Tokai Central Hospital of the Mutual Association of Public School Teachers
Early Detection of
Primary Hyperparathyroidism
from Health Screening Data
Effectiveness of Screening Using James-Formula Albumin-Corrected Calcium and Calcium–Phosphorus Difference
Ataru Okumura¹ · Tatsuya Bando² · Ryosei Ashida¹'⁴ · Mitsuhiro Kuno¹ ·
Naoki Tamaki¹ · Toshihiro Mizuguchi³ · Issei Uchida³ · Hiroshi Arima⁴
¹Dept. of Endocrinology & Diabetes, Tokai Central Hospital ²Pharmacy ³Health Screening Center
⁴Dept. of Diabetes & Endocrinology, Nagoya University Graduate School of Medicine
📰 BMC Endocrine Disorders — In Press
Notice to Our Patients
April 2026
1
To improve the accuracy of blood calcium assessment, we have applied James-formula albumin-corrected calcium values to clinical practice since 2021. The effectiveness of this approach has been confirmed through our research, accepted for publication in an international peer-reviewed journal.
2
Since introducing this method, we have been detecting Primary Hyperparathyroidism (PHPT) with significantly higher accuracy. Early treatment can prevent serious complications including osteoporosis, urolithiasis, and cardiovascular disease.
3
If an abnormal corrected calcium value is detected, your attending physician may contact you for further evaluation. Workup may include blood tests, ultrasound, CT scan, and bone density measurement. Please feel free to ask any questions.
4
As of April 2026, annual PHPT diagnoses at our hospital have increased approximately 5-fold, from 2.5 to 12.5 cases per year. More surgical candidates are being identified, enabling early intervention to prevent long-term complications.
Clinical Background
Background: Why Early Detection of PHPT Matters
Clinical Challenges of Primary Hyperparathyroidism (PHPT)
What is PHPT?
- Excess PTH secretion from parathyroid adenoma or hyperplasia
- Estimated prevalence ~0.18% in Asian populations
- Often asymptomatic; diagnosis frequently delayed
Screening Challenges
- Ionized Ca and PTH measurement impractical for routine screening (cost & technical barriers)
- Basic Metabolic Panel (BMP) not standardized in Japan
- Total calcium (tCa) alone misses many cases
- Optimal albumin correction formula had not been validated
Risks if Left Untreated
- Osteoporosis and fractures
- Nephrolithiasis / renal impairment
- Increased cardiovascular risk
- Cognitive decline
- Progression to dialysis
→ Study Objective: Establish the optimal screening index applicable to health checkups in Japan
Study Design: Three-Phase Analysis
Single-center study at Tokai Central Hospital
STEP 1
Formula Evaluation
Correction formula comparison
Retrospective analysis of simultaneous blood gas and peripheral blood samples
n = 5,550
(2017–2024)
Agreement between iCa and three correction formulas (Payne, KDOQI-2, James) assessed using weighted Cohen's κ
▶
STEP 2
Cutoff Determination
Defining PHPT thresholds
PHPT patients: 64
Controls: 87
(2013–2023)
ROC curve analysis to derive optimal cutoff values for each screening index
▶
STEP 3
Cohort Validation
Health screening cohort
Health screening participants
n = 2,562
(2017–2020)
Validated real-world screening performance, positive predictive value (PPV), and prevalence
Step 1: Evaluation of Albumin Correction Formulas
Agreement with ionized calcium (iCa), n = 5,550
| Index |
Overall Agreement |
Weighted κ |
Hypercalcemic Range |
Overall Rating |
| Total Calcium (uncorrected) |
59.9% | 0.572 |
Low |
Low |
| Payne-corrected Ca |
49.7% | 0.415 |
Low |
Low |
| KDOQI-2-corrected Ca |
57.2% | 0.513 |
Moderate |
Moderate |
| ★ James-corrected Ca |
64.1% | 0.604 |
Highest |
Highest |
Key Finding: James formula was the only method to achieve weighted κ ≥ 0.60 (substantial agreement), outperforming all other formulas — particularly in the hypercalcemic and upper-normal calcium range where PHPT typically manifests.
Step 2: ROC Curve Analysis — AUC Comparison
PHPT group n=64 vs. Control group n=87
AUC: Area Under the Curve (1.0 = perfect diagnosis) · Ca-P diff. = James-corrected Ca − serum phosphorus
0.965
★ Ca-P diff. (James) AUC
Sensitivity 88% / Specificity 94%
0.983
PTH (reference)
Highest accuracy, high cost
0.906
James-corrected Ca AUC
Highest among correction formulas
Step 3: Application to Health Screening Cohort (n = 2,562)
Number of candidates requiring further evaluation and PPV by screening index
2,562 Health Screening Participants
Candidates for workup
64
patients
PPV 6.3%
②
Albumin-Corrected Ca (James)
Candidates for workup
9–10
patients
PPV 40.0%
③
Ca-P Difference (James)
Candidates for workup
5–7
patients
PPV 66.7%
Prevalence 0.17% (4 confirmed cases) / After cutoff adjustment to ensure detection of all confirmed cases
Clinical Impact: Changes in Annual PHPT Diagnoses
Results Before and After Screening Implementation
Before
2.5
cases / year
Dependent on total calcium screening alone
→
After
12.5
cases / year
More surgical candidates identified
Early intervention preventing complications
Achieved at no additional cost using existing health screening data
— Contributing to early detection of patients at risk for osteoporosis, nephrolithiasis, and cardiovascular disease
Conclusions
Key Findings
1
James-formula albumin-corrected Ca was the only formula among three to achieve "substantial agreement (κ ≥ 0.60)" with ionized Ca
2
Ca-P difference (James) demonstrated AUC 0.965, sensitivity 88%, specificity 94% — comparable to PTH testing (AUC 0.983)
3
Application to the screening cohort reduced workup candidates from 64 to 5–7 (up to 93% reduction), with PPV improving from 6.3% to 66.7%
4
Annual PHPT diagnoses at our hospital increased dramatically from 2.5 to 12.5 cases per year. More surgical candidates identified, enabling early intervention