A 38-year-old woman presents with persistent depressed mood, loss of interest in activities, sleep disturbance, and feelings of worthlessness for the past 3 weeks. Clinical examination and basic metabolic panel are normal. Which investigation is most appropriate to confirm the diagnosis of Major Depressive Disorder and rule out organic causes?

Explanation

## Investigation of Choice in Major Depressive Disorder ### Why TSH and Free T4? **Key Point:** Thyroid dysfunction, particularly hypothyroidism, is the most common organic cause of depressive symptoms that must be excluded in every patient presenting with suspected Major Depressive Disorder. **High-Yield:** Hypothyroidism presents with depression, fatigue, weight gain, and psychomotor slowing—features that overlap significantly with MDD. TSH elevation with low free T4 confirms primary hypothyroidism; TSH suppression with low free T4 suggests secondary hypothyroidism or central hypothyroidism. **Clinical Pearl:** Thyroid screening is part of the standard workup for depression in all major guidelines (DSM-5, ICD-11). Untreated hypothyroidism can perpetuate depressive symptoms even with antidepressant therapy. ### Rationale for Thyroid Testing 1. **Prevalence**: Hypothyroidism occurs in 5–10% of patients presenting with depression 2. **Cost-effectiveness**: TSH and free T4 are inexpensive, widely available, and non-invasive 3. **Guideline-mandated**: Recommended as first-line screening in all suspected MDD cases 4. **Reversibility**: If thyroid dysfunction is identified, treatment can resolve depressive symptoms ### Differential Approach to Other Investigations | Investigation | Indication | Limitation in MDD | |---|---|---| | **TSH + Free T4** | Rule out hypothyroidism (organic cause) | Standard screening—must do | | **PET scan** | Research tool; no diagnostic role in MDD | Expensive, not clinically indicated, no diagnostic value | | **EEG** | Seizure disorders, sleep disorders | No diagnostic role in uncomplicated MDD | | **Brain MRI** | Structural lesions, dementia, stroke | No diagnostic role unless focal neurological signs present | **Key Point:** MDD is a clinical diagnosis based on DSM-5 criteria (depressed mood, anhedonia, neurovegetative symptoms for ≥2 weeks). No biological marker or imaging study confirms MDD; investigations serve to exclude organic mimics. **Mnemonic: ORGANIC CAUSES TO EXCLUDE IN DEPRESSION — THIEF** - **T**hyroid disease (hypothyroidism) - **H**ypercalcemia, **H**yponatremia - **I**nfections (neurosyphilis, HIV, TB) - **E**ndocrine (Cushing's, Addison's) - **F**olate/B12 deficiency [cite:Harrison 21e Ch 470]