Residency · Residency · Psychiatry
Psychiatric Manifestations of Medical Illness
Introduction
Medical illnesses frequently present with psychiatric symptoms, and failing to recognize the underlying medical etiology can lead to misdiagnosis, inappropriate treatment, and significant patient harm. The consultation-liaison psychiatrist must maintain a high index of suspicion for organic causes of psychiatric presentations, particularly when symptoms are atypical, occur with new-onset in older adults, or are accompanied by abnormal vital signs or neurological findings.
Red Flags Suggesting a Medical Etiology
New-onset psychiatric symptoms after age 40 with no prior psychiatric history. Acute onset and rapid progression. Visual hallucinations (strongly suggest delirium or organic cause) Fluctuating level of consciousness. Abnormal vital signs or focal neurological deficits. Disorientation, especially to time and place. Failure to respond to standard psychiatric treatment. History of recent surgery, new medications, or substance use.
Endocrine Disorders
| Condition | Psychiatric Mimicry | Key Screening Test | Distinguishing Clue |
|---|---|---|---|
| Hyperthyroidism | Anxiety, panic, mania, psychosis | TSH, free T4 | Tremor, weight loss, heat intolerance, tachycardia |
| Hypothyroidism | Depression, cognitive slowing, psychosis | TSH, free T4 | Fatigue, weight gain, cold intolerance, constipation |
| Cushing syndrome | Depression (50-80%), anxiety, psychosis | 24-hr cortisol, dexamethasone suppression | Moon facies, striae, central obesity |
| Addison disease | Depression, apathy, delirium | AM cortisol, ACTH stimulation | Hyperpigmentation, hypotension, hyponatremia |
| Hypercalcemia | Depression, confusion, psychosis | Serum calcium, PTH | "Stones, bones, groans, moans" |
| Hypocalcemia | Anxiety, irritability, delirium | Serum calcium, ionized calcium | Chvostek/Trousseau signs, tetany |
| Pheochromocytoma | Panic disorder | Plasma metanephrines | Episodic hypertension, headache, diaphoresis |
Thyroid Disease
Hyperthyroidism mimics anxiety disorders: tremor, palpitations, irritability, insomnia, weight loss. Hypothyroidism mimics depression: fatigue, cognitive slowing, weight gain, psychomotor retardation. Severe hypothyroidism can cause myxedema madness with psychosis and delirium. Screen with TSH in all new psychiatric presentations.
Adrenal Disorders
Cushing syndrome is associated with depression (50-80%), anxiety, cognitive impairment, and psychosis. Addison disease presents with fatigue, apathy, depression, and delirium in crisis. Exogenous corticosteroid use can cause mania, psychosis, depression, or mixed states.
Parathyroid and Calcium
Hypercalcemia causes depression, confusion, psychosis, and coma at high levels. Hypocalcemia causes anxiety, irritability, delirium, and seizures. Always check calcium in new-onset psychiatric symptoms.
Neurological Disorders
Epilepsy
Ictal phenomena: fear, deja vu, hallucinations (olfactory, gustatory), automatisms. Interictal psychosis: schizophrenia-like presentation with preserved affect, visual hallucinations. Postictal psychosis: psychosis occurring after a lucid interval following seizure clusters. Temporal lobe epilepsy has the strongest association with psychiatric symptoms.
Multiple Sclerosis
Depression affects 50% of MS patients (higher than any other neurological condition) Pseudobulbar affect (pathological laughing/crying) occurs due to disruption of corticobulbar tracts. Euphoria and disinhibition may occur with frontal lobe plaques. Psychosis is rare but can occur.
Cerebrovascular Disease
Post-stroke depression affects approximately 30% of stroke survivors. Left frontal strokes carry higher depression risk (though evidence is debated) Post-stroke mania, psychosis, and apathy can also occur. Vascular dementia presents with stepwise cognitive decline and executive dysfunction.
Autoimmune Encephalitis
Anti-NMDA receptor encephalitis presents with psychiatric symptoms (psychosis, agitation, catatonia) before neurological signs. Should be considered in young women with new-onset psychosis, especially if accompanied by seizures, movement disorders, or autonomic instability. Hashimoto encephalopathy can present with psychosis, cognitive decline, and seizures with elevated anti-TPO antibodies.
Infectious Diseases
HIV/AIDS: depression, mania, psychosis (especially with CNS involvement), neurocognitive disorder. Neurosyphilis: personality change, psychosis, dementia (the "great imitator") Lyme disease: depression, cognitive impairment, rarely psychosis. Herpes simplex encephalitis: personality change, psychosis, memory impairment (temporal lobe predilection) COVID-19: associated with new-onset anxiety, depression, psychosis, and delirium.
Metabolic and Nutritional Disorders
Hepatic encephalopathy: personality change, confusion, asterixis, progressing to coma. Uremia: cognitive impairment, delirium, psychosis. Vitamin B12 deficiency: depression, psychosis, dementia, peripheral neuropathy (can occur without anemia) Thiamine deficiency (Wernicke encephalopathy): confusion, ophthalmoplegia, ataxia. Folate deficiency: depression, cognitive impairment. Wilson disease: psychiatric symptoms in 30-40%; includes personality change, depression, psychosis.
Systemic and Autoimmune Conditions
Systemic lupus erythematosus (SLE): neuropsychiatric lupus causes psychosis, mood disorders, cognitive impairment, seizures. Porphyria: acute intermittent porphyria causes anxiety, psychosis, confusion during acute attacks. Sarcoidosis: neurosarcoidosis can cause depression, psychosis, cognitive impairment.
The Diagnostic Workup
Recommended Baseline Investigations
Complete blood count, comprehensive metabolic panel. Thyroid function tests (TSH, free T4) Vitamin B12 and folate levels. Urinalysis and urine drug screen. HIV testing, RPR/VDRL for syphilis. Brain imaging (MRI preferred) for new-onset psychosis, atypical presentations. EEG if seizures or encephalitis suspected. Lumbar puncture if autoimmune or infectious encephalitis is considered.
Key Clinical Pearls
The maxim "never let a psychiatric diagnosis kill a patient" underscores the importance of ruling out medical etiologies before attributing symptoms to a primary psychiatric disorder. Anti-NMDA receptor encephalitis is one of the most important diagnoses not to miss; it is treatable, and young patients with new-onset psychosis should be evaluated for it. Visual hallucinations, fluctuating consciousness, and disorientation should always prompt consideration of delirium before a primary psychotic disorder. A thorough medication reconciliation is critical; many common medications (corticosteroids, anticholinergics, dopamine agonists, fluoroquinolones) can cause psychiatric symptoms.
References
- Kayser MS, Dalmau J. Anti-NMDA receptor encephalitis, autoimmunity, and psychosis. Schizophr Res. 2016;176(1):36-40.
- Scarff JR, Lippmann S. When should you suspect psychiatric symptoms are due to a medical illness? Current Psychiatry. 2012;11(4):43-48.
- Levenson JL, ed. The American Psychiatric Association Publishing Textbook of Psychosomatic Medicine and Consultation-Liaison Psychiatry. 3rd ed. 2019.
- Fricchione GL, et al. Psychiatric aspects of medical illness. In: Stern TA, et al., eds. Massachusetts General Hospital Handbook of General Hospital Psychiatry. 7th ed. Elsevier; 2018.