Predicting hyperparathyroidism in patients with benign thyroid nodules

An interdisciplinary team of researchers led by Chris Hollenbeak, professor and head of the Department of Health Policy and Administration at Penn State, recently developed and examined a predictive model of primary hyperparathyroidism (pHPT) — a condition where the parathyroid glands produce excess amounts of parathyroid hormone — among patients with benign thyroid nodules. Benign thyroid nodules are non-cancerous growths in the thyroid gland, and affect approximately 50% of the adult population in the United States. 

Undiagnosed pHPT is one of the leading causes of hypercalcemia — a condition where there is an abnormally high amount of calcium in an individual’s blood. While many individuals undergo calcium screening as part of routine lab tests, 75% of hypercalcemia cases go undiagnosed. 

When left untreated, hypercalcemia can lead to osteoporosis — a condition that weakens bones, making them more prone to fractures — or osteopenia — a condition where bone mineral density is lower than normal, but not low enough to be diagnosed as osteoporosis. Prolonged hypercalcemia can also result in a chronic decline in kidney function. 

To help clinicians better understand and identify who may be at risk of undiagnosed pHPT, the researchers examined a dataset of 2,568,901 patients across 1,100 academic medical centers and their affiliated hospital systems across the nation who were diagnosed with thyroid nodules between 2020 and 2023. Their analysis demonstrated that it is possible to predict which patients with benign thyroid nodules will develop pHPT. Their findings were published in Head & Neck.  

“pHPT often goes undiagnosed, leading to additional complications,” Hollenbeak said. “This study indicated when it might be a good idea for clinicians to consider pHPT as a possible diagnosis using this new model. The implementation of modeling could suggest which patients should pursue additional diagnostic testing.” 

The researchers found that patients with pHPT were older, typically between 65 and 79 years of age, more likely to be female, more likely to be white but less likely to be Black or Asian, and more likely to have certain comorbidities, including obesity, chronic kidney disease, and diabetes. They were less likely to have other comorbidities, like hypertension, and less likely to have a history of tobacco use. 

“Our hope is for this work to help reduce under-diagnosis of pHPT,” Hollenbeak said. “If it can, then there is potential for patients to receive an earlier diagnosis, and more timely treatment, and they may not suffer the consequences of bone loss. This can give them a better quality of life, which is increasingly important as our population ages.” 

Originally published in September 2025.