Our study in patients with different types of HPT, negative/discordant conventional imaging and a high rate of concomitant thyroid pathologies and redo-surgeries respectively found a) an excellent per-patient and per-lesion sensitivity in patients with pHPT for preoperative detection of hyperfunctioning parathyroid tissue leading b) to a cure rate of almost 100% in all patient groups. The perioperative complication rate was very low.
Parathyroidectomy is the only definite treatment of HPT [25]. However, parathyroid surgery remains a challenge for every endocrine surgeon. The range of clinical scenarios varies from exact identification of a single diseased gland with cervical ultrasonography leading to focused exploration to unidentified multiglandular disease with negative preoperative imaging leading to bilateral exploration. The surgical outcome depends on the patient's individual pathology and surgical expertise. High-resolution imaging combined with intraoperative parathyroid hormone measurement are important pillars for high cure rates. Identifying the patient at risk for a potentially unsuccessful surgical exploration is the common goal of the treating interdisciplinary team. Successful preoperative localization of enlarged and hyperfunctioning parathyroids increases cure rates. If preoperative imaging results remain negative, surgical success rates are reduced [26]. Also cases of postoperatively persistent or recurrent disease remain a challenging entity [27]. At the same time imaging results should not be used to select patients for surgical referral. Patients with negative imaging results still remain surgical candidates.
During the past 20 years new preoperative localization techniques, such as sestamibi-SPECT, 4D-CT or PET/CT with various tracers were introduced. All modalities depend on the investigator's experience, technical factors and the anatomical localization of the pathology.
In Switzerland, the use of 18F-Fluorocholine-PET/CT is well established and nowadays reimbursed by the insurance in patients with negative/equivocal conventional imaging. The use of alternative tracers (methionine-PET/CT) has been described in the literature [28]. Currently both, 11C-methionine and 18F-fluorocholine tracers provide excellent results with detection rates of approximately 90% for single-gland adenoma, detect parathyroid adenoma in atypical localization (i.e. mediastinum) and are therefore recommended for further localization studies [29]. Compared to scintigraphy PET offers several advantages: a higher spatial resolution and a lower radiation dose [30]. The disadvantage in both methods is lower localization rates for multiglandular disease, relatively high costs, the potential for a false-positive in thyroid-nodules and lymph nodes and a potentially restricted availability of the tracers.
This single-center retrospective study shows that strategically well-planned parathyroid exploration and high cure-rates for hyperparathyroidism (HPT) can be successfully achieved using 18F-Fluorocholine-PET/CT in the preoperative work-up of patients with negative or equivocal imaging. We included morphological and functional imaging of the parathyroid in our clinical protocol and based our preoperative clinical algorithm on our previously published study [21]. In this study the per-patient and per-lesion sensitivity of 18F-Fluorocholine-PET/CT in patients with pHPT was high and compares to other existing studies [17, 18, 31–33].
However, sensitivity showed marked differences between the patient groups. It was highest in the pHPT group but lowest in the familial HPT group with a per-lesion sensitivity of only 14.6%. All of these patients were cured and showed normal serum calcium levels postoperatively underlining the importance of the above mentioned sophisticated surgical approach. Keeping in mind that the number of patients with familial HPT was low it can be speculated that compared to a single adenoma in pHPT detection multiglandular hyperplasia of all 4 glands in MEN-1-patients remains much more difficult even when PET-techniques are applied. Nevertheless, we emphasize the use of 18F-fluorocholine-PET/CT in patients with fHPT as an important preoperative procedure allowing the detection of the leading pathologies and the exclusion of ectopic localization of parathyroid glands.
Our study has limitations. Apart from the retrospective nature a quite high percentage of patients underwent scanning with 18F-fluorocholin-PET/CT but then were not operated and included in the final analysis. The reasons were manifold, and we are aware that this could have led to a selection bias. Of these 10 had negative PET/CT. According to guidelines we defined cure of the HPT (in primary and familial forms) as a normal serum calcium 6 months postoperatively. The duration of the long-term follow-up after apparently curative parathyroidectomy is still controversially discussed [34, 35]. However, this study has also several strengths: We included quite a high number of patients with complex pathologies, we studied the entire broad clinical spectrum of hyperparathyroidism and our follow-up rate nearly was 100%.
Curative parathyroidectomy is of paramount importance for the patient and justifies extensive preoperative work-up. The study shows that positive imaging with 18F-Fluorocholine-PET/CT successfully guides surgical strategy but also that patients with negative imaging with 18F-Fluorocholine-PET/CT can still have a high cure rate in the hands of experienced endocrine surgeons. Both focused, image-guided surgery (targeted parathyroidectomy) and bilateral exploration are appropriate operations that achieve high cure rates. Based on the growing experience with 18F-Fluorocholine-PET/CT this method might replace other methods of preoperative imaging in the long-run [36]. From a clinical point of view the cure of patients with hyperparathyroidism always rests on the combination of a reliable and sensitive preoperative imaging technique together with an experienced surgical approach.