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
Spectrum & course of Plummer’s diseaseSpectrum & course of Plummer’s disease
AgeAge Goiter/Goiter/nodularitynodularity
AutomaticityAutomaticity
Spectrum & course of Plummer’s diseaseSpectrum & course of Plummer’s disease
AgeAge Goiter/Goiter/nodularitynodularity
AutomaticityAutomaticity ThyrotoxicosisThyrotoxicosis
Spectrum & course of Plummer’s diseaseSpectrum & course of Plummer’s disease
AgeAge Goiter/Goiter/nodularitynodularity
AutomaticityAutomaticity ThyrotoxicosisThyrotoxicosis
adolescentadolescent ++non-non-
autonomousautonomous euthyroideuthyroid
Spectrum & course of Plummer’s diseaseSpectrum & course of Plummer’s disease
AgeAge Goiter/Goiter/nodularitynodularity
AutomaticityAutomaticity ThyrotoxicosisThyrotoxicosis
adolescentadolescent ++non-non-
autonomousautonomous euthyroideuthyroid
4040 ++++ autonomousautonomous euthyroid euthyroid
Spectrum & course of Plummer’s diseaseSpectrum & course of Plummer’s disease
AgeAge Goiter/Goiter/nodularitynodularity
AutomaticityAutomaticity ThyrotoxicosisThyrotoxicosis
adolescentadolescent ++non-non-
autonomousautonomous euthyroideuthyroid
4040 ++++ autonomousautonomous euthyroid euthyroid
Plummer’s disease
Spectrum & course of Plummer’s diseaseSpectrum & course of Plummer’s disease
AgeAge Goiter/Goiter/nodularitynodularity
AutomaticityAutomaticity ThyrotoxicosisThyrotoxicosis
adolescentadolescent ++non-non-
autonomousautonomous euthyroideuthyroid
4040 ++++ autonomousautonomous euthyroid euthyroid
6060 ++++++ autonomousautonomous subclinical subclinical hyperthyroidismhyperthyroidism
Spectrum & course of Plummer’s diseaseSpectrum & course of Plummer’s disease
AgeAge Goiter/Goiter/nodularitynodularity
AutomaticityAutomaticity ThyrotoxicosisThyrotoxicosis
adolescentadolescent ++non-non-
autonomousautonomous euthyroideuthyroid
4040 ++++ autonomousautonomous euthyroid euthyroid
6060 ++++++ autonomousautonomous subclinical subclinical hyperthyroidismhyperthyroidism
Toxic multinodular goiter
AgeAge Goiter/Goiter/nodularitynodularity
AutomaticityAutomaticity ThyrotoxicosisThyrotoxicosis
adolescentadolescent ++non-non-
autonomousautonomous euthyroideuthyroid
4040 ++++ autonomousautonomous euthyroid euthyroid
6060 ++++++ autonomousautonomous subclinical subclinical hyperthyroidismhyperthyroidism
> 60> 60 mass mass effecteffect
autonomousautonomous overt overt hyperthyroidismhyperthyroidism
Spectrum & course of Plummer’s diseaseSpectrum & course of Plummer’s disease
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)
Overt thyrotoxicosis in toxic MNGOvert thyrotoxicosis in toxic MNG
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
Overt thyrotoxicosis in toxic MNGOvert thyrotoxicosis in toxic MNG
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!
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