Joint Hospital Surgical Grandround Management of Toxic Multinodular

Joint Hospital Surgical Grandround Management of Toxic Multinodular Goiter - Role of surgery Shi LAM Queen Mary Hospital

“. . two distinct types of thyroid intoxication…” – H. S Plummer 1913 n Hyperplastic (Grave’s) n Non-hyperplastic (Plummer’s) n n Solitary toxic nodule n Toxic multinodular goiter Two major causes (> 80%) of hyperthyroidism worldwide

Multinodular Goiters (MNG) n n Commonly adopted definition n thyroid volume > 20 ml n nodular lesions > 5 – 10 mm Prevalence determined by iodine intake n palpation: 3 – 5% n USG screening: 10 - 50% n endemic in regions of low iodine intake n risk factors: age, female, parity, smoking, obesity

Hong Kong is a region of borderline iodine deficiency n n Chinese Nutrition Society Recommendation n adolescent / adult : 150 ug / day n pregnant / lactating women: 250 ug / day n upper limit 1000 ug/day Center food safety report 2011 n median daily food iodine content 44 ug/day n 59% of population has iodine intake < 50 ug / day n iodine rich food: seaweed > crustaceans > eggs > milk > fish n iodine scarce food: grains, meat, vegetable, tea / coffee

Natural history – nodule growth n n Alexander et al. Ann Intern Med 2003 n USG follow-up of 330 benign nodules n 39% nodules increase volume by 15% in 35 months n cystic nodules tend to remain static n age, gender and TSH level were not predictive of nodule growth Papini et al. J Clin Endocrinol Metab. 1998 n 45% increase volume, 25% in nodule number in 5 years

Natural history - thyrotoxicosis n n Prospective cohorts n Elte et al. Postgrad Med J 1990 n Wiener et al. Clin Nucl Med. 1979 n 158 euthyroid MNG patients with autonomous functioning thyroid n mean follow-up 4 – 12. 2 years n 10% patients develop thyrotoxicosis Factors associated with hyperthyroidism n older age n hyperfunctional nodules size > 3 cm n autonomously functioning thyroid volume > 16 ml

Spectrum & course of Plummer’s disease Age Goiter/ nodularity

Spectrum & course of Plummer’s disease Age Goiter/ nodularity Automaticity

Spectrum & course of Plummer’s disease Age Goiter/ nodularity Automaticity Thyrotoxicosis

Spectrum & course of Plummer’s disease Age adolescent Goiter/ nodularity + Automaticity nonautonomous Thyrotoxicosis euthyroid

Spectrum & course of Plummer’s disease Age adolescent Goiter/ nodularity + Automaticity nonautonomous Thyrotoxicosis euthyroid 40 ++ autonomous euthyroid

Spectrum & course of Plummer’s disease Age adolescent Goiter/ nodularity + Automaticity nonautonomous Thyrotoxicosis euthyroid 40 ++ autonomous Plummer’s disease euthyroid

Spectrum & course of Plummer’s disease Age adolescent Goiter/ nodularity + Automaticity nonautonomous Thyrotoxicosis euthyroid 40 ++ autonomous euthyroid 60 +++ autonomous subclinical hyperthyroidism

Spectrum & course of Plummer’s disease Age adolescent Goiter/ nodularity + Automaticity Thyrotoxicosis nonautonomous euthyroid 40 ++ autonomous euthyroid 60 +++ autonomous subclinical hyperthyroidism Toxic multinodular goiter

Spectrum & course of Plummer’s disease Age adolescent Goiter/ nodularity + Automaticity nonautonomous Thyrotoxicosis euthyroid 40 ++ autonomous euthyroid 60 +++ autonomous > 60 mass effect subclinical hyperthyroidism Iodine exposure autonomous overt hyperthyroidism

Management of toxic MNG n Goals n n n correct dysfunction – mass / thyrotoxicosis exclude / treat malignancy Options n n medical radio-active iodine surgery percutaneous ablations

Overt thyrotoxicosis in toxic MNG n Preferred treatment options n surgery n n n n total / near-total thyroidectomy immediate restoration of euthyroidism retrosternal goiters, weight > 90 g <1% retreatment rate <2% permanent recurrent laryngeal nerve injury <2% permanent hypoparathyroidism contraindications: pregnancy (1 st and 3 rd trimester)

Overt thyrotoxicosis in toxic MNG n Preferred treatment options n 131 I n avoids surgical / anaesthetic risk n euthyroidism: 3 months – 60%, 6 months – 80% n hypothyroidism: 1 year – 3%, 24 years – 64%; n 40% size reduction n contraindications: n lactating n pregnant / planning pregnant in 6 months

Overt thyrotoxicosis in toxic MNG n Other treatment options n n Anti-thyroid medications n does not induce remission n for patients not fit for surgery, limitted life expectancy Percutaneous ablation (ethanol / radio-frequency / high intensity focused ultrasound ) n lack of long-term experience

Subclinical thyrotoxicosis n Common in toxic multinodular goiter n Porterfield et al. World J Surg 2008 n n 438 / 586 (82%) patients with toxic nodular goiter Long-term consequence n Sawin et al. NEJM 1994 n prospective cohort of 2007 subjects > 60 years old n follow-up: 10 years n subjects with subclinical hyperthyroidism (TSH < 0. 1 m. U/L) have 3 -fold increased risk in developing atrial fibrillation

Risk of malignancy n Incidental carcinoma in toxic multinodular goiter: n Review by Pazaitou et al. Horm Metab Res 2012 n n n 7 retrospective cohorts of toxic nodular goiter 1611 subjects Cancer in 1. 6 – 8. 8% Microcarcinoma (<10 mm): 35 – 88% of tumors Excellent prognosis compared with euthyroid patients QMH (unpublished) n n n Toxic multinodular goiter operated for non-suspicious causes Excluded FNAC confirmed or suspicious nodules 16/178 (9%) found to have carcinoma 15 papillary carcinoma, 1 Hurthle cell carcinoma Mean diameter 12 mm

Risk of malignancy n ? Clinical significance n n n higher reported prevalence due to more detailed pathological examination ? hyperthyroidism not previously identified as risk factors for manifesting carcinoma of thyroid ? Pre-operative risk stratification n n cold nodules on scintigraphy family history exposure to neck irradiation USG findings > 50% carcinomas found outside of “dominant” / “cold” nodules

Summary n Toxic multinodular goiter is the manifesting stage of a chronic process of hyperplasia and acquisition of automaticity in the thyroid gland. n Hyperthyroidism, overt or subclinical, is an indication for definitive interventions, in the form of thyroidectomy or radio-active iodine ablation. n In the absence of suspicion of malignancy, surgery is probably still a “safer offer” in younger patients in view of the accumulated life-time risk for an incidental carcinoma to progress into a manifesting cancer.

Acknowledgement Dr. Brian Lang

Thank you!