ECE2019 Poster Presentations Diabetes, Obesity and Metabolism 1 (104 abstracts)
Acquired generalized lipodystrophy: a new cause of Anti-PD-1 immune-related diabetes
Christine Cugnet Anceau 1, , Alexandre Jehl 1, , Corinne Vigouroux 4, , Stephane Dalle 2, , Olivier Harou 2, , Lucien Marchand 8 , Olivier Lascols 4, , Cyrielle Caussy 1, , Charles Thivolet 1, , Martine Laville 1, & Emmanuel Disse 1,
1Hospices Civils de Lyon, Lyon Sud Hospital, Endocrinology Diabetology and Nutrition Department, Pierre Benite, France; 2ImmuCare, Cancer Institute of Hospices Civils de Lyon, Lyon, France; 3Lyon University, Université Claude Bernard Lyon 1, Lyon, France; 4Assistance Publique-Hôpital de Paris, Saint Antoine Hospital, Biology and Molecular Genetics and Endocrinology Departments, Paris, France; 5Sorbonne University, INSERM UMR S938, Saint Antoine REsearch Center (CRSA), Paris, France; 6Hospices Civils de Lyon, Lyon Sud Hospital, Dermatology Department, Pierre Benite, France; 7Hospices Civils de Lyon, Lyon Sud Hospital, Anatomopathology Department, Pierre Benite, France; 8Saint Luc Saint Joseph Hospital, Endocrinology Department, Lyon, France.
Context: Anti-programmed cell death-1 (Anti-PD-1) antibodies have revolutionized advanced cancer therapy. Anti-PD1 therapy is responsible for immune-related adverse events, with frequent endocrine manifestations. Acquired generalized lipodystrophy (AGL), is a rare disease, thought to be immune-mediated, characterized by loss of adipose tissue and insulin resistance-associated complications. We describe the first case of AGL induced by immune checkpoint therapy.
Case description: A 62-year-old woman is treated with nivolumab for metastatic melanoma. After 18 months of treatment (34 courses), the patient developed a severe and rapidly progressive weight loss. The computed tomography revealed a major liver steatosis hitherto unknown, which was associated with hepatic cytolysis. Autoimmune and viral hepatitis were ruled out, and the liver biopsy showed a nonalcoholic steatohepatitis. One month later, the patient presented with a severe nonketotic hyperglycemia (24.9 mmol/L) and HbA1c 11.4% (97 mmol/mol). Aniti-GAD, IA2 and ZNT8 autoantibodies were negative although the patient exhibited a DR4 haplotype for class II HLA genes (DRB1*04 DQA1*03 DQB1*03:02) conferring a high risk of type 1 diabetes. Her pancreas was morphologically normal at abdominal CT and serum lipases were in a normal range. Fasting plasma insulin and HOMA-IR were strongly increased (40 mUI/L and 44.5, respectively). Diabetes was associated with severe insulin resistance and undetectable plasma leptin. She had presented with a rapidly progressive generalized loss of subcutaneous adipose tissue. The search for serum autoantibodies against insulin and insulin receptor was negative. The pathogenic variant in 23 genes of associated with lipodystrophy was absent. The complement system was unaffected and non-organ-specific autoantibodies were negative. The initiated treatment was composed with high-dose basal-bolus insulin regimen (1.6 U/kg/d) and metformin. Subcutaneous biopsy showed that atrophic adipose tissue was extensively infiltrated with cytotoxic CD8+T lymphocytes and fibrosis.
Conclusions: AGL should be added to the list of immune-related adverse events associated with anti-PD-1 treatment for malignancies. It is associated to a new pathophysiological mechanism of anti-PD-1 related diabetes that should be suspected from recent modification of body appearance with unusual fat loss. The benefit/risk ratio of leptin replacement on metabolic improvement, tumor progression and responsiveness to immunotherapy, needs to be evaluated in that setting.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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