Tertiary Hyperparathyroidism

How to Cite This Chapter: Khan S, Alsarraf F, Al-Alwani H, Young JEM, Rodríguez-Gutiérrez R, Khan A, Kokot F, Franek E, Płaczkiewicz-Jankowska E. Tertiary Hyperparathyroidism. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.10.2.3. Accessed February 10, 2025.
Last Reviewed: January 8, 2025
Last Updated: January 8, 2025
Chapter Information

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 mostly observed in patients with a history of chronic kidney disease (CKD) previously treated with chronic hemodialysis or peritoneal dialysis, who received a functioning kidney 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).  

The term tertiary hyperparathyroidism has also been described in the literature to include a combination of progressively increasing hyperplasia, hypertrophy, and autonomy of the parathyroid glands accompanied by hypercalcemia in patients with end-stage kidney disease. This process can also be classified as advanced secondary hyperparathyroidism (see Secondary Hyperparathyroidism).

Clinical Features and Natural HistoryTop

Symptoms of tertiary hyperparathyroidism include symptoms of hypercalcemia (eg, increased thirst, pruritis, muscle weakness, fatigue, bone pain and fragility fracture) in addition to those of the underlying CKD, most of which will resolve after successful kidney transplant (see Chronic Kidney Disease).

DiagnosisTop

Diagnostic Tests

1. Biochemical tests: Hypercalcemia, high PTH levels (>10 × upper limit of normal), hyperphosphatemia (in patients with CKD).

2. Imaging studies: Imaging studies are not required to make a diagnosis of tertiary hyperparathyroidism. When performed, they may reveal enlarged parathyroid glands and various bone lesions like those found in primary hyperparathyroidism.

Diagnostic Criteria

Hypercalcemia and elevated PTH levels in a patient with treated secondary hyperparathyroidism in the setting of advanced CKD, in whom other causes of hypercalcemia and hyperparathyroidism have been excluded.

TreatmentTop

Management of tertiary hyperparathyroidism depends on the degree of symptoms, risk of complications (primarily damage to the transplanted kidney), and levels of calcium and PTH.

Pharmacotherapy

As in secondary hyperparathyroidism.

Surgical Treatment

Parathyroidectomy is indicated in tertiary hyperparathyroidism when medical treatment fails. However, there are no evidence-based guidelines defining the PTH and calcium cutoff values for surgery. Medical treatment failure can be defined as persistently high PTH levels, hypercalcemia, as well as symptoms of hypercalcemia despite medical therapy. Two surgical procedures are commonly used: total parathyroidectomy with autotransplant and subtotal parathyroidectomy. Total parathyroidectomy with autotransplant involves resection of all 4 parathyroid glands followed by implantation of half of the resected parathyroid gland into the sternocleidomastoid muscle in the neck or brachioradial muscle in the forearm. Subtotal parathyroidectomy entails the resection of 3.5 parathyroid glands, with half of the most normal appearing gland left in place. Both surgical approaches have been shown to reduce the risk of postoperative hypoparathyroidism and adynamic bone disease, with subtotal parathyroidectomy performing better in terms of hypoparathyroidism incidence. Cure rates with both surgeries are comparable.

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