Reversible Cerebral Vasoconstriction Syndrome with Hyperthyroidism

Abstract

A 55-year-old woman presented with a recurrent thunderclap headache triggered by bathing, showering, and the Valsalva maneuver. Laboratory investigations revealed hyperthyroidism, whereas magnetic resonance imaging demonstrated a convexity subarachnoid hemorrhage and vasospasm of the cerebral arteries. The patient was diagnosed with reversible cerebral vasoconstriction syndrome (RCVS) and hyperthyroidism. The association between RCVS and hyperthyroidism has received only limited attention in literature. We herein report a case of RCVS with hyperthyroidism and discuss the association between RCVS and the thyroid function.

Introduction

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headache and segmental constriction of the intracranial arteries (1). RCVS can cause complications, such as a convexity subarachnoid hemorrhage (cSAH), intracranial hemorrhage, and ischemic stroke (1,2). Many factors are known to trigger RCVS, including postpartum vasoactive drugs, blood products, head trauma, carotid endarterectomy, and catecholamine-secreting tumors (1). However, thyrotoxicosis is not generally listed as a trigger for RCVS. To the best of our knowledge, only two cases of RCVS with thyrotoxicosis have been reported previously (3,4). Therefore, we herein report the third known case of RCVS with hyperthyroidism and discuss the association between RCVS and the thyroid hormone levels.

Case Report

A 55-year-old woman was transferred to our department with a recurrent thunderclap headache. Her headache was severe and holocranial and it was precipitated by bathing, showering, and Valsalva maneuvers. The attacks lasted for approximately one hour, recurred several times daily, and followed a waxing and waning course lasting for approximately one week. She had been diagnosed with Graves' disease 10 years previously and achieved remission within a year of receiving medication. Since then, she had not experienced symptoms suggestive of thyrotoxicosis, such as weight loss, diarrhea, or tremors. Physical examination revealed no neurological defects or meningeal irritations. Laboratory investigations indicated a low thyroid-stimulating hormone (TSH) level (＜0.0090 μIU/mL), a high free T4 level (1.66 ng/dL), and a high free T3 level (5.40 pg/mL). Tests for thyroid-stimulating antibody, anti-thyroid peroxidase antibody, and anti-thyroglobulin antibody were all positive. Computed tomography (CT) and magnetic resonance (MR) imaging demonstrated cSAH (Figure A-C), and MR angiography revealed segmental narrowing and dilation of the intracranial artery (Figure D).

Figure.

Initial CT and MR images showing a convexity subarachnoid hemorrhage (A-C). Segmental narrowing and dilation of the intracranial artery (arrows) was demonstrated in MR angiography on day 1 (D) and normalized in follow-up imaging by day 42 (E).

The patient was diagnosed with recurrent Graves' disease and RCVS. Subsequently, verapamil, thiamazole, and potassium iodide were administered. The free T4 level normalized on day 23 and the free TSH level normalized on day 69. Follow-up MR imaging on day 42 revealed neither any additional complications nor normalized angiographic findings (Figure E). The headache gradually improved after treatment initiation and disappeared after three months.

Discussion

Overall, we describe a case of RCVS with hyperthyroidism, which is clinically important because the association between RCVS and thyrotoxicosis has only been scarcely reported. While the relationship between cerebral vasospasm and thyroid hormones has rarely been discussed, several reports have indicated a relationship between the thyroid function and coronary vasospasm in the cardiovascular field. For example, one observational study showed that hyperthyroidism was more common in patients with vasospastic angina (VA) than those in the non-VA group (5). In another study, VA with thyrotoxicosis was associated with a more severe course than VA without thyrotoxicosis (6). Although it is unclear whether thyroid hormones exert the same effects on the cerebral arteries as on coronary arteries, thyrotoxicosis may potentially be associated with cerebral vasospasm.

While the detailed pathophysiology of RCVS remains unclear, the dysregulation of the cerebrovascular tone with sympathetic overactivity is considered to play a significant role in its development (1,7). A prior study on the forearm blood flow in patients with hyperthyroidism showed that hyperthyroidism induces a marked basal vasodilation by triggering excessive endothelial nitric oxide production and enhances sensitivity to the norepinephrine-induced vasoconstrictive reaction (8). Although data on whether thyroid hormones exert the same effects on the forearm arteries and cerebral vessels are lacking, the enhancement of norepinephrine-induced vasoconstriction by thyroid hormones may be associated with the development of sympathetic overactivity-related cerebrovascular dysregulation. This previous study further showed that thyrotoxicosis treatment normalizes the abnormal vascular activities observed in hyperthyroidism (8). Therefore, the treatment of thyrotoxicosis may help to effectively manage RCVS in patients with Graves' disease.

In the present case, despite the absence of clinical features suggestive of thyrotoxicosis, the thyroid function was assessed based on the patient's history of Graves'. Of the two previously reported cases, one had been diagnosed with Graves' disease before the onset of RCVS (3), whereas the other presented with clinical features indicative of thyrotoxicosis, including an increased appetite, weight loss, and sweating (4). As the thyroid function is not routinely tested in patients with RCVS in general medical settings, the prevalence of thyrotoxicosis in patients with RCVS may be underestimated. Screening for the thyroid function may be useful for the management of patients with RCVS.

Despite the high prevalence of thyrotoxicosis, reports of RCVS are extremely rare. We have therefore formulated several hypotheses to explain this phenomenon. First, we hypothesized that the prevalence of thyrotoxicosis in patients with RCVS might have been underestimated, as previously mentioned. Conversely, the possibility that RCVS may sometimes be overlooked in patients with thyrotoxicosis presenting with headaches should also be considered. The second hypothesis involves a two-hit model: in studies of the forearm artery, thyroid hormones alone were found to cause vasodilation, whereas vasoconstriction occurred when norepinephrine was present (8). Therefore, elevated thyroid hormone levels alone may not be sufficient to trigger RCVS. Therefore, it is possible that RCVS develops only when additional factors, such as norepinephrine, coexist with hyperthyroidism.

Thyrotoxicosis is a potential precipitator of RCVS. To the best of our knowledge, this is only the third reported case of RCVS associated with hyperthyroidism. As this report is based on a single case, further investigations are required to definitively determine the association between RCVS and thyroid hormones.

The authors state that they have no Conflict of Interest (COI).