Magnitude of parathyroid hormone elevation in primary hyperparathyroidism: Does time of day matter?

Parathyroid hormone demonstrates a circadian rhythm in nondiseased patients, but it is unclear if this diurnal variation persists in the context of primary hyperparathyroidism. We anecdotally noticed that parathyroid hormone levels drawn early on the morning of parathyroid surgery (preincision parathyroid hormone), were of lower magnitude than values obtained at later times in the day. If present, a time-of-day based variation in parathyroid hormone could have important clinical implications on intraoperative surgical decision making.

We performed an Institutional Review Board-approved, retrospective chart review of patients undergoing parathyroidectomy for primary hyperparathyroidism between October 2019 and February 2022 at a quaternary care referral center. Demographic, laboratory, imaging, and operative parameters were extracted. Analysis was performed using mixed models for repeated measures with a first order autoregression correlation structure. Parathyroid hormone values were compared before and after hourly intervals between 6:00 A.M. and 12:00 P.M.

Of 418 patients, the mean age was 61 years old, 80% of patients were female, and two-thirds had single-gland disease. A total of 933 parathyroid hormone levels were included in the analysis and median parathyroid hormone was 97.3 pg/mL. Parathyroid hormone levels were noted to be significantly lower if they were drawn before 7:00 A.M. This diurnal variation persisted in patients with single-gland and advanced hyperparathyroidism but was abrogated in multi-gland and low-baseline-parathyroid hormone disease.

In patients with primary hyperparathyroidism, parathyroid hormone levels were significantly lower in the early morning hours, especially in patients with single-gland and high-baseline-parathyroid hormone hyperparathyroidism. This may have implications for intraoperative decision making when utilizing an early morning, preincision parathyroid hormone value.