Temporal Relationship between Vitamin D Status and Parathyroid Hormone in the United States

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Abstract

Background

Interpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season.

Objective

Characterize the temporal relationship between 25-hydroxyvitamin D ₃ levels [25(OH)D ₃] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D ₂ [25(OH)D ₂] levels with PTH levels and total 25(OH)D levels.

Method

We retrospectively determined population weekly-mean concentrations of unpaired [25(OH)D ₂ and 25(OH)D ₃] and iPTH using 3.8 million laboratory results of adults. The 25(OH)D ₃ and iPTH distributions were normalized and the means fit with a sinusoidal function for both gender and latitudes: North >40, Central 32–40 and South <32 degrees. We analyzed PTH and total 25(OH)D separately in samples with detectable 25(OH)D ₂ (≥4 ng/mL).

Findings

Seasonal variation was observed for all genders and latitudes. 25(OH)D ₃ peaks occurred in September and troughs in March. iPTH levels showed an inverted pattern of peaks and troughs relative to 25(OH)D ₃, with a delay of 4 weeks. Vitamin D deficiency and insufficiency was common (33% <20 ng/mL; 60% <30 ng/mL) as was elevated iPTH levels (33%>65 pg/mL). The percentage of patients deficient in 25(OH)D ₃ seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OH)D ₂ had higher PTH levels and 57% of the samples with a total 25(OH)D > 50 ng/mL had detectable 25(OH)D ₂.

Interpretation

25(OH)D ₃ and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D ₂ treated patients; 25(OH)D ₃, being higher in the summer and lower in the winter months, with iPTH showing the reverse pattern. A large percentage of the tested population showed vitamin D deficiency and secondary hyperparathyroidism. These observations held across three latitudinal regions, both genders, multiple-years, and in the presence or absence of detectable 25(OH)D ₂, and thus are applicable for patient care.

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Most cited references 18

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Calcium absorption across epithelia.

René Bindels, Bernd Nilius, J. Hoenderop (2004)

Ca(2+) is an essential ion in all organisms, where it plays a crucial role in processes ranging from the formation and maintenance of the skeleton to the temporal and spatial regulation of neuronal function. The Ca(2+) balance is maintained by the concerted action of three organ systems, including the gastrointestinal tract, bone, and kidney. An adult ingests on average 1 g Ca(2+) daily from which 0.35 g is absorbed in the small intestine by a mechanism that is controlled primarily by the calciotropic hormones. To maintain the Ca(2+) balance, the kidney must excrete the same amount of Ca(2+) that the small intestine absorbs. This is accomplished by a combination of filtration of Ca(2+) across the glomeruli and subsequent reabsorption of the filtered Ca(2+) along the renal tubules. Bone turnover is a continuous process involving both resorption of existing bone and deposition of new bone. The above-mentioned Ca(2+) fluxes are stimulated by the synergistic actions of active vitamin D (1,25-dihydroxyvitamin D(3)) and parathyroid hormone. Until recently, the mechanism by which Ca(2+) enter the absorptive epithelia was unknown. A major breakthrough in completing the molecular details of these pathways was the identification of the epithelial Ca(2+) channel family consisting of two members: TRPV5 and TRPV6. Functional analysis indicated that these Ca(2+) channels constitute the rate-limiting step in Ca(2+)-transporting epithelia. They form the prime target for hormonal control of the active Ca(2+) flux from the intestinal lumen or urine space to the blood compartment. This review describes the characteristics of epithelial Ca(2+) transport in general and highlights in particular the distinctive features and the physiological relevance of the new epithelial Ca(2+) channels accumulating in a comprehensive model for epithelial Ca(2+) absorption.

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Serum 25-hydroxyvitamin D status of the US population: 1988-1994 compared with 2000-2004.

Mary Frances Picciano, Rosemary L Schleicher, H Looker … (2008)

Changes in serum 25-hydroxyvitamin D [25(OH)D] concentrations in the US population have not been described. We used data from the National Health and Nutrition Examination Surveys (NHANES) to compare serum 25(OH)D concentrations in the US population in 2000-2004 with those in 1988-1994 and to identify contributing factors. Serum 25(OH)D was measured with a radioimmunoassay kit in 20 289 participants in NHANES 2000-2004 and in 18 158 participants in NHANES III (1988-1994). Body mass index (BMI) was calculated from measured height and weight. Milk intake and sun protection were assessed by questionnaire. Assay differences were assessed by re-analyzing 150 stored serum specimens from NHANES III with the current assay. Age-adjusted mean serum 25(OH)D concentrations were 5-20 nmol/L lower in NHANES 2000-2004 than in NHANES III. After adjustment for assay shifts, age-adjusted means in NHANES 2000-2004 remained significantly lower (by 5-9 nmol/L) in most males, but not in most females. In a study subsample, adjustment for the confounding effects of assay differences changed mean serum 25(OH)D concentrations by approximately 10 nmol/L, and adjustment for changes in the factors likely related to real changes in vitamin D status (ie, BMI, milk intake, and sun protection) changed mean serum 25(OH)D concentrations by 1-1.6 nmol/L. Overall, mean serum 25(OH)D was lower in 2000-2004 than 1988-1994. Assay changes unrelated to changes in vitamin D status accounted for much of the difference in most population groups. In an adult subgroup, combined changes in BMI, milk intake, and sun protection appeared to contribute to a real decline in vitamin D status.

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Vitamin D: a D-Lightful health perspective.

M Holick (2008)

Sunlight provides most humans with their vitamin D requirement. Adequate vitamin D(3) by synthesis in the skin or from dietary and supplemental sources is essential for bone health throughout life. Vitamin D deficiency is defined as a 25(OH)D concentration 30 ng/mL (75 nmol/L), and insufficiency as 21-29 ng/mL. Vitamin D deficiency and insufficiency has been linked to a wide variety of chronic diseases including common cancers, autoimmune, cardiovascular, and infectious diseases. Healthcare professionals need to be aware of the vitamin D deficiency pandemic. Guidelines for sensible sun exposure and supplemental vitamin D of 800-1000 IU/day are needed.

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Author and article information

Contributors

Martin H de Borst: Role: Academic Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 4 March 2015

Publication date Collection: 2015

Volume: 10

Issue: 3

Electronic Location Identifier: e0118108

Affiliations

[1 ]Quest Diagnostics, 3 Giralda Farms, Madison, NJ, United States of America

[2 ]Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, United States of America

[3 ]Office of Statistical Consulting, Department of Statistics and Biostatistics, Rutgers University, 110 Frelinghuysen Road, Piscataway, NJ, United States of America

[4 ]Department of Biostatistics, Yale University School of Public Health, 300 George Street, New Haven, CT, United States of America

[5 ]Department of Medicine, Physiology and Biophysics at Boston University School of Medicine, Boston University School of Medicine, 88 East Newton, Boston, MA, 02118, United States of America

University Medical Center Groningen and University of Groningen, NETHERLANDS

Author notes

Competing Interests: Michael F. Holick has read the journal’s policy and the authors of this manuscript have the following competing interests: this work was funded by Quest Diagnostics. Stephen Suffin, Caixia Bi, Martin Kroll, Carl Garber, and Harvey Kaufman were employed by and received stock/stock options from Quest Diagnostics. Martin Kroll’s prior employer was Boston University. Dungang Liu, Minge Xie, Anne Caston-Balderrama, Nigel Clarke, and Richard E. Reitz received a consulting fee or honorarium from Quest Diagnostics. Michael F. Holick was Academic Associate of Quest Diagnostics. This does not alter the authors’ adherence to PLoS ONE policies on sharing data and materials.

Conceived and designed the experiments: MHK HWK CCG NG RER MFH. Performed the experiments: MHK CB CCG HWK DL ACB KZ NC MX RER SCS MFH. Analyzed the data: MHK CB DL KZ MX RER ACB MFH. Contributed reagents/materials/analysis tools: MHK CB CCG HWK DL ACB KZ NC MX RER SCS MFH. Wrote the paper: MHK CB CCG HWK DL ACB KZ NC MX RER SCS MFH.

* E-mail: mfholick@ 123456bu.edu (MFH); Martin.H.Kroll@ 123456questdiagnostics.com (MHK)

Article

Publisher ID: PONE-D-14-33969

DOI: 10.1371/journal.pone.0118108

PMC ID: 4349787

PubMed ID: 25738588

SO-VID: 97321b52-e1e8-48d0-9790-102062947234

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

History

Date received : 30 July 2014

Date accepted : 31 December 2014

Page count

Figures: 5, Tables: 4, Pages: 13

Funding

This work was funded by Quest Diagnostics. All authors received salary support or consulting support from Quest Diagnostics. Quest Diagnostics provided support in the form of salaries for the authors, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of the authors are articulated in the ‘author contributions’ section.

Custom metadata

Data Availability Data have been deposited to Figshare: http://dx.doi.org/10.6084/m9.figshare.1285067.

Temporal Relationship between Vitamin D Status and Parathyroid Hormone in the United States

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Abstract

Background

Objective

Method

Findings

Interpretation

Related collections

PLOS Climate

Most cited references 18

Calcium absorption across epithelia.

Serum 25-hydroxyvitamin D status of the US population: 1988-1994 compared with 2000-2004.

Vitamin D: a D-Lightful health perspective.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Funding

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Custom metadata

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