Intraoperative Monitoring Of Intact Parathyroid Hormone Research Articles

Therapeutic and diagnostic algorithm for preoperative prediction of sporadic multigland parathyroid disease

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrinological disease that is characterized by autonomic increased synthesis of parathyroid hormone (PTH) with elevated or upper-normal levels of blood calcium [1]. In 80–85% of cases, the cause of sporadic PHPT is an adenoma of one parathyroid gland (PTG) (sigle-gland parathyroid disease), in 20–25% — a lesion of a larger number of PTGs (hyperplasia of all glands or double adenomas — multigland parathyroid disease) [2]. The complexity of clinical and laboratory prediction, low sensitivity of imaging methods, poor assessment of the radicalness of the operation by intraoperative monitoring of intact PTH (IMiPTH) are the components of the problem of multiple lesions in PHPT. Therefore, the improvement of existing and the development of new methods for diagnosing and treating this variant of the disease are urgent tasks of modern endocrine surgery.AIM: To develop an algorithm for the diagnosis and treatment of PHPT, aimed at preoperative detection of multigland parathyroid disease.MATERIALS AND METHODS: The study was based on a study of a continuous sample of 208 patients, of which 34 with multigland parathyroid disease in PHPT, 95 with single-gland parathyroid disease in PHPT, 69 with secondary hyperparathyroidism on renal replacement therapy (RRT) with hemodialysis, and 10 with tertiary hyperparathyroidism on RRT of LT. The work was performed on the basis of clinical, laboratory, instrumental, morphological and immunohistochemical studies. The nature of the expression of the calcium-sensitive receptor and the vitamin D receptor in the studied groups was studied as a pathogenetic substantiation of the proposed algorithm [3]. Based on the study of clinical and laboratory parameters and the results of preoperative imaging methods, predictors of multigland parathyroid disease in PHPT [4,5] were established, and a method for differential diagnosis of PTG lesions in PHPT was developed [6]. In addition, the results of surgical treatment of patients with multiple PTG lesions in various clinical variants of hyperparathyroidism were studied [7]. RESULTS: The proposed algorithm is used when the diagnosis of PHPT is already established and there are indications for surgical treatment. First of all, the level of GFR (CKD-EPI) is assessed in conjunction with the results of the “gold standard” preoperative imaging methods (ultrasound and scintigraphy), with an assessment of the number of localized increased PTG and the consistency of the results of preoperative methods.At a GFR level of more than 73 ml/min/1.73 m2, an increase of only 1 PTG according to the results of 2 imaging methods, provided that they are consistent, the PHPT variant is defined as a sigle-gland parathyroid disease. If there is an inconsistency between the 2 methods of preoperative imaging, we recommend calculating the scores according to the differential diagnosis scale for multiple lesions in PHPT [6]. At a GFR level of less than 73 ml/min/1.73 m2, an increase of >1 PTG according to the results of 2 imaging methods, we recommend calculating points according to the proposed scale [6].With the established variant of PHPT — sigle-gland parathyroid disease, the patient undergoes selective parathyroidectomy (PTE) with IMiPTH. When iPTH drops to reference values, the test is considered positive, and the operation ends there. If the test result is negative, a second test is required after 10 minutes. In the event that the repeated test is also negative, then the patient is shown a bilateral neck exploration (BNE) in accordance with the tactics for multigland parathyroid disease (see below).With the established variant of PHPT — multigland parathyroid disease, the following tactics are used:BNE with obligatory exploration of all four PTGs;Macroscopic assessment of the PTG found.When making a decision about 2 pathologically changed enlarged PTG, and 2 others are intact and not enlarged, a double PTE with IMiPTH is performed. If after the removal of 2 pathologically altered PTGs, the IMiPTH test is negative, then a second one is necessary after 10 minutes. In the event that the repeated test is negative, then from the 2 recognized intact ones, the least altered is determined and the scope of the operation is expanded to subtotal PTE (3.5 PTG), leaving ½ of the least altered PTG. The operation ends here.When deciding that 3 or more PTG are pathologically changed and enlarged, a subtotal PTE with IMiPTH is performed. In case of a negative IMiPTH test, the places of possible ectopic location of the PTG are examined: thyrothymic ligaments, upper thymus horns, fatty tissue along the carotid arteries. If there are no ectopically located PTGs in the indicated places, the operation is completed.CONCLUSION: The proposed treatment and diagnostic algorithm is pathogenetically substantiated, aimed at preoperative detection of multiple PTG lesions in PHPT and will improve the quality of life of this group of patients by reducing the persistence of the disease.

Treatment for secondary hyperparathyroidism focusing on parathyroidectomy.

Secondary hyperparathyroidism (SHPT) is a major problem for patients with chronic kidney disease and can cause many complications, including osteodystrophy, fractures, and cardiovascular diseases. Treatment for SHPT has changed radically with the advent of calcimimetics; however, parathyroidectomy (PTx) remains one of the most important treatments. For successful PTx, removing all parathyroid glands (PTGs) without complications is essential to prevent persistent or recurrent SHPT. Preoperative imaging studies for the localization of PTGs, such as ultrasonography, computed tomography, and 99mTc-Sestamibi scintigraphy, and intraoperative evaluation methods to confirm the removal of all PTGs, including, intraoperative intact parathyroid hormone monitoring and frozen section diagnosis, are useful. Functional and anatomical preservation of the recurrent laryngeal nerves can be confirmed via intraoperative nerve monitoring. Total or subtotal PTx with or without transcervical thymectomy and autotransplantation can also be performed. Appropriate operative methods for PTx should be selected according to the patients' need for kidney transplantation. In the case of persistent or recurrent SHPT after the initial PTx, localization of the causative PTGs with autotransplantation is challenging as causative PTGs can exist in the neck, mediastinum, or autotransplanted areas. Additionally, the efficacy and cost-effectiveness of calcimimetics and PTx are increasingly being discussed. In this review, medical and surgical treatments for SHPT are described.

Intraoperative intact parathyroid hormone monitoring and frozen section diagnosis are essential for successful parathyroidectomy in secondary hyperparathyroidism.

Total parathyroidectomy (PTx) is often performed to treat secondary hyperparathyroidism (SHPT). Successful PTx is essential to prevent recurrent and persistent SHPT because remnant parathyroid glands (PTGs) in the neck can be stimulated and may secrete excessive parathyroid hormone (PTH) in end-stage renal disease. However, to date, few studies have investigated factors contributing to successful PTx before the completion of surgery. Between August 2010 and February 2020, 344 patients underwent total PTx, transcervical thymectomy, and forearm autograft for SHPT at our institute. Factors contributing to successful PTx before the completion of surgery were investigated. Preoperative imaging diagnoses, including computed tomography, ultrasonography, technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy, intraoperative intact PTH (IOIPTH) monitoring, and frozen section histologic diagnosis, were performed. Successful PTx was defined as intact PTH level < 60 pg/mL on postoperative day 1. A sufficient decrease in IOIPTH level was defined as > 70% decrease in intact PTH levels measured 10 min after total PTx and transcervical thymectomy compared to intact PTH levels measured before skin incision. Logistic regression analysis was conducted to investigate factors contributing to PTx success. Univariate analysis showed that the number of all PTGs identified preoperatively by imaging modalities and the specimens submitted for frozen section diagnosis, which surgeon presumed to be PTGs, were not significant factors contributing to successful PTx. However, multivariate analysis revealed that the number of PTGs identified by frozen section diagnosis (P < 0.001, odds ratio [OR] 4.356, 95% confidence interval [CI] 2.499-7.592) and sufficient decrease in IOIPTH levels (P = 0.001, OR 7.847, 95% CI 2.443-25.204) significantly contributed to successful PTx. Sufficient intact PTH level decrease observed on IOIPTH monitoring and the number of PTGs identified by frozen section diagnosis contributed to successful PTx for SHPT. IOIPTH monitoring and frozen section diagnosis are essential for achieving successful PTx for SHPT.

Diagnostic Accuracy of Intraoperative Intact Parathyroid Hormone Monitoring for Surgical Outcomes of Secondary Hyperparathyroidism.

BackgroundIntraoperative intact parathyroid hormone (IO-iPTH) monitoring has not reached a consensus in predicting surgical outcomes of secondary hyperparathyroidism. Here, we explore the predictive effect of IO-iPTH monitoring on surgical outcomes of secondary hyperparathyroidism as a potentially effective standard.Material/MethodsWe enrolled 119 patients who underwent total parathyroidectomy with autotransplantation from January 2016 to August 2019. Intact parathyroid hormone (iPTH) levels were tested 1 day before surgery (iPTHpre), 10 min after glands resection (iPTH10min), and 1 and 7 days after the operation (iPTHd1, iPTHd7). According to iPTHpre levels, patients were divided into a <2000 pg/ml group and a ≥2000 pg/ml group, and the cutoff values were compared. In patients with successful parathyroidectomy, the value of iPTHpre minus iPTH10min (iPTHdec) and relative-iPTH10min were compared between groups.ResultsUsing cutoff values, the predictive criterion was defined as iPTH10min ≤314.5 pg/ml or relative-iPTH10min ≤12.4%. In the iPTHpre ≥2000 pg/ml group, iPTH10min had a higher predictive value (318 pg/ml vs 218 pg/ml) whereas relative-iPTH10min had a lower predictive value (12.1% vs 20.3%). In patients with successful PTX, the iPTHdec value of the iPTHpre ≥2000 pg/ml group was significantly higher than that of the <2000 pg/ml group. Additionally, the relative-iPTH10min was significantly lower in the ≥2000 pg/ml group than in the <2000 pg/ml group.ConclusionsAn intraoperative predictive criterion of iPTH10min ≤314.5 pg/ml or relative-iPTH10min ≤12.4% is associated with effectively predicting surgical success of secondary hyperparathyroidism. The predictive value is affected by iPTHpre level; therefore, a variable prediction standard based on iPTHpre levels shall be established.

A Retrospective Study of the Impact of Intraoperative Intact Parathyroid Hormone Monitoring During Total Parathyroidectomy for Secondary Hyperparathyroidism

A Retrospective Study of the Impact of Intraoperative Intact Parathyroid Hormone Monitoring During Total Parathyroidectomy for Secondary Hyperparathyroidism

A Retrospective Study of the Impact of Intraoperative Intact Parathyroid Hormone Monitoring During Total Parathyroidectomy for Secondary Hyperparathyroidism: STARD Study.

The study aimed to evaluate the diagnostic accuracy of intraoperative intact parathyroid hormone (IO-iPTH) in patients with secondary hyperparathyroidism (HPT).The cut-off for IO-iPTH monitoring remains unknown.This was a single-center retrospective review of 226 consecutive patients (107 males and 119 females) who underwent parathyroidectomy data for secondary HPT between May 2010 and March 2014. The predetermined cut-off for IO-iPTH was a 70% IO-iPTH drop from baseline 10 minutes after total parathyroidectomy and thymectomy. We used <60 pg/mL iPTH value on postoperative day 1 (POD1) as an indicator of successful removal of parathyroid glands and reviewed the frequency of reoperation other than in autografted sites during the observation period. This study was based on the Standards for the Reporting of Diagnositic accuracy compliant.The reoperation rate in patients with >60 pg/mL iPTH value (POD1) was significantly higher than that in patients with <60 pg/mL iPTH value (POD1), (13.0% versus 0.5% P = 0.003). Sensitivity, specificity, and accuracy of >70% IO-iPTH drop were 97.5%, 52.2%, and 92.9%, respectively, this criterion was demonstrated to be beneficial in 26 patients. In 5 patients, <70% IO-iPTH drop was observed and further exploration enabled sufficient removal of parathyroid glands. In 21 patients, although fewer than 4 parathyroid glands were removed after enough explorations, >70% IO-iPTH drop enabled termination of operations and iPTH value (POD1) was <60 pg/mL.An iPTH value of <60 pg/mL (POD1) was a good predictor for successful parathyroidectomy. A 70% IO-iPTH drop from the baseline was appropriate to determine sufficient parathyroid gland removal during parathyroidectomy for patients with secondary HPT.

No Need to Abandon Focused Unilateral Exploration for Primary Hyperparathyroidism with Intraoperative Monitoring of Intact Parathyroid Hormone

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.

Can the use of intraoperative intact parathyroid hormone monitoring be abandoned in patients with hyperparathyroidism?

BackgroundUltrasound (US) and technetium-99m sestamibi scintigraphy (MIBI) are used to determine the localization of abnormal glands in cases of primary hyperparathyroidism (PHPT). Intraoperative intact parathyroid hormone (iPTH) monitoring is a reliable examination used to cure PHPT. The aim was to assess the necessity of intraoperative iPTH monitoring. MethodsSixty patients were examined using preoperative MIBI and US. iPTH was measured at 3 time points: (1) at the start of surgery; (2) 10 minutes after gland resection; and (3) more than 60 minutes after surgery. We defined a decreased iPTH level as an iPTH measured 10 minutes after resection that was less than 50% of the preoperative level. ResultsThe iPTH of 55 patients with concordant lesions decreased to within the normal range more than 60 minutes after surgery. ConclusionsIt is not necessary to monitor intraoperative iPTH when single concordant lesions are preoperatively identified on both MIBI and US.

Validity and limits of intraoperative parathyroid hormone monitoring during minimally invasive parathyroidectomy: a 10-year experience

The availability of intraoperative intact parathyroid hormone monitoring allows the success of minimally invasive parathyroidectomy to be ensured during the operation. However, false-negative results leading to unnecessary explorations and difficulties in interpreting the data raise concern about the effectiveness of the method. Patients with primary hyperparathyroidism (pHPT) and one unequivocally enlarged parathyroid gland on preoperative ultrasound or (99m)Tc-SestaMIBI scintigraphy underwent minimally invasive video-assisted parathyroidectomy according to the technique initially described by Miccoli. Intraoperatively, rapid electrochemiluminescence immunoassay was used to measure intact parathyroid hormone (iPTH) levels before the operation, after complete mobilization of the adenoma (preexcision value), and 5, 10, and 15 min after the excision. The operation was considered successful when more than a 50% decrease in preexcision iPTH levels and subsequent attainment of the normal range within 15 min were observed. Between November 1999 and November 2009, 235 (43%) of 546 patients with pHPT were eligible for a minimally invasive approach. Intraoperative iPTH monitoring showed 221 true-positive, 1 false-positive, 6 false-negative, and 7 true-negative results. This calculated to a sensitivity of 97% and a specificity of 88%. Despite the availability of high-resolution ultrasound and (99m)Tc-SestaMIBI scintigraphy, the presence of multiple glandular disease cannot be ruled out completely. Although the authors observed six false-negative results, they believe that intraoperative iPTH monitoring represents a valuable asset for minimally invasive parathyroidectomy because it identifies sporadic hyperplasia.

Minimally invasive parathyroid surgery in 103 patients with local/regional anesthesia, without exclusion criteria

Background. Parathyroid surgery for sporadic primary hyperparathyroidism (pHPT) can be accomplished with local/regional anesthesia and intraoperative monitoring of intact parathyroid hormone without exclusion criteria through a 1.0- to 1.25-inch (2.5- to 3.2-cm) incision (MIPL) in a high proportion of patients. Methods. One hundred thirty-one consecutive patients with pHPT were offered MIPL. One hundred three patients elected to have this procedure. Patients were not excluded because of inadequate localization, previous parathyroid surgery, or need for concomitant thyroid surgery. Preoperative localization with ultrasound and/or sestamibi-single photon emission computed tomography scan was done in all patients. Almost all patients had intraoperative monitoring of intact parathyroid hormone (IMPTH). Results. MIPL was accomplished in 89 of these 103 patients (86.4%), but 14 required conversion to general anesthesia. The main reasons for conversion were concomitant thyroid surgery, no positive preoperative localization, and previous parathyroid surgery. This procedure was accomplished in 13 patients requiring a bilateral procedure, 5 patients requiring thyroid surgery, 4 patients with no positive preoperative localization, and in 3 patients with previous parathyroid surgery. The complications of MIPL were comparable to the traditional bilateral exploration with general anesthesia. No patient experienced permanent hypoparathyroidism or postoperative bleeding. Two patients had transient recurrent laryngeal nerve paresis, and surgery failed to correct hypercalcemia in 5 (4.9%) of the patients. There appears to be less need for antiemetic medication in the MIPL patients compared with patients who had general anesthesia. Conclusions. Parathyroid surgery for sporadic pHPT can be accomplished through a 1.0- to 1.25-inch (2.5- to 3.2-cm) incision with local/regional anesthesia, without exclusion criteria. Accurate preoperative localization, particularly localization to the same site by both ultrasound and 99mTc-sestamibi scan, and IMPTH can limit the surgery to a unilateral approach. One should be cautious in proceeding with MIPL in patients with need for concomitant thyroid surgery, no preoperative localization, or previous parathyroid surgery. (Surgery 2002;131:502-8.)