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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
Diseases of Thyroid• hyperthyroidism • hypothyroidism• goiter• thyroiditis• neoplasms of thyroid
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
Diseases of Thyroid• hyperthyroidism • hypothyroidism• goiter• thyroiditis• neoplasms of thyroid
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
Diseases of Thyroid• hyperthyroidism • hypothyroidism• goiter• thyroiditis• neoplasms of thyroid
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
Diseases of Thyroid• hyperthyroidism • hypothyroidism• goiter• thyroiditis• neoplasms of thyroid
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
Disorders of Adrenal Gland
• Hypercortisolism (Cushing Syndrome)• Adrenocortical Insufficiency• Adrenocortical Neoplasms• Pheochromocytoma
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
Disorders of Adrenal Gland
• Hypercortisolism (Cushing Syndrome)• Adrenocortical Insufficiency• Adrenocortical Neoplasms• Pheochromocytoma
Adrenocortical Neoplasms
• Adrenocortical adenoma
• Adrenocortical carcinoma
1.3 cm adrenal adenoma
adrenocortical adenoma
Adrenocortical carcinoma
Disorders of Adrenal Gland
• Hypercortisolism (Cushing Syndrome)• Adrenocortical Insufficiency• Adrenocortical Neoplasms• Pheochromocytoma
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)
Morphology & Late Complication
• Pancreas• Vascular system• Diabetic microangiopathy• Diabetic nephropathy• Diabetic ocular complications• Diabetic neuropathy
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
Morphology & Late Complication
• Pancreas• Vascular system• Diabetic microangiopathy• Diabetic nephropathy• Diabetic ocular complications• Diabetic neuropathy
Morphology & Late Complication
• Pancreas• Vascular system• Diabetic microangiopathy• Diabetic nephropathy• Diabetic ocular complications• Diabetic neuropathy
Diabetic nephropathy
• Glomerular lesions thickening of glomerular capillary basement
membranes diffuse glomerulosclerosis nodular glomerulosclerosis
• Renal vascular lesions arteriolosclerosis• Pyelonephritis
diffuse glomerulosclerosis
nodular glomerulosclerosis
nephrosclerosis
Morphology & Late Complication
• Pancreas• Vascular system• Diabetic microangiopathy• Diabetic nephropathy• Diabetic ocular complications• Diabetic neuropathy
Morphology & Late Complication
• Pancreas• Vascular system• Diabetic microangiopathy• Diabetic nephropathy• Diabetic ocular complications• Diabetic neuropathy