Treatment of hypothyroidism and psychosis

To the Editor

Primary hypothyroidism is generally associated with depressive symptoms but the relationship between psychosis and hypothyroidism is well recognised (Heinrich and Grahm, 2003). We report here a case of hypothyroidism and psychosis that was slow to respond despite rapid thyroid replacement.

Ms X was a 34-year-old woman who had a total thyroidectomy for poorly regulated Graves’ disease with subsequent hypothyroidism 5 years prior to presentation. She demonstrated distractibility, agitation, grandiosity, persecutory and bizarre delusions and tactile and visual hallucinations. Collateral information indicated a 3-year history of irritability, emotional lability and aggressive behaviour. No prior or family history of psychiatric illness was evident and she denied substance use.

Physical examination showed a disoriented, overweight woman with dry skin, swollen ankles and sluggish deep tendon reflexes. The lab results indicated highly raised thyroid stimulating hormone (TSH) levels > 100 mIU/l (reference range 0.5–4.5 mIU) with low free T₄ levels < 5.0 pmol/l (reference range 10–20 pmol/l). A review of previous results showed consistently deranged thyroid function over the last 5 years.

Her psychosis was managed with quetiapine to 800 mg/day and rapid thyroid replacement (initial high doses of T₄ with a short course of triiodothyronine T₃ orally). Despite normalisation of her serum thyroid function in 2 weeks, her psychosis persisted for a further month and on discharge there were residual grandiose delusions.

This clinical scenario reflects the association between hypothyroidism and psychosis described by Asher in 1949 and termed ‘myxoedema madness’ (Azzopardi et al., 2010). Animal studies suggest a rise in cerebral dopamine with increased tyrosine hydroxylase activity as a potential aetiology. Evidence suggests that 5–15% of hypothyroid patients may develop some form of psychosis, independent of the clinical extent of the thyroid deficiency (Heinrich and Grahm, 2003).

We postulate that intense thyroid replacement does not expedite the improvement in psychotic symptoms despite normalisation of thyroid function. The reported time to recovery is quite variable but may be more dependent on the duration of hypothyroidism and may take months (Azzopardi et al., 2010). So we would suggest that rapid thyroid normalisation is only warranted if medically indicated.

To better control the symptomology, we also suggest initiating antipsychotic treatment at the earliest opportunity and one may need higher doses of antipsychotics for at least 3–6 months (Lehrmann and Jain, 2002).