Sage Journals: Discover world-class research

Abstract

Background:

In patients with renal hyperparathyroidism the choice of surgery varies between total parathyroidectomy with autotransplantation (TPTx + AT) and subtotal parathyroidectomy (SPT) with variable outcomes. The present study investigated the risk of extracervical recurrences in patients who underwent total parathyroidectomy with autotransplantation for dialysis patients with renal hyperparathyroidism.

Methods:

A retrospective cohort analysis of patients who underwent TPTx + AT for renal hyperparathyroidism between the years 2000 and 2023 at a tertiary referral hospital. Patient demographic profiles, biochemical and surgical data, incidence of recurrence and outcomes of intervention were collected.

Results:

Some 142 (71M:71 F) patients with a mean age of 58.6 ± 11.2 years underwent total parathyroidectomy and autotransplantation during the study period. The mean dialysis vintage was 6.3 ± 3.2 years. Extracervical recurrence was seen in 25 (17.6%) of 142 patients, after a mean follow-up of 9 (±4.2) years, with the common sites of recurrence being the deltoid autotransplant site (73.1%) and the mediastinum (11.5%), while 7.7% of recurrences were biochemical with no localized site. Of the recurrences, 19 of 25 (76%) underwent explant of the deltoid autotransplant, and two in the mediastinum underwent minimally invasive excision (one video assisted thoracic surgery and one robotic excision) of the parathyroid lesion. The median parathyroid hormone level at the time of recurrence was 109.4 pg/ml compared with 17.2 ng/L postexcision or explantation. The only factor predictive for recurrences in the cohort on multivariable analysis was postoperative serum PTH (p = 0.001). Log-rank test showed no statistically significant difference in survival between the two groups (p = 0.355).

Conclusion:

Extracervical recurrences in the autotransplant are not uncommon in the long-term following total parathyroidectomy and autotransplantation for patients with renal hyperparathyroidism. These recurrences need explantation or excision to reduce the PTH burden in patients who cannot avail a renal transplant.

Keywords

Hyperparathyroidism cinacalcet parathyroidectomy recurrence auto transplantation renal hyperparathyroidism total parathyroidectomy

Context and relevance

What was known?

Autotransplantation of the parathyroid gland is a well-established surgical technique, especially in the context of renal (secondary or tertiary) hyperparathyroidism following total parathyroidectomy with or without thymectomy.

Autotransplantation prevents permanent hypoparathyroidism, provides a controlled source of PTH post-op, and in the presence of recurrence the autograft is easier to resect than re-exploring the neck.

Recurrence of the autografts following autotransplantation is reported to be approximately 8% but literature in this regard is sparse.

What this study adds?

Long-term extracervical recurrence following total parathyroidectomy and autotransplantation is not uncommon with an incidence of 18%.

Most recurrences are in the deltoid explant.

Elevated postoperative PTH well above the normal range is a predictor of long-term recurrence.

Potential impact:

Explantation of the autotransplant is required to mitigate the severe hypophosphatemia and elevated PTH.

Not all cases of elevated PTH are due to recurrence, but may be due to prolonged dialysis after parathyroidectomy.

Long-term surveillance is necessary in patients following TPTX + AT for early detection of recurrence.

Introduction

Chronic kidney disease (CKD) is a common condition globally, affecting 5% to 10% of the population, with significant impact on health.¹ Worsening renal function over decades would eventually result in end-stage renal disease (ESRD), associated with increased serum parathyroid hormone (PTH), phosphorus and derangement of calcium, 25-hydroxyvitamin D (25(OH)D),1,25-dihydroxyvitamin D (1,25(OH)2D), fibroblast growth factor-23 (FGF-23), and growth hormone. Given the fact that patients with ESRD commonly develop mineral and bone disorders, known as CKD-MBD, this prompted Kidney Disease Improving Global Outcomes (KDIGO) to produce clinical guidelines for the management of this condition.² CKD-MB has a prevalence of about 55% as shown by a study from Singapore.³

A manifestation of CKD-MB is renal hyperparathyroidism associated with elevated PTH and parathyroid gland hyperplasia. The mineral abnormalities and the increased PTH can be toxic to bone, heart muscle, and other organs.⁴ Increased parathyroid hormone levels promote cardiovascular sequelae such as left ventricular hypertrophy, arrhythmias, and rates of incident heart disease.⁵ In addition, the deranged bone and mineral metabolism has shown to be associated with extraskeletal calcification, especially in the vasculature.^6,7 The treatment of CKD-MB generally involves medical therapy to control the levels of phosphate, calcium, vitamin D, and PTH levels. Common measures include administering phosphate binders, calcium and Vitamin D supplements, reducing phosphate intake and oral cinacalcet therapy. Patients who fail conservative therapy, require surgical parathyroidectomy.

Surgical treatment options for renal hyperparathyroidism includes total parathyroidectomy (TPTx), subtotal parathyroidectomy (STTPTx), and total parathyroidectomy with auto transplantation (TPTx + AT), with or without transcervical thymectomy.^8,9 In patients who undergo TPTx + AT common sites for autotransplantation include the deltoid, brachioradialis and sternocleidomastoid muscles.^10–12 AT help regulate the levels of parathyroid hormone and other minerals in the blood, and thereby alleviate the complications associated with low level of parathyroid hormones in renal hyperparathyroidism, seen in patients who undergo TPTx alone.^8,13 However, despite the potential benefits of TPTx + AT, recurrences are not uncommon in the autograft.^14,15 The aim of this study was to examine the outcomes of recurrences in patients on long-term surveillance following TPTx with deltoid autotransplantation.

Methods

This retrospective study evaluated all patients diagnosed with renal hyperparathyroidism who underwent total parathyroidectomy with deltoid autotransplantation between 2000 and 2022. The study adhered to the Declaration of Helsinki and was approved by the institution’s research ethics committee (IRB no 2022/00647). Variables extracted from the electronic medical records included clinical characteristics such as age at the time of the total parathyroidectomy, gender, race, dialysis vintage, tumor size, and thymectomy status. In addition, preoperative and postoperative biochemical indices—including serum calcium, parathyroid hormone, phosphate, and bone alkaline phosphatase levels—were reviewed.

Hospital medical records and prospectively maintained outpatient clinic records were examined to assess the incidence of postoperative hypocalcemia and hungry bone syndrome, as well as overall survival and recurrence. Recurrence data included the site, parathyroid hormone levels, and the management of recurrence. Recurrence was defined as initial decrease of serum PTH, followed by a subsequent increase in PTH, usually after 6 months or reappearance of elevated parathyroid hormone (greater than 6.8 pmol/L) and/or hypercalcemia (more than 2.6mmol/L) after a normalization or near normalization level post operative parathyroidectomy.^16–19 All patients received a cervical ultrasound and a Sestamibi-scintigraphy prior to intervention. Overall survival was calculated as the time interval from the date of definitive surgery to mortality, regardless of the cause. The last follow-up date was December 2023. Patients with subtotal parathyroidectomy, cervical recurrences post total or subtotal parathyroidectomy and post renal transplant hyperparathyroidism were excluded from the study.

Data were recorded in Microsoft Excel (Microsoft Corp., Redmond, WA, USA). Patients were categorized based on recurrence status. Descriptive statistics are presented as mean (standard deviation), median (inter-quartile range), and frequencies (percentages) as appropriate. Continuous variables were compared using the student’s t-test or Mann–Whitney U test, while categorical variables were analyzed with the Chi-square test or Fisher’s exact test. The 5-year overall survival between the two groups was evaluated using the Log-Rank (Mantel-Cox) test and Kaplan-Meier survival curve. Univariate analysis of recurrence was performed using Cox regression analysis, with variables having a p-value < 0.2 included in the multivariable analysis. Hazard ratios and their 95% confidence intervals were calculated for each variable, with a p-value < 0.05 considered statistically significant. All statistical analyses were conducted using JASP version 0.18.3 (Netherlands) and IBM SPSS Statistics version 26 (IBM Corp., Armonk, NY, USA) for Windows.

Results

A total of 142 patients with renal hyperparathyroidism underwent total parathyroidectomy, comprising 71 males and 71 females (as shown in Fig. 1). The mean age of the patients was 58.3 ± 11.3 years. Of these, 25 patients (17.6%) experienced recurrence of hyperparathyroidism. The mean time to recurrence after index surgery was 5.1 years (± 2.4), with most of the recurrences prior to 2014 as shown in Fig. 2. There were no significant differences in the clinical profiles between the recurrence and nonrecurrence groups (Table 1). Preoperatively, only alkaline phosphatase was significantly higher in the no recurrence group (median 285 vs 107.5 (IU/L), p < 0.001). Serum calcium, PTH, and phosphate did not differ significantly between the two groups (Table 1).

Fig. 1.

PRISMA of the study cohort.

Fig. 2.

Number of recurrences over the period of study showing a higher recurrence rate prior to 2014, and change in PTH after treatment of recurrences in 21 patients (19 deltoid explants and 2 mediastinal excision of hyperplastic glands).

Table 1.

Clinical and biochemical profile of patients (n = 141) with total parathyroidectomy and autotransplantation.

	No recurrence (n = 116)	Recurrence (n = 25)	p-value
Age (years)	58.1 ± 11.6	59.1 ± 9.9	0.696
Sex
FemaleMale	55 (47.4%)61 (52.6%)	16 (61.5%)10 (38.5%)	0.278
Thymectomy
NoYes	73 (62.9%)43 (37.1%)	12 (46.2%)14 (53.8%)	0.127
Dialysis vintage (years)	6.8 ± 4.3	5.9 ± 2.2	0.288
Size of the glands (cm)	1.8 ± 0.6	1.7 ± 0.4	0.400
Renal Tx
NoYes	77 (66.4%)39 (33.6%)	19 (73.1%)7 (26.9%)	0.644
Post Tx RHPT
NoYes	106 (91.4%)10 (8.6%)	21 (80.8%)5 (19.2%)	0.152
Preoperative Biochemistry Indices
Calcium (mmol/L)	2.4 ± 0.2	2.4 ± 0.3	0.388
PTH (ng/L)	195 ± 79	196.1 ± 66.6	0.947
PO4 (mmol/L)	1.7 ± 0.5	1.6 ± 0.3	0.326
ALP (IU/L)^a	285 (136–488)	107.5 (81.2–208.5)	< 0.001
Postoperative Biochemistry Indices
Calcium (mmol/L)	2.3 ± 0.3	2.3 ± 0.2	0.622
PTH (ng/L)^a	4.4 (1.7–8.5)	22.6 (7.9–47.8)	< 0.001
PO4 (mmol/L)	1.5 ± 0.4	1.3 ± 0.4	0.105
ALP (IU/L)^a	89 (71–136.8)	107 (81–187.5)	0.235
Hypocalcemia
NoYes	91 (78.4%)25 (21.6%)	21 (80.8%) 5 (19.2%)	1.000
HBS
NoYes	108 (93.1%)8 (6.9%)	24 (92.3%)2 (7.7%)	1.000

Median (IQR 25th–75th percentile).

Postoperatively, the parathyroid hormone level was significantly higher in the recurrence group (median of 22.6 vs 4.4 ng/L, p < 0.001). Other postoperative parameters, including serum calcium, phosphate, alkaline phosphatase levels, as well as the incidence of hypocalcemia and hungry bone syndrome, were similar between the two groups (Table 1). The most common sites of recurrence were the deltoid (73.1%) and the mediastinum (11.5%), while 7.7% of recurrences were biochemical with no localized site. The median parathyroid hormone level at the time of recurrence was 109.4 ng/L. Among the 25 patients with recurrence, 80.8% underwent explantation of the deltoid autograft, with a median parathyroid hormone level of 17.2 ng/L postexcision or explantation (Table 2). Four patients (one with mediastinal, one forearm recurrence, and two with biochemical hyperparathyroidism) chose not to have any revision surgery for the recurrences. The two patients with persistent biochemical elevation of PTH had negative imaging on both US of the neck, deltoid and Sestamibi scans.

Table 2.

Recurrent renal hyperparathyroidism outcomes and management.

	N = 25
Site of recurrence
Deltoid	19 (73.1%)
Mediastinum	3 (11.5%)
Unknown/biochemical	2 (7.7%)
Forearm	1 (3.8%)
PTH level (ng/L)
Diagnosis of recurrence^a	109.4 (57.7–125.9)
Postexcision/explantation^a	17.2 (7.4–50.6)
Management of recurrence
Exploration + Excision/Explantation	21 (80.8%)
Conservative	4 (19.2%)

Median (IQR 25th–75th percentile).

In the 19 patients with deltoid autograft who underwent explantation and two patients with mediastinal excision, the change in PTH is shown in Fig. 2. Of the 19 patients, four continue to have very elevated PTH (more than five times the upper limit of normal) despite surgical intervention and of these two patients had previous thymectomy performed at index surgery. The mediastinal recurrence in two patients was treated with VATS approach (n = 1) and robotic surgery (n = 1). In terms of complications, symptomatic hypocalcaemia was seen in two (4%) and hungry bone syndrome in one (2%) of the patients with recurrent surgery.

Univariate Cox regression analysis revealed that postoperative PTH (HR = 1.049, 95% CI: 1.035–1.064; p < 0.001) were associated with recurrence. Multivariable analysis confirmed that only postoperative PTH remained a strong predictor of recurrence (HR = 1.043, 95% CI: 1.027–1.060; p < 0.001) (Table 3). The 5-year overall survival rate was 92.9% for patients with recurrence and 84% for those without recurrence. However, the log-rank test showed no statistically significant difference between the two survival rates (p = 0.355). The mean overall survival time was 204.5 months for the recurrence group and 211.1 months for the nonrecurrence group (Fig. 3).

Table 3.

Uni-and multivariable Cox regression analysis for recurrence total parathyroidectomy and autotransplantation.

Variable	Univariate	95% CI		p-value	Multivariate	95% CI		p-value
	HR	Lower	Upper		HR	Lower	Upper
Age (years)	1.007	0.974	1.041	0.666
Sex (male/female^a)	0.649	0.294	1.433	0.285
Thymectomy (Yes/No^a)	1.580	0.730	3.422	0.246
Dialysis vintage	0.949	0.844	1.067	0.380
Size of the glands	0.892	0.433	1.837	0.757
Renal Tx (Yes/No^a)	0.679	0.285	1.619	0.383
Post Tx RHPT (Yes/No^a)	1.816	0.683	4.826	0.232
Preop Calcium	1.853	0.413	8.322	0.421
Preop PTH	1.001	0.996	1.006	0.790
Preop PO4	0.677	0.305	1.504	0.338
Preop ALP	0.998	0.996	1.000	0.048	0.999	0.997	1.001	0.189
Post-op Calcium	2.086	0.506	8.596	0.309
Post-op PTH	1.049	1.035	1.064	<0.001	1.043	1.027	1.060	<0.001
Post-op PO4	0.367	0.125	1.078	0.068	0.548	0.211	1.420	0.215
Post-op ALP	1.001	0.999	1.003	0.332
Hypocalcemia (Yes/No^a)	0.864	0.326	2.293	0.770
HBS (Yes/No^a)	0.989	0.233	4.206	0.988

Reference.

The p-value indicates statistical significance (p < 0.05).

Fig. 3.

Overall survival between the recurrence and no recurrence groups after total parathyroidectomy for renal hyperparathyroidism.

Discussion

The incidence of long-term extracervical recurrence following TPTx + AT is about 18%, with nearly three quarters of them in the deltoid autograft, and mediastinum. In such extracervical recurrences, interventions like deltoid parathyroid explant or mediastinal exploration may be required to render the patients euparathyroid. This long-term study shows a higher incidence of autografted hyperplasia with continuing severe CKD, though with no impact on mortality. The predictors of long-term recurrence in this study include higher postoperative PTH levels and longer duration of CKD. The findings from the study align with previous research that there is a continued high secretion of PTH following TPTx.²⁰

Patients with CKD have hyperplasia of the parathyroid glands and usually require removal of all the glands and the choice of nature of the parathyroid surgery depends on a few factors. Subtotal PTx is the preferred choice of surgery in patients with tertiary hyperparathyroidism post renal transplantation where only one or two glands may be hyperplastic.^21,22 TPTx + AT is preferred in patients with co-existent thyroid pathologies that may require further interventions, medical comorbidities precluding safe general anesthesia or surgery, or previous neck surgeries.²³ Review of articles published in the literature comparing outcomes of TPTx + AT with subtotal PTx showed superior benefits in terms of recurrence with TPTx + AT.^{13,14,24–27} In a previous study we had shown superior outcomes in the short term TPTx + AT in our institution, with subtotal PTx being preferred in transplanted patients with tertiary hyperparathyroidism.¹⁴

Following total parathyroidectomy for refractory secondary or tertiary hyperparathyroidism, a small amount of viable parathyroid tissue is often ectopically implanted to maintain controlled parathyroid hormone (PTH) production and prevent permanent hypoparathyroidism. The Wells’ method is the most employed technique, involving transplantation of parathyroid tissue into the forearm muscle (typically brachioradialis).^12,28 This approach offers a surgically accessible site for potential future re-excision and facilitates PTH monitoring from the graft site via selective blood sampling. However, the technique is not without drawbacks, with a common concern being potential interference with vascular access. To address these concerns, minimally invasive alternatives have been proposed, including subcutaneous injection or Intramuscular injection of finely minced parathyroid tissue, which are the techniques employed in our institution.^10,11,29

While parathyroid autograft is effective in preventing permanent hypoparathyroidism following total parathyroidectomy, it is not without potential complications. One notable concern is the development of autograft hyperplasia, the incidence of which is reported to be approximately 8%, and the risk appears to be closely linked to the selection of the reimplanted parathyroid tissue.^15,16,30 Reimplantation of hyperplastic, nodular, or otherwise diseased tissue can lead to recurrent or persistent hyperparathyroidism originating from the graft site. To mitigate this risk, it is recommended that the reimplanted tissue be carefully selected intraoperatively, ideally using the most normal looking gland in size and architecture, and confirmed, when possible, by frozen section analysis. In addition, dividing the tissue into multiple small fragments implanted into separate pockets within the muscle can help reduce the likelihood of overgrowth and facilitate targeted re-excision if necessary. The institutional practice for the last 15 years has been to use about 30-40 mg of the most normal looking parathyroid and mince it before implanting into the deltoid and this has been shown to be very effective maintaining the PTH levels.^10,11

Several factors can contribute to the recurrence of hyperparathyroidism following parathyroidectomy in patients with renal hyperparathyroidism and include incomplete removal of the parathyroid glands during the initial surgery, the presence of supernumerary or more than four glands or ectopic parathyroid glands, and the development of new hyperplastic glands over time. In the study reported here, long-term recurrence in the deltoid autotransplant was seen in nearly 10% of the cohort, similar to that reported by Tominaga et al.³⁰ in their series of 2669 patients requiring deltoid explant in 9.3%. Supernumerary glands in the neck and mediastinum were seen in 12 (6%) of patients, with half of them requiring surgical intervention. Numano et al.³¹ reported the presence of supernumerary glands in their cohort of 870 patients, with 12 (2%) requiring reintervention for recurrent/persistent disease. Where deltoid autograft is the site of recurrence, en bloc resection of autograft with surrounding muscle is required.³⁰

Thymectomy along with subtotal or total PTx would decrease persistent or recurrent disease due to the presence of supernumerary or thymic parathyroids. Supernumerary parathyroid glands have been reported in over 10% of random autopsies, and in 30% of patients with renal hyperparathyroidism usually located in the neck in the retroesophageal grove or carotid sheath, and extracervical in the thymus and mediastinum.³² In this study, three parathyroids were localized in the superior mediastinum, of whom two patients underwent re-exploration and were cured. A similar study showed intrathymic parathyroids at recurrent surgery in 28% of patients, found to be ectopic in 17 (63.0 %) patients and supernumerary in eight (29.6 %).³³ Thus, routine transcervical thymectomy should be performed where possible in patients on permanent hemodialysis with no potential for renal transplantation to decrease this risk of recurrent disease and reoperative morbidity.^32–35

The findings from this study align with existing literature on the predictors and outcomes of recurrent renal hyperparathyroidism (rHPT) posttotal parathyroidectomy (TPTx). Previous research identified higher preoperative parathyroid hormone (PTH) levels and longer duration of renal disease post parathyroidectomy as significant predictors of recurrence, mirroring this study’s conclusions.²⁰ A recent meta-analysis showed a strong correlation between intraoperative parathyroid hormone (ioPTH) levels and early postoperative PTH measurements, indicating that ioPTH monitoring is a reliable intraoperative marker during parathyroidectomy (PTX) for renal hyperparathyroidism (rHPT).³⁶ In patients where there is no significant drop at 20 min with IOPTH may require closer PTH monitoring looking for persistent or recurrent disease. This is reinforced by the findings of Xu et al.³⁷ who emphasized that elevated PTH levels immediately after surgery are indicative of recurrence risk. However, not all biochemical PTH elevation post parathyroidectomy can be attributed to treatment failure or recurrence, after parathyroidectomy, as continued PTH secretion occurs in response to the uremic stimulus, and early hypocalcaemia. These studies collectively highlight the necessity of early surgical intervention and vigilant biochemical surveillance to mitigate the risk of recurrence and manage patient outcomes effectively. In this study, biochemical elevation of high PTH was seen in four patients, despite intervention to explant the deltoid autograft.

Management of recurrence following total parathyroidectomy can be troublesome. Our findings indicate that while recurrence is a relatively common occurrence, it does not significantly impact overall survival in this patient population. Improved surgical techniques and postoperative care may have contributed to effective outcomes in our cohort. However, patients experiencing recurrence had a significantly longer follow-up duration, suggesting they may require more intensive monitoring and management. This longer follow-up period (9.4 years for the recurrence group vs 7.3 years for the nonrecurrence group) underscores the need for vigilant long-term surveillance to detect and manage potential complications early.

Conclusion

In the long-term, extracervical recurrence is not uncommon following total parathyroidectomy and autotransplantation for renal hyperparathyroidism. When recurrences are detected, explantation of the autotransplant may be required to mitigate the severe hypophosphatemia and elevated PTH. Not all cases of elevated PTH are due to recurrence, but may be due to prolonged dialysis after parathyroidectomy, and in such cases continued medical therapy is required with long-term follow-up.

Footnotes

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Dan Cortes, Sujith Wijerethne, James Lee, Ngiam Kee Yuan, and Rajeev Parameswaran. Statistical analysis was performed by Ralph Victor Yap. The first draft of the manuscript was written by Dan Cortes & Sujith Wijerethne and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

The study adhered to the Declaration of Helsinki and was approved by the institution’s research ethics committee (IRB no 2022/00647).

ORCID iD

Rajeev Parameswaran

References

Eknoyan

Lameire

Barsoum

, et al: The burden of kidney disease: Improving global outcomes. Kidney Int 2004;66: 1310–1314.

KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 2009;76:S1–130.

Chuang

Wong

Vathsala

, et al: Prevalence of chronic kidney disease-mineral and bone disorder in incident peritoneal dialysis patients and its association with short-term outcomes. Singapore Med J 2016;57(11):603–609.

Moe

Drüeke

Cunningham

, et al: Definition, evaluation, and classification of renal osteodystrophy: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006;69(11):1945–1953.

Palmer

Hayen

Macaskill

, et al: Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: A systematic review and meta-analysis. JAMA 2011; 305:1119–1127.

Reiss

Miyawaki

Moon

, et al: CKD, arterial calcification, atherosclerosis and bone health: Inter-relationships and controversies. Atherosclerosis 2018;278:49–59.

Kaur

Singh

. Mechanistic insights into CKD-MBD-related vascular calcification and its clinical implications. Life Sci 2022;311:121148.

Chen

Jia

Kong

, et al: Total parathyroidectomy with autotransplantation versus subtotal parathyroidectomy for renal hyperparathyroidism: A systematic review and meta-analysis. Nephrology (Carlton) 2017;22(5):388–396.

Hiramitsu

Hasegawa

Futamura

, et al: Treatment for secondary hyperparathyroidism focusing on parathyroidectomy. Front Endocrinol (Lausanne) 2023;14:1169793.

10.

Tan

Cheah

Tan

, et al: Intramuscular injection of parathyroid autografts is a viable option after total parathyroidectomy. World J Surg 2010;34(6):1332–1336.

11.

Wang

Chua

, et al: Subcutaneous injection is a simple and reproducible option to restore parathyroid function after total parathyroidectomy in patients with secondary hyperparathyroidism. Surgery 2014;155(4):682–688.

12.

Wells

Jr. Gunnells

Shelburne

, et al: Transplantation of the parathyroid glands in man: Clinical indications and results. Surgery 1975;78(1):34–44.

13.

Liu

Qiu

Zha

, et al: To assess the effects of parathyroidectomy (TPTX versus TPTX+AT) for secondary hyperparathyroidism in chronic renal failure: A systematic review and meta-analysis. Int J Surg 2017;44:353–362.

14.

Rajeev

Lee

Tang

, et al: Outcomes of parathyroidectomy in renal hyperparathyroidism in patients with no access to renal transplantation in Singapore. Int J Surg 2016;25:64–68.

15.

Niederle

Hörandner

Roka

, et al: Parathyreoidektomie und Autotransplantation beim renalen Hyperparathyreoidismus. I. Klinische und Laborchemische Untersuchungen zur Gewebeauswahl. Chirurg 1989;60:665–670.

16.

Agha

Loss

Schlitt

, et al: Recurrence of secondary hyperparathyroidism in patients after total parathyroidectomy with autotransplantation: Technical and therapeutic aspects. Eur Arch Otorhinolaryngol 2012;269(5):1519–1525.

17.

Dream

Kuo

, et al: The American Association of Endocrine Surgeons Guidelines for the definitive surgical management of secondary and tertiary renal hyperparathyroidism. Annals of Surgery 2022;276:e141–e176.

18.

Lorenz

Bartsch

Sancho

, et al: Surgical management of secondary hyperparathyroidism in chronic kidney disease—A consensus report of the European Society of Endocrine Surgeons. Langenbecks Arch Surg 2015;400(8):907–927.

19.

Ketteler

Evenepoel

Holden

, et al: Chronic kidney disease–mineral and bone disorder: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference. Kidney Int 2025;107:405–423.

20.

Stratton

Simcock

Thompson

, et al: Predictors of recurrent hyperparathyroidism after total parathyroidectomy in chronic renal failure. Nephron Clin Pract 2003;95(1):c15–22.

21.

Nichol

Starling

Mack

, et al: Long-term follow-up of patients with tertiary hyperparathyroidism treated by resection of a single or double adenoma. Ann Surg 2002;235:673–678; discussion 678–680.

22.

van der Plas

Kruijff

Sidhu

, et al: Parathyroidectomy for patients with secondary hyperparathyroidism in a changing landscape for the management of end-stage renal disease. Surgery 2021;169:275–281.

23.

Almquist

Isaksson

Clyne

. The treatment of renal hyperparathyroidism. Endocr Relat Cancer 2020;27:R21–R34.

24.

Xiao

, et al: Total parathyroidectomy with forearm auto-transplantation improves the quality of life and reduces the recurrence of secondary hyperparathyroidism in chronic kidney disease patients. Medicine (Baltimore) 2017; 96(49):e9050.

25.

Zmijewski

Staloff

Wozniak

, et al: Subtotal parathyroidectomy vs total parathyroidectomy with autotransplantation for secondary hyperparathyroidism in dialysis patients: Short- and long-term outcomes. J Am Coll Surg 2019;228(6):831–838.

26.

Hou

Shan

Zhang

, et al: Network meta-analysis of surgical treatment for secondary hyperparathyroidism. Am J Otolaryngol 2020;41(2):102370.

27.

Wang

, et al: Total parathyroidectomy versus total parathyroidectomy with autotransplantation for secondary hyperparathyroidism: Systematic review and meta-analysis. Ren Fail 2017;39:678–687.

28.

Tominaga

Uchida

Haba

, et al: More than 1,000 cases of total parathyroidectomy with forearm autograft for renal hyperparathyroidism. Am J Kidney Dis 2001;38(4, Suppl. 1):S168–S171.

29.

Hsu

Hung

. Intramuscular and subcutaneous forearm parathyroid autograft hyperplasia in renal dialysis patients: A retrospective cohort study. Surgery 2015;158(5):1331–1338.

30.

Tominaga

Matsuoka

Uno

, et al: Removal of autografted parathyroid tissue for recurrent renal hyperparathyroidism in hemodialysis patients. World J Surg 2010;34(6):1312–1317.

31.

Numano

Tominaga

Uchida

, et al: Surgical significance of supernumerary parathyroid glands in renal hyperparathyroidism. World J Surg 1998;22:1098–1102; discussion 1103.

32.

Pattou

Pellissier

Noël

, et al: Supernumerary parathyroid glands: Frequency and surgical significance in treatment of renal hyperparathyroidism. World J Surg 2000;24(11):1330–1334.

33.

Schneider

Bartsch

Schlosser

. Relevance of bilateral cervical thymectomy in patients with renal hyperparathyroidism: Analysis of 161 patients undergoing reoperative parathyroidectomy. World J Surg 2013;37(9):2155–2161.

34.

Uludag

Yetkin

Citgez

, et al: The role of cervical thymectomy in surgical treatment of secondary hyperparathyroidism. Bratisl Lek Listy 2011;112(7):385–389.

35.

Soares

Cavalcanti

Iwakura

, et al: Analysis of the role of thyroidectomy and thymectomy in the surgical treatment of secondary hyperparathyroidism. Am J Otolaryngol 2019; 40(1):67–69.

36.

van Beek

Fredriksson

Haegele

, et al: Use of intraoperative parathyroid hormone measurements during parathyroidectomy to predict postoperative parathyroid hormone levels in patients with renal hyperparathyroidism: Meta-analysis. BJS Open 2022;6:zrab151.

37.

Yin

Hou

, et al: Surgical management of secondary hyperparathyroidism: How to effectively reduce recurrence at the time of primary surgery. J Endocrinol Invest 2016;39(5): 509–514.

Management of extracervical recurrence following total parathyroidectomy and autotransplantation for renal hyperparathyroidism

Abstract

Background:

Methods:

Results:

Conclusion:

Keywords

Context and relevance

Introduction

Methods

Results

Discussion

Conclusion

Footnotes

Author contributions

Declaration of conflicting interests

Funding

Ethical approval

ORCID iD

References