Primary hyperparathyroidism (PHPT), increasingly diagnosed in its asymptomatic form, is associated with clinically significant neuromuscular dysfunction. Growing evidence indicates that skeletal muscle is a direct target of parathyroid hormone (PTH), with chronic PTH excess impairing mitochondrial bioenergetics, promoting proteolysis, and altering muscle–bone–adipose endocrine crosstalk. Experimental studies confirm PTH receptor (PTHR1) expression in muscle fibers and satellite cells, while transcriptomic analyses of PHPT muscle reveal dysregulation of calcium signaling and oxidative metabolic pathways. Clinically, patients with PHPT, irrespective of hypercalcemia, demonstrate reduced grip strength, slower gait speed, impaired chair-stand performance, and diminished postural stability. Parathyroidectomy improves several of these deficits, with studies reporting increases in grip strength, knee extension force, ambulatory capacity, and, in some cohorts, improved muscle composition and metabolic gene expression. However, available data are heterogeneous and derived primarily from small cohorts with variable functional measures. Current evidence implicates PTH-mediated skeletal muscle dysfunction as a reversible component of PHPT, yet key mechanistic and clinical gaps remain. Standardized functional assessments and larger prospective studies are needed to clarify biological pathways, identify predictors of postoperative recovery, and inform the integration of muscle health into PHPT management. The focus of this review was to explore evidence linking PTH excess and skeletal muscle pathophysiology and review the relationship between PHPT and parathyroidectomy on physical function.
Kabbash et al. (Wed,) studied this question.