The present study offers insights into a 16-year surgical experience with pHPT analyzing the preoperative tests for biochemical diagnosis and the techniques utilized for parathyroid localization before surgery. In our comprehensive case series, preoperative imaging demonstrated its pivotal role, with US emerging as the most frequently utilized modality (employed in 98% of patients). Before the advent of 18F-FCH PET/CT, our clinic predominantly relied on MIBI scintigraphy as the second-level imaging modality. However, this approach proved to be less reliable, yielding negative results in 17.5% of cases (false-negative results), which posed challenges in surgical planning.

In our case series, a total of 21 patients presented a negative US and MIBI scintigraphy (2 in Group 1 and 19 in Group 2). In one case, a 4D-CT scan was performed and confirmed the presence of an adenoma; in 19 cases, a 18F-FCH PET/CT confirmed the presence of an adenoma, but 1 patient underwent surgery with negative US and MIBI scintigraphy. In the latter case, parathyroid cancer was found. In addition, the positivity of ultrasound as the first diagnostic level was higher in the first group compared to the second group, respectively, 82.5% and 20.7% with statistical significance (P < 0.001). Similarly, the negativity in both ultrasound and MIBI scintigraphy was higher in the second group compared with the first group, respectively, 79.3% and 86.25%, with statistical significance (P < 0.001). This points out the importance of 18 F-FCH PET/CT positivity in unclear cases when ultrasound and/or MIBI scintigraphy were negative. These findings could lead to several considerations. First of all, localizing parathyroid glands can be challenging. These discrepancies might stem from various factors, such as the size of the glands, their location within the neck, or variations in individual anatomy. Furthermore, in case of conflicting or inconclusive results from imaging, surgeons potentially have more difficulties in locating and removing the affected parathyroid glands. Therefore, alternative or more advanced imaging methods may be considered.

The introduction of 18F-FCH PET/CT marked a significant turning point in our approach. This advanced imaging technique consistently confirmed the preoperative diagnosis in all cases, enabling us to precisely identify the parathyroid glands targeted for removal [19, 20]. Remarkably, we were able to locate the parathyroid in 91.3% of cases directly, with only 8.7% classified as having BNE. In terms of postoperative outcomes, our study reported a 14.5% complication rate, excluding BNE. There were three cases necessitating reintervention and another that required calcium therapy at the end of the 30-day follow-up, with persistent hypoparathyroidism at 6 months after surgery. These findings emphasize the importance of accurate preoperative imaging in optimizing the management of pHPT and minimizing postoperative complications. No differences were found in terms of intraoperative and postoperative data when the population was divided according to the preoperative imaging or according to the presence of a preoperative 18F-FCH PET/CT.

Regarding the three cases reoperated for parathyroidectomy, there were 2 cases in group 1 (without PET/CT) and one in group 2 (with PET/CT). The patients were reoperated respectively after 5 and 4 years after the first intervention and were studied by a MIBI scintigraphy (group 1) and on the contrary the last patient (group 2) was reoperated after 2 years and a parathyroidectomy was performed, discovered by PET/CT.

As highlighted in the existing literature, the ability to accurately localize the affected parathyroid gland prior to surgery has far-reaching benefits. It not only enhances the planning of the surgical approach but also increases the feasibility of performing minimally invasive surgery, which in turn reduces postoperative pain, shortens the LOS, and ultimately leads to improved esthetic outcomes [21]. Targeted surgery, as opposed to the traditional BNE, not only achieves better overall results but also minimizes morbidity.

The combination of US and MIBI scintigraphy has been a well-established approach, with the potential to attain a sensitivity ranging from 80 to 90% [22]. In our cohort of patients, the combined use of US and MIBI scintigraphy proved sufficient for the localization of the hypersecretory gland in a commendable 76.7% of cases. However, the most remarkable results were observed when utilizing 18F-FCH PET/CT, as it facilitated the identification of the abnormal gland in 100% of cases. Impressively, in 93.3% (14 out of 15) of patients with positive 18F-FCH PET/CT results, MIP became a feasible option. Only one patient, who underwent 18F-FCH PET/CT, necessitated BNE.

The reason for the exceptional success of 18F-FCH PET/CT lies in its superior spatial resolution of the tracer, which enables the detection of even smaller adenomas. This enhanced resolution is a result of the rapid kinetics of choline, which proves particularly advantageous in identifying and localizing these abnormal parathyroid glands [14]. These findings underscore the significant advancement that 18F-FCH PET/CT represents in preoperative imaging for primary hyperparathyroidism, with the potential to revolutionize surgical planning and outcomes. Considering our experience, we propose the flow diagram in Fig. 3. 18F–FCH PET/CT can be useful also when US and MIBI scintigraphy are both positive but in different locations [23, 24].

Within our patient cohort, the pathological findings revealed a diverse spectrum of parathyroid conditions. Most cases consisted of parathyroid adenomas, accounting for 131 cases or 76.2% of the total patients. Atypical adenomas were identified in 6 patients, representing 3.5% of the cohort. Additionally, 16 cases (9.3%) were characterized by parathyroid hyperplasia, and another 5 cases (2.9%) were determined to be parathyroid cancers. These findings are consistent with the current body of literature, further validating the prevalence of these parathyroid pathologies [5, 25]. Intriguingly, in 6 cases (3.5%), the initially suspected parathyroid adenoma was not found during the surgical procedure. In one case, the 18F-FCH PET/CT revealed the presence of an adenoma. However, in other cases, this imaging was not conducted as it was not available in our facility at that time. Given that the patients had pHPT, the potential utilization of this examination could have offered an opportunity for a more comprehensive diagnostic approach, potentially leading to improved diagnosis and management.

Regarding the population included in the study and considering the preoperative diagnosis, in our series, about 22.5% of patients presented a normocalcemic primary hyperparathyroidism (nPHPT). This condition is not well understood in medical literature. Normocalcemic hyperparathyroidism presents a unique diagnostic challenge due to its normal serum calcium levels despite elevated parathyroid hormone levels. nPHPT can overlap with primary or secondary hyperparathyroidism, necessitating thorough evaluation to differentiate between these conditions. The diagnosis of nPHPT requires excluding secondary causes of elevated parathyroid hormone through a comprehensive clinical history, physical examination, and targeted laboratory investigations. Treatment strategies for nPHPT focus on addressing the underlying parathyroid gland abnormalities, surgical parathyroidectomy in select patients, and long-term monitoring to assess treatment efficacy and prevent the recurrence of hyperparathyroidism-related complications [26,27,28,29].

It is important to acknowledge certain limitations of our study, primarily its retrospective design, which may introduce inherent biases. Therefore, prospective studies specifically designed to investigate the localization of parathyroid glands could provide more robust and reliable evidence. Additionally, not all patients had the opportunity to undergo 18F-FCH PET/CT, as this modality was introduced later in our clinical practice. However, it is worth noting that the study's strengths lie in the extensive 16-year study period, allowing for a comprehensive analysis of the cases, and the fact that all surgeries were performed by experienced endocrine surgeons. These factors contribute to the robustness and reliability of the data, underscoring the clinical significance of the findings in the context of managing primary hyperparathyroidism.

Moreover, the success of minimally invasive surgery in managing pHPT critically hinges on the precise preoperative localization of the overactive parathyroid gland. For patients initially presenting with negative preoperative imaging, 18F-FCH PET/CT scans have emerged as a valuable diagnostic tool. These scans have demonstrated their ability to reveal even small parathyroid adenomas, even in cases where patients may exhibit normal calcium levels or hyperparathyroidism with normal parathormone levels, rendering ioPTH measurement less informative.

In our series, the use of the ioPTH assay enables the effectiveness of parathyroidectomy operations as there is a connecting factor between hormone kinetics during the operation and the removal of pathological parathyroid gland. A reduction in the ioPTH serum levels of over 50% with respect to the basal swab is considered a significant drop and is a confirmation of the adequacy of the surgical treatment.

The recent literature underscores the effectiveness and high accuracy of 18F-FCH PET/CT scans as a preoperative localization method for parathyroid adenomas, positioning it as a viable alternative to conventional imaging techniques [9, 10, 14]. This advanced technology offers superior spatial resolution, shorter scanning times, and reduced radiation exposure compared to methods like MIBI scintigraphy and 4D-CT, consistently delivering detection rates exceeding 90% [30]. It is important to note that 18F-FCH PET/CT is typically not recommended as the first-line imaging modality but rather reserved for patients with negative or inconclusive initial imaging results [9, 10, 14, 31]. In the future, it is conceivable that 18F-FCH PET/CT scans could become integrated into the first-level imaging for pHPT diagnosis, given their exceptional performance. Since the introduction of 18F-FCH PET/CT scans in our clinical practice, we have observed a notable increase in the number of hyperparathyroidism patients scheduled for surgery. Beyond providing a biochemical diagnosis, this technique offers the crucial advantage of precisely localizing the presumed adenoma. Nevertheless, it is essential to recognize that due to its remarkable accuracy, and 18F-FCH PET/CT can identify even the tiniest adenomas that may not be visually apparent during surgery. Consequently, in cases where ioPTH cannot be employed or in situations of pHPT with normal PTH levels, frozen section analysis stands as a reliable and complementary confirmation method [32]. This multimodal approach ensures the best possible outcomes in the management of pHPT, emphasizing the importance of ongoing advancements in diagnostic tools and surgical techniques.