Surgical treatment of asymmetrical multinodular goiter Antonio Sitges-Serra, FRCS EndocrineSurgery Unit Hospital del Mar, Barcelona

A chat in the internet: “… well, I have been today to visit my surgeon. He told me that my left thyroid lobe should be removed because of a 5 cm. benign nodule but he said that the right lobe will be untouched because only two 4 and 7 mm. nodules are there. He says that nothing has to be done for nodules under 15 mm.”

Is the surgeon right? Why 15 mm.? Should he remove the contralateral lobe? What are the risks? What’s the chance of cancer? How often is hemiTX followed by hypothyroidism? How often is hemiTX followed by recurrence?

Yes, thesurgeonwasright, said Dr. H. Chen Lessmorbidity of hemithyroidectomy (2 vs. 9%) Lesshypocalcemia (0 vs. 6%) Reasonablereoperationrate (11 vs 3% at 3-11 yrs) Recurrencedoesnotequalreoperation Reoperationdoesnotincreasemorbidity Olson SE, Starling J, Chen H. Symptomatic benign multinodular goiter: Unilateral or bilateral thyroidectomy? Surgery 2007;142(4):458-62.

Manymethodologicalissues Starting with a definition: Asymmetrical goiter is a clinically solitary unilateral “benign” thyroid nodule which, in thyroid imaging, shows evidence of contralateral subclinical (<10 mm) nodular disease.

Prevalence of US-AMG in solitary thyroid nodules 50% Tan G et al., Arch Int Med 1995

(69 cases, US-normal contralaterallobe) Recurrenceafterhemithyroidectomyforbenign TN (69 cases, US-normal contralaterallobe) At least 10 yrs. of follow-up Nodular hyperplasiaorfollicular adenoma US-recurrence rate Nodular hyperplasia: 70% (mean size 13 mm) Follicular adenoma: 60% (mean size 9 mm) No reoperations during the interval 50% treated with T4 (non-suppressive) Hemi-TX advisablefor US-unilateral benign TN Lozano-Gómez MJ et al., CirEsp 2006

Recurrence after hemithyroidectomy for benign TN Randomized trial of suppressive T4, 140 cases US-normal contralaterallobe 5-year of follow-up data Nodular hyperplasia or follicular adenoma US-recurrence rate (NT>3mm): 13/145 (9%) 24% hypothyroidism (non-treated group) Seven (5%) reoperations during the interval Suspicious FNA: 4 cases Compressive symptoms: 3 cases Favors suppressive T4 in I-deficient patients Hemi-TX advisablefor US-unilateral benign TN Barczynski M et al., World J Surg 2010

Recurrence after hemithyroidectomy for benign TN (104 patients, prospective study) 39 mos. follow-up data Nodular hyperplasia or follicular adenoma US-recurrence rate (NT>3mm): 60/104 (60%) Multinodularity as a risk factor Three (2.9%) reoperations during the interval Suspicious FNA: 3 cases (follicular neoplasia) Hemi-TX advisablefor US-unilateral benign TN Yetkin G et al., EndocrPract 2010

Decisionmaking in patientswith AMG Whatis at stake? Extensive thyroidectomy Limited thyroidectomy + + + +/- Recurrence + + + + Hypothyroidism - + Hypoparathyroidism +/- + RLNparalysis + ++ Incidental carcinoma

Some data from the literature More recurrences with limited resections Recurrence related to any residual tissue Surgery for recurrence a mean of 18 yrs. Higher hypocalcemia rates (T&P) after total thyroidectomy Reoperation carries higher complication rates Permanent hypopara: 0-22 vs 0-4% Permanent RLN injury: 0-13 vs 0-4% Factors for recurrence: young age and multiple nodules Moalem J et al., World J Surg 2008 Erbil Y et al., Langenbeck’sArchSurg2006 Gibelin H et al., World J Surg2004

Some data from the literature Farkas EA et al., AmSurg 2002

Studydesign: Multicenter, randomizedclinical trial comparingextensivevs. limitedsurgeryforAMG (18-65 yrs.)

Studydesign: Randomization Multicenter, randomizedclinical trial comparingextensivevs. limitedsurgeryforAMG (18-65 yrs.) Randomization

118 randomized 65 Hemi -TX 53 Dunhill 59 Hemi -TX 49 IQ Dunhill 53 2 Dunhill preferred 1 Hemi-TX preferred 3 Randomization error 3 Randomization error 1 Papillary ca. Intraop DX 59 Hemi -TX 49 IQ Dunhill 5 Papillary ca. (3 follicular variant) 3 Papillary ca. 1 Follicular ca. 53 Benign 45 Benign 7 FU losses 1 FU losses 46 Evaluable 44 Evaluable

Group homogeneity GLOBAL (n=90) HEMI TX (n=47) DUNHILL (n=43) P Sex Male Female 7 (7.8%) 83 (92.2%) 1(2.1%) 46 (97.9%) 6 (14.0%) 37 (86.0%) 0.51 Age (y) 43.6 ± 10.6 41.4 ± 9.6 46 ± 11.2 0.038* Past medical history Clinical features LAB Endemic goiter area Family history Smoking Alcohol consumption Beta blockers Iodine intake Hormonal therapy Menopause Compressive simptoms Hyperfunction signs Estimated evolution TSH Free T4 s-Ca / s-P Auto antibodies 20

Grouphomogeneity Size of thedominantnodule N.S. 21

Grouphomogeneity Subclinical contralateral nodules Global N =90 Hemi TX N = 47 Dunhill N = 43 P Number of nodules 1.7±0.9 1.5±0.1 1.8±0.2 0.11 Maximum size (mm) 6.8±2.2 6.6±2.2 6.9±2.3 0.95 Minimum size (mm) 5.8±2.3 5.9±2.5 5.6±2.1 0.53 22

The typical patient profile Woman 47 y/o. Normal thyroidfunction 36 mm 5.8 mm 23

Operative time N.S. 13’ 24

Identification of RLN 25

Parathyroid gland identification 26

Parathyroidglandidentification Accidental PTX PT autotransplantation N.S. N.S. 3/47 3/43 5/47 6/43 27

Postoperativehypocalcemia (<8 mg/dL at 24h) Treatment P<0.0001 No cal afegir la P de gràficaesquerra? 28

Postoperative stay P<0.005 29

Thyroid function (last FU visit) Onthyroxine: Dunhill 41/43 (95%) 108 ± 24 mcg/day HemiTX14/47 (30%) 66 ± 30 mcg/day Free T4 : Dunhill: 1.26 ± 0.4 ng/dL HemiTX: 1.07 ± 0.3 ng/dL TSH: Dunhill: 3.77 ± 4.5 UI/mL HemiTX: 3.03 ± 2.0UI/mL P= 0.0001 N.S. Aquí invertirial’odrecoalsaltresllocs. Primer hemo i desprésdun N.S. 30

Long term parathyroid function (no permanent hypoparathyroidism in either group) s-Ca: Dunhill: 8.9 ± 0.4 mg/dL HemiTX: 8.9 ± 0,4 mg/dLN.S. iPTH: Dunhill: 32.3 ± 2.6 pg/mL HemiTX: 31.2 ± 1.8 pg/mLN.S. 31

Remnantsize at last FU visit(55 ± 34 mo) P<0.0001 32

Remnant size evolution (55 ± 34 mo) ≈ 20% ≈ 0% BerghoutA et al., Am J Med 1990; 89:602-8. 33

New nodules on remnant P=0.0001 26/47 6/43 34

Reoperations HemiTX Dunhill P(1) Early redo (Intentiontotreat) 5/65 (7.7%) 1*/53 (1.8%) 0.22 DuringFollow-Up (Per protocol) 1/53 (1.9%) 0/45 1.00 Overall (Intentiontotreat) 6/65 (9.2%) * 1 FTC (3 PTC detected but NOT reoperated) (1) Fisher exact-test 35

59 Hemi -TX 49 IQ Dunhill 1TT 3 131I 5TT 1 TT 53 Benign 45 Benign 46 1 Papillaryca. Intraop DX 59 Hemi -TX 49 IQ Dunhill 1TT 5 Papillaryca. 3 PTC 3 131I 5TT 1 FTC 1 TT 53 Benign 45 Benign 7 FU losses 1 FU losses 46 Evaluable 44 Evaluable 3 Micro PTC 1 MNG progression 42 MNG SURVEILLANCE TX 5 Micro PTC 39 MNG SURVEILLANCE TX

Conclusions Hemi TX and Dunhill have a similar intra and postop course Reoperation rate higher in hemiTX The presence of unsuspected carcinoma favors Dunhill Growth of remnant significant for hemiTX (4% per year) No remnant growth after Dunhill Accidental PTX same for both procedures 30% of HemiTX end up on thyroxine