Endocrine System 2

THYROID
ANATOMY:
• location: front of trachea and
below the level of cricoid
cartilage
• weighs 15-40 gm
• composed of two lateral
lobes connected in the
midline by a broad isthmus
• may have a pyramidal lobe
extending upwards
• c/s reddish -yellow and
translucent
HISTOLOGY:
• composed of lobules of
follicles/acini filled with
colloid
• lobules are enclosed by
fibrovascular septa
• follicles
– functional units of thyroid
– lined by cuboidal epithelium
with numerous fine
microvilli
• colloid contains glycoprotein,
thyroglobulin
HISTOLOGY:
• follicles are separated from each other by delicate
fibrous tissue that contains blood vessels, lymphatics and
nerves
• calcitonin secreting C-cells or parafollicular cells are
dispersed within the follicles; identified by silver stains
and immunohistochemical methods
Disorders of Thyroid:
• Functional disorders
– Hyperthyroidism (thyrotoxicosis)
– hypothyroidism
• Thyroiditis
• Multinodular Goiter
• Neoplasms
• Congenital – Thyroglossal cyst
HYPERTHYROIDISM
Causes:
Most common Less common
Graves’disease hypersecretion of pituitary TSH
(diffuse toxic goitre) • pituitary tumour
• hypersecretion of TRH

toxic multinodular thyroiditis

goitre struma ovarii
congenital hyperthyroidism

toxic adenoma metastatic tumours of the thyroid

hCG-secreting tumours
• hydatidiform mole
• choriocarcinoma
• testicular tumours

jodbasedow disease (excessive doses of

thyroid hormones or iodine)
Clinical features:
HYPOTHYROIDISM:
• hypometabolic clinical state resulting from:
- inadequate production of thyroid hormones
- resistance of the peripheral tissues to the effects of
thyroid hormones
• The clinical manifestations of hypothyroidism,
depending upon the age at onset are divided into:

Cretinism or congenital Myxoedema

hypothyroidism

during infancy and adulthood

childhood
Clinical Features:
Thyroiditis
HASHIMOTO’S (AUTOIMMUNE/CHRONIC
LYMPHOCYTIC) THYROIDITIS
• characterised by 3 principal features:
– diffuse goitrous enlargement of the thyroid
– lymphocytic infiltration
– thyroid autoantibodies
• age 30-50 yrs; F>>M ( 5-7:1)
• rare in children
• autoimmune thyroiditis
• most common cause of goitrous hypothyroidism in
regions where iodine supplies are adequate
Pathogenesis:
• association with other autoimmune diseases
• immune destruction of thyroid cells
– CD4+ T helper and CD8+ T cytotoxic cells
• autoantibodies
– Thyroid microsomal autoantibodies (against the microsomes of
the follicular cells)
– Thyroglobulin autoantibodies
– TSH receptor autoantibodies
• inhibitory TSH-receptor antibodies
• genetic basis
– HLA-DR3 and HLA-DR5 subtypes
Gross:
• diffuse, symmetric, firm and
rubbery enlargement of the thyroid
• weigh 100-300 gm
• c/s fleshly with accentuation of
normal lobulations
• normal shape of the gland retained
Microscopic:
• extensive infiltration of the gland
by lymphocytes, plasma cells,
immunoblasts and macrophages,
with formation of lymphoid
follicles having germinal centres
Microscopic:
• thyroid follicles
– decreased number
– atrophic
– devoid of colloid
• Hurthle cell change
– abundant oxyphilic or
eosinophilic and granular
– large bizarre nuclei
• slight fibrous thickening of
the septa
Clinical features:
• usually presents with hypothyroidism; most common
cause of hypothyroidism
• rarely hyperthyroidism (Hashitoxicosis)
• high risk of B cell lymphoma
• but no increased risk of developing thyroid carcinoma
DE QUERVAIN THYROIDITIS (GRANULOMATOUS/
SUBACUTE/GIANT CELL THYROIDITIS)
• etiology possibly viral
• common in young and middle-aged women
• presents with painful, moderate thyroid enlargement with
fever, features of hyperthyroidism in the early phase and
hypothyroidism if the damage to the thyroid gland is
extensive
• self-limiting; complete recovery of thyroid function in about
6 months
Gross:
• moderate enlargement of the gland;
asymmetric or focal
• cut surfac firm and yellowish-white
Microscopic:
• acute inflammatory destruction of the thyroid
parenchyma and formation of microabscesses.
• granulomas c/o central colloid material surrounded by
histiocytes and scattered multinucleate giant cells
• fibroblastic proliferation in advanced cases
RIEDEL’S THYROIDITIS
• rare chronic disease
• char. by stony-hard thyroid densely adherent to the
adjacent structures in the neck
• presents with compressive clinical features
– dysphagia
– dyspnoea
– recurrent laryngeal nerve paralysis
– stridor
• simulates malignancy
• more common in females; 4th to 7th decades of life
• part of multifocal idiopathic fibrosclerosis (group of
disorders includes: idiopathic retroperitoneal, mediastinal
and retro-orbital fibrosis, and sclerosing cholangitis)
Gross:
• gland contracted, stony-hard,
asymmetric and firmly adherent
to the adjacent structure
• cut section is hard, gray white
and devoid of lobulations
Microscopic:
• extensive fibrocollagenous
replacement
• atrophy of the thyroid
parenchyma
• focal lymphocytic infiltration
• invasion of he adjacent muscle
tissue
GOITRE
Definition: thyroid enlargement caused by compensatory
hyperplasia and hypertrophy of the follicular epithelium
in response to thyroid hormone deficiency
• morphologic forms
– diffuse (simple nontoxic or colloid goitre)
– nodular (multinodular or adenomatous goitre)
Pathogenesis:
Etiology:
Epidemiologically two forms:
Endemic Non endmic/sporadic
prevalence of goitre in a geographic less common than the endemic variety
area in more than 10% of the population

mountainous regions far from the sea

(iodine content of drinking water and
food is low) such as Himalayas

Causes etioloy unknown

dietary lack of iodine suboptimal iodine intake in conditions
goitrogens of increased demand as in puberty and
cabbage pregnancy
cauliflower genetic factors
turnips dietary goitrogenes
cassava roots dyshormonogenesis
drugs inborn errors of iodine metabolism
Morphological Features
Gross:
• diffuse and symmetric
enlargement of thyroid
• weighs up to 100-150 gm
• c/s gelatinous and
translucent brown
Microscopic:
Two stages
• Hyperplastic
• involution stage
Morphological Features
Microscopic:
• hyperplastic
– early stage
– characterised by tall
columnar follicular
epithelium showing
papillary infoldings and
formation of small new
follicles
• involution stage
– large follicles distended by
colloid and lined by
flattened follicular
epithelium
GRAVES DISEASE
• also known as Basedow’s
disease, primary
hyperplasia, exophthalmic
goitre, and diffuse toxic
goitre
• triad of features:
– hyperthyroidism
(thyrotoxicosis)
– diffuse thyroid
enlargement
– ophthalmopathy
• more common in females
(20-40yrs)
Etiopathogenesis:
• autoimmune
• Ab to TSH receptor – Long Acting Thyroid Stimulator
Gross:
• moderate enlargement of thyroid
• diffuse and symmetric enlarged
• weigh up to 70-90 gm
• c/s homogeneous, red-brown and
meaty and lacks the normal
translucency
Microscopic:-
• epithelial hyperplasia and
hypertrophy of follicular cells
• formation of papillary
infoldings
• colloid
– markedly diminished
– lightly staining
– watery
– finely vacuolated
• stroma shows increased
vascularity and accumulation
of lymphoid cells
THYROID TUMORS

BENIGN MALIGNANT
Adenoma Papillary carcinoma (75-80%)
Follicular carcinoma (10-20%)
Medullary carcinoma (5%)
Anaplastic carcinoma (5%)
Lymphomas
FOLLICULAR ADENOMA
• most common benign thyroid tumour
• more frequently in adult women
• presents as a solitary nodule
• important to distinguish adenomas from nodular goitre
and thyroid carcinoma
• most adenomas behave as a ‘cold nodule’
• adenomas rarely become malignant

cold nodule on scan

Gross:
• small (up to 3 cm in diameter)
and spherical
• solitary nodule
• well encapsulated
• c/s grey-white to red-brown
• contain less colloid
• degenerative changes seen-
fibrous scarring, focal
calcification, haemorrhages
and cyst formation
Microscopic:
• the tumour shows complete fibrous encapsulation
• tumour cells are benign follicular epithelial cells forming
– follicles of various sizes
– trabeculae
– solid sheets
– cords
• many patterns: micro, macrofollicular, and cord-like
• follicular growth pattern within adenoma is distinct from
adjacent non-neoplastic thyroid
✔ Adenomas do not show capsular and vascular
invasion—features distinguishing it from follicular
carcinoma
✔ FNAC has limited value in differentiating follicular
adenoma from carcinoma
✔ requires histological examination for definite diagnosis
PAPILLARY CARCINOMA
• most common thyroid cancer
• commonest thyroid cancer associated with radiation
• more common in females
• age: 20-50 years
• presents as asymptomatic thyroid nodule
• lymphatic spread common
• first & sole manifestation may be a cervical node mass
• prognosis is excellent
• adverse outcome may be associated with age>40,
extrathyroidal extension & metastases
Gross:
• may range from microscopic
foci to nodules upto 10 cm in
diameter
• poorly delineated
• c/s is greyish-white and hard in
consistency
• cyst formation and calcification
may occur
Microscopic:
• papillae with fibrovascular
core and covered by single layer
of tumour cells- predominant
feature
• tumour cells with characteristic
nuclear features
– ground glass or optically clear
nuclei (orphan Annie eyed)
– nuclear grooves
– intranuclear pseudoinclusions
– clear or oxyphilic cytoplasm
• tumour cells may also form
follicles and solid sheets
• psammoma bodies are typical
small, concentric, calcified
spherules present in the stroma
• tumour cells invade the capsule
and intrathyroid lymphatics but
invasion of blood vessels is rare
FOLLICULAR CARCINOMA
• comprises about 10-20% of all thyroid carcinomas
• more common in middle and old age
• F:M (2.5:1)
• multi nodular goitre may predispose to follicular
carcinomas
• presents clinically either as a solitary nodule or as an
irregular, firm and nodular thyroid enlargement
• grows more rapidly than papillary carcinoma
• distant metastases by haematogenous route common
(lungs and bones)
• regional lymph node metastases are rare
Gross:
• circumscribed nodule or
irregular thyroid enlargement
• c/s grey-white with areas of
haemorrhages, necrosis and
cyst formation
Microscopic:
• follicular pattern: composed
of follicles of various sizes
and may show trabecular or
solid pattern
• variants
– clear cell
– Hurthle cell (oxyphilic)
• tumour lacks papillae,
ground-glass nuclei of
tumour cells and psammoma
bodies
• capsular and vascular
invasion are significant
features but lymphatic
invasion is rare
MEDULLARY CARCINOMA
• derived from thyroid parafollicular C cells
• may be sporadic or part of MEN syndrome
• associated with calcitonin secretion
• stroma contains Amyloid deposits
• variable prognosis: better in sporadic
& aggressive in familial
Gross:
• unilateral solitary nodule (sporadic form)
• bilateral and multicentric (familial form)
• c/s of tumour is firm to hard, grey-white
to yellow-brown with areas of
haemorrhage and necrosis
Microscopic:
• tumour cells:
– arranged in nests, sheets, ribbons
pseudopapillae or small follicles
– nests of tumour cells separated by
fibrovascular
– uniform and have the structural and
functional characteristics of C-cells
– neoplastic cells may be spindle-
shaped
• amyloid stroma:
– derived from altered calcitonin
– calcification may be present
• C-cell hyperplasia
– familial cases
ANAPLASTIC CARCINOMA
• comprises less than 5% of all thyroid cancers
• one of the most malignant tumour in human
• old age (7th-8th decades)
• more common in females (F:M ratio 1.5:1)
• aggressive and rapidly growing; poor prognosis
Clinical Presentation:
• rapidly-growing tumour in the neck
• dyspnoea
• dysphagia
• hoarseness of voice
• metastasises to regional lymph nodes and to distant
organs such as the lungs
Gross:
• tumour is large and irregular,
often invading the adjacent
structures
• c/s of the tumour is white and
firm with areas of necrosis and
haemorrhage
Microscopic:
• poorly-differentiated tumor
• composed of 3 types of cells
– small cells: closely packed small
cells having hyperchromatic
nuclei and numerous mitoses
– spindle cells: resembling sarcoma
 – spindle cells: resembling
sarcoma
– giant cells: highly anaplastic
giant cells showing numerous
atypical mitoses bizarre and
lobed nuclei and some
assuming spindle shapes
• histological variants are
named according to the
predominant cell type
Feature Papillary Ca Follicular Ca Medullary Ca Anaplastic Ca
Frequency 75-80% 10-20% 5% 5%
Age all ages middle to old old age old age
age, familial
F:M ratio 3:1 2.5:1 1:1 1.5:1
Relation to maximum present none present
radiation
Genetic ret gene over- ras mutation ret point p53 loss, beta
alterations expression mutation catenin
mutation
Cell of origin follicular follicular para-follicular follicular
Gross small, multifocal moderate size, moderate size invasive growth
nodular
Microscopy papillary vascular and solid nests, undifferentiated
pattern capsular amyloid stroma spindle shaped
char. nuclear invasion and giant cells
features
LN metastases common rare common common
Distant rare common rare common
metastases