Parathyroidectomy is recommended for both symptomatic and asymptomatic PHPT, as successful parathyroidectomy could make PHPT patients achieve long-term normocalcemia(9, 25). Our current study demonstrated that US-guided RFA also significantly decreased serum iPTH and ALP, and it normalized Ca and phosphorus levels with sustained efficacy in most patients with PHPT. Among patients who were followed for longer than 6 months, serum total Ca return to mormal range in 31 of 32 patients (96.88%) and iPTH return to mormal range in 27 of 32 patients (84.38%). In addition, one patient had P-PHPT and one had R-PHPT.
However, before satisfactory sustained efficacy was achieved, there were changing process about serum iPTH and calcium levels. Hypocalcemia is a common complication that occurs 1–3 days after thermal ablation(26). Hypocalcemia can manifest as numbness, paresthesia, and muscular twitching and in severe cases it may present with bronchospasm, cardiac arrhythmias, angina, heart failure, syncope, and seizures(27). Early identification of risk factors in patients with PHPT may ensure early identification and treatment of potential postoperative hypocalcemia, and may also ensure that serious sequelae are avoided. In our study, 13 of the 44 patients developed hypocalcemia within 72 h after ablation. Our current study also found that serum total Ca levels before RFA were significantly higher in patients with ALP ≥ 261.5 U/L than in patients with ALP < 261.5 U/L but for those patients with ALP ≥ 261.5 U/L, serum total Ca levels were significantly lower in patients with with ALP < 261.5 U/L at 1 day, 3 days and 1 month after RFA (all, P < 0.05). We believe that this was due to the fact that there was insufficient parathyroid function due to slow or delayed functional recovery of the remaining parathyroid tissue after ablation of the hyperfunctional PHPT nodule. Previous studies have demonstrated that serum ALP is a marker of bone formation and thus reflects the degree of osteoclastic activity and bone resorption. Bone resorption immediately decreases after surgery, but the changes in bone formation are not obvious over a short period(28). The high ALP value before ablation indicates that high bone turnover is associated with significant risk of hypocalcemia.
The iPTH measurements post-ablation immediate fall to undetectable or significantly lower levels suggests that the functional parathyroid gland was destroyed by RFA. Since the half-life of iPTH is short (4 min), serum iPTH rapidly decreases after RFA(29). The remaining parathyroid glands are temporarily suppressed following autonomous parathyroid tissue ablation. It takes suppressed parathyroid glands half an hour to several days to recover PTH secretion. The rapid return of PTH secretion may be caused by the direct response of the remaining parathyroid glands to hypocalcemia(30).
Previous studies showed that long-term elevation of PTH without hypercalcemia would linked to a spectrum of bone, kidney, and the cardiovascular system complications(31, 32). In the current study, the serum iPTH level was significantly elevated at 1 month post-ablation and the difference remained statistically significant compared with baseline levels. Seventeen of the 39 patients (43.59%) developed ePTH 1 month after RFA. There were similar findings in patients treated with parathyroidectomy or thermal ablations in previous studies(22, 26). Possible hypotheses include incomplete ablation or the presence of ectopic parathyroid glands, vitamin D deficiency, renal resistance to PTH and a compensatory response to imbalance calcium homeostasis(33, 34). Fan et al.(35) found elevated serum iPTH levels at 1 month after MWA for PHPT, but their study did not investigate the risk factors for elevated iPTH levels with normocalcemia. Yen et al.(36) suggested that an elevated postoperative iPTH concentration does not predict surgical failure as measured by recurrent hypercalcemia. Carsello et al.(37) have shown that Patients with elevated PTH values after parathyroidectomy do not have greater rates of recurrence than patients with normal PTH values. In the current study, we compared the pre-ablative clinical and laboratory data between the two groups. The ePTH group had higher iPTH and lower serum 25 (OH) D3 levels before RFA than the normal group. Based on our results, a baseline serum iPTH level of more than 172.4 pg/mL could be considered a risk factor for ePTH at 1 month after RFA. A higher baseline level of iPTH indicates a longer-standing disease. In patients with a longer-standing disease, cortical bone remineralization lead to significant bone turnover after ablation. In order to maintain normal extracellular calcium concentration, so there is a compensatory increase in serum iPTH(38). In our study, a lower baseline 25 (OH) D3 level was also a significant factor predicting ePTH after RFA. Untch et al.(39) demonstrated Patients in PHPT with vitamin D deficiency associated with higher baseline PTH levels and higher postoperative PTH levels. That is may be explained by vitamin D deficiency may be stimulate the secretion of serum iPTH. Based on our results, the serum iPTH tended to be stable and normal when the Ca level remained within normal range 3 months after RFA.
Additionally, the parathyroid glands are located behind the thyroid gland and are closely adjacent to the trachea and esophagus, the internal jugular vein and recurrent laryngeal nerve, and they are posterior to the long cervical and sympathetic nerves(40). Injury to the RLN is a serious complication after thyroid and parathyroid region thermal ablation or surgery(13, 41). In our study, 2 patients(4.5%) developed temporary laryngeal nerve palsy and all of them recovered spontaneously within 2–3 months. No one had permanent RLN injury. The rate of permanent RLN injury has been reported to as close to 0% while temporary RLN injury is seen in 2.5% after parathyroidectomy(42, 43). The prevalence of permanent RLN injury observed in this study is consistent with previous studies but the rate of temporary laryngeal nerve palsy was slightly higher than those reported in previous studies. The main factor of slightly high temporary RLN injury rate may be related to potential thermal damage. Ultrasound imaging can show the ablated tissue as dynamic expanding echogenic region, which is helpful to identify the margins of the ablated lesion and reduce the collateral damage and local recurrence. To reduce the incidence of thermal injury of the recurrent laryngeal nerve, continuous injection of 5% dextrose solution should be performed during the ablation process to remove the potential thermal damage. Our method did not affect the volume of the ablation zone. Therefore, US-guided RFA is a safe and feasible method for clinical management of PHPT patients.
This study was subject to several limitations. First, the sample size was relatively small, which may have influenced the statistical analysis and validity of our findings. Second, the follow-up time was relatively short, and more follow-up time is necessary to determine the long-term effectiveness of the treatment of RFA for PHPT. Third, this was a non-randomized retrospective study, which may have induced selection bias.
In conclusion, US-guided RFA for patients with PHPT is safe and feasible. It may be an alternative treatment for patients with PHPT who refuse or are unsuitable for parathyroidectomy. The risk of ePTH decreased by 21.7% for every 1 ng/mL increase in 25 (OH) D3. Significantly more patients developed hypocalcemia, ePTH when the pre-ablative ALP, iPTH were more than 261.5 U/L, 172.4 pg/mL, respectively. More attention should be paid to serum Ca and iPTH levels after RFA in patients with higher serum iPTH and ALP levels and lower 25 (OH) D3 levels before RFA.