Pathology of the Endocrine System Zhang Wenyan Department of Pathology Sichuan University 2003

Pathology of the Endocrine System

Zhang Wenyan Department of Pathology

Sichuan University2003

Endocrine System

• Endocrine glands （ pituitary, thyroid, par

athyroid, adrenal gland, pineal body,

and islet ）

• Dispersed neuroendocrine cells （ thyroid

C cells, gastrointestinal and bronchopulma

ry neuroendocrine cells ）

Purpose of Endocrine System

• To maintain a state of homeostasis

among the various organs of the body

• Endocrine cells secrete hormones to

regulate the activity of target organs

T3, T4

TRH

TSH

Abnormal activity of Endocrine System

• Impaired synthesis or release of

hormones

• Abnormal interactions between

hormones and their target tissues

• Abnormal responses of target organs to

their hormones

hyperplasianeoplasminflammation disturbance of blood supply genitics factors

over-/underproduction of hormones

biochemical consequences

hyperplasia, hypertrophy oratrophy of target organs/tissue

clinic consequences

A proper understanding of

endocrine diseases requires a

careful integration of morphologic

findings with biochemical

measurements of the levels of

hormones, their regulators, and

other metabolites.

contents

• Pituitary Adenomas

• Diseases of Thyroid

• Diseases of Adrenal Gland

• Diabetes Mellitus

Posterior pituitary

• Antidiuretic hormone, ADH

• Oxytocin, OT

Anterior pituitary

• Acidophile cell Growth hormone, GH

Prolactin, PRL• Basophile cell

Thyroid stimulating hormone, TSH Follicle stimulating hormone, FSH Luteinizing hormone, LH Adrenocoticotrophin hormone, ACTH Lipotrophic hormone, LPH

• Chromophobe cell

Pituitary1.5×0.9×0.6cm

0.5~0.9g

Anterior pituitary

Prolactin, PRL

Pituitary Adenoma

• Benign neoplasm arising from anterior pituitary cells

• 25% of all intracranial tumors• 20% of the general population• Their prevalence increases with advancing age• Both sexes are equally affected• They are usually invasive in children

Pituitary adenoma

Microadenoma • diameter ＜ 1cm• 5%~10% of the adults• rare functional

Clinical Features

• Hyperpituitarism

• Hypopituitarism

• Local mass effects

Gigantism• Growth hormone

adenoma occurs before

puberty

• Generalized increase in

body size

Acromegaly• Growth hormone adenom

a occurs after puberty

• Protruding jaw

• Broaden lower face

• Enlarged hands

acromegaly

Pituitary Adenomas

Diseases of Thyroid

Diseases of Adrenal

Gland

Diabetes Mellitus

normal thyroid gland

Diseases of Thyroid• hyperthyroidism • hypothyroidism• goiter• thyroiditis• neoplasms of thyroid

Hyperthyroidism

• Excessive secretion of thyroid

hormones

• A consequence of an increase in

body’s metabolism

Clinical Features of Hyperthyroidism

• feeling hot• increased sweating• weight loss, with proximal muscle weakness• rapid heart rate, palpitations• atrial fibrillation (occasionally)• diarrhoea• anxiety and restless hyperactivity


Hypothyroidism

Decreased production of thyroid hormone

• Hypothyroidism present at birth: cretinism

• Hypothyroidism present in adults: myxoedema

cretinism• mental retardation

• short stature

• coarse facial

features

• protruding tongue

• umbilical hernia

myxoedema


Goiter

Simple enlargement of the thyroid• diffuse toxic goiter/Grave’s disease• diffuse nontoxic goiter

Diffuse Toxic Goiter/Graves Disease

• Excessive secretion of thyroid

hormones in the bloodstream

• Organ-specific autoimmune

disorder

• Occurs primarily in younger adults

• F ︰ M ＝ 8 ︰ 1

Graves disease

Histological changes

• Hyperplasia of follicular epithelium

• Reduction of stored colloid

• Local accumulation of lymphocytes

Clinical features

• Diffuse enlargement of the thyroid

• Exophthalmos (protruding eyes)

• Hyperthyroidism

• Pretibial myxedema

exophthalmic goiter

Diffuse Nontoxic Goiter / Multinodular Goiter

• Most common thyroid disease

• Most common cause for an

enlarged

thyroid

Pathogenesis

dietary iodine

deficiencyimpairment of thyroid hormone

synthesiscompensatory rise in the serum TSH

levelhypertrophy & hyperplasia of

thyroid follicular cells

gross enlargement of the thyroid

gland

diffuse nontoxic goiter

multinodular goiter

multinodular goiter

multinodular goiter

Clinical features• Neck mass• Compression symptoms airway obstruction dysphagia compression of large vessels compression of upper thorax

• normal thyroid function


Hashimoto’s thyroiditis/ chronic lymphocytic thyroiditis

anti-thyroglobulin antibody

thyroid gland (atrophy)

subacute granulomatous thyroiditis (DeQuervain's disease)

Clinical features of subacute granulomatous thyroiditis

• Painful enlarged thyroid

• Self-limited clinical course


Neoplasms of thyroid gland

• Range from adenoma to carcinoma

• Present with thyroid nodules

• Carcinomas of thyroid are uncommon,

accounting for under 1% of thyroid

nodules

Clinical criteria to the nature of a thyroid nodule (Ⅰ)

• Solitary nodules are more likely to be neoplastic tha

n are multiple nodules

• Solid nodules are more likely to be neoplastic than a

re cystic nodules

• Nodules in younger patients are more likely to be ne

oplastic than are those in older patients

Clinical criteria to the nature of a thyroid nodule (Ⅱ)

• Nodules in males are more likely to be neoplastic tha

n are those in females

• Nodules that do not take up radioactive iodine in im

aging studies ( “cold” nodules ) are more likely to b

e neoplastic, “hot” nodules are almost benign

follicular adenoma. follicular adenoma.

Thyroid Adenoma

Thyroid Carcinoma

• Papillary carcinoma (75%~85% of cases)• Follicular carcinoma (10%~20% of cases)• Anaplastic carcinoma (5% of cases)• Medullary carcinoma (5% of cases)

Papillary

Carcinoma

Follicular Carcinoma

•F

Medullary Carcinoma

• Neoroendocrine neoplasm derived from parafollicular cells

• Secrete carcitonin, the measurement of which play an important role in the diagnosis and postoperation follow-up of patients

Medullary carcinoma

Congo red staining

anaplastic carcinoma

anaplastic carcinoma

Pituitary Adenomas

Diseases of Thyroid

Diseases of Adrenal

Gland

Diabetes Mellitus

Hormones of the adrenal gland

• Cortex

• Medulla

MineralocorticoidGlucocorticoidAndrogen / Estrogen

Catecholamines (Adrenaline, Noradrenaline)

Disorders of Adrenal Gland

• Hypercortisolism (Cushing Syndrome)• Adrenocortical Insufficiency• Adrenocortical Neoplasms• Pheochromocytoma

Cushing Syndrome

The symptoms and signs are associate

d with prolonged inappropriate elevatio

n of glucocorticoid levels.

Forms of Cushing syndrome

• Endogenous Cushing syndrome

• Exogenous Cushing syndrome

Primary hypothalamic-pituitary diseases associated with hypersecretion of ACTH

Primary adrenocortical hyperplasia or neoplasia

The section of ectopic ACTH by nonendocrine neoplasms

Administration of exogenous glucocorticoids

Clinic features• Central obesity and moon face• Plethora and acne• Menstrual irregularity• Hirsutism and hair thinning• Hypertension• Diabetes• Osteoporosis• Muscle wasting and weakness• Atrophy of skin and dermis: paper thin skin with bruising tendency, purple stride

Cushing syndrome

Normal Cushing syndrome



Primary adrenocortical insufficiency

• Chronic adrenocortical insufficiency

(Addison disease)• Acute adrenocortical insufficiency

Clinical features of Addison disease• gastrointestinal disturbances• hyperpigmentation• hyperkalemia• hyponatremia• volume depletion• hypotension

Waterhouse-Friderichsen syndrome

• Primary acute adrenal insufficiency

• Caused by G- (usually meningococcal) septicaemia

• Bilateral adrenal hemorrhage

Waterhouse-Friderichsen syndrome



Adrenocortical Neoplasms

• Adrenocortical adenoma

• Adrenocortical carcinoma

1.3 cm adrenal adenoma

adrenocortical adenoma

Adrenocortical carcinoma



Pheochromocytoma

Neoplasm composed of chromaffin cel

ls, which synthesize and release catech

olamines

Rule of 10s

• 10% of pheochromocytomas arise in association wi

th one of several familial syndromes

• 10% of pheochromocytomas are extra-adrenal

• 10% of adrenal pheochromocytomas are bilateral

• 10% of adrenal pheochromocytomas are biological

ly malignant

Bilateral pheochromocytoma

Clinic features

Hypertension

an abrupt, precipitous elevation in blood pre

ssure, associated with tachycardia, palpitati

on, headache, sweating, tremor,and a sense

of apprehension

Pituitary Adenomas

Diseases of Thyroid

Diseases of Adrenal

Gland

Diabetes Mellitus

normal pancreatic islet

Pancreatic islet

• 10%~15% of the pancreatic substance

• Each islet contains 1000 cells beta cells alpha cells delta cells PP (pancreatic polypeptide) cells

insulin glucagon

Diabetes Mellitus, DM

Definition

A chronic disorder of carbohydrate,

fat, and protein metabolism, which is

characterized by hyperglycemia due

to inadequate insulin

action/production

Incidence

• Affects 13million people in U.S.A.

• Annual mortality rate of 35,000

• The seventh leading cause of

death in U.S.A.

Classification

• Type 1 diabetes (insulin-dependent DM, IDDM)

immune mediated (type 1A)

idiopathic

• Type 2 diabetes (non-insulin-dependent DM,

NIDDM)

• Other specific types of diabetes

• Gestational diabetes mellitus

Type 1 Type 2childhood/adolescent middle-aged/elderly

1/3 2/3 F=M F>M(by4:1) acute/subacute gradual thin obese ketoacidosis common ketoacidosis rareplasma insulin absent/low normal/raised insulin sensitive insulin insensitive autoimmune mechanism non-autoimmunegenetic predisposition polygenic inheritanceassociated with HLA-DR

Diagnosis

Diagnosis Venous whole blood glucose fasting sample 2hs after 75g

glucose load

Normal ＜ 5.6mmol/l ＜ 6.7mmol/l Impaired ＜ 6.7mmol/l 6.7~10mmol/lglucose toleranceDiabetic mellitus ＞ 6.7mmol/l ＞ 10mmol/l

Morphology & Late Complication

• Pancreas• Vascular system• Diabetic microangiopathy• Diabetic nephropathy• Diabetic ocular complications• Diabetic neuropathy

Insulitis (type 1 diabetes mellitus)

Amyloidosis (type 2 diabetes mellitus)



Late Complication of Vascular System

• Accelerated severe atherosclerosis in aor

ta, large- and medium-sized arteries

• Myocardial infarction

• Gangrene of the lower extremities

• Hyaline arteriolosclerosis

Hyaline arteriolosclerosis in afferent arteriole of the kidney





Diabetic nephropathy

• Glomerular lesions thickening of glomerular capillary basement

membranes diffuse glomerulosclerosis nodular glomerulosclerosis

• Renal vascular lesions arteriolosclerosis• Pyelonephritis

diffuse glomerulosclerosis

nodular glomerulosclerosis

nephrosclerosis





Documents

Pathology of the Endocrine System Zhang Wenyan Department of Pathology Sichuan University 2003