Pathology of the Endocrine System Zhang Wenyan Department of Pathology Sichuan University 2003
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Transcript of Pathology of the Endocrine System Zhang Wenyan Department of Pathology Sichuan University 2003
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Pathology of the Endocrine System
Zhang Wenyan Department of Pathology
Sichuan University2003
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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 )
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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
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T3, T4
TRH
TSH
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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
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hyperplasianeoplasminflammation disturbance of blood supply genitics factors
over-/underproduction of hormones
biochemical consequences
hyperplasia, hypertrophy oratrophy of target organs/tissue
clinic consequences
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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.
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contents
• Pituitary Adenomas
• Diseases of Thyroid
• Diseases of Adrenal Gland
• Diabetes Mellitus
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Posterior pituitary
• Antidiuretic hormone, ADH
• Oxytocin, OT
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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
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Pituitary1.5×0.9×0.6cm
0.5~0.9g
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Anterior pituitary
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Prolactin, PRL
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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
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Pituitary adenoma
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Microadenoma • diameter < 1cm• 5%~10% of the adults• rare functional
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Clinical Features
• Hyperpituitarism
• Hypopituitarism
• Local mass effects
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Gigantism• Growth hormone
adenoma occurs before
puberty
• Generalized increase in
body size
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Acromegaly• Growth hormone adenom
a occurs after puberty
• Protruding jaw
• Broaden lower face
• Enlarged hands
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acromegaly
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Pituitary Adenomas
Diseases of Thyroid
Diseases of Adrenal
Gland
Diabetes Mellitus
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normal thyroid gland
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Diseases of Thyroid• hyperthyroidism • hypothyroidism• goiter• thyroiditis• neoplasms of thyroid
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Hyperthyroidism
• Excessive secretion of thyroid
hormones
• A consequence of an increase in
body’s metabolism
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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
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Diseases of Thyroid• hyperthyroidism • hypothyroidism• goiter• thyroiditis• neoplasms of thyroid
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Hypothyroidism
Decreased production of thyroid hormone
• Hypothyroidism present at birth: cretinism
• Hypothyroidism present in adults: myxoedema
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cretinism• mental retardation
• short stature
• coarse facial
features
• protruding tongue
• umbilical hernia
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myxoedema
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Diseases of Thyroid• hyperthyroidism • hypothyroidism• goiter• thyroiditis• neoplasms of thyroid
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Goiter
Simple enlargement of the thyroid• diffuse toxic goiter/Grave’s disease• diffuse nontoxic goiter
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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
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Graves disease
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Histological changes
• Hyperplasia of follicular epithelium
• Reduction of stored colloid
• Local accumulation of lymphocytes
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Clinical features
• Diffuse enlargement of the thyroid
• Exophthalmos (protruding eyes)
• Hyperthyroidism
• Pretibial myxedema
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exophthalmic goiter
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Diffuse Nontoxic Goiter / Multinodular Goiter
• Most common thyroid disease
• Most common cause for an
enlarged
thyroid
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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
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diffuse nontoxic goiter
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multinodular goiter
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multinodular goiter
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multinodular goiter
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Clinical features• Neck mass• Compression symptoms airway obstruction dysphagia compression of large vessels compression of upper thorax
• normal thyroid function
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Diseases of Thyroid• hyperthyroidism • hypothyroidism• goiter• thyroiditis• neoplasms of thyroid
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Hashimoto’s thyroiditis/ chronic lymphocytic thyroiditis
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anti-thyroglobulin antibody
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thyroid gland (atrophy)
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subacute granulomatous thyroiditis (DeQuervain's disease)
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Clinical features of subacute granulomatous thyroiditis
• Painful enlarged thyroid
• Self-limited clinical course
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Diseases of Thyroid• hyperthyroidism • hypothyroidism• goiter• thyroiditis• neoplasms of thyroid
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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
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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
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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
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follicular adenoma. follicular adenoma.
Thyroid Adenoma
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Thyroid Carcinoma
• Papillary carcinoma (75%~85% of cases)• Follicular carcinoma (10%~20% of cases)• Anaplastic carcinoma (5% of cases)• Medullary carcinoma (5% of cases)
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Papillary
Carcinoma
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Follicular Carcinoma
•F
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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
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Medullary carcinoma
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Congo red staining
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anaplastic carcinoma
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anaplastic carcinoma
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Pituitary Adenomas
Diseases of Thyroid
Diseases of Adrenal
Gland
Diabetes Mellitus
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Hormones of the adrenal gland
• Cortex
• Medulla
MineralocorticoidGlucocorticoidAndrogen / Estrogen
Catecholamines (Adrenaline, Noradrenaline)
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Disorders of Adrenal Gland
• Hypercortisolism (Cushing Syndrome)• Adrenocortical Insufficiency• Adrenocortical Neoplasms• Pheochromocytoma
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Cushing Syndrome
The symptoms and signs are associate
d with prolonged inappropriate elevatio
n of glucocorticoid levels.
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Forms of Cushing syndrome
• Endogenous Cushing syndrome
• Exogenous Cushing syndrome
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Primary hypothalamic-pituitary diseases associated with hypersecretion of ACTH
Primary adrenocortical hyperplasia or neoplasia
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The section of ectopic ACTH by nonendocrine neoplasms
Administration of exogenous glucocorticoids
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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
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Cushing syndrome
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Normal Cushing syndrome
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Disorders of Adrenal Gland
• Hypercortisolism (Cushing Syndrome)• Adrenocortical Insufficiency• Adrenocortical Neoplasms• Pheochromocytoma
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Primary adrenocortical insufficiency
• Chronic adrenocortical insufficiency
(Addison disease)• Acute adrenocortical insufficiency
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Clinical features of Addison disease• gastrointestinal disturbances• hyperpigmentation• hyperkalemia• hyponatremia• volume depletion• hypotension
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Waterhouse-Friderichsen syndrome
• Primary acute adrenal insufficiency
• Caused by G- (usually meningococcal) septicaemia
• Bilateral adrenal hemorrhage
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Waterhouse-Friderichsen syndrome
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Disorders of Adrenal Gland
• Hypercortisolism (Cushing Syndrome)• Adrenocortical Insufficiency• Adrenocortical Neoplasms• Pheochromocytoma
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Adrenocortical Neoplasms
• Adrenocortical adenoma
• Adrenocortical carcinoma
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1.3 cm adrenal adenoma
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adrenocortical adenoma
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Adrenocortical carcinoma
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Disorders of Adrenal Gland
• Hypercortisolism (Cushing Syndrome)• Adrenocortical Insufficiency• Adrenocortical Neoplasms• Pheochromocytoma
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Pheochromocytoma
Neoplasm composed of chromaffin cel
ls, which synthesize and release catech
olamines
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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
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Bilateral pheochromocytoma
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Clinic features
Hypertension
an abrupt, precipitous elevation in blood pre
ssure, associated with tachycardia, palpitati
on, headache, sweating, tremor,and a sense
of apprehension
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Pituitary Adenomas
Diseases of Thyroid
Diseases of Adrenal
Gland
Diabetes Mellitus
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normal pancreatic islet
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Pancreatic islet
• 10%~15% of the pancreatic substance
• Each islet contains 1000 cells beta cells alpha cells delta cells PP (pancreatic polypeptide) cells
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insulin glucagon
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Diabetes Mellitus, DM
Definition
A chronic disorder of carbohydrate,
fat, and protein metabolism, which is
characterized by hyperglycemia due
to inadequate insulin
action/production
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Incidence
• Affects 13million people in U.S.A.
• Annual mortality rate of 35,000
• The seventh leading cause of
death in U.S.A.
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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
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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
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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
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Morphology & Late Complication
• Pancreas• Vascular system• Diabetic microangiopathy• Diabetic nephropathy• Diabetic ocular complications• Diabetic neuropathy
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Insulitis (type 1 diabetes mellitus)
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Amyloidosis (type 2 diabetes mellitus)
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Morphology & Late Complication
• Pancreas• Vascular system• Diabetic microangiopathy• Diabetic nephropathy• Diabetic ocular complications• Diabetic neuropathy
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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
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Hyaline arteriolosclerosis in afferent arteriole of the kidney
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Morphology & Late Complication
• Pancreas• Vascular system• Diabetic microangiopathy• Diabetic nephropathy• Diabetic ocular complications• Diabetic neuropathy
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Morphology & Late Complication
• Pancreas• Vascular system• Diabetic microangiopathy• Diabetic nephropathy• Diabetic ocular complications• Diabetic neuropathy
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Diabetic nephropathy
• Glomerular lesions thickening of glomerular capillary basement
membranes diffuse glomerulosclerosis nodular glomerulosclerosis
• Renal vascular lesions arteriolosclerosis• Pyelonephritis
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diffuse glomerulosclerosis
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nodular glomerulosclerosis
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nephrosclerosis
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Morphology & Late Complication
• Pancreas• Vascular system• Diabetic microangiopathy• Diabetic nephropathy• Diabetic ocular complications• Diabetic neuropathy
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Morphology & Late Complication
• Pancreas• Vascular system• Diabetic microangiopathy• Diabetic nephropathy• Diabetic ocular complications• Diabetic neuropathy
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