Thyroid Pathologies- Introduction, Benign diseases and Carcinoma Thyroid

THYROID

INTRODUCTION

AN OVRVIEW

Dr.B.Selvaraj MS;Mch;FICS;Professor of Surgery

Melaka Manipal Medical collegeMelaka 75150 Malaysia

Must To Know Core Clinical Problems

1.Acute RLQ pain2.Acute RUQ pain3.Acute epigastric pain4.Acute LLQ pain5.Dysphagia6.Abdominal lumps7.Upper GI hemorrhage8.Lower GI hemorrhage9.Obstructive Jaundice

10.Breast lumps, Mastalgia & Nipple discharge 11.Neck swellings- Thyroid & Non thyroidal12.Groin swellings13.Scrotal swellings14.Limb ischemia- Acute & Chronic15.Varicose veins16.Renal & Ureteric colic17.Hematuria18.Acute retention of urine

THYROID

Surgical Anatomy Surgical Physiology Surgical Pathology Symptomatology Investigations

ANATOMY

PHYSIOLOGY

PHYSIOLOGY

Thyroid- Pathology

Simple (non-toxic) goiterSimple hyperplastic goiterMultinodular goiter & Solitary noduleToxic goitreDiffuse goiter (Graves’ disease)Toxic multinodular goiter(Plummer’s disease)Toxic nodule (Gotsche’s disease)Neoplastic goiterBenignAdenoma

MalignantPapillaryFollicularAnaplasticMedullaryInflammatoryDe Quervain’s thyroiditisRiedel’s thyroiditisAutoimmuneHashimoto’s thyroiditis

Goiter- Enlargement of thyroid gland

Thyroid- Symptoms

Symptoms of Hyperthyroidism Loss of weight inspite of voracious

appetite Heat intolerance Nervous & irritable Loose stools Oligomenorrhea/AmenorrheaSymptoms of Hypothyroidism Weight gain- obese Hoarseness of voice Loss of eyebrow lashes laterally

Symptoms of pressure effects Dyspnea Dysphagia Recurrent laryngeal nerve palsySymptoms of distant metastasis Chest pain, cough and hemoptysis Headache and seizures Abdominal distension and pain Generalised bone pain

Cardinal Symptom Enlargement of Thyroid Goiter

Thyroid- Investigations

Thyroid function test - T3, T4 and TSH USG Neck - Solid or cystic swelling FNAC of the thyroid swelling - Benign or malignant except follicular Ca Radioactive iodine I123 scan - Especially in Solitary nodule Warm, hot or cold

THYROID

Benign Thyroid Diseases

AN OVRVIEWDr.B.Selvaraj MS;Mch;FICS;

Professor of Surgery

Melaka Manipal Medical college

Melaka 75150 Malaysia

Thyroid- Pathology Simple (non-toxic) goiter

Simple hyperplastic goiter

Multinodular goiter & Solitary nodule

Toxic goiter

Diffuse goiter (Graves’ disease)

Toxic multinodular goiter(Plummer’s

disease)

Toxic nodule (Goetsch’s disease)

Neoplastic goiter

Benign

Adenoma

Malignant

Papillary

Follicular

Anaplastic

Medullary

Inflammatory

Autoimmune: Chronic lymphocytic thyroiditis

Hashimoto’s disease

Granulomatous: De Quervain’s thyroiditis

Fibrosing: Riedel’s thyroiditis

Infective: Acute (bacterial thyroiditis,

viral thyroiditis ‘subacute thyroiditis’)

Chronic (tuberculous,syphilitic)

Other: Amyloid- colloid goiter

Simple Goiter

Simple (non-toxic) goiter

Simple hyperplastic goiter

Diffuse enlargement of the whole

thyroid gland because of iodine

deficiency, physiological stress

like puberty and pregnancy

Multinodular goiter &

Solitary nodule

Focal enlargement of the gland

either mono-nodular or

multinodular

Pathogenesis of a thyroid nodule

✓ TSH stimulation will lead on to diffuse hyperplasia

composed of active follicles. This is called diffuse

hyperplastic goiter which is reversible.✓ Later as a result of fluctuating TSH stimulation, mixed

patterns of active and inactive lobules develop

✓ Active lobules become more vascular, hyperplastic

followed by hemorrhage and central necrosis

✓ The necrotic lobules coalesce to form a nodule filled with

either iodine-free colloid or inactive follicles

✓ Repetition of this process will result in a nodular goiter.

Most nodules are inactive and active follicles are present

only in the internodular tissue.

Thyroid- Definitions

GOITER: any enlargement of thyroid gland

Thyrotoxicosis : Symptoms of thyroid hormone excess due to

increased synthesis in thyroid follicles or exogenous thyroid

hormone supplementation.

Hyperthyroidism : Features of thyroid hormone excess due to

increased synthesis of thyroid hormone by the gland.

Causes of Thyrotoxicosis

✓ Diffuse toxic goitre (Grave’s disease)

✓ Toxic nodular goitre (Toxic MNG)- Plummer’s disease

✓ Toxic nodule (Toxic adenoma)- Goetsch’s disease

✓ Thyrotoxicosis factitia (Due to excess exogenous thyroid hormone

supplementation)

✓ Jod-Basedow thyrotoxicosis (Iodide induced)

✓ Thyroiditis

✓ Malignancies of thyroid.

✓ Trophoblastic tumor (Due to thyroid stimulating action of HCG produced by

this tumor)

✓ Ectopic thyroid tissue (Struma ovarii)

Toxic Goiter-Graves Disease

✓Described by Irish physician Dr.Robert Graves in 1835

✓Common in females

✓Age : 20-40 years

✓Pathogenesis:

Thyroid stimulating immunoglobulins (TSI) of IgG class produced by lymphocytes

stimulate TSH receptor.

✓Ophthalmopathy: Fibroblast proliferation and increased glycosaminoglycans

production induced by TSI (?antigenic similarity between orbital tissues and

thyroid.)

Graves Disease- Symptoms✓Calorigenic :Weight loss inspite of

voracious appetite,heat intolerance,

increased sweating, tiredness

✓Nervous :

Tremors,anxiety,nervousness,

increased activity.

✓CVS: Dyspnoea, palpitations, pedal

edema (due to CCF)

✓Menstrual : Amenorrhoea/

oligomenorrhoea

✓Miscellaneous: Loose stools

✓Ocular : Diplopia, pain and increased

lacrimation (due to corneal ulcer)

Graves Disease- Signs

✓Thyroid :Diffuse enlargement with

bruit and visible pulsations

✓CVS

✓Pulse : Increased sleeping pulse rate

with wide pulse pressure.

✓Stages of development of thyrotoxic

arrhythmias : Multiple extra systoles

→ Paroxysmal atrial tachycardia →

Paroxysmal atrial fibrillation →

Persistent AF not responding to

digoxin.

✓ Dermopathy : Pretibial myxedema

due to increased mucopolysaccharide

deposition.

✓ Thyroid acropachy : Dermopathy

associated with clubbing of toes

✓ Tremors: Outstretched hands,tongue

✓ Hyerreflexia: Increased reflexs

✓ Plummer’s Sign: Proximal myopathy

Graves Disease- Eye Signs

✓Von Graefe’s sign (lid lag)

✓Stellwag’s sign (characteristic stare

with infrequent blinking)

✓Dalrymple’s sign (widened

palpebral fissure)

✓ Naffziger’s sign : For proptosis

✓ Moebius sign : Loss of convergence

(Due to ophthalmoplegia)

✓ Joffroy’s sign: Absence of wrinkling

of forehead on looking up.

✓ Graves disease is diagnosed when features of thyrotoxicosis

is associated with ophthalmopathy +/- dermopathy

Graves Disease- Signs

Graves Disease- Eye Signs +Pretibial Myxedema

Graves Disease- Diagnosis

✓Most cases can be diagnosed clinically.

✓Thyroid function test : Raised T3,T4 with decreased

TSH.

✓Thyroid scan : I123 scan-Diffuse increased uptake.

✓FNAC : Relative contraindication in the presence of

thyrotoxicosis.

Graves Disease- I123 Scan

Graves Disease-Histopathology

Follicular hypertrophy with scanty colloid

Graves Disease-Treatment

✓ Medical

✓ Radio-Iodine

✓ Surgery

Medical Treatment

✓ Anti thyroid drugs : Carbimazole and propylthiouracil

✓ Mechanism of action : Inhibit thyroid peroxidase and thereby interfere with

iodination of tyrosine residues in thyroglobulin and coupling of iodotyrosine

residues to form T3 and T4.

✓ Dose : Start with high dose (Carbimazole 10mg TDS ) once control is achieved

dose is reduced (5 mg BD or TDS)

✓ Alternatively block and replacement regimen is used – Continue with high

dose of antithyroid drugs with thyroxine supplementation (0.1 mg OD) .

Decreased risk of iatrogenic hypothyroidism .

✓ Adverse effects : Granulocytopenia, Aplastic anemia

Medical Treatment

Can be used even in children and young adults.

Hypothyroidism if induced is reversible

No complications associated with surgery.

Disadvantages:

Prolonged treatment is required since relapse rate is high.

Drug toxicity

Advantages:

Medical Treatment-Beta blockers

✓ Propranolol most commonly used

✓ Indications :

✓ For symptomatic control

When antithyroid drugs are initiated till biochemical control is achieved

✓ Thyroid storm

Along with iodide for preop preparation.

✓ Dose : 20-40 mg QID (Max dose – 600mg/day)

Medical Treatment-Iodides

✓ Lugol’s iodine most commonly used preparation (5% iodine in 10% potassium

iodide solution).

✓ Mechanism of action :

Inhibition of thyroid hormone release (Thyroid constipation)

Decreases vascularity of the gland

✓ Uses:

Preop preparation : 10-14 days prior to surgery

Thyroid storm :iodinated contrast agents (sodium iopodate ) given i.v.

✓ Dose : Lugol’s iodine 5 drops TDS in milk.

Radioactive Iodine Ablation

✓ I131 most commonly used

✓ Indications :

✓ Patients with small to moderate enlargement of gland and in whom

antithyroid drugs have clearly not worked.

✓ Patients not willing for surgery or for whom surgery is contraindicated.

✓ Recurrence after surgical or medical therapy.

Radioactive Iodine Ablation

1.Euthyroid state achieved by using antithyroid drugs for

3-4weeks before treatment.

2.Interruption of antithyroid drugs for 3-4 days before and after Iodine

treatment to permit adequate accumulation and retention of administered

iodine.

3.Pretreatment radioiodine scan done (25-100 micro curie of I131 given) to

calculate therapeutic dose.

4.Therapeutic dose of radio-iodine given (usually 8-12 milli curie) orally.

Radioactive Iodine Ablation

✓ Patient rendered euthyroid by 8-12 weeks after treatment.

✓ Disadvantages :

✓ Hypothyroidism : incidence 10-15% by 1 year which increases by 3% in each

succeeding year.

✓ Exacerbation of cardiac arrhythmias in elderly

✓ Fetal damage-hence contraindicated in pregnant and lactating women

✓ Also contraindicated in children

✓ Worsening of ophthalmopathy – avoided by using prophylactic steroids

✓ Can induce Thyroid storm if patients are not rendered euthyroid before radio-

iodine administration

SURGERY

✓ Indications :

✓ Failure of medical/radioiodine treatment

✓ Younger patients particularly adolescents

✓ Pregnant patients

✓ Patients with suspicious masses contained within the large

thyroid.

✓ Patients with severe cosmetic deformities or tracheal

compression causing discomfort.

SURGERY

✓ Extent of surgery : Subtotal or Total thyroidectomy

✓ Advantage of total thyroidectomy :

✓ Recurrence is avoided

✓ Patients with ophthalmopathy are stabilized most successfully

by total thyroidectomy.(Due to removal of entire antigenic

focus)

✓ Patients should be rendered euthyroid before surgery to avoid

thyroid storm.

Complications of Surgery

Tension hematoma

Thyroid Storm-Treatment

✓ Supportive measures : Correction of

dehydration with I.V fluids and

hyperpyrexia with cooling blankets

✓ Antithyroid drugs : Propylthiouracil

preferred.Given through Ryle’s tube if

patient can’t take orally.(Parenteral

forms not available).

✓ Iodinated contrast agents (sodium

iopodate)-1gm given I.V

✓ Propranolol 2mg I.V with ECG

monitoring (if patient cannot take

orally) or 40-80mg Q6h

✓ Large doses of dexamethasone :

2mg Q6h (inhibit hormone release,

peripheral conversion of T4toT3 and

provide adrenal support).

✓ Life threatening circumstances :

Peritoneal or hemodialysis to lower

T3 andT4 levels.

Ophthalmopathy-Treatment

✓ Mild disease – Conservative measures: Elevating the head at night

Protection of eye ball and avoiding corneal drying by applying

1%methylcellulose eye drops or plastic shields.

✓ Severe cases –large doses of prednisolone (100-120 mg/day)

✓ Malignant exopthalmos : Orbital decompression

Thyrotoxicosis in Pregnancy

✓ Radio-Iodine : Contraindicated.

✓ Surgery : Can be done in second trimester

Chance of miscarriage with surgery.

✓ Antithyroid drugs : Propylthiouracil preferred (Placental transfer less)

Can cause fetal goitre. Avoided by keeping antithyroid drug dosage to

minimum to prevent rise in TSH.

Toxic Multinodular Goiter-

Plummer’s Disease

✓ Seen in long standing goiter when one or more nodules become

autonomous.

✓ Cardiovascular symptoms predominate

✓ Radionuclide scan: Can demonstrate autonomous nodules.

✓ Treatment :

✓ Antithyroid drugs : Can control symptoms but relapse invariably occurs

with discontinuation of medications.

✓ Propranolol can be used for symptomatic control.

✓ Radio-iodine : Effective. But larger doses are required 20-30 milli curie

Toxic Multinodular Goiter-

Plummer’s Disease

✓ Chance of hypothyroidism with

radio-iodine is less compared to

grave’s disease due to variable

activity of different portion of the

gland allowing previously

quiescent area to function in place

of those destroyed by I131.

✓ Surgery : Preferred treatment

(Total thyroidectomy)

Primary Vs Secondary Thyrotoxicosis

Toxic Nodular Goiter-

Goetsch’s Disease

TreatmentHemithyroidectomy after

making patient euthyroid

Small nodule Radio

active iodine ablation

THYROIDITIS

ACUTE THYROIDITIS

SUBACUTE THYROIDITIS

De Quervain’s Thyroiditis

CHRONIC THYROIDITIS

Hashimoto’s Thyroiditis

CHRONIC THYROIDITIS

Reidel’s Thyroiditis

THYROID

CARCINOMA THYROID

AN OVRVIEWDr.B.Selvaraj MS;Mch;FICS;

Professor of Surgery

Melaka Manipal Medical college

Melaka 75150 Malaysia

Ca Thyroid- Objectives

OBJECTIVES

✓ Classification

✓ Etiology

✓ Pathophysiology

✓ Histology

✓ Presentation

✓ Diagnosis of various Carcinomas

✓ Treatment

Neoplastic Goiter Classification

✓ Adenoma

✓ Carcinoma

✓ Primary

-A.Epithelial diffrentiated –

1.Papillary 2.Follicular

-B. Epithelial Undiffrentiated- 3.Anaplastic

-C. Parafollicular cells - 4. Medullary

-D. Lymphoid cell -5. Lymphoma

✓ Secondary- Melanoma, Ca breast, Renal

Ca

Ca Thyroid- Etiology

✓ Female gender

✓ History of radiation administered in infancy and

childhood , [ in 9 %]

Avg. Latent Period >10 yrs Papillary Ca

✓ Excessive Iodine Consumption Papillary Ca

✓ History of goiter Anaplastic / Follicular Ca

✓ Frankshift Mutation of RET gene Papillary Ca

✓ Point Mutation of RET gene Medullary Ca

✓ P53 gene mutation Anaplastic Ca

✓ Loss of Gene at 11q Follicular Ca

AdenomaThyroid

✓ Benign lesion derived from Follicular

Epithelium

✓ Usually single,well encapsulated

✓ Present as painless single nodule

✓ Discrete lesions with glandular /

acinar Follicular pattern.

✓ Papillary change is not typical but if

present suggests Papillary Ca

✓ Trucut biopsy to confirm diagnosis

✓ FNAC can not make out

capsular/vascular invasion

✓ Treatment: Hemithyroidectomy

✓ Closely packed

follicles, trabeculae

or solid sheets

✓ No capsular or

vascular invasion

✓ Completely

enveloped by thin

fibrous capsule

✓ Different from

surrounding gland

AdenomaThyroid- FNAC

Papillary Ca Thyroid

✓ Most common type of Thyroid ca – 75 to 80%.

✓ Female : Male = 2 : 1 .

✓ Mean age at presentation – 35 yrs.

✓ More common in persons exposed

to radiation.

✓ Macroscopic – Hard, whitish,

calcified,Unencapsulated

✓ Slow growing malignant tumor which is multifocal in

origin

✓ Often present as painless neck mass or lateral

cervical lymphadenopathy

Papillary Ca Thyroid

Papillary Ca Thyroid

✓ Microscopic features –

1. Cuboidal cells with abundant cytoplasm

2. Intranuclear cytoplasmic inclusions

‘ORPHAN ANNIE EYED NUCLEI’ .

3. Fibrovascular stroma with calcium

deposits ‘PSAMOMMA BODIES’.

✓ Lymphatic spread – Intrathyroidal ~90%

and to Paratracheal and cervical LN ~50%

Papillary Ca Thyroid

Follicular Ca Thyroid

✓ Female : Male = 3 : 1 .

✓ Accounts for 15 to 20 % of all Thyroid Ca

✓ Mean age at presentation – 50 yrs.

✓ More frequent in IODINE DEFICIENT

AREAS.

✓ History of long standing goitre .

✓ PATHOLOGY -

✓ Usually ENCAPSULATED & SOLITARY.

✓ Spreads usually By Blood ,Most commonly to

Lungs, Brain & Bone.

✓ Lymph node metastases in <10 % cases.

Follicular Ca Thyroid

Follicular Ca Thyroid ✓ Currently, a follicular carcinoma cannot be

distinguished from a follicular adenoma

based on cytologic, sonographic, or clinical

features alone.

✓ Pathogenesis of follicular carcinoma may be

related to iodine deficiency and various

oncogene and/or microRNA activation.

✓ Follicular carcinoma tends to be more cellular

with a thick irregular capsule, and often with

areas of necrosis and more frequent mitoses.

✓ It is distinguished from a follicular adenoma

on the basis of capsular invasion and

vascular invasion

Follicular Ca Thyroid

Hurthle Cell Carcinoma

✓ Variant of FOLLICULAR CELL Ca.

✓ Derived from ‘OXYPHIL CELLS’ of

thyroid. Function of these cells is not

known.

✓ Cells are stuffed with mitochondria &

possess the TSH receptors and produce

thyroglobulin.

✓ As compared to follicular type –

usually multifocal & bilateral and

more likely to metastatise to LN

[ >25%].

✓ HCC are encapsulated thyroid tumours that

contain more than 75% oncocytic cells, which

stain pink under the microscope as they are

packed with mitochondria

✓ The characteristic feature is the distinct

granular acidophilic cytoplasm

Medullary Ca Thyroid ✓ Female : Male = 1.5 : 1 .

✓ Accounts for 15 to 20 % of all Thyroid Ca

✓ Mean age at presentation – 50 to 60 yrs.

✓ Can occur in four clinical settings:

✓ 1. Sporadic - ~ 70 % cases,usually

unilateral

✓ 2. Familial - ~ 30 % ,cases,usually Bilateral

Medullary Ca Thyroid

✓ Pathology –

1. Usually occurs in upper poles

2. Originates from Parafollicular \ C cells

✓ Gross: Single or multiple

✓ Typically nonencapsulated

✓ Solid, gray / tan / yellow, firm, may be

infiltrative

✓ Larger lesions have hemorrhage and

necrosis, tumor usually in mid or upper

portion of gland (with higher

concentration of C cells)

Medullary Ca Thyroid ✓ Pathology –

✓ Microscopic – Why called Medullary ?

✓ Sheets of Spindle shaped neoplastic cells

with AMYLOID [Altered Calcitonin] in

between. Cells Stains for Calcitonin, CEA,

Serotonin, VIP

✓ Spreads to LN Initially ~ 75 %

✓ Cellular specimen staining positively for

calcitonin with immunoperoxidase.

✓ Loosely cohesive fragments of spindle-

shaped cells; amyloid is present as

amorphous blue material intimately

associated with neoplastic cells.

Medullary Ca Thyroid

Anaplastic Ca Thyroid

✓ Accounts for ~ 8 to 10 % of all Thyroid

Ca

✓ Female : Male = 1.5 : 1 .

✓ Mean age at presentation – 70 to 80

yrs.

✓ Most aggressive thyroid

malignancy,with median survial only ~

3 months.

✓ Iodine deficiency goitre is precursor .

✓ All patients are considered to have

stage IV disease.

Thyroid Lymphoma ✓ Accounts for ~ 8 to 10 % of all Thyroid

Ca

✓ Women > 70 yrs are usually affected.

✓ In 70 to 80 %, it arises in Preexisting

Chronic Lymphocitic thyroditis with

Subclinical or overt Hypothyroidism,

in association with Hashimoto’s

thyroiditis.

✓ Almost always Non-Hodgkin B-cell

lymphoma

✓ Usually presents as Rapidly growing

mass,with obstructive symptoms as

dyspnea and dysphagia.

Thyroid Metastasis

✓Usually Rare

✓Common Primary sites are -

1. Skin – Melanoma ~39 %

2. Breast ~ 21%

3. Renal cell Ca ~ 10 %

✓Usually Presents as Painless

Lump with signs / symptoms

of Primary.

✓FNAC is Diagnostic

Recurrent Thyroid Ca

✓Approximately 10% to 30% of patients after initial treatment

✓ 80% recur with disease in the neck

✓ 20% with Distant Recurrennce.

✓Most common site of distant metastasis is the lung.

✓Median time of Recurrence ~ 2.6 yrs

✓Prognosis for clinically detectable recurrences is generally poor,

regardless of cell type.

✓Local and regional recurrences detected by I131 scan and not

clinically apparent and have an excellent prognosis

Staging Of Thyroid Ca

Clinical Presentation

✓ Usual Presentation

✓ - A lump in the neck

✓ - Pain in the neck

✓ - Hoarseness

✓ - Trouble swallowing

✓ - Breathing problems

✓ Usual Presentation

✓ - Follicular Ca - ~1 % as Hyperthyroidism

✓ - Medullary Ca - ~ 2 – 4 % as Cushing Syn .

Hypertension, Diarrhea

✓ - Papillary Ca – as LATERAL ABERRANT THYROID

Benign Vs Malignant Thyroid Swellings

BENIGN MALIGNANT

Thyroid Carcinomas

Investigations

Thyroid CarcinomasPathology & Clinical Features

Thyroid Carcinomas

Treatment