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SUMMARY. Glomerular filtration rate (GFR) is frequently reduced in elder1 -Rople. However, the effect of this on mineral metabolism in this population has recr3ved little attention. GFR, serum intact parathyroid hormone (PTH) and vitamin D mdabolites , were measured in 37 patients admitted to hospital for various reasons. In 20 patier>:--wirli GFR > 50 mL/min, an elevated serum intact PTH concentration (> 5 . 4 pmol/L) was found in two, while in 17 patients with GFR < 50 mL/min PTH was elevated in 13. One of this group was hypercalcaemic and presumed to have primary hyperparathyroidism. Adjusted calcium was normal in all other patients. Two patients had a low serum 25-hydroxyvitamin D concentration (< 9 nmol/L) suggesting vitamin D insufficiency while a further five had a reduced 1,25-dihydroxyvitamin D concentration, four of these having a GFR < 50 mL/min. We conclude that hyperparathyroidism is common in hospitalized elderly patients, particularly in those with mild to moderate renal insufficiency. This may contribute to bone mineral loss in such patients. Additional key phrases: glomerular filtration rate; intact parathyroid hormone; 2s-hydroxyvitamin D; 1,2S-dihydroxyvitamin DAbnormalities of bone and mineral metabolism are an almost inevitable consequence of renal failure. Secondary hyperparathyroidism, which undoubtedly contributes to these abnormalities, occurs early in the course of chronic renal insufficiency and may result from decreased calcium absorption as a consequence of reduced renal synthesis of 1,25-dihydroxyvitamin D (1,25(OH),D). However, because of the frequent absence of specific symptoms, relatively few data have appeared on calciotropic hormone levels in patients with mild to moderate renal impairment. I Glomerular filtration rate (GFR) decreases with age2 and elderly patients may thus provide a population on whom to study biochemical markers of calcium and bone metabolism in mild renal insufficiency. Moreover, ageing itself has important effects on bone homeostasis. Everyone loses bone with ageing, though in women the rate of loss is greater than in men.' The factors responsible for the loss of cortical and trabecular bone It is well established that parathyroid hormone (PTH) is a key regulator of 1,25(OH),D synthesis which ultimately regulates calcium absorption. Responsiveness within this regulatory pathway appears to become impaired in elderly osteoporotic patient^.^ There have been reports that serum PTH levels increase with age,6s7 which could result from functional impairment of the ageing kidney or could reflect altered vitamin D metabolism.* However, previous studies have involved the use of assays of PTH which recognize carboxy-terminal hormone fragments. Though known to accumulate in renal insuffi~iency,~ such fragments are of no known biological significance and do not reflect parathyroid secretory activity. In contrast, assays recognizing the amino terminal segment of the PTH moleculelo have suitable specificity in biological terms but lack the sensitivity needed to detect sm...

Basal parathyroid hormone (PTH) levels measured by a chemiluminescent immunoassay for intact PTH showed good discrimination between normal, n=82 (1.2–9.4 pmol/l), and hyperparathyroid subjects, n=55 (9–200 pmol/l). In malignant hypercalcemia, all PTH levels were within the normal range or suppressed (0.8–5.2 pmol/l). Dynamic studies of PTH release in response to intramuscular salmon calcitonin (100 u) showed no significant rise out of the normal range in controls, but adenoma patients demonstrated a mean rise at 120, 180, and 240 minutes of 22%, 22%, and 35%, respectively, and hyperplasia patients a mean rise of 44%, 63%, and 46%, respectively. The mean absolute rise in PTH concentration was 10.6±7.2 pmol/g parathyroid adenoma and 26.6±19.2 pmol/g hyperplastic parathyroid tissue; this difference being significant (p <0.01). In vitro studies were performed in which dispersed cells prepared from both parathyroid adenomas and hyperplastic tissue were exposed to low (0.5 mM) and high (2.5 mM) extracellular calcium. Intact PTH secretion was measured under these conditions and compared with the results obtained by a mid‐region (44–68) specific immunoassay for PTH. There was parallel secretion of intact and mid‐region hormone under all conditions, the secretion rate of hyperplastic cells being greater than that of adenomas. Suppressibility of PTH release by high extracellular calcium was significantly greater in hyperplasia than in adenomas. These differences in the behavior of adenomatous and hyperplastic tissues both in vivo, in response to calcitonin, and in vitro, in response to changes in extracellular calcium concentration, suggest that the underlying pathogenesis of hyperparathyroidism may be heterogenous at the cellular level.

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