U.S. flag

An official website of the United States government

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Cover of Evidence review for surgical interventions

Evidence review for surgical interventions

Hyperparathyroidism (primary): diagnosis, assessment and initial management

Evidence review E

NICE Guideline, No. 132

.

London: National Institute for Health and Care Excellence (NICE); .
ISBN-13: 978-1-4731-3415-7

1. Surgical interventions

1.1. Review question: What is the clinical and cost effectiveness of different types of surgical intervention, for example 4-gland exploration, compared with minimally invasive techniques?

1.2. Introduction

In the majority of cases, primary hyperparathyroidism (PHPT) is caused by a benign tumour (adenoma) of one of the parathyroid glands. Less commonly 2 or more glands are involved or all 4 glands can be enlarged due to parathyroid hyperplasia. If pre-operative imaging is able to identify a single adenoma, focused surgery is usually performed. The alternative approach is bilateral neck exploration (also known as 4-gland exploration). Focused surgery can be performed under local or general anaesthesia and involves a slightly smaller incision than bilateral neck exploration, which can only be performed under general anaesthesia. Bilateral neck exploration enables the surgeon to visualise all 4 glands.

1.3. PICO table

For full details see the review protocol in appendix A.

Table 1. PICO characteristics of review question.

Table 1

PICO characteristics of review question.

The aim of this review was to investigate the effectiveness of different types of surgical interventions. Hence, this review compares focused/targeted surgical interventions with non-focused/non-targeted interventions/4-gland exploration (with or without any one or combination of the localisation techniques or intra-operative techniques) and does not include studies comparing individual surgical interventions with each other. The committee defined focused/targeted parathyroidectomy to include minimally invasive parathyroidectomy and all other remaining surgical interventions to be non-focused/non-targeted/4-gland exploration.

1.4. Clinical evidence

1.4.1. Included studies

A search was conducted for randomised controlled trials assessing the effectiveness of different types of surgical interventions for treatment of people with primary hyperparathyroidism caused by single adenoma, 4-gland hyperplasia, double adenoma or ectopic adenoma.

Five studies were included in the review; Bergenfelz 20054, Miccoli 199917, Russell 200623, Sadik 201124, Slepavicius 200827 these are summarised in Table 2 below. Evidence from these studies is summarised in the clinical evidence summary tables below (Table 3, Table 4, Table 5 and Table 6). See also the study selection flow chart in appendix C, forest plots in appendix E, study evidence tables in appendix D and GRADE tables in appendix F.

All studies included patients diagnosed with PHPT having indications for surgery, however in 4 studies (Bergenfelz 20054, Sadik 201124, Russell 200623, Micolli 1999 17) there was pre-selection of patients with solitary parathyroid adenoma. In the study Slepavicius 200827 although there was no pre-selection of patients, if hyperplasia of parathyroid glands was found during the surgery, those patients were excluded from the study (solitary parathyroid adenoma was confirmed by pathological examination in majority of the patients in this study).

All included studies compared focused with non-focused parathyroidectomy/4-gland exploration; however there was a variation in the localisation/intra-operative techniques used in the studies. Pre-operative localisation was used for both the groups in 4 out of 5 studies; and in one study pre-operative localisation was used in the focused group only. Three studies had intra-operative techniques in addition to pre-operative localisation studies. In two studies (Bergenfelz 20054, Russell 200623) all patients had pre-surgery sestamibi scintigraphy for localisation of single parathyroid adenomas; in the study Miccoli 199917 the focused (MIP) group had intra-operative qPTHa and the classic bilateral neck group had intra-operative frozen section (pre-surgery localisation for both groups); in the study Sadik 201124 the focused group had intra-operative surgical sonography and the conventional unilateral open procedure group did not have intra-operative sonography (pre-surgery localisation with imaging using 99mTc-sestamibi for both groups); in the study Slepavicius 200827 the focused group had pre-surgery localisation and intact intra-operative parathyroid hormone monitoring (IIPTH) and the conventional parathyroidectomy did not have pre-operative localisation and IIPTH.

Frozen section analysis for tissue confirmation was used in both the groups in Bergenfelz 20054 and used only in the bilateral conventional surgery group in Miccoli 199917.

Different modes of anaesthesia were used in the studies. Only two studies (Bergenfelz 20054 and Miccoli 199917) used local anaesthesia in the focused group; the rest of the studies used general anaesthesia for both the groups. In the study Bergenfelz 20054, conventional bilateral surgery was conducted under general anaesthesia and local anaesthesia in focused/MIP group; in the study Miccoli 199917, bilateral neck exploration was conducted under GA and focused/VAP under general endotracheal anaesthesia or bilateral superficial cervical block in association with laryngeal mask; mode of anaesthesia was not reported in the study Russell 200623; in the study Sadik 201124, patients underwent general anaesthesia with endotracheal intubation in both groups; in the study Slepavicius 200827 all patients underwent parathyroidectomy under general anaesthesia.

All studies were small with less than 100 patients.

There was a variation in the terminologies for the various types of surgeries conducted in the studies and these have been reported as in the papers. Also in some studies, definition of surgical procedures was not clearly defined.

Although all studies compared focused with non-focused parathyroidectomy/4-gland exploration, there was a variation in the use of pre-operative localisation and intra-operative techniques, hence all studies were not pooled together.

The following comparisons have been used for analysis in the review:

  1. Focused unilateral parathyroidectomy vs standard bilateral parathyroid exploration [pre-surgery localisation for all patients] – 2 studies for this comparison (Russell 200623 and Bergenfelz 20054).
  2. Minimally invasive parathyroidectomy with intra-operative surgical sonography (MIPUSS) vs conventional unilateral open procedure (OP) without intra-operative sonography [pre-surgery localisation with imaging for all patients] – 1 study (Sadik 201124)
  3. Focused parathyroidectomy with pre-operative localisation+ intra-operative intact parathyroid hormone monitoring (IIPTH) vs conventional parathyroidectomy without localisation and IIPTH – 1 study (Slepavicius 200827)
  4. Video assisted parathyroidectomy (VAP) (type of minimally invasive) + intra-operative qPTHa vs classic bilateral neck exploration + intra-operative frozen section (no qPTHa) [pre-surgery localisation for both groups] – 1 study (Miccoli 199917)

All studies were analysed in the stratum single parathyroid adenoma. There was an insufficient number of studies to conduct sub-group analysis.

None of the studies reported the critical outcomes mortality and quality of life. The majority of the studies reported the adverse outcomes (temporary/permanent recurrent laryngeal nerve injury, hypocalcaemia, wound infection, drainage of a wound seroma) either at post-operative period or at 1 month and 6 months after surgery. There was evidence from one study each for the outcomes re-operation and length of hospital stay (hours).

There was no clear definition for the outcome success/cure or failure of surgery in the studies; some studies defined success based on serum calcium levels/normocalcaemia/hypercalcaemia/ supplementation prescribed/incision used; also, success was defined at different end points in the studies, for example post-operative/6 months after surgery; studies did not report the data in an analysable format. Hence, the results for this outcome have been reported narratively in the review.

1.4.2. Excluded studies

See the excluded studies list in appendix I.

1.4.3. Summary of clinical studies included in the evidence review

Table 2. Summary of studies included in the evidence review.

Table 2

Summary of studies included in the evidence review.

See appendix D for full evidence tables.

1.4.4. Quality assessment of clinical studies included in the evidence review

Table 3. Clinical evidence summary: Focused unilateral parathyroidectomy compared to standard bilateral parathyroid exploration [pre-surgery localisation for all patients].

Table 3

Clinical evidence summary: Focused unilateral parathyroidectomy compared to standard bilateral parathyroid exploration [pre-surgery localisation for all patients]. Results stratum: single parathyroid adenoma

Table 4. Clinical evidence summary: Minimally invasive parathyroidectomy with intra-operative surgical sonography (MIPUSS) compared to conventional unilateral open procedure (OP) without intra-operative sonography [pre-surgery localisation with imaging for all patients].

Table 4

Clinical evidence summary: Minimally invasive parathyroidectomy with intra-operative surgical sonography (MIPUSS) compared to conventional unilateral open procedure (OP) without intra-operative sonography [pre-surgery localisation with imaging for all (more...)

Table 5. Clinical evidence summary: Focused parathyroidectomy with pre-operative localisation+ intra-operative intact parathyroid hormone monitoring (IIPTH) compared to conventional parathyroidectomy without localisation and IIPTH.

Table 5

Clinical evidence summary: Focused parathyroidectomy with pre-operative localisation+ intra-operative intact parathyroid hormone monitoring (IIPTH) compared to conventional parathyroidectomy without localisation and IIPTH. Results stratum: single parathyroid (more...)

Table 6. Clinical evidence summary: Video assisted parathyroidectomy (VAP) (type of minimally invasive) + intra-operative qPTHa compared to classic bilateral neck exploration + intra-operative frozen section (without qPTHa) [pre-surgery localisation for both groups].

Table 6

Clinical evidence summary: Video assisted parathyroidectomy (VAP) (type of minimally invasive) + intra-operative qPTHa compared to classic bilateral neck exploration + intra-operative frozen section (without qPTHa) [pre-surgery localisation for both groups]. (more...)

Narrative data for the outcome success/failure

Russell 2006 – Success/cure not clearly defined. Study reported that all 100 patients were cured of PHPT as assessed by immediate return of the serum calcium level to normal in the post-operative period and maintenance of normocalcaemia for a mean of 23 (range 3–65) months follow-up.

Bergenfelz 2005 – Success/failure was not reported

Slepavicius 2008 – Study reported that if blood test indicated normocalcaemia or hypocalcaemia 6 months after surgery, a patient is completely recovered. Study reported that 6 months after surgery all patients were eucalcaemic.

Sadik 2011 – Definition of success not reported – study reports that MIPUSS was successful in 18/20 patients; it reported that in 2/20 cases the incision was extended as the adenoma was difficult to localise. At 30 day follow-up, all patients were well and asymptomatic. Calcium levels were returned to normal and no patients required supplementation.

Miccoli 1999 – Success/failure was not an outcome. Study reported that all patients were normocalcaemic 6 months after surgery.

See appendix F for full GRADE tables.

1.5. Economic evidence

1.5.1. Included studies

No relevant health economic studies were identified.

1.5.2. Excluded studies

No health economic studies that were relevant to this question were excluded due to assessment of limited applicability or methodological limitations.

1.5.3. Unit costs

Below are unit costs of surgery for primary hyperparathyroidism, from NHS reference costs.

Table 7. Parathyroid procedures costs (Elective inpatient schedule).

Table 7

Parathyroid procedures costs (Elective inpatient schedule).

1.6. Resource costs

The recommendations made by the committee on the type of surgery that is to be used based on this review are not expected to have a substantial impact on resources.

The committee has made a recommendation based on this review that 4-gland exploration should be ‘considered’ if pre-operative imaging is discordant.

Unlike for stronger recommendations stating that interventions should be adopted, it is not possible to make a judgement about the potential resource impact to the NHS of recommendations regarding interventions that could be used, as uptake is too difficult to predict.

However, the committee noted that where this recommendation is implemented there would be additional costs relating to increased number of surgical parathyroidectomies compared to current practice.

1.7. Evidence statements

1.7.1. Clinical evidence statements

1.7.1.1. Focused unilateral parathyroidectomy vs standard bilateral parathyroid exploration in patients with single parathyroid adenoma [pre-surgery localisation for all patients]

There was no difference between focused unilateral parathyroidectomy and standard bilateral parathyroid exploration for temporary vocal cord palsy (1 study, n=50; Very Low quality); drainage of a wound seroma (1 study, n=50; Very Low quality); symptomatic hypocalcaemia (2 studies, n=150; Very Low quality); re-operation (for missed hyperplasia) (1 study, n=50; Very Low quality); and permanent unilateral vocal cord paralysis (1 study, n=100; Very Low quality).

No evidence was identified for the outcomes HRQOL; mortality; success (cure) / failure; bleeding (return to theatre); hypercalcemia; haematoma; BMD of the distal radius or the lumbar spine; deterioration in renal function; fractures (vertebral or long bone); length of hospital stay; occurrence of kidney stones; persistent hypercalcaemia; re-operation; unnecessary neck exploration.

1.7.1.2. Minimally invasive parathyroidectomy with intra-operative surgical sonography (MIPUSS) vs conventional unilateral open procedure (OP) without intra-operative sonography in patients with single parathyroid adenoma [pre-surgery localisation with imaging for all patients]

There was a clinically important benefit of minimally invasive parathyroidectomy with intra-operative surgical sonography (MIPUSS) compared to conventional unilateral open procedure (OP) without intra-operative sonography for temporary hypocalcaemia (1 study, n=30; Very Low quality); hospital stay (hours) (1 study, n=30; Low quality).

There was no difference between minimally invasive parathyroidectomy with intra-operative surgical sonography (MIPUSS) and conventional unilateral open procedure (OP) without intra-operative sonography for temporary recurrent laryngeal nerve injury (1 study, n=30; very low quality).

No evidence was identified for the outcomes HRQOL; mortality; success (cure) / failure; bleeding (return to theatre); hypercalcemia; haematoma; infection; BMD of the distal radius or the lumbar spine; deterioration in renal function; fractures (vertebral or long bone); occurrence of kidney stones; persistent hypercalcaemia; re-operation; unnecessary neck exploration.

1.7.1.3. Focused parathyroidectomy with pre-operative localisation + intra-operative intact parathyroid hormone monitoring (IIPTH) compared to conventional parathyroidectomy without localisation and IIPTH in patients with single parathyroid adenoma

There was no difference between focused parathyroidectomy with pre-operative localisation+ intra-operative intact parathyroid hormone monitoring (IIPTH) and conventional parathyroidectomy without localisation and IIPTH for transient hypocalcaemia (post-operative) (1 study, n=42; Very Low quality); and temporary vocal cord palsy (1 study, n=42; Very Low quality).

No evidence was identified for the outcomes HRQOL; mortality; success (cure) / failure; bleeding (return to theatre, hypercalcemia; haematoma; infection; BMD of the distal radius or the lumbar spine; deterioration in renal function; fractures (vertebral or long bone); length of hospital stay; occurrence of kidney stones; persistent hypercalcaemia; re-operation; unnecessary neck exploration.

1.7.1.4. Video assisted parathyroidectomy (VAP) (type of minimally invasive) + intra-operative qPTHa vs classic bilateral neck exploration + intra-operative frozen section (without qPTHa) in patients with single parathyroid adenoma [pre-surgery localisation for both groups]

There was a clinically important benefit of video assisted parathyroidectomy (VAP) (type of minimally invasive) + intra-operative qPTHa compared to classic bilateral neck exploration + intra-operative frozen section (without qPTHa) for symptomatic transient hypocalcaemia and for post-operative fever (1 study, n=38; Very Low quality).

There was no difference between Video assisted parathyroidectomy (VAP) (type of minimally invasive) + intra-operative qPTHa and classic bilateral neck exploration + intra-operative frozen section (without qPTHa) for permanent laryngeal nerve palsy (1 study, n=38; Very Low quality); wound infection (1 study, n=38; Very Low quality).

No evidence was identified for the outcomes HRQOL; mortality; success (cure) / failure; bleeding (return to theatre); hypercalcemia; haematoma; BMD of the distal radius or the lumbar spine; deterioration in renal function; fractures (vertebral or long bone); length of hospital stay; occurrence of kidney stones; persistent hypercalcaemia; re-operation; unnecessary neck exploration.

1.7.2. Health economic evidence statements

No relevant economic evaluations were identified.

1.8. The committee’s discussion of the evidence

1.8.1. Interpreting the evidence

1.8.1.1. The outcomes that matter most

The committee considered the outcomes of health-related quality of life, mortality and success (cure) / failure of surgery as critical outcomes for decision making. Other important outcomes included adverse events (bleeding [return to theatre], severe hypocalcaemia, hypercalcemia, laryngeal nerve injury, vocal cord paralysis/laryngeal nerve injury, haematoma, infection), bone mass density (BMD) of the distal radius or the lumbar spine, deterioration in renal function, fractures (vertebral or long bone), length of hospital stay, occurrence of kidney stones, persistent hypercalcaemia, reoperation and unnecessary neck exploration.

Across comparisons, no evidence was available for the critical outcomes mortality and quality of life. No evidence was identified for important outcomes: hypercalcaemia; haematoma; BMD of the distal radius or the lumbar spine; deterioration in renal function; fractures (vertebral or long bone); occurrence of kidney stones; persistent hypercalcaemia; re-operation; unnecessary neck exploration.

1.8.1.2. The quality of the evidence

There was evidence from 5 randomised controlled trials (RCTs) comparing focused surgery with 4-gland exploration.

All studies included patients diagnosed with primary hyperparathyroidism and having indications for surgery, however in 4 studies there was pre-selection of patients with solitary parathyroid adenoma and in one study, although there was no pre-selection of patients, if hyperplasia of parathyroid glands was found during the surgery, those patients were excluded from the study (solitary parathyroid adenoma was confirmed by pathological examination in majority of the patients in this study).

The committee noted that the evidence did not cover patients with double adenoma, ectopic adenoma and 4-gland hyperplasia.

All of the included studies compared focused surgery with 4-gland exploration; however there was a variation in the localisation/intra-operative techniques used in the studies.

Pre-operative localisation was used for both the groups in 4 out of 5 studies; and in one study pre-operative localisation was used in the focused surgery group only. Three studies used intra-operative techniques (intra-operative qPTHa in one study, intra-operative sonography in one study, and intact intra-operative parathyroid hormone monitoring (IIPTH) in one study) in addition to pre-operative localisation studies.

Different modes of anaesthesia were used in the studies. Only 2 studies used local anaesthesia in the focused surgery group; the rest of the studies used general anaesthesia for both the groups.

The evidence for all outcomes was graded Very Low quality due to risk of bias and imprecision, decreasing our confidence in the estimate of effect of the surgery techniques of interest.

1.8.1.3. Benefits and harms

All studies were analysed in the stratum single parathyroid adenoma. There were an insufficient number of studies to conduct subgroup analysis.

There was no evidence available for the critical outcomes of mortality and quality of life. The majority of the studies reported adverse outcomes (temporary/permanent recurrent laryngeal nerve injury, hypocalcaemia, wound infection, drainage of a wound seroma) either at post-operative period or at 1 month and 6 months after surgery. There was evidence from one study each for the outcomes re-operation and length of hospital stay (hours).

There was no clear definition for the outcome success/cure or failure of surgery in the studies and the studies did not report the data in an analysable format. Hence, the results for this outcome were reported narratively in the review.

Although all studies compared focused surgery with 4-gland exploration, there was a variation in the use of pre-operative localisation and intra-operative techniques; hence all the studies were not pooled together.

The following comparisons were used for analysis in the review: focused unilateral parathyroidectomy versus standard bilateral parathyroid exploration; minimally invasive parathyroidectomy with intra-operative surgical sonography (MIPUSS) versus conventional unilateral open procedure (OP) without intra-operative sonography; focused parathyroidectomy with pre-operative localisation+ intra-operative intact parathyroid hormone monitoring (IIPTH) versus conventional parathyroidectomy without localisation and IIPTH; video assisted parathyroidectomy (VAP) (type of minimally invasive) + quick intra-operative parathyroid hormone assay (qPTHa) vs classic bilateral neck exploration + intra-operative frozen section (no qPTHa).

The evidence for the comparison focused unilateral parathyroidectomy versus standard bilateral parathyroid exploration (2 RCTs) suggested that there was no difference between the groups for the outcomes temporary vocal cord palsy, drainage of a wound seroma, symptomatic hypocalcaemia, re-operation (for missed hyperplasia), and permanent unilateral vocal cord paralysis. The estimates were imprecise for all the above outcomes. The evidence for all outcomes except one (permanent unilateral vocal cord paralysis) was based on one event.

The evidence for the comparison minimally invasive parathyroidectomy with intra-operative surgical sonography (MIPUSS) versus conventional unilateral open procedure (OP) without intra-operative sonography (1 RCT) suggested that there was a clinical benefit of MIPUSS for hospital stay (hours) and temporary hypocalcaemia. Evidence for this comparison suggested there was no difference between the groups for the outcome temporary recurrent laryngeal nerve injury. The evidence for temporary laryngeal nerve injury was based on one event. The committee highlighted that from their clinical experience, laryngeal nerve injury is a very rare event in first-time parathyroid surgery.

The evidence for the comparison focused parathyroidectomy with pre-operative localisation+ intra-operative intact parathyroid hormone monitoring (IIPTH) compared to conventional parathyroidectomy without localisation and IIPTH (1 RCT) suggested that that there was no difference between the groups for the outcomes transient hypocalcaemia (post-operative), and temporary vocal cord palsy. The estimates were imprecise for both the outcomes. The evidence for the outcome temporary vocal cord palsy was based on one event in each group.

The evidence for the comparison video assisted parathyroidectomy (VAP) (type of minimally invasive surgery) + intra-operative qPTHa compared to classic bilateral neck exploration + intra-operative frozen section (without qPTHa) (1 RCT) suggested that that there was a clinically important benefit of VAP + intra-operative qPTHa for symptomatic transient hypocalcaemia and for post-operative fever. The evidence suggested there was no difference between the groups for the outcomes permanent laryngeal nerve palsy (documented with laryngoscopy 6 months after surgery) and wound infection. The evidence for the outcomes permanent laryngeal nerve palsy and wound infection was based on one event.

Narrative evidence from 4 studies suggested that all patients were cured in both the groups (follow-up at 23 months, 3 months and 6 months after surgery). None of the studies reported the critical outcomes mortality and quality of life.

The evidence for the majority of the outcomes was based on one event from very small studies and was of Very Low quality. Hence, the committee also took their clinical experiences into account when making their recommendations.

The committee from their experience noted that focused surgery was associated with marginal benefits of lower temporary hypocalcaemia, shorter surgery time and cosmesis. The committee from their experience stated that surgery time was approximately 40 minutes to 1 hour for 4-gland exploration and between 20 to 40 minutes for focused surgery. The committee however highlighted that the cosmetic benefit with focused surgery was minimal; with the difference in incision for focused surgery and 4-gland exploration being approximately 2 cm. They noted that the incision for focused surgery was approximately 3cm and 4-5 cm for 4-gland exploration except in obese patients. The committee agreed that there was no difference in nerve injury rate between focused surgery and 4-gland exploration.

The committee highlighted that in focused surgery for single parathyroid adenoma there was a slightly higher chance of recurrence (normal calcium after surgery but patients develop adenoma after years) or persistent disease (hypercalcaemia after surgery suggesting disease in other gland/s)

The committee noted that the alternatives to focused surgery for solitary parathyroid adenoma are unilateral exploration and 4-gland exploration. The committee discussed that if 4-gland exploration is performed for single adenoma, the chance of recurrence would be very low.

The committee stated that historically, surgical treatment of primary hyperparathyroidism was by traditional bilateral 4-gland exploration. However, more recently, focused surgery has been preferred because of its cosmetic benefits. The committee discussed that cure rate in 4-gland exploration was marginally higher than in focused surgery and this was attributable to better visualisation of all four glands during 4-gland exploration. The committee from their experience noted that the cure rate is approximately 95% with 4 gland exploration and between 90 to 95% with focused surgery.

The committee agreed that one of the adverse effects of 4-gland exploration was marginally higher temporary hypocalcaemia and that the surgery time was marginally longer than focused surgery. However, in the experience of the committee there was no difference in hospital stay for focused surgery and 4-gland exploration. The committee therefore, based on their experience and Low quality evidence, agreed that people should be offered a choice of focused parathyroidectomy or 4-gland exploration if the preoperative imaging shows a single adenoma in the neck. The committee agreed on the basis of their clinical experience that for people whose pre-operative imaging (first modality scan with or without a second modality scan) is negative or does not identify a single adenoma, 4-gland exploration should be offered. The committee discussed that in patients with negative imaging, 4-gland exploration is the optimal management because of the increased frequency of multi-glandular disease in such cases. An experienced parathyroid surgeon can identify pathological parathyroid tissue with greater sensitivity than the best current imaging modalities.

The committee discussed that people with pre-operative imaging suggesting hyperplasia or multiple adenoma should have a 4-gland exploration performed by a surgeon with expertise in complex parathyroid surgery.

The committee agreed that if the first and second-modality scans are discordant, 4-gland exploration should be considered. This is because the specific anatomical location of the adenoma cannot be assured.

The committee discussed that in a minority of cases (~1–2%) pre-operative imaging of the parathyroid glands identifies a potential adenoma lying in an ectopic position. The committee discussed that the anatomical location of ectopic parathyroid adenoma is varied and agreed that such cases should be referred to surgeons with expertise at that particular site. The committee noted that for example, an ectopic parathyroid identified in the anterior mediastinum may require additional surgical skills in the use of mediastinoscopy and sternotomy.

The committee discussed that cost saving is not an option when considering focused surgery or 4-gland exploration as all patients get localisation studies, as this makes operation easier. Current practice is that patients with positive imaging can undergo focused surgery; patients with negative scans undergo 4-gland explorations; and those with mixed localisation have focused surgery sometimes with IOPTH or 4-gland exploration.

The committee also noted that irrespective of the technique adopted, there was a strong expertise element attributable to the success of surgery. The committee considered that good outcomes of surgery are also dependent on other factors such as interpretation of imaging by radiologists, high volume centres etc.

1.8.2. Cost effectiveness and resource use

No relevant health economic evaluations were identified for this question.

Unit costs of surgical interventions were presented to the committee for consideration. NHS reference costs do not distinguish between the types of surgical interventions, with the national average cost of parathyroid procedures (consisting of both focused surgery and 4-gland exploration, and including complications and excess bed days) estimated to be £3,327. Potential differences in cost between focused surgery and 4-gland exploration were therefore discussed with the committee. As mentioned in the benefits and harms section above, the committee noted that 4-gland exploration often requires longer operating times, and as a result 4-gland exploration is likely to be slightly more costly than focused surgery when factoring in the time of the clinicians required during surgery (for example surgeon(s), anaesthetist, nurse(s)). However, the committee discussed that this does not necessarily translate to a material cost saving as these shorter operating times are unlikely to result in more operations being conducted over a set time period. Furthermore, as surgical staff are remunerated at a set salary, the costs incurred in terms of personnel costs are likewise unlikely to change.

However, the committee also considered that 4-gland exploration is more likely to have a marginally higher cure rate than focused surgery as all four glands are explored, thus mitigating the risk of missing additional adenomas. Failure to cure often results in the need for additional treatment – including repeat surgery. Consequently there could be additional resource and cost associated with focused surgery, although this is likely to be small.

The committee suggested that there is no difference in recovery time between focused surgery and 4-gland exploration. For both interventions, the proportion of patients treated as day cases or overnight cases are similar. Hence, it was suggested that the type of surgery does not affect resource use with regards to hospital stay.

Taking all of the above into consideration, overall the committee did not consider that there would be a significant cost difference between the two interventions.

However, the committee expressed concern that currently, people with primary hyperparathyroidism who are eligible for surgery are potentially not being referred to have surgery if their preoperative imaging does not identify a single adenoma. However, it is not certain to what extent this occurs. The committee did not consider this to be best practice, and therefore made a recommendation that 4-gland exploration should be undertaken if pre-operative imaging does not identify a single adenoma, as this group will more frequently have multigland disease. The committee agreed that 4-gland exploration should be considered if the first and second imaging modalities are discordant. This is because the specific anatomical location of the adenoma cannot be assured. The committee noted that there is uncertainty about how much the recommendation will bring about an increase in the number surgeries carried out. Therefore, there is potential for a substantial resource impact.

The committee noted that an important factor in determining the success of parathyroid surgery is the skill of the surgeon. Hence, focused surgery is not considered to be inherently more effective than 4-gland exploration. As well as this, advances in surgical technique for 4-gland exploration have led to similar outcomes in terms of quality of life – for example, the length of hospital stay and size of surgical scar for people undergoing 4-gland exploration may not be significantly different from those who have focused surgery. Consequently, there is not a notable advantage in terms of quality of life in either type of surgery.

Given that surgery is the only definitive cure for primary hyperparathyroidism, the committee emphasised that the lack of confirmation of a single adenoma in preoperative imaging should not deter clinicians from referring patients to have surgery. With consideration for potential future savings from avoidable costs – for example, use of expensive pharmacological treatments such as calcimimetics or the costs associated with a clinical event resulting from primary hyperparathyroidism – the committee was of the consensus that surgery is a cost effective intervention for people with primary hyperparathyroidism.

1.8.3. Other factors the committee took into account

The committee was aware of data from the Fifth National Audit Report 2017 of The British Association of Endocrine and Thyroid Surgeons 7. The audit reported that mortality after parathyroid surgery was very infrequent. The requirement for calcium ± vitamin D supplementation at 6 months post-operatively was significantly greater after 4-gland exploration (presumed bilateral exploration) than focused surgery for first-time primary hyperparathyroidism. There was an increase in the extent of pre-operative imaging (frequency of usage and number of modalities) prior to parathyroid surgery, even for first-time surgery; however this was not associated with an increase in the rate of focused surgery nor improved cure rates for primary hyperparathyroidism. It also reported that there was a wide variation between surgeons with respect to the proportion of their cases having an initial targeted approach at first-time surgery for primary hyperparathyroidism and this may reflect different philosophies between surgeons regarding the advantages of targeted surgery versus traditional bilateral neck exploration; variation in the accuracy of pre-operative imaging, and in surgeons’ confidence in this; differences in local referral practice and variation in surgeons’ confidence in performing bilateral neck exploration, with some surgeons referring on cases with negative imaging to colleagues 7.

The report also stated that the overall rate of conversion of planned focused parathyroidectomy to conventional surgery (presumably bilateral neck exploration) for primary hyperparathyroidism is 7.8%. The data suggest that the main reason for conversion is multigland disease (as a significant proportion of converted cases have excision of 2 or more parathyroid glands); or failure to locate the abnormal parathyroid gland during minimal access surgery, or due to a requirement for greater access due to intra-operative difficulties such as large lesion size or bleeding 7.

From clinical experience, the committee stated that 85–90% of patients undergoing parathyroid surgery have a single adenoma, 10–15% have hyperplasia and less than 1% have a parathyroid carcinoma. Ectopic parathyroid glands may occur in any of the above scenarios.

References

1.
Aarum S, NordenstromJ, ReihnerE, ZedeniusJ, JacobssonH, DanielssonR et al. Operation for primary hyperparathyroidism: the new versus the old order. A randomised controlled trial of preoperative localisation. Scandinavian Journal of Surgery. 2007; 96(1):26–30 [PubMed: 17461308]
2.
Agus ZS. Conservative vs surgical treatment of hyperparathyroidism: which to choose, and when? Cleveland Clinic Journal of Medicine. 1993; 60(3):191–2 [PubMed: 8513538]
3.
Barczynski M, CichoS, KonturekA, CichoW. Minimally invasive video-assisted parathyroidectomy versus open minimally invasive parathyroidectomy for a solitary parathyroid adenoma: a prospective, randomized, blinded trial World Journal of Surgery. 2006; 30(5):721–31 [PubMed: 16547619]
4.
Bergenfelz A, KanngiesserV, ZielkeA, NiesC, RothmundM. Conventional bilateral cervical exploration versus open minimally invasive parathyroidectomy under local anaesthesia for primary hyperparathyroidism. British Journal of Surgery. 2005; 92(2):190–7 [PubMed: 15573366]
5.
Bergenfelz A, LindblomP, TibblinS, WesterdahlJ. Unilateral versus bilateral neck exploration for primary hyperparathyroidism: A prospective randomized controlled trial. Annals of Surgery. 2002; 236(5):543–51 [PMC free article: PMC1422609] [PubMed: 12409657]
6.
Bruno I, CollarinoA, PerottiG, Di GiudaD, CannarileA, NegriM et al. Diagnostic accuracy of 99mTc-Sestamibi dual-phase parathyroid scintigraphy and integrated imaging of thyroid in patients submitted to video-assisted minimally invasive parathyroidectomy. European Journal of Nuclear Medicine and Molecular Imaging. 2010; 37:(2 Suppl):S446–7
7.
Chadwick D, KinsmanR, WaltonP. Fifth national audit report. The British Association of Endocrine & Thyroid Surgeons, 2017. Available from: http://www​.baets.org​.uk/wp-content/uploads​/BAETS-Audit-National-Report-2017.pdf
8.
Chen H, SokollLJ, UdelsmanR. Outpatient minimally invasive parathyroidectomy: A combination of sestamibi-SPECT localization, cervical block anesthesia, and intra-operative parathyroid hormone assay. Surgery. 1999; 126(6):1016–22 [PubMed: 10598182]
9.
Department of Health. NHS reference costs 2016/2017. Available from: https://improvement​.nhs​.uk/resources/reference-costs/ Last accessed: 17/01/2018.
10.
Gracie D, HussainSSM. Use of minimally invasive parathyroidectomy techniques in sporadic primary hyperparathyroidism: Systematic review. Journal of Laryngology and Otology. 2012; 126(3):221–7 [PubMed: 22032618]
11.
Hessman O, WesterdahlJ, Al-SulimanN, ChristiansenP, HellmanP, BergenfelzA. Randomized clinical trial comparing open with video-assisted minimally invasive parathyroid surgery for primary hyperparathyroidism. British Journal of Surgery. 2010; 97(2):177–84 [PubMed: 20035529]
12.
Jinih M, O’ConnellE, O’LearyD P, LiewA, RedmondHP. Focused parathyroidectomy versus open parathyroidectomy for primary hyperparathyroidism: A meta-analysis. Irish Journal of Medical Science. 2016; 185:(Suppl 2):S85
13.
Jinih M, O’ConnellE, O’LearyDP, LiewA, RedmondHP. Focused versus bilateral parathyroid exploration for primary hyperparathyroidism: A systematic review and meta-analysis. Annals of Surgical Oncology. 2017; 24(7):1924–34 [PubMed: 27896505]
14.
Kreidieh OI, AhmadiehH, AklEA, El-HajjFG. Minimally invasive parathyroidectomy guided by intra-operative parathyroid hormone monitoring (IOPTH) and preoperative imaging versus bilateral neck exploration for primary hyperparathyroidism in adults. Cochrane Database of Systematic Reviews2013, Issue 10. Art. No.: CD010787. DOI: 10.1002/14651858.CD010787. [PMC free article: PMC8094219] [PubMed: 33085088] [CrossRef]
15.
Laird AM, LibuttiSK. Minimally invasive parathyroidectomy versus bilateral neck exploration for primary hyperparathyroidism. Surgical Oncology Clinics of North America. 2016; 25(1):103–18 [PubMed: 26610777]
16.
Lombardi CP, RaffaelliM, TrainiE, De CreaC, CorselloSM, BellantoneR. Video-assisted minimally invasive parathyroidectomy: Benefits and long-term results. World Journal of Surgery. 2009; 33(11):2266–81 [PubMed: 19219494]
17.
Miccoli P, BendinelliC, BertiP, VignaliE, PincheraA, MarcocciC. Video-assisted versus conventional parathyroidectomy in primary hyperparathyroidism: a prospective randomized study. Surgery. 1999; 126(6):1117–21; discussion 1121-2 [PubMed: 10598196]
18.
Miccoli P, BertiP, MaterazziG, AmbrosiniCE, FregoliL, DonatiniG. Endoscopic bilateral neck exploration versus quick intra-operative parathormone assay (qPTHa) during endoscopic parathyroidectomy: A prospective randomized trial. Surgical Endoscopy. 2008; 22(2):398–400 [PubMed: 17522920]
19.
National Institute for Health and Care Excellence. Developing NICE guidelines: the manual. London. National Institute for Health and Care Excellence, 2014. Available from: http://www​.nice.org.uk​/article/PMG20/chapter​/1%20Introduction%20and%20overview [PubMed: 26677490]
20.
Nelson CM, VictorNS. Rapid intra-operative parathyroid hormone assay in the surgical management of hyperparathyroidism. Permanente Journal. 2007; 11(1):3–6 [PMC free article: PMC3061375] [PubMed: 21472047]
21.
Norlen O, WangKC, TayYK, JohnsonWR, GrodskiS, YeungM et al. No need to abandon focused parathyroidectomy: A multicenter study of long-term outcome after surgery for primary hyperparathyroidism. Annals of Surgery. 2015; 261(5):991–6 [PubMed: 25565223]
22.
Reeve TS, BabidgeWJ, ParkynRF, EdisAJ, DelbridgeLW, DevittPG et al. Minimally invasive surgery for primary hyperparathyroidism: A systematic review. Australian and New Zealand Journal of Surgery. 2000; 70(4):244–50 [PubMed: 10779053]
23.
Russell CF, DolanSJ, LairdJD. Randomized clinical trial comparing scan-directed unilateral versus bilateral cervical exploration for primary hyperparathyroidism due to solitary adenoma. British Journal of Surgery. 2006; 93(4):418–21 [PubMed: 16392100]
24.
Sadik KW, KellM, GoreyT. Minimally invasive parathyroidectomy using surgical sonography. International Journal of Medical Sciences. 2011; 8(4):283–6 [PMC free article: PMC3085174] [PubMed: 21537491]
25.
Simonella G, MassaccesiE, MarziC, StaffolaniP, FalcoA, MorosiniP. [Minimally invasive surgery versus bilateral neck exploration for primary hyperparathyroidism: controlled prospective study. Role of intra-operative rapid parathyroid hormone assay and radiological preoperative detection of adenomas]. Recenti Progressi in Medicina. 2005; 96(10):483–7 [PubMed: 16491770]
26.
Singh Ospina N, MarakaS, Rodriguez-GutierrezR, Espinosa de YcazaAE, JasimS, GionfriddoM et al. Comparative efficacy of parathyroidectomy and active surveillance in patients with mild primary hyperparathyroidism: a systematic review and meta-analysis. Osteoporosis International. 2016; 27(12):3395–407 [PubMed: 27562567]
27.
Slepavicius A, BeisaV, JanusonisV, StrupasK. Focused versus conventional parathyroidectomy for primary hyperparathyroidism: a prospective, randomized, blinded trial. Langenbeck’s Archives of Surgery. 2008; 393(5):659–66 [PubMed: 18704485]
28.
Sozio A, SchietromaM, FranchiL, MazzottaC, CappelliS, AmicucciG. [Parathyroidectomy: bilateral exploration of the neck vs minimally invasive radioguided treatment]. Minerva Chirurgica. 2005; 60(2):83–9 [PubMed: 15973213]
29.
Taieb A, SemanM, MenegauxF, TresalletC. Surgical technique parathyroidectomy through a minimally invasive gland-centered localized approach for primary hyperparathyroidism. Journal of Visceral Surgery. 2013; 150(6):403–6 [PubMed: 24183298]
30.
Westerdahl J, BergenfelzA. Unilateral versus bilateral neck exploration for primary hyperparathyroidism: five-year follow-up of a randomized controlled trial. Annals of Surgery. 2007; 246(6):976–80; discussion 980-1 [PubMed: 18043099]

Appendices

Appendix B. Literature search strategies

The literature searches for this review are detailed below and complied with the methodology outlined in Developing NICE guidelines: the manual 2014, updated 2017 https://www.nice.org.uk/guidance/pmg20/resources/developing-nice-guidelines-the-manual-pdf-72286708700869

For more detailed information, please see the Methodology Review.

B.1. Clinical search literature search strategy

Searches were constructed using a PICO framework where population (P) terms were combined with Intervention (I) and in some cases Comparison (C) terms. Outcomes (O) are rarely used in search strategies for interventions as these concepts may not be well described in title, abstract or indexes and are therefore difficult to retrieve. Search filters were applied to the search where appropriate.

Table 10. Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

Cochrane Library (Wiley) search terms

CINAHL (EBSCO) search terms

PsycINFO (ProQuest) search terms

B.2. Health Economics literature search strategy

Health economic evidence was identified by conducting a broad search relating to primary hyperparathyroidism population in the NHS Economic Evaluation Database (NHS EED – this ceased to be updated after March 2015) and the Health Technology Assessment database (HTA) with no date restrictions. The NHS EED and HTA databases are hosted by the Centre for Research and Dissemination (CRD). Additional searches were run on Medline and Embase for health economics papers published since 2002.

Table 11. Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

NHS EED and HTA (CRD) search terms

Appendix D. Clinical evidence tables

Download PDF (247K)

Appendix E. Forest plots

E.2. Minimally invasive parathyroidectomy with intra-operative surgical sonography (MIPUSS) versus conventional unilateral open procedure (OP) without intra-operative sonography [pre-surgery localisation with imaging for all patients]

Figure 7. Temporary recurrent laryngeal nerve injury

Figure 8. Temporary hypocalcaemia

Figure 9. Hospital stay (hours)

E.3. Focused parathyroidectomy with pre-operative localisation+ intra-operative intact parathyroid hormone monitoring (IIPTH) versus conventional parathyroidectomy without localisation and IIPTH

Figure 10. Transient hypocalcaemia (post-operative)

Figure 11. Temporary vocal cord palsy

E.4. Video assisted parathyroidectomy (VAP) (type of minimally invasive) + intra-operative qPTHa versus classic bilateral neck exploration + intra-operative frozen section (without qPTHa) [pre- surgery localisation for both groups]

Figure 12. Permanent laryngeal nerve palsy

Figure 13. Symptomatic transient hypocalcaemia

Figure 14. Wound infection

Figure 15. Post-operative fever

Appendix H. Health economic evidence tables

No economic studies were included in this review.

Appendix I. Excluded studies

I.2. Excluded health economic studies

None.

Final

Intervention evidence review

This evidence review was developed by the National Guideline Centre

Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.

Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.

NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.

Copyright © NICE 2019.
Bookshelf ID: NBK577893PMID: 35167210

Views

  • PubReader
  • Print View
  • Cite this Page
  • PDF version of this title (1.2M)

In this Page

Other titles in this collection

Related NICE guidance and evidence

Supplemental NICE documents

Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed

Similar articles in PubMed

See reviews...See all...

Recent Activity

ClearTurn OffTurn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...