Resting energy expenditure is decreased in pseudohypoparathyroidism type 1A

Context: Pseudohypoparathyroidism type 1A (PHP1A) is caused by loss-of-function mutations on the maternally inherited GNAS allele and is associated with early-onset obesity, neurocognitive defects, and resistance to multiple hormones. The role of energy intake vs central regulation of energy expenditure in the pathophysiology of obesity remains unclear. Objective: The aim of this study was to evaluate resting energy expenditure (REE) in participants with PHP1A. Design: We assessed REE, biochemical, endocrine, and auxological status of 12 participants with PHP1A who had normal or elevated body mass index; controls were a cohort of 156 obese participants. Setting: This study took place at Children's Hospital in Philadelphia and Sick Children's Hospital in Toronto. Main Outcome Measures: REE as a percent of predicted REE was the outcome measure. Results: PHP1A participants had normal endocrine status while receiving appropriate hormone replacement therapy, but had significantly decreased REE as a percent of predicted REE (using the modified Schofield equation). Conclusion: Our results are consistent with REE being the principal cause of obesity in PHP1A rather than it being caused by excessive energy intake or endocrine dysfunction.