IMPORTANCE Untreated primary hyperparathyroidism impairs quality of life and incurs substantial costs. Parathyroidectomy is a low-risk, high-success, definitive intervention.OBJECTIVES To determine the appropriateness of diagnostic evaluation for primary hyperparathyroidism in patients with hypercalcemia and the use of parathyroidectomy for the treatment of primary hyperparathyroidism across the Veterans Affairs (VA) health care system. DESIGN, SETTING, AND PARTICIPANTSA retrospective cohort study of veterans with hypercalcemia and primary hyperparathyroidism was conducted from January 1, 2000, through September 30, 2015, using the VA Corporate Data Warehouse, a national electronic health record-based repository. The study included 371 370 veterans with chronic hypercalcemia and 47 158 veterans with biochemical evidence of primary hyperparathyroidism diagnosed by hypercalcemia, elevated serum parathyroid hormone levels, and near-normal serum creatinine levels. Statistical analysis was performed from April 21, 2017, to April 10, 2019. MAIN OUTCOMES AND MEASURESThe proportion of veterans with hypercalcemia who have parathyroid hormone levels evaluated, the proportion of veterans with hyperparathyroidism who are treated surgically, and the factors associated with parathyroidectomy using generalized linear latent and mixed model regression. RESULTSOf 371 370 patients with chronic hypercalcemia, 86 887 (23.4%) received further testing with parathyroid hormone level. Of 47 158 patients meeting diagnostic criteria for primary hyperparathyroidism (42 737 men [90.6%] and 4421 women [9.4%]; mean [SD] age, 67.3 [11.8] years), 6048 (12.8%) underwent parathyroidectomy. Of 5793 patients with primary hyperparathyroidism presenting with a serum calcium level more than 1 mg/dL above the upper limit of normal, 1501 (25.9%) underwent parathyroidectomy. There was a decreasing trend in the use of parathyroidectomy over time. Factors positively associated with parathyroidectomy were nephrolithiasis (odds ratio [OR], 2.23; 95% CI, 1.90-2.61) and non-Hispanic white race/ethnicity (OR, 1.31; 95% CI, 1.17-1.46), while age (OR, 0.95; 95% CI, 0.95-0.96), Elixhauser Comorbidity Index score (OR, 0.76; 95% CI, 0.72-0.80), decreased estimated glomerular filtration rate (OR, 0.52; 95% CI, 0.45-0.60), and diagnosis of osteoporosis (OR, 0.65; 95% CI, 0.52-0.80) were inversely related to surgery.CONCLUSIONS AND RELEVANCE From this study's findings, parathyroid hormone level is infrequently tested in patients with hypercalcemia, suggesting underdiagnosis of primary hyperparathyroidism. Patients meeting diagnostic criteria for primary hyperparathyroidism are undertreated with recommended parathyroidectomy. Similar gaps have previously been observed in non-VA care of primary hyperparathyroidism, suggesting the need for a systematic evaluation of barriers to diagnosis and treatment that informs intervention design.

The signs and symptoms of peripheral arterial occlusive disease (PAD), including claudication, rest pain, and tissue loss, are consequences of compromised bioenergetics and oxidative tissue injury within the affected lower extremities. Compromised bioenergetics is the result of a combination of low blood flow through diseased arteries and diminished adenosine triphosphate production by dysfunctional mitochondria. The tissue injury appears to be secondary to increased production of reactive oxygen species by dysfunctional mitochondria and by inflammation, in association with ischemia and ischemia/reperfusion. In this review, we present the current histomorphologic, physiologic, and biochemical evidence defining the nature of this mitochondriopathy and discuss its contribution to the pathogenesis and clinical manifestations of PAD.