Pathology of The

Thyroid Gland
Dr Wale TITILOYE

Normal Thyroid Gland

Thyroid - Normal

Normal resting Thyroid

Thyroid Physiology:
Hypothalamus
TRH
T3, T4

Pituitary
TSH
Thyroid

Role of Thyroglobulin
Role of Iodine
Release of thyroid hormones
Role of T3,T4 (transport via
transthyretin and thyroxine binding
globulin,binding to thyroid hormone
nuclear receptor, formation of thyroid
hormone receptor complex and
binding with thyroid hormone
response elements in target genes
and transcription.

Role of Goitrogens
Note the role of certain drugs
1. Propythiouracil- inhibit the oxidation
of iodide and block production of
thyroid hormones, inhibits the
peripheral deiodination of T4 to T3
2. Iodide administration(in large
quantity) to patients with thyroid
hyperfunction inhibit proteolysis of
thyroglobulin thus block release of
thyroid hormones

Parafollicular cells or Ccells

ofhormone
thyroid
follicle
Secretes
calcitonin

Calcitonin promotes absorbtion of

calcium by skeletal system and
inhibits the resorbtion of bone by
osteoclasts

Disorders of Thyroid:

Hyperthyroidism
Hypothyroidism
Thyroiditis
Diffuse multinodular Goiter.
Neoplasms adenoma/carcinoma.
Congenital Thyroglossal cyst/duct.

Hyperthyroidism

Thyrotoxicosis

High T3/T4, low TSH

Hyperthyroidism is a cause of thyrotoxicosis. The term
primary and secondary hyperthyroididm are
applicable
Different entities in hyperthyroidism

1. Diffuse toxic hyperplasia (Graves)

2. Toxic multinodular goitre
3. Toxic adenoma
4. Thyroiditis (subacute granulomatous
thyroiditis, subacute lymphocytic thyroiditis)
5. Functioning thyroid carcinoma
6. TSH secreting pituitary adenoma

Hyperthyroidism
Features:

Graves Disease:

Commonest cause of endogenous

hyperthyroidism
Commoner in Females(10x), 2% of
Female in USA affected
20-40y, Autoimmune.
Triad of clinical features,
Hyperthyroidism
exophthalmos
Pretibial myxedema.

Genetic susceptibility is linked to

polymorphism in immune function
genes like CTLA4,PTPN22 and and
HLADR3 Allele
Pathogenesis is breakdown of self
tolerance to thyroid autoantigens most
importantly TSH receptor and
production of multiple autoantibodies
1. Thyroid stimulating immunoglobulins
(LATS)
2. Thyroid growth-stimulating
immunoglobulins
3. TSH-binding inhibitor immunoglobulins

Morphology

Symetrically enlarged thyroid gland

because of diffuse hypertrophy and
hyperplasia
Tall columnar follicular cells, papillary
folds.
Scalloped, pale, scanty colloid.

Graves Thyroiditis:

Graves Disease

Hypothyroidism
Cretinism / Myxedema Low T3/T4, High TSH
Causes:
1. Hashimotos thyroiditis - autoimmune
2. Iodine deficiency
3. Drugs iodides, lithium
4. Developmental Atrophy, hypoplasia
Pituitary disorders
5. Radiation/Surgery

Hypothyroidism

Cretinism (child)
Impaired cns &
bone growth
Mental retardation
Short stature
Coarse facial
features
Protruding tongue
Umbilical hernia

Myxedema (adult)
Slow physical and
mental activity
Cold intolerance
Over weight
Low cardiac output
Constipation and
decreased sweating
Cool pale thick skin

Hypothyroidism
Myxedema
Features:

Thyroid Atrophy

Hashimoto Thyroiditis

Common non endemic goitre.

more common in females (45-65yr).
Autoimmune
Increase susceptibility is associated with
polymorphism in multiple immune regulation
associated gene
1. Cytotoxic T lymphocyte associated antigen
4(negative regulator of T cell response)
2. Protein Tyrosine Phosphate-22 gene that
encode lymphoid tyrosine phosphatase
which also inhibit T cell function.

Antithyroglobulin antibody
Antithyroid peroxidase antibody

Immunological mechanism
1. CD8+ cytotoxic T-Cell-Mediated cell
death
2. Cytokine mediated cell death
3. Binding of antibodies followed by
antibody mediated cytotoxicity

Morphology

Firm diffuse enlarged thyroid.

Follicle atrophy with lymphocytic
infilterate with well developed germinal
centers.
Hrthle cells eosinophilic epithelial
cells.
Initial hyperthyroidism.
Patient are at risk for other autoimmune
diseases e.g Mysthaenia gravis , SLE
High risk of B cell Non Hodgkins
lymphoma (MALT Lymphomas)

Hashimotos Thyroiditis:

Hashimotos Disease

Hashimotos Disease

Antithyroglobulin Antibody

Antimicrosomal Autoantibody

Granulomatous Thyroiditis:

Subacute or DeQuervain thyroiditis.

Less common, Females, 30-60 years
Pain, fever, fatigue, myalgia.
Post viral syndrome.
Genetic association - HLA B35
Patchy microabscess, granulomas
with giant cells.
Hyperthyroidism.
Heals with normal thyroid function.

DeQuervain's Disease - SAGT

Diffuse Non Toxic (simple) and

Endemic
Multinodular
goitre
(affect more than
10% of a

population or sporadic types

Dietary Cassava thiocyanate iodide
transport.
Other Goitrogens- Cabbage,
cauliflower, Brussels sprouts, turnips
Like cassava, they are vegetables
belonging to Barcicacea (cruciferae)
family

Sporadic rare, females, young.

Hyperplastic stage & Colloid stage.
Repeated attacks multinodular.
Hyperplasia, fibrosis, cystic, necrosis
Mass effect, dysphagia, airway
obstruction
Most cases are euthytoid
Rarely toxic hyperthyroidism
plummer syndrome

Goitre Iodine Deficiency

Multinodular Goitre with

Papillary Carcinoma

Colloid Cysts in MNG

Multinodular Goitre

Neoplasms of Thyroid

Usually solitary, benign.

Good prognosis - <1% cancer mort.
May be functional hot nodule.
Malignancy - Infiltration fixation,
hoarseness, recurrent laryngeal
nerve damage.

Neoplasms of Thyroid

Adenoma Follicular adenoma

usually hot
Papillary Carcinoma 75-80%
Follicular carcinoma - 10-20%
Medullary carcinoma 5%
Anaplastic carcinoma - <5%

Adenoma

Follicular common, rarely Papillary

Compact follicles (large in MNG)
Solitary, rarely Functional or hot.
Centre may show necrosis/hem.
Well capsulated.
Compressed normal gland.

Follicular Adenoma

Follicular Adenoma

Solitary Adenoma

Follicular Adenoma

Thyroid Carcinoma

Uncommon child elderly.

Common - Papillary adenocarcinoma.
Associated with radiation exposure.

Thyroid Carcinoma
Type

% Age

Spread Prognosis

Papillary

65 Young <45y Lymph Excellent

Follicular

20 Middle age

B.V.

Good

Anaplastic 10 elderly

Local

Poor

Medullary 5

All

variable

Elderly
familial

Papillary Carcinoma

Most common cancer 75-80%

Idiopathic, Radiation, Gardner &
Cowden syndromes.
Papillary folds, Psammoma bodies,
Orphan-anne nucleus.
98% 10year survival when localized.

Papillary Carcinoma

Papillary Carcinoma

Medullary Carcinoma

Amyloid in Medullary Carcinoma

Polarised microscopy

Papillary Carcinoma

Anaplastic Carcinoma

Normal

Technetium
Scan
Hot nodules

Cold nodule

Ultrasound
Scan
Solid nodule:

Conclusions:

Hyperthyroidism
Graves, thyrotoxicosis, LATS.
Hypermetabolism, high T3/T4, low TSH

hypothyroidism:

Antithyroglobulin, anti microsomal

Hypometabolism, Low T3/T4, high TSH.

Multinodular goitre low iodine.

Neoplasms
Follicular adenoma capsulated, single.
Carcinoma: Papillary follicular, medullary,
anaplastic.

C
A 25 year old presented with anterior neck swelling, exophthalmia and
pre-tibial myxoedema. Histology shows a diffuse hyperplasia of the
follicular cells with most of them having papillary folds and
thyroid
1. The
pathology of this disease is the presence of
contained scalloped pale scanty colloid. No capsular invasion was seen.

antibodies to thyroid stimulating hormone

receptors.T
2. Long acting thyroid stimulants LATS stimulates
the production of thyroid hormone from the
follicular cells.T
3. This disease is more common in male.F
4. This disease usually presents with
hypothyroidism.F
5. Weight loss, menorrhagia and osteoporosis are
possibilities in this disease.T

A child presents with umbilical hernia, protruding

tongue, short stature and mental retardation. He was
described to be gentle. Hormonal assay shows low
T3/ T4 and high TSH.
6. The adult form of this condition is myxoedema T
7. This condition may be associated with
Hashimoto thyroiditis in the adult T
8. Drugs like iodine and Lithium may cause this
condition in the adult F
9. Sub acute thyroiditis in the adult will present in
this form F
10. Presence of antimicrosomal and antimicrobial
antibodies in the adult form is diagnostic of Riedel
thyroiditis F

A 35 year old woman presents with anterior neck

swelling. On histology, malignant cells growing in
papillary folds with presence of orphan annie
11. The
diagnosis
in this case is
medullary
nucleus
and psammoma
bodies
were seen
carcinoma F
12. Amyloids demonstrated by polarized microscopy
is a diagnostic feature of this cancer F
13. The morphology described above is the most
common type of thyroid cancer T
14. The morphology described above carries the
worst prognosis among the thyroid cancers T
15. This morphology is associated with lymphatic
spread T