Introduction

Nowadays, in the armamentarium of the endocrine surgeon, there is a wide variety of imaging techniques, surgical approaches and intraoperative adjuncts for patients diagnosed with primary hyperparathyroidism (pHPT). In the absence of large-scale randomized studies addressing the long-term effects of surgical versus conservative management for pHPT, the recommendations derived from the positional statement of the European Society of Endocrine Surgeons (ESES) on modern techniques in pHPT surgery [1] and the Third and Fourth International Workshop on the management of asymptomatic primary hyperparathyroidism [2–4] can help us in the decision making process.

Some recent publications have analyzed through surveys the current practice of endocrinologists and endocrine surgeons in the management of pHPT patients coming from the USA [5], Europe [6], and specifically Spain [7], Switzerland [8] and Norway [9], as well as in renal hyperparathyroidism [10]. However, none of the published surveys specifically analyzes the endocrine surgeons’ compliance with the recommendations of the above mentioned Consensus Conferences.

Because of this, there is a lack of information about the current surgical management of patients with pHPT in the real practice. Also, to gain further insights about how endocrine surgeons are dealing with this specific disease, more data are needed regarding the composition and type of surgical units, their surgical caseload, the pHPT surgical indications, the preoperative workup, the type of surgery performed, and the results obtained. We present herein the results of a survey carried out in two European countries. It is aimed to analyze all these details and to know the degree of adherence of endocrine surgeons to these recommendations. Furthermore, it is also aimed to identify which factors may have potential influence on the pHPT patient’s surgical outcomes.

Methods

The Capítulo de Cirurgia Endócrina de la Sociedade Portuguesa de Cirurgia (CCE-SPC) and the Sección de Cirugía Endocrina de la Asociación Española de Cirujanos (SCE-AEC) sponsored this online study to determine the practice of this surgery in institutions from Portugal and Spain. In June 2014, a 35-item questionnaire (Appendix 1) was distributed to the members of both organizations, asking about organizational data of the hospital and department, surgical activity within the period 2008–2013, operative indications, preoperative workup, preferred surgical approaches, use of intraoperative adjuncts, anesthetic related aspects, type of hospitalization, and results obtained.

Those questionnaires filled in and returned before 14 January 2015 were considered valid. All data were entered into a database (Access 2007®). Qualitative data were summarized in percentages and quantitative ones by indicating the median and interquartile range (IR). The cure was defined as the attainment of postoperative normocalcemia and its maintenance for at least 6 months after surgery.

To clarify those factors that may influence on the achievement of optimal results by the different participating centers, we divided the responding institutions into two groups, placing the cut-off point among them in the median of the cure rate of all hospitals. Analysis was performed by χ 2 and Fisher’s exact tests. A p value <0.05 was set for significance. SPSS v.20.0 (SPSS Ibérica, Madrid, Spain) was used for the statistical analyses.

Results

Involved institutions

Fifty-seven centers returned the questionnaire. Forty-one completed surveys (72 % of participating centers) came from Spain and 16 from Portugal (28 %). The response rate was 32 % from the affiliated centers from SCE-AEC, and 40 % of the participants from CCE-SPC. Fifty-three hospitals were public (covering a population of 22.5 million inhabitants), three private, and with a mixed model in a last case.

In relation to the size of the hospital, seven of them were small (having fewer than 250 beds), 20 medium-sized (between 250 and 500 beds), and 30 were large centers (having more than 500 beds). In the abovementioned period, 5696 parathyroidectomies due to pHPT were performed in all centers, with an annual median of 14 per center (IR 8.5–23). Only 23 % of the centers (12 % in Portugal, 27 % in Spain) performed more than 25 surgeries per year.

Forty-six institutions (81 %) reported to have endocrine surgery units (ESU): 69 % in Portugal and 85 % in Spain. In 81 % of the centers, regularly scheduled endocrine pathology multidisciplinary meetings took place. These meetings were more frequently performed in those hospitals with ESU (93 vs. 27 %). The median of the surgeons who carried out parathyroid surgery was 3 (IR 2–3), with a median of 6 per surgeon/year procedures (IR 3.4–9.3).

Surgical indications

The criteria derived from the Third International Workshop on the management of asymptomatic primary hyperparathyroidism [4] were used by 94 % of the surveyed centers. However, 51 % of institutions considered other surgical indications for asymptomatic pHPT, not covered in this guideline. They included patient preferences (15.8 % of all units), patients older than 50 (12.2 %), in cases of difficult follow-up (10.5 %), the existence of nephrolithiasis (8.7 %), vague symptoms like weakness, fatigue, depression, and anxiety, decreased memory and concentration, irritability, and disturbed sleep (8.7 %), a corrected serum calcium above 11 mgr/dL (5.2 %) and in cases with simultaneous thyroidectomy (5.2 %). Those situations discouraging pHPT surgical treatment are shown in Table 1, both overall and disaggregated by country.

Table 1 Situations that discourage the surgical indication
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Preoperative workup

All surgical units systematically order serum calcium and iPTH levels. Regarding 25-OH vitamin D, urinary calcium levels, and Ca/ creatinine clearance ratio, the percentages of institutions ordering for dropped at 66, 58, and 30 %, respectively. Although no unit was practiced as a routine, 81 and 38 % of surveyed surgeons considered in some cases genetic tests and selective venous sampling (SVS), respectively.

Regarding the evaluation of target organs of the disease, only 46 % requested routine bone densitometry and 25 % renal ultrasound. Concerning image techniques, the most frequent routinely ordered test was (99 m) Tc-MIBI scintigraphy (91 % of units), followed by ultrasonography (US) of the neck (88 %). Computed tomography (CT) was ordered on routine basis only in 2 % of units. In 18 % of the hospitals, fusion techniques as single-photon emission computed tomography (SPECT-CT) complemented all MIBI scintigraphies.

According to the opinion of 77 % of the surveyed surgeons, the most reliable imaging technique was MIBI scintigraphy. Otherwise, 16 % of them considered neck ultrasound a more reliable technique, and 7 % relied equally in both. In 95 % of the centers, radiologists performed cervical ultrasound, in 20 %, endocrinologists performed US as well, and in 10 %, surgeons are those who usually perform this technique.

Facing a negative ultrasound and MIBI scan, the attitude of surgeons varied depending on whether it was primary surgery or reoperation. In the first scenario, 56 % of surgeons proposed surgery through bilateral neck exploration, while 44 % would request additional imaging techniques. Otherwise, only 16 % of surgeons would go straight to the surgery by bilateral approach, and 84 % require additional tests when facing reoperations. Most ordered imaging techniques for this clinical setting were magnetic resonance imaging (MRI) (59 %), and CT scan (52 %), followed by SPECT-CT and positron emission tomography (PET) scan. A fifth of the surveyed surgeons would have ordered a SVS facing a reoperation with negative ultrasound and MIBI scan.

Surgical approaches

The indications for selective parathyroidectomy considered by the respondents are listed in Table 2. A selective parathyroidectomy was a feasible technique in case of persistent or recurrent pHPT for 49 % of surgeons, while for 51 %, a bilateral neck exploration would be the preferred approach regardless of the preoperative imaging findings. Among surgeons performing selective approaches, 91 % carried out open minimally invasive parathyroidectomy (OMIP), 13 % minimally invasive video-assisted parathyroidectomies (MIVAP), and 2 % endoscopic parathyroidectomies via a lateral approach. The median percentage of focused approaches on the total of parathyroidectomies performed was 58 % (IR 25–83).

Table 2 Indications for selective parathyroidectomy
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Intraoperative adjuncts

Intraoperative iPTH measurements were used by 92 % of departments. In 88 % of institutions, this technique was performed even when preoperative localization techniques were concordant for single-gland disease. Regarding the biochemical cure criteria, Miami criteria [11] were the most used (68 % of centers), followed by Vienna [12] (28 %), and Rome criteria [13], used by 4 % of departments.

Regarding the surveyed nations, 50 % of Portuguese surgeons preferred Vienna criteria, comparing to 19 % of Spanish surgeons. Facing a lack of decline in iPTH levels under requested values at 10 min post resection, 68 % of centers proposed to obtain a new sample before converting to bilateral neck exploration. The delay in obtaining results of intraoperative PTH measurement had a median of 30 min (IR 20–40) in the participating centers. Three out of five surgeons recognized that not all patients were kept anesthetized until the reception of results.

Use of routine frozen section was supported by 42 % of departments. Radio-guided surgery, intraoperative neuromonitoring, and methylene blue injection were selectively used in 34, 29, and 9 % of centers, respectively. The use of other intraoperative adjuncts (venous sampling, PTH measurement on aspirated samples, or scintigraphy) was anecdotally reported.

Types of anesthesia and hospital admission

Concerning the anesthesia modalities available, in addition to general anesthesia, in 12 and 4 % of hospitals, pHPT surgery could also be performed under local and regional anesthesia, respectively. In relation to the types of admission scheduled, in 81 % of institutions (56 % in Portugal, 90 % in Spain) parathyroid surgery was performed as day surgery, and in 23 % of centers (27 % in Spain, 13 % in Portugal), it was also carried out on ambulatory basis (discharge 4–8 h after surgery).

Results of surgery. Analysis of factors that impact on cure rate

The duration of postoperative follow-up varied widely among participating centers, with a median of 6 months (IR 1–12). We received outcomes data from 54 centers. During the surveyed period, a total of 5507 patients underwent parathyroidectomy for pHPT in these institutions. Among them, 196 (3.5 %) were not cured with surgery. A cure rate above 95 % was achieved in 41 of the 54 institutions (76 %), and the median for all departments was 97 % (IR 95–98). Factors with potential impact on cure rate and the results of the analysis are shown in Table 3.

Table 3 Factors with possible impact on cure rate
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Discussion

Key results

In this study, we found that parathyroid surgery is carried out in institutions with a wide range of complexity, generally within specialized surgical units, with a scarce number of procedures performed yearly by institution and surgeon. Regarding indications, the majority of departments followed the recommendations from the Third and Fourth International Workshop on the management of asymptomatic primary hyperparathyroidism, although more than half of the respondents recognize accepting other indications not covered by the guidelines. The preoperative study (except for the scarcely assessed target organs of the disease) and the surgical approach performed adhere quite well with the recommendations from the ESES positional statement, emphasizing the limited use of video-assisted approaches. Intraoperative PTHi determination is widely used, being Miami the preferred criteria for cure by the Iberian surgeons. The cure rate after surgical treatment of pHPT was very adequate in most institutions, and the existence of specialized endocrine surgery units positively influence on it.

Interpretation of results

Only a quarter of all participant centers performed an average of more than 25 procedures per year. This condition was among the requirements for institutions to be considered as a referral center in the “Certification system for thyroid and parathyroid surgery Units” of the German Society of General and Digestive Surgery [14]. This requirement has been established as a suitable grouping criterion by the Iberpara group. The finding of a median of 14 procedures per year in our study compares favorably with the 12 procedures found at the Spanish endocrinologists survey [7], although is slightly lower than the 18 annual cases documented in the Norwegian study [9], and well below the average of 33 cases from the US study [5]. This data can be explained either by some degree of underdiagnosis of this entity, by the absence of a real policy for referring patients to reference surgical centers in our countries, or by a lower rate of surgical indication by the endocrinologist. In the survey of Spanish endocrinologists [7], approximately 60 % of newly diagnosed patients were referred for parathyroidectomy. In the European survey, similar figures for symptomatic pHPT were obtained from Germany (74 %), UK (72 %), France (64 %), and lower for Italy (42 %) [6].

In our survey, 20 % of participating institutions do not have a formal well-established endocrine surgery unit, and as far we are concerned, there is not published data regarding the effect of the presence of an endocrine surgical unit on the rate of cure in pHPT. In our study, we found that the presence of these units was the only factor with positive impact on the results. Nevertheless, probably the definition of endocrine surgery unit should be addressed since the limited number of procedures performed yearly by surgeon does not fit properly with the idea of a devoted surgical unit.

Surgical indications for asymptomatic pHPT comply quite well with the guidelines derived from the Third Workshop on management of asymptomatic primary hyperparathyroidism [4]. However, more than half of the surveyed surgeons included other situations, showing a trend towards a more comprehensive surgical treatment of asymptomatic pHPT. Furthermore, we have shown that the surgical indication owing to the presence of nephrolithiasis or nephrocalcinosis have been already incorporated even before that the Fourth Workshop on management of asymptomatic primary hyperparathyroidism elicited guidelines were published [2, 3].

Regarding those situations discouraging the surgical indication of pHPT, in 11 % of institutions, surgery is still contraindicated in patients with negative localization testing, despite the published recommendations [1, 2, 4]. This percentage is a little bit lower than the 15 % obtained at the survey of Spanish endocrinologists [7]. The proportion of institutions that considered a surgical contraindication the asymptomatic pHPT was low (4 %), while 30 % of surgeons did not consider normocalcemic pHPT as a surgical indication. Because of the fact that we do not find data on surgery referral policies in normocalcemic pHPT, we are not able to read into such figures. Although many physicians use to approach to normocalcemic pHPT in a similar manner to asymptomatic pHPT, evidence-based guidelines on this issue are lacking [15].

The preoperative workup employed by the participating units was generally consistent with the current international recommendations. However, facing negative or non-concordant results of neck ultrasound and MIBI scan, 44 % of surgeons ordered additional tests before first-time surgery. In this clinical scenario, the ESES positional statement recommends a bilateral neck exploration without further imaging. Then, in this situation, nearly half of the surveyed surgeons were prone to ensure preoperative localization to enhance the possibility for the selective surgical approach. It is noteworthy that very few of the interviewed surgeons are aware of tests for the disease’s target organs, as only 46 % of the departments requested a routine bone densitometry, and 25 % a renal ultrasound. The guideline of the IV Workshop on management of asymptomatic pHPT is expected to improve this figure, by including the presence of nephrolithiasis or nephrocalcinosis as an indication of parathyroidectomy in asymptomatic pHPT [3].

The indication of selective and minimally invasive parathyroidectomy collected in this survey was in accordance with the current recommendations in cases of first-time surgery. However, for persistent or recurrent pHPT, 51 % of participating institutions do not share the criteria from the ESES positional statement which considers that whenever possible, a selective image-guided approach is preferred. It is possible that these responses correspond to centers with low-activity volume and less experience, although we could not detect worse results in practice from low-volume departments.

It is remarkable how small was the number of centers that have incorporated the techniques of assisted endoscopic resection. Techniques like the endoscopic parathyroidectomy [16], MIVAP technique [17], and endoscopic parathyroidectomy via a lateral approach [18] are only implemented in 15 % of institutions, more than 10 years after its description. Some factors can justify this fact, among them, the lack of training centers and patient centralization policies, the need to overcome a learning curve, and probably some pressures to improve the efficiency of surgical sessions, along with the few perceived advantages with respect to OMIP approach.

Related to intraoperative adjuncts, the intraoperative parathormone measurement was widely implemented, being performed in 92 % of centers. However, the cost-effectiveness of its current use has been controversial: it was performed in 88 % of centers when preoperative localization techniques were concordant for single-gland disease. In that situation, the positional statement of ESES considers it of little added value [1]. Moreover, more than half of the participant surgeons recognize that in their centers, not all patients scheduled for intraoperative PTH measurement are kept anesthetized until the results are received. This could be due to both the pressure to optimize the operating room time and perhaps a merely academic interest in many participating centers regarding this technique.

In connection with the analysis of factors that may have influenced the results, we found no differences depending on the country. Data seems to show minimal differences between the two nations in terms of volume of procedures, situations that discourage the surgical indication, indications for selective parathyroidectomy, and hospitalization types, but these have no impact on the outcomes regarding the achieved cure rate. Moreover, we have not found differences in outcomes related to the size of the institution or its volume of parathyroid surgery, or whether they had multidisciplinary endocrine pathology meetings. The opinions of surveyed surgeons on the attitude when facing negative imaging techniques, the preferred image exploration, or whether they believe that selective approach is appropriate for a persistent pHPT, have no impact on the outcomes.

In our study, the percentage of curative interventions was 96.5 %. This percentage is somewhat higher than the previous Spanish reported rate of 90 % [7], and similar to the other series, ranging between 95 and 98 % at first surgery [12]. Our findings underscore the importance of training experienced surgical teams for improving results. Furthermore, the impact of the availability of a minimally invasive surgical procedure on the number of patients referred for surgery seems to be considerable. In the Swiss survey, 61 % of the endocrinologists would expand the indication for surgery if the operation could be done by a limited surgical approach [8].

Limitations and generalizability of the results

Although hospitals were encouraged to assess clinical databases for reporting data, differences in quality of databases could have influenced the results. On the other hand, the low participation rate obtained, a limit of the study, can be related to the comprehensiveness of the information requested, which could have imposed a selection bias, since respondents may not represent all Spain and Portuguese surgeons. Other reason related to low participation rate could be the fact of being an unpaid study. Unlike the European and Spanish endocrinologists studies [6, 7], we decided not to seek the support of industry to encourage participation, avoiding a potential source of conflicts of interest.

There may be also a selection bias since we do not know the percentage of not surgically treated cases in the same period. It is possible that high-volume and experienced institutions were less selective in accepting cases. In less experienced departments, the results of the operated patients could have been improved by excluding a substantial percentage of patients with vague symptoms and negative localization tests, with lower cure rates.

Despite all previous limitations, the absence of current data in our two countries about pHPT surgical management makes our results of relevance. Our study is the largest multicenter and multinational European survey ever reported on surgical management on pHPT and the first attempt to know how endocrine surgeons comply with current recommendations on surgery for primary hyperparathyroidism.

Conclusion

The surgical treatment of pHPT is practiced in Portugal and Spain in institutions of different complexity, usually within specialized endocrine surgery units. The number of annual procedures is relatively low in most of them. The surgical indications and the preoperative workup generally comply with the current international recommendations, except for a scarce study of the target organs of the disease.

The indication of selective and minimally invasive parathyroidectomy was also adapted to current recommendations, even though to a lesser extent in persistent pHPT. Most units have not implemented the endoscopically-assisted resection techniques.

Intraoperative PTH determination is widely implemented, although the cost-effectiveness of its current use is debatable. The rest of intraoperative adjuncts are rarely used, as well as the locoregional anesthesia. There is a positive impact on the results of this surgery by its performance within specialized surgical units.