Current Status of Surgery For Primary and Secondary Hyperparathyroidism Surgery Grand Rounds 20 Aug., 2014 W. G. Schenk III Disclosures 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 PTH and CALCIUM HOMEOSTASIS + PTH - CALCIUM PTH and CALCIUM HOMEOSTASIS n-PTH c-PTH Renal c-AMP PTH Vit D3 _ Bone Osteoclast Phos GI, Renal : 1,25 D Ca++ Calcitonin (?) GI Absorption (Albumin) CALCIUM + HYPERPARATHYROIDISM Inappropriate excess secretion of Parathyroid Hormone in Primary Hyperparathyroidism Appropriate Hypersecretion in Secondary Hyperparathyroidism HYPERPARATHYROIDISM SURGICAL APPROACES Embryology 3rd Branchial Pouch: Thymus and Lower PTH’s 4th Branchial Pouch: Upper PTH’s Ectopic (5%) and supranumerary (15%) DIAGNOSIS OF HYPERPARATHYROIDISM PTH Primary Secondary Tertiary FHH Syndrome Malignancy Ca++ PO4 U. Ca++ Cl / PO4 > 33 Ca x PO4 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) Symptoms of Primary Hyperparathyroidism Constitutional Fatigue, Wt loss, Anorexia Neurologic Headache, memory loss Neurosis, Psychosis GI Peptic Ulcer Disease Nausea, Vomiting Cardiovascular Hypertension Musculoskeletal Bone and joint pain Muscle weakness Nephrologic Stones, Renal impairment Dermatologic Pruritis, brittle nails Symptoms of Primary Hyperparathyroidism “ASYMPTOMATIC” Some symptoms can usually be elicited by careful questioning. Rationale for surgical Rx in asyptomatic patient. 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) 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) 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 PTH Levels in Primary Hyperparathyroidism INDICATIONS FOR SURGERY IN PRIMARY HYPERPARATHYROIDISM (No prior neck surgery) Diagnosis of Hyperparathyroidism Questionable Secure Symptomatic Asymptomatic Significant Calcium Surgical risk 10.5 Prohibitive 11.0 Low HYPERPARATHYROIDISM SURGICAL APPROACES ANATOMIC CORRELATION: “Sporadic” Primary – single gland (95%) Familial Primary Secondary Tertiary Multigland Hyperplasia Sporadic Primary Hyperpara: Single Parathyroid Adenoma Hypercellular Parathyroid 800 mg 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 “The only pre-op localization necessary is to locate an experienced neck surgeon” John Doppman NIH Concensus Conference 1980 Hyperparathyroidism Evolution of Imaging Relevence Improvement in imaging technology Popularity of limited exploration Development of rapid PTH Assay Economic pressures 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 Surgeon-Performed Ultrasound for Primary Hyperparathyroidism Schenk WG, Hanks JB, Smith PW Convenience, Efficiency Surgical / Anatomic Correlation Volume of positive studies Additional relevant findings Surgeon-Performed Ultrasound for Primary Hyperparathyroidism Classification of pre-op Neck Ultrasound Class 1: Hi Confidence Class 2: “Possible” Class 0: None seen Primary Hyper PTH: Pre-Op Imaging Results Class 1: 111/200 (55%) 3 patients deferred surgery 107/108 Intra-op agreement 108/108 Cured 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 Tc-99m sestamibi scan Coronal slice and 3D reconstruction from a 4DCT 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 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. 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 DIAGNOSIS OF HYPERPARATHYROIDISM PTH Ca++ PO4 U. Ca++ Cl / PO4 Ca x PO4 Primary Secondary Tertiary FHH Syndrome Malignancy + >55 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. SECONDARY HYPERPARATHYROIDISM Indications for Surgery Failure of reliable maximal medical Rx. Development of significant symptoms: Musculoskeletal, pruritis, calcinosis cutis, neuro-psych. Calcium x Phosphorus product above 70. Osteopenia, decreasing measured bone density, bone biopsy. Development of Tertiary Hyper-PTH SECONDARY HYPERPARATHYROIDISM PRE-OP EVALUATION General condition - operative risk. Virtually all are dialysis-dependant Alk Phos Ultrasound (optional); Sestamibi scan not helpful. Neck Exploration Identification of all Parathyroid Glands 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 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 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 Any Questions ?