Intraoperative parathyroid hormone (IOPTH) monitoring is recommended by the American Association of Endocrine Surgeons for use during parathyroidectomy for patients with primary hyperparathyroidism (PHPT), but there is no clinician consensus regarding the IOPTH monitoring criteria that optimize diagnostic accuracy.

To evaluate and rank the diagnostic properties of IOPTH monitoring criteria used during surgery for patients with PHPT.

A bayesian diagnostic test accuracy network meta-analysis (DTA-NMA) was performed, in which peer-reviewed citations from January 1, 1990, to July 22, 2023, were searched for in MEDLINE, Embase, Web of Science, CENTRAL, and CINAHL.

All full-text study designs that evaluated any IOPTH monitoring criteria as a diagnostic test were included in this meta-analysis. Any studies evaluating adult patients diagnosed with PHPT undergoing parathyroidectomy were also included. The reference standard used in this study was normalization of calcium and/or parathyroid hormone levels within 1 year of surgery.

This DTA-NMA was reported in accordance with the applicable Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Two reviewers evaluated all abstracts and full-text articles using a piloted extraction form. A third author resolved any conflicts. There are no published Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) resources for DTA-NMA. The following conventional monitoring criteria were included: Halle, Miami, Rome, Vienna, and PTH normalization, and the following modified criteria were included: Miami and PTH normalization, modified Miami, and modified Vienna. A bayesian hierarchical DTA-NMA model with corresponding 95% credible intervals (CrIs) was used to describe the pooled diagnostic characteristics of the evaluated IOPTH monitoring criteria.

Main outcomes included pooled diagnostic test properties, including sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio.

A total of 72 studies, which included 19 072 patients, met the inclusion criteria. Sixty-nine studies (95.8%) investigated classic PHPT. In PHPT, the Miami criteria were investigated most often and had the best diagnostic properties (diagnostic odds ratio, 60.00 [95% CrI, 32.00-145.00]) when compared to other conventional criteria. Moreover, the modified Miami criteria, which measures a postexcision IOPTH level 15 minutes or more postexcision of all hyperfunctioning parathyroid tissue, were the overall best criteria (diagnostic odds ratio, 79.71 [95% CrI, 22.46-816.67]). There was a low risk of study bias and no publication bias.

The results of this meta-analysis suggest that surgeons should use the modified Miami criteria when performing IOPTH-guided surgery for patients with PHPT because these criteria optimize intraoperative diagnostic accuracy by minimizing unnecessary neck exploration and revision surgery rates.

Primary hyperparathyroidism (PHPT) is caused by the overproduction of parathyroid hormone by 1 or more parathyroid glands resulting in hypercalcemia and its downstream clinical consequences. The definitive management of PHPT is surgery. Approaches to successful surgery include bilateral exploration or focused parathyroidectomy with intraoperative parathyroid hormone monitoring, which in experienced hands are both associated with a low risk of complications.

The primary goal of this study was to determine in patients with normohormonal primary hyperparathyroidism (NHHPT) what percent reduction in post-excision intraoperative parathyroid hormone (IOPTH) from baseline would yield a rate of cure comparable to that in patients with classical primary hyperparathyroidism (PHPT).

This is a retrospective cohort study of patients who underwent parathyroidectomy between July 2013 and February 2020. Demographic data, preoperative, intraoperative, and postoperative metrics were collected. Patients with NHHPT were compared to those with classical PHPT. Subgroup analyses were performed.

Of the 496 patients included in the study, 66 (13.3%) were of the normohormonal variant based on preoperative intact parathyroid hormone (PTH) levels and 28 (5.6%) based on baseline IOPTH levels. The cure rates in the two normohormonal groups were not significantly different from their classical counterparts (98.4% and 100.0% vs. 97.1%, p = 1.000). The median percent decline in post-excision IOPTH from baseline that achieved cure in the normohormonal groups were 82.6% and 80.4% compared to their respective controls at 87.3%, p = 0.011 and p = 0.001. Although the rate of multiglandular disease was higher in one of the normohormonal variant groups, this difference was due to a higher rate of double adenomas, not four-gland hyperplasia.

Patients with NHHPT undergoing parathyroidectomy can expect cure rates similar to that in patients with classical PHPT. The results of this study indicate that achieving an 80% drop or more in IOPTH levels predicts a high likelihood of cure. This is true irrespective of whether the patient is deemed normohormonal based on preoperative or intraoperative testing.

3 Laryngoscope, 134:2480-2484, 2024.

Patients with primary hyperparathyroidism (1HPT) undergoing reoperative or subtotal parathyroidectomy (PTX) may undergo autotransplantation (ATX) when the viability of remaining tissue is unknown. This study aims to identify whether intraoperative parathyroid hormone levels (IOPTH) can determine ATX candidacy.

Patients with 1HPT who underwent PTX with ATX at our institution were identified. IOPTH and PTH values within 24 h, 2-4 weeks, and >1 month postoperative were analyzed. Patients were classified as either a candidate for ATX (low PTH after 2-4 weeks) or not a candidate based on postoperative PTH (normal PTH after 2-4 weeks). Associations of ATX candidate status with demographic and clinical attributes were studied.

268 had a reoperative (49%) or subtotal PTX with ATX. 151 had data for PTH analysis, and 21 (14%) were identified as candidates for ATX. The mean % decline in IOPTH from baseline to 20 min post-excision was 51% in noncandidates vs 73% in candidates (P = .002). The mean change in IOPTH from baseline to final was 52% in noncandidates and 83% in candidates (P = .009). A decrease in IOPTH from baseline to 20 min post-excision of 23.4% or greater or a final PTH of 52 pg/mL or less would be an indication for ATX. Of the 21 who needed an ATX, it failed in 10.

Parathyroid ATX is frequently unnecessary, and the viability is less than expected. While candidates for ATX have a greater IOPTH % decline at all points during surgery and a lower final IOPTH, the clinical practicality of using IOPTH to determine ATX candidacy is limited.

Focused parathyroidectomy (F-PTX) guided by intraoperative parathormone (ioPTH) monitoring may result in higher operative failure rates from missed multiglandular disease (MGD) in patients with sporadic primary hyperparathyroidism (spHPT) when ioPTH levels do not reach normal range.

A retrospective review included 690 patients with spHPT who underwent F-PTX and ioPTH monitoring were divided into 2 groups: >50% ioPTH decrease to normal range, and >50% ioPTH decrease to above normal range. Operative success, recurrence, bilateral/unilateral neck exploration (BNE/UNE), MGD were evaluated.

533 patients demonstrated >50% ioPTH decrease to normal range, and 157 patients >50% ioPTH decrease to above normal range. There were no differences in operative success 99% vs. 97%, recurrence 2.5% vs. 5%, BNE 12% vs. 11%, UNE 4% vs. 5%, or MGD 4% vs. 4%, (p > 0.05) with 46 months mean follow-up.

There were no differences in operative success, failure, BNE, UNE or MGD regardless of ioPTH criterion used for F-PTX.

The use of Rapid Intraoperative parathyroid hormone (Io-PTH) assay during surgery in the management of parathyroid tissue in cases of primary hyperparathyroidism has been proven to be effective, while its utilization in secondary hyperparathyroidism (SHPT) has been rarely reported. In the present study, we aim to demonstrate the application of rapid Io-PTH assay in patients with SHPT following chronic kidney disease undergoing parathyroidectomy surgery.

In this prospective study, five blood samples were taken from patients undergoing parathyroidectomy and upper thymectomy. Among the samples, two were pre-excision, including prior to the first incision, after exploration, and before parathyroids resection. Two additional samples were taken 10 and 20 min after the excision of the parathyroid glands. Another sample was collected twenty-four hours after the operation. Serum Calcium levels and PTH levels were evaluated and analyzed.

We successfully managed SHPT in all 36 patients in our study. The patients included 24 males (66.7%) with a mean age of 49.97 ± 14.92. The mean PTH decreased significantly at 10 min, 20 min, one day, and six months after surgery (P < 0.001). The highest reduction occurred 10 min after removal of the parathyroid glands so the mean PTH compared to time zero was reduced from 1737 to 439, and in 100% of cases, more than 50% reduction was seen in PTH.

A 60% or more reduction in PTH Rapid at 10 min after parathyroidectomy has an accuracy of 94.4% and a positive predictive value of 100%. Thus, if the PTH level does not decrease by more than 60% at 10 min or more than 80% at 20 min, tissue exploration is continued with the aim of finding the ectopic parathyroid gland.

Recent changes in the landscape of endocrine surgery include a shift from total thyroidectomy for almost all patients with papillary thyroid cancer to the incorporation of thyroid lobectomy for well-selected patients with low-risk disease; minimally invasive parathyroidectomy with, and potentially without, intraoperative parathyroid hormone monitoring for patients with well-localized primary hyperparathyroidism; improvement in the management of parathyroid cancer with the incorporation of immune checkpoint blockade and/or targeted therapies; and the incorporation of minimally invasive techniques in the management of patients with benign tumors and selected secondary malignancies of the adrenal gland.

Parathyroidectomy (PTX) is the treatment of choice for symptomatic primary hyperparathyroidism (PHPT). It is also the treatment of choice in asymptomatic PHPT with evidence for target organ involvement. This review updates surgical aspects of PHPT and proposes the following definitions based on international expert consensus: selective PTX (and reasons for conversion to an extended procedure), bilateral neck exploration for non-localized or multigland disease, subtotal PTX, total PTX with immediate or delayed autotransplantation, and transcervical thymectomy and extended en bloc PTX for parathyroid carcinoma. The systematic literature reviews discussed covered (i) the use of intraoperative PTH (ioPTH) for localized single-gland disease and (ii) the management of low BMD after PTX. Updates based on prospective observational studies are presented concerning PTX for multigland disease and hereditary PHPT syndromes, histopathology, intraoperative adjuncts, localization techniques, perioperative management, "reoperative" surgery and volume/outcome data. Postoperative complications are few and uncommon (<3%) in centers performing over 40 PTXs per year. This review is the first global consensus about surgery in PHPT and reflects the current practice in leading endocrine surgery units worldwide. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The history and evolution of parathyroid hormone is a true testament to inter-disciplinary collaboration among anatomists, biochemists and surgeons. The parathyroid glands were the last endocrine glands to be discovered in the mid-1800s. Over the next century, progress in the evaluation of primary hyperparathyroidism, the identification of parathyroid hormone (PTH) and its application for use in the field of parathyroid surgery have led to a significant improvement in surgical cure rates, accompanied by a shift toward minimally invasive surgical options. This chapter provides a historical lens through which we can view these relatively recent advancements, as well as the current role of parathyroid hormone, both with regards to pre-operative localization and intra-operative detection of abnormal glands. Furthermore, we discuss the importance of parathyroid hormone in the management of complex multiglandular disease and reoperative cases, as well as the significance of persistently elevated PTH levels post-parathyroidectomy.

Primary hyperparathyroidism can be asymptomatic or symptomatic, as well as classic, normocalcemic, or normohormonal. It is important to rule out other causes of hypercalcemia or hyperparathyroidism. Preoperative localization with imaging is necessary for a minimally invasive approach and can be helpful even if planning 4-gland exploration. There are a variety of intraoperative techniques that can assist with localization as well as confirming success. Standard of care remains surgical resection of affected glands. However, there are less invasive management strategies that can be considered for poor surgical candidates.

Genetic, symptomatic, and biochemical heterogeneity of patients with primary hyperparathyroidism (PHPT) has become apparent in recent years. An in-depth, evidence-based review of the phenotypes of PHPT was conducted. This review was intended to provide the resulting information to surgeons who operate on patients with hyperparathyroidism. This review revealed that the once relatively clear distinction between familial and sporadic PHPT has become more challenging by the finding of various germline mutations in patients with seemingly sporadic PHPT. On the one hand, the genetic and clinical characteristics of some syndromes in which PHPT is an important component are now better understood. On the other hand, knowledge is emerging about novel syndromes, such as the rare multiple endocrine neoplasia type IV (MEN4), in which PHPT occurs frequently. It also revealed that, currently, the classical array of symptoms of PHPT is seen rarely upon initial presentation for evaluation. More common are nonspecific, nonclassical symptoms and signs of PHPT. In areas of the world where serum calcium levels are checked routinely, most patients today are "asymptomatic" and they are diagnosed after an incidental finding of hypercalcemia; however, some of them have subclinical involvement of bones and kidneys, which is demonstrated on radiographs, ultrasound, and modern imaging techniques. Last, the review points out that there are three distinct biochemical phenotypes of PHPT. The classical phenotype in which calcium and parathyroid hormone levels are both elevated, and other disease presentations in which the serum levels of calcium or intact parathyroid hormone are normal. Today several, distinct phenotypes of the disease can be identified, and they have implications in the diagnostic evaluation and treatment of patients, as well as possible screening of relatives.

Primary hyperparathyroidism is an endocrine pathology that affects calcium metabolism. Patients with primary hyperparathyroidism have high concentrations of serum calcium or high concentrations of parathyroid hormone, or incorrect parathyroid hormone levels for serum calcium values. Primary hyperparathyroidism is due to the presence of an adenoma/single-gland disease in 80-85%. Multiple gland disease or hyperplasia accounts for 10-15% of cases of primary hyperparathyroidism. Atypical parathyroid adenoma and parathyroid carcinoma are both responsible for about 1.2-1.3% and 1% or less of primary hyperparathyroidism, respectively.

We performed a retrospective cohort study and enrolled 117 patients with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy. Histological and immunohistochemical examination showed that 107 patients (91.5%) were diagnosed with typical adenoma (group A), while 10 patients (8.5%) were diagnosed with atypical parathyroid adenoma (group B). None of the patients were affected by parathyroid carcinoma.

Significant statistical differences were found in histological and immunohistochemical parameters as pseudocapsular invasion (p <  0.001), bands of fibrosis (p <  0.001), pronounced trabecular growth (p <  0.001), mitotic rates of > 1/10 high-power fields (HPFs) (p <  0.001), nuclear pleomorphism (p = 0.036), thick capsule (p <  0.001), Ki-67+ > 4% (p <  0.001), galectin-3 + (p = 0.002), and protein gene product (PGP) 9.5 + (p = 0.038).

Atypical parathyroid adenoma is a tumor that has characteristics both of typical adenoma and parathyroid carcinoma. The diagnosis is reached by excluding with strict methods the presence of malignancy criteria. Atypical parathyroid adenoma compared to typical adenoma showed significant clinical, hematochemical, histological, and immunohistochemical differences. We did not find any disease relapse in the 10 patients with atypical parathyroid adenoma during 60 months of follow-up time.

In this study, we aimed to evaluate demographic characteristics, preoperative adenoma localization, surgical techniques selected according to the size and localization of adenoma, and clinical results of patients undergoing mediastinal parathyroid adenoma excision.

Medical records of a total of 11 patients (4 males, 7 females; mean age 52.6 years; range, 25 to 65 years) who underwent excision of mediastinal parathyroid adenoma in our clinic between January 2011 and June 2019 were retrospectively reviewed. Data including demographic characteristics, complaints, preoperative serum calcium, phosphorus, and parathyroid hormone levels, preoperative imaging methods, surgical method, localization and size of adenoma, length of hospital stay, and duration and amount of drainage were recorded.

Adenoma was localized in anterior mediastinum in seven patients and in the middle mediastinum in four patients. The mean diameter calculated by taking into account the longest diameter of parathyroid adenoma was 21.1 mm. The mean drainage duration was 3.5 days in two patients undergoing median sternotomy, five days in one patient undergoing thoracotomy, 1.2 days in three patients undergoing video-assisted thoracoscopic surgery, and 0.6 days in five patients undergoing robotic surgery.

Minimally invasive approaches such as videoassisted thoracoscopic surgery and robotic-assisted surgery are safe and effective approaches for excision of mediastinal parathyroid adenoma.

The study objective was to evaluate the intraoperative 50% decrease in PTH level ± PTH normalization for its accuracy and efficiency in predicting cure during parathyroidectomy (PTx) for the treatment of primary hyperparathyroidism (PHP).

A retrospective review of patients undergoing PTx was conducted. The timepoints at which the 50% PTH decrease was reached were recorded. The accuracy of intraoperative PTH for predicting cure, defined as normocalcemia at 6 months postoperatively, was evaluated.

The study population was made up of 248 PHP patients, with 247 patients achieving normocalcemia at 6 months postoperatively. If a 50% PTH decrease was used to indicate operation conclusion, 1 patient would not be cured. Persistent PTH elevation above normal range at T10 had a PPV of 77%, NPV of 99.5%, sensitivity of 95.2% and specificity of 97.3% for predicting the presence of a contralateral pathological parathyroid gland. For the study cohort, 24.5 h of cumulative operating time would be saved if the 50% PTH decrease triggered operation conclusion.

A decrease in the pre-excision PTH level to 50% of the baseline level, or a decrease in the higher of the baseline or pre-excision PTH levels by 50% at 5 or 10 min post pathological parathyroid gland removal, regardless of whether the PTH level normalizes, reliably predicts cure from PHP and should be used to guide the surgeon during parathyroidectomy.

Intraoperative parathyroid hormone monitoring (IPM) has been shown to be a useful adjunct during parathyroidectomy to ensure operative success at many specialized medical centers worldwide. Using the Miami or ">50% intraoperative PTH drop" criterion, IPM confirms the complete excision of all hyperfunctioning parathyroid tissue before the operation is finished, and helps guide the surgeon to identify additional hyperfunctioning parathyroid glands that may necessitate further extensive neck exploration when intraoperative parathyroid hormone (PTH) levels do not drop sufficiently. The intraoperative PTH assay is also used to differentiate parathyroid from non-parathyroid tissues during operations using fine needle aspiration samples and to lateralize the side of the neck harboring the hypersecreting parathyroid through differential jugular venous sampling when preoperative localization studies are negative or equivocal. The use of IPM underscores the recognition and understanding of sporadic primary hyperparathyroidism (SPHPT) as a disease of function rather than form, where the surgeon is better equipped to treat such patients with quantitative instead of qualitative information for durable long-term operative success. There has been a significant paradigm shift over the last 2 decades from conventional to focused parathyroidectomy guided by IPM. This approach has proven to be a safe and rapid operation requiring minimal dissection performed in an ambulatory setting for the treatment of SPHPT.

To evaluate a single-center extensive experience and effectiveness in surgical treatment of primary hyperparathyroidism (pHPT) with the use of rapid intraoperative parathyroid hormone (ioPTH) monitoring in patients with single gland (SGpH) or multiple gland (MGpH) disease.

This retrospective, single-center cohort study included 214 patients with pHPT treated from January 2010 to June 2017. In total, 172 patients fulfilled the inclusion criteria having at least one preoperative localization image study and measurement of ioPTH. Statistical analysis was made by the chi-square test and Student's t tests.

Of the 172 patients, 146 were women (85%) and 26 men (15%), with a mean age of 56.9 years; 153 (89%) had SGpH and 19 (11%) MGpH. The mean follow-up was 41.8 months. A total of 153 surgical procedures were performed as minimal invasive parathyroidectomy (MIP) based on a SGpH diagnosis; operative success was achieved in 150 cases (98%), according to ioPTH concentrations. The remainder (19 procedures) were performed as bilateral neck exploration (BNE) based on a MGpH diagnosis; operative success was achieved in 16 cases (84%). ioPTH correctly modified the initially planned operation in 26.3% of patients with MGpH.

ioPTH enables the surgical treatment of patients with pHPT with focused approaches and excellent results, as it helps the surgeon to identify cases of MGpH. ioPTH adds value to cases where preoperative imaging failed to detect the affected gland or the results are inconclusive. According to the literature, its application seems to be of marginal benefit in cases in which there are two concordant preoperative imaging studies.

Practice variations exist amongst parathyroid surgeons depending on their expertise and resources. Our study aims to elucidate the choice of surgical techniques and adjuncts used in parathyroid surgery by surgeons in the Asia-Pacific region.

A 25-question online survey was sent to members of five endocrine surgery associations. Questions covered training background, practice environment and preferred techniques in parathyroid surgery. Respondents were divided into three regions: Australia/New Zealand, South/South East Asia and East Asia, and responses were analysed according to region, specialty, case volume and years in practice.

One hundred ninety-six surgeons returned the questionnaire. Most surgeons (98%) routinely perform preoperative imaging, with 75% preferring dual imaging with ^99mTcsestamibi and ultrasound. Ten per cent of surgeons use parathyroid 4DCT as first-line imaging, more commonly in East Asia (p = 0.038). Minimally invasive parathyroidectomy is the favoured technique of choice (97%). Most surgeons reporting robotic or endoscopic approaches are from East Asia. Rapid intraoperative parathyroid hormone is accessible to just under half of the surgeons but less available in Australian/New Zealand (p < 0.001). The use of intraoperative neuromonitoring is not commonly used, even less so amongst Asian surgeons (p = 0.048) and surgeons with low case load (p = 0.013).

Dual localisation techniques are the preferred choice of investigations in preparation for parathyroid surgery, with minimally invasive surgery without neuromonitoring the preferred approach. Use of adjuncts is sporadic and limited to certain centres.

We compared the rates of intraoperative parathyroid hormone (PTH) decline using the Siemens Immulite^® Turbo PTH and Roche Elecsys^® short turnaround time PTH assays in 95 consecutive surgical patients to investigate analytical and turnaround time (TAT) differences between the tests performed in the operating room (OR) vs the central clinical chemistry laboratory (CCL).

Serial blood samples from 95 patients undergoing parathyroidectomy were collected and measured using the 2 immunoassays. Specimens from the first 15 patients were measured simultaneously in the OR and CCL and used for the TAT study. In addition to 2 baseline samples, specimens were collected at 5, 10, and 15 min (for some patients, >15 min) after parathyroidectomy.

In the TAT study, a significant difference was observed (OR median 20 min vs CCL median 27 min; P < 0.05). Of the 95 patient series, slower rates of parathyroid hormone decrease were observed in approximately 20% of the patients when comparing the Roche with the Immulite immunoassay.

There was a slightly longer TAT in the CCL compared with running the assay directly within the OR (median difference of approximately 7 min). For a majority of the patients, both methods showed equivalent rates of PTH decline; however, for approximately 20% of the patients, there was a slower rate of PTH decline using the Roche assay.

Parathyroidectomy guided by intraoperative parathormone (ioPTH) monitoring for primary hyperparathyroidism (pHPT) confirms removal of all hyperfunctioning parathyroid glands. This study evaluates the utility of an additional 20-min ioPTH measurement in patients who fail to meet the >50% ioPTH drop criterion.

A retrospective review of prospectively collected data of 706 patients with pHPT who underwent parathyroidectomy guided by ioPTH monitoring was performed. When a >50% ioPTH decrease from the highest either preincision or preexcision level was achieved after 10 min, parathyroidectomy was completed. If this criterion was not met, further exploration was performed or an additional 20-min ioPTH measurement was obtained.

Of 706 patients, 72 (10%) patients did not meet the >50% ioPTH drop criterion at 10 min. Of these patients, 67% (48/72) underwent immediate bilateral neck exploration (BNE). For the other 33% of patients (24/72), a 20-min parathormone (PTH) measurement was drawn. Of patients with an additional 20-min PTH measurement, 46% (11/24) had a >50% ioPTH decrease at 20 min where BNE was avoided and parathyroidectomy completed, whereas 54% (13/24) did not. Compared to patients with insufficient ioPTH drop at 10 min and subsequent BNE, there was a statistically significant 46% reduction of BNE in patients with a 20-min PTH level (P < 0.01).

A 20-min ioPTH measurement is useful in preventing unnecessary BNE in some patients who undergo focused parathyroidectomy with a delayed >50% ioPTH drop.

In the United States, the number of parathyroidectomies among patients with chronic dialysis has remained stable in the last decade. A fall in serum calcium concentration is common postparathyroidectomy in patients with hyperparathyroidism, which usually resolves in 2-4 days. A severe drop in serum total calcium concentration less than 2.1 mmol/L and/or prolonged hypocalcemia for more than 4 days postparathyroidectomy is called hungry bone syndrome (HBS). Concomitant hypophosphatemia, hypomagnesemia, and hyperkalemia can be seen. Hypocalcemia and hypophosphatemia can persist for months to years. In contemporary clinical practice, HBS may be more commonly seen in patients with secondary compared to primary hyperparathyroidism. Preoperative radiological changes in bone, elevated serum alkaline phosphatase and parathyroid hormone (PTH) levels, and high numbers of osteoclasts on bone biopsy may identify patients at risk. Treatment consists of high-dose oral calcium and calcitriol supplementation. A low-dose pamidronate infusion 1-2 days prior to surgery may prevent HBS.

Recent in-vitro studies reported net calcium movement into bone because of a sudden fall in serum PTH level after a prolonged period of elevation. This supports a previous hypothesis that a sudden drop in serum PTH level after surgery results in the unopposed action of osteoblasts and influx of calcium into bone.

Incidence of HBS and its association with morbidity and mortality remains unclear in contemporary clinical practice. It is more common to encounter HBS in chronic dialysis patients with secondary hyperparathyroidism than those with primary hyperparathyroidism that undergo parathyroidectomies. Use of bisphosphonates to prevent HBS should be explored in future studies.

Many adjuncts guide surgical decision making in parathyroidectomy, yet their independent associations with outcome are poorly characterized. We examined a broad range of perioperative factors and used multivariate techniques to identify independent predictors of operative failure (persistent disease) after parathyroidectomy.

This was a retrospective review of 2239 patients with primary hyperparathyroidism who underwent parathyroidectomy at a single-center from 1999 to 2014. We used multivariate logistic regress to measure associations between multiple perioperative factors and an operative failure (persistent hypercalcemia).

Operative failure was identified in 67 patients (3.0%). The following variables were independently associated with operative failure on multivariate analysis: IOPTH criteria met (protective, OR = 0.22, P < 0.001), preoperative calcium (risk factor, OR = 2.27 per unit increase, P < 0.001), weight of excised gland(s) (protective, OR = 0.70 per two-fold increase, P = 0.003), and preoperative PTH (protective, OR = 0.55 per two-fold increase, P = 0.008).

In addition to the well-established IOPTH criteria, we suggest that consideration of the above independent perioperative risk factors may further inform surgical decision-making in parathyroidectomy.

During parathyroidectomy with intraoperative parathyroid hormone monitoring, the successful removal of a hypersecreting gland(s) resulting in normocalcemia is indicated by a >50% decrease in intraoperative parathyroid hormone level, typically into the normal range. Some patients, however, will have baseline parathyroid hormone levels within the normal range. We sought to determine the utility of intraoperative parathyroid hormone testing in these patients.

We retrospectively studied all patients who underwent parathyroidectomy for primary hyperparathyroidism at our institution over a 10-year period.

Overall, 317 (17%) patients had parathyroid hormone within the normal range at the onset of operation (baseline intraoperative parathyroid hormone), and 1,544 (83%) had classic primary hyperparathyroidism. The intraoperative parathyroid hormone degradation was slower in normal baseline intraoperative parathyroid hormone patients than classic primary hyperparathyroidism patients, though this did not reach statistical significance (P < .254). A >50% intraoperative parathyroid hormone decrease predicted cure in 98.7% of normal baseline patients and 98.8% of classic primary hyperparathyroidism patients (P = .810). Normal baseline patients had a lesser cure rate the longer it took to achieve a 50% decrease intraoperatively; however, the cure rate was constant at any time point the 50% decrease occurred in patients with classic primary hyperparathyroidism (P < .05).

The 50% rule delineating operative cure can be applied with equal confidence to patients with normal range, baseline intraoperative parathyroid hormone. Moreover, the time at which the 50% drop is achieved impacts operative success rates in these patients.

The usefulness, the methods and the criteria of intra-operative monitoring of the parathyroid hormone (ioPTH) during parathyroidectomy (PTX) for renal secondary hyperparathyroidism (rSHPT) in patients on chronic hemodialysis remain still matter of debate. The present study aimed to evaluate the ability of a low cost central-laboratory second generation PTH assay to predict an incomplete resection of parathyroid glands (PTG).

The ioPTH decay was determined In 42 consecutive patients undergoing PTX (15 subtotal and 27 total without auto-transplant of PTG) for rSHPT. The ioPTH monitoring included five samples: pre-intubation, post-manipulation of PTG and at 10, 20 and 30min post-PTG excision. The patients with PTH exceeding the normal value (65pg/ml) at the first postoperative week, 6 and 12months were classified as persistent rSHPT.

The concentrations of ioPTH declined significantly over time in patients who received total or subtotal PTX; however, no difference was found between the two types of PTX. Irrespective of the type of PTX and the number of PTG removed, combining the absolute and percentage of ioPTH decay at 30min after PTG excision, we found high sensitivity (100%), specificity (92%), negative predictive value (100%) and accuracy (93%) in predicting the persistence of rSHPT.

The monitoring of the ioPTH decline by a low cost central-laboratory second generation assay is extremely accurate in predicting the persistence of disease in patients on maintenance hemodialysis undergoing surgery for rSHPT.

Intraoperative parathyroid hormone (IOPTH) monitoring is a highly accurate surgical adjunct used to determine the extent of surgery in the setting of primary hyperparathyroidism. It is the successful interpretation of changes in PTH levels that is essential for using this technique in a way to optimize cure. Thus, it is imperative that the surgeon has an understanding of PTH dynamics and carefully chooses the appropriate IOPTH protocol and interpretation criteria that will best predict operative success, minimize unnecessary bilateral exploration, decrease the likelihood of resecting parathyroid glands that are not hypersecreting, and prevent recurrence.

Traditionally, bilateral cervical exploration for localization of all four parathyroid glands and removal of any that are grossly enlarged has been the standard surgical treatment for primary hyperparathyroidism (PHPT). With the advances in preoperative localization studies and greater public demand for less invasive procedures, novel targeted, minimally invasive techniques to the parathyroid glands have been described and practiced over the past 2 decades. Minimally invasive parathyroidectomy (MIP) can be done either through the standard Kocher incision, a smaller midline incision, with video assistance (purely endoscopic and video-assisted techniques), or through an ectopically placed, extracervical, incision. In current practice, once PHPT is diagnosed, preoperative evaluation using high-resolution radiographic imaging to localize the offending parathyroid gland is essential if MIP is to be considered. The imaging study results suggest where the surgeon should begin the focused procedure and serve as a road map to allow tailoring of an efficient, imaging-guided dissection while eliminating the unnecessary dissection of multiple glands or a bilateral exploration. Intraoperative parathyroid hormone (IOPTH) levels may be measured during the procedure, or a gamma probe used during radioguided parathyroidectomy, to ascertain that the correct gland has been excised and that no other hyperfunctional tissue is present. MIP has many advantages over the traditional bilateral, four-gland exploration. MIP can be performed using local anesthesia, requires less operative time, results in fewer complications, and offers an improved cosmetic result and greater patient satisfaction. Additional advantages of MIP are earlier hospital discharge and decreased overall associated costs. This article aims to address the considerations for accomplishing MIP, including the role of preoperative imaging studies, intraoperative adjuncts, and surgical techniques.

We investigated the rate of persistent and recurrent hyperparathyroidism after focused unilateral exploration (UE) with intraoperative monitoring of intact parathyroid hormone (IOPTH).

A prospective cohort of 915 patients with primary hyperparathyroidism (PHP) underwent parathyroid surgery by a single surgeon from January 2003 to September 2013. A total of 556 patients with at least a single positive preoperative localization by ultrasound (US) and/or sestamibi scan (STS) underwent UE with IOPTH. The criterion for completion of surgery was an IOPTH fall of 50% from the highest intraoperative level and into the normal range 5 to 10 minutes after resection of the localized gland.

Fifteen patients had either persistent or recurrent PHP, yielding a 2.7% (95% CI 1.6% to 4.4%) overall recurrence rate based on the refined Wilson method with continuity correction. Four patients had persistent PHP. Three of these patients were cured with reoperation, and the fourth patient was followed nonoperatively. Eleven patients had recurrent PHP, with 5 corrected by surgery and 6 patients followed nonoperatively. The mean postoperative serum calcium (Ca) level was 9.4 mg/dL over a mean follow-up interval of 44.0 months. Preoperative localization rates by each localization study were: US 74.3% (n = 413), STS 86.9% (n = 483), and US and STS 71.4% (n = 397). There was no difference in the preoperative study that localized the hyperfunctional parathyroid gland in recurrent vs nonrecurrent patients by the Fisher's exact test (US, p =1.00; STS, p =0.65; US and STS, p =1.00).

The low rate of recurrent PHP after focused unilateral exploration with IOPTH suggests that this procedure should not be abandoned.

To determine the sensitivity and clinical application of 4-dimensional computed tomography (4D CT) for the localization of patients with primary hyperparathyroidism when ultrasonography (US) and sestamibi scans (STS) are negative.

We compiled a database of 872 patients with primary hyperparathyroidism who underwent parathyroid operation by a single surgeon from January 2003 to September 2013. Seventy-three patients who failed to have positive localization by US or STS were identified. Thirty-six underwent operation without a preoperative 4D CT, and 37 underwent operation after 4D CT.

In patients not localized by US or STS, 4D CT was 89% sensitive in localizing an abnormal parathyroid gland when reviewed blindly by a radiologist specializing in endocrine localization studies, yielding a positive likelihood ratio of 0.89 and positive predictive value of 74%. Sensitivity, positive likelihood ratio, and positive predictive value for correct gland lateralization were 93%, 0.93, and 80%. The average size of parathyroid glands removed after preoperative localization by 4D CT was 404 mg and 0.57 cm3 (SD = 280, 0.64), compared with 259 mg and 0.39 cm3 (SD = 166, 0.21) in patients not localized by 4D CT. A focused, unilateral exploration was performed in 38% of patients with preoperative localization by 4D CT compared with 19% of patients without 4D CT (χ2 = 3.0, P = .041).

4D CT provided a positive localization in a clinically substantial number of patients not able to be localized by US or STS, which enabled an increased rate of successful, focused, unilateral operations compared with patients who did not undergo a 4D CT.

After parathyroidectomy for sporadic primary hyperparathyroidism (PHPT), overall rates of persistence/recurrence are extremely low. A marker of increased risk for persistence/recurrence is needed. We hypothesized that final intraoperative parathyroid hormone (FioPTH) ≥40 pg/mL is indicative of increased risk for disease persistence/recurrence, and can be used to selectively determine the degree of follow-up.

A retrospective review of PHPT patients undergoing parathyroidectomy with ioPTH monitoring was performed. An ioPTH decline of 50 % was the only criteria for operation termination. Patients were grouped based on FioPTH of <40, 40-59, and >60 pg/mL.

Between 2001 and 2012, 1,371 patients were included. Mean age was 61 ± 0.4 years, and 78°% were female. Overall persistence rate was 1.4°%, with a 2.9°% recurrence rate. Overall, 976 (71°%) patients had FioPTH < 40, 228 (16.6°%) had FioPTH 40-59, and 167 (12.2°%) had FioPTH ≥60. Mean follow-up was 21 ± 0.6 months. Patients with FioPTH <40 were younger, with lower preoperative serum calcium, PTH, and creatinine (all p ≤ 0.001). Patients with FioPTH <40 had the lowest persistence rate (0.2 %) versus patients with FioPTH 40-59 (3.5 %) or FioPTH ≥60 (5.4 %; p < 0.001). Recurrence rate was also lowest in patients with FioPTH <40 (1.3 vs. 5.9 vs. 8.2 %, respectively; p < 0.001). Disease-free status was greatest in patients with FioPTH <40 at 2 years (98.5 vs. 96.8 vs. 90.5 %, respectively) and 5 years (95.7 vs. 72.3 vs. 74.8 %, respectively; p < 0.01).

Patients with FioPTH < 40 pg/mL had lower rates of persistence and recurrence, than patients with FioPTH 40-59, or ≥60. Differences became more apparent after 2 years of follow-up. Patients with FioPTH ≥40 pg/mL warrant close and prolonged follow-up.

The biochemical profile of classic primary hyperparathyroidism (pHPT) consists of both elevated calcium and parathyroid hormone levels. The standard of care is parathyroidectomy unless prohibited by medical comorbidities. Because more patients are undergoing routine bone density evaluation and neck imaging studies for other purposes, there is a subset of people identified with a biochemically mild form of the pHPT that expresses itself as either elevated calcium or parathyroid hormone levels. These patients often do not fall into the criteria for operation based on the National Institutes of Health consensus guidelines, and they can present a challenge of diagnosis and management. The purpose of this paper is to review the available literature on mild pHPT in an effort to better characterize this patient population and to determine whether patients benefit from parathyroidectomy. Evidence suggests that there are patients with mild pHPT who have overt symptoms that are found to improve after parathyroidectomy. There is also a group of patients with biochemically mild pHPT who are found to progress to classic pHPT over time; however, it is not predictable which group of patients this will be. Early intervention for this group with mild pHPT may prevent progression of bone, psychiatric, and renal complications, and parathyroidectomy has proven safe in appropriately selected patients at high volume centers.

Parathyroidectomy is the most cost-effective treatment for hyperparathyroidism. Randomized prospective trials have shown no difference in cure rate between focused parathyroidectomy and bilateral exploration. Costs of the two techniques differ depending on the preoperative and intraoperative localization used, speed of the operation, ability to discharge the patient on the same day as the operation, cure rate, and complications. It may be less costly and more effective to use a policy of routine 4-gland exploration without the use of preoperative or intraoperative localization studies. The potential economic impact and the expected outcome of the various strategies should be formally evaluated.

Some published criteria for intraoperative monitoring of PTH serum concentrations may cause misleading results, since the timing of samples measured between the pre-incision and pre-excision phase of surgery is often unrecorded. In our opinion this information is critical, as the time of an intermediate sample during surgical manipulation may represent the "true" beginning of the PTH decay. We modified the usual criterion of monitoring (cut-off at 10 minutes after clamping) proposing a further check at manipulation in case the primary check at clamping produces an apparently negative result. On the basis of a mathematical model, false negative curves were simulated by means of a time shift. This shift was assumed to be the interval between manipulation and clamping. Analysing the decay curve, we used the 50% cut-off at 10 minutes after the supposed "true" origin (clamping or manipulation). Using a rapid immunochemiluminometric assay (ICMA), data were collected from 22 patients successfully operated for parathyroid adenoma. The check at clamping correctly diagnosed 13 patients. Among the 9 false negative cases, 6 were correctly diagnosed considering the manipulation as the baseline value. In the remaining 3 patients, diagnosis required prolonged observation of the curves. In case the iPTH decay does not follow the expected curve, it can be useful to check the decay normalising to a pre-excision value. The advantages of our criterion are both the prompt recognition of false negative results and the construction of a "true" decay curve for each patient, supporting the surgeon during the excision of hyperfunctioning parathyroid tissue.

Minimally invasive parathyroidectomy using intraoperative parathyroid hormone monitoring remains the standard approach to the majority of patients with primary hyperparathyroidism. This study demonstrates that individual patient characteristics do not affect existing criteria for intraoperative parathyroid hormone monitoring.

To identify patient characteristics, such as age, sex, race, body mass index (BMI), and renal function, that may affect existing criteria for intraoperative parathyroid hormone (IOPTH) levels during minimally invasive parathyroidectomy.

Retrospective review of a prospectively collected parathyroid database populated from August 2005 to April 2011.

Academic medical center.

Three hundred six patients with sporadic primary hyperparathyroidism who underwent initial parathyroidectomy between August 2005 and April 2011.

All patients underwent minimally invasive parathyroidectomy with complete IOPTH information.

Individual IOPTH kinetic profiles were fitted with an exponential decay curve and individual IOPTH half-lives were determined. Univariate and multivariate analyses were performed to determine the association between patient demographics or laboratory data and IOPTH half-life.

Mean age of the cohort was 60 years, 78.4% were female, 90.2% were white, and median BMI was 28.3. Overall, median IOPTH half-life was 3 minutes, 9 seconds. On univariate analysis, there was no association between IOPTH half-life and patient age, renal function, or preoperative serum calcium or parathyroid hormone levels. Age, BMI, and an age × BMI interaction were included in the final multivariate median regression analysis; race, sex, and glomerular filtration rate were not predictors of IOPTH half-life. The IOPTH half-life increased with increasing BMI, an effect that diminished with increasing age and was negligible after age 55 years (P = .001).

Body mass index, especially in younger patients, may have a role in the IOPTH half-life of patients undergoing parathyroidectomy. However, the differences in half-life are relatively small and the clinical implications are likely not significant. Current IOPTH criteria can continue to be applied to all patients undergoing parathyroidectomy for sporadic primary hyperparathyroidism.

Intra-operative parathyroid hormone (IOPTH) kinetics and therefore the efficacy of IOPTH utilization as a predictor of cure are likely to be affected by baseline IOPTH levels, vitamin D deficiency and parathyroid weight.

Consecutive subjects with primary hyperparathyroidism (PHPT, n = 51) undergoing parathyroidectomy with IOPTH monitoring were studied prospectively during the period October 2009-November 2011. Samples were collected pre-incision, pre-excision and post-excision (5, 10, 15 min). Iterative analysis of IOPTH kinetics and half-life calculation was carried out in subgroups. Nonparametric testing was used for group statistics.

Hypovitaminosis D (25(OH)D3 < 50 nm) was present in 39 (76%), serum PTH > 1000 ng/l in 23 (45%), and giant parathyroid adenoma (weight > 3000 mg) in 23 (45%). The percentage drop at 10 min was significantly higher in large adenomas (weight > 3000 mg). Miami and 5 min criteria showed the highest negative predictive value and maximum accuracy. The average percentage IOPTH drop observed at 5 min post-excision was 79.8%. Kinetic analysis showed a mean half-life of PTH of 2.57 ± 0.27 min (range: 0.07-11.55).

IOPTH monitoring is reliable even in patients with extremely high baseline IOPTH value, with a greater percentage drop at 5 and 10 min post-excision. In patients with high baseline IOPTH, a 50% decay in PTH value at 5 min may be indicative of cure, obviating the need for 10 and 15 min samples. IOPTH kinetics are altered by adenoma weight but not affected by vitamin D status or baseline IOPTH levels.

We hypothesized that patients referred for the evaluation and management of primary hyperparathyroidism (pHPT) often do not have pHPT and that they may be harmed by unwarranted parathyroidectomy (PTX).

We reviewed all patients who were referred to our endocrine surgery practice between 2008 and 2011 with International Classification of Diseases, Ninth Revision codes for HPT (252.00), benign or malignant parathyroid tumors (227.1, 194.1, respectively), or hypercalcemia (275.42). Patients with renal failure were excluded. Clinical parameters for investigation included age, sex, presentation, laboratories, imaging studies, and referring physician.

Three hundred twenty-four patients were referred for pHPT. The diagnosis was confirmed in 265 (82%), of whom 211 (80%) underwent PTX. Misdiagnoses occurred in 60 of 324 patients (19%). Of these, 54 (90%) had secondary HPT and 6 (10%) had hypercalcemia but no pHPT. Before referral, 70% of misdiagnosed patients underwent localizing studies, 57% of which suggested a positive finding.

Considerable confusion exists regarding the differentiation of primary and secondary HPT. Surgeons should be cautioned that patients who are referred for parathyroidectomy, even those with complete laboratory and radiographic evaluations, might not have pHPT at all.

Parathyroid hormone (PTH) secretion is partially regulated by circulating catecholamines. We examined the effect of different anesthetic techniques on intraoperative PTH (IOPTH) levels in patients undergoing parathyroidectomy for primary hyperparathyroidism.

We prospectively studied 132 patients divided into 3 anesthetic cohorts: monitored anesthetic care (MAC; n = 45), general anesthesia with laryngeal mask airway (LMA; n = 43), or general endotracheal anesthesia (GETA; n = 39). IOPTH levels were drawn before induction and at defined intervals postinduction.

All anesthetic techniques increased IOPTH levels from preinduction to 3 minutes postinduction (MAC, 28%; LMA, 45%; GETA, 65%; P < .001). Temporal trends in postinduction IOPTH levels were similar in patients receiving general anesthesia, characterized by a peak effect at 6 minutes. Using a multivariate logistic regression analysis, GETA was >7 times more likely to increase the preinduction IOPTH by ≥ 50% at 3 minutes postinduction compared with MAC (P < .0001). Using immediate postinduction IOPTH levels in surgical decision making would have led to failed surgery in 2 of 6 patients with multiple gland disease receiving GETA.

Preincision IOPTH samples should be drawn before induction to avoid incorporation of potentially misleading anesthetic-related IOPTH elevations into surgical decision making.