Indication and Procedure Selection
The total parathyroidectomy with autotransplantation (TPTX+AT)is the standard procedure for the surgical treatment of therapy-refractory secondary hyperparathyroidism (sHPT) in chronic kidney disease. Equivalent alternative procedures include subtotal parathyroidectomy (SPTX) and TPTX without autotransplantation. The choice of procedure depends on the clinical situation and the surgeon's preference. In cases of expected kidney transplantation, the balance between "recurrence risk vs. permanent hypoparathyroidism" is often weighted differently than in "permanent dialysis."
Regarding the recurrence issue, TPTX+AT offers the clinical advantage that in transplant-dependent recurrence, only the forearm autograft needs to be resected, and a renewed neck exploration is unnecessary.
The KDIGO recommends 2017 in a guideline update on the diagnosis, evaluation, prevention, and treatment of chronic kidney disease and associated mineral and bone disorder (CKD-MBD) a parathyroidectomy (PTX) in patients with CKD (Chronic Kidney Disease) ≥ stage 3a, whose PTH levels cannot be maintained in the range of 2–9 times the upper normal limit despite maximum medical therapy [7]. The guideline forms the basis for the indication for surgical treatment of secondary hyperparathyroidism.
In familial multiglandular disease, particularly MEN1, TPTX+AT is also an established procedure. The current MEN1 guidelines recommend bilateral cervical exploration with identification of all glands and either SPTX (≥3.5 glands) or TPTX+AT [8,9]. The choice of procedure is additionally influenced here by the increased recurrence risk and the need for concomitant thymectomy, see below.
TPTX+AT versus SPTX in Secondary Hyperparathyroidism
Meta-analyses show comparable efficacy of TPTX+AT and subtotal parathyroidectomy (SPTX) in sHPT [1-3].
Yuan et al. showed in a meta-analysis of 18 studies with 3,656 patients that both procedures (SPTX vs. TPTX+AT) are equally effective in controlling sHPT. There is no significant difference in symptom improvements, radiological changes, or recurrence rates. With longer operating times for TPTX+AT, the need for vitamin D analogs is lower after 12 months [1].
Li et al. analyzed 11 studies with 1,108 patients, where for TPTX without AT, the recurrence risk was reduced compared to TPTX+AT, but the risk for hypoparathyroidism was increased. Both procedures appear safe with comparable rates of operative complications and mortality [2].
For tertiary hyperparathyroidism, Albuck et al. confirmed in 28 studies (1,000 patients) comparable efficacy and safety of SPTX and TPTX+AT [3].
Tertiary hyperparathyroidism is a well-known complication after kidney transplantation in preexisting mineral metabolism disorders due to chronic kidney disease. Parathyroidectomy represents the only definitively curative treatment option for tertiary hyperparathyroidism. The optimal timing of parathyroidectomy – before or after transplantation – is controversially discussed in the literature. Karniadakis et al. investigated in his meta-analysis (3 studies with 223 patients) whether the timing of parathyroidectomy influences the successful remission of tertiary hyperparathyroidism in patients with functioning kidney transplant. No significant difference was found between pre- and post-transplantation PTX regarding PTH and calcium levels [33].
A randomized pilot study by Rothmund et al. in 40 patients showed after TPTX+AT a more frequent normalization of serum calcium and alkaline phosphatase than after SPTX, as well as a stronger improvement in pruritus and muscle weakness [9].
Quality of life improves significantly after parathyroidectomy: Alves Filho et al. documented in a meta-analysis of 9 studies an effect size difference (Hedges’ g) of 1.05 for global quality of life. Both subtotal and total PTX showed comparable benefits. [10].
Parathyroidectomy in MEN1-Associated pHPT
Familial forms of primary hyperparathyroidism (pHPT) are characterized by multiglandular disease, in which all four (or more) parathyroid glands may be affected. The most common cause is multiple endocrine neoplasia type 1 (MEN1). In contrast to sporadic pHPT, where usually a single adenoma is present, the familial form requires a more radical surgical approach.
In MEN1, multiglandular disease is present in over 90% of cases. The current guidelines recommend bilateral cervical exploration with SPTX or TPTX+AT with concomitant thymectomy [18,19]. Manoharan et al. compared three procedures in a cohort of 89 MEN1 patients: TPTX showed the lowest recurrence rate (10.5%), followed by SPTX (39.1%) and single gland excision (67.9%). This is offset by a higher risk of permanent hypoparathyroidism: TPTX 32%, SPTX 17%, single gland excision 0% [20]. Tonelli et al. reported on 51 MEN1 patients with TPTX + thymectomy and found no case of cervical recurrence, but a forearm recurrence in about 10% after 7±5 years [21]. Landry et al. analyzed 206 MEN1 patients and identified resection of ≥4 glands and an immediate postoperative PTH value <15 pg/mL as risk factors for hypoparathyroidism ≥6 months; in 30% of these cases, parathyroid function recovered spontaneously [22].
Evidence on Routine Thymectomy in Total Parathyroidectomy
Role of Routine Thymectomy in sHPT
The European consensus of the ESES (European Society of Endocrine Surgeons) advocates routine cervical thymectomy in both total and subtotal parathyroidectomy to reduce the risk of recurrence. This is the authoritative European guideline on the surgical treatment of sHPT [14].
In favor: The high prevalence of ectopic and supernumerary parathyroid glands in the thymus. Schneider et al. found intrathymic glands in 44.5% of 461 patients (ectopic 39.3%, supernumerary 6.5%) [11]. Pattou et al. identified supernumerary glands in 30% of patients with renal HPT. These were responsible for 32% of persistent or recurrent diseases [12]. The thymus is the most common location of ectopic glands at 58% [13]. An analysis of 161 reoperations showed that intrathymic parathyroid glands were found in 28.4% of neck re-explorations, while initially only 12.6% had received a thymectomy [16]. Missing thymectomy was an independent predictor for reintervention [17].
Against: Done et al. showed in a large multicenter database study a decline in the thymectomy rate from 25.5% (2005) to 10.1% (2023), without significant impact on the recurrence rate [15]. The application rate is clearly declining in practice. The TOPAR pilot study (Schlosser 2016) found better results without thymectomy/AT [26].
Trend: In summary, the evidence on routine thymectomy in sHPT is heterogeneous. The current trend is toward an individualized decision based on intraoperative findings. In cases of fewer than 4 identified glands intraoperatively or suspicion of ectopic location, thymectomy remains clearly indicated. As a blanket routine procedure, it is increasingly being questioned.
Thymectomy in MEN1
In contrast to sHPT, in MEN1 there is a dual indication for thymectomy: First, the removal of ectopic and supernumerary parathyroid glands, second, the possible prevention of thymic carcinoids – a rare but potentially lethal MEN1-associated neoplasm.
The authoritative clinical guideline for MEN1 recommends bilateral cervical exploration with identification of all four glands, subtotal PTX (≥3.5 glands) or total PTX with autotransplantation, as well as cervical thymectomy [8].
Nilubol et al. found in 60 MEN1 patients 20 ectopic glands at 24 locations, of which 75% [18,24] in the thymus. Preoperative imaging identified only 38% of ectopic glands and none of the supernumerary ones [23]. D’Alessandro et al. documented supernumerary glands in 12.2% of MEN1 patients, with one patient developing a recurrence 10 years after four-gland PTX without thymectomy and requiring sternotomy [24]. Salmeron et al. identified performed thymectomy as a significantly protective factor against recurrences in MEN1 (p < 0,003) [25].
The currently strongest evidence is provided by the 2025 published meta-analysis by Toraih et al. with 6 comparative studies and 306 patients: Transcervical thymectomy significantly reduced the rate of persistent pHPT (RR 0.15; 3.1% vs. 21.9%) and recurrent pHPT (RR 0.34; 12.9% vs. 43.8%). In addition, the rate of permanent recurrent laryngeal nerve injuries was lower [5]. These data strongly support routine thymectomy in MEN1-associated pHPT.
For the prevention of thymic carcinoids in multiple endocrine neoplasia type 1 (MEN1), the evidence is not as clear [6]; concomitant imaging surveillance remains necessary.
PTX and Thymectomy in Other Familial Syndromes
In other familial syndromes (MEN2A, FIHP, HPT-JT), the approach is guided by the syndrome-specific characteristics of multiglandular disease.
In MEN2A (RET mutation), the HPT prevalence is 20–30%; the disease usually progresses mildly. Selective resection of enlarged glands is preferred; thymectomy is often performed anyway as part of concomitant thyroidectomy due to medullary thyroid carcinoma [28]. In familial isolated hyperparathyroidism (FIHP), SPTX or TPTX+AT with concomitant thymectomy is recommended analogous to the MEN1 approach [28,29]. Hyperparathyroidism-jaw tumor syndrome (HPT-JT, CDC73 mutation) differs fundamentally: In 80% of cases, single-gland disease is present, with a 20% risk of parathyroid carcinoma. Unilateral resection is often sufficient [28]. For MEN4 (CDKN1B mutation), similar recommendations as for MEN1 apply due to rarity; specific data on thymectomy are lacking.
Hungry Bone Syndrome
Hungry bone syndrome (HBS) is a common complication after parathyroidectomy and occurs in up to 34% of patients. It causes acute, severe hypocalcemia typically within about four days after surgery.
HBS arises from the sudden drop in parathyroid hormone (PTH), which stops bone resorption and leads to rapid mineralization with increased uptake of calcium and phosphate into the bones.
In a recent study with 91 patients, the incidence in sHPT was significantly higher (72.2%) than in tertiary HPT. Hungry bone syndrome (HBS) occurred in 31 patients (34.1%), including all patients who underwent total parathyroidectomy with autotransplantation (TPTX + AT) [30]. Crucial for identifying high-risk patients are serum calcium, intact PTH, phosphate, and alkaline phosphatase (ALP). A low preoperative calcium level as well as elevated values of ALP and intact PTH are predictive of the occurrence of HBS [30].
Calcimimetics(Cinacalcet, Etelcalcetide)
Due to their widespread use, a global decline in parathyroidectomies is recorded. Sevva et al. were able to determine in a retrospective 5-year study of 52 dialysis patients on calcimimetics over 5 years (2018–2023) a PTH decline of up to 57%. None required a PTX [32].
Mogl et al. showed in 196 operations that pretreatment with cinacalcet influences neither recurrence rate nor complications and is safely usable as bridging therapy[31].
Cryopreservation
Cryopreservation of parathyroid tissue is recommended in all familial forms of HPT [28]; the utilization rate is 10%, the success of delayed autografts is 50% [22].
Ablative Procedures
The thermal ablation procedures used in secondary hyperparathyroidism (sHPT) include the two most commonly used methods, microwave ablation (MWA) [38,39] and radiofrequency ablation (RFA) [40], as well as the less common procedures of laser ablation [41] and high-intensity focused ultrasound (HIFU) [42]. These procedures represent less invasive methods as an option for patients at high risk for general anesthesia or for those who refuse surgery. They enable rapid recovery, simple implementation, and offer relative safety compared to parathyroidectomy (PTX). The cited sources show promising results