Recognizing ‘myxedema madness’
Detecting and treating myxedema in patients with treatment-resistant psychosis can resolve psychiatric and medical symptoms and restore quality of life. Left untreated, it can impair cognitive function and cause lethargy, dysarthria, myopathy, neuropathy, status epilepticus, and coma.5-7
Myxedema can impair perception and intellectual functioning,9 and acute mania has been reported in some cases.10 Increasing delirium reduces integration of perceptual input, leading to misidentification and disorientation. Cognitive functioning may be impaired, and abnormal thyroid hormone levels might delay event-related brain potential.11
Physical signs also can be telling. The patient might show general psychomotor retardation and slowed speech. The tongue might be swollen, the voice hoarse and croaking. Hair is often coarse and brittle, with hair loss along the sides of the eyebrows. Body temperature often dips below normal.4
Dr. Lachover’s observations
Detecting Ms. A’s hypothyroidism early could have prevented needless hospitalizations and failed treatment. Order a baseline thyroid panel for every patient who presents with psychotic symptoms or depression, which is the primary affective disturbance seen in myxedema.
What causes psychosis, depression in myxedema?
Serum cholesterol >200 mg/dL, anemia and hypertension, basal metabolic rate≤20% of normal levels, triiodothyronine (T3) 4.5 mIU/L suggest myxedema (Table 2).Researchers have proposed many potential causes for the psychotic and depressive symptoms seen in myxedema.
Psychotic symptoms. Tonks1 has attributed psychosis in myxedema to decreases in cerebral oxygenation and glucose metabolism, resulting in a relative cerebral hypoxia. Among patients with myxedema, Sheinberg et al2 reported markedly reduced cardiac output and found that:
- cerebral blood flow was reduced 38%
- oxygen and glucose absorption were decreased approximately 30%
- cerebrovascular resistance was notably increased.
Depressive symptoms. Catecholamine deficiency at the neuronal receptor sites might cause depression in hypothyroidism. Evidence suggests that thyroid hormone influences catecholamine function at the neuronal level.3
Monoamine oxidase, which is increased in myxedema, has also been implicated. This enzyme might lead to depression by helping to break down catecholamines at the neuronal axon-dendrite levels.3
Diffuse slowing of background activity is the most common EEG change found in myxedema.13 ECG might show slow, regular sinus rhythm or bradycardia, low voltage, prolonged QTc interval, and flattened T waves.14 Prolonged QRS complexes on ECG indicate delayed ventricular repolarization.11,15 Torsades de pointes, the potentially fatal ventricular tachycardia, can result from a prolonged QTc interval in rare myxedema cases.16
Table 2
Is it myxedema? Check the lab findings
| Component | Values that suggest myxedema |
| Serum cholesterol | >200 mg/dL |
| Free T4 | |
| Total T4 (serum thyroxine) | |
| Total T3 (serum triiodothyronine) | |
| TSH (thyrotropin) | >4.5 mIU/L |
| EEG | Diffuse slowing |
| EKG | Prolonged QTc interval |
Treating 2 sets of symptoms
Prescribe concomitant dessicated thyroid and low-dose antipsychotics over 4 to 6 months to treat both the thyroid dysfunction and psychosis. Because weight gain is common in myxedema, choose an antipsychotic that carries a relatively low risk of weight gain, such as risperidone, 2 mg bid, or aripiprazole, 5 to 10 mg/d.
Many patients reach euthyroidism and their psychosis improves gradually but notably over weeks or months after starting thyroid hormone replacement. Psychosis could recur if desiccated thyroid is stopped; restarting it will improve the patient’s mental state.17 Recovery takes about 3 months on average.4
Continue the SGA until delusion perception is gone and reality testing improves, then taper the medication until all psychotic symptoms have abated. Monitor thyroid function monthly.
For patients with myxedema-induced depression, supplement thyroid hormone replacement with a selective serotonin reuptake inhibitor such as sertraline at regular starting dosages.
Dr. Lachover’s observations
Consider contributing medical illness in any patient with psychosis, particularly with psychotic symptom onset after age 40 and lack of response to weeks of adequate antipsychotic therapy.
A meticulous search to rule out medical disorders in all patients with psychosis and/or depression is essential to planning treatment. Testing is especially urgent for elderly patients, as multiple medical comorbidities or medication side effects can mask hypothyroidism’s signs and symptoms and delay diagnosis.18