SUN-325 - Methimazole-Associated Cholestatic Liver Injury with Marked LDL Elevation from Lipoprotein-X in an Elderly Patient

Background
Methimazole is commonly used for hyperthyroidism and is generally well tolerated. Rarely, it can
cause drug-induced liver injury, typically within the first three months of therapy.

Case Presentation
An 84-year-old woman presented to outpatient endocrinology for unintentional 100-pound
weight loss over one year. Thyroid testing showed suppressed TSH (0.03 μIU/mL) with
near-normal free T4 (1.43 ng/dL). Neck ultrasound identified a thyroid nodule, and radionuclide
uptake scan demonstrated focal increased uptake in the right thyroid lobe, consistent with a
toxic thyroid nodule. Methimazole 10 mg daily was initiated. Approximately six weeks later, she
developed progressive jaundice and generalized pruritus and was hospitalized. Labs revealed
total bilirubin 17.4 mg/dL, AST 514 U/L, ALT 881 U/L, alkaline phosphatase 842 U/L, and INR
0.87. A markedly elevated LDL cholesterol level was also noted despite previously normal lipid
levels. Abdominal imaging showed no biliary obstruction. Methimazole was discontinued, and
liver biopsy demonstrated portal and lobular hepatitis with spotty necrosis and a cholestatic
pattern of injury without fibrosis or plasma cell infiltrates.

Discussion
Drug-induced liver injury was favored given the close temporal association with methimazole
initiation, the cholestatic laboratory profile, exclusion of obstructive and autoimmune etiologies,
and supportive histopathology. Methimazole-associated hepatotoxicity is uncommon reported in
< 1% of treated patients and most often occurs within the first three months of therapy. Marked
“LDL” elevation in severe cholestasis may reflect lipoprotein-X, an abnormal cholesterol-rich
lipoprotein formed during cholestasis that can be misclassified as LDL on standard assays and
is considered non-atherogenic. Apolipoprotein B measurement can help distinguish
lipoprotein-X–related pseudohypercholesterolemia from true atherogenic dyslipidemia, and
management should focus on treating the cholestatic process rather than initiating or escalating
statin therapy.

Conclusion
This case highlights methimazole as a rare cause of severe cholestatic liver injury and
emphasizes recognition of lipoprotein-X–mediated pseudohypercholesterolemia as an important
diagnostic pitfall during cholestasis.

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