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Vitamin D Status and Redefining Serum PTH Reference Range in the Elderly

Department of Core Clinical Pathology and Biochemistry, Royal Perth Hospital, Perth, Western Australia 6008

Address correspondence to: Paul Glendenning, Ph.D., Department of Core Clinical Pathology and Biochemistry, Royal Perth Hospital, Perth, Western Australia 6008.

To the editor:

The recent article by Souberbielle et al. (1) is a welcome addition to a controversial area, and we agree with the authors that vitamin D status should be considered when establishing reference values for serum PTH. However, we believe these issues apply to younger as well as older individuals and the serum 25-hydroxyvitamin D (25 OHD) that defines vitamin D sufficiency maybe much higher than Souberbielle et al. (1) state in their article.

We defined our serum intact PTH (iPTH) reference range using 197 healthy blood donors in Perth, Western Australia (2). Approximately one half were male and less than 60 yr of age. Of the 98 females, one half were less than 50 yr of age. All had serum creatinine less than 120 µmol/liter. 25 OHD was measured by RIA (DiaSorin, Inc., Stillwater, MN) and iPTH by chemiluminescent immunoassay (Immulite 2000; Diagnostics Products). We calculated the 95% confidence interval for iPTH for all 197 individuals as 2.0–10.7 pmol/liter with the upper value appreciably higher than the reference range quoted by the manufacturer (1.3–7.6 pmol/liter). When we excluded 70 individuals (31%) with 25 OHD below 50 nmol/liter, the recalculated iPTH reference range was 2.0–7.2 pmol/liter, close to the quoted manufacturers’ reference range. This effect was not apparent when we used the lower 25 OHD value of 30 nmol/liter as suggested by Souberbielle et al. (1).

Souberbielle et al. (1) raise an important issue regarding which assay to use for the measurement of iPTH. Because 25 OHD is critically important in defining the reference range for iPTH, it is equally important that the assay used to measure 25 OHD is accurate and precise. Although Souberbielle et al. (1) use a competitive protein binding assay, many laboratories are now using RIAs to measure 25 OHD. This is relevant because recent evidence has questioned the ability of a commonly used commercial RIA method for 25 OHD (IDS Ltd., Tyne and Wear, UK) to measure 25 OHD₂ as well as 25 OHD₃. In that study, the IDS 25 OHD assay did not detect both circulating forms of 25 OHD equally, unlike the other RIA (DiaSorin, Inc.) or high-performance liquid chromatography (3). Further work in this area is clearly needed.

In conclusion, excluding individuals with vitamin D insufficiency (as defined by a 25 OHD below 50 nmol/liter) makes a significant impact on the calculated PTH reference range and our ability to detect secondary hyperparathyroidism due to mild vitamin D insufficiency (2). These issues are pertinent to young as well as old individuals and to individuals living in environments with plentiful sunshine, such as Perth, Western Australia, as well as colder climates. As Souberbielle et al. (1) indicate, these issues also become critically important when considering the diagnosis of other metabolic bone conditions, such as primary hyperparathyroidism (4).

Received August 28, 2001.

References

1. Souberbielle JC, Cormier C, Kindermans C, Gao P, Cantor T, Forette F, Baulieu EE 2001 Vitamin D status and redefining serum parathyroid hormone reference range in the elderly. J Clin Endocrinol Metab 86:3086–3090[Abstract/Free Full Text]
2. Vasikaran SD, Sturdy G, Musk AA, Flicker L 2000 Vitamin D insufficiency and hyperparathyroidism in Perth blood donors. Med J Aust 172:406–407[Medline]
3. Hollis BW 2000 Comparison of commercially available (125)I-based RIA methods for the determination of circulating 25-hydroxyvitamin D. Clin Chem 46:1657–1661[Abstract/Free Full Text]
4. Glendenning P, Gutteridge DH, Retallack RW, Stuckey BG, Kermode DG, Kent GN 1998 High prevalence of normal total calcium and intact PTH in 60 patients with proven primary hyperparathyroidism: a challenge to current diagnostic criteria. Aust NZ J Med 28:173–178[Medline]

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