Association of Serum Parathyroid Hormone Levels with All-Cause and Cause-Specific Mortality Among U.S. Adults, with a Focus on the Parathyroid Hormone Levels Within the Normal Range: a Population-Based Cohort Study from NHANES 2003-2006.
Cheng X, Mu L, et al. • Calcified tissue international • 2026
High-normal (42-74 pg/ml) and high (>74 pg/ml) serum PTH levels were both associated with higher risks of all-cause and cardiovascular mortality among U.S. adults, with ideal outcomes observed at the lower level of the normal range (18-41 pg/ml).
Key Findings
Results
Participants with high-normal PTH levels (42-74 pg/ml) had significantly increased risks of all-cause and cardiovascular mortality compared to those with low-normal PTH levels (18-41 pg/ml).
High-normal PTH range (42-74 pg/ml) accounted for 40.4% of the entire normal PTH range population.
All-cause mortality risk was 22% higher in the high-normal group (HR: 1.22, 95% CI 1.02-1.46).
Cardiovascular mortality risk was 66% higher in the high-normal group (HR: 1.66, 95% CI 1.20-2.30).
No statistically significant association with cancer-related mortality was observed for this group.
Multivariate Cox proportional hazards models were used to calculate these hazard ratios.
Results
Participants with high PTH levels (>74 pg/ml) had significantly increased risks of all-cause, cardiovascular, and non-cardiovascular-non-cancer mortality.
All-cause mortality risk was 34% higher in the high PTH group (HR: 1.34, 95% CI 1.08-1.68).
Cardiovascular mortality risk was 59% higher in the high PTH group (HR: 1.59, 95% CI 1.03-2.46).
Non-cardiovascular-non-cancer mortality risk was 44% higher in the high PTH group (HR: 1.44, 95% CI 1.02-2.04).
The reference group was participants with low-normal PTH levels (18-41 pg/ml).
Results
Restricted cubic spline analysis indicated that ideal mortality outcomes were observed with serum PTH at the lower level of the normal range (18-41 pg/ml).
Restricted cubic splines were used to depict the dose-response relationship between serum PTH and mortality risks.
The analysis suggested a non-linear relationship between PTH levels and mortality risk.
The lower portion of the normal PTH range (18-41 pg/ml) was identified as the optimal range for survival outcomes.
Methods
The study cohort included 6633 non-hypoparathyroid participants, among whom 1309 deaths occurred during follow-up.
Participants were aged ≥20 years and drawn from the National Health and Nutrition Examination Survey (NHANES) 2003-2006.
Of the 1309 total deaths, 437 were cardiovascular deaths, 316 were cancer-related deaths, and 556 were non-cardiovascular-non-cancer deaths.
This was a prospective cohort study design with linkage to mortality data.
Participants with hypoparathyroidism were excluded from the analysis.
Discussion
Individuals with high-normal PTH levels represent a substantial proportion of the normal-range population but typically receive insufficient clinical attention.
The high-normal PTH group (42-74 pg/ml) accounted for 40.4% of all participants within the normal PTH range.
Current clinical practice generally does not differentiate management between low-normal and high-normal PTH levels.
The authors call for further studies to evaluate the clinical implications of screening and management for this high-risk population.
The study highlights a potential gap in clinical attention for those with high-normal PTH levels despite their elevated mortality risk.
What This Means
This research suggests that parathyroid hormone (PTH) — a hormone that regulates calcium levels in the body — is linked to the risk of death even when its levels fall within the range considered medically 'normal.' Using data from over 6,600 American adults followed over time through the NHANES survey, researchers found that people whose PTH was in the upper portion of the normal range (42-74 pg/ml) had a 22% higher risk of dying from any cause and a 66% higher risk of dying from cardiovascular disease, compared to those with PTH in the lower portion of the normal range (18-41 pg/ml). People with PTH above the normal range entirely had even higher risks across multiple causes of death.
What makes this finding particularly notable is that the 'high-normal' group — those whose PTH is technically within accepted limits but on the higher end — made up about 40% of all people with normal PTH levels. Despite this large proportion and the associated mortality risks, these individuals would not typically receive any additional monitoring or intervention under current clinical practice, since their values fall within the normal reference range.
This research suggests that the current 'normal' PTH range may be too broad and that doctors and researchers may need to reconsider what PTH level is truly optimal for long-term health. The findings point to a need for further studies to determine whether identifying and managing people with high-normal PTH could reduce their risk of cardiovascular disease and premature death, and whether screening efforts should be expanded to capture this overlooked group.
Cheng X, Mu L, Wang Z, Li H, Qu X, Liu D, et al.. (2026). Association of Serum Parathyroid Hormone Levels with All-Cause and Cause-Specific Mortality Among U.S. Adults, with a Focus on the Parathyroid Hormone Levels Within the Normal Range: a Population-Based Cohort Study from NHANES 2003-2006.. Calcified tissue international. https://doi.org/10.1007/s00223-026-01604-9