Current Status of Surgery For Primary and Secondary Hyperparathyroidism

1. Current Status of Surgery For Primary and Secondary Hyperparathyroidism Surgery Grand Rounds 20 Aug., 2014 W. G. Schenk III

2. Disclosures

3. HYPERPARATHYROIDISM Basic Physiology, Anatomy, Embryology Primary Hyperpara Clinical Presentations Evolution of surgical approach and pre-op imaging Secondary Hyperpara Clinical Presentation Indications for Surgical Rx Surgical Options

4. PTH and CALCIUM HOMEOSTASIS + PTH CALCIUM -

5. PTH and CALCIUM HOMEOSTASIS n-PTH c-PTH Renal c-AMP Bone Osteoclast GI Absorption GI, Renal : 1,25 D PTH _ Vit D3 Phos ++ Ca (Albumin) Calcitonin (?) + CALCIUM

6. HYPERPARATHYROIDISM Inappropriate excess secretion of Parathyroid Hormone in Primary Hyperparathyroidism Appropriate Hypersecretion in Secondary Hyperparathyroidism

8. HYPERPARATHYROIDISM SURGICAL APPROACES Embryology 3rd Branchial Pouch: Thymus and Lower PTH’s 4th Branchial Pouch: Upper PTH’s Ectopic (5%) and supranumerary (15%)

9. DIAGNOSIS OF HYPERPARATHYROIDISM PTH Ca++ PO4 U. Ca++ Cl / PO4 Ca x PO4 > 33 Primary Secondary Tertiary FHH Syndrome Malignancy

10. Differential Diagnosis of Hypercalcemia  Primary Hyperparathyroidism  Malignancy Bone Metastases Paraneoplastic  Medication Lithium, Vit. A,D, Thiazides  Granulomatous Disease  Excess intake,Dehydration, Immobilization  Familial Hypocalciuric Hypercalcemia (FHH)

11. Symptoms of Primary Hyperparathyroidism Neurologic Headache, memory loss Neurosis, Psychosis Cardiovascular Hypertension Nephrologic Stones, Renal impairment Dermatologic Pruritis, brittle nails Constitutional Fatigue, Wt loss, Anorexia GI Peptic Ulcer Disease Nausea, Vomiting Musculoskeletal Bone and joint pain Muscle weakness

12. Symptoms of Primary Hyperparathyroidism “ASYMPTOMATIC” Some symptoms can usually be elicited by careful questioning. Rationale for surgical Rx in asyptomatic patient.

13. PRIMARY HYPERPARATHYROIDISM Family History  MEN I (Wermer’s Syndrome) Pituitary, Panc Islet Cell  MEN II (Sipple’s Syndrome) MCT, Pheo (MEN IIb)  FHH (Familial Hypocalciuric Hypercalcemia)

14. PRIMARY HYPERPARATHYROIDISM Physical Exam  General : BP, Neuro, Cardiac, Operative risk  Neck Exam: Thyroid abnormality adenopathy, palpable mass Vocal cord function, neck mobility  Occult Malignancy (Breast, Prostate)

15. LABORATORY EVAL IN PRIMARY HYPER-PTH Calcium Determination(s) Cl, Po4, Alb, Tot Protein, BUN, Creat., Alk Phos. ** Cl/Po4 ratio > 33 24-hr Urine ** Ca > 100 mg / day U-creat., Ca/Cr Clearance ratio, Cyclic AMP  Chest X-ray Hand, Bone Xrays (optional) PTH Radioimmunoassay

16. PTH Levels in Primary Hyperparathyroidism

17. INDICATIONS FOR SURGERY IN PRIMARY HYPERPARATHYROIDISM (No prior neck surgery) Diagnosis of Hyperparathyroidism Questionable Secure Symptomatic Asymptomatic Significant Calcium 10.5 11.0 Surgical risk Prohibitive Low

18. HYPERPARATHYROIDISM SURGICAL APPROACES ANATOMIC CORRELATION: “Sporadic” Primary – single gland (95%) Familial Primary Secondary Multigland Hyperplasia Tertiary

19. Sporadic Primary Hyperpara: Single Parathyroid Adenoma

20. Hypercellular Parathyroid 800 mg

21. Rationale for Pre-op Imaging in Primary Hyper-PTH •  Identify ectopic and supernumerary glands • Identify multiple adenomas • Provide pre-op anatomic confirmation of biochemical Dx • Reduce incidence of persistent/recurrent hyper-para • Permit “limited exploration” • Reduce complication risk

22. “The only pre-op localization necessary is to locate an experienced neck surgeon” John Doppman NIH Concensus Conference 1980

23. Hyperparathyroidism Evolution of Imaging Relevence •  Improvement in imaging technology •  Popularity of limited exploration • Development of rapid PTH Assay •  Economic pressures

24. Jim Norman (based on the past 15,000 PTH operations): “Our patients get the exact same operation regardless of scan findings – we simply do not care if their scans are positive or negative” Norman J, Lopez J, Politz D; Abandoning Unilateral Parathyroidectomy; JACS Mar 2012 ; 214(3) : 260-269

25. Surgeon-Performed Ultrasound for Primary Hyperparathyroidism Schenk WG, Hanks JB, Smith PW  Convenience, Efficiency  Surgical / Anatomic Correlation  Volume of positive studies  Additional relevant findings

26. Surgeon-Performed Ultrasound for Primary Hyperparathyroidism Classification of pre-op Neck Ultrasound  Class 1: Hi Confidence  Class 2: “Possible”  Class 0: None seen

27. Primary Hyper PTH: Pre-Op Imaging

28. Results Class 1: 111/200 (55%) 3 patients deferred surgery 107/108 Intra-op agreement 108/108 Cured

29. Results Class 1: 111/200 (55%) 3 patients deferred surgery 107/108 Intra-op agreement 108/108 Cured Class 0 : 4-D CT Scan Class 2 : Surgery w or w/o imaging

30. Tc-99m sestamibi scan Coronal slice and 3D reconstruction from a 4DCT

32. CURRENT CONTROVERSIES: “SPORADIC” PRIMARY HYPERPARA “Limited Exploration” vs. Complete Exploration Pre-op Imaging Intra-op PTH Assay Evolving Approaches: Minimally invasive / Robotic Regional Anesthesia Ambulatory/Outpatient

33. SECONDARY HYPERPARATHYROIDISM Appropriate PTH level (Nutritional or Renal). Renal Failure: Numerous influences on Ca homeostasis High proportion of Dialysis pts have elevated PTH. Less than ten percent should require surgical Rx.

34. Effects of Renal Failure on PTH Homeostasis  Diminished renal hydroxylation of D3  Decreased GI absorption of Calcium  Decreased suppression of PTH by D3  Decreased (total) serum Calcium  Decreased renal excretion of phosphorus  Direct effect of Hyperphosphatemia  Decreased ionized Calcium  Elevated “set point” of PTH responsiveness  Osteoblast resistance to PTH  Autonomous Hypersecretion from Hyperplasia

35. DIAGNOSIS OF HYPERPARATHYROIDISM PTH Ca++ PO4 U. Ca++ Cl / PO4 Ca x PO4 Primary Secondary Tertiary FHH Syndrome Malignancy + >55

36. PTH Levels in Secondary Hyperparathyroidism The majority of dialysis patients have some elevation in PTH. A level in the 100- 300 pg/ml range is common. Elevated level alone is not an indication for surgical Rx.

37. SECONDARY HYPERPARATHYROIDISM Indications for Surgery  Failure of reliable maximal medical Rx.  Development of significant symptoms: Musculo- skeletal, pruritis, calcinosis cutis, neuro-psych.  Calcium x Phosphorus product above 70.  Osteopenia, decreasing measured bone density, bone biopsy.  Development of Tertiary Hyper-PTH

39. SECONDARY HYPERPARATHYROIDISM PRE-OP EVALUATION  General condition - operative risk.  Virtually all are dialysis-dependant  Alk Phos  Ultrasound (optional); Sestamibi scan not helpful.

40. Neck Exploration Identification of all Parathyroid Glands

41. SECONDARY HYPERPARATHYROIDISM Surgical Options Subtotal Parathyroidectomy or Total Parathyroidectomy with PTH Autotransplant Essential Components of Either Procedure: • Complete Neck Exploration • Identification of All PTH’s • Ablation of Hyperplastic Glands • Leave 40-70 mg Functioning PTH • Consider temporary central line

42. SURGERY: FAMILIAL PRIMARY (MEN) SECONDARY AND TERTIARY  Subtotal (3 ½ gland) resection  Total Parathyroidectomy with Autotransplant. Special Considerations •  MEN I Syndrome • Calcinosis/Calciphylaxis • Tertiary after transplant

46. Subtotal PTH-x vs Total PTH-x with AutoTx Long – term Recurrence of Secondary Hyper PTH Patient Compliance Complexity and Duration of Surgery Ease / Cost of Post-op Care Calcinosis – special situation

47. Any Questions ?