management of toxic multinodular goiter - r ole of surgery

Management of Management of Toxic Multinodular GoiterToxic Multinodular Goiter

- - Role of surgeryRole of surgery

Shi LAMShi LAMQueen Mary HospitalQueen Mary Hospital

Joint Hospital Surgical GrandroundJoint Hospital Surgical Grandround

““..two distinct types of thyroid intoxication…” ..two distinct types of thyroid intoxication…” – H.S Plummer 1913– H.S Plummer 1913

Hyperplastic (Grave’s)Hyperplastic (Grave’s)

Non-hyperplastic (Plummer’s) Non-hyperplastic (Plummer’s) Solitary toxic noduleSolitary toxic nodule

Toxic multinodular goiterToxic multinodular goiter

Two major causes (> 80%) of Two major causes (> 80%) of

hyperthyroidism worldwidehyperthyroidism worldwide

Multinodular Goiters (MNG)Multinodular Goiters (MNG)

Commonly adopted definitionCommonly adopted definition thyroid volume > 20mlthyroid volume > 20ml

nodular lesions > 5 – 10mmnodular lesions > 5 – 10mm

Prevalence determined by iodine intakePrevalence determined by iodine intake palpation: 3 – 5%palpation: 3 – 5%

USG screening: 10 - 50%USG screening: 10 - 50%

endemic in regions of low iodine intakeendemic in regions of low iodine intake

risk factors: age, female, parity, smoking, obesityrisk factors: age, female, parity, smoking, obesity

Hong Kong is a region of Hong Kong is a region of borderline iodine deficiencyborderline iodine deficiency

Chinese Nutrition Society RecommendationChinese Nutrition Society Recommendation adolescent / adult : 150 uadolescent / adult : 150 ug / dayg / day pregnant / lactating women: 250 ug / daypregnant / lactating women: 250 ug / day upper limit 1000 ug/dayupper limit 1000 ug/day

Center for food safety report 2011Center for food safety report 2011 median daily food iodine content 44 ug/daymedian daily food iodine content 44 ug/day 59% of population has iodine intake < 50 ug / day59% of population has iodine intake < 50 ug / day iodine rich food: seaweed > crustaceans > eggs > milk > fish iodine rich food: seaweed > crustaceans > eggs > milk > fish iodine scarce food: grains, meat, vegetable, tea / coffeeiodine scarce food: grains, meat, vegetable, tea / coffee

Natural history – nodule growthNatural history – nodule growth

Alexander et al. Alexander et al. Ann Intern Med 2003Ann Intern Med 2003

USG follow-up of 330 benign nodules USG follow-up of 330 benign nodules

39% nodules increase volume by 15% in 35 months39% nodules increase volume by 15% in 35 months

cystic nodules tend to remain staticcystic nodules tend to remain static

age, gender and TSH level were not predictive of nodule growthage, gender and TSH level were not predictive of nodule growth

Papini et al. Papini et al. J Clin Endocrinol Metab. 1998J Clin Endocrinol Metab. 1998

45% increase volume, 25% in nodule number in 5 years45% increase volume, 25% in nodule number in 5 years

Natural history - thyrotoxicosisNatural history - thyrotoxicosis

Prospective cohorts Prospective cohorts Elte et al. Elte et al. Postgrad Med J 1990Postgrad Med J 1990

Wiener et al. Wiener et al. Clin Nucl Med. 1979Clin Nucl Med. 1979

158 euthyroid MNG patients with autonomous functioning thyroid158 euthyroid MNG patients with autonomous functioning thyroid mean follow-up 4 – 12.2 yearsmean follow-up 4 – 12.2 years 10% patients develop thyrotoxicosis10% patients develop thyrotoxicosis

Factors associated with hyperthyroidismFactors associated with hyperthyroidism older ageolder age hyperfunctional nodules size > 3cmhyperfunctional nodules size > 3cm autonomously functioning thyroid volume > 16mlautonomously functioning thyroid volume > 16ml

Spectrum & course of Plummer’s diseaseSpectrum & course of Plummer’s disease

AgeAge Goiter/Goiter/nodularitynodularity



AutomaticityAutomaticity



AutomaticityAutomaticity ThyrotoxicosisThyrotoxicosis




adolescentadolescent ++non-non-

autonomousautonomous euthyroideuthyroid






4040 ++++ autonomousautonomous euthyroid euthyroid







Plummer’s disease







6060 ++++++ autonomousautonomous subclinical subclinical hyperthyroidismhyperthyroidism








Toxic multinodular goiter







> 60> 60 mass mass effecteffect

autonomousautonomous overt overt hyperthyroidismhyperthyroidism


Iodine exposure

Management of toxic MNG Management of toxic MNG

GoalsGoals correct dysfunction – mass / thyrotoxicosiscorrect dysfunction – mass / thyrotoxicosis exclude / treat malignancyexclude / treat malignancy

OptionsOptions medicalmedical radio-active iodineradio-active iodine surgerysurgery percutaneous ablationspercutaneous ablations

Overt thyrotoxicosis in toxic MNGOvert thyrotoxicosis in toxic MNG

Preferred treatment optionsPreferred treatment options

surgerysurgery total / near-total thyroidectomytotal / near-total thyroidectomy immediate restoration of euthyroidismimmediate restoration of euthyroidism retrosternal goiters, weight > 90gretrosternal goiters, weight > 90g <1% retreatment rate<1% retreatment rate <2% permanent recurrent laryngeal nerve injury<2% permanent recurrent laryngeal nerve injury <2% permanent hypoparathyroidism<2% permanent hypoparathyroidism contraindications: pregnancy (1contraindications: pregnancy (1stst and 3 and 3rdrd trimester) trimester)


Preferred treatment optionsPreferred treatment options

131131II avoids surgical / anaesthetic riskavoids surgical / anaesthetic risk

euthyroidism: 3 months – 60%, 6 months – 80%euthyroidism: 3 months – 60%, 6 months – 80%

hypothyroidism: 1 year – 3%, 24 years – 64%; hypothyroidism: 1 year – 3%, 24 years – 64%;

40% size reduction40% size reduction

contraindications: contraindications: lactatinglactating

pregnant / planning pregnant in 6 monthspregnant / planning pregnant in 6 months


Other treatment optionsOther treatment options

Anti-thyroid medicationsAnti-thyroid medications does not induce remissiondoes not induce remission

for patients not fit for surgery, limitted life expectancyfor patients not fit for surgery, limitted life expectancy

Percutaneous ablation (ethanol / radio-frequency / Percutaneous ablation (ethanol / radio-frequency /

high intensity focused ultrasound )high intensity focused ultrasound ) lack of long-term experiencelack of long-term experience

Subclinical thyrotoxicosisSubclinical thyrotoxicosis

Common in toxic multinodular goiterCommon in toxic multinodular goiter Porterfield et al. Porterfield et al. World J Surg 2008World J Surg 2008

438 / 586 (82%) patients with toxic nodular goiter438 / 586 (82%) patients with toxic nodular goiter

Long-term consequenceLong-term consequence Sawin et al. Sawin et al. NEJM 1994NEJM 1994

prospective cohort of 2007 subjects > 60 years old prospective cohort of 2007 subjects > 60 years old

follow-up: 10 yearsfollow-up: 10 years

subjects with subclinical hyperthyroidism (TSH < 0.1 subjects with subclinical hyperthyroidism (TSH < 0.1

mU/L) have 3-fold increased risk in developing atrial mU/L) have 3-fold increased risk in developing atrial

fibrillationfibrillation

Risk of malignancyRisk of malignancy

Incidental carcinoma in toxic multinodular goiter:Incidental carcinoma in toxic multinodular goiter: Review by Pazaitou et al. Review by Pazaitou et al. Horm Metab Res 2012Horm Metab Res 2012

7 retrospective cohorts of toxic nodular goiter7 retrospective cohorts of toxic nodular goiter 1611 subjects1611 subjects Cancer in 1.6 – 8.8%Cancer in 1.6 – 8.8% Microcarcinoma (<10mm): 35 – 88% of tumorsMicrocarcinoma (<10mm): 35 – 88% of tumors Excellent prognosis compared with euthyroid patientsExcellent prognosis compared with euthyroid patients

QMH QMH (unpublished)(unpublished) Toxic multinodular goiter operated for non-suspicious causesToxic multinodular goiter operated for non-suspicious causes Excluded FNAC confirmed or suspicious nodulesExcluded FNAC confirmed or suspicious nodules 16/178 (9%) found to have carcinoma16/178 (9%) found to have carcinoma 15 papillary carcinoma, 1 Hurthle cell carcinoma15 papillary carcinoma, 1 Hurthle cell carcinoma Mean diameter 12mmMean diameter 12mm

Risk of malignancyRisk of malignancy

? Clinical significance? Clinical significance higher reported prevalence due to more detailed pathological higher reported prevalence due to more detailed pathological

examination ?examination ? hyperthyroidism not previously identified as risk factors for hyperthyroidism not previously identified as risk factors for

manifesting carcinoma of thyroidmanifesting carcinoma of thyroid

? Pre-operative risk stratification? Pre-operative risk stratification cold nodules on scintigraphycold nodules on scintigraphy family historyfamily history exposure to neck irradiationexposure to neck irradiation USG findingsUSG findings > 50% carcinomas found outside of “dominant” / “cold” nodules > 50% carcinomas found outside of “dominant” / “cold” nodules

SummarySummary Toxic multinodular goiter is the manifesting stage of a Toxic multinodular goiter is the manifesting stage of a

chronic process of hyperplasia and acquisition of chronic process of hyperplasia and acquisition of automaticity in the thyroid gland.automaticity in the thyroid gland.

Hyperthyroidism, overt or subclinical, is an indication for Hyperthyroidism, overt or subclinical, is an indication for definitive interventions, in the form of thyroidectomy or definitive interventions, in the form of thyroidectomy or radio-active iodine ablation.radio-active iodine ablation.

In the absence of suspicion of malignancy, surgery is In the absence of suspicion of malignancy, surgery is probably still a “safer offer” in younger patients in view of probably still a “safer offer” in younger patients in view of the accumulated life-time risk for an incidental carcinoma the accumulated life-time risk for an incidental carcinoma to progress into a manifesting cancer.to progress into a manifesting cancer.

AcknowledgementAcknowledgement

Dr. Brian LangDr. Brian Lang

Thank you!Thank you!

management of toxic multinodular goiter - r ole of surgery

Documents

iodine intakepalpation

increase volume

definitionthyroid volume

benign nodules

monthscystic nodules

ug dayiodine rich food

food safety report

nodule number