Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Background: Hypoparathyroidism (hypoPT) is an uncommon condition in which the body produces abnormally low levels of parathyroid hormone (PTH). The incidence ranges between 6.4 to 37 per 100000. External beam radiation is a known, albeit uncommon, cause of hypoPT. However, few studies have characterized the magnitude of this risk or the timeline of the development of hypoparathyroidism following radiation therapy delivered to the head/neck. Large databases provide large sample sizes capable of studying rare outcomes, such as hypoPT following radiation therapy. To our knowledge, this represents the largest cohort study examining this association.
Methods: A retrospective cohort study was conducted using the TriNetX Research Network database to query patients who underwent radiation therapy to the head or neck regions and had at least five years of follow-up documented. These patients' propensity scores were matched according to age, sex, and neck surgeries to a control cohort of patients who did not receive head/neck radiation of any type. Relative risk (RR) of hypoparathyroidism diagnosis (ICD-10-CM E20) and follow-up statistical analyses were determined within the TriNetX platform. The relative risk of serum hypocalcemia (<8.5 mg/dL) and low parathyroid hormone levels (<10mg/mL) were also determined.
Results: We identified 25839 patients from 56 healthcare organizations who underwent head and neck radiation and were surveilled for at least five years following treatment. The mean age of patients in this cohort was 63.9 years, with 59.0% male and 75.4% white. The incidence rate of hypoparathyroidism within the non-irradiated cohort was approximately 17.9 per 100000 person-years compared to 75.8 per 100000 person-years among patients receiving head/neck radiation. After matching, there was a 1.53 five-year relative risk of hypoPT development among irradiated patients compared to those not irradiated (95% CI 1.12-2.10, p<0.01). The median time to diagnosis was 259 days. Patients who had received head/neck radiation therapy had a 1.31 RR of hypocalcemia (95%CI 1.25-1.37, p<0.01) and a 1.16 RR of low parathyroid hormone (0.84-1.59, p=0.34) according to 5-year lab values compared to the matched control cohort.
Conclusions: Compared to the a non-irradiated population, patients who receive therapeutic head/neck radiation have a significantly increased incidence of hypoparathyroidism. Among matched cohorts, radiation therapy was found to be associated with a significantly elevated risk for the development of hypoparathyroidism as well as hypocalcemia. This is likely due to radiation-driven destruction of the parathyroid glands. This is the first large database study to characterize the association between patients receiving head and/or neck radiation and the development of hypoparathyroidism.