A 32-year-old man presents with a 3-week history of elevated mood, decreased need for sleep (4 hours/night), racing thoughts, and increased goal-directed activity. He reports a previous depressive episode lasting 2 months 18 months ago. Physical examination and basic metabolic panel are unremarkable. Which investigation is most appropriate to confirm the diagnosis and rule out secondary causes?

Explanation

## Diagnostic Approach to Suspected Bipolar Disorder ### Role of Investigations in Bipolar Disorder **Key Point:** Bipolar Disorder I and II are clinical diagnoses based on DSM-5 criteria; no single pathognomonic investigation exists. However, investigations are essential to exclude secondary causes of mood elevation (secondary mania). ### Why TSH and Free T4 Are the Investigation of Choice **High-Yield:** Thyroid dysfunction—particularly hyperthyroidism and thyroiditis—is the most common medical cause of secondary mania and must be ruled out in every patient presenting with a manic or hypomanic episode. **Clinical Pearl:** Thyroid disorders are frequently missed in psychiatric practice. Hyperthyroidism can mimic mania (tachycardia, insomnia, agitation, increased speech), and thyroiditis can present with mood elevation followed by depression. TSH is the single most sensitive screening test. ### Differential Diagnosis: Secondary Causes of Mania | Cause | Key Feature | Investigation | |-------|-------------|---------------| | Hyperthyroidism | Tachycardia, weight loss, tremor | TSH, free T4 | | Thyroiditis | Biphasic mood (mania → depression) | TSH, free T4, TPO antibodies | | Pheochromocytoma | Episodic hypertension, sweating | 24-h urine metanephrine | | CNS lesion | Focal neurological signs | MRI brain | | Substance-induced | Clear temporal relationship | Urine drug screen | **Key Point:** TSH suppression (low TSH with normal/elevated T4) is the hallmark of hyperthyroidism and the most common reversible cause of secondary mania in clinical practice. ### Standard Workup for Suspected Bipolar Disorder 1. **Mandatory baseline investigations:** - TSH and free T4 (rule out thyroid disease) - Urine drug screen (rule out stimulant use) - Fasting glucose and lipid profile (baseline before mood stabilizers) - Renal function and electrolytes (lithium requires normal renal function) - Liver function tests (valproate and carbamazepine require hepatic monitoring) 2. **Selective investigations (if clinically indicated):** - 24-hour urine metanephrine (if episodic hypertension or sweating) - MRI brain (if focal neurological signs, age >40 with first episode, or atypical presentation) - EEG (only if seizure suspected) **Mnemonic:** **FLUTE** — **F**asting glucose, **L**ipids, **U**rine drug screen, **T**hyroid (TSH/free T4), **E**lectrolytes (K, Na, Cr) — baseline investigations for mood disorder. ### Why This Patient Requires TSH/Free T4 - **Clinical presentation:** Elevated mood, insomnia, racing thoughts, increased goal-directed activity = classic mania - **Age and sex:** 32-year-old male; thyroid disease can present at any age - **No contraindication:** No focal neurological signs, no episodic hypertension, no clear substance use history - **Guideline standard:** All patients with first manic episode require thyroid screening [cite:DSM-5 Bipolar Disorder diagnostic criteria] --- ## Why Each Distractor Is Incorrect | Option | Why Wrong | |--------|----------| | 24-hour urine metanephrine and plasma catecholamine levels | Pheochromocytoma is a rare cause of secondary mania and typically presents with episodic hypertension, severe headache, and diaphoresis. This patient has no hypertension or adrenergic symptoms. Reserved for selective use when clinical suspicion is high. | | Magnetic resonance imaging (MRI) brain with contrast | MRI is not first-line for suspected bipolar disorder. It is indicated only if focal neurological signs, age >40 with first episode, or atypical/rapid-cycling presentation. This patient has no such features. | | Electroencephalography (EEG) | EEG has no role in diagnosing bipolar disorder. It is used only if seizure disorder is suspected (e.g., loss of consciousness, postictal confusion). This patient has no seizure features. | --- ## Summary **Key Point:** TSH and free T4 are the investigation of choice for all patients presenting with suspected mania because thyroid disease is the most common and most readily reversible medical cause of secondary mania.