Parathyroidectomy Restores Skeletal Muscle Strength and Transcriptome in Individuals with Primary Hyperparathyroidism

Background: Primary hyperparathyroidism (pHPT) is a common endocrine disorder leading to hypercalcemia and skeletal muscle dysfunction. Muscle weakness is associated with increased risk of morbidity and mortality but is overlooked in surgical guidelines for parathyroidectomy. While parathyroidectomy is the only curative treatment, its effects on skeletal muscle strength and molecular remodelling remain underexplored. Methods: We conducted a prospective observational cohort study involving 21 postmenopausal women with pHPT, of whom 15 completed the full protocol. Clinical assessments, magnetic resonance imaging (MRI), and skeletal muscle biopsies were performed before and three months post-parathyroidectomy. Muscle strength was evaluated using the timed stand test (TST) and isokinetic dynamometry, while RNA sequencing characterized transcriptomic changes in muscle biopsies. Findings: Parathyroidectomy normalized calcium and PTH levels, accompanied by significant improvements in muscle strength and composition. MRI revealed an increase in muscle volume and a reduction in fat fraction, without changes in physical activity levels. Transcriptomic analysis identified 981 differentially expressed genes post-surgery, enriched in pathways related to extracellular matrix remodelling, angiogenesis, and mitochondrial metabolism. Notably, transcriptional changes mirrored exercise-induced adaptations. Overall design: RNA-seq profiling of skeletal muscle tissue from women pre- and post-parathyroidectomy