Hyperthyroid dementia: clinicoradiological findings and response to treatment

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Abstract

Dementia associated with hyperthyroidism is less well documented than is hypothyroid dementia. Therapeutic response of hyperthyroid dementia and associated cerebral circulatory and/or metabolic abnormalities has not been elucidated. We described a patient with hyperthyroid dementia and clinicoradiological response to treatment. Single photon emission computed tomographic (SPECT) study was repeated and analyzed semiquantitatively. A 67-year-old man experienced progressive impairments of attention, memory, constructive skills and behavior as well as hand tremor and weight loss of two-year duration. Laboratory findings were compatible with Graves’ disease. The initial SPECT showed diffuse tracer uptake defect with an accentuation in the bilateral temporoparietal regions. Clinical and SPECT findings both suggested concurrent ‘possible’ Alzheimer’s disease. However, initial treatment with a beta-blocker improved behavior and attention-related cognitive functions as well as tracer uptake in the frontal lobes. Subsequent treatment with additional methimazole then improved memory and constructive abilities when a euthyroid state was established. Uptake defect in the temporoparietal regions also responded gradually to the medication. We suggest that the present patient represent hyperthyroid dementia, which responds favorably to treatment with regard to clinical symptoms and SPECT findings. We also suggest that thyroid function be measured in patients with ‘possible’ Alzheimer’s disease because treatable hyperthyroid dementia may not be identified.

Introduction

Dementia associated with thyroid dysfunction deserves closer attention because of its risk of being unrecognized or misdiagnosed as dementia from other causes. Dementia is associated more frequently with hypothyroidism than hyperthyroidism. Slowing of mentation, apathy or defects of memory are noted in 70 to 90% of patients with hypothyroidism [1], [2]. Single photon emission computed tomography (SPECT) features diffuse uptake defect, which is reversible to a normal pattern as thyroid function returns normal [3].

On the other hand, affective psychoses and schizophrenia-like symptoms are more prevalent in hyperthyroidism [4], [5], [6], especially in younger patients [2], [7]. Dementia is reportedly less common and severe than in hypothyroidism [2], [8] and may appear in elderly hyperthyroid patients in conjunction with confusion, apathy or depression [2], [7]. Martin et al. found agitation in 58%, dementia in 33%, confusion in 18% and apathy in 15% of 60 elderly patients with hyperthyroidism [7]. Anti-thyroid therapy is effective in improving cognitive and psychic impairments [9], [10], [11], [12] as well as abnormalities of electroencephalogram (EEG) [12]. However, subjective impairments in memory, attention, planning or productivity [11], and objective evidence of defects in cognition and behavior [6], [12], [13] may persist after proper treatment. Moreover, subclinical [14] and remitted [15] hyperthyroidism is associated with subjective impairment of physical and psychological well-being.

Some studies maintain clinical [16], [17], genetic [18] or pathophysiological [19] link between Alzheimer’s disease (AD) and thyroid dysfunction or thyroid-related autoantibodies in certain patient populations. However, other studies have reached a negative conclusion with regard to the association between AD and thyroid [20], [21], [22], [23], [24], [25], [26], [27], implicating independence of hyperthyroid dementia from degenerative dementia such as AD.

Radiologically, Sensenbach et al. found in a study using the nitrous oxide method a general increase in cerebral blood flow in hyperthyroid state and a decrease in hypothyroid state, both of which returned to normal in euthyroid [28]. However, they did not refer to regional difference in blood flow or their association with cognitive function. Conversely, Bhatara et al. [29] using magnetic resonance spectroscopy found decreased levels of choline-related compounds in the right frontal lobe of hyperthyroid patients that moved toward normal after anti-thyroid treatment. They suggested that chemical imbalance between cholinergic and adrenergic systems may be associated with prefrontal lobe dysfunction in hyperthyroid patients. Although epochal, the authors prudently considered these results preliminary. Thus, clinicoradiological correlation of hyperthyroid dementia and their chronological response to treatment has not yet been fully elucidated.

The purpose of this study is to contribute to these issues by describing a hyperthyroid patient who had evidence of dementia and characteristic SPECT findings, both of which responded favorably to treatment.

Section snippets

Patient

A 67-year-old right-handed carpenter had been in good health. He had a medical history of hypertension since 59 years-of-age, Bell’s palsy on the left at 60 and transient depression at 64 when his beloved dog died. In the same year of 1997, the patient began to experience unusual thirst, progressive body weight loss and hand tremor. The patient made carpentry errors and on some occasions he had to re-make his products several times because of consecutive measuring mistakes, which was highly

Discussion

Distinctive features of the present patient are two-fold. First, dementia improved in response to treatment for hyperthyroidism, and second, SPECT findings shared characteristic abnormalities claimed specific for AD, which furthermore were normalized steadily as the hyperthyroid state was corrected. To the best of our knowledge, there has been no description of similar patients in the literature.

When progressive amnesia accompanies multiple cognitive impairments, diffuse brain atrophy on MRI

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