The endocrine systemic disease Li xiao yun 李晓昀. Thyroid gland disease.

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The endocrine The endocrine systemic diseasesystemic disease

Li xiao yun 李晓昀

Thyroid gland diseaseThyroid gland disease

A. Introduction A. Introduction

Hypothalamus (TRF)

+ - Pituitary (TSH)

+ - Thyroid gland (T3,T4)

1. Anatomy and histology of thyroid 1. Anatomy and histology of thyroid glandgland

Thyroid consists of two bulky lobes.

Weight: 15~20 gram; color: red-brown. Histologic basic unite is thyroid follicle lined by si

ngle layer of cuboidal epithelial cells. Follicular lumina contain colloid ,which is accumul

ating thyroglobulins(TG) secreted by follicular cells.

Follicular cells produce and secrete the thyroid hormone.

Parafollicular cells ,located between follicles or between follicular cells, secrete calcitonin.

2. Physiologic function of thyroid hormone—T3 and T4

Enhancement of basal metabolic rate and the

nervous system excitability.

Promotion of growth and development.

Great influence on growth of skeleton and

central nervous system especially in the fetal

and infant period.

3. Classification of thyroid gland diseases

Most of thyroid gland diseases are usually more common in women than in men

Thyroid tumor Goiter Thyroid inflammation

B. Thyroid tumorB. Thyroid tumor

1. Thyroid adenoma1. Thyroid adenoma Benigh tumor derived from thyroid follicular epith

elium

Grossly: Grossly: Solitary,spherical nodule with intact capsule,a

nd 1~10 cm in diameter. The nodule may compress adjacent thyroid tis

sue.

The cut surface is gray–white or red-brown,depending on the colloid content of adenoma .

The tumor lesion may have hemmorage,fibrosis, calcification ,and cystic change.

Slide 26.13

Microscopy:Microscopy:

(1). Embryonal adenoma:Tumor cells are small and closely packed to form cords or trabeculae,while follicles are seldom formed.

(2). Fetal adenoma : Tumor tissue resembles fetal thyroid tissue. Tumor lesion is mainly composed of small and uniform-appearing follicles with a tiny amount of colloid. Follicular cells are cuboidal

(3). Simple adenoma: Tumor mainly consists of follicles.The size and colloid content of follicles are similar to those of normal thyroid follicles.

(4). Colloid adenoma: Tumor mainly consists of large,colloid-rich follicles lined by flattened epithelial cells.Follicles may be not the same in size,sometimes merge into cystides.

Slide 26.14

(5). Acidophilic cell adenoma: Seldom.

Tumor cells are large, polygonal, eosinophilic, and contain abundant cytoplasm.There are eosinophilic granules within cytoplasm.Cells form cords or sheets,while follicle are seldom formed.

2. Thyroid carcinoma2. Thyroid carcinoma

Malignant tumor derived from thyroid follicular

epithelial cells or parafollicular cells,often acc

ompanied by hemmorage, necrosis,fibrosis,c

alcification or cystis formation.

Pathologic classification

Papillary carcinoma:60-70%

Follicular carcinoma:20%

Medullary carcinoma:5%

Undifferentiated carcinoma:15%

(1) Papillary carcinomaGrossly:Grossly: Tumors are usually solitary,spherical and firm

lesions with 2~3cm in diameter. The cut surface is gray-white,and sometimes

papillary foci may be seen. Most tumors have no capsules,but their

circumscriptions are still recognizable.

Microscopy:Microscopy: Tumors mainly consists of a large number of papillae

with many branches. There is fibrovascular stalk within papilla. Tumor nuclei are ground-glass: loose chromatins,unclear nucleolus,big and empty nucle

us. A single to multiple layers of cuboidal epithelial cells c

overing the papillae arrange disorderly, and are obviously atypical.

Calcified structures termed psammoma bodies are often present within tumor stroma,especially within the stalks of papillae.

Slide 26.16

Behavior:

slow growth,

low grade malignant

good prognosis

regional lymphoid nodule metastasis

5-year survival rate:90%

10 -year survival rate:85%

(2)Follicular carcinoma

Grossly:Grossly:

Most tumors are single, well-

circumscribed nodules,and capsules are usually

not intact.The cut surface is gray-white.

Slide 26.17

Microscopy:Microscopy:

The tumor lesions have different

differentiation degree of follicles,but no

papillae.The nuclei lack ground-glass

features.

Well-differentiated carcinomaWell-differentiated carcinoma

It resembles thyroid adenoma,but capsules and blood vessels have been invaded by tumor cells.

Tumor cells form many follicles,cell atypia is relatively less obvious.

Slide 26.18

Poor-differentiated carcinomaPoor-differentiated carcinoma

Tumor cells are apparently atypical and

form solid nests or sheets,while follicles

are less seen and usually not intact.

Behavior:

Middle grade malignant

Early bloodstream metastasis

5-year survival rate: 30-40%

(3). Medullary carcinoma:(3). Medullary carcinoma:

Malignant tumors derived from parafollicula

r cells, APUD tumor.Tumor cells secrete ca

lcitonin and other hormones.

Grossly :Grossly :

Tumors can arise as solitary nodules or multiple

lesions and may have fake capsules.The cut

surface is gray-white or tan, and the consistency is

soft.

Slide 26.19

Microscopy:Microscopy:

Tumors are composed of round, polygonal or spindle cells,

which may form solid nests or sheets. Pink amyloid depo

sits are often present in tumor stroma.Electron microscop

y reveals variable number of nervous endocrine granules

within cytoplasm.

Slide 26.20

Slide 26.21

Behavior:

Middle grade malignant

5-year survival rate:50%

(4)Undifferentiated carcinoma:(4)Undifferentiated carcinoma:

Grossly: Grossly: Tumors are massive,ill-circumscribed nodules

without capsules,and surrounding tissues are invaded by tumor cells. The cut surface is gray-white. Hemorrhage and necrosis often occur in tumor lesions.

Microscopy:Microscopy:

Tumors mainly consist of highly anaplastic cells,including 3 types of pathological classification.

(Anaplasia: malignant tumor cells lack differentiation and show high atypia.)

Small cell type:

Tumor cells are small and similar to

lymphocytes,closely arranging to form nests

or cords with some abortive follicles.

Spindle cell type :

Tumor cells are spindle and resemble fib

rosarcoma cells , so this type should be

distinguished from sarcomas.

Giant cell type:

Tumor cells are giant and often multinuclear.

Behavior: High grade malignant

Rapid growth

Early infiltration and metastasis

Most cases die within 2 years.

C . Goiter

Thyroid enlargement due to non-tumor

hyperplasia

1. Nontoxic goiter (Endemic goiter)

Definition : The deficient secretion of thyroid hormone leads

to a compensatory rise in serum TSH level,which ,in turn,causes hyperplasia of thyroid follicular epithelia and colloid accumulation,and ultimately gross enlargement of the thyroid gland,usually without hyperthyroidism.

Clinical symptom:

The enlargement of thyroid gland in neck.

Excessive enlargement may compress surrounding structures of thyroid gland and cause the difficulties in swallow and breath.

Etiology and pathogenesis (1) Iodine deficiency .

TSH epithelium hyperplasia

thyroid hormone

Iodine glandDeficiency enlargement thyroglobulin within follicular lumina can’t iodinate and then can’t be resorbed by epithelia colloid accumulation within follicles

(2) goitrogenic factions:

(3) Heredity and immunology

•Pathologic changes:

(1) Hyperplastic stage (diffuse hyperplastic goiter)

Grossly:Grossly:

The thyroid gland is diffusely, bilaterally,symmetrically and moderately enlarged,the gland rarely exceeds 150 gram,and the surface is smooth.

Microscopy:Microscopy:

Follicular epithelial cells proliferate and become cuboidal or low and columnar, sometimes forming small follicles and fake papillae.

Follicular lumina contain less colloid,and stroma shows hyperemia.

(2)Colloid accumulation stage (diffuse colloid goiter)

Involution occurs in this stage.Grossly:Grossly: The gland is diffusely, bilaterally ,

symmetrically , and conspicuously enlarged ,and the weight is approximately 200-300 gram.

The surface of gland is smooth,and the cut surface is brown,somewhat glassy, translucent, and colloidal.

Microscopy:Microscopy:

The majority of follicular lumina are highly enl

arged, containing abundant colloid,and the ep

ithelial cells involute and become flattened.

(3) Nodular stage (Nodular goiter)

The recurrent hyperplasia and involution of fol

licular cells

The formation of fibre interval and nodules

Grossly:Grossly: Nodular goiters are multinodular, bilaterally, asym

metrically enlarged,which may achieve a weight of more than 2000 gram.

Nodules are not uniform in size and are well-circumscribed, without capsules or with incomplete capsules.

On cut section , hemorrhage, fibrosis, calcification, and cystic change are often seen.

Slide 26.12

Microscopy:Microscopy:

Follicles are not uniform in size.

Partial follicles are highly enlarged and colloid-rich,and

the epithelial cells involute and become flattened.

Partial follicular cells proliferate and become columnar

or form fake papillae or small follicles.

The hyperplastic connective tissue divide and enclose t

hyroid tissue to result in the formation of irregular nodule

s.

Results:

Hypofunction of thyroid

Malignant change :1-5%.

2. Diffuse toxic goiter

Definition :

Hyperthyroidism: Hyperthyroidism is a clinical syndrome caused by excessive thyroid hormone in serum acting on tissue of the whole body, manifesting the rise of basal metabolic rate and the nervous system excitability.

Diffuse toxic goiter (Graves disease, Exophthalmic goiter) :

Conspicuous hyperplasia of thyroid follicular cells makes thyroid gland enlarged,accompanied by hyperthyroidism.

Clinical menifestation:

The enlargement of thyroid, exophthalmia, palpitation, rapid pulse, excitable, easily sweaty ,finger shake,eating too much,easily hungry, emaciated.

Pathologic changes:

Grossly:Grossly: Thyroid gland is usually diffusely, bilaterally,

symmetrically enlarged,and its surface is smooth.The cut surface is gray-red or brown and shows meaty appearance.The gland usually weigh more than 80 gram.

Slide 26.8

Microscopy:Microscopy:

a. Follicular epithelial cells diffusely proliferate

and become tall and columnar.The hyperplasia of

epithelial cells may result in the formation of fake

papillae,small follicles ,or solid cell nests.

b. The colloid within follicular lumen is thin with scalloped margins.

c. In the interfollicular stroma,there are abundant blood vessels, hyperemia, the infiltration of lymphocytes and the formation of lymphoid follicles.

Slide 26.11

Etiology and pathogenesis:

An autoimmune disorder produced by autoantibodies to the TSH receptor.

Important Abs include:thyroid-stimulating immunoglobulin(TSI),thyroid growth-stimulating immunoglobulin(TGI).

The two Abs combine with TSH receptors to respectively stimulate excessive secretion of thyroid hormone and the hyperplasia of follicular epithelia.

D .Hypothyroidism

Definition:

Hypothyroidism is a syndrome caused by

deficiency in synthesis and release of thyroid

hormone.

• Classification

1. Cretinism:

Hypothyroidism developing in fetal period ,infancy ,or early childhood results in impaired development of the skeleton system and the central nervous system, characterized by mental retardation,low intelligence,dementia expression,stupid facial features,short stature,and dwarf,and so on.

2. Myxedema:

Hypothyroidism developing in youth or adult

results in the decrease of basal metabolic rat

e and the nervous system excitability and the

accumulation of mucoid matrix in stroma.

The clinical manifestations include listlessnes

s,fatigue,sleepiness,apathetic expression,ment

al retardation,intolerant cold,cool and coarse ski

n, edema,and other symptoms related to mucoi

d matrix deposition in other different organs.

•Cause of hypothyroidism:Cause of hypothyroidism:

Thyroid injury: thyroiditis,

thyroid surgery or radiation

Suppressed synthesis of thyroid hormone.

Autoimmune disease

Pituitary or hypothalamus disease.

E .Thyroiditis

1. Subacute thyroiditis (Granulomatous thyroiditi

s):

A granulomatous inflammation usually cause

d by virus infection.

Grossly:Grossly: The gland is unilaterally or bilaterally,

asymmetrically,lightly enlarged,and may be

adherent to surrounding structures.

The cut surface is yellow-white and firm,and

may contain areas of necrosis or fibrosis.

Microscopy :Microscopy : Partial follicles are destroyed and then release c

olloid. Neutrophils, macrophages, lymphocytes,and plasma cells aggregate about collapsed follicles.Macrophages engulf released colloid and then convert into multinuclear giant cells,which results in the formation of granulomas similar to tuberculoma ,but without caseous necrosis.

In later stages, lesions have fibrosis or scar formation,and regeneration of follicular cells.

Slide 26.10

Clinical manifestation:

Thyroid gland is enlarged and pain.

2. Chronic lymphocytic thyroiditis(Hashim

oto’s thyroiditis):

Autoimmune disease.

Grossly:Grossly:

Gland is diffusely enlarged and firm,the cut surface is gray-white or gray-yellow.

Microscopy:Microscopy:

Thyroid gland structure is extensively destroyed,and follicles atrophy and disappear .

In lesion,there are infiltration of a large number of lymphocytes,formation of lymphoid follicles,and hyperplasia of fibers.

Slide 26.9

Clinical manifestation:

Enlargement of gland

Hypothyroidism(usually in later stage)

3. Fibrous thyroiditis (Chronic woody thyroiditis):

Grossly :Grossly :

Gland is asymmetrically enlarged, hard as wood, and obviously adherent to surrounding structures.

The cut is pray-white,and show nodular appearance.

Microscopy:Microscopy: Atrophy and destruction of the majority of follicles. Hyperplasia of a large amount of fibre tissue. Hyaline change Scar formation The infiltration of a tiny number of lymphocytes

Clinical:

Enlargement of gland,hard consistency

Hypothyroidism

Compression symptoms

Adenoma Nodular goiter

Capsule Intact Not intact

Nodular number Usually single Multinodular,usually bilateral

Structure Relatively uniform Not uniform. Follicles of unequal size

Adjacent thyroid tissue Follicles are compressed and deformed

There are pathologic changes similar to those of nodules,but no compression phenomenon

The distinction between adenoma and nodular goiter