In most patients with end-stage renal disease (ESRD), even advanced 2° hyperparathyroidism remains a clinically silent disease. Clinical manifestations are generally related to severe osteitis fibrosa and to the consequences of a high serum Ca x P product.

Osteo-articular pain may be present. When patients become symptomatic, they usually complain of pain on exertion in skeletal sites that are subjected to biomechanical stress. Pain at rest and localized pain are rather unusual and suggest other underlying causes. Severe proximal myopathy is seen in some patients, even in the absence of vitamin D deficiency. These symptoms and signs are more frequent in patients who suffer from mixed renal osteodystrophy, resulting from a combination of parathyroid overfunction and vitamin D deficiency. Skeletal fractures have been found to be weakly associated with serum PTH in a U-shaped type of relationship, with the lowest risk observed around an “intact” PTH concentration of 300 pg/mL . They may occur after only minor injury. They may also develop on the ground of cystic bone lesions, the so-called “brown tumors”, which occur for still unknown reasons in a small number of uremic patients with 2° hyperparathyroidism. Rupture of the patella or avulsion of tendons may be seen in advanced cases.

Uremic pruritus is most often associated with an elevated Ca x P product although other factors may also be involved. Related symptoms and signs are the red eye syndrome due to the deposition of calcium in the conjunctiva, cutaneous calcification, and pseudogout. The latter is a form of painful arthralgia of acute or subacute onset caused by intra-articular deposition of radio-opaque crystals of calcium pyrophosphate dehydrate.

The syndrome of “calciphylaxis” is an infrequent manifestation of cutaneous and vascular calcification in uremic patients which may occur in association with 2° hyperparathyroidism, although this association is by no means constant. It is characterized by a rapidly progressive skin necrosis involving buttocks and the legs, particularly the thighs. It can produce gangrene and may be fatal. It occurs as the result of arteriolar calcification and has more recently been termed “calcific uremic arteriolopathy” to reflect more accurately the nature of the lesion.