Severe Hyperferritinemia in Metabolic Dysfunction-Associated Steatotic Liver Disease With Normal Transferrin Saturation and Polyclonal Hypergammaglobulinemia Mimicking Iron Overload
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic immunometabolic disorder characterized by the interplay between insulin resistance, hepatic lipid accumulation, and chronic low-grade inflammation. While mild elevations in serum ferritin are frequently observed in MASLD, markedly elevated ferritin levels often prompt evaluation for iron overload syndromes, inflammatory disorders, or malignancy. The coexistence of polyclonal hypergammaglobulinemia further complicates diagnostic interpretation. We report a 36-year-old female with overweight status, insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR) = 6.3), prediabetes (glycosylated hemoglobin = 6.1%), hypertriglyceridemia, and hyperuricemia, who demonstrated persistent hyperferritinemia (1281-1642 ng/mL) over 19 months with normal transferrin saturation (23%). Liver enzymes were mildly elevated, while bilirubin, gamma-glutamyl transferase, lactate dehydrogenase, C-reactive protein, and renal function remained normal. Serum protein electrophoresis revealed polyclonal hypergammaglobulinemia with elevated IgG. Imaging confirmed severe hepatic steatosis (S3) without fibrosis. MRI-based liver iron quantification demonstrated normal liver iron concentration (LIC = 2.70 mg/g), definitively excluding iron overload. Extensive evaluation excluded iron overload, autoimmune disease, and hematologic pathology. This case illustrates a clinically important…
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