Thyroid crisis or “storm” refers to a fulminant increase in the symptoms and signs of thyrotoxicosis—extreme restlessness, tachycardia, fever, vomiting, and diarrhea—leading to delirium or coma. In the past, this was a not uncommon postoperative event in patients poorly prepared for thyroid surgery. Now it is seen mainly in patients with inadequately treated or untreated thyrotoxicosis complicated by serious medical or surgical illness.
Brain and associates described an encephalopathy consisting of confusion, altered consciousness, and prominent myoclonus in patients with Hashimoto disease. The details were further elaborated by Shaw and colleagues and by Chong and associates. Some cases have had a relapsing course over months or years. It is important to note that most have had normal thyroid function. There are in these cases, however, high titers of several antithyroid antibodies, particularly antibodies against thyroid peroxidase and thyroglobulin; some affected individuals have more than one such antibody. Ferracci and colleagues found evidence of the production of these antibodies in the nervous system and of their presence in spinal fluid. One must be cautious, however, in interpreting the presence of antithyroid antibodies in the blood, as they are detected in many people without an encephalopathy, particularly older women, and in two-thirds of patients with Graves disease.
The most commonly observed syndrome is of confusion or stupor accompanied by multifocal myoclonus, but seizures—including myoclonic and rarely, nonconvulsive status epilepticus, may occur as well. Hemiparesis, ataxia, psychosis, and unusual tremors, including those of the palate, have been reported in individual cases as in the series reported by Castillo and colleagues; they found tremor, transient aphasia, myoclonus, ataxia and seizures to be present in that order of frequency. Many had liver function abnormalities and one-fifth showed inflammatory changes in the CSF. Some of the reports included children.
Often there are other members of the family with a different autoimmune disease. It has been the myoclonic aspect of the encephalopathy, a feature of all of the cases we have observed, which has usually led to consideration of this diagnosis. It is not uncommon for such cases to be mistaken for Creutzfeldt-Jakob disease (subacute spongiform encephalopathy). Early descriptions of the illness included a pleocytosis of the spinal fluid and white matter lesions, but we have not consistently noted these abnormalities. What limited pathology there is, in a case studied after 5 months of illness, has shown only nonspecific activation of microglia cells (Perrot et al).
Treatment The encephalopathic symptoms and high titers of antithyroid antibodies respond well to steroid therapy (see Chong et al). In the case reported by Newcomer and associates, a rapid reversal of thyrotoxic coma (and corticospinal signs) was effected by plasma exchange, in parallel with a reduction in T4 and T3 levels, and similar results were reported by Boers and Colebatch. The circulating antibodies and the response to corticosteroids and plasma exchange implicate an immune pathogenesis, perhaps similar to paraneoplastic limbic encephalitis (see “Encephalomyelitis Associated With Carcinoma and Limbic Encephalitis” in Chap. 30) such as the encephalitis that may accompany ovarian teratoma, and to lupus.