The Parathyroid Glands and Parathyroid Surgery in End Stage Renal Failure

Abstract

Background Since the 1850s, parathyroid surgery continues to evolve through improved understanding of the pathophysiology. Dialysis dependant end stage renal failure (ESRF), the major cause of secondary hyperparathyroidism continues to rise in the western world. Other than renal transplantation, parathyroidectomy may provide a substantial cure for longstanding renal hyperparathyroidism in dialysis dependant patients. In 2004, cinacalcet was introduced as an alternative to the surgical management of renal hyperparathyroidism. However, cinacalcet was withdrawn from Australia’s Pharmaceutical Benefits Scheme (PBS) in 2015, as the EVOLVE study failed to demonstrate a statistically significant reduction in the time to death, or non-fatal cardiovascular events in those treated with cinacalcet with renal hyperparathyroidism. This led to a re-emergence in parathyroidectomy. Additionally in our institution, patients who had been on cinacalcet, and subsequently underwent parathyroidectomy because of refractory disease or intolerance to cinacalcet, were noted to experience greater hyperkalaemia and hypocalcaemia in the intraoperative and immediate postoperative period.

Aims • To review the engrossing history of the discovery and progression of parathyroid surgery since the 19th century;

• To correlate the embryology, anatomy, histology, physiology and pathophysiology of parathyroid glands in end stage renal failure;

• To provide up to date review in regards to investigation and the surgical management of renal hyperparathyroidism;

• Conduct a cohort study on the association of cinacalcet use with greater likelihood of intraoperative and immediate postoperative hyperkalaemia and hypocalcaemia following parathyroidectomy in renal hyperparathyroidism.

Methods Literature reviews utilizing MEDLINE and Cochrane review databases, life science journals and textbooks were utilized. Hospital medical records from The Canberra Hospital were studied to collect data on the cohort case series. Analysis of data was performed using SPSS Statistics and Microsoft Excel.

Results Sir Richard Owen is reputed to be the first person to discover the existence of parathyroid glands when examining a rhinoceros in 1852. In the spirit of mortui vivos docent, Captain Charles Martell in the 1930s had significantly increased our understanding of the existence of ectopic locations of parathyroid glands, as well as operative planning. The physiology and pathophysiology of parathyroid glands in chronic renal failure is multifaceted, with a complex interplay between bone, kidneys, intestine, vitamin D, potassium, phosphate and magnesium. There are a range of investigative strategies for localizing parathyroid glands, often yielding greater sensitivity and specificity when utilizing a combination of imaging tools. The choice of operative strategy for parathyroidectomy is often influenced by surgeon’s preference and the institution’s resources, due to paucity of good randomized trials and meta-analysis. Finally, our cohort study has shown that prior cinacalcet use was linked closely with severe intraoperative and immediate postoperative hyperkalaemia, and greater hypocalcaemia compared to control patients who underwent parathyroidectomy for renal hyperparathyroidism.

Conclusions The continued inquiry into the basic sciences around renal hyperparathyroidism ensures that we are able to question traditional protocols, and practice the best evidence based medicine. From this, cinacalcet emerged to change the medical and surgical landscape in the treatment of hyperparathyroidism. The results of the cohort study led to development of a protocol for the perioperative management of renal hyperparathyroidism in cinacalcet treated patients requiring parathyroidectomy.