presents with a constellation of symptoms highly suggestive of carcinoid syndrome:

• Flushing and warmth
• Dizziness when changing positions
• Itchy skin
• Abdominal cramping
• Watery diarrhea
• Wheezing on respiratory exam
• Systolic murmur on cardiac exam

These findings represent the classic triad of carcinoid syndrome: cutaneous flushing, gastrointestinal hypermotility, and bronchospasm, along with potential cardiac involvement.

Diagnostic Reasoning

Why 5-HIAA is the Correct Choice:

• The combination of flushing, diarrhea, wheezing, and cardiac murmur strongly suggests carcinoid syndrome 1
• Carcinoid tumors secrete serotonin, which is metabolized to 5-HIAA and excreted in urine
• The NCCN guidelines specifically recommend 24-hour urine collection for 5-HIAA for evaluation of suspected carcinoid syndrome, particularly when symptoms of flushing and diarrhea are present 1
• The systolic murmur suggests possible carcinoid heart disease (tricuspid regurgitation), which occurs in 50-66% of patients with carcinoid syndrome 1

Why Other Options Are Less Appropriate:

1. Abdominal and pelvic US (Option A):

   • While imaging will eventually be needed to locate the tumor, biochemical confirmation of carcinoid syndrome should precede imaging
   • Normal abdominal exam makes this less urgent than confirming the diagnosis

2. Barium enema (Option B):

   • Outdated for evaluation of suspected carcinoid tumors
   • Not sensitive for small intestinal carcinoid tumors, which are the most common source of carcinoid syndrome

3. Serum amylase and lipase (Option C):

   • These tests evaluate for pancreatitis
   • Patient's symptoms are not typical for pancreatitis (no severe abdominal pain)
   • Normal abdominal exam makes pancreatitis less likely

Diagnostic Approach to Suspected Carcinoid Syndrome

1. Biochemical confirmation:

   • 24-hour urine collection for 5-HIAA is the gold standard initial test 1, 2
   • Serum serotonin and chromogranin A can be additional biomarkers 2

2. Important considerations for 5-HIAA testing:

   • Patient should avoid serotonin-rich foods (bananas, avocados, plums, eggplant, tomatoes, walnuts) for 3 days before collection 3
   • Certain medications can cause false elevations (acetaminophen, 5-HTP supplements) 3
   • Reference range is typically <45 μmol/day or <15 mg/day 4
   • Plasma/serum 5-HIAA can be an alternative if 24-hour collection is difficult 5

3. After biochemical confirmation:

   • Multiphase CT or MRI scans to locate the primary tumor and assess for liver metastases 1
   • Somatostatin receptor scintigraphy (Octreoscan) or Gallium-68 DOTATATE PET/CT for tumor localization 1
   • Echocardiography to assess for carcinoid heart disease if cardiac murmur is present 1

Clinical Pearls and Pitfalls

• Key point: Carcinoid syndrome typically occurs only after liver metastases have developed, as the liver normally metabolizes the hormones produced by intestinal NETs 1

• Pitfall: False positive 5-HIAA results can occur with certain foods and medications; proper patient preparation is essential 3, 4

• Caution: While 5-HIAA has diagnostic value, its prognostic value is limited once other biomarkers and tumor grading are considered 6

• Important: Dizziness upon rising may represent orthostatic hypotension from the vasodilatory effects of the vasoactive substances released by the tumor

The clinical presentation with the triad of flushing, diarrhea, and wheezing, along with a cardiac murmur, makes carcinoid syndrome the most likely diagnosis, and measuring urinary 5-HIAA is the appropriate next step in confirming this diagnosis.