How are thyroid function tests monitored in a patient with myasthenia gravis (Myasthenia Gravis, MG)?

Thyroid Function Monitoring in Myasthenia Gravis

Screening at Diagnosis and Periodically Thereafter

Patients with myasthenia gravis should undergo thyroid function testing at diagnosis and periodically during follow-up, as thyroid dysfunction occurs in 6-20% of MG patients, with hypothyroidism being more common than hyperthyroidism in most populations. 1, 2, 3

Initial Screening Protocol

• Measure TSH and free T4 at the time of MG diagnosis to establish baseline thyroid status, as thyroid dysfunction is significantly more prevalent in MG patients than in the general population 1
• Test for anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies soon after diagnosis, as these predict future thyroid dysfunction and are present in 27-38% of MG patients 1, 2, 4, 5
• Avoid testing during acute MG exacerbation or immediately after high-dose corticosteroid initiation, as these can cause transient thyroid function abnormalities (euthyroid sick syndrome) 1

Frequency of Ongoing Monitoring

• Recheck TSH every 1-2 years in patients with normal initial thyroid function 1
• Monitor more frequently (every 6-12 months) if thyroid antibodies are positive, as these patients have 4.3% annual progression risk to overt hypothyroidism versus 2.6% in antibody-negative individuals 1, 6
• Test sooner if symptoms develop suggestive of thyroid dysfunction, including unexplained fatigue worsening, weight changes, temperature intolerance, or changes in MG symptom severity 1

Thyroid Dysfunction Patterns in MG

Hypothyroidism Predominates in Most Populations

• Hypothyroidism is the most common thyroid abnormality in MG patients, occurring in 1.9-5.2% with overt disease and 3.4-3.8% with subclinical disease 2, 4, 3
• Iranian and some Asian populations show even higher hypothyroidism rates (5.2% in one Iranian cohort), with hypothyroidism being the predominant thyroid dysfunction rather than hyperthyroidism 3
• Ocular MG patients have higher TSH levels (mean 2.9 mIU/L) compared to generalized MG patients (mean 1.5 mIU/L), suggesting greater susceptibility to thyroid dysfunction in the ocular subtype 5

Hyperthyroidism Also Occurs

• Hyperthyroidism affects 2-17.5% of MG patients, though rates vary widely by population and study methodology 2, 4, 7
• Graves' disease is the typical cause when hyperthyroidism coexists with MG 7
• Hyperthyroidism can worsen MG symptoms and precipitate myasthenic crisis, making prompt recognition critical 7

Subclinical Disease and Antibody Positivity

• Preclinical hyperthyroidism occurs in approximately 10% of MG patients based on TRH stimulation testing, likely representing autonomous thyroid function 2
• Anti-thyroglobulin antibodies are present in 11.5% and anti-microsomal antibodies in 27% of MG patients, rates substantially higher than the general population 2, 4
• Euthyroid MG patients with positive thyroid antibodies show exaggerated TSH response to TRH stimulation, indicating they are at high risk for future hypothyroidism 2

Clinical Implications of Thyroid-MG Coexistence

Bidirectional Screening is Essential

• Clinicians should actively look for MG in hyperthyroid patients and vice versa, especially when symptoms of either condition worsen unexpectedly 7
• The association is more than coincidence, reflecting shared autoimmune pathophysiology 1, 7

Treatment of Thyroid Disease May Improve MG

• Correction of hyperthyroidism can improve MG symptoms, as demonstrated in cases where radioiodine treatment for Graves' disease led to MG improvement 7
• Treatment of hypothyroidism may stabilize MG course, though the relationship is less well-defined than with hyperthyroidism 5

Thyroid Antibodies and MG Prognosis

• MG patients with Hashimoto thyroiditis and positive thyroid antibodies may be more responsive to glucocorticoid therapy, with relatively better short-term prognosis 5
• Higher antibody levels correlate with longer time to progression from ocular to generalized MG (P=0.04), suggesting a potential protective or modifying effect 5
• However, thyroid antibody levels do not predict long-term MG remission rates at 1,2, or 5 years of follow-up 5

Critical Pitfalls to Avoid

Don't Overlook Thyroid Disease in MG

• Failing to screen for thyroid dysfunction at MG diagnosis misses a treatable comorbidity that affects up to 43% of patients when including antibody positivity and subclinical disease 5
• Assuming fatigue is solely due to MG without checking thyroid function can lead to prolonged, unnecessary suffering from untreated hypothyroidism 1, 3

Recognize Atypical Presentations

• Hyperthyroidism in MG may present with worsening myasthenic symptoms rather than classic hypermetabolic features, particularly in elderly patients 7
• Ocular MG patients are more susceptible to hypothyroidism than generalized MG patients, warranting heightened vigilance in this subgroup 5

Timing of Testing Matters

• Testing during acute illness, MG crisis, or immediately after starting high-dose steroids can yield misleading results due to euthyroid sick syndrome 1
• Wait until metabolic stability is achieved (typically 3-6 weeks after acute events) before interpreting borderline thyroid function tests 1

Don't Ignore Positive Antibodies in Euthyroid Patients

• Euthyroid MG patients with positive thyroid antibodies require closer monitoring (every 6-12 months rather than every 1-2 years) due to 4.3% annual progression risk to overt hypothyroidism 1, 6, 2