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J R Soc Med. 2004 June; 97(6): 287–288.
PMCID: PMC1079496

Encephalopathy with hypothyroidism

An occasional associated feature in Hashimoto's thyroiditis is encephalopathy. Whether this amounts to ‘Hashimoto's encephalopathy’ is disputed.

CASE HISTORY

A man of 50 was admitted drowsy and confused after experiencing three generalized seizures, each lasting 3-4 minutes, over two days. For the past four months he had been acting strangely, putting things in wrong places, and tremors of the hands had developed. Two months before the present admission he had been admitted elsewhere with a generalized tonic-clonic seizure and disinhibited behaviour, and had been discharged on phenytoin. Thereafter he became withdrawn and stopped speaking.

On admission, he was mildly pyrexial and was noted to have bilateral xanthelasma (cholesterol 7.5 mmol/L). He was conscious but drowsy, and disoriented in time, place and person. He was experiencing hallucinations and delusions and displayed disinhibited behaviour. Tremors were seen in all four limbs. Muscle tone, power and reflexes were normal. There was no sensory or cerebellar dysfunction and signs of meningeal irritation were absent. White cell count was 13.2 × 109/L and electrolyte and liver profiles were normal except for a raised gamma-glutamyltransferase (296 U/L); blood alcohol was zero and the phenytoin was within the therapeutic range at 15.2 mg/L. On the electroencephalogram (EEG) there was general slowing consistent with encephalopathy. CT of the head was normal and MRI showed a high signal in the right frontal lobe. Cerebrospinal fluid had a raised protein of 1.67 g/L but there was no pleocytosis; polymerase chain reaction for herpes simplex virus was negative, as were bacterial cultures. He had biochemical evidence of mild hypothyroidism with TSH 17 mU/L (normal 0.35-5.0) and FT4 16.2 mmol/L (11-25). Antithyroid peroxidase antibodies titres were very high at 2699 IU/mL (0-75). Tests for rheumatoid factor, antinuclear antibody, HIV and viral hepatitis were all negative and serum copper was within the normal range.

All the initial tests for common causes of metabolic encephalopathy were thus negative. A diagnosis of Hashimoto's encephalitis was based on clinical picture, high antithyroid antibody titres, altered thyroid functions and raised CSF proteins. After 4 days' treatment with oral prednisolone 60 mg per day he was oriented and behaving much more normally. On repeat testing TSH had risen to 85 mU/L, FT4 had fallen to 3.2 mmol/L. He was started on thyroxine. Before discharge his Mini Mental State Examination score was 29/30 and the EEG was within the normal range.

COMMENT

The first case of ‘Hashimoto's encephalopathy’ was reported in 1966.1 In the few cases on record since then, the mean age at presentation was 41 years. This condition has been reported in children and has a female preponderance (ratio 3.6:1).2

The diagnosis is challenging to make since the underlying thyroid disease is often subclinical and the symptoms mimic other neurological conditions. The encephalopathy tends to present acutely with confusional state, focal or generalized seizures and stroke-like episodes.3 Other presentations are dysarthria, hallucinations, stupor, headaches and myoclonus.2 The diagnosis is supported by the finding of raised antithyroid antibodies (antithyroglobulin, antithyroid peroxidase, anti-TSH-receptor, anticytoplasmic).3 The main EEG abnormalities are generalized slowing, frontal rhythmical slowing and triphasic waves. The cerebrospinal fluid protein is above normal in up to 75% of patients and oligoclonal bands may be seen.2 MRI scans are normal in most of the patients and the reported abnormalities include generalized cerebral atrophy and reversible subcortical signal abnormalities. Single photon emission computed tomography has shown multiple areas of hypoperfusion in a few cases.

Hashimoto's encephalopathy is thought to be due to an autoimmune vasculitis, and this notion is backed by the identification of α-enolase autoantigen. Anti-α-enolase antibodies are associated with other forms of autoimmune vasculitic diseases including systemic lupus erythematosus.4 Some workers object to the term Hashimoto's encephalopathy on the argument that thyroid autoantibodies may simply be a marker for other autoantibodies, as yet unidentified, that cause cerebral vasculitis. In the absence of proof of a causal connection between thyroid autoantibodies and encephalopathy, a more appropriate name might be encephalopathy associated with autoimmune thyroiditis.5 Steroids seem an effective treatment in these conditions, though no formal trials have been conducted. Other immunosuppressants have been reported effective. Some patients with hypothyroidism have responded completely to levothyroxine.6

References

1. Brain L, Jellinek E, Ball K. Hashimoto's disease and encephalopathy. Lancet 1966;2: 512-14 [PubMed]
2. Peschen Rosin R, Schabet M, Dichgans J. Manifestation of Hashimoto's encephalopathy years before onset of thyroid disease. Europ Neurol 1999;41: 79-84 [PubMed]
3. Shaw PJ, Wells TJ, Newman PK, Cleland PG, Cartlidge NEF. Hashimoto's encephalopathy: a steroid responsive disorder associated with high anti-thyroid antibody titres—report of 5 cases. Neurology 1991;41: 228-33 [PubMed]
4. Ochi H, Horiuchi I, Araki N. Proteomic analysis of human brain identifies α enolase as a novel autoantigen in Hashimoto's encephalopathy. FEBS 2002;528: 197-202 [PubMed]
5. Sawka A, Fatourechi V, Boeve B, Makri B. Rarity of encephalopathy associated with autoimmune thyroiditis: a case series from Mayo Clinic from 1950 to 1996. Thyroid 2002;12: 393-8 [PubMed]
6. Ferraci F, Moretto G, Candeago RM, Cimini N, Conte F, Gentile M. Antithyroid antibodies in the CSF. Their role in the pathogenesis of Hashimoto's encephalopathy. Neurology 2003;60: 712-14 [PubMed]

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press