Endocrine Abstracts

We present the case of 60 year old male with acquired generalised lipodystrophy secondary to nivolumab therapy (immune checkpoint inhibitor) which he received for two years following relapse of treated renal clear cell cancer (nephrectomy; pazopanib treatment on initial relapse). He had excellent response to nivolumab and completed treatment, but a month later he developed significant weight loss, starting with fat loss from his face. His wife identified some case reports of lipodystrophy as rare side-effect of nivolumab. He was referred to the nationally commissioned, highly specialised insulin resistance/lipodystrophy service at Addenbrooke’s Hospital who confirmed the diagnosis of acquired generalised lipodystrophy. He had low subcutaneous fat mass, low leptin concentration, hypertriglyceridaemia, hyperinsulinaemia, hyperglycaemia and hepatic steatosis on serial MRI imaging (but no hepatic fibrosis). He was initially managed with metformin, fenofibrate and specialist dietitian input (low fat diet), along with increased physical activity. He declined starting a statin despite increased cardiovascular risk. It was later advised that he start metreleptin replacement therapy but he has currently declined this. Acquired generalized lipodystrophy is a very rare disorder and hence under-recognised. It is difficult to recognise initially as the clinical appearance overlaps with other causes of weight loss and the changes in fat distribution can easily be missed. In patients with acquired lipodystrophy, metabolic abnormalities associated with severe insulin resistance include hypertriglyceridemia, diabetes mellitus, hepatic steatosis and acanthosis nigricans may develop soon after the onset of subcutaneous fat loss. Immune checkpoint inhibitor (nivolumab, pemrozulimab) induced acquired generalized lipodystrophy has been reported in few case reports only and it is important to highlight to health care professionals to consider this as a differential diagnosis in patients losing weight after receiving these therapies, due to increasing use of these agents and the rarity of this syndrome.