History: ‘They want to kill me’
Police and security agents arrest Ms. A, age 64, at a metropolitan airport. She is extremely agitated and behaving bizarrely, yelling that “the Mafia” is trying to kill her. She has spent 3 days hiding in area hotels, fleeing her “assailants.”
Police arrange Ms. A’s return home; under court order, she is hospitalized in a psychiatric facility. She is diagnosed with paranoid schizophrenia and receives IM haloperidol, 2 mg bid, but shows minimal improvement after 2½ weeks. Her psychotic symptoms improve slightly after the psychiatrist switches her to risperidone, 2 mg bid, but she still cannot function normally. Three weeks after admission, she is transferred to a nursing home for long-term care. She continues risperidone but remains paranoid and delusional.
Three months later, Ms. A is rehospitalized. She is anxious, delusional, confused, and hallucinating at admission. The patient is verbally and physically combative, fearful that medical staff will harm her. She is too violent to be examined, but staff notice that her skin appears thickened, her eyes puffy, and her hair coarse. Her voice sounds low and raspy.
I speak with Ms. A’s son, who reports that before his mother’s arrest he found her in the kitchen wielding a knife, exclaiming she wanted to kill herself. He says she heard a “whoosh” or “ringing” in her right ear while a male voice in her left ear told her, “End it, end it.”
Ms. A is severely obese (weight 325 lbs, body mass index 49 kg/m2). Blood pressure is 140/90 mm Hg, and she is taking captopril, 50 mg bid, for hypertension. Pulse rate and temperature are normal.
Dr. Lachover’s observations
Ms. A’s hallucinatory experiences are atypical, and her psychotic symptoms show little response after 2 months of aggressive inpatient treatment. Three months after discharge, she is rehospitalized in a florid paranoid psychotic state.
The patient’s weight poses an additional obstacle. I avoided second-generation antipsychotics (SGAs) that can cause weight gain, such as clozapine or olanzapine. I tried the SGA risperidone after IM haloperidol, a first-generation antipsychotic, produced minimal response.
Ms. A’s physical symptoms (thickened skin, coarse hair, puffiness under her eyes, and vocal raspiness) suggest an underlying organic process that might be causing her psychosis.
TESTING: Telling results
I order laboratory and other tests to check for an underlying organic disorder:
- Brain MRI is normal, as are CBC, renal and liver function, and serum copper, ceruloplasmin, vitamin B12, and heavy metal levels.
- Slit lamp eye exam reveals no Kayser-Fleischer ring, which would have indicated Wilson’s disease.
- EEG shows a diffuse, nonspecific, abnormal pattern of slowing and decreased amplitude, suggesting diffuse cerebral dysfunction.
- ECG shows sinus bradycardia and a significantly prolonged corrected QT (QTc) interval, indicating delayed ventricular repolarization.
- Thyroid panel is abnormal with markedly elevated thyrotropin (31.07 mIU/L).
Across 3 weeks, Ms. A’s delusional perceptions and hallucination intensity decrease, and her reality testing and socialization skills improve. She is discharged, after which the internist and I see her weekly to monitor thyroid function and psychiatric symptoms, respectively. Thyroid function gradually returns to normal over 4 to 6 months, and she is maintained on levothyroxine, 0.025 mg/d. Her weight gradually decreases over 12 months to 229 lbs.
Six months after discharge, Ms. A is notably more adept at activities of daily living. Mental status exam shows progressively improved reality testing and decreased paranoia. She is more active, and her mood and affect have brightened. Risperidone is stopped 10 months after discharge, and she has not been rehospitalized for psychiatric problems.
Table 1
Ms. A’s thyroid panel values
| Component | Ms. A’s readings | Normal values |
| Serum cholesterol | 310 mg/dL | 100 to 199 mg/dL |
| TSH (thyrotropin) | 31.07 mIU/L | 0.25 to 4.30 mIU/L |
| Free T4 | 0.34 ng/dL | 0.80 to 1.80 ng/dL |
| Total T4 (serum thyroxine) | 1.5 µg/dL | 4.6 to 12 µg/dL |
| Total T3 (serum triiodothyronine) | 67 ng/dL | 70 to 180 ng/dL |
Dr. Lachover’s observations
Erroneously diagnosed with paranoid schizophrenia, Ms. A endured 2 extended hospitalizations. Her psychosis and mental state—both of which improved with thyroid replacement therapy—appear to have been a psychiatric manifestation of severe hypothyroidism, or “myxedema madness” (Box).1-3
Myxedema prevalence in the general public has been reported at 0.5% to 18%. It is roughly 10 times more common in women than in men,4 and 5% to 15% of patients with myxedema might develop signs of psychosis.4 Myxedema-induced psychosis usually occurs during middle age but has been reported between ages 18 and 73. Prevalence increases with age.4