The biochemical diagnosis of 2° hyperparathyroidism relies since approximately 20 years on the determination of plasma intact PTH. This is true for 1° and 2° forms of hyperparathyroidism. In patients with CRF, it has however become apparent in recent years that there are some limitations for intact PTH in plasma. Normal intact PTH plasma values are not normal for uremic patients since values in the normal range are generally associated with low bone turnover (adynamic bone disease) whereas normal bone turnover may be observed in presence of elevated plasma intact PTH levels . It is currently unclear to what extent this is due to imperfections in the PTH assays used (see below), PTH receptor state, post-receptor events, non-PTH-mediated changes in bone metabolism (e.g. supply of vitamin D or its metabolites, supply of estrogens or androgens), or a combination of these factors.

The accumulation of a large non (1-84) molecular form of PTH, which is detected by intact PTH assays, has been described in patients with CRF . The large PTH fragment was tentatively identified as hPTH(7-84) . This finding is of importance in the interpretation of PTH values, since true hPTH(1-84) represents only about 50-60% of the levels detected by the currently used intact PTH assays, and since PTH(7-84) antagonizes PTH(1-84) effects on serum calcium and on osteoblasts. Moreover, the secretory responses of hPTH(1-84) and non-hPTH(1-84) to changes in extracellular calcium concentration are not proportional for these two PTH moieties . A novel immunoradiometric assay has been developed which detects full-length (whole) human PTH, but not amino-terminally truncated fragments . Monier-Faugere et al proposed to further improve the assessment of uremic hyperparathyroidism and the associated increase in bone turnover by calculating the ratio of PTH-(1-84) to large C-PTH fragments . The usefulness in the clinical setting of the whole PTH assay or of the ratio of whole PTH to PTH fragments has however not been established at present for the diagnosis of parathyroid overfunction in adult dialysis patients or pediatric dialysis patients.

The radiological diagnosis is relatively easy in advanced stages of 2° hyperparathyroidism. Typical lesions include resorptive defects on the external and internal surfaces of cortical bone, particularly resorption on the subperiosteal surface. Resorption within cortical bone enlarges the Haversian channels, resulting in longitudinal striation; resorption at the endosteal surface causes cortical thinning. These lesions can be generally detected first in the hand skeleton, most characteristically at the periosteal surface of the middle phalanges (Figure 13). Accelerated bone deposition at this site (periosteal neostosis) can also be seen. Another characteristic feature is resorptive loss of acral bone (acro-osteolysis), in particular at the terminal phalanges, at the distal end of the clavicles, and in the skull (‘pepper-pot’ aspect) (Figure 14). Whereas cortical bone is progressively thinning, the mass of spongy bone tends to increase, particularly in the metaphyses. The latter phenomenon results in a characteristic sclerotic aspect of the upper and lower thirds of the vertebrae, contrasting with rarefaction of the center (‘rugger jersey spine’). Osteosclerosis is also commonly seen in radiographs of the metaphyses of the radius and tibia.

In addition to the skeletal lesions, radiographs often reveal various types of soft tissue calcification in CKD patients. These comprise vascular calcifications, i.e. calcification of intimal plaques (aorta, iliac arteries), as well as focal or diffuse calcification (Mönckeberg type) of the media of peripheral muscular arteries (Figure 13a). The propensity to calcify soft tissues is not limited to ESRD since CKD stage 3-5 has been found to be associated with increased coronary artery calcification . The association was particularly marked in diabetic patients with CKD. Calcium deposits may also be seen in periarticular tissue or bursas and may exhibit tumor-like features (Figure 15). Recently, electron-beam computed tomography (EBCT) and multiple slice computed tomography (MSCT) have become available as more reliable means to assess quantitatively vascular calcification and its progression in uremic patients. However, these techniques are not universally available and costly. Moreover, they do not allow a distinction between arterial intima and media calcifications. Such a distinction can be obtained by radiograms of the pelvis and the thigh, combined with ultrasonography of the common carotid artery. Using such semiquantative assessment methods, London et al could show that the survival of hemodialysis patients with arterial media calcification better than that of those with arterial intima calcification, but in turn their survival was significantly shorter than that of hemodialysis patients without calcifications . From an etiological point of view, it appears that both severe hyperparathyroidism and marked hypoparathyroidism favor the occurrence of the two types of calcification in ESRD patients . This observation tends to demonstrate that normal parathyroid function is required not only for the maintenance of optimal bone structure and function, but also as an efficacious defense against soft tissue calcification. Of interest, media calcification of digital arteries can entirely regress after surgical parathyroidectomy in CKD patients with severe hyperparathyroidism (Figure 13b) , but not in patients with no parathyroid overfunction. In the latter context, it is of note that the intermittent administration of human PTH (1-34), also called teriparatide, was able to inhibit osteogenic vascular calcification in diabetic low density lipoprotein receptor-deficient mice.