ENDOCRINE SYSTEM

Dr. Tasnim Rahman

Associate professor
Department of Pathology
Gazi Medical College, Khulna
Learning objectives:
Diseases of the thyroid glands as a whole
Hyperthyroidism
Hypothyroidism
Goiter
Thyroiditis
Hashimoto thyroiditis
Graves’ disease
Thyroid tumour
 Introduction

• The thyroid gland is located in the anterior

aspect of the neck opposite the C5-T1 vertebrae.
• The thyroid gland is an endocrine structure.

• It plays a key role in regulating the metabolic

rate of the body.
• The thyroid gland produces hormones that are
essential for normal body metabolism.
 Thyroid hormones

Hormones produced by thyroid gland :

i. Thyroxine (T4) and
ii. Triiodothyronine (T3)
iii. Calcitonin
 Once released from the thyroid gland into the blood, a
large amount of T4 is converted into T3 - the active
hormone that affects the metabolism of cells.
• The most important thyroid hormones are:

i. Thyroxine (T4) -99.9% and

ii. Triiodothyronine (T3)- 0.1%

• T4 is the main hormone.

• The most biological active form is T3 that has a

greater impact on cells and metabolism.
• Additionally, calcitonin helps to regulate
calcium and phosphate levels.
 Disease of thyroid gland
Congenital:

• Thyroglossal duct cyst: Persistence of the

remnants of thyroglossal duct in adult.

• Lingual thyroid: Presence of ectopic thyroid

tissue at the base of the tongue.

 Disease of thyroid gland

Acquired:
• Hypothyroidism
• Hyperthyroidism
• Thyroiditis
• Graves disease
• Goiter
• Tumors
 Hyperthyroidism
Hyperthyroidism:
It is a condition in which the thyroid gland becomes
hyperfunctioning and produces excessive amounts of thyroid
hormones.

Subclinical hyperthyroidism:
It is a condition where thyroid hormone levels are within the
normal range, but the thyroid-stimulating hormone (TSH) is
below the normal range.

This indicates a mild form of hyperthyroidism, often without

noticeable symptoms, though some individuals may
experience subtle signs.
 Hyperthyroidism
Primary hyperthyroidism:
The term primary hyperthyroidism are used to
designate hyperthyroidism arising from an
intrinsic thyroid abnormality.

Secondary hyperthyroidism:
The term secondary hyperthyroidism are used
to designate hyperthyroidism arising from
processes outside of the thyroid, such as a TSH-
secreting pituitary tumor.
 Causes of hyperthyroidism
Primary:
• Diffuse hyperplasia of thyroid (Graves’ disease)
• Hyperfunctional multinodular goiter
• Hyperfunctional thyroid adenoma
• Thyrotoxicosis
• Carcinoma
• Neonatal thyrotoxicosis associated with maternal
graves’ disease

Secondary:
TSH-secreting pituitary adenoma (rare)
 Features of Hyperthyroidism
• Hypermetabolism: Increased basal metabolic
rate, Weight loss
• Cardiac manifestation: Tachycardia, palpitations
• Goiter
• Exophthalmos
• Tremor
• GI hypermotility
• Irregular menstruation, amenorrhea
• Increased serum T3, T4 level
 Hypothyroidism
Primary hypothyroidism:
Hypothyroidism is a condition caused by a structural
or functional derangement of thyroid gland itself that
interferes with the production of thyroid hormones.
Secondary hypothyroidism:
Secondary hypothyroidism occurs when the
hypothalamus produces insufficient thyrotropin-
releasing hormone (TRH) or the pituitary produces
insufficient TSH.
 Sometimes, deficient TSH secretion due to deficient
TRH secretion is termed tertiary hypothyroidism.
How to distinguish between secondary and tertiary

hypothyroidism?

Only blood tests can identify a particular type of

hypothyroidism:

• Primary hypothyroidism causes low T3 and T4 but high

TSH.

• Secondary hypothyroidism causes low T3, T4, and TSH.

• Tertiary hypothyroidism causes low T3, T4, TSH and TRH

 Causes of hypothyroidism

Primary:

• Genetic defect in thyroid development

• Postablative- surgery, radioiodine therapy,

external irradiation

• Auto-immune (i.e. Hashimoto’s thyroiditis)

• Iodine deficiency
 Causes of hypothyroidism
Primary:
• Drugs (Li+, iodides, p-aminosalicylic acid)
• Thyroid hormone resistance syndrome
• Congenital biosynthetic defect
(dyshormonogenetic goiter)

Secondary:
• Pituitary failure (rare)
• Hypothalamic failure (rare)
Clinical features of hypothyroidism

• Cretinism:
Cretinism refers to hypothyroidism that
develops in infancy or early childhood.
 Clinical features of cretinism
 Severe mental retardation

 Impaired CNS development

 Impaired musculoskeletal system development

 Short stature

 Protruding tongue

 Umbilical hernia

 Maternal iodine deficiency

Picture of cretinism
 Hypothyroidism

Myxedema:

The term myxedema is applied to hypothyroidism

developing in the older child or adult.

Measurement of the serum TSH level is the most sensitive

screening test for this disorder.

Clinical features of myxedema

– Generalized fatigue, apathy, mental

sluggishness
– Cold intolerance, overweight
– Nonpitting oedema
– Hoarseness of voice
– Cool skin, ↑cholesterol
– Infertility, menorrhagia
Picture of Myxedema patient
 GOITERS
(Thyromegaly, diffuse or nodular)

• Any enlargement of thyroid gland is

known as goiter.
• It is usually caused by impaired synthesis
of thyroid hormone, which is most often
the result of dietary iodine deficiency.
 GOITERS
(Thyromegaly, diffuse or nodular)

• Iodine deficiency

• Increased TSH

• Associated with goitrogens, e.g.,

cabbage, Brussels sprouts, cauliflower,
turnips, cassava, certain drugs for eg.
amiodarone)
 GOITER
Impairment of thyroid hormone synthesis
leads to a compensatory rise in the serum
TSH level, which, in turn, causes hypertrophy
and hyperplasia of thyroid follicular cells
and ultimately gross enlargement of the
thyroid gland.
 GOITER

The compensatory increase in functional

mass of the thyroid gland overcomes the
hormone deficiency, ensuring a euthyroid
metabolic state in most individuals.
 GOITER

Goiters can broadly be divided into two types:

1. Diffuse nontoxic (simple) goiter

2. Multinodular goiter
 Thyroiditis
• Inflammation of thyroid gland is called
thyroiditis.
• It encompasses a diverse group of disorders
characterized by some form of thyroid
inflammation.
• Three most common and clinically significant
subtypes.
 Thyroiditis

1. Hashimoto (Auto-Immune) thyroiditis

2. Granulomatous (De Quervain) thyroiditis

3. Subacute lymphocytic (painless)

thyroiditis
 Hashimoto thyroiditis

Hashimoto thyroiditis is an autoimmune disease

that results in destruction of the thyroid gland and
gradual and progressive thyroid failure.
 Hashimoto's thyroiditis is named after Japanese
physician Hakaru Hashimoto, who first described
the condition in 1912.
Hashimoto thyroiditis
Hashimoto thyroiditis
 Hashimoto thyroiditis

 It is the most common cause of hypothyroidism in areas

of the world where iodine levels are sufficient.

 It is most prevalent between 45 and 65 years of age.

 More common in females (10:1 to 20:1).

 Can also occur in children and a major cause of

nonendemic goiter in the pediatric population.

 Hashimoto thyroiditis
 Hashimoto thyroiditis is an autoimmune disease
which is caused by breakdown in self-tolerance to
thyroid autoantigens.
 The immune system produces antibodies,
specifically anti-thyroid peroxidase (anti-TPO) and
anti-thyroglobulin (anti-Tg) antibodies, against
thyroid peroxidase and thyroglobulin respectively
 Hashimoto thyroiditis

 Induction of thyroid autoimmunity is

accompanied by a progressive depletion of

thyroid epithelial cells by apoptosis and

replacement of thyroid parenchyma by

mononuclear cell infiltration and fibrosis.

 Morphology of Hashimoto thyroiditis
 Thyroid gland id usually diffusely enlarged.
 The capsule is intact and the gland is well
demarcated from adjacent structures.
 The cut surface is pale, yellow-tan, firm and
somewhat nodular.
 Microscopic examination reveals extensive
infiltration of the parenchyma by a mononuclear
inflammatory infiltrate containing small
lymphocytes, plasma cells and well-developed
germinal centers.
 Morphology of Hashimoto thyroiditis

 The thyroid follicles are atrophic and are lined by

Hṻrthle cells (abundant eosinophilic granular
cytoplasm) in many areas.
 In fine-needle aspiration biopsy samples, the
presence of Hṻrthle cells in conjunction with a
heterogenous population of lymphocytes is
characteristic of Hashimoto thyroiditis.
Clinical features of Hashimoto thyroiditis:
• Diffuse symmetric, painless enlargement of
thyroid gland.
• Gradual hypothyroidism
• Middle aged woman

Laboratory findings of Hashimoto thyroiditis:

1. Decreased free T 3 & T 4 level
2. Elevated TSH levels
3. Detection of antithyroid autoantibodies
4. Radioactive iodine ( 123I)uptake scan
 GRAVES DISEASE (diffuse toxic goiter)

• Graves disease is the most common causes

of endogenous hyperthyroidism.
• Age incidence: 20 to 40 years of age

• Female are affected 10 times more than

male.
 GRAVES DISEASE
( diffuse toxic goiter)
• The disease is characterized by a triad of
clinical findings:
 Hyperthyroidism associated with diffuse
enlargement of the gland
 Infiltrative ophthalmopathy with resultant
exophthalmos
 Localized, infiltrative dermopathy, sometimes
called pretibial myxedema, which is present in
minority of the patients.
 Graves disease (Pathogenesis)

Production of autoantibodies against multiple

thyroid proteins, most importantly the TSH receptor.

The most common antibody subtype is thyroid

stimulating immunoglobulin (TSI)

TSI binds to the TSH receptor

It mimics it’s action by stimulating adenyl cyclase and

increase the release of thyroid hormones
 GRAVES DISEASE (diffuse toxic goiter)

Morphology:
Gross feature:
The thyroid gland is symmetrically enlarged due to
diffuse hypertrophy and hyperplasia of thyroid
follicular epithelial cells.

On cut section, the parenchyma has a soft, meaty

appearance resembling muscle.
 GRAVES DISEASE
( diffuse toxic goiter)
Morphology:
Microscopic feature:
The follicle epithelial cells are tall and more crowded than usual.
The follicles are lined by tall, columnar epithelium. The crowded,
enlarged epithelial cells project into the lumens of the follicles.
These cells actively resorb the colloid in the centers of the
follicles, resulting in the scalloped appearance of the edges of the
colloid. (Hurayra 785)
 Graves Disease (Microscopic feature)

Graves disease Normal thyroid

Graves Disease (Microscopic feature)
Graves Disease (Microscopic feature)
Graves Disease- Histopathology
Clinical features of Graves Disease:
 Eye sign of Graves Disease
• Exophthalmos:
Abnormal protrusion of eyeball. Extra ocular
muscles are often weak.
• Lid lag:

Due to sympathetic overstimulation of the superior

tarsal muscle, which functions alongside the levator
palpebrae superioris muscle to raise the upper
eyelid.
 Eye sign of Graves Disease
Lid lag:

• This refers to the upper eyelid's delayed descent when the eyes
move downward. Normally, the eyelid smoothly follows the eye's
movement. In lid lag, a gap appears between the upper eyelid and
the top of the iris during downgaze.

• The upper eyelid lags behind the eye when it moves downward.

• Associated with thyroid eye disease (TED), also known as Graves'

ophthalmopathy.
 Eye sign of Graves Disease

Wide staring gaze:

The wide, staring appearance is due to upper
eyelid retraction, where the upper eyelid is
positioned higher than normal. This can make
the eyes appear prominent.
 Graves Disease

Laboratory findings :
• Free T4 and T3 levels are increased.

• TSH level is decreased.

• Radioiodine scans show a diffusely increased

uptake of iodine.
 Tumors
A) Primary:
1. Benign:
– Follicular adenoma
2. Malignant:
– Papillary thyroid carcinoma {(PTC),(80% to 85%)}
– Follicular carcinoma (10% -15 % of cases)
– Medullary carcinoma (5%, amyloid)
– Anaplastic (<5%, worst)
[Link] primary tumors:
– Lymphoma
– Sarcoma Metastatic
B) Secondary:
 Papillary Carcinoma
 Gross feature:
 May be solitary or multifocal.

 Some tumors are well circumscribed and encapsulated.

 Others infiltrate the adjacent parenchyma and have ill-

defined margins.
 May contain areas of fibrosis and calcification, often cystic.

 The cut surface sometimes reveals papillary foci that point

to the diagnosis.
 Papillary Carcinoma

Gross feature:

May be solitary or multifocal. Some tumors are well

circumscribed and encapsulated. Others infiltrate
the adjacent parenchyma and have ill-defined
margins. The tumor may contain areas of fibrosis and
calcification, often cystic. The cut surface sometimes
reveals papillary foci that point to the diagnosis.
Fig: Papillary Carcinoma
 Papillary Carcinoma (contd.)

Microscopic features:
 May contain branching papilla having a fibro
vascular stalk covered by a single to multiple
layers of cuboidal epithelial cells.
 The nuclei contain finely dispersed chromatin
which imparts an optically clear or empty
appearance giving rise to the designation
ground-glass or Orphan Annie Eye nuclei.
 Papillary Carcinoma (contd.)

 Invaginations of the cytoplasm may give the

appearance of intranuclear inclusions (pseudo-

inclusions) or intranuclear grooves.

 Sometimes Psammoma bodies (concentric

calcified structure in the core of papillae) can be

present.
 Papillary Carcinoma (contd.)

 Foci of lymphatic invasion by tumor are often

present

The diagnosis of papillary carcinoma can be

made based on these nuclear features, even

in the absence of papillary architecture.

Papillary Carcinoma
Papillary Carcinoma
Papillary Carcinoma
Papillary Carcinoma
Papillary Carcinoma

Papilla
Papillary Carcinoma
Papillary Carcinoma
Papillary Carcinoma
 Metastasis

• Papillary CA lymph nodes (commonly

cervical)

• Follicular CA  blood vessels, bone

Difference between papillary and
follicular carcinoma
Traits Papillary carcinoma Follicular carcinoma

Occurrence Most common (75-85%) 10-20%

Age 20-40 years 40-50 years

Rotes of metastasis Lymphatic Vascular

Prognosis Excellent (10 yr survival Bad (Depend on extent of

>95%) invasion)

Gross Solitary or multifocal Single, well circumscribed

lesion nodule

microscopic Well formed papillae, Follicular or trabecular

ground glass nuclei, pattern, no grooves, no
grooves and inclusions overlap, hyperchromatic

Psammoma bodies Common none

 ENDOCRINE SYSTEM (Questions)

1. Tell the morphology of PTC (papillary thyroid carcinoma)

2. Classify thyroid neoplasm/ Name the malignant tumor of thyroid.
3. Tell the difference between papillary and follicular carcinoma
4. Mention the causes and clinical features of hypothyroidism
5. Mention the causes and clinical features of hyperthyroidism
6. Tell the level of thyroid hormone in hypothyroidism/lab diagnosis of
hypothyroidism
7. Tell the level of thyroid hormone in hyperthyroidism/lab diagnosis of
hyperthyroidism
8. What are the types of thyroiditis?
9. What are the autoimmune diseases of thyroid?
 ENDOCRINE SYSTEM (Questions)

10. A 55-year-old female presents with a one-month history of fatigue,

weight gain, and constipation. She also reports feeling cold intolerance
and dry skin. Her TSH level is elevated, and her T4 level is low. What is
the most likely diagnosis and what further investigations would be
helpful?
11. A 32-year-old female presents with a two-month history of
unintentional weight loss, despite increased appetite. A physical exam
reveals enlarged thyroid gland. Her TSH is low, and her T4 is
elevated. What is the most likely diagnosis and what further
investigations would be helpful?