New-Onset Psychosis in Hospital: Metabolic and Endocrine Causes

A Comprehensive Review for Practitioners

Dr Neeraj Manikath, Claude.ai

Abstract

Background: New-onset psychosis in hospitalized patients presents a diagnostic challenge, particularly in critical care settings where multiple metabolic and endocrine derangements can manifest with psychiatric symptoms. Early recognition and appropriate management of underlying organic causes are crucial for patient outcomes.

Objective: To provide a comprehensive review of metabolic and endocrine causes of hospital-onset psychosis, emphasizing differential diagnosis between delirium and true psychosis, and offering practical diagnostic and management strategies.

Methods: Narrative review of current literature focusing on steroid-induced psychosis, thyrotoxicosis, hepatic encephalopathy, uremic encephalopathy, and diagnostic approaches including ammonia levels, thyroid function tests, and electroencephalography.

Conclusions: Systematic evaluation of metabolic and endocrine parameters, combined with careful clinical assessment, enables accurate diagnosis and targeted treatment of organic causes of psychosis in hospitalized patients.

Keywords: Psychosis, delirium, steroid psychosis, thyrotoxicosis, hepatic encephalopathy, uremic encephalopathy

Introduction

New-onset psychosis in hospitalized patients represents a medical emergency requiring immediate attention and systematic evaluation. Unlike primary psychiatric disorders, hospital-onset psychosis frequently has identifiable organic causes, particularly metabolic and endocrine derangements that are potentially reversible with appropriate treatment.¹

The prevalence of organic psychosis in hospital settings ranges from 5-15% of all psychiatric consultations, with higher rates observed in intensive care units where metabolic disturbances are more common.² Critical care physicians must maintain high clinical suspicion for underlying organic causes, as delayed recognition can lead to irreversible neurological damage and prolonged hospitalization.

This review focuses on the most clinically relevant metabolic and endocrine causes of hospital-onset psychosis, providing practical diagnostic and management strategies for postgraduate trainees and practicing intensivists.

Pathophysiology of Organic Psychosis

Organic psychosis results from disruption of normal neurotransmitter systems, particularly dopaminergic, cholinergic, and GABAergic pathways.³ Metabolic and endocrine disturbances affect these systems through various mechanisms:

Dopaminergic Dysfunction:

Excess cortisol enhances dopamine synthesis and release
Thyroid hormones modulate dopamine receptor sensitivity
Uremic toxins interfere with dopamine metabolism

Cholinergic Imbalance:

Hepatic encephalopathy reduces acetylcholine synthesis
Inflammatory cytokines suppress cholinergic activity
Electrolyte disturbances affect acetylcholine release

GABA System Disruption:

Ammonia interferes with GABA-glutamate balance
Steroid hormones modulate GABA receptor function
Metabolic acidosis affects GABA synthesis

Clinical Pearl Box 1: Delirium vs. Psychosis - The Critical Distinction

Delirium Characteristics:

Fluctuating consciousness level
Disorganized thinking
Acute onset with rapid fluctuation
Prominent attention deficits
Often hyper/hypoactive motor changes

True Psychosis Features:

Clear consciousness (alert and oriented)
Organized delusions or hallucinations
Stable presentation over hours/days
Preserved attention span
Normal psychomotor activity

The Overlap Zone:

Mixed presentations are common
Delirium can have psychotic features
Underlying cause may produce both
Serial assessments are crucial

Major Metabolic and Endocrine Causes

1. Steroid-Induced Psychosis

Corticosteroid-induced psychiatric symptoms occur in 5-18% of patients receiving therapeutic doses, with psychosis being the most severe manifestation.⁴

Risk Factors:

Dose >40mg prednisolone equivalent daily
Rapid dose escalation
Previous psychiatric history
Female gender
Advanced age

Clinical Presentation:

Onset typically within first week of treatment
Manic-like symptoms predominate
Grandiose or paranoid delusions
Visual/auditory hallucinations
Severe insomnia and agitation

Diagnostic Approach:

Temporal relationship with steroid initiation/escalation
Exclude other organic causes
Consider dexamethasone suppression test if endogenous Cushing's suspected

Management Strategy:

Gradual steroid tapering if clinically feasible
Antipsychotics: Haloperidol 2-5mg or Olanzapine 5-10mg
Mood stabilizers for manic features
Close monitoring during steroid withdrawal

2. Thyrotoxic Psychosis

Psychiatric symptoms occur in up to 20% of patients with severe hyperthyroidism, with psychosis representing the most serious neuropsychiatric complication.⁵

Clinical Spectrum:

Anxiety and agitation (early)
Manic-like behavior
Paranoid delusions
Command hallucinations
Catatonic features (rare but severe)

Diagnostic Workup:

Free T4, T3, TSH levels
Thyroid antibodies (TRAb, Anti-TPO)
Thyroid uptake scan if etiology unclear
Cardiac evaluation (ECG, echocardiogram)

Treatment Protocol:

Immediate antithyroid therapy (Methimazole 20-40mg daily)
Beta-blockade for sympathetic symptoms
Iodine therapy in severe cases
Antipsychotics with caution (risk of hyperthermia)
Plasmapheresis for refractory cases

3. Hepatic Encephalopathy with Psychotic Features

While typically presenting as delirium, hepatic encephalopathy can manifest with prominent psychotic symptoms, particularly in chronic cases.⁶

Pathophysiological Mechanisms:

Ammonia accumulation crosses blood-brain barrier
False neurotransmitter production
Manganese deposition in basal ganglia
GABA-benzodiazepine pathway activation

Clinical Grading and Features:

Grade I: Mild confusion, personality changes
Grade II: Disorientation, inappropriate behavior
Grade III: Stupor, severe confusion, psychotic features
Grade IV: Coma

Diagnostic Investigations:

Serum ammonia levels (>100 μmol/L significant)
Liver function tests
Arterial blood gas analysis
EEG showing triphasic waves
Brain MRI (T1 hyperintensity in globus pallidus)

Management Approach:

Lactulose 30-60ml every 6 hours (target 2-3 soft stools daily)
Rifaximin 550mg twice daily
Protein restriction (0.8-1.2g/kg/day)
Identify and treat precipitating factors
L-ornithine L-aspartate for refractory cases

4. Uremic Encephalopathy

Uremic encephalopathy affects 60-90% of patients with severe kidney disease and can present with psychotic symptoms before overt uremic signs develop.⁷

Pathogenic Factors:

Urea and creatinine accumulation
Electrolyte disturbances (Na⁺, Ca²⁺, Mg²⁺)
Metabolic acidosis
Uremic toxin accumulation
Fluid overload and hypertension

Clinical Presentation:

Early: Fatigue, difficulty concentrating
Intermediate: Confusion, psychotic symptoms
Late: Seizures, coma, movement disorders

Laboratory Assessment:

BUN >100 mg/dL (>35.7 mmol/L)
Creatinine >10 mg/dL (>884 μmol/L)
Electrolyte panel including phosphate
Arterial blood gas analysis
Parathyroid hormone levels

Treatment Strategies:

Urgent hemodialysis or continuous renal replacement therapy
Correction of electrolyte abnormalities
Management of metabolic acidosis
Blood pressure control
Cautious use of renally-cleared medications

Diagnostic Pearls and Clinical Hacks

Pearl 1: The "Ammonia Paradox"

Normal ammonia levels don't exclude hepatic encephalopathy. Up to 10% of patients with clinical HE have normal ammonia levels. Conversely, elevated ammonia without liver disease suggests rare metabolic disorders.

Pearl 2: Steroid Timeline Rule

Steroid psychosis typically occurs within 5 days of initiation or dose increase. Onset >2 weeks after stable dosing suggests alternative etiology.

Pearl 3: Thyroid Storm Triad

Look for the triad of hyperthermia (>38.5°C), tachycardia (>130 bpm), and altered mental status. Psychosis may be the presenting feature before other classic signs.

Pearl 4: The "Uremic Frost" Sign

White, powdery deposits on skin from urea crystallization indicate severe uremia and imminent encephalopathy risk.

Advanced Diagnostic Strategies

Electroencephalography (EEG) in Organic Psychosis

EEG provides valuable diagnostic information and helps differentiate organic from functional psychosis:⁸

Characteristic Patterns:

Hepatic Encephalopathy: Triphasic waves, generalized slowing
Uremic Encephalopathy: Diffuse slowing, occasional epileptiform activity
Thyrotoxicosis: Fast activity, decreased alpha rhythm
Steroid Psychosis: Usually normal or minimal changes

Clinical Hack: Continuous EEG monitoring in ICU patients with psychosis can detect subclinical seizures (present in 20% of cases).

Laboratory Investigation Protocol

Tier 1 (Immediate):

Complete metabolic panel
Liver function tests
Thyroid function (TSH, Free T4)
Arterial blood gas
Serum ammonia

Tier 2 (Within 24 hours):

Free T3, TRAb if T4 elevated
Cortisol level (8 AM)
Vitamin B12, folate
Magnesium, phosphate
Urinalysis and microscopy

Tier 3 (If indicated):

24-hour urine cortisol
Dexamethasone suppression test
Autoimmune encephalitis panel
Lumbar puncture
Brain MRI with contrast

Management Oysters (Common Pitfalls)

Oyster 1: The Antipsychotic Trap in Thyrotoxicosis

Standard antipsychotics can precipitate hyperthermia in thyrotoxic patients. Use low-dose atypical antipsychotics with careful temperature monitoring.

Oyster 2: Lactulose Overdose

Excessive lactulose can cause severe diarrhea, dehydration, and hypernatremia, worsening encephalopathy. Target 2-3 soft stools daily, not liquid diarrhea.

Oyster 3: Rapid Steroid Withdrawal

Abrupt steroid cessation can cause adrenal crisis. Taper gradually even when treating steroid psychosis, unless life-threatening.

Oyster 4: Missing Mixed Pictures

Patients can have multiple simultaneous causes (e.g., steroid psychosis + hepatic encephalopathy). Address all identified abnormalities.

Special Populations and Considerations

Elderly Patients

Higher susceptibility to all organic causes
Polypharmacy interactions
Reduced drug clearance
Higher mortality risk

Critically Ill Patients

Multiple organ dysfunction
Drug interactions
Sedation effects
ICU-acquired weakness

Post-Surgical Patients

Anesthesia effects
Pain medication influence
Electrolyte shifts
Stress response

Monitoring and Follow-up

Acute Phase Monitoring

Hourly neurological assessments
Continuous cardiac monitoring
Frequent vital signs
Serial laboratory tests

Recovery Phase Indicators

Improved sleep-wake cycle
Decreased agitation
Appropriate social interaction
Normal thought processes

Long-term Follow-up

Endocrine function reassessment
Neuropsychological testing
Medication adjustment
Relapse prevention strategies

Quality Improvement and System-Based Practice

Rapid Response Protocols

Develop institutional protocols for:

Early recognition criteria
Diagnostic algorithms
Treatment standardization
Consultation pathways

Educational Initiatives

Nursing education on recognition
Pharmacy protocols for high-risk medications
Multidisciplinary team training
Family education resources

Future Directions and Research

Emerging areas of investigation include:

Biomarker development for early detection
Neuroprotective strategies
Personalized medicine approaches
Artificial intelligence diagnostic tools

Conclusion

New-onset psychosis in hospitalized patients demands systematic evaluation for metabolic and endocrine causes. Early recognition through careful clinical assessment, appropriate laboratory testing, and judicious use of EEG can identify reversible organic causes. The key principles include maintaining high clinical suspicion, understanding the pathophysiology of common causes, differentiating delirium from true psychosis, and implementing targeted treatment strategies while avoiding common pitfalls.

Success in managing these complex patients requires a multidisciplinary approach combining critical care expertise, psychiatric knowledge, and systems-based practice improvements. As our understanding of organic psychosis evolves, continued research and education will further improve outcomes for this vulnerable patient population.

References

Oldham MA, Lee HB, Desan PH. Diagnosis and treatment of psychiatric disorders in the medical setting. Prim Care Companion CNS Disord. 2016;18(5):PCC.16r02057.
Grover S, Ghosh A. Somatic symptom and related disorders in medical settings. Indian J Psychiatry. 2014;56(1):52-57.
Brown TM, Boyle MF. Delirium. BMJ. 2002;325(7365):644-647.
Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc. 2006;81(10):1361-1367.
Boelaert K, Franklyn JA. Thyroid hormone in health and disease. J Endocrinol. 2005;187(1):1-15.
Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in cirrhosis: implications for the assessment of hepatic encephalopathy. Hepatology. 2009;50(6):2014-2021.
Seifter JL, Samuels MA. Uremic encephalopathy and other brain disorders associated with renal failure. Semin Neurol. 2011;31(2):139-143.
Kaplan PW. The EEG in metabolic encephalopathy and coma. J Clin Neurophysiol. 2004;21(5):307-318.

Author Information

Conflicts of Interest: None declared

Funding: None

Monday, August 4, 2025