surgery is currently the only available cure for primary hyperparathyroidism ( php ) . in selected patients , minimally invasive parathyroidectomy ( mip ) offers the benefits of decreased morbidity and shorter hospital stay ; hence , it is increasingly replacing the traditional bilateral neck exploration ( bne ) and four - gland evaluation .
this technique depends on successful preoperative imaging and localization of the abnormal gland , using ultrasound ( uss ) and technetium tc sestamibi scanning with single - photon emission tomography ( spect ) . using a combination of these imaging modalities
however , the two imaging methods are concordant in only up to 64% of patients with php , and their accuracy is decreased in multiglandular disease ( mgd ) .
identification of a macroscopically abnormal parathyroid gland during mip does not exclude abnormalities of the rest of the glands such as double adenoma , multiglandular disease , or malignant tumours , which may be difficult to distinguish from benign adenomas , especially in light of the above limitations of preoperative imaging . on the other hand , histopathology of excised abnormal parathyroid glands is not predictive of the secretory function of the remaining parathyroid glands left in situ .
intraoperative parathyroid hormone ( iopth ) measurement has recently been introduced as a useful adjunct in confirming the successful excision of a parathyroid adenoma .
the method is based on the short half - life of the intact pth ( 4 - 5 minutes ) ; successful removal of diseased parathyroid tissue is predicted by corresponding decrease of serum pth concentrations .
we present our initial experience of patients with php treated surgically with minimally invasive parathyroidectomy and iopth measurement , and we evaluate the safety , efficacy , and clinical usefulness of the method in a district general hospital .
the study included eleven consecutive patients ( two male and nine female ) who underwent surgery for php over 6 months period in a district general hospital serving a population of approximately 300,000 .
ten patients were operated as elective cases because of severe hypercalcaemia complicated with decreased bone density .
one patient was operated as an emergency due to extreme hypercalcaemia ( adjusted serum calcium level , 6.49  mmol / l ) with grossly elevated pth concentration of 1059  pg / ml ( reference range 1565  pg / ml ) , serum   phosphate 1.79  mmol / l , creatinine 124  mol / l , and urea 16.0  mmol / l .
two weeks prior to admission , she had sustained right scaphoid fracture following a fall and was diagnosed with primary hyperparathyroidism ( phpt ) , awaiting elective parathyroidectomy .
all eleven patients had ultrasound scan of the neck preoperatively whereas sestamibi scan was feasible in all but one patient , who was severely kyphotic .
three patients underwent planned full neck exploration facilitated by iopth measurements , during the initial period of method validation . in the remaining 8 patients ,
mip surgery was initiated under general anaesthesia via a 3  cm skin crease incision approximately 1  cm above the clavicle and centred over the anterior border of sternoceidomastoid muscle .
biochemical profile was assayed on a cobas 6000 analyser ( roche diagnostics , mannheim , germany ) using standard methods .  
serum calcium was assayed by a method according to schwarzenbach   with o - cresolphthalein complexone   and serum albumin was measured by a colourimetric assay .  
intraoperative measurement of serum pth was performed at baseline ( immediately after the adenoma was resected , t0 ) and then at every 5 minutes post excision of the macroscopically abnormal parathyroid gland for 15 minutes ( t5 , t10 , and t15 ) . a fall in serum pth level by at least 50% of the baseline value within 15 minutes
excision of parathyroid adenoma was followed by the predicted fall in intraoperative serum pth concentration of > 50% in ten patients . in one patient ,
the pth levels increased and remained high for up to 30 minutes post excision , implying the presence of multiglandular disease ; further neck exploration identified an ipsilateral second adenoma , not localised preoperatively by either ultrasound or sestamibi scan .
removal of the second adenoma was followed by the expected fall in serum pth concentration of > 50% confirming successful surgery ( figure 1 ) . in another patient ,
the operation was converted to standard collar incision because the localised parathyroid adenoma macroscopically resembled a thyroid nodule ; therefore , better access was deemed necessary ; histology confirmed the presence of a parathyroid adenoma only . in all cases ,
histology confirmed the presence of discrete , encapsulated adenomas , containing sheets and islands of eosenophilic and chief cells , with no capsular invasion .
there was no evidence of hyperplasia or carcinoma in either of the eleven patients . during the postoperative period ,
ten patients had normal pth and remained normocalcaemic to a median ( range ) follow up of 6 ( 110 ) months .
recurrent elevation of serum pth concentration was noted postoperatively in one patient despite a fall of > 50% of baseline intraoperatively .
mmol / l ) and during the first postoperative week requiring calcium and vitamin - d supplementation orally .
the patient who had parathyroidectomy as an emergency when admitted with hypercalcaemic crisis stayed in the hospital for a total of 7 days in order to be monitored for potential complications of extreme hypercalcaemia .
the incidence since the introduction of multichannel analysers is approximately 1  :  1000 , with the relatively asymptomatic older female being the typical patient .   a prevalence of up to 2.1% in postmenopausal women has been reported in population - based health screening .
however , in the minority ( less than 10% ) of affected patients , php is associated with a number of distinct hereditary syndromes including multiple endocrine neoplasia ( men ) types 1 and 2a ( men 1 , men 2a ) , hyperparathyroidism - jaw tumour ( hpt - jt ) syndrome , and familial isolated hyperparathyroidism .
multinodular parathyroid hyperplasia accounts for 15%20% of cases   and only occasionally php is caused by parathyroid carcinoma .  
this retrospective study was based on a small preliminary series of patients and is not devoid of the relevant methodological weaknesses , such as incomplete data ( e.g preoperative levels of 25-oh vitamin d , urine calcium levels ) , accounted for by local policies and the retrospective data collection method ; these have been addressed in prospective larger series [ 2022 ] .
however , it has demonstrated that minimally invasive parathyroidectomy is a safe and effective method of surgical treatment of php , constituting a simple procedure that can be carried out in a district general hospital as day surgery or with overnight stay ; most of our patients are now discharged within 24 hours with calcium and vitamin - d supplements . although the role of iopth measurement is debatable , in our study , it incurred substantial clinical benefit by identifying the correct pathology in one patient with discordant preoperative imaging and in one patient with double adenoma .
it also facilitated successful excision of adenomas without the need for intraoperative frozen section , which can be disconcordant with the definitive histology in up to 10% of cases [ 23 , 24 ] .  
tc sestamibi scanning , using either single - photon emission computed tomography ( spect ) or oblique pinhole images , is able to localize over 90% of adenomas , including ectopic glands , but is less accurate in multiglandular disease .
when ultrasound scan ( uss ) and technetium tc sestamibi scanning are concordant their accuracy increases , but this is feasible in only two thirds of patients with php ( best concordance rate 64% ) . in our case series , intraoperative serum pth level quantification had higher sensitivity ( 100% ) in detecting the parathyroid pathology ( single or double adenoma ) compared to each imaging technique alone .
concordance between uss , sestamibi scan and iopth was noted in 9 ( 82% ) patients .
the false negative rate for uss alone was 18% ( 2 in 11 patients ) and for sestamibi scan alone 10% ( 1 in 10 patients ) .
combination of all three methods facilitated optimum selection of patients for minimally invasive surgery .  
a major benefit yielded by use of iopth measurement in this study was the diagnosis of a double adenoma that had not been detected preoperatively .
double adenomas have been reported to occur in 2%15% of patients undergoing operation for php   and can be missed in up to 15% of patients diagnosed with a single adenoma by sestamibi scan [ 29 , 30 ] .
they have a nonuniform distribution , likely to involve both sides of the neck and they can easily be missed when a focused mip approach is employed . failure to recognise the double pathology can lead to unsuccessful surgical outcome , unnecessary patient distress , and exposure to the risks of a redo operation and anaesthesia , along with further potential cost .  
failure of serum pth to appropriately decrease after excision of a single adenoma should raise suspicion of additional adenomas and the surgical approach should be modified accordingly , if necessary by converting mip to a standard full neck exploration .  
although intraoperative serum pth level quantification was first introduced in 1990 , it has yet to be universally accepted as a routine adjunct in surgery for php .
opponents of the method claim the additional incurring cost of surgery , prolongation of the operating time of mip and the reported false negative rate .
we did not perform a cost analysis during this small study , but it is anticipated that the short median hospital stay of our patients was cost effective ; the additional cost of pth assays of  32 per patient ( 4 intraoperative measurements ) has been offset by reducing the hospital stay ( cost of  657 per overnight stay per patient ) and by eliminating the cost of intraoperative frozen section (  150 per patient ) .
the use of iopth measurement in our series added 510 minutes extra to the operating time of minimally invasive procedure .
mip in experienced hands has been shown to be associated with shorter operating times   comparing to the conventional neck exploration , but studies providing high levels of evidence are lacking in this respect .  
one patient in our study was found to have elevated serum pth during follow up , despite appropriate intraoperative pth fall after excision of adenoma , but remains normocalcaemic and asymptomatic ; hence , no further imaging has been deemed clinically necessary .
this phenomenon is not uncommon and its significance is uncertain ; between 8%40% of patients with normocalcemia after surgery have elevated pth levels at follow up [ 35 , 36 ] . in a recent study , ning et al .   demonstrated that 95% of these patients do not develop recurrent hyperparathyroidism ( rhp ) . proposed
potential risk factors include higher preoperative pth concentrations , higher alkaline phosphatase activities , and older age ( associated with impaired renal function , bone remineralization , and low vitamin d ) .
they supported the hypothesis that persistently elevated pth may be , in part , secondary to  bone hunger  and suggested that rhp in their series was more likely if postoperative serum calcium was higher than 9.7  mg / dl ( 2.42 mmol / l ) .
long follow up with yearly serum pth and calcium levels is necessary to detect potential recurrence at an early stage . in summary ,
the results of our small case series suggest that minimally invasive parathyroidectomy with intraoperative pth measurement is a feasible , safe , and effective method for treatment of primary hyperparathyroidism in the context of a district general hospital .
our findings are in accordance with similar studies appealing for its wider use in the uk .
there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported .
this research did not receive any specific grant from any funding agency in the public , commercial or not - for - profit sector .
 
 background . minimally invasive 
 parathyroidectomy ( mip ) is increasingly replacing the traditional bilateral neck exploration in the treatment of primary hyperparathyroidism ( php ) . 
 intraoperative pth ( iopth ) measurement has recently been introduced as a useful adjunct in confirming successful excision of abnormal parathyroid gland . aims . 
 we evaluate the safety , efficacy , and clinical usefulness of iopth measurement during mip in a district general hospital . methods . 
 retrospective review of eleven consecutive patients with php who underwent mip with iopth , following preoperative assessment with ultrasound and sestamibi scans . results . 
 all patients had successful removal of the abnormal parathyroid gland . 
 the concordance rate between ultrasound and sestamibi scan in localising the parathyroid adenoma was 82% . 
 iopth measurement confirmed the removal of adenoma in all cases and , in one case , led to identification of a second adenoma , not localised preoperatively . 
 the median hospital stay was 2 days ( range 17 days ) . 
 all patients remained normocalcaemic after a median of 6 months ( range 110 months ) . 
 conclusions . 
 minimally invasive parathyroidectomy is a feasible , safe , and effective method for treatment of php . 
 the use of iopth monitoring potentially offers increased sensitivity in detecting multiglandular disease , can minimise the need and risk associated with recurrent operations , and may facilitate cost - effective minimally invasive surgery . 
1. Introduction
2. Subjects and Methods
3. Results
4. Discussion
 Declaration of Interest
 Funding