Definition, Etiology, PathogenesisTop
Tertiary hyperparathyroidism refers to the development of hypercalcemia in a patient with previous secondary hyperparathyroidism due to increasingly autonomous parathyroid hormone (PTH) secretion. It usually results from ineffective treatment of secondary hyperparathyroidism, which causes long-term stimulation of parathyroid cells that consequently leads to their hyperplasia and an increased autonomous production of PTH. Tertiary hyperparathyroidism is most commonly observed in patients with chronic kidney disease (CKD) in chronic hemodialysis or peritoneal dialysis. Some authors consider the term “tertiary hyperthyroidism” as best describing the situation of patients with CKD who have long-standing secondary hyperparathyroidism and then receive a successful renal transplant but the parathyroid glands fail to involute. Patients with tertiary hyperparathyroidism have a significant risk of calciphylaxis and other complications of simultaneous high serum calcium and phosphate levels. Many of these individuals require subsequent subtotal or total parathyroidectomy (see Primary Hyperparathyroidism).
Clinical Features and Natural HistoryTop
Signs and symptoms of the underlying condition (most frequently advanced CKD), hypercalcemic crisis (see Hypercalcemia), and renal osteodystrophy (see Chronic Kidney Disease). Untreated tertiary hyperparathyroidism leads to cardiovascular complications (vascular and valvular calcifications), soft tissue calcifications, severe osteodystrophy, immunodeficiency, and erythropoietin-resistant anemia. Patients develop persistent pruritus, and in some cases spontaneous ruptures of tendons are observed. In 90% of patients undergoing renal transplantation, hyperparathyroidism resolves spontaneously within several months of the procedure; in a small group of patients, this does not occur and they need to be considered for surgical treatment because the persistent elevation of PTH and calcium levels may lead to damage to the new kidney.
1. Biochemical tests: Hypercalcemia, high serum PTH levels (>10 × the upper limit of normal), hyperphosphatemia (in patients with CKD), elevated levels of bone turnover markers (markers of osteolysis and of osteogenesis).
2. Imaging studies may reveal enlarged parathyroid glands and various bone lesions similar to those found in primary hyperparathyroidism.
Hypercalcemia in a patient with secondary hyperparathyroidism in whom other causes of hypercalcemia have been excluded.
Total or subtotal parathyroidectomy in patients with serum PTH levels >1000 pg/mL despite medical treatment; hypercalcemia >3 mmol/L; persistent pruritus, bone pain, extraskeletal calcifications (lungs, muscles, skin), or severe myopathy. A complication of total parathyroidectomy may be adynamic bone disease (low-turnover bone disease). For discussion on the choice of surgery, see Appendix 1.
The management of tertiary hyperparathyroidism depends on the degree of symptoms, the risk of complications (primarily calciphylaxis and increased cardiac risk), and values of calcium and PTH. Patients requiring surgery need either total parathyroidectomy and transplant or subtotal parathyroidectomy with the preservation of a small (approximately 3- to 4-mm) piece of the parathyroid tissue.