What is the association between Moya Moya disease and endocrine disorders, and how are they managed?

Moyamoya Disease and Endocrine Disorders: Association and Management

Key Association with Hyperthyroidism

The most recent 2023 American Heart Association/American Stroke Association guidelines explicitly exclude hyperthyroidism from the diagnostic criteria for Moyamoya syndrome, indicating no universal agreement on this association, though clinical case series demonstrate a clear temporal relationship between Graves' disease and Moyamoya-like vasculopathy. 1

Evidence for Thyroid Disease Association

The relationship between Moyamoya and thyroid disorders, particularly Graves' disease, presents a clinical paradox:

• Guideline Position: The 2021 Research Committee on Moyamoya Disease (RCMD) Guidelines removed hyperthyroidism from the list of conditions associated with Moyamoya syndrome, suggesting it should not be classified as secondary Moyamoya when thyroid disease is present 1

• Clinical Reality: Multiple case series demonstrate that Moyamoya vasculopathy frequently coexists with Graves' disease, with 18 of 21 patients (86%) manifesting Moyamoya symptoms during hyperthyroid states 2, and all 12 patients in another series presenting with ischemic events while thyrotoxic 3

Proposed Mechanisms

The pathophysiologic link between Graves' disease and Moyamoya-like vasculopathy likely involves:

• Hemodynamic alterations from thyrotoxicosis causing increased cerebral blood flow demands in already compromised vessels 3, 4
• Anti-TSH receptor antibodies potentially exerting toxic vascular effects 4
• Shared genetic and autoimmune factors that may predispose to both conditions 2, 5

Clinical Presentation Patterns

Demographics and Timing

• Moyamoya with concurrent Graves' disease predominantly affects adult females (16 of 21 patients in one series) 2
• Symptoms typically manifest during active hyperthyroidism, with 86% presenting while thyrotoxic 2
• Both bilateral (18/21) and unilateral (3/21) vascular involvement can occur 2

Symptom Profile

• Ischemic events dominate: 19 of 21 patients showed cerebral infarction 2, and 11 of 12 patients in another series presented with stroke or TIA 3
• Asymmetric stenosis patterns are common when associated with Graves' disease 3

Management Algorithm

Step 1: Thyroid Function Assessment

Screen all patients with suspected Moyamoya for thyroid disease, as treating hyperthyroidism may suffice to improve neurological symptoms without requiring immediate surgical intervention. 4

• Obtain thyroid function tests (TSH, free T4, free T3) and anti-TSH receptor antibodies 3, 4
• Document thyroid status at time of neurological symptom onset 2

Step 2: Antithyroid Treatment First

• Initiate antithyroid therapy (methimazole or propylthiouracil) to achieve euthyroid state before considering revascularization 2, 5
• Normalize thyroid hormone and blood glucose levels (if diabetic) prior to surgical intervention 5
• Critical warning: Two patients experienced recurrent ischemic attacks after antithyroid drug withdrawal, indicating the need for sustained thyroid control 3

Step 3: Cerebrovascular Evaluation During Treatment

• Perform digital subtraction angiography (DSA) or magnetic resonance angiography (MRA) to confirm Moyamoya vasculopathy 3
• Assess cerebral perfusion with CT perfusion or MRI arterial spin labeling to identify hemodynamically compromised territories 6, 7
• Monitor for progression with serial imaging, as 20% of patients show disease progression over mean 6-year follow-up 7

Step 4: Surgical Revascularization Criteria

Proceed with encephaloduroarteriosynangiosis (EDAS) or direct bypass surgery after achieving euthyroid state if:

• Ongoing ischemic symptoms persist despite optimal medical management 7
• Evidence of compromised cerebral perfusion on imaging studies 7
• Recurrent TIAs or strokes occur 2

Step 5: Surgical Outcomes

• 17 of 20 patients (85%) achieved good recovery after EDAS surgery following antithyroid treatment 2
• Post-operative DSA demonstrated good collateral circulation from superficial temporal artery in all examined patients 2
• Direct bypass reduces hemorrhagic risk from 7.6% to 2.7% per year (p=0.04) 7

Other Endocrine Associations

Diabetes Mellitus

• Coexistence of Moyamoya, Graves' disease, and type 2 diabetes mellitus has been reported, though extremely rare 5
• Normalize blood glucose levels before revascularization surgery 5
• Genetic and autoimmune factors may link these conditions 5

Excluded Associations

The 2023 AHA/ASA guidelines do not list any endocrine disorders among the established comorbidities for Moyamoya syndrome, which include: autoimmune diseases, meningitis, brain tumors, Down syndrome, neurofibromatosis type 1, head irradiation, and sickle cell disease 1

Critical Clinical Pitfalls

Diagnostic Errors

• Do not dismiss thyroid disease as coincidental when Moyamoya vasculopathy is present—the temporal relationship with hyperthyroidism is too consistent to ignore 2, 3
• Recognize that asymmetric stenosis patterns are more common in Graves-associated cases than in idiopathic Moyamoya 3

Treatment Sequencing Errors

• Never proceed directly to surgery without first achieving euthyroid state, as uncontrolled hyperthyroidism increases perioperative stroke risk 2, 5
• Maintain long-term antithyroid therapy—drug withdrawal precipitates recurrent ischemic events 3

Monitoring Failures

• Conservative management carries 65% 5-year risk of recurrent ischemic events for unilateral disease and 82% for bilateral involvement 6
• Serial follow-up is mandatory given the 5% annual cerebrovascular event risk even in asymptomatic patients 7

Geographic and Ethnic Considerations

• While Moyamoya-Graves' association is well-documented in Asian populations 2, 3, it also occurs in Caucasian Europeans 4
• The first reported case in Western European Caucasians emphasizes that thyroid screening should be universal regardless of ethnicity when Moyamoya is suspected 4