Endocrine Abstracts

Introduction: Obesity is a complex and multifactorial disease with a chronic and relapsing nature, and is associated with over 200 co-morbidities. In a minority of patients, the obesity is caused by gene defects in the leptin-melanocortin pathway. As lifestyle interventions often fail in these patients, additional anti-obesity pharmacotherapy is needed. In this case report, we describe the therapeutic journey of a patient with early-onset obesity and hyperphagia due to heterozygous melanocortin-4 receptor deficiency.

Case presentation: A 33-year-old woman presented herself at our outpatient clinic with severe obesity, hyperphagia, and mild intellectual deficit. She developed obesity at the age of 6 years, resulting from hyperphagia. After regular lifestyle treatment without sufficient effect, a gastric bypass was performed at the age of 26 years leading to -40 kg weight loss, but eventually in greater weight regain. At the age of 27 years, genetic testing revealed a heterozygous pathogenic variant in the melanocortin-4 receptorgene, explaining her early-onset severe obesity and hyperphagia. Glucagon-like peptide-1 receptor agonist (GLP-1 RA) treatment, i.e. liraglutide 3 mg, was started which resulted in -7.3 kg of body weight (-3.8%, weight at start 193.5 kg), sustained hyperphagia (after a temporary, short term decrease), and increased fasting insulin after 5 months of treatment. GLP-1 RA treatment was therefore terminated and treatment with metformin was started at a dosage of 1500 per day, without any effects on weight or hyperphagia. Additionally, naltrexone-bupropion treatment was initiated after a 2.5 months wash-out period of liraglutide. In 6 months of naltrexone-bupropion treatment, she lost -29.5 kg of weight (-15.8%, weight at start 186.4 kg), of which -27.9 kg (-7.3%) was fat mass. Most importantly, her subjectively reported hyperphagia, satiety, and subsequently quality of life improved.

Discussion: To our knowledge, this case report is the first to describe that naltrexone-bupropion can effectively reduce weight and improve subjectively reported hyperphagia and quality of life in a patient with genetic obesity. This extensive journey learns us that in patients with genetic obesity various anti-obesity agents can be initiated and when ineffective terminated and substituted to another anti-obesity agent to find the most efficient treatment with regard to weight loss, hyperphagia, and quality of life. It also demonstrates that genetic screening should be considered in patients with early-onset obesity, hyperphagia, or other specific symptoms of monogenic obesity, prior to bariatric surgery as they are at higher risk for weight regain.