Intraoperative Parathyroid Hormone Assay-Guided Parathyroidectomy

1. Intraoperative Parathyroid Hormone Assay-Guided Parathyroidectomy By: Jeffrey A. Neale MD

2. Background WHAT is it ?Measurement of Parathyroid hormone in plasma WHAT has it done? a.) Changed our understanding and management of sporadic primary hyperparathyroidism (SPHPT). SPHPT a.) Autonomous hypersecretion of parathormone by one or more parathyroid glands. b.) The etiology is unclear, c.) IT is different from secondary hyperparathyroidism > Chronic renal failure > Familial disorders (MEN syndromes).

3. Background The GOAL OF Treatment 1.) Identifying and remove hypersecreting parathyroid tissue 2.) Preserve normal functioning gland = maintain calcium homeostasis. Operative approaches: 1.) The traditional parathyroidectomy 2.) The quantitative parathyroidectomy a.) Guided by parathyroid hormone (PTH) dynamics

4. Who Qualifies IF diagnosis of SPHPT is SECURED: Significant and persistent hypercalcemia, Elevated PTH level, Normal renal function, Normal or elevated urinary calcium, No family history of hyperparathyroidism

5. PTH ASSAY The traditional operation a.) Bilateral neck exploration, b.) Identification of four parathyroids, c.) Based on the surgeon's judgment, excision of all grossly enlarged glands. d.) All normal-sized parathyroid glands assumed to be functioning normally are left in situ. PROBLEMS 1.) The size of a parathyroid gland is not always related to its secretory function. 2.) THEREFORE Experience of the surgeon is very important. 3.) If any hypersecreting gland is left behind= hypercalcemia =-resulting in a failed Operation 4.) EXCISION of nl parathyroids are excised 5.) COMPRIMISED BLOOD SUPPLY, during an extensive exploration, Above (4 +5) can result in hypocalcemia and tetany

6. Success Rates 95% to 99% = Experienced endocrine surgeons. 70% = occasional operation by inexperienced surgeons.

7. The Catalyst For the Quantative Method A Hypersecreting parathyroid that was missed after excision of a single enlarged gland during bilateral neck exploration.

8. History of Parathormone Measurement in Man The diagnostic accuracy= improved after Reiss and Canterbury first described an antibody with good affinity for PTH in man that could be measured with an immunoradiometric assay. BUT the assay was limited as it recognized only part of the PTH molecule. 1987, Nussbaum et al. described a two-site antibody technique a.) MORE SENSTIVE b.) MORE SPECIFIC that proved more sensitive and specific than previous assays. T c.) PTH HALF LIFE was 3 to 5 minutes d.) THEY SUGGESTED there may be a benefit to the surgeon e.) The assay changed forms Radionuclear >>>> Immunochemiluminescent technology using a light source

9. History of Parathormone Measurement in Man Commercially available for intraoperative use in 1996 Positive Attributes of the ASSAY a.) Surgeons confirm the complete excision of all hyperfunctioning parathyroid tissue b.) IF anticipated decrease of PTH does not occur Alert the surgeon of an incomplete removal Indicates the need for further exploration

10. How Does QPTH Work? The Secreted Hormone from the Hyperfunctioning gland a.) Is measured by a two-site antibody immunochemiluminescent, b.) Nonradioactive, that captures and quantifies the unknown amount of hormone in a sample of plasma. c.) The intraoperative assay in OR = rapid reaction time > Less sensitive than the standard > However, QPTH works very well when plasma PTH levels are elevated.

11. Why the difference in Techniques? 1.) The assay time is shortened by increasing the antibody content in the intraoperative test to speed the reaction. 2.) Rapid results are essential if the surgeon to guide the parathyroidectomy. 3.) Most intraoperative assays have result times of 8 to 30 minutes, 4.) The dynamic changes shown by these rapid assays correlate well with standard diagnostic assays.

12. How Does the Surgeon Use QPTH? Measure only circulating amount of hormone at the time . Is an effective guide if the surgeon must be attentive and direct the sampling times as related to the stages of the operative procedure. Predict postoperative calcium levels following excision of hyperfunctioning glands. a.) The most accurate = drop in PTH of 50% or more from the highest level, 10 minutes after complete resection of all hyperfunctioning tissue.

13. How Does the Surgeon Use QPTH? The protocol, a.) Developed at the University of Miami, b.) Peripheral venous or arterial access is obtained+ stopcock= Multiple samples c.) The catheter is kept open with a slow infusion of saline, d.) 4 mL of whole blood are collected in an EDTA tube at specific times: > Skin preincision, > Pre-excision = TIME 0 (After dissection and just before clamping the suspected gland's blood supply) > 5 min > 10 min after excision of the suspected abnormal gland.

14. PREDICTING NL OR LOW POST OP SERUM CALCIUM LEVELS  Drop in PTH a.) 50% or more from the highest either pre-incision or pre-excision levels b.) 10 minutes after the excision of all abnormal parathyroid gland(s), THE ABOVE = TELLS THE SURGEON 1.) NO NEED FOR FURTHER a.) Exploration b.) Identification of remaining glands

15. QPTH ASSAY Measure in picograms per milliliter, BUT usually report from the highest measured level EXAMPLE Excision of a single hypersecreting gland, The peripheral plasma hormone levels in each sample were :a.) 69 pg/mL preincision, b.) 230 pg/mL pre-excision, c.) 55 pg/mL at 5 minutes after excision, d.) 38 pg/mL at 10 minutes. e.) Drop at the 10-minute postexcision interval of 83% from the highest PTH level,

16. QPTH ASSAY THERFEORE predicts a postoperative EUCALCEMIA + SUCCESSFUL OPERATION. DOES NOT PREDICT 1.) Late recurrence of hyperparathyroidism (following at least 6 months of eucalcemia), PREDICTS a.) Hypersecreting glands have been excised b.) Only normally functioning glands remain in situ at the time of the parathyroidectomy.

18. Results of QPTH-Guided Parathyroidectomy A limited parathyroidectomy without a continued search for the remaining normal glands can be performed. Enabled many surgeons to change their operative approach in treating patients with SPHPT. QPTH has eliminated the subjective evaluation of parathyroid hypersecretion based on observed gland size, Improved the operative success rate of parathyroidectomy. > Operative success = postoperative eucalcemia > 6months a.) Achieved in 97% of 421 consecutive patients. b.) The estimated 5-year recurrence-free rate was 97% (95% confidence interval, 91% to 99%), c.) Similar to that reported following traditional parathyroidectomy

20. Preoperative Localization Studies Important role in these less-extensive operations a.) Identify the anatomical site ( hypersecreting, enlarged gland. The most reliable MIBI scan Cervical ultrasonography. GOAL: When a suspected abnormal gland is localized preoperatively, a.) Allows the surgeon to perform minimal dissection of the targeted area b.) Excision of an abnormal gland. c.) QPTH then signals whether all hypersecreting tissue has been removed or not

24. Preoperative Localization studies Often incorrect or do not recognize the presence of multiglandular disease. THEREFORE, QPTH = Essential for operative success. IE For instance, you excise only the identified focus of activity on a nuclear scan, a high operative failure rate can be expected

25. Other Benefits Shorter operating time, Use of local or light general anesthesia, Same-day discharge without overnight stay, and cost savings.

26. Study conducted by the AUTHOURS of the chapter 1.) Preoperative localization correctly identified all abnormal parathyroid glands in 80% of patients with SPHPT. BUT a.) MIBI scans were completely negative (7%), b.) Had a single wrong focus (7%), c.) Showed multiple foci, both correct and incorrect (4%), d.) Missed multiple gland involvement (3%). QPTH used as a parathyroidectomy adjunct 1.) Changed the operative management in 89% (77/88) pt with incorrect or negative MIBI scans 2.) HELPED success rate of 97% in these patients

27. The Ultrasound Helps ID thyroid abnormalities a.) Gives a false focus of activity in MIBI scans. b.) Sensitivity and specificity as the nuclear scan, c.) Depends on QPTH to assure operative success when a limited or minimal operative approach is used. 

28. If Problems with imaging Differential venous sampling of the jugular veins for lateralization in the neck. The assay is also useful in the search for �hard-to-find� glands a. ) Provides a rapid identification of suspected tissue by fine-needle aspiration and hormone measurement without biopsy and frozen section.

29. QPTH OVERALL SENSITIVTIY of 98%, SPECIFICITY of 96%, PPV of 99%, NPV 90%, OVERALL accuracy of 97%.