What is the recommended lab workup for a patient presenting with new acute mania to rule out organic causes?

Laboratory Workup for New Acute Mania to Rule Out Organic Causes

For patients presenting with new acute mania, a targeted laboratory workup guided by history, physical examination, and risk factors is more effective than routine extensive testing, with essential tests including glucose, electrolytes (especially sodium), thyroid function, toxicology screen, and CBC when clinically indicated. 1

Risk Stratification Determines Testing Intensity

High-risk patients require more extensive evaluation and include: 1, 2

• Age >35 years at first manic episode (bipolar disorder typically presents between late adolescence and age 25) 3
• Age >65 years (significantly higher rates of organic causes) 1
• No prior psychiatric history 1
• Abnormal vital signs (fever, tachycardia, hypertension, hypotension) 2, 4
• Altered mental status, disorientation, or confusion (suggests delirium rather than primary mania) 1, 2
• Focal neurological deficits 1
• Substance abuse history 1

Essential Laboratory Tests (Tier 1)

Always Check:

• Serum glucose: Hypoglycemia and hyperglycemia can present with manic symptoms 2, 4
• Thyroid function tests (TSH, free T4): Primary hypothyroidism paradoxically can cause acute mania, not just hyperthyroidism 1, 5
• Comprehensive metabolic panel including electrolytes: Hyponatremia is a documented cause of organic mania 6
• Toxicology screen (urine and serum): 30% of new psychiatric presentations have toxicologic etiologies; alcohol/drug screens identified causes in 28% of cases 1

Selective Testing Based on Clinical Indicators:

• Complete blood count (CBC): Order when infection suspected based on fever or immunocompromised status 2, 4
• Liver function tests: Consider with alcohol history or medication concerns 1
• Calcium and magnesium: Check if hypocalcemia or hypomagnesemia suspected based on renal disease, alcoholism, or medication use 2
• Vitamin B12 and folate: Particularly in elderly patients with cognitive changes 4
• HIV testing and syphilis serology (RPR/VDRL): Based on risk factors 1, 2

Neuroimaging Considerations

Brain imaging is NOT routinely indicated for uncomplicated new-onset mania without neurological findings. 1

Obtain CT head (or MRI if stable) when: 1

• Focal neurological deficits present
• First-episode psychosis with atypical features
• History of head trauma
• New or worsening headaches
• Age >35 with first manic episode (higher suspicion for organic causes including tumors, stroke, multiple sclerosis) 3, 7
• Abnormal neurological examination

The American College of Emergency Physicians found inadequate literature supporting routine neuroimaging for new-onset psychosis/mania without neurological deficits, recommending individual risk assessment instead. 1

Additional Testing for Specific Scenarios

If Seizure Activity Suspected:

• Electroencephalogram (EEG) 1

If CNS Infection Suspected (fever, immunocompromised):

• Lumbar puncture with CSF analysis 1, 2

In Children and Adolescents:

• All above tests PLUS: 1, 2
• Chromosomal analysis if developmental syndrome features present (e.g., velocardiofacial syndrome)
• Lower threshold for toxicology screens (up to 50% comorbid substance abuse in adolescent psychosis)

Critical Evidence-Based Principles

History and physical examination identify 94% of organic causes, making them far more valuable than reflexive laboratory ordering. 1 In one study of 100 patients with new psychiatric symptoms, 63% had organic etiologies, but medical history was significant in 27%, physical examination in 6%, and alcohol/drug screens in 28%. 1

Routine extensive laboratory panels have extremely low yield: Studies show only 0.8-1.4% of routine screening tests contribute meaningfully to diagnosis or treatment when not guided by history and physical examination. 1 False-positive results are 8 times more common than true-positives with indiscriminate testing. 1

Common Pitfalls to Avoid

• Never assume primary psychiatric disorder in patients >35 years with first manic episode without thorough organic workup 3, 8
• Do not overlook hypothyroidism: The classic teaching of "hyperthyroidism causes mania" is incomplete—primary hypothyroidism can also cause acute mania 5
• Avoid missing hyponatremia: This electrolyte disturbance can present as isolated mania and resolves completely with sodium correction 6
• Do not order CBC, PT, or extensive panels reflexively: These were the only tests in one study that did NOT lead to identification of medical illness 1
• Remember substance-induced symptoms can persist >1 week: If psychotic/manic symptoms continue beyond one week despite documented detoxification, consider primary psychotic disorder rather than substance-induced 1

Practical Algorithm

1. Obtain detailed history focusing on: age of onset, prior psychiatric history, substance use, medications, recent infections, head trauma, family psychiatric history 3
2. Complete physical and neurological examination with vital signs 1, 2
3. Order Tier 1 labs: glucose, comprehensive metabolic panel (including sodium), TSH/free T4, toxicology screen 2, 5, 6
4. Add selective tests based on clinical findings: CBC if infection suspected, calcium/magnesium if indicated, HIV/syphilis if risk factors 2
5. Obtain neuroimaging only if focal deficits, head trauma, age >35 first episode, or atypical presentation 1, 3
6. Consider EEG or lumbar puncture only with specific clinical indicators 1