Type B insulin-resistance syndrome presenting as autoimmune hypoglycemia, associated with systemic lupus erythematosus and interstitial lung disease
A 38-year-old Korean woman suffered an episode of unconsciousness and was transferred to an emergency center where her blood glucose was found to be 18 mg/dL. She recovered her senses after intravenous infusion of distilled water containing 50% dextrose. She had no relevant medical or family history except the development of the skin rashes after sunlight exposure. The patient denied any use of exogenous insulin or oral hypoglycemic agents and she was not employed in a health-related profession. Her vital signs were as follows: blood pressure, 120/70 mmHg, heart rate, 75/min, and body temperature, 36.7℃. A physical examination was unremarkable other than the presence of fixed erythematous plaques on her cheeks. During the hypoglycemic episode, her serum insulin level was very high (2,207.1 pmol/L; normal range, 18 to 173) and the C-peptide level was elevated (1.7 nmol/L; normal range, 0.37 to 1.47). The patient underwent a diagnostic fasting test. After 4 hours of fasting, she developed symptomatic hypoglycemia, with a glucose level of 32 mg/dL, accompanied by an inappropriately high serum insulin level of 1,430.1 pmol/L and a C-peptide level of 1.6 nmol/L. For the differential diagnosis of hypoglycemia associated with unsuppressed insulin level, a computed tomography (CT) scan of the abdomen was performed, but it failed to localize any pancreatic tumor, such as an insulinoma. Instead, the abdominal CT revealed ground-glass opacities and intralobular reticular pattern densities on both lower-lung fields (), although there was no abnormal finding on her chest radiographs () and she did not complain of respiratory symptoms, such as dyspnea, cough, sputum production, or chest tightness. An additional high-resolution CT (HRCT) scan showed the same findings, suggesting interstitial lung disease (ILD) (). Further biochemical and serologic studies showed following abnormal values: positive titer for antinuclear antibodies, anti-double-stranded DNA (dsDNA) antibodies, anti SS-A/SS-B antibodies, and anti.ribonucleoprotein antibodies, erythrocyte sedimentation rate 85 mm/hr, C3 0.821 g/dL, and C4 0.096 g/dL. Other tests, including complete blood count, hepatic and renal function, thyroid function, urinalysis, anti-phospholipid antibody, and anti-insulin antibody were unremarkable. Considering all these facts, the presence of type B insulin-resistance syndrome associated with SLE was suggested, and a confirmed diagnosis was made after a positive anti-insulin receptor antibody radioreceptor assay. For a definitive diagnosis of the lung lesions, video-associated thoracoscopic surgery was performed and the histopathological findings showed a pattern of fibrotic non-specific interstitial pneumonia. The patient was referred to the Department of Rheumatology and Immunosuppressive Therapy, and a combination of prednisolone 30 mg/day, hydroxychloroquine 300 mg/day, and azathioprine 50 mg/day was started. She has had no further recurrence of hypoglycemia, and the dose of prednisolone has since then been decreased gradually to 5 mg/day during her outpatient follow-up.