What could cause new onset delusions and paranoia in an elderly patient with a history of polymyalgia rheumatica (PMR) and recent pituitary resection who has been on chronic prednisone therapy?

Differential Diagnosis of New Onset Delusions and Paranoia in This Clinical Context

The most likely cause of new onset delusions and paranoia in this elderly patient on chronic prednisone therapy is corticosteroid-induced psychiatric disorder, which occurs in approximately 10% of patients treated with prednisone ≥1 mg/kg and manifests primarily as mood disorder (93%) but can present as psychosis with delusions and hallucinations. 1

Primary Consideration: Corticosteroid-Induced Psychosis

Prednisone can cause psychiatric derangements ranging from euphoria, insomnia, mood swings, and personality changes to severe depression and frank psychotic manifestations including delusions and hallucinations. 2

Key Clinical Features:

• Dose-dependent risk: Higher doses (>40-60 mg/day) carry greater risk, though psychiatric symptoms can occur at any dose 2
• Timing: Can occur at any point during chronic therapy 2
• Manifestations: The FDA label specifically lists schizophrenia, psychotic manifestations, delirium, dementia, hallucinations, and personality changes as adverse effects 2
• Reversibility: A case report of a 72-year-old man with polymyalgia rheumatica taking 100 mg prednisone for 3 months developed psychosis followed by dementia that completely reversed upon steroid discontinuation 3

Secondary Considerations Requiring Urgent Evaluation

Adrenal Insufficiency Post-Pituitary Resection

Given the recent pituitary resection, secondary adrenal insufficiency is a critical consideration that can present with neuropsychiatric symptoms including confusion, delirium, and altered mental status. 2

• Patients on chronic corticosteroids develop adrenal suppression and become dependent on exogenous steroids 2
• Pituitary surgery further compromises the hypothalamic-pituitary-adrenal axis
• Acute adrenal crisis can manifest with severe psychiatric symptoms and requires immediate evaluation and treatment

Acute Confusional State/Delirium

Elderly patients are particularly vulnerable to acute confusional states, which are characterized by acute onset and fluctuating level of consciousness with decreased attention. 1

Critical evaluation needed for:

• CNS infections (requiring CSF examination) 1
• Metabolic disturbances 1
• Electrolyte abnormalities (particularly hypokalemia from chronic steroid use) 2
• Hypoglycemia or hyperglycemia (steroids increase blood glucose) 2

Diagnostic Workup Algorithm

Immediate Laboratory Assessment:

• Morning cortisol level and ACTH to evaluate for adrenal insufficiency
• Comprehensive metabolic panel including glucose, electrolytes (particularly potassium) 2
• Complete blood count to evaluate for infection 1
• Inflammatory markers (ESR/CRP) to assess PMR disease activity 1

Neuroimaging:

• Brain MRI is indicated given the recent pituitary surgery and to exclude structural causes, though sensitivity for steroid-induced psychiatric disorders is limited 1
• Consider if focal neurological signs, fever, or initial workup unrevealing 1

Additional Evaluation:

• Medication review for drug interactions or other psychoactive medications 2
• Thyroid function tests (hypothyroidism or hyperthyroidism can occur with steroid use) 2
• Infection screening including urinalysis, chest imaging if clinically indicated 1

Management Approach

If Corticosteroid-Induced Psychosis is Confirmed:

The primary intervention is dose reduction or discontinuation of prednisone, but this must be done carefully given chronic use and recent pituitary surgery. 2, 3

1. Coordinate with endocrinology to manage steroid taper and assess adrenal function
2. Symptomatic management with haloperidol or atypical antipsychotics only after excluding other causes 1
3. Stress-dose steroids may be needed during acute illness given adrenal suppression 2

For PMR Management During Psychiatric Crisis:

• Standard PMR treatment uses 12.5-25 mg prednisone daily 1, 4
• If patient was on higher doses, this may explain psychiatric symptoms
• Consider intramuscular methylprednisolone as alternative to oral prednisone to potentially reduce CNS effects 1
• Add methotrexate 7.5-10 mg/week as steroid-sparing agent to facilitate prednisone reduction 1, 4

Critical Pitfalls to Avoid

• Never abruptly discontinue corticosteroids in a patient on chronic therapy, especially post-pituitary surgery—this can precipitate life-threatening adrenal crisis 2
• Do not assume psychiatric symptoms are solely steroid-related without excluding metabolic, infectious, and structural causes 1, 2
• Recognize that "reversible dementia" from steroids is underdiagnosed and can be mistaken for neurodegenerative disease 3
• Monitor for cardiac complications as congestive heart failure and other cardiovascular effects can occur with chronic steroid use and contribute to altered mental status 2

Prognosis and Follow-up

If steroid-induced, psychiatric symptoms typically resolve within 2-4 weeks of dose reduction or discontinuation, though recovery may require weeks to years in severe cases. 1, 3

• Close monitoring required during steroid taper
• Psychiatric symptoms may worsen initially during withdrawal 2
• Long-term follow-up needed to ensure PMR remains controlled at lower steroid doses 1