Neuropsychiatric Disturbance with Autoimmune Thyroid Disease is Underrecognized
June 1, 1997
Neuropsychiatric Disturbance with Autoimmune Thyroid Disease is Underrecognized
ABSTRACTS & COMMENTARY
Sources: Ghika-Schmid F, et al. Hashimoto’s myoclonic encephalopathy: An underdiagnosed treatable condition? Movement Disorder 1996;11:555-562; Cohen L, et al. A woman with relapsing psychosis who got better with prednisone. Lancet 1996;347:1228; Marino M, et al. Mild clinical expression of myasthenia gravis associated with autoimmune thyroid diseases. J Clin Endocrinol Metabol 1997;82:438-443.
Ghika-schmid et al report on two elderly female patients (ages 73 and 78) who presented with a subacute encephalopathy, hypertonia, myoclonus, partial complex and generalized seizures. Thyroid function tests were within normal limits, with the exception of a slightly elevated TSH, and high titers of antithyroglobulin antibodies (1325 and 1638). One of the patients additionally had hyponatremia (Na = 125 mmol/L) consistent with SIADH. Both patients were treated with corticosteroids (hydrocortisone or methylprednisolone, 150-1000 mg initially) and experienced slow clinical improvement over 2-6 weeks with a corresponding reduction in antithyroid antibodies. One of the patients relapsed two months after discontinuation of corticosteroids. Antibodies increased and were successfully retreated.
Cohen et al describe a 59-year-old woman admitted to the Neurology service in the Hopital de la Salpetriere with a provisional diagnosis of CJD. Her initial symptoms ranged from confusion, "depression," and "acute psychosis," precipitating a psychiatric hospitalization for six months. A TSH was noted to be elevated with a normal T4, and the patient was treated with thyroxine 50- 125 mcg without clinical improvement. She progressed with encephalopathic features, gait disorder, myoclonus, and eventually generalized seizures. High titers of antithyroperoxidase and antithyroglobulin antibodies were discovered, at which time the patient was started on prednisone (1 mg/kg/d) with significant clinical improvement over several weeks, and a 2.5- to five-fold reduction in antithyroid antibody levels. As the prednisone was slowly tapered over six months, a brief relapse occurred which responded to raising the dose of steroid.
Marino et al evaluated a total of 129 myasthenia gravis (MG) patients of whom 56 were found to have associated autoimmune thyroid disease (25 with Hashimoto’s thyroiditis, 31 with Graves disease). Compared to the other 73 MG patients, the patients with autoimmune thyroid disease had a measurably higher incidence of ocular MG and a lower incidence of generalized MG, thymus abnormalities, or acetylcholine receptor antibodies.
COMMENTARY
The complex spectrum of neuropsychiatric disturbance associated with Hashimoto’s thyroiditis is described in part with the above case reports. Ghika-Schmid et al also provide a helpful table that reviews the limited neurologic literature of this disorder with clinical and lab findings, including Lord Brain’s description from more than 30 years ago (Brain et al. Lancet 1966;2:512-514). They summarize 30 patients in the literature (26 F/4 M) with most patients presenting in their mid 30s to mid 50s (range, 14-78 years) as might be expected for this autoimmune thyroid disorder. The only subtle lab abnormality in routine TFTs might be a slightly elevated TSH with otherwise normal T4 levels, which should lead the astute clinician to test for antithyroid antibodies despite the patient appearing to be clinically euthyroid. A greater awareness of "subclinical hypothyroidism" has developed with the standard measurement of serum TSH levels and antithyroglobulin and thyroperoxidase antibodies. The mechanism of Hashimoto’s encephalopathy is poorly understood, since the neurologic disturbance appears not to be related to a derangement in the absolute level of thyroid hormone (such as in true hypothyroid myxedema coma or Graves thyrotoxicosis). Nor are antithyroid antibodies likely to be pathogenic, as the latest understanding is that they are merely an epiphenomenon of T-cell mediated thyroid destruction (Tomer Y. Clin Immunol Immunopathol 1997;82:3-11). Rather, there may be a subset of autoimmune thyroid disease in which central neural substrates are additionally targeted by immune processes.
In more overt forms of disease, the patient may present with diffuse encephalopathy and myoclonus. However, in persons with mild or early forms, there may be more subtle cognitive and psychiatric complaints, ranging from impaired concentration to mood changes. Thus, Hashimoto’s encephalopathy may be underrecognized and hence undertreated in clinical practice. In our experience from a select population of patients in the Multiple Sclerosis Center, two patients with clinically definite established MS but minor demyelinating disease had subsequent onset of cognitive and psychiatric symptoms associated with high (> 1000) antithyroglobulin antibodies, minor elevation in TSH, and otherwise normal TFTs. They underwent striking clinical improvement over 3-4 weeks following corticosteroid treatment. Interestingly, several of the prior case reports reviewed by Ghika-Schmid also demonstrated multiple white matter lesions on brain MRI, raising the possibility of a superimposed autoimmune demyelinating or vasculopathic disorder. Indeed, others have suggested a possible form of encephalomyelitis in Hashimoto’s encephalopathy (Shaw, et al. Neurology 1991;41:228-233).
Thus, in patients presenting with clinical features consistent with Hashimoto’s encephalopathy, empiric therapy with corticosteroids and possibly low-dose thyroxine should be initiated. Other concomitant autoimmune disease, either a systemic or a primary neurologic disorder (e.g., SLE or MS), should be considered. Careful monitoring of clinical status and antibody titers will aid in determining a tapering schedule for corticosteroids. Relapses, however, can often occur. ba
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