What is the best course of action for a 16-year-old patient with anxiety and depression, presenting with mildly elevated C-Reactive Protein (CRP) and elevated Gamma-Glutamyl Transferase (GGT), but otherwise normal laboratory results?

Management of Mildly Elevated CRP and Elevated GGT in a 16-Year-Old with Anxiety/Depression

In this adolescent with anxiety/depression, the elevated GGT warrants a focused hepatobiliary workup while the mildly elevated CRP is likely unrelated to the psychiatric symptoms and does not require specific intervention. 1, 2

Understanding the CRP Elevation in Context

The mildly elevated CRP in this adolescent is not clinically significant for several important reasons:

• CRP does not correlate with mood and anxiety symptoms in adolescents, unlike in adults where associations are more consistently documented 2
• A large study of 127 psychotropic medication-free adolescents found no group differences in CRP levels between psychiatric patients and healthy controls, and no correlations between CRP and depressive, anxiety, anhedonia, or suicidality symptoms 2
• CRP values >10 mg/L are not always indicative of acute infection or injury, and can be influenced by demographic, behavioral, and technical factors 1
• Inflammation in pediatric depression appears more narrowly delimited at symptom onset and may only become systemic with chronicity, unlike adult depression 2

Do not pursue the CRP elevation further unless it exceeds 10 mg/L or the patient develops fever, infection symptoms, or other acute illness indicators 1

Focused Evaluation of the Elevated GGT

The elevated GGT requires systematic investigation as it may indicate early liver pathology, even with normal transaminases:

Complete the Initial Liver Panel

Order the following tests immediately to establish the pattern of liver enzyme abnormalities 1, 3:

• Bilirubin, albumin, ALT, AST, and ALP (if not already done) 1, 3
• Complete blood count (if not done within 12 months) 1
• Calculate AST:ALT ratio - a ratio >1 indicates advanced fibrosis/cirrhosis even when both values are in normal range 1, 3

Assess for Common Causes in Adolescents

Medication review is critical - the following psychiatric medications can elevate GGT 4:

• Antipsychotics
• SSRIs/SNRIs (if the patient is on sertraline 5 or fluoxetine 6)
• Any other psychotropic medications

Screen for metabolic risk factors 3, 7:

• Body mass index (obesity is a common cause) 4
• Signs of insulin resistance or diabetes 4
• Dietary habits and physical activity level

Alcohol screening is mandatory even in adolescents, as alcohol is the most common cause of elevated GGT (75% of habitual drinkers) 3, 4:

• Use AUDIT-C questionnaire followed by full AUDIT if positive 7
• GGT has 73% sensitivity for detecting daily ethanol consumption >50g 4

Second-Line Etiologic Testing

If GGT remains elevated after addressing medications and lifestyle factors, proceed with standard liver etiology panel 1, 3:

• Viral hepatitis: Hepatitis B surface antigen, Hepatitis C antibody 1, 3
• Iron studies: Ferritin and transferrin saturation 1, 3
• Autoimmune markers: Anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, serum immunoglobulins 1, 3
• Metabolic screening: Alpha-1-antitrypsin level, thyroid function tests, ceruloplasmin (age <40 years) 1, 3

Imaging Studies

Order abdominal ultrasonography with Doppler as first-line imaging to evaluate liver parenchyma, biliary tree, and vascular structures 3

Management Algorithm

If Medication-Related:

• Consider switching to alternative psychiatric medication if clinically appropriate 3, 7
• Recheck GGT in 2-4 weeks after medication change to establish trend 3

If Lifestyle/Metabolic-Related:

• Implement weight loss and exercise program if obesity or metabolic syndrome present 3, 7
• Monitor GGT every 2-4 weeks initially to establish trend 3

If No Clear Cause Identified:

• Repeat liver panel in 3 months for mild elevations 7
• Monitor every 1-2 months if GGT significantly elevated 7

Referral Criteria to Gastroenterology/Hepatology

Refer immediately if 3:

• GGT elevation persists >3 months despite addressing modifiable factors
• AST:ALT ratio >1 (suggests advanced fibrosis/cirrhosis)
• Imaging shows structural liver or biliary disease
• Positive autoimmune markers
• GGT >100 U/L (warrants fibrosis assessment even with normal transaminases) 7

Critical Pitfalls to Avoid

• Do not attribute elevated GGT solely to psychiatric medications without proper investigation of other causes 3, 4
• Do not assume normal AST/ALT excludes significant liver disease - both can be normal even in cirrhosis 1, 3, 7
• Do not pursue inflammatory workup for mildly elevated CRP in this adolescent psychiatric patient, as it lacks clinical significance 2
• Do not delay alcohol screening due to patient age - use validated tools systematically 7

Monitoring the Psychiatric Condition

Continue standard psychiatric care with awareness that 5, 6:

• SSRIs (sertraline, fluoxetine) can cause GGT elevation and should be monitored 4, 5, 6
• Monitor for suicidal ideation closely, especially in first months of treatment or dose changes 5, 6
• Hypoglycemia can occur with fluoxetine therapy 6