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Thyroid Surgery for Graves Disease

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Slide 1 :

Thyroid Surgery for Graves’ Disease Alexander Shifrin, MD Department of Surgery Jersey Shore University Medical Center

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Case # 1 30 y.o. female with 5 year history of Graves’ disease Treated with PTU x 2 years, came off, developed more symptoms of hyperthyroidism plus dermatitis Restarted on Methimazol, feels better Unable to come off medications Unable to get pregnant Came for advice on therapy options?

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Surgery – total thyroidectomy (same day, under local/regional block) Path – multinodular goiter, chronic thyroiditis c/w Graves’ disease 2 weeks post op Case # 1

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Case # 2 43 yo f with Graves x 8 years. C/o inability to perform day-by-day functions (stopped her martial arts, unable to catch her breath, palpitations, anxiety). Unable to come off of anti-thyroid meds Developed 2cm, solid right thyroid nodule (US 3/2008) FNA Bx – negative for malig. cells Fam Hx – neg; No h/o radiation Surgery – total thyroidectomy (same day, under local/regional block) Path – follicular variant of papillary thyroid carcinoma, 1 cm, no LN 2 weeks post op

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Case # 3 57 y.o. female with 7 year history of Graves’ disease Treated with Methimazol, can not come off of meds f/u US (1/2008) - developed multinodular goiter with solid 3.8 cm cold nodule on Uptake scan + increased uptake throughout the rest of the thyroid (43% @ 24hr) compressive symptoms: swallowing, breathing difficulties in supine position Came for second opinion? US guided FNA Bx – suspicious for papillary thyroid carcinoma Surgery – (5/15/2008) total thyroidectomy (same day, under local regional block) Path – papillary and follicular variant of papillary thyroid carcinoma, 1.8 x 1.6 cm

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Case # 4 54 yo female, h/o Graves’ for 4 years. Suffered of severe, panic disorder with intolerable anxiety attacks, which precluded her daily life activities; problems with people relationship, lost her job because of it. Anxiety was worse when she was off thyroid meds. Symptoms of difficulty swallowing solid – “stack in her throat”, hoarseness, shortness of breath. Thyroid US – MNG; Nuclear Med Thyroid Uptake - c/w Graves’. TFT’s – wnl on Methimazol Meds: Methimazol, Propronalol, Lexapro, Xanax Fam Hx: Mother – thyroidectomy for goiter, breast Ca. Cousin – thyroid Ca

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Case # 4 Came for consultation with her friend – unable to control her panic attacks, so her friend can speak for her. Very emotional, constantly crying. Surgery – total thyroidectomy. Path – multinodular goiter Follow-up in two weeks: - panic attacks resolved - stopped taking Xanax since surgery only on Lexapro - able to control her life, can deal with problems without tears and emotion - compressive symptoms resolved (swallowing, breathing problems) 2 weeks post op

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Toxic diffuse goiter Robert James Graves – in the English-speaking world Carl Adolph von Basedow - in continental Europe

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Graves’ disease: facts Autoimmune disorder with an unpredictable clinical course. Symptoms directly related to hormone excess Manifestations in connective tissue: Graves´ ophthalmopathy and dermopathy annual incidences: 40 per 100,000 in the US 4 to 6 times more common in females, mostly between age 20 to 50. 1% to 5% of patients with GD are children (peak at age 11 to 14 years)

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Graves disease: facts strong hereditary and genetic component Smoking is weakly associated with GD but strongly with the development of Graves ophtalmopathy thyroid receptor antibodies activates the thyrotropin receptor (TSHR), leading to synthesis and production of thyroid hormones in the follicular cells and infiltration of lymphocytes in the thyroid

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Antithyroid medication Radioactive iodine ablation (131I) Thyroidectomy. Indications vary based on geographical location: Radioactive iodine ablation preferred in the US Europe and Asia - antithyroid drugs or surgery are favored. Treatment options

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Absolute indications for surgery include the following: Presence of GD and an associated suspicious or malignant thyroid nodule Pregnancy, not controlled with antithyroid medication Local compressive symptoms Children before age 5 yo

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Is radioactive iodine safe? No data for small dose (Graves’) but there are date for iodine dose in patients treated for thyroid cancer.

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The Risk of Second Primary Malignancies up to Three Decades after the Treatment of Differentiated Thyroid Cancer Brown AP,Tward JD. J Clin Endocrinol Metab. 2008 Feb;93(2):504-15 METHODS: 30,278 patients with differentiated thyroid cancer (from 1973 to 2002) from centers participating in the NCI Surveillance, Epidemiology, and End Results program. Median follow-up - 103 months (2-359 months). Risk was assessed for radioisotope therapy, gender, latency to development of secondary cancer, and age at thyroid cancer diagnosis.

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The Risk of Second Primary Malignancies up to Three Decades after the Treatment of Differentiated Thyroid Cancer Brown AP,Tward JD. J Clin Endocrinol Metab. 2008 Feb;93(2):504-15 RESULTS: 2158 patients developed a total of 2338 nonthyroid second primary malignancies, significantly more than that in the general population [P < 0.05]. The increased risk was greater for the irradiated vs. the unirradiated cohort (P < 0.05). The greatest risk of second primary cancers occurred within 5 yr of diagnosis and was elevated for younger patients. CONCLUSIONS: The overall risk of second primary malignancies is increased for thyroid cancer survivors and varies by radioisotope therapy, latency, and age at diagnosis (leukemia, breast, prostate).

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Why not go straight to the surgery? Is surgery safe? What are side effects and complications of the surgery?

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Side effects/complications of the surgery 1-2 % risk or permanent RLN injury (In non-thyroid specialized surgeon – up to 10-15% reported) ~15-20% risk of temporary hoarseness Up to 15-20% chances of the EBSRN injury – high pitched voice 1-2% risk of permanent hypoparathyroidism 0.5 - 1% risk of bleeding 0.5 - 1% risk of infection Scar Lifelong thyroid replacement

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Surgical Treatment of Graves' Disease: Evidence-Based approach. Stalberg P, at al. World J Surg. 2008 Mar 8 The optimal treatment of Graves disease (GD) is still controversial: antithyroid medication? vs radioactive iodine (RAI)? vs Surgery?: 1) Is surgery better than RAI or long-term antithyroid medication? 2) What is the recommended surgical approach? 3) How does the presence of Graves' ophthalmopathy (GO) influence the role of surgery? 4) What is the role of surgery in children with GD? METHODS: a systematic review of the literature using evidence-based criteria regarding these four issues.

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Surgical Treatment of Graves' Disease: Evidence-Based approach. Stålberg P, at al. World J Surg. 2008 Mar 8 RESULTS: 1) There are no preference in the treatment options for adults. 2) Total thyroidectomy has same complication rates as subtotal, but higher cure rates and negligible recurrence rates (grade A recommendation). 3) If severe GO is present, surgery or RAI combined with glucocorticoids (grade B recommendation). 4) The extent of thyroid resection does not influence the outcome of GO (grade B recommendation). 5) RAI or surgery advocated for children (grade C recommendation - lack of studies). 6) Increased cancer risk with RAI in children below the age of 5 years supports surgery in this setting (grade A recommendation).

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Surgical Treatment of Graves' Disease: Evidence-Based Approach. Stålberg P, at al. World J Surg. 2008 Mar 8 CONCLUSION: If surgery is considered - evidence-based criteria support total thyroidectomy as the surgical technique of choice for GD. Available evidence supports surgery in the presence of severe GO. Children with GD should be treated with an ablative strategy. Whether total thyroidectomy or RAI - still debatable. Data on long-term cancer risk are missing or conflicting; and until RAI has proven harmless in children, we continue to recommend surgery in this group.

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How get patient ready for the safe surgery?

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The effect of anti-thyroid drug treatment duration on thyroid gland microvessel density and intraoperative blood loss in patients with Graves' disease. Erbil Y et al. Surgery. 2008 Feb;143(2):216-25 Preoperative preparation of the patient with Graves' disease is crucial to avoid intraoperative or postoperative complications associated with anesthesia or surgery 43 patients were treated with Methimazole &/or Propylthiouracil, preoperatively Thyroid blood flow was measured by Doppler, microvessel density was assessed immunohistochemically CONCLUTION: Longer treatment duration had a 142-fold decreased rate of intraoperative blood loss.

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Effect of Lugol solution on thyroid gland blood flow and microvessel density in the patients with Graves' disease. Erbil Y et al J Clin Endocrinol Metab. 2007 Jun;92(6):2182-9 36 patients were randomly assigned to or not to receive preoperative treatment with Lugol solution Thyroid blood flow was measured by Doppler, microvessel density was assessed immunohistochemically Lugol solution treatment resulted in a 9.33-fold decreased rate of intraoperative blood loss CONCLUSION: Lugol decreased thyroid vascularity, and intraoperative blood loss during thyroidectomy.

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Total or subtotal thyroidectomy?

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Total or subtotal thyroidectomy? Equal rate of complications – RLN palsy (0.7% - 0.9%) Equal rate of transient hypocalcemia (9.6% - 7.4%) Equal rate of permanent hyporarathyroidism (0.9% - 1.0%) Total thyroidectomy – no recurrence Subtotal thyroidectomy – 7.9% recurrence Palit. Et al 2000 J. Surg Res Witte et al 2000 WJ Surg Unpredictable rate of euthyroidism after subtotal (how mach to leave?) up to 70% develops long term hypothyroidism Michie 1975 Br J Surg Micropapillary thyroid carcinoma found in 8% of patients with GD Stalberg. 2008 WJ Surg

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Incidental thyroid carcinoma in patients with Graves' disease. Phitayakorn R, Case Western, Cleveland. Am J Surg. 2008 Mar;195(3) 93 pt - thyroidectomy for Graves' disease, 2 pt (2.2%) had an incidental papillary carcinoma The prevalence of incidental thyroid cancer was 3.6% and 6.2% in patients with nontoxic nodular goiter and toxic multinodular goiter, respectively - no statistical difference Total thyroidectomy is the preferred treatment for patients with Graves' disease and a thyroid nodule. Boostrom S. University of Texas. Otolaryngol Head Neck Surg. 2007 Feb;136 49 prospective pt - thyroidectomy for Graves' disease, Papillary thyroid carcinoma in 10% (60% multifocal, 60% lymph node metastases) CONCLUSION: Total thyroidectomy for Graves' has minimal morbidity. Patients with Graves' and a thyroid nodule are at an increased risk for malignancy and should be treated with a total thyroidectomy.

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Instruments and Technique Why the thyroid surgery is safer at these days?

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Chose the right tools: 1) surgeon 2) instruments / technology

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“Surgeon volume as a predictor of outcomes in inpatient and outpatient endocrine surgery.” Stavrakis A, at al Endocrine Surgical Unit and Center for Surgical Outcomes and Quality, VA System, Los Angeles Surgery. 2007 Dec;142(6):887 the effect of surgeon volume on clinical and economic outcomes for thyroid, parathyroid, and adrenal surgery were examined (New York and Florida state discharge data (2002)) Surgeons were grouped by annual endocrine operative volume: Group A: 1 to 3 operations; B: 4 - 8; C: 9 - 19; D: 20 - 50; E: 51 - 99; and F: >100. Complications, length of stay, and total charges were analyzed. CONCLUSION: Surgeon volume correlates inversely with complication rates, length of stay , and total charges. The lowest complication rates are achieved by surgeons performing >or=100 endocrine operations annually.

Slide 30 :

The importance of surgeon experience for clinical and economic outcomes from thyroidectomy. Sosa JA, Udelsman R at alAnn Surg. 1998 Sep;228(3). The Johns Hopkins University . Surgeons were categorized by volume of thyroidectomies over the 6-year study period: A (1 to 9 cases), B (10 - 29), C (30 - 100), and D (>100). 5860 patients (Maryland hospital discharge data base) relation between surgeon caseload and in-hospital complications, length of stay, and total hospital charges were analyzed Results: highest-volume surgeons had the shortest length of stay (1.4 days for gr B vs 1.9 days for gr A) and the lowest complication rate (5.1 % for gr B vs 8.6% for gr A). Length of stay and complications were more determined by surgeon experience than hospital volume. Individual surgeon experience was significantly associated with complication rates and length of stay for thyroidectomy.

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Effect of hospital volume of thyroidectomies on outcomes following substernal thyroidectomy. World J Surg. 2008 May;32(5):740-6. Pieracci FM, Fahey TJ, Cornell University Volume of thyroidectomies was divided into low (<33 per year), middle (33-99 per year), and high (>/=100 per year) Outcome: hospital length of stay, recurrent laryngeal nerve injury, hypoparathyroidism, bleeding, respiratory failure, blood transfusion, and mortality. total of 1153 pt: 372 (32.2%) were performed at low-volume centers, 388 (33.7%) at middle-volume centers, and 393 (34.0%) at high-volume centers (the New York State Statewide Planning and Research Cooperative System database ) Results: complication rate and mortality rate were significantly associated with volume. They were decreased when surgery occurred at hospitals that perform a high volume of thyroidectomies

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Chose the right instruments

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VERY OLD INSTRUMENTS – Ancient Roman Surgical Instruments Pompeii, Italy, 1st Century A.D.

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Old instruments & techniques Multiple ties bovi Multiple clamps JP drain

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New devices & technology Harmonic FOCUS device

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Randomized controlled trial of harmonic scalpel use during thyroidectomy . Miccoli at al. Arch Otolaryngol Head Neck Surg. 2006 Oct;132(10):1069-73 OBJECTIVE: To compare operative factors, postoperative outcomes, and surgical complications of thyroidectomy when using the harmonic scalpel (HS) vs conventional hemostasis (CH). DESIGN: 100 patients. Single-blind, randomized controlled trial. INTERVENTION: total thyroidectomy with either the HS or CH. CONCLUSIONS: Use of the HS reduce postoperative pain, drainage volume, and transient hypocalcemia in patients undergoing thyroidectomy. Shorter operative times and improved outcomes might justify the cost of the HS compared with that of CH.

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NIM Nerve monitoring for selected high-risk thyroidectomies For reoperative thyroidectomy to monitor recurrent laryngeal nerve For professions requiring voice or speech (singers and teachers) – to monitor external branch of the superior laryngeal nerve Chan W, Surgery, Dec 2006 Snyder, Surgery, Dec 2005

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Thyroid surgery under local anesthesia “Thyroidectomy Using Local Anesthesia: a report of 1,025 cases over 16 years.” K. Spanknebel, J. Chabot, M. DiGiorgi, K. Cheung, S. Lee, J. Allendorf, P. LoGerfo JAMS, Vol 201, 3, p 375-385 - conversion to general anesthesia - 3.3% - outpatient procedures - 96%

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Safety of Same Day Discharge: local vs general anesthesia Inabnet, Shifrin, at al. Thyroid. 2008 Jan;18(1):57-61 224 consecutive patients underwent thyroid surgery using the LigaSure for hemostasis. Morbidity not different: 1 – hematoma (local) 4 – transient nerve injury (local), 1 - permanent nerve injury (local), 1 - permanent nerve injury (G) 3 – temporary hypocalcemia (l) – brief ED visit for Ca Total major complications: local 1.2%, Gen – 2.7 % 88% percent of the local anesthesia patients were discharged same day of surgery compared to 45% of the general anesthesia patients CONCLUSIONS: The electrothermal sealing system permits safe, same day discharge after thyroid surgery with a low complication rate irrespective of the type of anesthesia

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What is minimally invasive thyroid surgery?

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Minimally invasive thyroid surgery Same day surgery – d/c 6 hr post-op Small incision: 3 to 5 cm Incision in the natural skin crease Minimum stitches, no ties – only electrical energy devices No drains No flap creation, no major dissection - minimum scaring No big dressing – just skin glue No pain because of neck block Stitch is removed the day of surgery (6 hr post-op) in OR – immediately pos-op 1 week pos-op

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Total thyroidectomy Left thyroid lobectomy 2 weeks post-op 3 weeks post-op

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Minimally invasive thyroid surgery video-endoscopic surgery: video-assisted, totally endoscopic, axillary approach. sutureless thyroid with Harmonic or other vessel-sealing devices intra – operative nerve monitoring for r.laryngeal and external branch of the superior laryngeal nerve Intraoperative flexible laryngoscopy for vocal cord evaluation before and after the procedure

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Thyroid Surgery in GD: conclusions Antithyroid medication is the preferred initial therapy in US, RAI ablation or surgery - when drug therapy fails or in case of recurrence. Surgery is indicated in GD with MNG, suspiciuse for malignancy, compressive symptoms, pregnancy and inability to control with meds. Graves ophthalmopathy is relative indication (Grade B evidence) Effect of RAI on children in long term is not known, surgery is advisable. Children younger than 5 yo – absolute. 6 weeks of preoperative anti-thyroid medication (methimazol or PTU) is advisable. Lugol solution 10 days preoperatively helps to decrease thyroid gland vascularity. Total thyroidectomy rather than subtotal (Grade A evidence)

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the effect of surgeon volume on clinical and economic outcomes for thyroid, parathyroid, and adrena more the effect of surgeon volume on clinical and economic outcomes for thyroid, parathyroid, and adrenal surgery were examined (New York and Florida state ... less

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