The Role of Measurement of Plasma 25-hydroxy Vitamin D in Assessing Parathyroid Hormone (PTH) Status

Eric Espiner and John Livesey

It has been recognised recently that vitamin D status may affect the PTH reference range. This is not surprising, as low vitamin D levels - by reducing calcium absorption - will tend to raise PTH secretion. Most population surveys, from which reference ranges for PTH are drawn, do not take vitamin D status into account. Thus it is likely that the upper limit of normal for the PTH range - especially in elderly subjects - is set too high.

We have examined the relationship, if any, between vitamin D and PTH results for our Endolab assays for samples analysed over the period May 2001 - March 2002. Values were only included if both assays (vitamin D and PTH) had been performed on the same plasma sample. Two hundred and twenty four such pairs of measurements (originally analysed for diagnostic purposes) from 208 different patients were available for study. Of these 22 pairs (10%) were excluded for reasons of establised primary hyperparathyroidism, severe renal failure or PTH resistance syndrome (n = 8), or because of insufficent data to allow exclusion of these disorders (n = 14, shown as triangles in Fig. 1). The remaining 202 data pairs from 186 patients are shown as circles in Figure 1.

The figure clearly shows the hyperbolic relationship between PTH and 25-OH vitamin D. As others have found in studies of medical admissions ¹, PTH tends to increase as 25-OH vitamin D levels fall below 10-15ng/mL (25-38nmol/L). The relationship between plasma PTH and 25-OH vitamin D for the acceptable data points (circles in Fig. 1) in our series is well described by the function

[PTH] = 1/(0.0238[Vit_D] - 0.0074) + 1.04

which is shown as the smooth curve in the figure. For this function fitted by least squares to our data, R² = 0.447, df = 201 and p < 0.001.

Clinical Comment

Severe vitamin D deficiency is likely to raise PTH to levels above the reference range ("secondary hyperparathyroidism"), irrespective of the plasma calcium or phosphate level. However not all patients with hypovitaminosis D will necessarily show "hyperparathyroidism". In this survey of 208 subjects, 8 with very low 25-OH vitamin D levels (< 7.5ng/mL, mean 6.4ng/mL; < 19nmol/L, mean 16.0nmol/L) had "normal" levels of PTH (mean 4.8pmol/L) for no obvious reason. Further study is required to explain these variations in the response to a low plasma 25-OH vitamin D level.

1. Thomas MK, Lloyd-Jones DM, Thadhani RI et al. Hypovitaminosis D in medical inpatients. New England Journal of Medicine 338:777-83 (1998).