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Definition, Etiology, PathogenesisTop
Tertiary hyperparathyroidism is best described as the persistence of increasingly autonomously functioning hypertrophied parathyroid glands with parathyroid hormone (PTH) hypersecretion and hypercalcemia in a patient after correction of causes of secondary hyperparathyroidism. Tertiary hyperparathyroidism is most commonly observed in patients with a history of chronic kidney disease (CKD) previously treated with chronic hemodialysis or peritoneal dialysis who received a functioning renal transplant but in whom the parathyroid glands fail to involute. Approximately 10% to 20% of these patients require subsequent subtotal or total parathyroidectomy (see Primary Hyperparathyroidism).
Of note, the traditional concept of tertiary hyperparathyroidism also includes a combination of progressively increasing hyperplasia, hypertrophy, and autonomy of the parathyroid glands accompanied by hypercalcemia—a process that we describe as advanced secondary hyperparathyroidism (see Secondary Hyperparathyroidism).
Clinical Features and Natural HistoryTop
Since renal transplant removes many of the symptoms of CKD, including weakness and tiredness, symptoms of tertiary hyperparathyroidism are considerably less severe than that of advanced secondary hyperparathyroidism and the need for surgery depends on careful evaluation of blood calcium and PTH levels and frequent reassessment of symptoms that persist. In 80% to 90% of such patients hyperparathyroidism resolves spontaneously within several months of transplant, as measured by decreasing calcium and PTH levels. In a small group of patients, when this involution of the parathyroid glands does not occur, surgery needs to be considered, because the persistent elevation of PTH and calcium levels may lead to damage to the new kidney.
DiagnosisTop
1. Biochemical tests: Hypercalcemia, high serum PTH levels (>10 × 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 and elevated PTH in a patient with treated secondary hyperparathyroidism in whom other causes of hypercalcemia have been excluded.
TreatmentTop
As in secondary hyperparathyroidism.
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). Discussion on the choice of surgery: see Appendix 1.
AppendiXTop
The management of tertiary hyperparathyroidism depends on the degree of symptoms, risk of complications (primarily damage to the transplanted kidney), 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, often with a backup parathyroid transplant in case the preserved fragment of tissue does not survive. Occasionally at surgery only some of the parathyroid glands are significantly enlarged and only these need to be removed.
