Is intraoperative parathyroid monitoring during minimally invasive parathyroidectomy still justified?

Introduction: Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. With parathyroidectomy, a cure rate of over 95% at initial surgery is reported. Localization of the abnormal parathyroid gland is critical for the operation to be successful. The aim of this study is to analyze data of patients with single gland disease (SGD) and positive concordant localization imaging undergoing minimally invasive parathyroidectomy (MIP) and intraoperative parathyroid hormone monitoring (IOPTH) to evaluate if IOPTH is still justified in patients with localized SGD. Methods: A retrospective database analysis of all minimally invasive operations with IOPTH for PHPT and positive concordant localization in ultrasound (US) and 99mTc-sestamibi scintigraphy (MIBI) between 2016-2021. When both US and MIBI were negative, patients underwent either choline or methionine PET-CT. The patients were also analyzed a second time without applying IOPTH. Results: In total, 198 patients were included in the study. The sensitivity of US, MIBI and PET-CT was 96%, 94% and 100%, respectively. Positive predictive value was 88%, 89% and 94% with US, MIBI and PET-CT, respectively. IOPTH was true positive in 185 (93.4%) patients. In 13 (6.6%) patients, no adequate IOPTH decline was observed after localizing and extirpating the assumed enlarged parathyroid gland. Without IOPTH, the cure rate decreased from 195 (98.5%) to 182 (92%) patients and the rate of persisting disease increased from 2 (1.0%) to 15 (7.5%) patients. Conclusion: Discontinuing IOPTH significantly increases the persistence rate by a factor of 7.5 in patients with concordantly localized adenoma. Therefore, IOPTH appears to remain necessary even for this group of patients.

A 15-year experience: intraoperative parathyroid hormone assay for the management of primary hyperparathyroidism in a UK endocrine surgical unit.

PURPOSE: This study aims to evaluate the outcomes of first-time parathyroidectomy for primary hyperparathyroidism using intraoperative PTH (IOPTH) assay in the light of the UK National Institute for Health and Care Excellence (NICE) guidelines for the management of primary hyperparathyroidism. METHOD: This is a retrospective cohort analysis of a prospectively maintained database of endocrine surgery in a tertiary centre. Preoperative radiological localisation (concordance and accuracy), intraoperative PTH parameters and adjusted serum calcium at minimum 6-month follow-up were analysed. The accuracy of IOPTH to predict post-operative normocalcaemia and the number needed to treat (NNT) within the cohort when IOPTH was utilised were determined. Differences between groups were evaluated with Chi-squared and Fisher's exact test. RESULTS: Between January 2004 and September 2018, 849 patients (75.4% women), median age 64 years (IQR 54-72), were analysed. The median preoperative adjusted serum calcium was 2.80mmol/l (IQR 2.78-2.90), and the median preoperative PTH was 14.20pmol/l (IQR 10.70-20.25). The overall first-time cure (normocalcaemia) rate was 96.4%. The sensitivity, specificity, positive predictive value and negative predictive values of IOPTH were 96.8%, 83.2%, 97.6% and 78.8%, respectively, with an accuracy of 95.1%. For patients with concordant scans (48.3%), a targeted approach without IOPTH would have achieved a cure rate of 94.1% compared with 98.0% using IOPTH (p<0.01) CONCLUSION: The use of IOPTH assay significantly improved the rate of normocalcaemia at 6 months. The low NNT to benefit from IOPTH, particularly those patients with a single positive scan, and the inevitable reduction in the potential costs incurred from failure and reoperation justify its utilisation.

Positive predictive values of ultrasound-guided fine-needle aspiration with parathyroid hormone assay and Tc-99m sestamibi scintigraphy in sporadic primary hyperparathyroidism.

OBJECTIVES: Ultrasonography (US) and Tc-99m sestamibi scintigraphy (SS) are usually performed as preoperative imaging modalities for patients with sporadic primary hyperparathyroidism (SPHP). Fine-needle aspiration (FNA) under US guidance for parathyroid hormone (PH) assay can enhance the diagnostic accuracy of US. The main aim of the present study was to compare positive predictive values between US-FNA and SS. The secondary aim was to draw up a decision-tree for FNA and SS. METHODS: The single-center retrospective study included patients with previously non-operated SPHP. They underwent US-guided FNA, PET-CT SS, and 18 F-choline scintigraphy if the first two methods were inconclusive. PH washout level was considered pathological when greater than the serum PH level. Postoperative histology data were correlated to imaging data. RESULTS: In total, 117 patients were included, with a mean age of 64 years (range, 26-89 years). A single adenoma was identified on pathology in 101 patients (89%). FNA findings were pathologic for 64 patients (55%), with a mean PH level of 2,604ng/L [range, 585-9,074ng/L], higher than the serum level of 179ng/L [range, 60-1,000ng/L]. US-guided FNA showed sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of respectively 72%, 92%, 99% and 28%, compared to 89%, 42%, 93% and 32% for SS. The rate of error in locating the parathyroid gland was 8% for US-guided FNA versus 12% for SS. Comparison of the two methods showed better sensitivity for SS (P=0.0052) and better specificity for FNA (P=0.0143), with no significant difference in PPV or NPV. 18 F-choline scintigraphy detected the hyperfunctioning parathyroid in 11 out of the 15 patients. CONCLUSION: PPV did not significantly differ between FNA and SS. US-guided FNA performed by an experienced operator could be a simple first-line method for more than 50% of patients with non-operated SPHP, with 99% PPV. In case of negative or doubtful FNA findings, SS can be performed in second line.

Localization of Ectopic Mediastinal Parathyroid Adenomas Using Indigo Carmine Injection for Surgical Management: A Preliminary Report.

An ectopic parathyroid adenoma (EPA) is a rare entity. The aim of this study was to report our experience in the preoperative localization and surgical management of EPAs. This was a multicenter retrospective study involving patients diagnosed with an EPA (three males and seven females) from January 2005 to November 2021. The clinical features, preoperative management, and surgical procedures were analyzed. A cervical neck ultrasound was performed in all patients and showed a focus in eight patients. Cervicothoracic enhanced computed tomography was performed in all patients and showed a focus in nine patients. The 99mTc-MIBI scintigraphy was performed in eight patients and showed uptake in six of them. We performed a neck dissection and thoracotomy in one patient, a thoracoscopy in one patient, surgery with a focused approach in seven patients, four of whom were injected with indigo carmine blue, and surgery with a bilateral approach in one patient. 1 h following the parathyroidectomy, the parathyroid hormone (PTH) concentration was decreased to 40-80% of the baseline value. Establishing a preoperative diagnosis of an EPA is challenging for the surgeon, despite the progress in the morphologic assessment. An intraoperative PTH assay and injection of indigo carmine have been shown to be valuable tools in the appropriate surgical management of an EPA.

Application of Tissue Aspirate Parathyroid Hormone Assay for Imaging Suspicious Neck Lesions in Patients with Complicated Recurrent or Persistent Renal Hyperparathyroidism.

BACKGROUND: Comprehensive pre-reoperative localization is essential in complicated persistent or recurrent renal hyperparathyroidism. The widely used imaging studies sometimes lead to ambiguous results. Our study aimed to clarify the role of tissue aspirate parathyroid hormone (PTH) assay with a new positive assay definition for imaging suspicious neck lesions in these challenging scenarios. METHODS: All patients with complicated recurrent or persistent renal hyperparathyroidism underwent parathyroid sonography and scintigraphy. Echo-guided tissue aspirate PTH assay was performed in suspicious lesions revealed by localization imaging studies. The tissue aspirate PTH level was determined by an immunoradiometric assay. We proposed a newly-developed definition for positive assay as a washout level higher than one-thirtieth of the serum PTH level obtained at the same time. The final diagnosis after re-operation was confirmed by the pathologists. RESULTS: In total, 50 tissue aspirate PTH assays were performed in 32 patients with imaging suspicious neck lesions, including discrepant results between scintigraphy and sonography in 47 lesions (94%), unusual locations in 19 lesions (38%), multiple foci in 28 lesions (56%), and locations over previously explored areas in 31 lesions (62%). Among 39 assay-positive lesions, 13 lesions (33.3%) were not identified by parathyroid scintigraphy, and 28 lesions (71.8%) had uncertain parathyroid sonography findings. The final pathology in patients who underwent re-operative surgery proved the tissue aspirate PTH assays had a 100% positive predictive value. CONCLUSIONS: Our findings suggest tissue aspirate PTH assay with this new positive assay definition is beneficial to clarify the nature of imaging suspicious lesions in patients with complicated persistent or recurrent renal hyperparathyroidism.

[Re-operation treatment in uremic patients complicated with persistent secondary hyperparathyroidism after parathyroidectomy with autotransplantation].

Objective:To analyze the clinical profile and therapeutic effect of re-operation treatment in uremic patients complicated with persistent secondary hyperparathyroidism(SHPT)after parathyroidectomy with autotransplantation.Method:Twelve persistent SHPT patients who were treated with reoperation of paramyroidectomy(PTX)were enrolled in this study during the period from Jan 2014 to Jul 2017 in our hospital.We evaluated the location of the remaining parathyroid glands by ultrasonography,dual-phase 99 Tcm-sestamibi scintigraphy,CT and MR imaging of the neck before the operation.We resected the parathyroid gland tissue in situ,and the ectopic parathyroid glands hiding in thymus,mediastinal,tracheal esophageal groove,thyroid gland and other locations in the neck.During the surgery,nanocarbon imaging was used to help identify the parathyroid gland and parathyroid hormone assay(IOPTH)was measured at the end of the surgery.We observed the changes of clinical symptoms after the surgery and collected blood parameters including serum intact aramyroidhomone(i-PTH),calcium(Ca),phosphoms(P),calcium and phosphorus product before and after surgery.Complications and failure were also analyzed.Result:All the 12 patients underwented successful operation.The postoperative pathological results were hyperplastic parathyroid glands tissue.22 parathyroid glands were resected,among which 14 were located at the neck in situ,8 were ectopic,i.e.,located at thymus in 4 cases,superior mediastinum in 2 cases and thyroid parenchyma in 2 cases.The clinical symptoms were significantly improved including osteoarthritis,skin itching and limb weakness.The levels of serum iPTH,calcium,phosphorus and calcium and phosphorus product were significantly lower than those before operation(P<0.05).Ten patients presented hypocalcemia after surgery and the level of calcium returned to normal after supplement of calcium.Temporary injury of laryngeal nerve was found in4 cases,but there was no patient with transient bucking,dyspnea or death.No recurrence was found during 1 year follow-up.Conclusion:It was very important to locate the residual parathyroid gland accurately with a variety of imaging methods in uremic patients complicated with persistent or recurrent SHPT when they needed re-operation.Surgeons should explorate ectopic parathyroid gland according to the concept of the superior mediastinum dissection and the central compartment neck dissection.Meanwhile,the use of nanocarbon assisted parathyroid gland negative imaging and rapid IOPTH can significantly improve the success rate of surgery and reduce surgical complications.

Parathyroid Hormone Assays following Total Thyroidectomy: Is There a Predictive Value?

OBJECTIVES: Parathyroid hormone (PTH) is a risk marker for hypoparathyroidism (hypoPTH). This study aimed to determine the predictive values of early PTH assays carried out at the moment of skin closure (PTH SC), to establish a treatment algorithm, identifying two threshold values. We assessed the reproducibility of this approach with two different immunoassay kits (hypoPTH) after total thyroidectomy, but its practical application is not consensual. STUDY DESIGN: We conducted a prospective descriptive study, including all patients who underwent a total thyroidectomy between March 2012 and November 2013. Postoperative PTH SC levels, corrected calcium on postoperative days, and occurrence of hypoPTH symptoms were collected. RESULTS: Of 257 patients, the rate of hypoPTH was 20%. Threshold values to obtain a 100% positive predictive value to identify patients for whom hypoPTH was absolutely certain were: PTH SC <7 ng/L for the Roche kit and PTH SC <4 ng/L for the Beckman-Coulter kit. Threshold values to obtain a 100% negative predictive value to identify patients for whom the absence of hypoPTH was absolutely certain were: PTH SC ≥19 ng/L for the Roche kit and PTH SC ≥9 ng/L the Beckman-Coulter kit. CONCLUSIONS: A single serum PTH sampled at skin closure is a reliable test to predict hypoPTH after a total thyroidectomy. The use of a threshold based on a 100% negative predictive value enables patients with no risk of hypoPTH to be safely discharged within the first 24 h postoperatively without unnecessary calcium and vitamin treatment. This medication can be given promptly to patients at risk of hypoPTH to limit the occurrence of hypocalcaemia.

Re-operation treatment in uremic patients complicated with persistent secondary hyperparathyroidism after parathyroidectomy with autotransplantation / 临床耳鼻咽喉头颈外科杂志

To analyze the clinical profile and therapeutic effect of re-operation treatment in uremic patients complicated with persistent secondary hyperparathyroidism(SHPT)after parathyroidectomy with autotransplantation.Twelve persistent SHPT patients who were treated with reoperation of paramyroidectomy(PTX)were enrolled in this study during the period from Jan 2014 to Jul 2017 in our hospital.We evaluated the location of the remaining parathyroid glands by ultrasonography,dual-phase 99 Tcm-sestamibi scintigraphy,CT and MR imaging of the neck before the operation.We resected the parathyroid gland tissue in situ,and the ectopic parathyroid glands hiding in thymus,mediastinal,tracheal esophageal groove,thyroid gland and other locations in the neck.During the surgery,nanocarbon imaging was used to help identify the parathyroid gland and parathyroid hormone assay(IOPTH)was measured at the end of the surgery.We observed the changes of clinical symptoms after the surgery and collected blood parameters including serum intact aramyroidhomone(i-PTH),calcium(Ca),phosphoms(P),calcium and phosphorus product before and after surgery.Complications and failure were also analyzed.All the 12 patients underwented successful operation.The postoperative pathological results were hyperplastic parathyroid glands tissue.22 parathyroid glands were resected,among which 14 were located at the neck in situ,8 were ectopic,i.e.,located at thymus in 4 cases,superior mediastinum in 2 cases and thyroid parenchyma in 2 cases.The clinical symptoms were significantly improved including osteoarthritis,skin itching and limb weakness.The levels of serum iPTH,calcium,phosphorus and calcium and phosphorus product were significantly lower than those before operation(<0.05).Ten patients presented hypocalcemia after surgery and the level of calcium returned to normal after supplement of calcium.Temporary injury of laryngeal nerve was found in4 cases,but there was no patient with transient bucking,dyspnea or death.No recurrence was found during 1 year follow-up.It was very important to locate the residual parathyroid gland accurately with a variety of imaging methods in uremic patients complicated with persistent or recurrent SHPT when they needed re-operation.Surgeons should explorate ectopic parathyroid gland according to the concept of the superior mediastinum dissection and the central compartment neck dissection.Meanwhile,the use of nanocarbon assisted parathyroid gland negative imaging and rapid IOPTH can significantly improve the success rate of surgery and reduce surgical complications.

Protean Presentations of Parathyroid Adenoma in Childhood.

Parathyroid adenoma is a rare disease which is known to present with protean manifestations, leading to misdiagnosis in the initial stage of the disease. It is known to pose a diagnostic dilemma to the clinician, in which a high index of suspicion alone often leads to a proper diagnosis and timely management. We encountered two such cases who presented to us with varied presentation, in which nuclear scintigraphy along with intraoperative parathyroid hormone assay played a major role in diagnosis and management.

Is intraoperative parathyroid hormone monitoring necessary in symptomatic primary hyperparathyroidism with concordant imaging?

INTRODUCTION: Symptomatic primary hyperparathyroidism (PHPT) is still seen frequently in referral centers all over India. These patients require parathyroidectomy and this study aimed to assess the roll of intraoperative parathyroid hormone (PTH) assay when concordant results of two localization studies were available. STUDY DESIGN: We analyzed the case records of patients who underwent parathyroidectomy for PHPT from January 2005 to June 2015. RESULTS: Of 143 patients included in the study, technetium 99m methoxyisobutylisonitrate dual phase scintigraphy showed true positive images in 93.7% and high definition ultrasonography in 84.6% of patients. Concordance in localization studies was observed in 121 (84.6%) patients, successful parathyroidectomy was done in 117 (96.7%) patients with concordant localization studies. Intraoperative PTH monitoring showed 97.84% sensitivity and 75% specificity and predicted failure in 2 patients with concordant imaging. However, re-exploration was not successful in these patients. CONCLUSION: When concordant result is available between parathyroid scintigraphy and anatomical imaging surgical cure rate is high in trained hands. Re-exploration is unlikely to be successful since these patients require higher imaging.

Comparison of Intraoperative versus Postoperative Parathyroid Hormone Levels to Predict Hypocalcemia Earlier after Total Thyroidectomy.

OBJECTIVE: To determine differences in the mean parathyroid hormone (PTH) levels for normocalcemic and hypocalcemic total thyroidectomy patients who were tested for PTH during the intraoperative or early postoperative period. DATA SOURCES: MEDLINE, the Cochrane Database, and other databases from 1960 to 2014 in the English language and specific to humans for relevant articles. REVIEW METHODS: Studies were included if PTH was obtained within 24 hours of thyroidectomy. Studies were excluded (1) if only a hemithyroidectomy was performed, (2) if means of studied PTH values were not reported in the article, or (3) if the time of the PTH draw fell outside of defined "intraoperative" or "early postoperative" windows. PTH values were divided into 3 groups: preoperative (control group), intraoperative (ie, discharge decisions were based on PTH values drawn in the operating room), and early postoperative (ie, PTH values at 1 to 4 hours after surgery were used as a guide). RESULTS: The reported means of perioperative PTH levels and percentage of patients who developed hypocalcemia were collected from 14 studies. PTH evaluated at both the intraoperative and early postoperative periods was significantly lower in patients who became hypocalcemic versus patients who remained normocalcemic. There was no significant difference when PTH was measured intraoperatively or early postoperatively. CONCLUSION: Intraoperative PTH has no significant disadvantage versus early postoperative PTH when used as a clinical guide for discharge after thyroidectomy.

Intraoperative parathyroid hormone assay-cutting the Gordian knot.

BACKGROUND: Hyperparathyroidism is treated by surgical excision of the hyperfunctioning parathyroid gland. In case of adenoma the single abnormal gland is removed, while in hyperplasias, a subtotal excision, that is, three-and-a-half of the four glands are removed. This therapeutic decision is made intraoperatively through frozen section evaluation and is sometimes problematic, due to a histological overlap between hyperplasia and the adenoma. The intraoperative parathyroid hormone (IOPTH) assay, propogated in recent years, offers an elegant solution, with a high success rate, due to its ability to identify the removal of all hyperfunctioning parathyroid tissue. AIM: To study the feasibility of using IOPTH in our setting. MATERIALS AND METHODS: Seven patients undergoing surgery for primary hyperparathyroidism had their IOPTH levels evaluated, along with the routine frozen and paraffin sections. RESULTS: All seven patients showed more than a 50% intraoperative fall in serum PTH after excision of the abnormal gland. This was indicative of an adenoma and was confirmed by histopathological examination and normalization of serum calcium postoperatively. CONCLUSION: The intraoperative parathyroid hormone is a sensitive and specific guide to a complete removal of the abnormal parathyroid tissue. It can be incorporated without difficulty as an intraoperative guide and is superior to frozen section diagnosis in parathyroid surgery.

A simplified approach to minimally invasive parathyroidectomy.

OBJECTIVES/HYPOTHESIS: To assess the feasibility of a simplified approach for the use of a rapid intraoperative parathyroid hormone (IOPTH) assay based on a single 10-minute post-excision level using the workup parathyroid hormone level (wPTH) as the baseline in minimally invasive parathyroidectomy (MIP) and to compare the predictive value of this criterion with other recommended criteria. STUDY DESIGN: Case series with chart review. METHODS: A single surgeon's prospectively maintained parathyroidectomy database at an academic center was reviewed over a 2-year period from June 2009 through June 2011. RESULTS: A total of 102 patients undergoing MIP met the inclusion criteria. An IOPTH threshold of a ≥ 50% drop at 10 minutes post-excision from the wPTH baseline resulted in acceptable false positive (1.9%) and false negative (0.9%) rates. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of this modified criterion was 98.9%, 71.4%, 98%, 83.3%, and 97%, respectively. CONCLUSIONS: In our patient cohort, the pre-incision and pre-excision IOPTH levels did not seem to change the overall accuracy of predicting surgical success in MIP if a single 10-minute post-excision IOPTH level is used along with the wPTH, and is commensurate with the commonly used Miami and Vienna criteria. A single intraoperative blood sample demonstrating a ≥50% drop from the wPTH at 10 minutes post-excision should be explored further as a feasible simplified criterion that avoids multiple IOPTH samples.

A retrospective case-controlled study of video-assisted versus open minimally invasive parathyroidectomy.

INTRODUCTION: Minimally invasive parathyroidectomy (MIP) with intraoperative parathyroid hormone assay (IOPTH) has successfully replaced conventional neck exploration in most patients with primary hyperparathyroidism (pHPT) and preoperatively localized parathyroid adenoma. AIM: To compare outcomes of video-assisted MIP (MIVAP) to open MIP (OMIP). MATERIAL AND METHODS: A retrospective case-controlled study of 455 patients with sporadic pHPT undergoing MIP with IOPTH at our institution in 2003-2012 was undertaken. The primary outcome measure was postoperative pain. Secondary outcome measures were: duration of surgery, recurrent laryngeal nerve (RLN) identification rate, conversion rate, length of hospital stay, cure rate, patients' satisfaction with cosmetic outcome, morbidity, costs, and diagnostic accuracy of IOPTH. RESULTS: Of 455 patients with pHPT and a solitary parathyroid adenoma on preoperative imaging, 151 underwent MIVAP and 304 had OMIP. The following outcomes were favourable for MIVAP vs. OMIP: lower pain intensity during 24 h postoperatively (p < 0.001), lower analgesia request rate (p < 0.001), lower analgesics consumption (p < 0.001), higher recurrent laryngeal nerve identification rate (p < 0.001), shorter scar length (p < 0.001), and better cosmetic satisfaction at 1 month (p = 0.013) and at 6 months (p = 0.024) after surgery. However, MIVAP vs. OMIP had longer duration of surgery (p < 0.001), and was more expensive (p < 0.001). No differences were noted in the conversion rate, length of hospital stay, and morbidity. CONCLUSIONS: Both MIVAP and OMIP approaches were equally safe and effective. However, the outcomes of MIVAP operations were superior to OMIP in terms of lesser postoperative pain, lower analgesics consumption, and better cosmetic satisfaction resulting from a smaller scar.

Successful Localization of Distant Metastasis in Parathyroid Carcinoma Using Intraoperative Parathyroid Hormone Assay

Intra-operative parathyroid hormone (IOPTH) assay is a useful tool to confirm complete excision of all hyper-functioning parathyroid gland tissue. In this report, we describe a case with successful localization of distant metastasis in a patient with parathyroid carcinoma using the IOPTH assay. A 53-year-old man presented to our clinic with a serum calcium level of 11.8 mg/dL and an intact PTH level of 233.3 pg/mL. He had been treated for parathyroid carcinoma eleven years ago. Two suspected metastatic lesions were detected on the chest computed tomography. Due to the vastly different surgical field necessary to excise each lesion, we preferentially removed only one lesion and we monitored the other remaining suspected lesion without resection via IOPTH assay. Six months later, the patient's serum calcium and intact PTH levels remained within their normal ranges. To the best of our knowledge, this is the first case to effectively utilize IOPTH assay for the management of metastatic parathyroid carcinoma.