Monitoring and Management of Elevated SHBG Levels in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Introduction to SHBG Elevation

Elevated SHBG levels can occur due to several factors, including medication-induced elevation, such as resmetirom therapy, which is an expected effect and reflects target engagement of the thyroid hormone receptor-β 1, 2
Resmetirom therapy is associated with SHBG elevation, which is a marker of target engagement and is expected during treatment 1, 2

The American Association for the Study of Liver Diseases recommends monitoring for thyroid function abnormalities and watching for potential long-term effects on gonadal or bone health in patients with elevated SHBG levels 1
A >120% increase in SHBG is associated with positive treatment response in MAESTRO-NASH trial, according to the American College of Gastroenterology 1
Monitoring of SHBG levels is crucial, and recheck of SHBG levels is recommended in 4-6 weeks if persistently elevated without explanation 1, 2

Despite SHBG elevation, free testosterone levels typically remain unchanged, and no significant changes in bone mineral density have been reported, according to the American College of Gastroenterology 2
Current safety data do not suggest cause for concern regarding the use of resmetirom in patients with elevated SHBG levels, as stated by the American Association for the Study of Liver Diseases 2

Measure TSH and free T4 to determine thyroid status, as recommended by the Endocrine Society 3
Elevated SHBG for a few weeks may indicate hyperthyroidism, and thyroid function tests should be continued in patients on resmetirom 1, 2

If a patient is on resmetirom, no specific intervention is needed unless symptoms develop, and SHBG elevation confirms target engagement, according to the American Association for the Study of Liver Diseases 1, 2
If a patient is not on resmetirom, evaluation for hyperthyroidism, assessment of liver function, and consideration of sex hormone evaluation are recommended, as stated by the American College of Gastroenterology 1, 2