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What I Want from My Endocrine Surgeon? Pre-Lecture Survey

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What I Want from My Endocrine Surgeon? Pre-Lecture Survey 5/3/2019 WHAT I WANT FROM MY ENDOCRINE SURGEON? DR. VANITHA SINGARAM, MD, FACE ENDOCRINOLOGIST IOWA DIABETES AND ENDOCRINOLOGY CENTER PRE-LECTURE SURVEY • 52 YEAR OLD MAN WITH A 5 CM RIGHT THYROID NODULE, FNA REVEALS PAPILLARY THYROID CARCINOMA. NEXT STEP? A. TOTAL THYROIDECTOMY B. TOTAL THYROIDECTOMY WITH CENTRAL COMPARTMENT DISSECTION C. US OR CT NECK D. PET 1 5/3/2019 PRE-LECTURE SURVEY 35 YR. OLD FEMALE WITH HYPERCALCEMIA, PARATHYROID LABS HIGH NORMAL, RECURRENT RENAL CALCULI ( CALCIUM STONES ), 24. HR. URINE CALCIUM 250 MG, SESTAMIBI SCAN DID NOT LOCALIZE AN ADENOMA ? NEXT STEP ? a. MEDICAL SURVEILLANCE b. REPEAT SCAN c. SURGERY PARATHYROID EXPLORATION d. REPEAT 24 HR. URINE CALCIUM TO EVALUATE FOR FAMILIAL HYPOCALCIURIC HYPERCALCEMIA PRE-LECTURE SURVEY • 48 YEAR OLD WOMAN WITH 6.3 CM ENHANCING HETEROGENOUS RIGHT ADRENAL MASS. SHE IS OTHERWISE HEALTHY WITH NO HISTORY OF HYPERTENSION OR SYSTEMIC ILLNESS. NEXT STEP? A. CT-GUIDED BIOPSY OF MASS B. RIGHT ADRENALECTOMY C. CHECK SERUM METANEPHRINES D. URINARY VMA E. NO FURTHER INTERVENTION 2 5/3/2019 DISCLAIMERS AND DISCLOSURES • NO FINANCIAL CONFLICTS OF INTEREST • NOOFF-LABEL DISCUSSION OBJECTIVES AND SCOPE • PROVIDE AN APPROACH TO WORKING UP INCIDENTALLY DISCOVERED ENDOCRINE NODULES • BRIDGE THE SURGICAL AND THE CLINICAL WORLDS • THYROID NODULES AND DIFFERENTIATED THYROID CANCER • PRIMARY HYPERPARATHYROIDISM • ADRENAL INCIDENTALOMAS INCLUDING PRIMARY HYPERALDOSTERONISM AND PHEOCHROMOCYTOMA 3 5/3/2019 THYROID INCIDENTALOMAS • COMMON: • PREVALENCE ( PALPATION ) : 5 % IN WOMEN, 1 % IN MEN • SONOGRAPHIC PREVALENCE UP TO 68 % • INCREASES WITH AGE • 27% IN < 50 YEAR OLDS • ~50% OF 50 YEAR OLDS • MORE COMMON IN WOMEN • KEY QUESTIONS : • ARE THEY AFFECTING THYROID FUNCTION? SERUM TSH • ARE THEY MALIGNANT? NO ROLE FOR SERUM THYROGLOBULIN Ezzat S. Arch Int Med 1994 Brander A. Radiology 1991 EVALUATION: • LABS: TSH TO ASSESS FOR HYPERTHYROIDISM • IF HYPERTHYROID- POSSIBILITY OF A HOT NODULE • NEXT STEP : I-123 UPTAKE & SCAN +/- REFERRAL TO ENDOCRINOLOGIST TO EVALUATE NEED FOR TREATMENT AND DISCUSS TREATMENT OPTIONS. • IMAGING: HIGH-SENSITIVITY ULTRASONOGRAPHY • SONOGRAPHIC RISK FACTORS • HYPOECHOIC NODULES • IRREGULAR MARGINS • INCREASED VASCULARITY • MICROCALCIFICATIONS Gharib H. Endocrinol Metab Clin N Am 2007 4 5/3/2019 OTHER MODALITIES : • FDG-PET – FOCAL UPTAKE WITH US CONFIRMED NODULES > 1 CM WARRANT FNA • FDG-PET – DIFFUSE UPTAKE WITH US AND BIOCHEMICAL EVIDENCE OF CHRONIC LYMPHOCYTIC THYROIDITIS DOES NOT WARRANT FNA • CT/MRI: • ONLY IF SUBSTERNAL, NODE MAPPING • RADIONUCLIDE UPTAKE & SCAN • ONLY IF HYPERTHYROID- TO CONFIRM HOT NODULE • COLD NODULE = MALIGNANCY? • BUT MOST COLD NODULES ARE BENIGN • AND MANY CANCERS DON’T APPEAR COLD ON IMAGING 5 5/3/2019 ULTRASOUND-GUIDED THYROID BIOPSY • US-GUIDED FNA • GOLD STANDARD • OFFICE BASED • MULTIPLE NODULES: • SONOGRAPHIC SUSPICION Khoo TK. Endocr Prac 2008 AACE/AME Task Force on Thyroid nodules. Endocr Prac 2006 6 5/3/2019 RESULTS AND IMPLICATIONS • DIAGNOSTIC • BENIGN • ATYPIA OR FOLLICULAR LESION OF UNDETERMINED SIGNIFICANCE • SUSPICIOUS FOR FOLLICULAR NEOPLASM OR MALIGNANCY • MALIGNANT • NONDIAGNOSTIC Cibas ES. Am J Clin Pathol 2009 ROLE OF MOLECULAR MARKERS 1. AFFIRMA GENE EXPRESSION CLASSIFIER : - MRNA EXPRESSION OF 167 GENES - NPV 95 % IN ATYPIA OF UNKNOWN SIGNIFICANCE/FOLLICULAR LESION OF UNKNOW SIGNIFICANCE, FOLLICULAR NEOPLASM ( BETHESDA III&IV) - PPV 37 % -GOOD ‘RULE OUT’ TEST IN INDETERMINATE NODULES. 2. THYGENX AND THYRAMIR : -GENE MUTATION : BRAF, RAS, RET/PET, PAX8/PPARΓ - NPV 94 %, PPV 74 % 3. THYROSEQ : -GENE MUTATION & FUSION PANEL - NPV 96 %, PPV 88 %, ‘RULE IN’ TEST LONG-TERM OUTCOME DATA INSUFFICIENT AT THIS POINT 7 5/3/2019 THYROID MALIGNANCY • ONLY 1 IN 20 NODULES IS MALIGNANT • 1% OF ALL CANCERS • 1975-2009 : INCIDENCE : 4.9 TO 14.3 /100,000 MORTALITY : STABLE 0.5 /100,000 Davies L. JAMA Otolaryngol Head & Neck Surgery 2014 Davies L. JAMA 2006 8 5/3/2019 SUBTYPES • FOLLICULAR-DERIVED • DIFFERENTIATED • 80 % PAPILLARY THYROID CARCINOMA (VARIANTS- TALL CELL, FOLLICULAR, CLEAR CELL) • 10 %FOLLICULAR THYROID CARCINOMA (HURTHLE CELL) • 1-2 % UNDIFFERENTIATED/ANAPLASTIC • 5 -10 % MEDULLARY • RARE – PRIMARY LYMPHOMAS & SARCOMA PAPILLARY THYROID CARCINOMA • INCIDENCE 8:100,000 • MICROPTC IN UP TO 30% OF AUTOPSIES • ~80% OF THYROID CANCERS • 50% ARE ≤ 1 CM • FEMALES > MALES • RISK FACTORS • RADIATION EXPOSURE • FAMILY HISTORY Davies L. JAMA 2006 Schlumberger MJ. N Engl J Med 1998 9 5/3/2019 PAPILLARY THYROID CARCINOMA • COMMONLY MULTICENTRIC- 20-80% OF CASES • LYMPH NODE METASTASIS • METS TO REGIONAL NODES UP TO 80%, EVEN IF SMALL, INTRATHYROIDAL • PRE-OPERATIVE NODAL EVALUATION SHOULD BE UNDERTAKEN! • U/S TO ASSESS LATERAL COMPARTMENTS • CT IF LIMITED EXPERIENCE IN U/S Schlumberger MJ. N Engl J Med 1998 Mazzaferri EL. Am J Med 1994 ATA Guidelines 2006 FOLLICULAR THYROID CARCINOMA • DISTINGUISHED FROM FOLLICULAR ADENOMAS FROM INVASION OF CAPSULE AND VESSELS • 10% OF THYROID CANCERS • LESS FREQUENTLY MULTICENTRIC, NODAL METS • HEMATOLOGIC METASTASES TO LUNGS, BONES • SLIGHTLY POORER PROGNOSIS Schlumberger MJ. N Engl J Med 1998 10 5/3/2019 TREATMENT: 3 STEP PROCESS • THYROIDECTOMY • PTC- ROUTINE CENTRAL COMPARTMENT DISSECTION? • 50% INVOLVEMENT • THYROID SUPPRESSION THERAPY –LEVOTHYROXINE 1.6MCG/KG & REFER BACK TO ENDOCRINOLOGIST TO ASSESS NEED FOR RAI AND PLAN SURVEILLANCE • RADIOIODINE REMNANT ABLATION • LOW RISK : NO RAI, FOLLOW WITH ULTRASOUND AND THYROGLOBULIN LEVELS. • HIGH RISK : RECOMBINANT TSH STIMULATED REMANANT ABLATION • NOT BE USED TO ‘CLEAN UP’ INADEQUATE SURGERY ATA Guidelines. Thyroid 2006 Hay I. Endocr Prac 2007 Mazzaferri EJ. Endocr Prac 2007 SUMMARY • THYROID NODULES ARE COMMON: - BIOCHEMICAL TESTING : TSH - BASED ON SIZE & CHARACTERISTICS : FNA • FOR PTC, STRONGLY CONSIDER PRE-OP NODAL IMAGING • CONSIDER CENTRAL COMPARTMENT DISSECTION FOR SELECT CASES • THYROID HORMONE REPLACEMENT : 1.6 MCG/KG/BODYWEIGHT • COMMUNICATE/REFER BACK TO ASSESS NEED FOR RAI 11 5/3/2019 PRIMARY HYPERPARATHYROIDISM • 1% OF ADULT POPULATION • 2% OR MORE > AGE 55 • 80-85% PARATHYROID ADENOMA • 10 % MULTI GLAND HYPERPLASIA • 4 % DOUBLE GLAND ADENOMA • 1% CARCINOMA • OVEREXPRESSION OF CYCLIN D1 & DEFICIENCY OF MEN-1 • PARATHYROIDECTOMY IS THE ONLY CURATIVE TREATMENT DIAGNOSIS • PERSISTENT HYPERCALCEMIA OR HIGH NORMAL CALCIUM LEVEL • INAPPROPRIATELY NORMAL OR ELEVATED PARATHYROID LEVELS • 24 HR. URINE CALCIUM AND CREATININE • CA/CR < 0.01 SUGGESTS FHH • PARATHYROID IMAGING DOES NOT AID DIAGNOSIS 12 5/3/2019 IMAGING MODALITIES • 99MTC-SESTAMIBI SCAN –SENSITIVITY : 88 % ADENOMA, 44 % HYPERPLASIA, 29 % WITH DOUBLE ADENOMA, 33 % CARCINOMA • HIGH RESOLUTION ULTRASOUND • SINGLE PHOTON EMISSION CT • NO SUBSTITUTE TO AN EXPERIENCE SURGEON !!! • MINIMALLY INVASIVE PARATHYROIDECTOMY • 4 GLAND EXPLORATION IN 20-40 % - NEGATIVE OR EQUIVOCAL SCAN • INTRA-OPERATIVE PTH LEVELS – GREATER CERTAINTY OF CURE INDICATIONS FOR SURGERY • NIH +NIDDK PANEL 2002 1. AGE < 50 2. CANNOT PARTICIPATE IN MEDICAL FOLLOW-UP 3. SERUM CALCIUM > 1MG/DL ABOVE UPPER LIMIT OF NORMAL 4. URINARY CALCIUM >400 MG/24 5. + 30 % DECLINE IN RENAL FUNCTION 6. NEPHROCALCINOSIS, OSTEOPOROSIS, PSYCHONEUROLOGIC DISORDER 13 5/3/2019 ADRENAL INCIDENTALOMAS • NOT UNCOMMON EITHER! • 4-10% OF ABDOMINAL SCANNING • AGE-DEPENDENT • QUESTIONS • IS THIS WORRISOME? • IS THIS AFFECTING THE FUNCTION? Bovio S. J Endocrinol Invest 2006 Terzolo M. Eur J Endocrinol 2011 “IS THIS WORRISOME?” • NEED A GOOD RADIOLOGIST! • IMAGING OF CHOICE-TRIPHASIC CT (MRI FOR PHEO) • BENIGN PHENOTYPE: • SIZE <4CM, MARGINS • DENSITY • HOUNSFIELD UNITS <10, >50% WASHOUT • WORRISOME PHENOTYPE • MICROCALCIFICATIONS • ADRENOCORTICAL CARCINOMA • HETEROGENOUS OR CYSTIC CHANGES • NO ROLE FOR CT-GUIDED BIOPSY! Szolar DH. Radiology 2005 14 5/3/2019 “IS THIS HYPERFUNCTIONING?” Aldosterone Cortisol Androgens Catecholamines Bovio S. J Endocrinol Invest 2006 Terzolo M. Eur J Endocrinol 2011 PRIMARY HYPERALDOSTERONISM • ALDOSTERONE PRIMARILY CONTROLLED BY RENIN-ANGIOTENSIN SYSTEM, NOT ACTH • OVERPRODUCTION LEADS TO SALT RETENTION AND CLINICAL HYPERTENSION • MAY SEE HYPOKALEMIA (9-37%) • NOT HYPERNATREMIA Mulatero P. J Clin Endocrinol Metab 2004 15 5/3/2019 INVESTIGATIONS • SCREEN: 8 AM ALDOSTERONE:RENIN • >30:1 & HIGH ABSOLUTE ALDOSTERONE >15 • CONFIRMATION • ORAL SALT LOADING: URINE NA >200 MG AND URINE ALDOSTERONE >12 IN 24 HOURS • SALINE INFUSION: 2 LITERS OVER 4 HOURS, SERUM ALDOSTERONE <10 Endocrine Society Clinical Practice Guideline 2008 Giacchetti G. J Hypertens 2006 TREATMENT • MEDICAL THERAPY • SPIRONOLACTONE OR EPLERENONE • HIGHLY EFFECTIVE • UNILATERAL ADRENALECTOMY • MUST BE PRECEDED BY ADRENAL VEIN SAMPLING TO CONFIRM UNILATERAL, IPSILATERAL DISEASE • ALDOSTERONE, CORTISOL SAMPLES TAKEN AND COMPARED Young WF. Surgery 2004 16 5/3/2019 PHEOCHROMOCYTOMA • TUMORS OF NEUROENDOCRINE CELLS • CATECHOLAMINE-PRODUCING • EPINEPHRINE, NOREPINEPHRINE • ANNUAL INCIDENCE >0.8 PER 100,000 CLINICAL FEATURES • CLASSICAL: HEADACHES, DIAPHORESIS, PALPITATIONS • OTHERS: PAROXYSMAL HYPERTENSION, PALLOR, TREMORS, ANXIETY ATTACKS, ETC Stein PP. Medicine 1991 17 5/3/2019 HOWEVER: • 10-49% PRESENT AS INCIDENTAL FINDING • UPTO57.6% WERE ASYMPTOMATIC • THE MOST COMMON SIGN WAS HYPERTENSION • OFTEN SUSTAINED (NOT PAROXYSMAL) • OFTEN WELL-CONTROLLED WITH MEDICATIONS • SO, THE CLASSIC TRIAD, IS RARE • CANNOT RULE OUT PHEO ON BASIS OF HISTORY Kudva YC. The Endocrinologist 1999 Baguet JP. Eur J Endocrinol 2004 Motta-Ramirez GA. Am K Roentgenol 2005 INVESTIGATIONS: BIOCHEMISTRY • FRACTIONATED PLASMA METANEPHRINES OR • 24-HOUR URINE CATECHOLAMINES
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