Elsevier

Clinica Chimica Acta

Volume 426, 15 November 2013, Pages 41-45
Clinica Chimica Acta

Prevalence of vitamin D deficiency and consequences for PTH reference values

https://doi.org/10.1016/j.cca.2013.08.024Get rights and content

Highlights

  • PTH reference values are influenced by vitamin D levels

  • Reference values should be verified in an appropriate reference population

  • The reference population should be described in the package insert

  • Inform Clinicians on which 25OHD PTH reference values have been based

Abstract

Reference values of PTH depend on vitamin D status of the reference population. This is often not described in package inserts. The aim of the present study was therefore to calculate assay specific PTH reference levels in EDTA plasma for the Architect (Abbott) in relation to 25-hydroxyvitamin D (25OHD) levels.

The relation between PTH levels, 25OHD, BMI, age, gender and kidney function was determined in a cohort of older individuals from the Longitudinal Aging Study Amsterdam (LASA, n = 738, age 55–65 years) and in a cohort of healthy individuals from the Netherlands Study of Depression and Anxiety (NESDA, n = 633, 18–65 years). The LASA cohort is a representative sample of the Dutch older population.

As expected, PTH reference values were significantly lower in 25OHD sufficient subjects (25OHD > 50 nmol/L) than in 25OHD deficient and insufficient subjects. The 97.5th percentile of PTH in 25OHD sufficient subjects was 10 pmol/L (94.3 pg/mL), which was higher than the upper limit stated by the manufacturer (7.2 pmol/L or 68.3 pg/mL). The relation between vitamin D and PTH was independent of age, gender, BMI and kidney function. In conclusion, we have shown that it is important to establish PTH reference values in a local reference population taking 25OHD status into account.

Introduction

Standardization of PTH assays is lacking. Method comparison studies of PTH immunoassays from various suppliers show 2–3 fold differences in PTH levels [1], [2], [3], [4]. The lack of standardization has major clinical implications as PTH is used not only to exclude hyper- or hypoparathyroidism but also to monitor disease progression in patients with Chronic Kidney Disease (CKD) [2], [5], [6], [7]. To overcome these problems either a standardization program should be started or assay specific reference values or assay specific decision limits should be used [8], [9], [4]. In order to define assay specific reference values a proper description of the population characteristics such as age, gender, race, BMI and vitamin D levels is required [10]. These characteristics are often poorly described in the package inserts [9]. Recent studies have shown that 1–14% of the variation in PTH levels is explained by vitamin D status [11], [12]. Given the inverse relationship between PTH and 25-hydroxyvitamine D (25OHD), 25OHD levels should be simultaneously assessed while defining PTH reference values [10], [13]. Or alternatively, only vitamin D sufficient subjects should be included in the reference population [9], [11].

The aim of the present study was to examine the association between 25OHD levels and PTH in two large, healthy cohorts and calculate assay specific PTH reference levels on the Architect (Abbott) in EDTA plasma in relation to 25OHD levels.

Section snippets

Subjects

The LASA study is based on an age and sex-stratified representative healthy sample of Dutch, mainly Caucasian, older population as described earlier [14], [15]. In this study the baseline measurements of the second cohort were included. The samples from the LASA were collected in 2002. Blood samples were obtained in the morning after light breakfast without dairy products. The samples were centrifuged and stored at − 20 °C until analysis. PTH and vitamin D measurements were carried out in 2009 as

Study characteristics

Since PTH measurements were available in these large, well defined cohorts we used them in the current study to define PTH reference values. To establish PTH reference levels data from 738 subjects of the LASA cohort (mean age 60.0 ± 2.9 years) and 633 subjects of the NESDA cohort (mean age 41.0 ± 14.6 years), were included in the analysis (Table 1). Vitamin D deficiency or insufficiency (25OHD < 50 nmol/L) [22] was present in 41% and 29% of the LASA and NESDA cohorts, respectively.

Determinants of PTH

As shown in Table 2,

Discussion

In the current study we defined reference values for the Architect PTH assay while taking 25OHD concentrations and other possible confounding factors into account. In agreement with previous studies, higher PTH reference values were obtained in vitamin D deficient and insufficient subjects [9], [11], [12]. The 97.5th percentile obtained from our cohorts is 11.1 and 9.4 pmol/L, respectively which is significantly different from 7.2 pmol/L as stated by Abbott. To our knowledge this is the first

Acknowledgments

The Longitudinal Aging Study Amsterdam is largely supported by a grant from the Netherlands Ministry of Health Welfare and Sports, Directorate of Nursing Care and Older Persons. We would like to acknowledge our colleagues from the clinical laboratory of the Isala Klinieken (Weezenlanden) and Ziekenhuis Bernhoven in Oss and Veghel for measuring creatinine levels and Evelien Sohl for constructing the spline plots. The infrastructure for the NESDA study (www.nesda.nl) is funded through the

References (34)

  • S.M. Moe et al.

    KDIGO clinical practice guideline for the diagnosis, evaluation, prevention and treatment of chronic kidney disease mineral and bone disorder (CKD–MBD)

    Kidney Int Suppl

    (2009)
  • A. Almond et al.

    Current parathyroid hormone immunoassays do not adequately meet the needs of patients with chronic kidney disease

    Ann Clin Biochem

    (2012)
  • K. Wesseling et al.

    Chronic kidney disease mineral and bone disorder in children

    Pediatr Nephrol

    (2008)
  • C.M. Sturgeon et al.

    Variation in parathyroid hormone immunoassay results—a critical governance issue in the management of chronic kidney disease

    Nephrol Dial Transplant

    (2011)
  • E. Cavalier et al.

    Interpretation of serum PTH concentrations with different kits in dialysis patients according to the KDIGO guidelines: importance of the reference (normal) values

    Nephrol Dial Transplant

    (2012)
  • R. Eastell et al.

    Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop

    J Clin Endocrinol Metab

    (2009)
  • L. Rejnmark et al.

    Determinants of plasma PTH and their implication for defining a reference interval

    Clin Endocrinol (Oxf)

    (2011)
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