Serum PTH reference values established by an automated third-generation assay in vitamin D-replete subjects with normal renal function: consequences of diagnosing primary hyperparathyroidism and the classification of dialysis patients

Abstract

Objective: To determine parathyroid hormone (PTH) reference values in French healthy adults, taking into account serum 25-hydroxyvitamin D (25OHD), renal function, age, gender, and BMI. Participants and main biological measurements: We studied 898 healthy subjects (432 women) aged 18-89 years with a normal BMI and estimated glomerular filtration rate (eGFR), 81 patients with surgically proven primary hyperparathyroidism (PHPT), and 264 dialysis patients. 25OHD and third-generation PTH assays were implemented on the LIAISON XL platform. Results: Median PTH and 25OHD values in the 898 healthy subjects were 18.8 ng/l and 23.6 ng/ml respectively. PTH was lower in subjects with 25OHD R30 ng/ml than in those with lower values. Among the 183 subjects with 25OHD R30 ng/ml, those aged R60 years (nZ31) had higher PTH values than younger subjects, independent of 25OHD, BMI, and eGFR (P!0.001). Given the small number of subjects aged R60 years, we adopted the 95% CI of PTH values for the entire group of 183 vitamin D-replete subjects (9.4-28.9 ng/l) as our reference values. With 28.9 ng/l as the upper limit of normal (ULN) rather than the manufacturer's ULN of 38.4 ng/l, the percentage of PHPT patients with 'high' PTH values rose to 90.1% from 66.6% (P!0.001), and 18.6% of the dialysis patients were classified differently in view of the KDIGO target range (two to nine times the ULN). Conclusion: When only subjects with 25OHD R30 ng/ml were included in the reference population, the PTH ULN fell by 22.4%, diagnostic sensitivity for PHPT improved, and the classification of dialysis patients was modified.

Parathyroid hormone: Data mining for age‐related reference intervals in adults

“…Sex was not found to have a significant effect on PTH concentrations. This result is consistent with many direct studies conducted in healthy volunteers . One study did report a statistically significant difference; however, the effect was small: in a white population, values were 0.2 pmol/L higher in women than in men …”

“…This supports the conclusions of other reports, which have found an independent association between age and PTH concentration. 7,8,10 The study also demonstrated that, if age-related changes are not considered when setting PTH reference intervals, a significant number of patient results will be misclassified.…”

“…This finding, which supports the Endocrine Society's definition of vitamin D sufficiency, 29 is consistent with other investigations evaluating the relationship between 25-OHD and PTH. 8,9,28,30 Other lines of evidence also support this cut-off for optimal vitamin D status. For instance, an increase in intestinal calcium absorption has been documented in subjects when 25-OHD concentration was increased from 50 nmol/L to 88 nmol/L, but not when 25-OHD was increased from 75 nmol/L to 123 nmol/L.…”

“…This result is consistent with many direct studies conducted in healthy volunteers. 8,[25][26][27][28] One study did report a statistically significant difference; however, the effect was small: in a white population, values were 0.2 pmol/L higher in women than in men. 10 Vitamin D status significantly influenced PTH concentrations.…”

“…4,5 Additionally, when reference interval studies have excluded patients with vitamin D deficiency, they have been inconsistent in its definition: 25-OHD cut-offs from 38 to 80 nmol/L have been used. [6][7][8][9] Finally, PTH concentrations have been reported to increase with age, independent of these possible confounding factors. 7,10,11 The need for further study into PTH reference intervals, in particular age-and sex-associated changes, was recently highlighted.…”