The results of this study suggested a positive correlation between the volume of the parathyroid adenoma and preoperative PTH and calcium levels, while a negative correlation was seen with phosphate and Vitamin D.

Currently, discordant data regarding the correlation between adenoma volume and preoperative biomarkers are lacking and no definitive consensus has been reached. Several studies support our findings showing a similar correlation between the parathyroid adenoma volume and preoperative hormonal levels [18,19,20,21,22]; conversely, Randhawa et al. did not demonstrate any correlation between the pathological gland volume and preoperative laboratory variables [23].

The possible physiological reason supporting these results has not been well clarified. As Javadov et al. suggested, an increase in parathyroid gland volume is due to a rise in cell numbers, particularly the chief cells. These cells are mainly responsible for PTH secretion, and this may result in higher PTH and calcium levels together with lower phosphate levels [24]. In contrast, other authors have studied the chief cells and oxyphilic cells within parathyroid adenomas from a molecular perspective, without confirming a proportional relationship between the number of chief cells and calcium or PTH levels [25, 26].

Few data are currently available regarding the correlation between the volume of parathyroid adenomas and the clinical and biochemical manifestations of PHPT. A work from Kaszczewska et al. concluded that larger adenomas increase the risk of severe hypercalcemia, suggesting that adenoma size might influence the calcemia [27]. Another study by Gezer et al. pointed out a potential link between the volume of parathyroid adenomas and bone mineral loss at the distal forearm among patients with PHPT, suggesting that larger adenomas may contribute to greater skeletal demineralization in these patients [28].

With the exception of the study by Gezer [28], to our knowledge, no other studies specifically analyzed the relationship between parathyroid adenoma volume and BMD. However, it is well established that PHPT leads to alterations in bone mineralization, resulting in a reduction in BMD [29, 30]. Several studies have also reported that elevated levels of PTH are associated with bone density loss [31, 32]. A study conducted by Rubin et al. observed significant improvements in BMD in patients who underwent parathyroidectomy [33]. In contrast to these findings, our study did not observe any improvement in postoperative BMD at the 1-year follow-up. However, the retrospective design of the study together with the lack of a standardized postoperative protocol for long-term monitoring, including BMD assessment and outpatient follow-ups in cases without recurrence, prevents us from making general conclusions.

On the other hand, the results of this study did not show any significant difference between the volume of the adenoma and the onset of renal, muscular, or bone symptoms, or biochemical altered values (such as GFR or DXA). Concerning urological manifestation of PHPT a Danish study confirms the findings of the present study, showing that adenoma size does not seem to affect the incidence of kidney stones [34].

These findings highlight the complexity of understanding the potential relationship between adenoma volume and the clinical manifestations in patients with PHPT. While some studies have suggested a connection between larger adenomas and specific clinical conditions, such as hypercalcemia or bone mineral loss, others—including ours—have not found any direct association between adenoma size and the clinical manifestations. This underscores the need for further investigation in this area.

In addition, it is important to highlight that in our study cohort, the size of the parathyroid adenoma did not influence the surgical strategy. Our surgical approach consistently involved focused parathyroidectomy, guided by the precise measurement of PTH levels both prior to gland excision and 10–15 min post-excision, in accordance with the established Miami criteria. This method allowed us to ensure the accurate identification and removal of the pathological gland regardless the size. Importantly, unilateral or bilateral neck exploration was not deemed necessary in any of the cases, as our approach relied on preoperative localization studies and intraoperative PTH monitoring to confirm the success of the procedure. Moreover, to further optimize surgical precision and enhance patient safety, intraoperative neuromonitoring was routinely employed during every operation, irrespective of the adenoma’s size. By incorporating these standardized protocols, we were able to streamline the surgical process, minimize operative morbidity, and maintain a high level of confidence in the success of the focused parathyroidectomy approach.

According to Randhawa et al. [23], no correlation between adenoma weight and postoperative hypocalcemia was found. In the present study, the multivariate analysis of the three groups did not show any significant difference between the volume of the parathyroid gland and the onset of perioperative complications, considering particularly the vocal cord palsy or the postoperative hypocalcemia. In contrast, a retrospective national database review performed by Tang et al., which analyzed the rate of morbidity and mortality after parathyroidectomy for PHPT in 14.500 patients, suggested that postoperative complications are positively associated with elevated preoperative PTH and calcium levels [35]. However, specific considerations on parathyroid adenoma volume were not included [35].

Even though there is a paucity of studies specifically investigating the correlation between parathyroid adenoma volume and the incidence of both general and specific complications following parathyroidectomy, our study showed a comparable incidence of postoperative complications as described in the literature [22, 35,36,37]. Moreover, our results indicate that adenoma volume seems to not be a significant risk factor for the onset of perioperative morbidities. However, our findings must be carefully considered due to the retrospective design, the small population size, and the overall low rate of observed complications.