Post-Graft Recurrence Remains a Challenge for Primary Hyperparathyroidism

Post-graft recurrence is common among patients with primary hyperparathyroidism (PHPT) and surgical interventions remain a challenge, according to study findings in the Journal of the Endocrine Society.

Autologous grafting of parathyroid tissue is becoming an increasingly common procedure for PHPT, particularly in patients with multiple endocrine neoplasia type I (MEN1) syndrome. Previous studies have shown that there may be some underlying genetic and histologic patient factors that can influence euthyroid status. 

Researchers conducted a retrospective study in patients with PHPT who had received a parathyroid autograft to determine the long-term effects of this procedure. 

Patient data was pulled from the Natural History Study of Parathyroid Disorders study (ClinicalTrials.gov Identifier: NCT04969926) from 1991 to 2020. Researchers identified patients with PHPT who had received parathyroid autographs. PHPT was diagnosed based on abnormal elevations in parathyroid hormone (PTH) with normal or high serum calcium, normal kidney function, and replete vitamin D levels.

There were 115 patients identified with PHPT who had received parathyroid autographs, and 57% of participants were women. A majority of participants had a heritable form of PHPT (92%) with 81% of participants having MEN1. Patients with hyperparathyroid-jaw tumor syndrome were excluded from the study population. 

The primary study endpoints were long-term functional outcomes of parathyroid grafts and the recurrence of disease in the graft. At 6- and 12-months post-graft, graft function was assessed and placed into 3 overlapping categories based on serum biochemistry and the need for calcium supplementation: completely functional, partially functional, and nonfunctional.

Out of the 135 parathyroid grafts assessed, functional status could not be determined on 24, which were excluded from the analysis. There were 54 (49%) completely functional, 13 (12%) partially functional, and 44 (40%) nonfunctional grafts at the final follow-up. 

Subgroup analysis of immediate grafts vs delayed grafts revealed variations in functionality. There were 37 of 68 (54%) fully functional grafts in the immediate group compared with 17 of 43 (40%) fully functional grafts in the delayed group. Results show 6 (9%) partially functional grafts in the immediate group vs 7 (16%) partially functional grafts in the delayed group. There were 37% nonfunctional grafts in the immediate group and 44% in the delayed group.

Among the 54 fully functional grafts, 45 (83%) post-graft recurrences of PHPT were reported. The median time to recurrence was 8 years (95% CI, 4-15). A parathyroidectomy was performed on 42 of the recurrences, which cured 18 (43%) of the grafts. The cause of recurrence was graft-related issues (67%) or neck or mediastinal causes (33%). Median PTH levels were also increased among graft-related recurrence vs neck or mediastinal source (23 [95% CI, 20-27] vs 1.3 [95% CI, 1.2-2.5]; P =.03).

Study limitations are the changing reference values and treatment protocols over time, the small sample size, and the subjective dose adjustments for calcium supplementation.

“Physicians caring for these patients should elicit history of parathyroid autografts and routinely obtain serum PTH from bilateral antecubital veins (in patients with grafts to brachioradialis) to ascertain functional status of the graft and monitor for PHPT recurrence,” the study authors wrote.