Intraoperative Parathyroid Hormone Research Articles

12410 Intra-operative Parathyroid Hormone Monitoring: Comparative Evaluation Of Sampling Sites And Assay Methods

Abstract Disclosure: R. Kwayess: None. S. Ajjour: None. M. Rahme: None. M. Assaad: None. J. Abbas: None. S. Jabbour-Khoury: None. R. Daher: None. E. Cavalier: None. O. Kreidieh: None. M. Chakhtoura: None. G. El-Hajj Fuleihan: None. Background: Primary hyperparathyroidism is a common endocrine disorder increasingly managed by minimally invasive parathyroidectomy (MIP) with intra-operative parathyroid hormone (IOPTH) monitoring using 2nd generation parathyroid hormone (PTH) assay. Objective: Compare the use of central sampling versus peripheral sampling, and of 3rd as opposed to 2nd generation PTH assays’ performance. Methods: We collected preoperative baseline characteristics and laboratory values for consenting participants undergoing parathyroidectomy at our center. We then measured IOPTH levels from peripheral and central venous sites using 2nd and 3rd generation assays at various intraoperative time points. We calculated the maximal intraoperative PTH drop from highest baseline (pre-incision or pre-excision) at peripheral site and pre-excision at central site for participants who were normocalcemic at ≥ 6 months post-operatively. We used paired t-test to compare the mean % drop in IOPTH by 2nd vs 3rd generation assays, and peripheral vs central sampling. Results: Out of 88 participants enrolled, 63 had follow-up data at 6 months or beyond and normal serum calcium level (9.41 ± 0.43 mg/dL). Mean age was 56.16 ± 11.5 years, 77.8% females and 47.6% had osteoporosis or osteopenia. Pre-operative mean values were: serum calcium 10.94 ± 0.73 mg/dL, ionized calcium 5.6 ± 0.68 mg/dL, PTH 131.93 ± 120.1 pg/mL and creatinine 0.77 ± 0.19 mg/dL. The majority of patients underwent excision of one abnormal gland (79.4%). On average, 57.3% of patients had the highest PTH drop at 10 mins, 32.7% beyond 10 minutes, and 9.7% at 5 minutes, regardless of assay type and site. Median PTH decrements were 81% and 83.8% for 2nd generation assay, and 86.5% and 89% for 3rd generation assays, at peripheral and central sites, respectively. There was no significant difference in the PTH drop comparing central to peripheral sites using either assay. However, 3rd generation assays displayed a higher drop compared to 2nd generation assay, for both central and peripheral sites (p-value <0.001). Discussion/Conclusion: Our study shows no difference in % drop between peripheral and central sampling, using either 2nd or 3rd generation assays. Central PTH sampling is commonly used by surgeons because of ease of access, while applying the Miami criterion. However, the drop in median 3rd generation PTH level was higher compared to the 2nd generation assay, regardless of the sampling site. Our findings suggest the necessity of defining larger PTH drop cut-off values for 3rd generation PTH assay than the commonly used Miami criterion.

12350 A Rare Case Of Giant Parathyroid Adenoma Managed Medically For 8 Months: A Case Report

Abstract Disclosure: S. Labram: None. L. Bilandzic: None. Background: Single parathyroid adenoma is the most common cause of primary hyperparathyroidism, and is attributed to approximately 85% of cases[1]. However, those classified as giant (weighing over 3.5 g and having a size greater than 2cm2) are exceedingly rare. This reports a rare case of primary hyperparathyroidism caused by giant parathyroid adenoma and details biochemical response following medical and surgical management. Case Report: A 64 year old black female presented with severe abdominal pain, confusion and constipation. Investigations revealed severe hypercalcemia of 17.3 mg/dl with massively elevated parathyroid hormone of 1255 pg/mL. Ultrasound showed a large hypoechogenic lobulated mass inferior to the left thyroid lobe representing a giant parathyroid adenoma. Due to delayed surgery the patient was initially treated medically over the course of 8 months. Over these months she was admitted to hospital 3 times for symptomatic hypercalcemia and received a total of 3 zolendronic acid infusions. Despite this she was unable to achieve long term remission of hypercalcemia. Cinacalcet was added and tolerated at the dose of 30 mg daily. Hypercalcemia improved, but remained elevated at a range of 11-13 mg/dL and the symptoms of brain fog and constipation did not subside entirely. She was eventually able to undergo surgical resection, and a giant parathyroid adenoma weighing 8.9 g was excised. Intraoperative intact parathyroid hormone (IOiPTH) sampling showed > 50% reduction (prior to removal 878pg/mL, 10 minutes after removal 132 pg/ml, 20 minutes after removal 96pg/mL). Pathological review showed an atypical parathyroid tumor. As the tumor lacked invasive growth it did not meet criteria for carcinoma. Conclusions: This is a rare case of primary hyperparathyroidism caused by a giant solitary parathyroid adenoma. The gold standard for management of primary hyperparathyroidism secondary to parathyroid adenoma is minimally invasive parathyroidectomy. However in our case, due to inability to access immediate surgery, challenging and prolonged medical treatment of severe hypercalcemia followed for 8 months. Ultimately, normalization of calcium level was achieved only by surgical intervention. IOiPTH measurements showed appropriate decrease confirmatory for the complete removal of the adenoma.

8592 Parathyroid Carcinoma: A Rare Cause of Primary Hyperparathyroidism

Abstract Disclosure: S.E. Koshy: None. C.F. Mulcahy: None. P.S. Kothari: None. E.M. Jacobi: None. T.D. Cubb: None. Introduction: Parathyroid carcinoma (PC) is a rare malignancy that accounts for <1% of cases of primary hyperparathyroidism (PHPT). Patients often present with symptoms of hypercalcemia, serum calcium (Ca) >14 mg/dL, large tumor size, and a very high parathyroid hormone (PTH) level. We report a case of an asymptomatic patient with incidentally found hypercalcemia consistent with PHPT who was ultimately diagnosed with PC. Clinical Case: A 31yo male was found to have elevated serum Ca of 12.7 mg/dL (8.6-10.3 mg/dL) on labs obtained during routine physical exam. He had no known significant medical or family history and notably had no laboratory evaluation within the prior 10 years. He denied constipation, polyuria, confusion, depression, bone pain, and history of fractures or nephrolithiasis. Workup showed an inappropriately elevated PTH of 505 pg/mL (16-77 pg/mL). Neck ultrasound demonstrated a left inferior 3.9 cm complex thyroid nodule. Sestamibi scan confirmed increased uptake in the inferior left thyroid. Left neck exploration was performed. Intraoperatively, a 3.7 cm left parathyroid mass weighing 13.0 grams was encountered and excised in an en bloc fashion. The left superior parathyroid gland was evaluated and found to be normal. Intraoperative PTH level decreased from 529 pg/mL to 48 pg/mL 10 minutes after excision. Left hemithyroidectomy was not performed. Surgical pathology revealed PC with lymphovascular invasion, suspected capsular invasion, and negative margins. Immunohistochemical staining showed a Ki67 proliferation index up to 5% and complete loss of nuclear staining for parafibromin. Next generation sequencing demonstrated a somatic CDC73 p.L8fs mutation, tumor mutational burden 4.7m/MB, and stable microsatellite instability. Germline testing was negative for a CDC73 mutation. Postoperative staging did not demonstrate evidence of metastatic disease in the neck or chest. Serum Ca remained within normal limits. After multidisciplinary discussion, no further surgical intervention was recommended and plan was for ongoing biochemical and imaging surveillance. Conclusion: Though rare, PC should be considered as a cause of PHPT. The primary treatment is complete surgical resection. Unfortunately, there is a high rate of recurrence, >50%, with most occurring 2-5 years after initial surgery with a median overall survival of 14 years. Thus, long-term surveillance is of utmost importance. Treatment of recurrent disease is surgical resection when feasible as well as medical management of hypercalcemia. Further research is needed to better understand the role of targeted systemic therapy in addition to immunotherapy. PC is most commonly sporadic but can be hereditary, thus genetic evaluation is recommended. Given its rarity and complexity, PC is best managed in a multidisciplinary setting. Presentation: 6/1/2024

8592 Parathyroid Carcinoma: A Rare Cause of Primary Hyperparathyroidism

Abstract Disclosure: S.E. Koshy: None. C.F. Mulcahy: None. P.S. Kothari: None. E.M. Jacobi: None. T.D. Cubb: None. Introduction: Parathyroid carcinoma (PC) is a rare malignancy that accounts for <1% of cases of primary hyperparathyroidism (PHPT). Patients often present with symptoms of hypercalcemia, serum calcium (Ca) >14 mg/dL, large tumor size, and a very high parathyroid hormone (PTH) level. We report a case of an asymptomatic patient with incidentally found hypercalcemia consistent with PHPT who was ultimately diagnosed with PC. Clinical Case: A 31yo male was found to have elevated serum Ca of 12.7 mg/dL (8.6-10.3 mg/dL) on labs obtained during routine physical exam. He had no known significant medical or family history and notably had no laboratory evaluation within the prior 10 years. He denied constipation, polyuria, confusion, depression, bone pain, and history of fractures or nephrolithiasis. Workup showed an inappropriately elevated PTH of 505 pg/mL (16-77 pg/mL). Neck ultrasound demonstrated a left inferior 3.9 cm complex thyroid nodule. Sestamibi scan confirmed increased uptake in the inferior left thyroid. Left neck exploration was performed. Intraoperatively, a 3.7 cm left parathyroid mass weighing 13.0 grams was encountered and excised in an en bloc fashion. The left superior parathyroid gland was evaluated and found to be normal. Intraoperative PTH level decreased from 529 pg/mL to 48 pg/mL 10 minutes after excision. Left hemithyroidectomy was not performed. Surgical pathology revealed PC with lymphovascular invasion, suspected capsular invasion, and negative margins. Immunohistochemical staining showed a Ki67 proliferation index up to 5% and complete loss of nuclear staining for parafibromin. Next generation sequencing demonstrated a somatic CDC73 p.L8fs mutation, tumor mutational burden 4.7m/MB, and stable microsatellite instability. Germline testing was negative for a CDC73 mutation. Postoperative staging did not demonstrate evidence of metastatic disease in the neck or chest. Serum Ca remained within normal limits. After multidisciplinary discussion, no further surgical intervention was recommended and plan was for ongoing biochemical and imaging surveillance. Conclusion: Though rare, PC should be considered as a cause of PHPT. The primary treatment is complete surgical resection. Unfortunately, there is a high rate of recurrence, >50%, with most occurring 2-5 years after initial surgery with a median overall survival of 14 years. Thus, long-term surveillance is of utmost importance. Treatment of recurrent disease is surgical resection when feasible as well as medical management of hypercalcemia. Further research is needed to better understand the role of targeted systemic therapy in addition to immunotherapy. PC is most commonly sporadic but can be hereditary, thus genetic evaluation is recommended. Given its rarity and complexity, PC is best managed in a multidisciplinary setting. Presentation: 6/1/2024

12313 Parathyroid Carcinoma Presenting As Right Foot Pain And Swelling In A Young Male - A Case Report

Abstract Disclosure: F.E. Sorsona: None. L. Lopez: None. Parathyroid carcinoma is a rare cause of hyperparathyroidism that is challenging to diagnose. We report a case of parathyroid carcinoma with an unusual initial presentation of right foot pain and swelling in a young 26-year-old Filipino male. Physical examination revealed a palpable 1 x 1 cm mass with tenderness on his right foot. Initial work-up showed a persistently elevated serum ionized calcium (range: 1.7 - 2.19 mmol/L) with markedly high intact parathyroid hormone (1,890 pg/ml). A right foot x-ray revealed a lytic bone lesion on the 3rd metatarsal. Skeletal survey revealed diffuse lytic bone lesions. Comprehensive neck ultrasound showed a 4 x 1.6 x 2.5 cm complex nodule adjacent to the inferior pole of the left lobe of the thyroid gland with intralesional calcifications. A 4D CT scan showed a 3.3 x 2.2 x 2 cm hypervascular nodule inferior to the left thyroid lobe with early contrast washout, likely parathyroid in origin, and a possible brown tumor in the right fourth rib. Patient underwent parathyroidectomy with intraoperative PTH monitoring showing a marked reduction of intact PTH by 87% (235.9 pg/ml from 1,890 pg/ml), accompanied by reduction of serum ionized calcium. The histopathology reported parathyroid carcinoma highlighted by lymphovascular invasion, atypical round cells in sheets and nests, with enlarged, mildly pleomorphic, hyperchromatic nuclei and prominent nucleoli. Two months after surgery, normal serum ionized calcium was maintained with calcium supplementation with reported relief of right foot pain and swelling. The patient continues to follow up regularly for monitoring of treatment response. Presentation: 6/2/2024

7388 Rare Case of Mediastinal Parathyroid Carcinoma

Abstract Disclosure: Y. Esaki: None. J. Moalem: None. A. Israel: None. I. Shafiq: None. Introduction: Parathyroid carcinoma accounts for 1% of primary hyperparathyroidism with an estimated prevalence of 0.005% of all cancers. Ectopic locations of parathyroid tumors have been found in 6-16% of cases, most commonly in the thyroid, the thymus, or behind the esophagus. Parathyroid carcinoma is rarely found in the mediastinum and only 30 cases have been reported in the literature. Clinical Case: A 68-year-old male without significant past medical history was evaluated by his primary care physician for constipation, polyuria and 20 lb weight loss over the past year. He presented to the hospital after blood work revealed serum calcium of 13.5 mg/dl (8.6-10.2 mg/dl). Initial hospital workup demonstrated serum calcium 12.9 mg/dl, phosphorus 2.6 mg/dl (2.7-4.5 mg/dl), 25-OH vitamin D 21 ng/ml (30-60 ng/ml), 1,25-(OH)2 vitamin D 143.0 pg/ml (19.9-79.3 pg/ml), PTH-related protein < 2.0 pmol/L (0.0-2.3 pmol/L) and PTH 1,250.0 pg/ml (15.0-65.0 pg/ml). CT scan revealed a 3.5 cm x 2.6 cm heterogeneous right paratracheal soft tissue mass with areas of calcifications with mass effect on SVC. Thyroid ultrasound showed multinodular thyroid tissues with a left 1.1 cm heterogeneous solid nodule along the mid posterior aspect as well as a 0.5 cm hypoechoic lesion inferior to the left lobe. Sestamibi scan demonstrated a large area of increased uptake corresponding to the mass seen in the superior mediastinum on CT imaging. He underwent neck exploration and left hemithyroidectomy as well as median sternotomy with resection of the paratracheal mass. Intraoperative PTH decreased from the baseline of 1,177.0 pg/ml to 65.6pg/ml following the removal of the paratracheal mass. The final pathology of right anterior mediastinal mass was consistent with a 5 cm parathyroid carcinoma with angioinvasion, intermediate lymphatic invasion, invasion into adjacent structures, and Ki67 proliferative index focally > 5%. His post-operative course was complicated by hypocalcemia, which improved with treatment with calcitriol and calcium supplementation. He declined the genetic testing. His calcium and parathyroid hormone have remained in the normal range after 1 year. Conclusion: This case illustrates a rare case of parathyroid carcinoma found in the mediastinum. It is important to recognize that parathyroid carcinoma can present in ectopic locations including the mediastinum, as this can affect the preoperative investigation and management. Fine needle biopsy (FNA) prior to the initial operation is not recommended as it is difficult to differentiate the parathyroid carcinoma from benign disease based on FNA, and it may cause tumor rupture and seeding. Also, in the mediastinal parathyroid carcinoma, localization of the lesions including the size and invasiveness is critical in order to allow for radical surgery. Presentation: 6/3/2024

6487 Hypercalcemia In Pregnancy Due To An Ectopic Parathyroid Adenoma: A Diagnostic Dilemma

Abstract Disclosure: S.S. Patel: None. M.B. Sharma: None. Introduction: Hypercalcemia is a rare complication of pregnancy, with the most common cause being primary hyperparathyroidism due to a parathyroid adenoma. Ultrasound is the primary modality used for localization, as sestamibi and computed tomography (CT) carry the risk of potential harm to the fetus. We present the case of hypercalcemia in a pregnant female that failed to resolve after two gland parathyroidectomy, necessitating a sestamibi parathyroid scan to localize an ectopic parathyroid adenoma. Case: A 40-year-old pregnant woman at 12 weeks of gestation presented with hypercalcemia, with a corrected calcium level of 12.5 mg/dL (8.7-10.4 mg/dL). She complained of nausea and vomiting but denied any personal or family history of hypercalcemia. Further evaluation revealed primary hyperparathyroidism as the etiology, with Intact PTH of 429.2 pg/mL (18.5-88.0 pg/mL), ionized calcium of 1.45 mmol/L (1.12-1.32 mmol/L), 25-OH vitamin D of 16.4 ng/mL (30-100 ng/mL), phosphorus of 1.3 mg/dL (2.4-5.1 mg/dL), and creatinine of 0.71 mg/dL (0.5-0.8 mg/dL). Notably, her calcium level had been 19.2 mg/dL two weeks earlier during an episode of hyperemesis gravidarum. Hypercalcemia proved relatively resistant to treatment with intravenous hydration and subcutaneous calcitonin. Ultrasound of the neck failed to reveal a parathyroid adenoma. The patient then underwent surgical neck exploration, during which two parathyroid glands were removed, resulting in an intraoperative PTH drop from 440 to 340 pg/mL. Postoperative calcium levels remained elevated at 12.9 mg/dL, prompting the resumption of treatment. Oral sodium and potassium phosphate was added to bind dietary calcium. After an extensive multidisciplinary discussion, a 99mTc-sestamibi parathyroid scan with a lower dose of sestamibi and without CT was recommended. This revealed an ectopic parathyroid adenoma in the anterior mediastinum. Surgical removal of the ectopic parathyroid adenoma in the second trimester finally led to a significant intraoperative PTH drop from 315 to 28 pg/mL. The postoperative course was complicated by hypocalcemia and hypomagnesemia, requiring calcium, vitamin D, and magnesium supplements. These complications resolved over the following days. The patient remained normocalcemic for the remaining pregnancy and delivered a healthy male infant at 34 weeks. Conclusion: Hypercalcemia in pregnancy is associated with fetal and maternal complications, warranting adequate management and close follow-up. The use of 99mTc-sestamibi parathyroid scan is typically not recommended in pregnancy due to concern for fetal harm; however, there are a few studies showing no association with increased birth defects or adverse pregnancy outcomes at low radiotracer doses. Hence, a sestamibi parathyroid scan can be considered during pregnancy to localize an adenoma after a careful review of the benefits versus risks. Presentation: 6/2/2024

7752 Navigating Hypercalcemia in Pregnancy: A Case Report

Abstract Disclosure: J. Gabbay: None. S. Steinmetz-Wood: None. Introduction: Primary hyperparathyroidism (PHPT) in pregnancy is rare but presents many diagnostic and therapeutic challenges. Prompt diagnosis and treatment are important due to associated maternal and fetal risks, however evaluation of urine calcium to differentiate from Familial Hypocalciuric Hypercalcemia (FHH) becomes less reliable due to physiologic changes in pregnancy, sestamibi scans. CT scans require radiation, parathyroidectomy introduces surgical risk, and medical alternatives like bisphosphonates can interfere with fetal skeletal development. Clinical Case: A 24-year-old woman who presented to the emergency room for progressive nausea and abdominal pain was found to be pregnant with elevated serum calculated calcium to 11.4 mg/dL (2.84 mmol/L). She had a history of renal stones, longstanding hypercalcemia of unknown etiology and a remote family history of parathyroid “issues”. Follow up laboratory work showed a PTH of 75.8 pg/ml (8.04 pmol/L) with an elevated 24-hour urine calcium and a low 25OH vitamin D. Given her history of kidney stones and overt symptoms it was our clinical judgement that this was not a case of FHH. She was started on IV fluids twice weekly. After an unrevealing neck ultrasound, an MRI neck showed a 7 mm lesion along the posterior aspect of the left thyroid suggestive of a parathyroid adenoma. Sestamibi scan was avoided due to the risks of radiation to the developing fetus. Given the presumptive diagnosis of parathyroid adenoma, the lack of response to aggressive hydration, and the maternal and fetal risks of hypercalcemia during pregnancy, parathyroidectomy was pursued in her second trimester. Intra-operative inspection and biopsy showed the lesion to be only a lymph node. She underwent 4-gland exploration and the left inferior parathyroid gland, which appeared abnormal and enlarged, was removed. The intra-operative PTH dropped only from 98 to 80 (10.4 to 8.5 pmol/L). She otherwise had an unremarkable hospital course and at discharge her calcium was normal with an undetectable PTH, which can be an expected finding in pregnancy. On follow up she was feeling well with sustained normocalcemia and low PTH levels. Given the age at which her hyperparathyroidism started, she was referred to genetics for further evaluation. Clinical Lessons/Conclusion: There were significant biochemical and radiological limitations in the management of this case. Normally an inappropriately normal PTH with elevated serum calcium and normal urine calcium/creatinine clearance ratio confirms the diagnosis of PHPT, however in pregnancy it should be noted that FHH could also present with normal or elevated urine calcium due to absorptive hypercalciuria in pregnancy. Additional clinical history and reasoning was needed for management as well as a skilled surgeon, where preoperative localization was limited and was not ultimately helpful. Presentation: 6/2/2024

6424 From Hyperparathyroidism To Neurologic Crisis: A Tale Of Brown Tumor And Spinal Cord Compression

Abstract Disclosure: A. Kormanis: None. M. Anderson: None. M. McKnight: None. H. Darapu: None. Background/Objective: In this case, we present a rare and severe consequence of secondary hyperparathyroidism, a Brown tumor leading to spinal cord compression, in a young adult with end-stage renal disease. Case Report: A 26-year-old male with a medical history of polycystic kidney disease and IgA Nephropathy complicated by ESRD, history of brown cell tumors (s/p surgery) was admitted for hospitalization due to hypocalcemia after presenting to the Emergency Department with right lower extremity weakness. Examination revealed right hip flexor weakness and right foot clonus. Lab results showed serum calcium of 10.4 mg/dL . MRI displayed a 2.5cm X 3.7 cm soft tissue mass with circumferential encroachment of the epidural space leading to severe spinal canal stenosis of T4-T5 at the site of prior Brown tumor resection. Ultimately, the patient underwent subtotal parathyroidectomy with left cervical thymectomy, leading to an intra-operative PTH drop from >3500 to 247 pg/mL. Discussion: In the context of treating vertebral brown tumors, the consensus suggests that parathyroidectomy plays a crucial role in achieving both clinical and radiographical amelioration of the tumor. However, in cases like ours where paresis is present, surgical decompression of the tumor becomes imperative. Conclusion: The development of Brown tumors is a severe and rare long-term complication for hyperparathyroidism, and the location of a Brown tumor in the thoracic spine causing symptomatic cord compression is even more rare. Presentation: 6/2/2024

Predicting cure and hypocalcemia by intraoperative parathyroid hormone decline in normohormonal primary hyperparathyroidism: A multi-institutional validation study

BackgroundNormohormonal primary hyperparathyroidism is characterized by hypercalcemia and inappropriately normal parathyroid hormone levels. We previously reported that intraoperative parathyroid hormone decline of 50–70% for normohormonal and 75–88% for classic primary hyperparathyroidism during parathyroidectomy was predictive of (1) cure and (2) avoidance of hypocalcemia in a single-institution study (derivation cohort). We sought to externally validate these findings. MethodsWe performed a multi-institutional retrospective cohort study of patients undergoing parathyroidectomy for primary hyperparathyroidism from 2002 to 2019 (validation cohort). Primary outcomes were biochemical cure (calcium <10.3 mg/dL) and postoperative hypocalcemia (≤8.8 mg/dL) ≥6 months postoperatively. Test characteristics of the previously derived thresholds were evaluated in this cohort. ResultsA total of 163 (16%) of 1,037 patients had normohormonal primary hyperparathyroidism. Cure rates were similar for normohormonal and classic primary hyperparathyroidism (94% vs 92%, P = .41). In patients who were cured, the median intraoperative parathyroid hormone decrease was lower in normohormonal compared with classic primary hyperparathyroidism (56.8 vs 73.3%, P < .0001). Rates of hypocalcemia were similar for normohormonal and classic primary hyperparathyroidism (14.6% vs 11.9%, P = .44), but increasing percent intraoperative parathyroid hormone decrease beyond 65% disproportionately correlated with hypocalcemia in patients with normohormonal primary hyperparathyroidism. When intraoperative parathyroid hormone thresholds from the derivation cohort were applied, positive predictive values for cure were 97% and 94% for normohormonal and classic primary hyperparathyroidism, respectively; negative predictive values for hypocalcemia were 89% for both groups. For both cohorts combined, a minimal intraoperative parathyroid hormone of 50% provided similar cure rates between groups (95.4% vs 93.8%, P = .42), whereas intraoperative parathyroid hormone exceeding 65% correlated with a greater risk of hypocalcemia in normohormonal compared with classic primary hyperparathyroidism (13.4% vs 6.9%, P = .02). ConclusionThis multi-institutional study externally validated that intraoperative parathyroid hormone decrease of 50–65% predicts cure and hypocalcemia in patients with normohormonal primary hyperparathyroidism.

A-048 Reference Interval and Clinical Performance Studies for Vitros® Immunodiagnostic Products Intact PTH II Assay to Aid in Diagnosis of Calcium and Parathyroid Disorders and Intraoperative Testing

Abstract Background Intact parathyroid hormone (iPTH) measurements aid in the differential diagnosis of hypercalcemia, hypocalcemia, and parathyroid disorders. The National Academy of Clinical Biochemistry has established guidelines for intraoperative PTH testing to monitor surgical success during parathyroidectomies. Studies were conducted to define the reference interval and clinical performance of the Vitros Immunodiagnostic Products Intact PTH II (Vitros iPTH II) assay, using samples from healthy individuals and patients with conditions commonly requiring iPTH testing, including intraoperative cases. Methods The reference interval study was conducted in accordance with Clinical and Laboratory Standards Institute (CLSI) guideline EP28-A3c in serum samples from 134 healthy individuals. For the clinical performance study, serum samples from individuals with hypoparathyroidism, primary hyperparathyroidism, chronic renal failure (secondary or tertiary hyperparathyroidism), hypercalcemia, hypercalcemia of malignancies, and hypocalcemia were tested. Intraoperative samples used were collected from parathyroidectomy patients in series at each surgical timepoint along with the standard plasma samples used to determine surgical success. Results The reference samples were composed of 134 serum donors that met all inclusion/exclusion criteria for healthy donors and had a normal test result on calcium, TSH, alkaline phosphatase, creatinine, and phosphate assays. The reference interval for iPTH was determined to be 14.2-75.2 pg/mL. The results in various disease states demonstrated the clinical performance of the Vitros iPTH II assay. Of 32 intraoperative sample series included in the study, three samples demonstrated no intraoperative decrease in iPTH due to surgical failures. Consistent with the goal of the parathyroidectomy procedure, at least a 50% decrease in iPTH was observed between the presurgical and post-excision samples in all other sample series. The clinical concordance with the Roche PTH assay used intraoperatively in these procedures was 100%. Conclusions Defining the reference interval for a normal healthy population and results from the intended use population demonstrated that the Vitros iPTH II assay can be used as an aid in the diagnosis of calcium and parathyroid disorders and intraoperative testing.

PET-TC [18F]F-Colina y PTH intraoperatoria en el tratamiento quirúrgico del hiperparatiroidismo primario sin localización preoperatoria

Background and objectivesTo assess the feasibility of performing selective parathyroidectomy without intraoperative parathyroid hormone (PTHio) determination when first-line preoperative localization tests (ultrasonography and [99mTc]Tc-MIBI) are negative and/or discordant, and second-line [18F]F-Colina PET-CT, is positive. Materials and methodsRetrospective cohort study, including patients with negative or discordant ultrasound and MIBI scans and positive [18F]F-Colina PET-CT, who underwent selective parathyroidectomy between 2019 and 2022. Groups were compared based on PTHio determination. Study variables were: gender, mean age, biochemical cure assessed by PTH value (pg/mL) and corrected calcium by albumin (mg/dL) at 6 months post-surgery follow-up, and histopathological analysis. ResultsThe final sample included 42 patients. At 6 months post-surgery, in the PTHio group (20 patients), PTH values were 64.50 pg/mL and calcium 9.30 pg/mL, with 19 adenomas and 1 hyperplasia found. In the non-PTHio group (22 patients), PTH values were 61 pg/mL and calcium 9.37 pg/mL, with 22 adenomas found. No statistically significant differences were found between both groups. ConclusionsBased on the results obtained in our patient cohort, selective parathyroidectomy could be considered with negative or discordant first-line tests and positive [18F]F-Colina PET-CT, without intraoperative PTH determination.

Variable practice patterns in the surgical management of renal hyperparathyroidism

BackgroundHyperparathyroidism is common among patients with chronic kidney disease, end-stage kidney disease, and kidney transplant. The American Association for Endocrine Surgery published clinical practice guidelines that address the surgical treatment of secondary and tertiary hyperparathyroidism. The purpose of this study is to determine practice patterns for the surgical management of secondary and tertiary hyperparathyroidism prior to guideline publication. MethodsWith the approval of the American Association for Endocrine Surgery, a Qualtrics email survey was sent to the Association’s membership in 2022 about current clinical decision making for surgical treatment of secondary and tertiary hyperparathyroidism. Respondents were divided into groups based on surgical subspecialty (endocrine surgery versus non-endocrine surgery), yearly parathyroidectomy volume, and yearly parathyroidectomy volume for surgical treatment of secondary and tertiary hyperparathyroidism. Descriptive statistics were performed; the role of volume was evaluated. ResultsThere were 142 responses from 795 solicited email addresses (18% response rate); 114 (84%) identified as endocrine surgeons. The majority (62%) perform >50 parathyroidectomies yearly, but most perform <10 parathyroidectomies for surgical treatment of secondary and tertiary hyperparathyroidism per year (<10/y, 53.7%; 10–30/y, 41.9%; >30/y, 4.4%). Subtotal parathyroidectomy is most commonly performed for surgical treatment of secondary (83%) and tertiary (52%) hyperparathyroidism, but transcervical thymectomy variably performed for both. There was no consensus regarding starting calcitriol preoperatively (always 43%, never 25%, depends on vitamin D levels 24%) or stopping cinacalcet (2 weeks prior 28%, day of surgery 29%, postoperatively 20%). Surgeons who perform >10 parathyroidectomies per year for surgical treatment of secondary and tertiary hyperparathyroidism were less likely to consider the patient's preoperative vitamin D levels to inform their decision to start calcitriol before surgery (<10 cases/year, 34%; ≥10 cases/year 15%; P = .023), were more likely to have a postoperative hypocalcemia protocol managed by the surgical team (<10 cases/year, 49%; ≥10 cases/year, 58%; P = .029), and were more likely to use intraoperative parathyroid hormone monitoring for tertiary hyperparathyroidism (<10 cases/year, 70%; ≥10 cases/year, 87%; P = .046). ConclusionThe majority of respondents perform <10 parathyroidectomies yearly for surgical treatment of secondary and tertiary hyperparathyroidism. Subtotal parathyroidectomy was most commonly performed, but there was little other consensus regarding preoperative management, intraoperative decision-making, and postoperative care. Opportunity exists through guideline dissemination to improve heterogeneity of care provided to surgical treatment of secondary and tertiary hyperparathyroidism patients.

PET-TC [18F]F-choline and intraoperative PTH in the surgical treatment of the primary hyperparathyroidism without preoperative location

Background and objectivesTo assess the feasibility of performing selective parathyroidectomy without intraoperative parathyroid hormone (PTHio) determination when first-line preoperative localization tests (ultrasonography and [99mTc]Tc-MIBI) are negative and/or discordant, and second-line [18F]F-Colina PET-CT, is positive. Materials and methodsRetrospective cohort study, including patients with negative or discordant ultrasound and MIBI scans and positive [18F]F-Colina PET-CT, who underwent selective parathyroidectomy between 2019 and 2022. Groups were compared based on PTHio determination. Study variables were: gender, mean age, biochemical cure assessed by PTH value (pg/mL) and corrected calcium by albumin (mg/dL) at 6 months post-surgery follow-up, and histopathological analysis. ResultsThe final sample included 42 patients. At 6 months post-surgery, in the PTHio group (20 patients), PTH values were 64.50 pg/mL and calcium 9.30 pg/mL, with 19 adenomas and 1 hyperplasia found. In the non-PTHio group (22 patients), PTH values were 61 pg/mL and calcium 9.37 pg/mL, with 22 adenomas found. No statistically significant differences were found between both groups. ConclusionsBased on the results obtained in our patient cohort, selective parathyroidectomy could be considered with negative or discordant first-line tests and positive [18F]F-Colina PET-CT, without intraoperative PTH determination.

Intraoperative parathyroid hormone assay benefits surgery for primary hyperparathyroidism when preoperative localisation is negative or not performed.

Parathyroid localisation is now routine before first-time surgery for patients with primary hyperparathyroidism (PHPT). The aim of this study was to investigate the contribution of intraoperative parathyroid hormone (PTH) (ioPTH) in patients in whom localisation was either not undertaken or negative for a tumour. This was a retrospective study of patients undergoing first-time parathyroidectomy for PHPT in a regional endocrine centre. Data were collected prospectively (Microsoft Excel) and the all-Wales electronic patient record portal was used to retrieve missing data. Statistical analysis appropriate for nonparametric data was undertaken, with statistical significance reached when p<0.05. Between 1 July 2002 and 31 December 2022, 1,490 patients underwent a first-time parathyroidectomy for PHPT. Of this cohort, 1,133 patients had at least one positive imaging modality; the study group consisted of 343 patients that had negative imaging, and 13 that had no preoperative localisation. Patients with MEN-1 (n=26), an incorrect diagnosis (n=4), or less than six months follow-up (n=6) were excluded. Of the remaining 321, 106 patients underwent surgery without ioPTH (Group A), 215 cases with ioPTH (Group B). In Group B there were more women (170 female/45 male; 79% vs 67 female/37 male; 63% p=0.002, chi-squared), lower calcium (median [range] 2.77 [2.63-3.24] mmol/l; vs 2.85 [2.60-4.52] p=0.001) and lower PTH (12.0pmol/l [3.4-39.5] vs 14.4 [3.9-97.0] p=0.001) and smaller weights of resected tissue (320mg [50-9,000] vs 454 [46-8,280] p=0.02) (Student's t-test). The rate of multiple gland disease was similar (Group A 29%; Group B 27%). The rate of normocalcaemia at 6 months was significantly higher when ioPTH was used (Group B 202/215; 94% vs Group A 90/106; 85%) (p=0.014, chi-square test). The sensitivity and specificity of ioPTH was 98.5% [confidence interval (CI) 96.2-99.6] and 91.2% [80.7-97.0] (positive predictive value 99.9%, CI 93.6-100.0). Despite milder hyperparathyroidism and smaller tumour weight, the outcome in patients in whom ioPTH was used was superior, with failure rates 2.5-fold higher in the cohort where ioPTH was not utilised. The results of this study demonstrate that ioPTH is a valuable adjunct for the surgeon in cases where localisation has failed or not been undertaken.

Machine Learning Based Algorithm for the Early Prediction of Postoperative Hypocalcemia Risk After Thyroidectomy.

We used machine learning to develop and validate a multivariable algorithm allowing the accurate and early prediction of postoperative hypocalcemia risk. Post-operative hypocalcemia is frequent after total thyroidectomy. An early and accurate individualized prediction of the risk of hypocalcemia could guide the selective prescription of calcium supplementation only to patients most likely to present with hypocalcemia after total thyroidectomy. This retrospective study enrolled all patients undergoing total thyroidectomy in a single referral center between November 2019 and march 2022 (derivation cohort) and april 2022 and September 2022 (validation cohort) . The primary study outcome was post-operative hypocalcemia (serum calcium under 80mg/L). Exposures were multiple clinical and biological variables prospectively collected and analyzed with various machine learning methods, to develop and validate a multi variable prediction algorithm. Among 610 / 118 participants in the derivation / validation cohorts, 100 (16.4%) / 26 (22%) presented post-operative hypocalcemia. The most accurate prediction algorithm was obtained with random forest, and combined intraoperative parathyroid hormone measurements with three clinical variables (age, sex and body mass index), to calculate a postoperative hypocalcemia risk for each patient. After multiple cross validation, the area under the receiver operative characteristic curve was 0.902 (0.829-0.970) in the derivation cohort, and 0.928 (95% CI : 0.86; 0.97) in the validation cohort. Postoperative hypocalcemia risk values of 7% (low threshold) and 20% ( high threshold) had respectively a sensitivity of 92% and a negative likelihood ratio of 0.11, and a specificity of 90% and a positive of 7.6 for the prediction of postoperative hypocalcemia. Using machine learning, we developed and validated a simple multivariable model which allowed the accurate prediction of postoperative hypocalcemia. The resulting algorithm could be used at the point of care to guide clinical management after total thyroidectomy.

Is intraoperative parathyroid monitoring during minimally invasive parathyroidectomy still justified?

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. 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. 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. 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.

Trends in using intraoperative parathyroid hormone monitoring during parathyroidectomy: Protocol and rationale for a cross-sectional survey study of North American surgeons.

Hyperparathyroidism is a common endocrine disorder that occurs secondary to abnormal parathyroid gland functioning. Depending on the type of hyperparathyroidism, surgical extirpation of hyperfunctioning parathyroid glands can be considered for disease cure. Intraoperative parathyroid hormone (IOPTH) monitoring improves outcomes in patients undergoing surgery for primary hyperparathyroidism, but studies are needed to characterize its institutional adoption and its role in surgery for secondary and tertiary hyperparathyroidism, as these entities can be difficult to cure. Hence, we will perform a cross-sectional survey study of surgeon rationale, operational details, and barriers associated with IOPTH monitoring adoption across North America. We will utilize a convenience sampling technique to distribute an online survey to head and neck surgeons and endocrine surgeons across North America. This survey will be distributed via email to three North American professional societies (i.e., Canadian Society for Otolaryngologists-Head and Neck Surgeons, American Head and Neck Society, and American Association of Endocrine Surgeons). The survey will consist of 30 multiple choice questions that are divided into three concepts: (1) participant demographics and training details, (2) details of surgical adjuncts during parathyroidectomy, and (3) barriers to adoption of IOPTH. Descriptive analyses and multiple logistic regression will be used to evaluate the impact of demographic, institutional, and training variables on the use of IOPTH monitoring in surgery for all types of hyperparathyroidism and barriers to IOPTH monitoring adoption. Ethics approval was obtained by the Hamilton Integrated Research Ethics Board (2024-17173-GRA). These findings will characterize surgeon and institutional practices with regards to IOPTH monitoring during parathyroid surgery and will inform future trials aimed to optimize the use of IOPTH monitoring in secondary and tertiary hyperparathyroidism.

Evaluation of Focused Mini-Incision Parathyroidectomy in Primary Hyperparathyroidism

Abstract Background In the era of effective preoperative localization and availability of intraoperative parathyroid hormone (IOPTH) assay, the trend now in parathyroidectomy is shifting from bilateral neck exploration (BNE) into minimal invasive parathyroidectomy (MIP). The concept of MIP is based on the fact that 85% of cases have single adenoma. This study highlights the outcomes of focused mini- incision parathyroidectomy (FMIP) for the treatment of selected cases of primary hyperparathyroidism. Aim of study: To evaluate and assess the outcome and advantages of focused mini-incision parathyroidectomy in parathyroid adenoma of primary hyperparathyroidism. Patients and Methods This cohort study was conducted at endocrine surgery unit, Ain Shams University Hospital, and Sohag Cancer Institute including 22 patients with benign solitary parathyroid adenoma; 17 retrospective cases &amp; 5 prospective cases. These included patients had been operated with focused mini-incision parathyroidectomy within the time period from January 2018 to December 2020 as retrospective cases and from January 2021 to December 2021 as prospective cases. Results In this study, age ranged from 30 to 70 years with mean age 50.23 ± 10.71 years. The preoperative serum calcium level ranged from 10.8 to 14.2 mg/dl (mean 12.28 ± 1.16 mg/dl). The preoperative parathyroid hormone level was elevated ranging from 256 to 2090 pg/mL (mean 970.68 ± 563.97 pg/mL). In this study, the operative time ranged from 55 to 75 minutes with mean 64.36 ± 6.33 minutes, percentage of IOPTH decrease level ranged from 75-95 % with mean percentage 85.72 ± 6.28 %. There were no cases with intraoperative bleeding or recurrent laryngeal nerve (RLN) injury. Hospital stay ranged from 6-16 days with mean 10.77 ± 3.10 days. There is no wound infection in all cases. All cases reached a success rate up to 100% (decrease the IOPTH level ≥ 75 %, and resolution of preoperative hypercalcemic manifestations). Conclusion Depending to the high successful rate, very low intraoperative morbidity and better postoperative recovery and cosmoses of FMIP technique, it should be the first choice for pHPT cases with solitary parathyroid adenoma, provided by the concordance localization study of U/S and MIBI scan preoperative.

1053 Parathyroid Phenomenon Causing Primary Hyperparathyroidism: A Case for Surgeons, Radiologists and Pathologists

Abstract Background Parathyroid lipoadenomas are a rare parathyroid phenomenon and an unusual cause of primary hyperparathyroidism. The histological composition of these neoplasms makes them a diagnostic challenge, as their high adipose content leads to difficulty localising them on imaging and can lead pathologists towards a wrong diagnosis. There are less than 100 cases in the literature since they were first described in 1958, and to our knowledge this is the largest parathyroid lipoadenoma to be reported. Method A minimally invasive parathyroidectomy with intraoperative parathyroid hormone monitoring was performed in the case of a male with a large neck mass and symptomatic primary hyperparathyroidism. Results A giant parathyroid lipoadenoma was excised, with an appropriate decrease in intraoperative parathyroid hormone level observed. The patient has been cured of his primary hyperparathyroidism, with no issues following his discharge from our institution. Conclusions We highlight the importance of having the parathyroid lipoadenoma as a differential diagnosis for patients who develop primary hyperparathyroidism.