What is the appropriate diagnostic workup and treatment plan for a patient presenting with constipation, including a 6 marker study?

Six Marker Study for Constipation

The "6 marker study" refers to a colonic transit study using radiopaque markers, which is indicated only after failed empiric treatment with fiber and over-the-counter laxatives, and when slow-transit constipation is suspected based on clinical presentation. 1

When to Order the Six Marker Study

The American Gastroenterological Association recommends ordering colonic transit studies (including the radiopaque marker technique) only in specific clinical scenarios 1:

• After failed empiric therapy: Patients must first undergo a 1-2 week trial of fiber supplementation and over-the-counter laxatives without adequate response 1, 2
• When anorectal testing is normal: If anorectal manometry and balloon expulsion tests do not reveal defecatory disorders, proceed to transit assessment 2
• Persistent symptoms despite treatment: When symptoms continue after addressing any identified defecatory disorders 1

Clinical Context: What the Study Evaluates

The six marker study specifically assesses for slow-transit constipation (STC), which is characterized by 2:

• Reduced colonic propulsive activity
• Increased uncoordinated distal colonic motor activity
• Normal anorectal function (must be confirmed first)
• Infrequency of bowel movements as the predominant symptom (rather than straining with soft stools) 2

Critical Diagnostic Sequence Before Ordering

Do not order the six marker study until completing this algorithmic workup 1, 2:

Step 1: Initial Assessment

• Digital rectal examination assessing pelvic floor motion during simulated evacuation 1
• Complete blood count (the only routinely necessary laboratory test) 1, 3
• Corrected calcium and thyroid function only if clinically suspected based on other symptoms 4, 1

Step 2: Structural Evaluation (if indicated)

Colonoscopy is required first if any of these are present 1, 3:

• Alarm symptoms (blood in stool, anemia, weight loss)
• Age >50 without previous colorectal cancer screening
• Abrupt onset of constipation

Step 3: Anorectal Function Testing

This must precede transit studies 2:

• Anorectal manometry to assess sphincter function and pelvic floor coordination
• Balloon expulsion test
• These are indicated when digital rectal examination suggests dysfunction or when patients report prolonged straining, need for perineal/vaginal pressure to evacuate, or digital evacuation of stool 1

Step 4: Six Marker Study (Colonic Transit)

Only proceed if Steps 1-3 are completed and either 1, 2:

• Anorectal tests show no defecatory disorder, OR
• Symptoms persist despite treatment of identified defecatory disorder

Interpretation and Clinical Implications

The six marker study uses radiopaque markers ingested in a single capsule to assess colonic transit time 5. Results guide management:

• Normal transit with normal anorectal function: Suggests normal transit constipation (NTC), often associated with irritable bowel syndrome features; managed with continued laxative therapy 2
• Slow transit with normal anorectal function: Confirms slow-transit constipation; may require escalation to secretagogues, prokinetics, or in refractory cases, consideration of colectomy 6
• Abnormal transit with defecatory disorder: Requires treatment of both components 2

Common Pitfalls to Avoid

• Ordering transit studies before anorectal testing: This sequence error misses defecatory disorders, which are more common and require different treatment (biofeedback therapy) 1, 6
• Ordering without empiric treatment trial: The American Gastroenterological Association explicitly recommends against proceeding to specialized testing before attempting fiber and laxatives 1
• Ordering excessive metabolic testing: Glucose, calcium, and thyroid tests should not be routinely ordered unless other clinical features warrant them 1, 3
• Skipping structural evaluation in high-risk patients: Failure to perform colonoscopy when alarm features are present or age-appropriate screening is due can miss malignancy 1, 3

Treatment Algorithm Based on Results

Once slow-transit constipation is confirmed 6:

1. First-line pharmacologic escalation: Osmotic laxatives (PEG 17g/day preferred) or stimulant laxatives (senna, bisacodyl) 4
2. Second-line agents: Intestinal secretagogues (lubiprostone, linaclotide) or prokinetic agents 6
3. Refractory cases: Consider colonic manometry/barostat to assess colonic motility; surgical colectomy may be necessary for specific patients with documented colonic dysmotility 6

The key principle is that the six marker study is a specialized test reserved for patients who have failed standard therapy and require differentiation between normal transit and slow-transit constipation to guide further management decisions. 1, 6