Thyroid hormone plays a major role in the regulation of mood, cognition and behaviour. The effects of hypothyroidism on mental state were recognised as early as 1888 when the Clinical Society of London published a report on 109 cases of myxoedema with features of ‘acute or chronic manias, dementia, or melancholia’.
1 Published at a time when thyroid replacement therapy was unknown, the report claims: ‘Delusions and hallucinations occur in nearly half the cases, mainly where the disease is advanced’. The term ‘myxoedematous madness’ was coined in 1949 by Richard Asher.
2 Published in the BMJ, Asher's paper reviews 14 cases of hypothyroidism with psychotic illness. He described myxoedema as ‘one of the most important, one of the least known and one of the most frequently missed causes of organic psychoses’. Increased awareness of the condition, improved diagnostic tools and availability of treatment has since then transformed the management of thyroid deficiency with recent studies indicating that 5–15% of myxoedematous patients have some form of psychosis.
3No specific type of psychosis is characteristic of the myxoedematous patient. Possible presentations include delusions, auditory and visual hallucinations, perseveration and paranoia.
4 5 Physical symptoms of hypothyroidism usually precede onset of psychosis by several months or years.
6 However, thought disorders have been reported with clinical and subclinical hypothyroidism suggesting psychosis is not necessarily related to advanced disease.
7There are no well-defined diagnostic criteria for myxoedematous madness. Diagnosis usually relies on thyroid function laboratory investigations to confirm untreated hypothyroidism with exclusion of other causes of psychosis. Imaging techniques may reveal certain features associated with hypothyroidism. We note that other case reports have described white matter frontal lobe changes on MRI of the brain similar to the findings in our patient.
8 In addition, positron emission tomography and single photon emission CT studies have revealed a generalised decrease in cerebral perfusion and glucose metabolism in hypothyroid subjects, which may be reversible with treatment.
9 10 Meanwhile, a reversible reduction in wave activity on electroencephalogram has also been associated with hypothyroidism with psychiatric manifestations.
11Treatment for myxoedematous madness relies primarily on thyroid hormone replacement. Synthetic T4 is usually administered orally as a once daily dose. Thyroid stimulating hormone levels should be monitored and the dosage adjusted accordingly. The neuropyschiatric sequelae of hypothyroidism take longer than the physical features to resolve and, in some cases, may persist despite appropriate treatment, due to irreversible damage secondary to chronic metabolic changes.
Learning points- The wide variety of symptoms and their potential subtle manifestations make hypothyroidism a diagnosis that is easy to miss.
- A delay in effective treatment may result in irreversible metabolic changes; thus, recognition of thyroid deficiency early in its course is essential.
- Endocrinopathies, including thyroid hormone dysfunction, should be considered in all patients presenting with psychiatric symptoms.
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