Thyroid Pathologies- Introduction, Benign diseases and Carcinoma Thyroid
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Transcript of 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