Dr. YC Pang Department of Surgery United Christian Hospital

.. It seems hardly credible that the loss of bodies so tiny as the parathyroids should be follow by a result so disastrous. William S. Halsted, 1907 Halsted WS. Hypoparathyreosis, status parathyreoprivus, and transplantation of the parathyroid glands. Am J Med Sci 1907;134:1–12.

 Primary hyperparathyroidism (pHPT) - a common endocrine disorder  Classical manifestations - stones, bones, groans and moans  Asymptomatic primary hyperparathyroidism - increasingly diagnosed due to routine biochemical testing

Bilateral cervical exploration Focused parathyroidectomy

 localized by preoperative sestamibi scan or US  A central or lateral incision measuring from 2 to 4 cm over the targeted lesion  Only the abnormal parathyroid gland is identified and excised

Improved cosmetic results with smaller incisions Decreased pain, shorter operative time Ambulatory surgery Rapid postoperative recovery Less injury to the recurrent laryngeal nerve Decreased postoperative hypocalcaemia Comparable success rates to conventional BNE

Symptomatic - Clear indication for surgical treatment Asymptomatic - Serum calcium level 1.0 mg/dL (0.25mmol/L) or greater than the accepted normal range - 24-h urinary calcium excretion greater than 400 mg/day -Creatinine clearance reduced by 30% - T-score less than –2.5 at any site - age younger than 50 years NIH guidelines Bilezikian JP, Potts JT Jr, Fuleihan Gel H, et al. Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century. J Clin Endocrinol Metab 2002;87(12):5353– 61

Many experience surgeons basing the operative decision not only on these objective criteria but on subjective complaints as well Several studies showing improvements of depression, anxiety, sleep disturbances, poor memory, and cognitive impairment after parathyroidectomy Kouvaraki MA, Greer M, Sharma S, et al. Indications for operative intervention in patients with asymptomatic primary hyperparathyroidism: practice patterns of endocrine surgery. Surgery 2006;139:527–34 Pasieka JL, Parsons LL. Prospective surgical outcome study of relief of symptoms following surgery in patients with primary hyperparathyroidism. World J Surg 1998;22(6):513–9

 Recent evidence from a long-term study of primary hyperparathyroidism over 15 years suggests the NIH guidelines for parathyroidectomy do not reliably predict worsening disease progression in asymptomatic patients Rubin MR, Bilezikian JP, McMahon DJ, et al. The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years. J Clin Endocrinol Metab 2008;93(9):3462–70

 Most of them present with vague/non-specific symptoms  <5% truly asymptomatic  Evidence of improvement in objective and subjective parameters  Evolution of parathyroid surgery  Pro-active approach should be adopted

 The only localization that a patient needs who has primary hyperparathyroidism is the localization of an experienced surgeon! —John L. Doppmann, 1991 Brennan MF. Lessons learned. Ann Surg Oncol 2006;13(10):1322–8

 Sestamibi scintigraphy  Ultrasound  Sestamibi + SPECT  Combined Mibi and USG  CT/MRI

 Able to localize 80% to 90% of single abnormal parathyroid glands  Less sensitive in the diagnosis of multiglandular disease (MGD)  False positive: thyroid nodule, lymph node  False negative: small parathyroid lesion, suboptimal dose Carniero-Pla DM, Solorzano CC, Irvin GL. Consequences of targeted parathyroidectomy guide by localizing studies without intraoperative parathyroid hormone monitoring. J Am Coll Surg 2006;202:715–22

 Commonly used for preoperative parathyroid localization  Delineating an enlarged parathyroid gland from surrounding structures  70-80% accuracy Berri RN, Lloyd LR. Detection of parathyroid adenoma in patients with primary hyperparathyroidism: the use of office-based ultrasound in preoperative localization. Am J Surg 2006;191:311–4

 Obtain real-time information regarding the anatomical location of enlarged parathyroid glands among several other structures  Allows for evaluation of thyroid abnormalities that may require surgical treatment

 Particularly useful in detecting smaller parathyroid lesions that may reside posterior to thyroid gland, at retroesophagus or within mediastinum Yip L, Pryma DA, Yim JH, et al. Can a lightbulb sestamibi SPECT accurately predict single-gland disease in sporadic primary hyperparathyroidism. World J Surg 2008;32(5):784–92

 Increase accuracy of localization of a single adenoma from 94% to 99%  Operative success rate approach 99% when result concordant, obviating the need for Intraoperative PTH monitoring (IPM)  Concordant only 50% to 60% of the time Mihai R, Palazzo FF, Gleeson FV, et al. Minimally invasive parathyroidectomy without intraoperative parathyroid hormone monitoring in patients with primary hyperparathyroidism. Br J Surg 2007;94:42–7

 Intact PTH has short half-life (2-4 minutes)  Normal parathyroid glands in patients with hyperparathyroidism are suppressed by hypercalcemia  The changes in PTH detected by the rapid PTH assay preoperative, preexcision, and postexcision is able to confirm or refute biochemical cure

 A decrease of intact PTH levels greater than 50% from the highest value in 10 minutes after removal of all abnormal parathyroid tissue  Operative success with predictive cure in 97% of cases Carneiro DM, Solorzano CC, Nader MC, et al. Comparison of intraoperative iPTH assay (QPTH) criteria in guiding parathyroidectomy: which criterion is the most accurate? Surgery 2003;134(6):973–81

 Aspirate of parathyroid tissue diluted in a syringe containing 1 mL saline  Rapid assay yields PTH values greater than 1500 pg/mL confirm diagnosis

 Increase by 10% at initial operation  Increase by 18% in reoperative patients for failed parathyroidectomy Chen H, Pruhs Z, Starling JR, et al. Intraoperative parathyroid hormone testing improves cure rates in patients undergoing minimally invasive parathyroidectomy. Surgery 2005;138(4):583–90 Irvin GL, Molinari AS, Figueroa C, et al. Improved success rate in reoperative parathyroidectomy with intraoperative PTH assay. Ann Surg 1999;229(6):874–9

MIBI alone -multiple case series and a single retrospective comparative study recommend the use of IPM Concordant MIBI and USG -add little if any benefit to the rate of cure Discordant scans -IPM recommended Intraoperative adjuncts in surgery for primary hyperparathyroidism Barney J. Harrison & Frederic Triponez Langenbecks Arch Surg (2009) 394:799–809

Focused approach parathyroidectomy without intraoperative PTH monitoring is a safe and effective treatment for primary hyperparathyroidism Dr. YC Pang, Dr. KP Tsui, Dr. CY Choi, Dr. TL Chow, Dr. SH Lam Department of Surgery United Christian Hospital

 Focused parathyroidectomy  Primary hyperparathyroidism  Jan 2002 – June 2009

 82 patients - primary hyperparathyroidism  76(92.7%) - focused approach parathyroidectomy  Mean age 60.3 (21-88)  M:F 19:57  Mean pre-operative serum calcium: 2.8 mmol/L  Mean pre-op PTH : pmol/L

USG (Surgeon) MIBICT/MRI Successful localization Failed localization9177 Not done0465 Total76

UltrasoundMIBITotal Failed localization/ not done Able to localize Failed localization279 Able to localize Total215576

 Sensitivity of USG 67/76 (88.2%)  Sensitivity of MIBI 55/72 (76.4%)  Combined USG + MIBI 74/76 (97.4%)  2 failed localization by USG/MIBI  Localized by CT scan

 76 (92.7%) focused approach parathyroidectomy  49 (64.5%) LA  27 (35.5%) GA  Mean operating time 61.2 minutes  Use of IPM: 4 patients (5.3%)

70 (97.2%) operative success No persistent hypoparathyroidism 3 patients (3.9%) suffered from hungry bone syndrome requiring prolonged calcium supplement 4 patients (5.3%) transient RLN palsy 2 patients (2.6%) permanent RLN palsy

 Only 4 patients  All of them had > 50% reduction in PTH 10mins after excision  100% operative success  No recurrence  No hypocalcemia  No RLN palsy

 Focused parathyroidectomy is the well adopted treatment for most of the cases  Combined USG and MIBI scan increases accuracy of localization  Intraoperative PTH monitor is recommended in case of discordant scan to improve the operative success

 Resources govern the choice of pre-operative localization method, or intraoperative adjuncts  In properly selected case, focused parathyroidectomy without routine use of IPM is safe and effective treatment