Hyperparathyroidism Mancini

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Hyperparathyroidism Mancini

  1. 1. Hyperparathyroidism www.hi-dentfinishingschool.blogspot.com
  2. 2. Anatomy/Embryology <ul><li>endoderm of pharyngeal pouches III and IV </li></ul><ul><li>inferior parathyroid glands arise from pouch III </li></ul><ul><ul><li>migrate down with the thymus </li></ul></ul><ul><ul><li>usually located at inferior pole of the thyroid </li></ul></ul><ul><ul><li>associated with most variability in location </li></ul></ul><ul><li>superior parathyroid glands arise from pouch IV </li></ul><ul><ul><li>located just above the intersection of recurrent laryngeal nerve and the inferior thyroid artery </li></ul></ul><ul><li>usually 4 glands, supernumerary glands in 15% </li></ul>
  3. 3. Anatomy/Embryology <ul><li>parathyroid glands typically located posterolateral to the thyroid </li></ul><ul><li>arterial supply: inferior thyroid artery (superior thyroid, throidea ima) </li></ul><ul><li>venous drainage: inferior, middle, superior thyroid veins </li></ul><ul><li>adult parathyroid gland 50% parenchyma 50% fat </li></ul><ul><li>cell types: </li></ul><ul><li>chief cells (water clear cells) </li></ul><ul><li>oxyphil cells </li></ul>
  4. 4. Parathyroid Hormone <ul><li>secreted by chief cells </li></ul><ul><li>Release of PTH </li></ul><ul><li>Increased by: low serum calcium </li></ul><ul><li>Decreased by: high serum calcium, </li></ul><ul><li>low magnesium, </li></ul><ul><li>1,25 dihydroxy vitamin D </li></ul><ul><li>vitamin D3  25-OH vitamin D  1,25 OH 2 vitamin D </li></ul><ul><li>skin liver kidney </li></ul>
  5. 6. Parathyroid Hormone <ul><li>Type I PTH receptors present in bone, kidney and intestine </li></ul><ul><ul><li>Bone </li></ul></ul><ul><ul><ul><li>+ osteoclasts - osteoblasts </li></ul></ul></ul><ul><ul><ul><li>increased bone resorption </li></ul></ul></ul><ul><ul><ul><li>calcium and phosphorus release </li></ul></ul></ul><ul><ul><li>Kidney </li></ul></ul><ul><ul><ul><li>increased calcium resorption </li></ul></ul></ul><ul><ul><ul><li>increased phosphorus excretion </li></ul></ul></ul><ul><ul><ul><li>increased conversion of 25 hydroxy vitamin D to 1,25 dihydroxy vitamin D </li></ul></ul></ul><ul><ul><li>Intestines (indirect effect through vitamin D) </li></ul></ul><ul><ul><ul><li>increased calcium absorption </li></ul></ul></ul>
  6. 7. Hypercalcemia <ul><li>Calcium intake </li></ul><ul><li>Hyperparathyroidism </li></ul><ul><li>Hyperthyroidism </li></ul><ul><li>Immobilization </li></ul><ul><li>Milk Alkali Syndrome </li></ul><ul><li>Paget’s Disease </li></ul><ul><li>Adrenal Insufficiency </li></ul><ul><li>Neoplasm </li></ul><ul><li>Bone mets, bone tumors </li></ul><ul><li>PTH related peptide secreting tumors (small cell lung cancer) </li></ul><ul><li>Blast crisis </li></ul><ul><li>Primary malignancies </li></ul><ul><li>Zollinger Ellison (MEN I Syndrome) </li></ul><ul><li>Elevated Vitamin D </li></ul><ul><li>Elevated Vitamin A </li></ul><ul><li>Sarcoid and other granulomatous disorders </li></ul><ul><li>Familial hypocalciuric hypercalcemia </li></ul><ul><li>Lithium </li></ul><ul><li>Thiazide Diuretics </li></ul>
  7. 8. Hyperparathyroidism <ul><li>100,000 new cases per year in the US </li></ul><ul><li>2:1 female:male ratio </li></ul><ul><li>average age at diagnosis 55 </li></ul><ul><li>2/1000 people over the age 60 </li></ul>
  8. 9. Primary Hyperparathyroidism <ul><li>High serum calcium (ionized calcium) </li></ul><ul><li>High or high normal PTH levels </li></ul><ul><li>Solitary Parathyroid Adenoma ~85% </li></ul><ul><li>Multiple Adenomas, hyperplasia ~15% </li></ul><ul><li>Parathyroid Carcinoma ~1% </li></ul>
  9. 10. Manifestations of Primary Hyperparathyroidism <ul><li>Hypercalcemia </li></ul><ul><li>Hypercalciuria </li></ul><ul><li>Increased rate of bone turnover </li></ul>
  10. 11. Manifestations of Primary Hyperparathyroidism <ul><li>neurobehavioral symptoms: fatigue and weakness </li></ul><ul><li>nephrolithiasis 20% </li></ul><ul><li>cardiac calcification and LV hypertrophy </li></ul><ul><li>osteopenia </li></ul><ul><li>most patients asymptomatic although fatigue and weakness are undercounted as symptoms </li></ul><ul><li>25% of asymptomatic patients have progressive disease </li></ul>
  11. 12. Hereditary Primary Hyperparathyroidism <ul><li>MEN I : parathyroid, pancreatic (Zollinger Ellison), pituitary (prolactinoma) </li></ul><ul><li>tumor suppressor MENI gene, autosomal dominant inheritance </li></ul><ul><li>MEN 2A : parathyroid, pheochromocytoma, medullary thyroid cancer </li></ul><ul><li>RET proto-oncogene, autosomal dominant inheritance </li></ul><ul><li>Familial Hypocalciuric Hypercalcemia : autosomal dominant, surgery not indicated, PTH normal </li></ul><ul><li>Neonatal Severe Hyperparathyroidism </li></ul><ul><li>Hyperparathyroidism- Jaw Tumor Syndrome </li></ul>
  12. 13. Surgical Intervention in Primary Hyperparathyroidism <ul><li>NIH Criteria for Parathyroidectomy (1991, 2002) </li></ul><ul><li>Any of the following: </li></ul><ul><li>serum calcium > 1mg/dL above normal </li></ul><ul><li>history of life threatening hypercalcemia </li></ul><ul><li>abnormal serum Cr </li></ul><ul><li>elevated urine calcium, > 400mg/day </li></ul><ul><li>kidney stones </li></ul><ul><li>< 50 years old </li></ul><ul><li>bone density less than two standard deviations below the norm </li></ul><ul><li>neuromuscular symptoms </li></ul>
  13. 14. Surgical Intervention in Primary Hyperparathyroidism <ul><li>NIH criteria leave out patients who would benefit from parathyroidectomy </li></ul><ul><li>ParathyroidectomyBenefits </li></ul><ul><ul><li>neurobehavioral symptoms improve </li></ul></ul><ul><ul><li>bone mass increases </li></ul></ul><ul><ul><li>safe in patients over 70 years old </li></ul></ul><ul><ul><li>bilateral neck exploration cures 95-99% of patients with a 1-3% complication rate </li></ul></ul>
  14. 15. Preoperative Evaluation <ul><li>neck ultrasound </li></ul><ul><li>MRI </li></ul><ul><li>thallium-technetium dual isotope scintigraphy </li></ul><ul><li>technetium-99m sestamibi scan </li></ul><ul><li>SPECT sestamibi scan: allows for 3-D localization but is expensive </li></ul>
  15. 16. Preoperative Study Comparison <ul><li> Sens Spec </li></ul><ul><li>thall/techn scintigraphy 73% 94% </li></ul><ul><li>computed tomography 68% 92% </li></ul><ul><li>ultrasonography 55% 95% </li></ul><ul><li>MRI 50% 87% </li></ul><ul><li>Technetium-99m Sestamibi 91% 99% </li></ul>
  16. 17. Technetium-99m Sestamibi Scan
  17. 18. Technetium-99m Sestamibi Scan <ul><li>technetium 99m taken up by the thyroid </li></ul><ul><li>sestamibi taken up by both the parathyroid and thyroid tissue </li></ul><ul><li>sestamibi washes out of the thyroid faster </li></ul>
  18. 19. Preoperative Evaluation <ul><li>no consensus on whether preoperative localization necessary </li></ul><ul><li>preoperative localization can allow for unilateral focused parathyroidectomy </li></ul><ul><li>The combination often used is: </li></ul><ul><ul><li>sesatmibi for localization </li></ul></ul><ul><ul><li>ultrasound for information on size and relationship of the abnormal glands to surrounding tissue </li></ul></ul><ul><li>sestamibi scanning limited in identifying multiple adenomas and 4 gland hyperplasia </li></ul><ul><li>preoperative localization essential in reoperation cases </li></ul>
  19. 20. Parathyroidectomy <ul><li>Options: </li></ul><ul><li>bilateral neck exploration </li></ul><ul><li>unilateral focused parathyroidectomy </li></ul><ul><li>endoscopic parathyroidectomy </li></ul><ul><li>video assisted parathyroidectomy </li></ul>
  20. 21. Intraoperative Considerations <ul><li>Radioguided surgery: timing dependent </li></ul><ul><li>Intraoperative ultrasound </li></ul><ul><li>Intraopertive internal jugular PTH samples </li></ul><ul><li>PTH assay: </li></ul><ul><li>most widely used intraoperative test </li></ul><ul><li>provides an efficient means of determining adequacy of resection </li></ul><ul><li>allows for determination of the need for four gland exploration </li></ul>
  21. 22. PTH Assay <ul><li>collection from a peripheral venous sample, IJ sampling may be inaccurate </li></ul><ul><li>baseline measures are pre-incision and post-manipulation </li></ul><ul><li>propofol will interfere with the assay </li></ul><ul><li>samples sent at fixed time intervals after resection </li></ul><ul><li>Different standards for what constitutes a successful resection </li></ul><ul><ul><li>Drop of at least 50% from highest baseline value </li></ul></ul><ul><ul><li>Return of PTH level to normal (used at DHMC) </li></ul></ul>
  22. 23. Persistent Hyperparathyroidism <ul><li>5-10% of patients have persistent disease </li></ul><ul><li>Location of the abnormal glands at second operation </li></ul><ul><li>neck 30-54% </li></ul><ul><li>mediastinum 16-34% </li></ul><ul><li>retroesophageal 14-39% </li></ul><ul><li>upper cervical area 8% </li></ul><ul><li>aortic arch area 5% </li></ul>
  23. 24. Persistent Hyperparathyroidism <ul><li>localization studies necessary prior to reoperation </li></ul><ul><li>sestamibi, MRI and ultrasound together identify abnormal glands in 87% of patients </li></ul><ul><li>Invasive studies used if non-invasive methods cannot localize the abnormal gland </li></ul><ul><li>selective arteriography </li></ul><ul><li>selective venous sampling </li></ul><ul><li>FNA and PTH assay </li></ul><ul><li>Complication rate at reoperation for recurrent laryngeal nerve injury or hypoparathyroidism </li></ul><ul><li>1-2% </li></ul>
  24. 25. Secondary Hyperparathyroidism <ul><li>Hypocalcemia in chronic renal failure stimulates PTH secretion and parathyroid gland growth </li></ul><ul><li>Hypocalcemia in CRF caused by hyperphosphatemia and decreased renal production of 1,25 dihydroxy vitamin D </li></ul><ul><li>First line therapy: </li></ul><ul><ul><ul><li>phosphate binders </li></ul></ul></ul><ul><ul><ul><li>supplemental vitamin D </li></ul></ul></ul><ul><li>Severe or refractory cases of secondary hyperparathyroidism should undergo surgery </li></ul><ul><ul><ul><li>subtotal parathyroidectomy </li></ul></ul></ul><ul><ul><ul><li>total parathroidectomy with autotransplantation </li></ul></ul></ul>
  25. 26. Tertiary Hyperparathyroidism <ul><li>after renal transplant or as a progression of secondary hyperparathyroidism </li></ul><ul><li>hyperparathyroidism and hypercalcemia </li></ul><ul><li>1/3 of transplant patients </li></ul><ul><li>hyperclacemia can threaten the graft </li></ul><ul><li>usually subsides within months to years </li></ul><ul><li>1-3% of patients require parathyroidectomy </li></ul><ul><ul><ul><li>subtotal parathyroidectomy </li></ul></ul></ul><ul><ul><ul><li>total parathyroidectomy with autotransplantation </li></ul></ul></ul>
  26. 27. Parathyroid Carcinoma <ul><li>Occurs in ~1% of patients with hyperparathyroidism </li></ul><ul><li>Associated with genes: cyclin D1, MEN1, HRPT2 </li></ul><ul><li>Risk Factors </li></ul><ul><ul><ul><li>neck irradiation </li></ul></ul></ul><ul><ul><ul><li>ESRD </li></ul></ul></ul><ul><ul><ul><li>familial hyperparathyroidism (not MEN syndromes) </li></ul></ul></ul><ul><ul><ul><li>hyperparathyroidism- jaw tumor syndrome </li></ul></ul></ul>
  27. 28. Parathyroid Carcinoma <ul><li>more severe hypercalcemia 3-4 mg/dl above normal </li></ul><ul><li>nephrolithiasis 56% </li></ul><ul><li>renal insufficiency 84% </li></ul><ul><li>pathologic fractures or radiographic evidence of bone disease 40% </li></ul><ul><li>palpable neck mass 50% </li></ul><ul><li>hypercalcemic crisis 10% </li></ul>
  28. 29. Parathyroid Carcinoma <ul><li>Appearance </li></ul><ul><ul><ul><li>Adenoma: round, soft and reddish-brown </li></ul></ul></ul><ul><ul><ul><li>Parathyroid carcinoma: lobulated firm and adherent to surrounding tissue </li></ul></ul></ul><ul><ul><ul><li>Carcinoma often localized to inferior parathyroid glands </li></ul></ul></ul><ul><ul><ul><li>difficult to distinguish benign and malignant tumors histologically </li></ul></ul></ul>
  29. 30. Parathyroid Carcinoma <ul><li>Management </li></ul><ul><ul><ul><li>en bloc resection: ipsilateral thyroid lobe, overlying strap muscles and involved soft tissue </li></ul></ul></ul><ul><ul><ul><li>examination of all four parathyroid glands </li></ul></ul></ul><ul><ul><ul><li>modified radical neck dissection if lymph nodes involved (5% of the time) </li></ul></ul></ul><ul><ul><ul><li>intraoperative PTH monitoring </li></ul></ul></ul><ul><ul><ul><li>90% long term survival </li></ul></ul></ul><ul><ul><ul><li>if microscopic features of parathyroid carcinoma show up in post-op path reoperation is not indicated </li></ul></ul></ul>
  30. 31. Parathyroid Carcinoma <ul><li>Postoperatively </li></ul><ul><ul><ul><li>hungry bone syndrome: symptomatic hypocalcemia from calcium and phosphorus deposition into the bones </li></ul></ul></ul><ul><ul><ul><li>if hypocalcemia severe it’s treated with iv calcium and vitamin D </li></ul></ul></ul><ul><ul><ul><li>metastatic disease: cervical nodes, lung > liver> bone </li></ul></ul></ul><ul><ul><ul><li>metastatic disease should be resected  decreased tumor burden </li></ul></ul></ul><ul><ul><ul><li>no role for chemotherapy or XRT as primary therapy </li></ul></ul></ul><ul><ul><ul><li>XRT may be useful in the postoperative setting </li></ul></ul></ul>
  31. 32. Parathyroid Carcinoma <ul><li>Hypercalcemia </li></ul><ul><ul><ul><li>biggest problem in disseminated parathyroid carcinoma </li></ul></ul></ul><ul><ul><ul><li>acute management of hypercalcemia consists of : </li></ul></ul></ul><ul><ul><ul><ul><ul><li>normal saline </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>diuretic </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>osteoclast inhibitor (calcitonin, bisphosphonates) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>calcimimetic agent (cinacalcet) </li></ul></ul></ul></ul></ul>
  32. 33. A 45 yo man with preoperative diagnosis of primary hyperparathyroidism has a neck exploration. A large right lower parathyroid gland is removed and sent for frozen section examination. The specimen is identified as a parathyroid carcinoma. The next step should be. <ul><li>modified radical neck dissection </li></ul><ul><li>removal of the remaining 3 parathyroid glands and autotransplantation </li></ul><ul><li>exploration of the contralateral neck </li></ul><ul><li>ipsilateral thyroid lobectomy and lymph node dissection </li></ul><ul><li>biopsy of all 3 remaining parathyroid glands </li></ul>
  33. 34. A 45 yo man with preoperative diagnosis of primary hyperparathyroidism has a neck exploration. A large right lower parathyroid gland is removed and sent for frozen section examination. The specimen is identified as a parathyroid carcinoma. The next step should be. <ul><li>modified radical neck dissection </li></ul><ul><li>removal of the remaining 3 parathyroid glands and autotransplantation </li></ul><ul><li>exploration of the contralateral neck </li></ul><ul><li>ipsilateral thyroid lobectomy and lymph node dissection </li></ul><ul><li>biopsy of all 3 remaining parathyroid glands </li></ul>
  34. 35. In addition to calcium replacement, which of the following will promote correction of acute hypocalcemia after resection of a large parathyroid adenoma? <ul><li>phosphate binding acids </li></ul><ul><li>salt restriction </li></ul><ul><li>magnesium </li></ul><ul><li>zinc </li></ul><ul><li>calcitonin </li></ul>
  35. 36. In addition to calcium replacement, which of the following will promote correction of acute hypocalcemia after resection of a large parathyroid adenoma? <ul><li>phosphate binding acids </li></ul><ul><li>salt restriction </li></ul><ul><li>magnesium </li></ul><ul><li>zinc </li></ul><ul><li>calcitonin </li></ul>
  36. 37. Management of hypercalcemia associated with recurrence of parathyroid carcinoma could include administration of any of the following EXCEPT <ul><li>bisphosphonates </li></ul><ul><li>calcitonin </li></ul><ul><li>plicamycin </li></ul><ul><li>gallium nitrate </li></ul><ul><li>fluorouracil </li></ul>
  37. 38. Management of hypercalcemia associated with recurrence of parathyroid carcinoma could include administration of any of the following EXCEPT <ul><li>bisphosphonates </li></ul><ul><li>calcitonin </li></ul><ul><li>plicamycin </li></ul><ul><li>gallium nitrate </li></ul><ul><li>fluorouracil </li></ul>
  38. 39. Intraoperative parathormone assay. <ul><li>allows confirmation of removal of an adenoma </li></ul><ul><li>decreases operating time </li></ul><ul><li>decreases complications </li></ul><ul><li>is superior to preoperative localization with sestamibii scan </li></ul><ul><li>is inferior to gamma probe localization </li></ul>
  39. 40. Intraoperative parathormone assay. <ul><li>allows confirmation of removal of an adenoma </li></ul><ul><li>decreases operating time </li></ul><ul><li>decreases complications </li></ul><ul><li>is superior to preoperative localization with sestamibii scan </li></ul><ul><li>is inferior to gama probe localization </li></ul>
  40. 41. References <ul><li>Greenfield, Surgery 3 rd Edition 2001 </li></ul><ul><li>Schwartz’s Principles of Surgery 8 th Edition 2005 </li></ul><ul><li>Duh QY. What’s New in General Surgery: Endocrine Surgery. J. Am Coll Surg. November 2005; 201(5): 746-753 </li></ul><ul><li>Mittendorf EA, McHenry CR. Parathyroid Carcinoma. J Surg Onc 2005;89:136-142 </li></ul><ul><li>Lee JA, Inabnet WB. The Surgeon’s Armamentarium to the Surgical Treatment of Primary Hyperparathyroidism J Surg Onc 2005;89:130-135 </li></ul>

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