Casella C, Guarneri C, Campanile M, Adhoute X, Gelera PP, Morandi R. Surgical treatment of tertiary hyperparathyroidism: does one fit for all? Front Endocrinol (Lausanne). 2023 Nov 2;14:1226917. doi: 10.3389/fendo.2023.1226917. PMID: 38027172; PMCID: PMC10652876.
Choi HR, Aboueisha MA, Attia AS, et al. Outcomes of Subtotal Parathyroidectomy Versus Total Parathyroidectomy With Autotransplantation for Tertiary Hyperparathyroidism: Multi-institutional Study. Ann Surg. 2021 Oct 1;274(4):674-679. doi: 10.1097/SLA.0000000000005059. PMID: 34506323.
Tang JA, Friedman J, Hwang MS, Salapatas AM, Bonzelaar LB, Friedman M. Parathyroidectomy for tertiary hyperparathyroidism: A systematic review. Am J Otolaryngol. 2017 Sep-Oct;38(5):630-635. doi: 10.1016/j.amjoto.2017.06.009. Epub 2017 Jun 21. PMID: 28735762.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001. Epub 2017 Jun 21. Erratum in: Kidney Int Suppl (2011). 2017 Dec;7(3):e1. doi: 10.1016/j.kisu.2017.10.001. PMID: 30675420; PMCID: PMC6340919.
Lorenz K, Bartsch DK, Sancho JJ, Guigard S, Triponez F. Surgical management of secondary hyperparathyroidism in chronic kidney disease--a consensus report of the European Society of Endocrine Surgeons. Langenbecks Arch Surg. 2015 Dec;400(8):907-27. doi: 10.1007/s00423-015-1344-5. Epub 2015 Oct 2. PMID: 26429790.
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
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.
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.
As in secondary hyperparathyroidism.
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.