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Evidence review for indications for surgery

Hyperparathyroidism (primary): diagnosis, assessment and initial management

Evidence review C

NICE Guideline, No. 132

.

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

1. Indications for surgery

1.1. Review question

1.1.1. What is the clinical and cost effectiveness of surgery (parathyroidectomy) in people with primary hyperparathyroidism?

1.1.2. What are the indications for surgery (parathyroidectomy) in people with primary hyperparathyroidism?

1.2. Introduction

There is considerable variation in who is considered for surgical treatment of primary hyperparathyroidism (PHPT). Indications for surgery for symptomatic disease include the presence of end organ damage such as renal stones or reduced bone mineral density. There is much debate over whether surgery should be considered for people who are asymptomatic. In the UK, most practice adheres to the National Institute for Health consensus guidelines. They recommend surgery for the following indications:

  • Serum calcium (>upper limit of normal): 1.0 mg/dL (0.25 mmol/L);
  • BMD by DXA: T-score ≤2.5 at lumbar spine, total hip, femoral neck, or distal 1/3 radius;
  • Vertebral fracture by x-ray, CT, MRI, or VFA;
  • Creatinine clearance <60 cc/min; 24-h urine for calcium >400 mg/d (>10 mmol/d) and increased stone risk by biochemical stone risk analysis;
  • Presence of nephrolithiasis or nephrocalcinosis by x-ray, ultrasound, or CT;
  • <50 years

It is relevant to consider the evidence base underpinning these consensus-based US recommendations.

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 surgery (parathyroidectomy) in people with different ‘severities’ of PHPT. As there is no one tool to define severity of disease in PHPT, subgroup populations were included in the review protocol in order to investigate the subpopulations in which surgery is effective and should be recommended. The committee defined the subgroup populations using the same criteria as set out in the 4th International Guidelines for the Management of Asymptomatic PHPT, in order to determine in whom (the presence of which individual indications) surgery is effective and should be recommended. Therefore, evidence from this review informed review questions 1.1.1 and 1.1.2.

The committee did not define people with symptomatic and asymptomatic PHPT as separate strata or subgroups in the protocol, due to the difficulty in defining who is truly asymptomatic. Also, an absence of symptoms may not necessarily indicate milder disease, as end-organ effects can be present without symptoms. For these reasons, the committee wanted to move away from classifying people as symptomatic and asymptomatic.

As non-surgical options are available in people who do not have surgery, the comparators listed in the protocols also included non-surgical pharmacological options, in addition to conservative management (monitoring only).

1.4. Clinical evidence

1.4.1. Included studies

Eleven papers (reporting eight primary studies) were included in the review;7, 13, 27, 34, 50, 51, 64, 83, 87, 88, 90 these are summarised in Table 2 and Table 3 below. Evidence from these studies is summarised in the clinical evidence summary tables below (Table 4 and Table 5). See also the study selection flow chart in appendix C, study evidence tables in appendix D, forest plots in appendix E and GRADE tables in appendix F.

1.4.1.1. Included RCTs

Seven papers (reporting five studies) were RCTs included in the review. All studies compared surgery with conservative management.

For the comparison of surgery versus conservative management, all the available studies described the population as asymptomatic. As stated above, the committee defined subgroups in order to determine in whom (the presence of which indications) surgery is effective, with the aim of investigating the effectiveness of surgery in people with asymptomatic and biochemically mild PHPT. There were an insufficient number of studies to perform subgroup analysis for any of the protocol outcomes (to determine the effectiveness of surgery in people with or without the individual indications). However, the majority of the evidence was in people who overall do not meet the current criteria for surgery with the exception of one study34 in which the protocol subgroup criteria were unclear except to say people were free of symptoms, and another study7 which included a small number of people with osteoporosis (as it was based on the criteria for surgery prior to 2002); had the criteria of the 2002 Workshop on Asymptomatic PHPT been adopted, 29 of the 50 participants would have met these criteria for surgery. No studies were available in people with symptomatic disease or in people with asymptomatic disease who would be eligible for surgery under the current international consensus guidelines.

No RCT evidence was identified on the clinical effectiveness of surgery in any of the population strata listed in the protocol (people with normocalcaemic PHPT, people with previous unsuccessful parathyroidectomy or pregnant women).

For the comparison of surgery versus conservative management, the critical outcome of mortality was reported by one RCT, and the critical outcome of quality of life was reported in 4 of the 6 studies for this comparison. However, data from 3 of the studies reporting quality of life could not be analysed in the meta-analysis as it was only reported as graphs or narrative statements in the studies. The final study did report quality of life in a format that could be analysed, but each domain of the SF-36 was reported separately and the overall physical and mental components were not reported. This study also reported the SF-36 scores as estimated annual changes from the gradient of the slope, and did not report baseline to end of study change scores, or end of study final values. As there was insufficient evidence from RCTs for the critical outcome of quality of life for the comparison of surgery versus conservative management, NRSs meeting the study protocol were included. The outcome cardiovascular events was reported by one RCT for the comparison surgery versus conservative management, however a definition for this outcome was not provided in the study.

No RCT evidence was identified for the comparators of bisphosphonates, calcimimetics or combination treatment (calcimimetics and bisphosphonates). Therefore, NRSs meeting the study protocol were investigated to see if they reported outcomes for these comparisons.

1.4.1.2. Included NRS

Four papers (reporting 3 studies) were NRSs included in the review. All of these studies compared surgery with conservative management. No NRSs were identified comparing surgery with bisphosphonates or any of the other comparators listed in the protocol. Only NRSs that adjusted for confounding factors were included in the review, however none of the included studies adjusted for all the key confounders listed in our protocol.

For the comparison of surgery versus conservative management, the outcomes reported were fracture, mortality, kidney stones and cancer. No evidence was available for the critical outcome of QOL. Evidence for all of the reported outcomes was already available from RCT evidence, however the population represented by the NRSs is likely to be different to that represented by the RCTs. For the NRSs, details of the severity of PHPT or details to inform our protocol subgroups were not reported, but it is likely that these studies included a mixed population of people who would and would not be eligible for surgery according to the current guidelines (in contrast to the RCT evidence which was in people not currently eligible for surgery).

No evidence was identified for the outcome of persistent hypercalcaemia from either RCTs or NRSs.

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

See appendix D for full evidence tables.

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

Table 2

Summary of RCTs included in the evidence review.

Table 3. Summary of NRSs included in the evidence review.

Table 3

Summary of NRSs included in the evidence review.

1.4.4. Clinical evidence

Table 4. Clinical evidence summary: Surgery versus conservative management.

Table 4

Clinical evidence summary: Surgery versus conservative management.

Table 5. Clinical evidence summary: Surgery versus conservative treatment (non-randomised studies).

Table 5

Clinical evidence summary: Surgery versus conservative treatment (non-randomised studies).

See appendix F for full GRADE tables.

Narrative results

A modest but significant beneficial effect on quality of life [bodily pain (p=0.001); general health (p=0.008); vitality (p=0.003); and mental health (p=0.017)] was observed in patients after surgery compared with those followed without surgery. No difference was found in the remaining SF-36 and SCL-90R domains (Ambrogini). In comparison with the patients who did not have surgery, a statistically significant beneficial effect of parathyroidectomy was seen in two of the nine domains (social function, group difference p=0.007; and emotional role function, group difference, p=0.012 (Sudhaker). Concerning the physical domains, a slightly, but significant, decrease was observed over the two-year period in the medical observation group (p<0.01), whereas no change was seen in the operation group. The difference over time was significantly different in favour of surgery (p<0.01). The operation group scored slightly higher at year one, compared with baseline in the mental health subdomain and mental component summary score (p<0.05 for both), but not after two years of observation. For the mental health subdomain, the observation group scored higher at two years, compared with baseline (p<0.05). Although no longitudinal differences were observed in any group in the other psychological domains, the differences over time for the domain role emotional were in favour of surgery for both one and two years of observation13.

1.5. Economic evidence

1.5.1. Included studies

No relevant health economic studies were identified.

1.5.2. Excluded studies

One health economic study was identified relevant to this question, but was excluded due to a combination of limited applicability and methodological limitations.74 This is listed in appendix I, with reasons for exclusion given.

See also the health economic study selection flow chart in appendix G.

1.5.3. Unit costs

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

Table 6. Parathyroid procedures costs (elective inpatient schedule).

Table 6

Parathyroid procedures costs (elective inpatient schedule).

1.6. Resource costs

The recommendations made by the committee based on this review may have a substantial impact on resources.

Additional costs could be incurred where the recommendations lead to a change in practice for NHS providers. At present, people who are mostly asymptomatic are not routinely recommended for surgical intervention. If the recommendation lead to a large increase in the number of surgeries performed for PHPT, there will potentially be a large increase in healthcare resource use. However, it is unclear how widely this will be implemented.

1.7. Evidence statements

1.7.1. Clinical evidence statements

1.7.1.1. Surgery versus conservative management (randomised studies)

There was a clinically important benefit of surgery for QOL (SF-36 Social functioning subscale; SF-36 Emotional role functioning subscale) (1 study, n=53; follow-up 2 years; Very Low quality) vertebral fractures (3 studies, n=208; follow-up 1–5 years; Low quality); lumbar spine BMD % change from baseline (1 study, n=49; follow up 17 years; Very Low quality); distal radius BMD % change from baseline (1 study, n=49; follow-up 1 year; Low quality and cardiovascular events (1 study, n=145; follow-up 5 years; Very Low quality).

There was no difference between surgery and conservative management for QOL (SF-36 physical functioning subscale; SF-36 physical role functioning subscale; SF-36 mental health subscale; SF-36 vitality subscale; SF-36 bodily pain subscale; SF-36 general health subscale; SF-36 health transition) (1 study, n=53; follow-up 2 years; Very Low quality); mortality (1 study, n=191; follow-up 5 years; Very Low quality); renal dysfunction (2 studies, n=73; follow-up 2–17 years; Low quality); peripheral skeletal fractures (1 study, n=106; follow-up 5 years; Very Low quality); kidney stones (3 studies, n=208; follow-up 1–5 years; Very Low quality); lumbar spine BMD Z score final value (1 study, n=111; follow-up 5 years; Very Low quality); distal radius BMD (1 study, n=20; follow-up 17 years; Very Low quality); ultra-distal radius BMD (1 study, n=85; follow-up 5 years; Low quality); radius 33% BMD (1 study, n=86; follow-up 5 years; Very Low quality); adverse events (2 studies, n=102; follow-up 1–2 years; Very Low quality); and cancer (2 studies, n=194; follow-up 1–5 years; Very Low quality). No evidence was identified for the outcome of persistent hypercalcaemia.

1.7.1.2. Surgery versus conservative management (non-randomised studies)

There was a clinically important benefit of surgery for mortality (2 studies, n=3774; follow-up 6.1 years; Very Low quality) and fractures (2 studies, n=3746; follow-up 6.1–7.4 years; Very Low quality). There was clinical harm of surgery for the outcome kidney stones (1 study, n=3213; follow-up 6.1 years; Very Low quality). There was no difference between surgery and conservative management for cancer (1 study, n=3213; follow-up 6.1 years; Very Low quality). No evidence was identified for the outcomes persistent hypercalcaemia and health related QOL.

1.7.1.3. Surgery versus bisphosphonates

No evidence was identified.

1.7.1.4. Surgery versus calcimimetics

No evidence was identified.

1.7.1.5. Surgery versus combination treatment (calcimimetics and bisphosphonates)

No evidence was identified.

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 preservation of end organ function (bone mineral density, fractures, renal stones and renal function) as critical outcomes for decision making. Other important outcomes included adverse events, cancer incidence, cardiovascular events and persistent hypercalcaemia. The committee was interested in cardiovascular and cancer outcomes, as there is some observational prognostic evidence to suggest that the risk of these future events is higher in untreated primary hyperparathyroidism.

From the non-randomised studies (NRSs) no evidence was available for the critical outcome of quality of life. No evidence was identified for the outcome of persistent hypercalcaemia from either the randomised controlled trials (RCTs) or NRSs.

1.8.1.2. The quality of the evidence

All the evidence in this review (both RCTs and NRSs) compared surgery with conservative management. No evidence was available for the comparison of surgery with bisphosphonates, calcimimetics or combination treatment from either RCTs or NRSs.

The majority of the studies did not provide any details on conservative management; out of the 8 studies, 6 studies did not provide any details; one study stated ‘non-operative conservative management’ but did not provide any further details; another study reported ‘no surgery’ and follow-up every 6 months for at least 24 months with no further details.

All the available RCTs described the population as asymptomatic. The majority of the RCT evidence was in people who overall do not meet the current National Institutes of Health (NIH) criteria for surgery (with the exception of one study34 in which the protocol subgroup criteria were unclear except to say people were free of symptoms). There was another study which included a small number of people with osteoporosis as it was based on the criteria for surgery prior to 2002 – had the criteria of the 2002 Workshop on Asymptomatic primary hyperparathyroidism been adopted, 29 of the 50 participants would have met these criteria for surgery. No studies were available in people with symptomatic disease or in people with asymptomatic disease who would be eligible for surgery under the NIH guidelines. The current NIH criteria11 for surgery in people with asymptomatic primary hyperparathyroidism are as follows: serum calcium (>upper limit of normal): 1.0 mg/dL (0.25 mmol/L); BMD by DXA: T-score ≤2.5 at lumbar spine, total hip, femoral neck, or distal 1/3 radius; vertebral fracture by X-ray, CT, MRI, or VFA; creatinine clearance < 60 cc/min; 24-hour urine for calcium >400 mg/d (>10 mmol/d) and increased stone risk by biochemical stone risk analysis; presence of nephrolithiasis or nephrocalcinosis by X-ray, ultrasound, or CT; <50 years old.

For the RCTs comparing surgery with conservative management, the majority of the evidence was of Low to Very Low quality due to risk of bias and imprecision. This decreases our confidence in the estimate of effect of surgery.

For NRSs, details of the severity of primary hyperparathyroidism or to inform our protocol subgroups were not reported, but it is likely that these studies included a mixed population of people who would and would not be eligible for surgery according to the current guidelines (in contrast to the RCT evidence which was in people not currently eligible for surgery).

For the NRSs evidence all outcomes were graded as Very Low quality due to high risk of bias and imprecision.

1.8.1.3. Benefits and harms

As there is no one tool to define severity of disease in primary hyperparathyroidism, subgroup populations were included to investigate the populations in which surgery is effective and should be recommended. The guideline committee defined the subgroup populations using the same criteria as set out in the 4th International Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism, in order to determine in whom (the presence of which individual indications) surgery is effective and should be recommended.

The subgroups were: people with end-organ effects versus absence of end-organ effects (end organ effects defined as renal stones, history of fragility fractures or osteoporosis [BMD T-score <-2.5 at any site]); serum adjusted calcium > 0.25 mmol/litre above the ULN (same as ≥2.85 mmol/litre and <2.85 mmol/litre); reduction in creatinine clearance to <60 mL/minute; and age under 50 years versus ≥50 years. However, there were an insufficient number of studies to perform subgroup analysis for any of the protocol outcomes.

The committee also planned to consider the following population strata: people with normocalcaemic primary hyperparathyroidism (serum adjusted calcium ≤2.6 mmol/litre and an elevated PTH that cannot be explained by abnormal renal function or low 25OHD); previous unsuccessful parathyroidectomy (reoperation); and pregnant women. No evidence was identified on the clinical effectiveness of surgery in any of the population strata listed above.

The RCT evidence for the comparison surgery versus conservative management suggested that there was a clinical benefit of surgery for the outcomes quality of life (for 2 domains), vertebral fractures, lumbar spine BMD (% change from baseline); distal radius BMD % change from baseline (1 study, n=49; follow-up 1 year; Low quality) and cardiovascular events. The RCT evidence suggested that there was no difference between the groups surgery and conservative management for the outcomes mortality, quality of life (for 7 domains), renal dysfunction, peripheral skeletal fractures, renal stones, lumbar spine BMD Z score (final value), distal radius (BMD g/cm2), ultra-distal radius (BMD, g/cm2), radius 33% (BMD, g/cm2), adverse events and cancer. The estimates were imprecise for all the above outcomes except for distal radius BMD g/cm2, ultra-distal radius (BMD, g/cm2) and vertebral fractures.

The NRS evidence for the comparison surgery versus conservative management suggested that there was clinical benefit of surgery for the outcomes mortality and fractures. Although there was a clinical benefit for fractures it was noted that the estimate was imprecise. Evidence suggested that there was clinical harm of surgery for the outcome renal stones. Evidence suggested that there was no difference between the groups for the outcome cancer however the estimate was imprecise.

For the non-randomised studies, the committee noted the apparent raised risk of renal stones in people who had surgery but from their experience felt that this was likely to represent their higher risk, as once someone has had a renal stone they remain at higher risk of a recurrence. The non-randomised data on fracture was consistent with the randomised evidence. It was reassuring that there was a significantly lower mortality in the surgical arm but this was largely likely to be due to confounding factors (people selected for surgery tend to be fitter).

The committee discussed that surgery is the only definitive cure for primary hyperparathyroidism. They noted that surgery is likely to cure primary hyperparathyroidism and therefore cure hypercalcaemia and relieve patients of symptoms of hypercalcaemia such as thirst, polyuria and constipation. These are the classical symptoms of hypercalcaemia that will most robustly show improvement on resolution of primary hyperparathyroidism. The committee also discussed that surgery in this population could also prevent future events such as renal stones and fragility fractures from occurring. The committee considered that some primary hyperparathyroidism patients present with long standing non-specific/undifferentiated symptoms such as fatigue, depression, muscle weakness, abdominal pain, loss of concentration etc. However the committee considered that such symptoms occur in many other diseases and agreed not to make a recommendation for such non-specific symptoms as indications for surgery. The committee noted that primary hyperparathyroidism is associated with a decline in renal function but there is no evidence that parathyroidectomy leads to an improvement. They noted that specific thresholds for renal dysfunction (creatinine clearance, 24-hour urine calcium) have been used in other countries as indications for surgery, but there are no data available to suggest that these cut-offs in isolation would be an indication for parathyroidectomy. The committee noted that 24-hour calcium is a good predictor of renal stone formation in the future. They felt that renal function thresholds for deteriorating renal function can be considered as part of decision making.

The committee noted that there was no evidence to support a particular cut-off point for adjusted serum calcium requiring surgery but they felt that it was reasonable to define a threshold of 2.85 mmol/litre or above at which surgery would be recommended.

The committee considered that the evidence in favour of surgery in patients who do not already have indications for surgery in these trials provided indirect evidence of benefit in the population in whom surgery is currently performed for whom no randomised evidence was found. This is because the currently accepted indications are in people who are at higher risk of the adverse sequellae of primary hyperparathyroidism and therefore would in principle benefit more from the operation.

The committee considered that the absence of randomised evidence in the population that meet the NIH criteria reflects the broad international consensus that surgery is indicated in this group. For people with no symptoms or indications for surgery, the committee based their recommendation on limited evidence together with their clinical experience. The recommendation is for the person to be referred for surgery so that their specific risks and benefits can be discussed. Surgery would not be offered for all of these people. A proportion of these people would meet the current criteria for surgery in the future but the committee proposed to consider surgery earlier to avoid the potential consequences of primary hyperparathyroidism. The committee considered that the benefits of surgery shown in people with no symptoms or other indications for surgery would be magnified for people with more severe disease. The committee from clinical experience noted that primary hyperparathyroidism patients have lower bone density, increased fracture risk, osteoporosis; and surgery reduces the risk of fracture in such patients. The committee from their clinical experience also discussed that kidney stones are one of the end organ effects of primary hyperparathyroidism and the risk of developing renal stones decreases after surgery. The committee agreed that surgery should be considered in people who have risk factors which are predictors of end organ disease or progressive disease. Risk factors discussed included younger age with persistent hypercalcaemia but below the 2.85 mmol/litre threshold, and symptoms suggestive of renal stone disease without current stones but with elevated urinary calcium excretion.

The committee discussed that if surgery is to be offered, it is important that the risks and benefits of the procedure are fully explained so that the patient can make an informed choice.

The committee determined that whilst the current NIH criteria separates those who are below 50 and those who are over 50, it would not be appropriate to make this distinction in their recommendations to ensure equality of access to surgery regardless of age. The age of the person is a factor for the clinician to discuss with the person when considering whether surgery is a suitable option for them. The committee emphasised that the consideration is more about life expectancy than age, as performance status is not necessary correlated with age in a linear way.

The committee discussed the other management approaches compared to surgery including calcimimetics and bisphosphonates. The committee noted that cinacalcet (calcimimetics) should be an option in people who are unable to undergo surgery only and not as an alternative to surgery, as parathyroidectomy is the only definitive treatment option in people with primary hyperparathyroidism without surgical contraindication. The committee from their experience stated that cinacalcet does not directly stop bone loss or kidney problems due to primary hyperparathyroidism (for further discussion of this evidence please refer to Evidence review G). The committee also discussed that as bisphosphonates do not provide a cure for the underlying condition of primary hyperparathyroidism, they should not be considered as an alternative to curative measures such as surgery. However the committee agreed that bisphosphonates should be considered in people with primary hyperparathyroidism and bone end organ effects, to reduce fracture risk (for further discussion of this evidence please refer to Evidence review H).

1.8.2. Cost effectiveness and resource use

No relevant economic evaluations were identified for this question.

Unit costs were presented to the committee for consideration. The average cost of an elective inpatient parathyroid procedure is around £3,050, with an average length of stay of 1.5 days. This was estimated using NHS reference costs (2015–16), and takes into account complexity of procedure with regard to complications and comorbidities.

This area was initially identified as being high priority for original economic analysis. However, following the clinical review it was judged that economic modelling for this question would not be possible due to the lack of clinical evidence regarding the effectiveness of parathyroidectomy for people with either symptomatic or asymptomatic disease. Consequently, cost effectiveness of parathyroidectomy could not be calculated and is therefore highly uncertain.

However, the committee discussed that surgery is the only definitive cure for primary hyperparathyroidism. They noted that surgery is likely to cure primary hyperparathyroidism (current national cure rate around 94%) and therefore cure hypercalcaemia and relieve patients of symptoms such as thirst, polyuria and constipation. Furthermore, the committee considered that surgery in this population could also prevent future events such as renal stones and fragility fractures from occurring which will incur both a high cost to the NHS as well as reducing quality of life for the person. Furthermore, surgery would be more cost effective as it requires a one-off high cost with sustained benefit due to cure, whereas for example calcimimetics requires continuous high cost to maintain a similar benefit without providing a definitive cure of the primary hyperparathyroidism.

The committee considered that those with the greatest potential for quality of life gains and cost savings, and hence those for which surgery is most likely to be cost effective, are those who have symptoms of hypercalcaemia, or end organ disease, or those with a serum calcium level of 2.85 mmol/litre or above. They therefore agreed to offer surgery to this population. Therefore as mentioned in the benefits and harms section above, the population for which the committee have recommended surgery should be offered reflect broad international consensus, and as a result this recommendation is in line with current practice and therefore will not have a substantial resource impact.

The committee expressed concern that in current practice, people with primary hyperparathyroidism who may potentially be cured by surgery are not currently being referred to have surgery due to not meeting current NIH criteria. It was estimated this might affect around 15–20% of patients. Therefore, the committee also considered the cost effectiveness of surgery for those who do not meet these criteria – an ‘asymptomatic’ population. The committee discussed that as these people are generally ‘asymptomatic’ the likely quality of life gains initially after surgery are likely to be smaller, however they still considered there could be some improvement due to the possible resolution of non-specific symptoms people with ‘asymptomatic’ primary hyperparathyroidism can experience such as fatigue, depression and muscle weakness to name a few. The committee also discussed that if surgery was not considered in this population they would be monitored, which also incurs a cost. Furthermore the committee recognised that people may become eligible according to the recommendations at a later date due to disease progression. The committee discussed that by this point their quality of life could have worsened due to the development of symptoms of hypercalcaemia or possible due to end organ damage. However, as there are no data available to suggest the rate or proportion of people that are likely to become eligible for surgery according to these criteria, as well as a lack of data available on the effectiveness of monitoring in detecting potential disease progression prior to end organ damage occurring, the cost effectiveness of surgery in this population is highly uncertain. However, the committee considered that because future decrements in quality of life and cost of events associated with end organ damage could be avoided, surgery should be considered in this group.

It is uncertain how many additional surgeries would be performed as a result of this recommendation, but the committee do not anticipate there will be a significant increase in the number of referrals to result in a significant resource impact..

1.8.3. Other factors the committee took into account

The committee considered symptomatic primary hyperparathyroidism to include symptoms attributable to hypercalcaemia such as thirst, polyuria and constipation. They also recognised associations with non-specific symptoms such as fatigue, depression, muscle weakness, constipation, abdominal pain, loss of concentration, mild confusion etc. End organ disease refers particularly to disease of the kidney and bones as these are more commonly associated with primary hyperparathyroidism. The committee noted primary hyperparathyroidism was considered as a rare cause of pancreatitis, but there was no evidence to suggest that parathyroid surgery would improve the course of pancreatitis in such patients.

The committee noted that surgery is only offered if the benefits outweigh the risks. People may not be offered surgery if they have a very high operative risk, airway problems, distorted anatomy or short life expectancy.

The committee discussed the terminologies used for parathyroid surgery and stated that parathyroid surgery is surgery targeted at the parathyroid and parathyroidectomy is removal of parathyroid tissue. They noted that there may be failed parathyroidectomy (or unsuccessful) that is still parathyroid surgery.

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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 therefore difficult to retrieve. Search filters were applied to the search where appropriate.

Table 9. 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 the 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 10. 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 (333K)

Appendix H. Health economic evidence tables

None.

Appendix I. Excluded studies

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: NBK577892PMID: 35167216

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