The uptake of immune checkpoint inhibitor (ICI) therapies for the management of oncological conditions has significantly increased, and these therapies may cause off-target toxicities. Complications including endocrinopathies can cause significant morbidity which can be permanent. We report a case of significant generalised lipodystrophy and its related metabolic complications secondary to pembrolizumab therapy.
A 48-year-old Caucasian lady presented with rapid weight loss of 20 kg over several months. This occurred on a background of type 2 diabetes and lymph node metastatic breast cancer for which she had completed neoadjuvant/adjuvant systemic chemotherapy and pembrolizumab. She received a total of 14 months of pembrolizumab, with weight loss initially occurring towards the end of her treatment course. There were no concerns of recurrent disease as a cause for her weight loss.
Weight loss was associated with a decline in glycaemia, with an increase in HbA1c from 7.7% to 9.2% despite escalation of oral hypoglycaemic agents. On initial endocrinology review, severe generalised lipodystrophy was noted affecting the limbs and face, particularly with prominent zygomatic arches and loss of buccal fat pads. Acanthosis nigricans was present in the neck and axillae. Other causes of deteriorating glycaemia secondary to ICIs were excluded, with a robust C-peptide of 3.84nmol/L (paired glucose 7.6mmol/L) and a normal lipase level. New onset hypertriglyceridaemia was noted to 5.7mmol/L, alongside a decreased HDL. Other endocrinopathies including adrenal insufficiency and thyroid pathologies were absent. She was commenced on pioglitazone with some evidence of benefit in other causes of lipodystrophy. Medium-to-long term response to therapy will be assessed shortly.
This case highlights a rare complication of lipodystrophy from ICI therapy, with less than ten recorded cases worldwide [1]. Early detection for lipodystrophy is crucial in ensuring metabolic complications are screened in a timely manner, though reversibility of this condition currently remains unclear.