diseases of thyroid

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DISEASES OF THYROID GLAND
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FUNCTIONAL DISORDERS
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Hyperthyroidism.

• Aetiopathogenesis
• i. Grave's disease( diffuse toxic goitre).
• ii. Toxic multinodular goitre.
• iii. Toxic adenoma

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• Less frequent
• TSH oversecretion by pituitary tumour.
• Thyroiditis
• Metastatic thyroid tumours.
• Struma ovarii.
• HCG secreting tumours.
• Excessive doses of thyroxine or iodine.

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• Features
• Onset -insiduous.
• emotional instability, nervousness, palpitations.
• fatigue, weight loss ( despite very good
  appetite).
• heat intolerance, perspiration, fine tremors of
  hands.

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• menstrual abnormalities.
• cardiac manifestations.
• skin warm, moist and flushed .
• weakness of skeletal muscles and osteoporosis.
• T3 and T4 levels raised, TSH low.
• Thyroid "storm or crisis" may develop in some
  patients

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Hypothyroidism

• Usually due to low production of thyroid
  hormones.
• Rarely resistance of peripheral tissues to effect
  of thyroid hormones.
• Clinical manifestations
• i. Cretinism or congenital hypothyroidism-
  infancy childhood..
• ii. Myxoedema- adulthood hypothyroidism.

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Cretinism.

• Cretin a child with severe hypo-thyroidism.
• Present at birth or within first 2 years.
• Word cretin derived from French, meaning
  Christ-like, because these children are so
  mentally retarded that they are incapable of
  committing sin.

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• Aetiopathogenesis
• i. developmental anomalies - thyroid agenesis.
• ii. genetic defect in thyroid hormone synthesis.
• iii. foetal exposure to iodides and antithyroid
  drugs.
• iv. endemic cretinism.

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• Clinical features
• Few weeks to months after birth
• failure to thrive, poor feeding and
  constipation.
• dry scaly skin, hoarse cry and bradycardia.

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• As child grows up, clinical picture emerges
• impaired skeletal growth leading to dwarfism.
• rounded face, narrow forehead, and widely set
  eyes.
• flat and broad nose, big protruding tongue
  protruding abdomen.

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• neurological manifestations- deafness and mutism.
• severe mental retardation.
• lab findings Rise in TSH levels and fall in T3
  T4.

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Adult cretin
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Myxoedema

• Adult onset hypothyroidism
• Term connotes non-pitting oedema due to
  accumulation of mucopolysaccharides in skin and
  other tissues.

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• Pathogenesis.
• i. ablation of thyroid by surgery or radiation.
• ii. autoimmune ( lymphocytic) thyroiditis.
• iii. endemic or sporadic goitre.

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• iv. hypothalamic-pituitary diseases.
• v. thyroid cancer.
• vi. prolonged administration of antithyroid
  drugs.

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Clinical Features

• onset slow.
• fully developed clinical syndrome may appear
  after several years of hypothyroidism.
• Cold intolerance, mental and physical lethargy.
• constipation, slowing of speech and intellectual
  function.
• puffiness of face, loss of hair and altered skin
  texture

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Myxoedema B after treatment
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INFLAMMATORY DISORDERS( THYROIDITIS)

• Classified into
• 1. Autoimmune ( lymphocytic) thyroiditis.
• 2. Infectious thyroiditis
• 3. Granulomatous thyroiditis.
• 4. Riedel's thyroiditis.

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Autoimmune thyroiditis

• Characterized by infiltration of lymphocytes and
  plasma cells.
• Occurence of thyroid specific autoantibodies in
  serum.
• Includes 3 entities
• a. Hashimoto's thyroiditis
• b. Atrophic thyroiditis.
• c. Focal lymphocytic thyroiditis.

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A. Hashimoto's thyroiditis

• Also called diffuse lymphocytic thyroiditis or
  stroma lymphpomatosum or goitrous autoimmune
  thyroiditis.
• Features
• diffuse goitrous thyroid gland.
• lymphocytic infiltrate
• occurence of thyroid auto-antibodies.
• age 3rd and 5th decade, Females gt Males.

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• Pathogenesis
• Basically an autoimmune disorder.
• i. HLA association- occurrence of disease in
  HLA-DR5.

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• ii. Autoimmune disease association- may occur
  with other autoimmune diseases.
• HLA-DR5 association causes genetic defect in
  immune system.
• This results in destruction of thyroid tissue by
  release of cytotoxic auto-antibodies

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• But also Cell mediated immune mechanisms as well.
• Basic immunologic abnormality Activation of CD4
  T cells which induce CD8 cytotoxic T cells
  and formation of auto-antibodies.

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• Auto-antibodies detected against thyroid
  antigens
• 1. Thyroid microsomal auto-antibodies.
• 2. Thyroglobulin autoantibodies.
• 3. TSH receptor auto-antibodies.
• 4. Auto-antibodies vs follicular cell membranes,
  thyroid hormone and colloid component.

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• Pathology
• Gross Diffuse, symmetric , firm, rubbery
  enlarged gland. ( up to 300 gm)
• C/S-fleshy surface.

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• Histology
• i. lymphocytes, plasma cells , immunoblasts and
  macrophages infiltrate with formation of
  lymphoid follicles and germinal centres.
• ii. decreased number of thyroid follicles with
  atrophy and lack of colloid.

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• iii. Degenerate follicular epithelial cells form
  Hurthle cells( Askanazy or oxyphil cells.)
• These cells possess granular cytoplasm due to
  large number of mitochondria.

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Hashimotos disease
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• Clinical features
• painless , firm and moderate goitrous gland.
• may be associated with hypothyroidism.
• a few cases develop hyperthyroidism instead (so
  called Hashimotoxicosis) .
• increased risk of lymphomas but not carcinoma.

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B. Atrophic thyroiditis .

• gland decreased in size.
• clinically presents as spontaneous
  hypothyroidism.
• lymphocytic infiltrate, atrophic follicles and
  fibrosis present but no marked regeneration of
  cells.
• blocking antibodies against thyroid growth
  responsible for lack of regeneration.

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C. Focal lymphocytic thyroiditis

• shows only focal lymphocytic cell infiltrate.
• may be present in association with other thyroid
  diseases such as goiter, adenomas or carcinoma
• there is focal aggregates of lymphoid cells with
  germinal centres but no epithelial alteration.

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II. INFECTIVE THRYROIDITIS.

• Acute thyroiditis due to microbial infection
  rare.
• Generally a complication of infection elsewhere
• Usually transient and responds to treatment.

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Granulomatous thyroiditis.

• Also called de Quervains disease, subacute
  thyroiditis or giant cell thyroiditis.
• Aetiology not known.
• Usually preceded by an upper respiratory
  infection, viral.?

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• Symptoms signs
• More common in young and middle aged people.
• Clinically- painful, moderately enlarged thyroid
  gland.
• Fever.
• Features of hyperthyroidism in early phase of
  disease.

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• Hypothyroidism with severe damage to thyroid
  gland later.
• Condition self limiting, with complete recovery
  in about 6 months.

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• Pathology
• Moderate enlargement , usually asymmetrical or
  focal.
• C/S firm, yellowish-white.

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• Microscopy features according to stage of
  disease.
• Initially- an acute inflammatory destruction of
  gland with abscess formation.

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• Later, granuloma formation,colloid material
  surrounded by histiocytes and multinucleated
  giant cells.
• More advanced cases- fibroblastic proliferation
  and fibrosis.

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IV. Riedels thyroiditis

• Also called Riedels stroma or invasive fibrous
  thyroiditis.
• Chronic disease with stony hard thyroid, densely
  adherent to adjacent structures.
• May cause dysphagia, dyspnoea, recurrent
  laryngeal nerve paralysis and stridor, resembling
  cancer.

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• Aetiology unknown infectious agent ?
• Part of multifactorial idiopathic fibrosclerosis?
  ?.
• Pathology
• Gross stony hard, contracted, asymmetric, firmly
  adherent to adjacent structures.
• C/S hard, devoid of lobulations.

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• Microscopy
• Extensive fibro-collagenous formation,marked
  atrophy of parenchyma, focal lymphocytic
  infiltrate, with invasion of muscle.

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GRAVES DISEASE ( DIFFUSE TOXIC GOITRE).

• Also known as Basedows disease, exophthalmic
  goiter, primary thyrotoxicosis.
• Characterized by
• hyperthyroidism.
• diffuse thyroid enlargement.
• opthalmopathy.
• More frequent between 39-40 years of age in
  females.

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• Aetiopathogenesis
• An auto-immune disease.
• Many immunological similarities with Hashimotos
  disease.
• HLA association- genetic predisposition to HLA-DR
  5.
• May be found with other organ specific autoimmune
  diseases.

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• Basic immunological abnormality- genetically
  induced organ specific defect in suppressor T
  lymphocytes.
• Auto-antibodies against thyroid antigen are
  detected in serum of patients.
• Antibodies to TSH receptor, thyroglobulin,
  thyroid microsomes etc.

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• Pathogenesis of opthalmopathy is also of
  autoimmune origin.
• Evidence
• intense lymphocytic infiltrate around ocular
  muscles.
• Presence of circulating antibodies against
  muscle, cross reacting with thyroid microsomes.

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• Gross
• Diffusely enlarged red tan thyroid gland.
• Slight lobulation but no large cyst formed

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• Histology
• marked epithelial hyperplasia with formation of
  papillary infoldings.
• colloid markedly diminished, lightly staining and
  finely vacuolated.
• stroma shows increased vascularity and
  lymphocytic infiltrate.

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Graves disease
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• Features
• slow , insidious onset.
• patients usually young women.
• symmetric moderate enlargement of thyroid gland
  with features of thyrotoxicosis.
• ophthalmopathy and dermatopathy .
• ocular abnormalities such as lid lag, upper
  eyelid retraction, stare, weakness of eye
  muscles, and proptosis.

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Graves disease
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GOITRE.

• Enlargement of thyroid gland caused by
  compensatory hyperplasia of follicular
• epithelium in response to thyroid hormone
  deficiency.
• The end result of the hyperplasia is generally a
  euthyroid state.

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• Two forms
• i. Simple goitre ( diffuse non-toxic goiter,
  colloid goiter)
• ii. Nodular goiter ( multinodular or adenomatous
  goiter).

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• Pathogenesis
• fundamental defect is deficient production of
  thyroid hormones commonest iodine deficiency.
• deficient hormone causes TSH stimulation, leading
  to hyperplasia of follicular cells and formation
  of new follicles.

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• the hyperplastic stage followed by involution
  stage completes the picture of simple goiter.
• repeated and prolonged cyclic changes of
  hyperplasia and involution result in nodular
  goiter.

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SIMPLE GOITRE

• diffuse enlargement of thyroid gland
  unaccompanied by hyperthyroidism.
• Most cases euthyroid, though initially might
  have been hypothyroid ( inadequate iodine
  supply).
• Often appears at puberty or adolescence.
• TSH levels high.

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• Aetiology
• Endemic and Sporadic goitre.
• Endemic goiter
• termed when prevalence in a geographic region gt
  10 of population.
• Occurs in high mountainous areas far from the
  sea ( iodine in drinking water and food low.)

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• Some cases due to goitrogens ( substances
  interfering with synthesis of thyroid hormones).
• include drugs in the treatment of
  hyperthyrpoidism, certain foods such as cabbage,
  cauliflower, turnips and cassava roots.

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• Sporadic goiter.
• less common.
• aetiology- unknown.
• causal influences
• // Suboptimal iodine intake in conditions of
  increased demand eg puberty and pregnancy.
• // Genetic factors.
• // Dietary goitrogens.
• // Inborn error of iodine metabolism.

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• Pathology
• Gross moderate enlargement of gland, symmetric
  and diffuse.
• C/S gelatinous and transluscent brown.

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• Micro two stages
• a. hyperplastic stage- early stage of disease.
• tall columnar epithelial cells, papillary
  infoldings and new follicles.
• b. Involution stage- following hyperplastic
  stage.
• large follicles distended with colloid, lined by
  flattened follicular epithelium.

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NODULAR GOITRE

• Also called multinodular, adenomatous goitre.
• an end stage of long standing simple goiter.
• characterized by extreme degree of tumour -
  like enlargement of gland, with nodularity.

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• may cause dysphagia and choking due to
  compression of trachea and oesophagus.
• most cases are in euthyroid state.
• about 10 may develop thyrotoxicosis ( toxic
  nodular goiter).

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• Aetiology same as for endemic goiter.
• epithelial hyperplasia and generation of new
  follicles
• irregular accumulation of colloid in follicles
• Will result into increased tension, rupture of
  follicles and vessels.
• Followed by haemorrhage, scarring and
  calcification resulting into nodular pattern.

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• Pathology
• Gross asymmetric extreme enlargement 100-500 gm
  or larger.
• 5 cardinal macroscopic features
• i. nodularity.
• ii.fibrous scarring.
• iii.haemorrhages.
• iv.focal calcification
• v.cystic degeneration.
• C/S multinodularity becomes obvious.

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Nodular goitre
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• Histology heterogeneity as seen on macroscopy.
• complete encapsulation of nodules.
• Follicles of variable size lined by flat
  epithelium.
• Areas of haemorrhage, haemosiderin laden
  macrophages and cholesterol crystals.
• Fibrous scarring with foci of calcification.
• Microcyst formation.

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THYROID TUMOURS.
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BENIGN

• A. FOLLICULAR ADENOMA.
• Most common tumour.
• Appears as solitary nodule ( produced also by
  nodular goiter and carcinoma).
• Most behave as cold nodules, rarely produce
  hyperthyroidism.
• Very rare to turn into malignancy.

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• Pathology
• Gross 4 features
• i. solitary nodule.
• ii. complete encapsulation.
• iii. distinct architecture inside and outside
  capsule.
• iv. compression of thyroid parenchyma outside
  capsule.

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• Size- usually small ( lt 3 cm diameter) and
  spherical.
• C/S grey- white to red- brown.
• Less colloid than surrounding thyroid parenchyma.
• May undergo degenerative changes fibrous
  scarring, focal calcification , haemorrhage
  cyst formation.

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Adenoma thyroid
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• Histology
• Complete fibrous encapsulation.
• Benign follicular cells with variable size
  follicles.
• May show trabecular, solid and cord patterns with
  little follicle formation.

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Follicular adenoma
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• 6 types
• 1. microfollicular ( foetal) adenoma.
• 2. normofollicuar ( simple) adenoma.
• 3. macrofollicualr ( colloid) adenoma.
• 4. trabecular ( embryonal) adenoma.
• 5. hurthle cell ( oxyphil) adenoma.
• 6. atypical adenoma.

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THYROID CARCINOMA.

• 95 of all primary cancers are carcinomas.
• primary lymphomas about 5 .
• sarcomas very rare.
• metastases to thyroid relatively common.

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• Morphology 4 types
• a. Papillary carcinoma.
• b. Follicular carcinoma.
• c. Medullary carcinoma.
• d. Undifferentiated carcinoma.

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• Aetiology
• Exposure to external radiation of high dose
  associated with increased risk.
• Nodular goitre and certain autoimmune diseases
  possibly
• Mutation or activation of RET proto-oncogene or
  RAS gene

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PAPILLARY CARCINOMA.

• Most common carcinoma, 75-85 of cases.
• Can occur at any age, including children and
  young adults.
• But incidence increases with advancing age.
• More frequent in females than males.
• A slow growing tumour, with asymptomatic solitary
  nodule.
• Regional lymphnode spread quite common.

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• First presentation in some patients is regional
  lymphnode metastasis.
• Prognosis good- 10 year survival rate 80-90 .
• Gross ranges from microscopic foci to nodules up
  to 10 cm.
• C/S gray white, hard and scar-like.
• Sometimes transformed into a cyst, with numerous
  papillary projections into lumen ( papillary
  cystaenocarcinoma).

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• Sectioning through a lobe of excised thyroid
  gland reveals papillary carcinoma

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• Histology
• Papillary pattern
• Tumour cells- overlapping pale nuclei ( ground
  glass appearance) and clear cytoplasm.
• Invasion into capsule and or lymphatics.
• Intravascular invasion uncommon.
• Psammoma bodies- small concentric calcified
  spherules in stroma.

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Papillary carcinoma
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B.FOLLICULAR CARCINOMA

• Comprises about 10-20 of thyroid carcinomas.
• More common in middle and old age with female
  preponderance.
• Has positive correlation with endemic goiter.
• Role to external radiation is not clear.
• Clinically a solitary nodule or an irregular firm
  and nodular thyroid .

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• Slow growing, but more rapid than papillary
  carcinoma.
• Haematogenous spread more common than lymphatic.
• Prognosis between that of papillary carcinoma and
  undifferentiated carcinoma.
• 10 year survival rate 50-70 .

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• Gross
• A solitary nodule or irregular enlargement.
• C/S gray white with areas of haemorrhage.,
  necrosis and cyst formation.

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Solid or cystic pattern
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• Micro
• Follicles of variable size.
• May show solid or trabecular pattern.
• Variants include clear cell type, Hurthle cell (
  opxyphilic) type
• Vascular invasion and direct extension to
  adjacent structures quite significant.

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• Low power follicular carcinoma
• Note thick capsular invaded

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• Vascular invasion within capsule

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MEDULLARY CARCINOMA.

• Less common.
• Derived from parafollicular or C cells present in
  thyroid.
• Comprises 5 of thyroid carcinomas.
• Equally common in males and females.

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• 3 distinct features
• a. Its genetic association - 10 of cases-
  defect in chromosome 10.
• 90 are sporadic.
• Familial cases associated with MEN II A (
  phaechromcytoma and parathyroid adenoma OR with
  MEN II B ( phaecromocytoma with multiple
  neuromas
• Familial cases occur in 2nd to 3rd decade of life
  and usually bilateral multicentric

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• b. Secretion of calcitonin and other peptides.
• Tumour cells secrete calcitonin, prostaglandins,
  histamine, somatostatin, vasointestinal peptie
  (VIP) and ACTH.

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• These hormones are responsible for clinical
  syndromes such as carcinoid, Cushings syndrome
  and diarrhoeas.
• c. Amyloid stroma.- this is found in the stroma
  (Positive with Congo Red stain).

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• Histology organoid pattern, with nests of tumour
  cells with amyloid.

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Medullary carcinoma with amyloid
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Positive with Congo Red stain
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D.ANAPLASTIC CARCINOMA.

• 5 of carcinomas.
• Predominantly found in old age ( 7th 8th
  decade).
• Widely aggressive and rapidly growing.
• 5 year survival rate less than 10 .
• More common in females.
• Presentation- extensive invasion of adjacent soft
  tissue, trachea and oesophagus.
• Dyspnoea, hoarseness and dysphagia.

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• Pathology.
• Large irregular tumour.
• Commonly involves muscles
• Histology- poorly differentiated.
• 3 types of tumour cells
• i. small cell carcinoma- closely packed small
  cells with hyperchromatism and mitotic figures.
• ii. spindle cell carcinoma.
• iii. giant cell carcinoma.

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