Endocrine Abstracts

JOINT1903

Overweight and obesity occur frequently in pseudohypoparathyroidism/iPPSD, especially in children with PHP1A/iPPSD2, who may develop severe early-onset obesity. Both impaired lipolytic response to adrenaline and decreased resting energy expenditure may contribute to weight gain, sometimes accompanied by hyperphagia. Obesity is also reported in PHP1B/iPPSD3 and acrodysostosis. There are no specific treatments for obesity in PHP/iPPSD, except for isolated cases treated with a cannabinoid receptor type 1 antagonist or gastric bypass. To now, no data are available on the use of GLP-1 receptor agonists for weight management in these patients. We aim to describe two patients with PHP/iPPSD, actively followed-up in two tertiary European centers, treated with GLP-1ra for severe obesity. The first patient was diagnosed with PHP1B/iPPSD3 at 15 years of age. He always suffered of overweight, and the mother referred hyperphagia during infancy. At 14 years his BMI was 35 kg/m² and dyslipidemia, liver steatosis, insulin resistance and impaired glucose tolerance were also present. At 17 years metformin therapy was introduced to improve his metabolic profile and reduce the gradual weight gain. However, weight continued to raise and at 21 years BMI was 47.6 kg/m², thus gastric bypass was proposed. At the same time, we started GLP-1ra therapy with subcutaneous liraglutide, that has been recently shifted to subcutaneous semaglutide. After 23 months at the last follow-up visit, he has lost 14 kg, which represents a 11% decrease in body weight, reaching a BMI of 42.6 kg/m². The second patient was diagnosed with PHP1A/iPPSD2 at 3 years of age. She developed early-onset obesity as soon as 4 months of age and had persistent obesity reaching a BMI of 32 kg/m² (2.88 SD) at the age of 13 years despite practicing sports regularly and having a healthy lifestyle. At 13 years, the liver US showed steatosis, however the blood metabolic profile was normal; she was then started on liraglutide. Her BMI dropped from 32 to 29.6 kg/m² in 8 months, which represents a 7.5% decrease in body weight. She described a significant improvement in satiety. Despite this good response, she stopped treatment on her own and regained weight in the following 6 months, up to a BMI of 30.5 kg/m² at the last visit. For both patients, GLP-1 analogs were well tolerated despite nausea and inappetence at the beginning. These two cases suggest that GLP-1ra may represent a promising therapeutic approach for the management of obesity and overweight in PHP/iPPSD patients.