Marcin Barczynski, 1 Aleksander Konturek, 2 Alicja Hubalewska-Dydejczyk, 2. Filip Gołkowski, 1 Stanislaw Cichon, 1 Piotr Richter, 1 Wojciech Nowak

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1 3 rd Chair and Department of General Surgery 1 and Chair and Department of Endocrinology 2 Jagiellonian University, Medical College Head: Prof. Wojciech Nowak, MD, PhD INTRAOPERATIVE BILATERAL INTERNAL JUGULAR VENOUS SAMPLING AND RAPID PARATHYROID HORMONE TESTING IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM AND NEGATIVE SUBTRACTION SESTAMIBI SCAN. 1 Marcin Barczynski, 1 Aleksander Konturek, 2 Alicja Hubalewska-Dydejczyk, 2 Filip Gołkowski, 1 Stanislaw Cichon, 1 Piotr Richter, 1 Wojciech Nowak

2 Background & aims In patients with primary hyperparathyroidism (phpt) and negative sestamibi scan many surgeons recommend bilateral rather than unilateral neck exploration. However, intraoperative bilateral internal jugular venous sampling with rapid parathyroid hormone assay (BIJV-IOPTH) may be of help in lateralizing the side of the neck harboring parathyroid adenoma. This study was designed to test that hypothesis.

3 Methods A prospective, case-control study in 102 patients with phpt and a negative subtraction sestamibi scan ( ). Patients qualified for parathyroidectomy underwent BIJV-IOPTH (Future Diagnostics) as first part of the operation. Patients with a BIJV-IOPTH gradient of 10% or higher underwent unilateral neck exploration, whereas others underwent bilateral neck exploration.

4 Table 1. Preoperative characteristics of the patients. Patients Reference range N Age, years 38.0 ± Gender ratio (M:F) 12:90 - Total serum calcium, mmol/l 2.73 ± Plasma ipth level, ng/l ± Alkaline phosphatase, IU/l ± Creatinine, µmol/l 81.9 ±

5 Parathyroid subtraction scintigraphy Subtraction scintigraphy of the neck and superior mediastinum was performed at the Department of Endocrinology of Jagiellonian University College of Medicine, Krakow, Poland, prior to the referral for surgery. Anterior planar images of the neck and mediastinum were acquired by a computerized γ camera (Orbiter; Siemens, Erlangen, Germany) at 20 minutes following an i.v. injection of 2mCi (74 MBq) of 99m Tc-pertechnetate and followed by an i.v. injection of 5 mci (185 MBq) of 99m Tc-MIBI with additional images being acquired within 30 and 45 minutes. The final subtraction images were obtained after progressive subtraction of the pertechnetate image from the MIBI image. An image obtained after the subtraction procedure was considered to represent a parathyroid lesion. A study showing no foci of uptake was classified as negative.

6 Fig. 1. Negative result of 99m Tc-MIBI subtraction parathyroid scintigraphy.

7 Fig. 2. High resolution ultrasound imaging of parathyroid glands: A, 7mm solitary adenoma of the right inferior parathyroid gland (2D imaging); B, 5.2mm solitary adenoma of the left inferior parathyroid gland (2D imaging with Power-Doppler). High-resolution Doppler ultrasound of the neck with both 7.5MHz and 12MHz linear array transducers (Logiq 7; GE, Solingen, Germany) was performed during an outpatient visit prior to admission by an endocrine surgeon experienced in parathyroid ultrasound imaging (MB).

8 BIJV-IOPTH BIJV-IOPTH was done in the operating room, internal jugular venous blood was drawn from both left and right sides percutaneously using 23- to 25-G needle and 5 ml syringe with ultrasound guidance after induction of general anesthesia, but before skin incision. Blood samples were analyzed for ipth using STAT- IntraOperative-Intact-PTH Immunoassay (Future Diagnostics, Wijchen, the Netherlands). BIJV-IOPTH was considered as lateralizing and served for guidance of MIVAP if 10% differences were observed between the right and left internal jugular vein samples. However, the analysis for the utility of this technique was performed postoperatively once the ethiology of the phpt was identified.

9 Definitions according to Ito et al. True positive (TP) was when one side of BIJV-IOPTH was 10% greater than the other side and the operative finding concurred. True negative (TN) was when there were less than 10% differences between BIJV-IOPTH, and there were multiple bilateral hyperfunctioning parathyroid glands found at surgery. A false positive (FP) was when one side of BIJV-IOPTH was 10% greater than the other side of BIJV-IOPTH, whereas the operative findings revealed multiple bilateral gland disease or contralateral hyperfunctioning glands. A false negative (FN) was when there were less than 10% differences between BIJV-IOPTH, but unilateral hyperfunctioning glands were found at surgery.

10 Outcomes The primary outcome measure was number of patients with a single parathyroid adenoma who were eligible for a unilateral neck exploration.

11 Of 102 patients: Results (I) 73 (71.6%) had a single adenoma, 9 (8.8%) had double adenomas 20 (19.6%) had four-gland hyperplasia. BIJV-IOPTH was true positive in lateralizing the side of the neck harboring a solitary parathyroid adenoma in 49/73 (67.1%) of patients.

12 Table 2. Operative and follow-up data. Patients Etiology, n (%) Single parathyroid adenoma Double adenoma 4-gland hyperplasia 73 (71.6) 9 (8.8) 20 (19.6) Weight of resected parathyroid(s), mg Single parathyroid adenoma Double adenomas 4-gland hyperplasia 270 ± ± ± 127 Total serum calcium, mmol/l 2.34 ± 0.05 Plasma ipth level, ng/l 31.8 ± 12.0 Cure rate, % 100 Complications of BIJV-IOPTH 0

13 Results (II) BIJV-IOPTH was true positive: in 40/44 (90.9%) patients with superior parathyroid adenomas In 9/29 (31.0%) patients with inferior parathyroid adenomas.

14 Conclusions BIJV-IOPTH: was helpful in lateralizing the side of the neck harboring a single parathyroid in most patients with superior adenomas, but not inferior adenomas.

15 Thank you for the attention!