The biochemical features of PHPT in most publications depict the mild hypercalcaemic form of the disease as shown in Table 1. The serum calcium concentration is usually within 1 mg/ dl of the upper limits of normal. The serum phosphorus is rarely frankly below normal but values usually are in the low normal range. Circulating markers of bone turnover are often in the upper quartile of the normal range, but can be frankly elevated. The specific markers of bone turn over that are readily available and can be helpful in assessing the activity of the disease are the bone formation markers: bone- specific alkaline phosphatase activity and osteocalcin— and the bone resorption markers— serum CTx and urinary NTx.
Table1. Changes in biochemical indices in primary hyperparathyroidism over the past several decades. The data represent cohorts from earlier and more recent series
One has to go back to almost 50 years ago to appreciate the prescient work of Lumb and Stanbury who proposed that the clinical manifestations of PHPT are worsened by vitamin D deficiency. This association has since been substantiated by several studies. Even in mild, asymptomatic PHPT, indices of disease activity are more apparent when the 25- hydroxyvitamin D concentration is low. This association may be more difficult to detect in view of the fact that vitamin D deficiency in PHPT, is not as widespread as it used to be. This is because vitamin D supplements are now commonly used. The hypothesis that para thyroid disease is worse when vitamin D deficiency is present describes a stimulus for further stimulation of PTH synthesis by the abnormal parathyroid gland(s). Stein et al. has correlated low 25- hydroxyvitamin D levels with higher PTH level. The microstructural and densitometric profile is not as consistent as the biochemical correlates.
Levels of 25- hydroxyvitamin D will vary according to the country’s nutritional status. In the United States, a prototypical country in which the modern profile of PHPT the most common, 25- hydroxyvitamin D levels no longer tend to be below 30 ng/ ml. Over the past 15 years, with the population routinely taking vitamin D supplements, the average 25- hydroxyvitamin D from the centre in New York has increased from 21 ng/ ml to 36 ng/ ml. 1,25- dihydroxyvitamin D levels are no longer routinely measured in PHPT but as per previous experience, the level of this active form of vitamin D would be expected to be in the upper range of normal or frankly elevated. As previously shown, elevations in 1,25- dihydroxyvitamin D concentration can be seen in as many as 25% of the hyperparathyroid population. This observation is due to the catalytic effect of PTH on renal 1- alpha hydroxylase that con verts 25- hydroxyvitamin D to 1,25- dihydroxyvitamin D. PTH con serves renal tubular handling of calcium and, thus, for any level of the serum calcium, patients with PHPT will show reduced concentrations. The reason why hypercalciuria can be seen in as many as 40% of individuals with PHPT is because the filtered calcium load overwhelms the conserving capacity of the kidneys.
