UCI Otolaryngology Head and Neck Surgery

1. UCI Otolaryngology Head and Neck Surgery Thursday Morning Conference March 29, 2007 Paul K. Holden, MD

2. Case Presentation 47 yo female referred to you for the following laboratory value: Ca = 11.9

3. HPI / PMH Otherwise Healthy Hi Ca found on routine annual screening Repeat tests confirm similar result No h/o renal calculi, bone pain, other pain Admits to some vague symptoms of fatigue and low energy Takes hormone replacement and calcium supplements, otherwise no meds Wants to know if it is serious�

4. Question #1 Name the FOUR main organs that regulate blood Ca levels.

5. Question #2 Upon which main organ(s) does PTH directly act to regulate blood Ca levels? Kidney Bone (osteoclasts) Bonus: How do the kidneys act on the gut?

6. V I T A M I N D

7. C H I M P A N Z E E S

8. Calcium - exogenous Hyperparathyroidism Immobility Metastasis to bone Paget�s disease of bone Addison�s disease Neoplasm (prostate, lung, colon, breast, HNC) Zollinger Ellison Syndrome Excess of Vit A or D, thiazide, lithium, estrogen Endocrine disorder (other) thyroid, pheo, FHH Sarcoid (granulomatous diseases)

9. Question #3 What is the most common presentation for a patient with hyperparathyroidism? Asymptomatic Some will give vague symptoms of fatigue or limb discomfort after being prompted. Severe cases can present with �bones, stones, groans, psychic overtones�� Bones � osteitis fibross cystica, renal stones, abdominal/limb pain groans, depression, polyuria, constipationBones � osteitis fibross cystica, renal stones, abdominal/limb pain groans, depression, polyuria, constipation

10. Question #4 Which of the following is most likely primary hyperparathyroidism? ?Ca ?PTH ?Phos ?Ca ?PTH ?Phos ?Ca ?PTH ?Phos High or normal PTH in the face of high serum calcium and low phos is usually primary HPT.

11. Primary Hyperparathyroidism 85% caused by single adenoma Hyperplasia (8-10%) Double adenoma (3-5%) Parathyroid Carcinoma (1%) Tx is usually surgical.

12. Secondary Hyperparathyroidism Most common cause is Renal insufficiency � causes increased Phosphate, poor retention of Ca, poor conversion of 25 Vit D3 to 1,25 D3 Other diseases affecting bone � OI, Paget�s, myeloma, bone mets, Addison�s Tx is control cause, usually medical mgmt, phosphate binders, vit D, calcimimetics

13. Tertiary Hyperparathyroidism Development of uncontrollably high PTH levels due to long-term secondary hyperparathyroidism, calcium levels can also be high. Tx is usually surgical.

14. Pseudo Hyperparathyroidism Autosomal Dominant disease characterized by low calcium, high phosphate and insensitivity to PTH. Short stature, round face, shortened bones of hands and feet, dental hypoplasia, soft tissue calcifications Also called Albright Hereditary Osteodystrophy (AHO)

15. Back to Our Patient� What additional studies will help with the diagnosis/management of this patient�s disease? 24hr Urine Calcium is 550mg Intact PTH level is mildly elevated DEXA Shows T-Scores -2.0 in spine, hip, distal radius.

16. Is she a surgical candidate? NIH Position Statement (Updated 2002) Surgery indicated if one of the following is true: Ca > 1mg/dL over ULN (repeated) 24hr Urine Ca > 400mg CrCl decreased by 30% from normal T-score >2.5 of spine, hip or distal radius (any one site) Age < 50 yrs Pt request or surveillance will be difficult or impossible

17. Preoperative Imaging Which of the following has approximately 90% sensitivity in detecting a single cervical adenoma? MRI with contrast CT with contrast, fine cuts High resolution ultrasound Tc99 Sestamibi Scan

18. Preoperative Imaging Tc99 has a 91% sensitivity and 97% positive predictive value � helps localization, reduces morbidity, also good (less sensitive) for double adenoma. Tc99-SPECT incorporates 3-D positional information, no evidence it changes diagnostic sensitivity. Hi Res Ultrasound 90% sensitivity, esp helpful with negative/marginal Tc99 scan, helps localization and volume approximation, less sensitive with multinodular goiter.

19. Preoperative Imaging MRI � much less sensitive (appx 60%) but can help with mediastinal localization, expensive, no radiation. CT � essentially equivalent sensitivity to MRI, though less expensive, has radiation, also helps with mediastinal localization.

20. Where�s the Adenoma??

21. Where�s the Adenoma??

22. Where�s the Adenoma??

23. Where�s the Adenoma??

24. Our Patient�s Results Pt has Tc99 Sestamibi scan showing left inferior adenoma. HR Ultrasound confirms a 1cm nodule in approximately the same location.

25. What operation do you perform? A) Subtotal parathyroidectomy with reimplantation B) Bilateral exploration with selective gland removal, possible reimplantation C) Unilateral exploration of both glands, removal of adenoma D) Unilateral w/ possible bilateral exploration, intraopertive PTH monitoring

26. Intraoperative PTH Monitoring PTH has short half life, allowing for confirmation of appropriate drop in levels by 50% within 10 minutes. Can repeat at 20 mins if dropped but not quite enough. Most surgeons also prefer to see a drop into normal range. Limitation in patients with normal preop PTH levels.

27. Medical Management 25% progression of disease in 10 yrs (more likely in pts < 50yrs) Bisphosphonates � studies show increased bone denisty Ca/Vit D � help reduce bone loss Calcimimetics (Cincacalcet) � currently in use for parathyroid ca and secondary HPT SERMs � tamoxifen or raloxifene Monitor bone density every year and Ca level every 6 months

28. Hereditary Hyperparathyroidism Familial Hypocalciuric Hypercalcemia � Dx with 24 hr Urine Ca < 50mg/24 hrs MEN I and IIa Hyperparathyroidism � Jaw Tumor Syndrome Fibro-osseous jaw tumors; Renal cysts/tumors Familial Isolated Hyperparathyroidism � Other family members with HPT and no other hereditary issues. Usually hyperplasia.

29. FHH Autosomal Dominant Elevated Serum Calcium PTH low normal Low urinary excretion of Ca (<50mg/24hr) Hypermagnesemia Surgery is NOT corrective Prognosis excellent w/ confirmation of FHx and hypocalciuria

30. MEN I Hyperparathyroidism (95%) Hyperplasia Gastrinoma (45%) tumor of pancreas Pituitary Adenoma (25%) Also have facial angiofibromas (85%) and collagenomas (70%) Subtotal parathyroidectomy high success rate, but 50% recurrence at 10 yrs. Higher rate of postop hypocalcemia.

31. MEN IIa Medullary Thyroid Ca (95%) Pheochromacytoma (50%) Hyperparathyroidism (20%) usu adenoma RET mutation (98%) Higher surgical cure rate than MEN I and far less likely recurrence rate.

32. Final Quiz Questions 49 yo male with hyperparathyroidism and history of an ossifying fibroma of the mandible. Which of the following should you order: MRI of the IACs pre/post Gad Renal U/S Spiral Chest CT Barium Swallow

33. Final Quiz Questions Hyperparathyroidism plus the below findings, what is the disease?

34. Final Quiz Questions Identify any medications below that can cause hypercalcemia: Lithium Prilosec Cinacalcet Hydrochlorothiazide Aleve

35. Final Quiz Questions Recall the following numbers from the NIH guidelines: Serum Ca > ___ above ULN 24hr Urine Ca > ____ mg CrCl reduced by ____% below normal DEXA T-score of ____ in spine, wrist, hip Age < ____

36. Final Quiz Questions You are in multidisciplinary clinic presenting a patient with hyperparathyroidism. You are asked �What is the calcium-creatinine clearance ratio?� You reply �ask an endorinologist� You ask �the calcium creatinine what?� You say �Let me just answer this page, I�ll be right back� You ask �can I phone a friend?�

37. The Trivia CA/CRT ratio: (24 hr urine calciumXserum crt)/(24 hr urine crtXserum calcium) Rarely used in cases of tertiary HPT to decide for surgery referral. In those cases, the ratio is >70.

38. Thank You!