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Thyroid Nodules

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The Big Question

Is it cancer?

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A Brief History of the Thyroid

• 1816 – Prout successfully treats goiter with Iodine

• 1835-40 – Graves and von Basedow describe “Merseburg triad” of goiter, exophthalmos, and palpitations

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A Brief History of the Thyroid

• Marine – “Akron experiment” – dietary enrichment of iodine decreases goiter in schoolchildren

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A Brief History of the Thyroid

• 1929 – TSH identified• 1934 – Fermi – produces radioactive Iodine• 1950 – Duffy – associates XRT with thyroid

cancer• 1970’s – FNA comes into use

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History of Thyroid Surgery

• Condemned for years as heroic and butchery

• 1850 – French Academy of Medicine proscribed any thyroid surgery

• mid 1800’s – only 106 documented thyroidectomies– Mortality 40%: exsanguination and sepsis

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History of Thyroid Surgery

• 1842 – Crawford Long uses ether anesthesia

• 1846 – Morton demonstrates at MGH• 1867 – Lister describes antisepsis (Lancet)• 1874 – Pean – invents hemostat• 1883 – Neuber – Cap & gown (asepsis)

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History of Thyroid Surgery

• 1870’s-80’s – Billroth – emerges as leader in thyroid surgery (Vienna)– Mortality 8%– Shows need for RLN preservation– Defines need for parathyroid preservation (von

Eiselberg)– Emphasis on speed

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History of Thyroid Surgery

• Kocher – emerges as leader in thyroid surgery (Bern)– Mortality:

• 1889 – 2.4%• 1900 – 0.18%

– Emphasis on meticulous technique– Performed 5000 cases by death in 1917– Awarded 1909 Nobel Prize for efforts

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Epidemiology

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Epidemiology – Nodule

• Nodules common, whereas cancer relatively uncommon

• Goal is to minimize “unnecessary” surgery but not miss any cancer

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Epidemiology – Nodule

• Increases with age– Autopsy – 9th decade – 80% women, 65% men

• Higher in women (1.2:1 4.3:1)• Estimated 5-15% of nodules are cancerous• Although cancer more common in women,

a nodule in a man is more likely to be cancer

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Epidemiology – Pregnancy

• Pregnancy increases risk– Rosen: Nodules presenting during pregnancy –

• 30 patients, 43% were cancer• HCG may be growth promoter (TSH-like activity)

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Recommendations – Pregnancy

• Some author recommendations:– Surgery done for cancer before end of 2nd

trimester, else post-partum– Women with h/o thyroid cancer – avoid

pregnancy

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Epidemiology – Radiation

• Marshall Islanders exposed to nuclear fallout:– Nodules in 33%, 63% children < 10 at time

• Japanese: increased nodules in residents of Hiroshima / Nagasaki circa 1945– Increased occult thyroid ca in Japanese without

direct radiation exposure• Chernobyl – possible increase in neoplasms• Therapeutic XRT for malignancy raises risk

for thyroid neoplasia

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Radiation

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Epidemiology – Radiation

• Appears to be dose-dependent– ERR 7.7 at 100 cGy

• Maximum risk approximately 30 years later• Nodule in radiated patient: 35-40% cancer• Data suggest no more agggresive behavior

over spontaneously-occuring cancers, but may be larger at presentation

• Only unequivocal environmental cause of thyroid cancer

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Childhood Radiation

• Younger age – greater risk• Suppression may help decrease risk

– One study: 35.8% 8.4%

• I-131: risk of leukemia with high doses

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Epidemiology – Children

• Nodule more likely to be cancer than adults– approx 20%

• 10% thyroid cancer age <21• More likely to present with neck mets• Most common cause thyroid enlargement is

chronic lymphocytic thyroiditis

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Epidemiology – Children

• Medullary Thyroid Carcinoma– FMTC, MEN 2A, MEN 2B– RET proto-oncogene (chromosome 10)– Calcium / Pentagastrin stimulation– Prophylactic thyroidectomy recommended age

2-6

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Epidemiology – Carcinoma• Occult carcinoma in 6 – 35 % of glands at autopsy

(usu 4-10 mm)– Biologic behavior difficult to predict

• 12,000 new thyroid cancers / year• 1000 deaths / year• Surgically removed nodules:

– 42-77 % colloid nodules– 15-40 % adenomas– 8-17 % carcinomas

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Epidemiology – Cancer

• Histological subtype– Papillary – 70%– Follicular – 15%– Medullary – 5-10%– Anaplastic – 5%– Lymphoma – 5%– Mets

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Thyroid Mets• Breast• Lung• Renal• GI• Melanoma

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Papillary Carcinoma

• “Orphan Annie” nuclei

• Psamomma bodies

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Follicular Carcinoma

• Capsular invasion must be present• FNA inadequate for diagnosis

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Evaluation

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Differential Diagnosis

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History

• Age • Gender • Exposure to Radiation• Signs/symptoms of hyper- / hypo- thyroidism• Rapid change in size

– With pain may indicate hemorrhage into nodule– Without pain may be bad sign

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History

• Gardner Syndrome (familial adenomatous polyposis)– Association found with thyroid ca– Mostly in young women (94%) (RR 160)– Thyroid ca preceded dx of Garners 30% of time

• Cowden Syndrome– Mucocutaneous hamartomas,

keratoses,fibrocystic breast changes & GI polyps– Found to have association with thyroid ca (8/26

patients in one series)

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History

• Familial h/o medullary thyroid carcinoma– Familial MTC vs MEN II

• Family hx of other thyroid ca• H/o Hashimoto’s thyroiditis (lymphoma)

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History

• History elements suggestive of malignancy:– Progressive enlargement– Hoarseness– Dysphagia– Dyspnea– High-risk (fam hx, radiation)

• Not very sensitive / specific

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Physical Exam

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Physical

• Thyroid exam generally best from behind• Check for movement with swallowing

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Physical

• Complete Head & Neck exam• Vocal cord mobility (?Strobe)• Palpation thyroid• Cervical lymphadenopathy• Ophthalmopathy

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Physical

• Physical findings suggestive of malignancy:– Fixation– Adenopathy– Fixed cord– Induration– Stridor

• Not very sensitive / specific

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Graves Ophthalmopathy

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Graves Ophthalmopathy

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Neck Bruising

• Suggests hemorrhage into nodule

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Lingual Thyroid

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Lingual Thyroid

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Workup

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Serum Testing

• TSH – first-line serum test– Identifies subclinical thyrotoxicosis

• T4, T3• Calcium• Thyroglobulin

– Post-treatment good to detect recurrence• Calcitonin – only in cases of medullary• Antibodies – Hashimoto’s• RET proto-oncogene

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Flow Chart

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Fine-Needle Aspiration Biopsy

• Emerged in 1970s – has become standard first-line test for diagnosis

• Concept• Results comparable to large-needle biopsy, less

complications• Safe, efficacious, cost-effective• Allow preop diagnosis and therefore planning• Some use for sclerosing nodules

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Fine-Needle Aspiration Biopsy

• Results – Benign– Malignant– Suspicious/Indeterminate– Insufficient/Inadequate

• Pooled data from 9 series, 9119 pts:– 74, 4, 11, 11%, respectively

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Fine-Needle Aspiration Biopsy

• Technique:– 25-gauge needle– Multiple passes– Ideally from periphery of lesion– Reaspirate after fluid drawn– Immediately smeared and fixed– Papanicolaou stain common

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Fine-Needle Aspiration Biopsy

• Problems:– Sampling error

• Small (<1 cm)• Large (>4 cm)

– Hashimoto’s versus lymphoma– Follicular neoplasms– Fluid-only cysts– Somewhat dependent on skill of cytopathologist

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FNA of Papillary Ca

• NG: nuclear grooves

• IC: intranuclear inclusions

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Imaging

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Plain Films

• Not routinely ordered• May show:

– Tracheal deviation– Pulmonary metastasis– Calcifications (suggests papillary or medullary)

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Tracheal Deviation

• May be incidentally noted

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MRI of Last Patient

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Ultrasonography

• Thyroid vs. non-thyroid– Good screen for thyroid presence in children

• Cystic vs. solid• Localization for FNA or injection• Serial exam of nodule size

– 2-3 mm lower end of resolution• May distinguish solitary nodule from

multinodular goiter– Dominant nodule risks no different

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Ultrasonography

• Findings suggestive of malignancy:– Presence of halo– Irregular border– Presence of cystic components– Presence of calcifications– Heterogeneous echo pattern– Extrathyroidal extension

• No findings are definitive

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Nuclear Medicine• Concept• Uses

– Metabolic studies– Imaging

• Iodine is taken up by gland and organified• Technetium trapped but not organified• Usually only for papillary and follicular

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Nuclear Medicine

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Radioiodine Scan

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Nuclear Medicine

• Radioisotopes:– I-131– I-123– I-125– Tc-99m– Thallium-201– Gallium 67

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Nuclear Medicine• Technetium 99m

– Most commonly used isotope (some authors)– Administered as pertechnate (TcO4-)– Images can be obtained quickly

• “One-Stop” evaluation– Hot nodules need f/u Iodine scan

• Discordant nodules higher risk of malignancy

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Hot Nodule

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Nuclear Medicine

• Tc-99m versus I-123

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Nuclear Medicine

• Hurthle-cell neoplasms– Better imaged with Technetium sestamibi

• Concentrates in mitochondira– Poorly imaged with iodine

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Hot, Warm, Cold

• Study: 4457 patients with nodules– All scanned, all surgery– Results

• Cold 84% 16% cancer• Warm 10% 9% cancer• Hot 5.5% 4% cancer

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Hot Nodules

• Most authors feel that hot nodule in hyperthyroid pt has low malignancy risk

• Nodule in clinically hyperthyroid pt may be cold nodule against background of Graves, so scan may help

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Other Imaging Modalities

• CT– Keep in mind iodine in contrast

• MRI• PET

• Not first-line, but may be adjunctive

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Controversy

• Incidentally-found non-palpable nodule– One author’s recommendations:

• Ultrasound-guided FNA for– H/o radiation– >1.0 cm– Positive family history– Suspicious u/s features

• Else– 6-12 mo f/u

– Of course, keep overall clinical picture in mind

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Pearls from an Expert (Mazzaferri)• No imaging on asymptomatic pts with normal

glands by palpation – too many false positives• Symptoms suggestive of invasion need tissue dx• Two or more suspicious features need surgery,

regardless of FNA• Multinodular goiter carries a substantial risk of

cancer• Greater suspicion of nodules in males• Male over 60: consider surgery regardless of FNA,

due to high likelihood of cancer

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Flowchart

Thyroidectomy

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Minimally invasive thyroid surgery (MITS)

Surgical Technique

• Approach

– Cervical approach– Anterior chest approach– Axillary approach

• Create the working space at the neck

– CO2 insufflation (<10 mmHg)• Totally video-endoscopic• Potential risk for metabolic and hemodynamic

complications

– Gasless (skin lifting)• Endoscopic-assisted procedure

Skin lifting

Skin lifting

• Surgical procedure

Similar with conventional thyroidectomy

Advantages

• 1.Superior cosmetic appearance• 2.Less postoperative pain• 3.Earlier return to regular activities

Disadvantages

• 1.It is not suitable for huge goiters• 2.Longer operating time• 3.Requires special equipment and skills

Endoscopic surgery instruments

Incision

Create the working space

Pretracheal muscles

Sternocleidomastoid muscle

Thyroid nodule

Lower pole

Upper poleTrachea

The excised thyroid nodule

Most patients come with big thyroid nodule

More expensive than conventional thyroidectomy

Neck scar would be covered with the “jilbab”

MANAGEMENT OF THE MANAGEMENT OF THE COMPLICATIONS COMPLICATIONS

OFOFTHYROID SURGERYTHYROID SURGERY

IMMEDIATE IMMEDIATE COMPLICATIONSCOMPLICATIONS

• HEMORRHAGE• INFECTION• RECURRENT LARYNGEAL NERVE PALSY• THYROID CRISES OR STORM • RESPIRATORY OBSTRUCTION • PARATHYROID INSUFFICIENCY OR

TETANY

LATE COMPLICATIONSLATE COMPLICATIONS

• THYROID INSUFFIENCY

• RECURRENT THROTOXICOSIS

• PROGRESSIVE EXOPHTHALMOS

• HYPERTROPHIC SCAR OR KELOID.

HEMORRHAGEHEMORRHAGE• Incidence – 0.3-1%• Two types -

– Deep to deep fascia– Subcutaneous

• May be primary or reactionary• A deep bleeding produces tension hematoma. Usually

due to slipping of the ligature of the superior thyroid artery, though it can also be from a thyroid remnant or a thyroid vein. This compresses on the airway & potentially life threatening unlike the subcutaneous bleeding.

HEMORRHAGEHEMORRHAGE• GOOD INTRAOPERATIVE HEMOSTASIS• Don’t traumatize the thyroid• Avoid too much neck dressings • Suction drain ??• Do not waste time on imaging • A tension hematoma requires opening of the wound,

evacuation of hematoma & ligature of the bleeding vessels

• A subcutaneous hematoma can be aspirated.

INFECTIONINFECTION

• Cellulitis – erythema, warmth & tenderness around the wound

• Abscess – superficial / deep• Deep abscess associated with fever, leucocytosis,

tachycardia

INFECTIONINFECTION• Pus for Gram’s stain & culture• CT for deep neck abscess• Can be prevented by proper hemostasis at the time of

surgery & using suction drain. • Per-operative antibiotics not recommended.

• Once established – Antibiotics – Drainage of abscess.

RECURRENT LARYNGEAL RECURRENT LARYNGEAL NERVE PARALYSISNERVE PARALYSIS

• Temporary paralysis is due to pressure of hematoma on the nerve. Recovers in 3 weeks to 3 month.

• Permanent paralysis is rare (<2%) and is due to undue stretching or its inclusion in a ligature.

• Unilateral – – 1/3 rd are asymptomatic– Change in voice– Improves due to compensation by the healthy cord.

• Bilateral- dyspnea & biphasic stridor

RECURRENT LARYNGEAL RECURRENT LARYNGEAL NERVE PARALYSISNERVE PARALYSIS

• Prevent injury to the nerve by– Identify– ITA ligated far from lobe– Posterior layer of pretracheal fascia kept intact.

• Laryngoscopy, laryngeal EMG• For unilateral paralysis no treatment is required. • For bilateral paralysis

– Tracheostomy (with speaking valve. – Lateralization of cord

• Arytenoidectomy• Through endoscope• Thyroplasty type 2• Cordectomy• Nerve muscle implant

COMBINED PARALYSISCOMBINED PARALYSIS• Unilateral

– Vocal cord lies in cadaveric position– Hoarseness of voice & aspiration of liquids. – Ineffective cough

• Bilateral– Aphonia– Aspiration– Ineffective cough– Bronchopneumonia

• ONLY superior laryngeal nerve palsy also occurs rarely & presents with hoarseness & loss of voice stamina.

COMBINED PARALYSISCOMBINED PARALYSIS• Unilateral

– Speech therapy– Medialise of cord

• Teflon paste injection• Thyroplasty type 1• Muscle or cartilage implant• Arthrodesis of arytenoid joint

• Bilateral– Tracheostomy– Epiglottopexy– Vocal cord plication– Total laryngectomy

• SLN: speech therapy

THYROID CRISIS / STORMTHYROID CRISIS / STORM

• Acute exacerbation of hyperthyroidism as the patient has not been brought to the euthyroid state before operation.

• Tachycardia, fever(>1050C) , restlessness, delirium

• Mortality is 10%

THYROID CRISIS / STORMTHYROID CRISIS / STORM• Ensure euthyroid state before operation• Sedation – morphine / pethidine• Hyperpyrexia – ice bags. Tepid sponging, hypothermic blanket,

rectal ice irrigation• Oxygen administration• IV glucose-saline for dehydration• Potassium for tachycardia• Cortisone – 100mg IV• Carbimazole – 10- 20 mg 6th hourly• Lugol’s iodine 10 drops 8th hourly by mouth or potassium iodide 1g

IV• Propranolol – 20-40mg 6th hourly• Digoxin for atrial fibrillation• Diuretics for cardiac failure

RESPIRATORY OBSTRUCTIONRESPIRATORY OBSTRUCTION

• Laryngeal edema due to– Tension hematoma– Endotracheal intubation & surgical handling– More chance in vascular goiters.

• Collapse / kinking of the trachea• Bilateral recurrent nerve paralysis can

aggravate obstruction if edema is present.

RESPIRATORY OBSTRUCTIONRESPIRATORY OBSTRUCTION

• Open the wound & release the tension hematoma

• Endotracheal tube if no improvement. INTUBATION TO BE DONE BY AN EXPERIENCED ANESTHETIST as repeated attempts cause more edema leading to cerebral anoxia.

• The tube is left in place for several days & steroids given to reduce the edema.

PARATHYROID INSUFFICIENCYPARATHYROID INSUFFICIENCY• Due to removal of parathyroids or the parathyroid end artery.

• Incidence – 1-3%

• Occurs 2 – 5% after operation. Can be delayed for 2-3 weeks or hypocalcemia may be asymptomatic.

• Classic triad – – Carpopedal spasm– Stridor– Convulsions

• Latent tetany– Trousseau’s sign– Chvostek’s sign

• Persistant – grand mal epilepsy, cataracts, psychosis, calcification of basal ganglia, papilledema.

PARATHYROID INSUFFICIENCYPARATHYROID INSUFFICIENCY• Correct identification of the gland

• Ligate vessels distal to the parathyroids.

• Recognition of the parathyroid glands, which appear in a variety of shapes and have a caramel-like color, is critical. When they lose their blood supply, they turn black. The devascularized gland should be removed, cut into 1 to 2mm pieces, and reimplanted in the sternomastoid muscle or the forearm.

• Monitor serum Ca for 72 hrs post-operatively.

• 20 ml 10% solution of calcium gluconate IV• 10 ml injected IM• 2.5-5 G calcium carbonate / day

• PTH is unsatisfactory.• Alfacalcidol

THYROID INSUFFICIENCYTHYROID INSUFFICIENCY• INCIDENCE :20-25% of patients subjected to subtotal

thyroidectomy for diffuse toxic goiter & toxic nodular goiters with internodular hyperplasia

• Time: <2 yrs. May be delayed >5yrs.• Transient hypothyroidism may occur within 6 months

which is asymptomatic.• Due to change in nature of autoimmune response.• More chance if less residual thyroid tissue• Cold intolerance, fatigue constipation, weight gain,

myxedema.

THYROID INSUFFICIENCYTHYROID INSUFFICIENCY• Thyroxine – start with 50 mcg/d, 100mcg/d after 3

weeks, and 150 mcg/d thereafter. Taken as a single daily dose.

• Monitoring – – TSH in the lower end of reference range (0.15-3.5 mU / l) – T 4 normal or slightly raised. (10 – 27 pmol / l)

• Manage ischemic heart disease with beta blockers & vasodilators

• Increase thyroxine during pregnancy. (50 mcg)• Myxedema coma: IV thyroxine 20mcg 8th hourly

followed by oral.

RECURRENT THYROTOXICOSISRECURRENT THYROTOXICOSIS

• Incidence 5 – 10%• Due to inadequate removal or hyperplasia of remaining thyroid

tissue.

RECURRENT THYROTOXICOSISRECURRENT THYROTOXICOSIS

• Less than 40 yrs – carbimazole – 0-3wks 40-60mg/d– 4-8wks 20-40mg/d– 18-24 months 5-20mg/d

• More than 40 yrs – radioiodine– 5-10mCi oral; 75% respond in 4-12 weeks– Repeated after 12-24 weeks if no improvement.– Beta blocker / carbimazole cover during lag period.– Long term follow-up for hypothyroidism.

PROGRESSIVE / MALIGNANT PROGRESSIVE / MALIGNANT EXOPHTHALMOSEXOPHTHALMOS

• Occurs even when thyrotoxic features are regressing.

• Steroids & radiotherapy.

HYPERTROPHIC SCAR / KELOIDHYPERTROPHIC SCAR / KELOID

• Platysma to be divided at a higher level• Occurs if scar overlies the sternum• Some persons are more susceptible.• May follow wound infection.• Intradermal steroids, repeated monthly.

THANK YOUTHANK YOU