Transcript Medullary carcinoma

Pathology of
the Endocrine System
Zhang Wenyan
Department of Pathology
Sichuan University
2003
Endocrine System
• Endocrine glands（pituitary, thyroid,
parathyroid, adrenal gland, pineal body,
and islet）
• Dispersed neuroendocrine cells（thyroid C
cells, gastrointestinal and bronchopulmary
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
TRH
TSH
T3, T4
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
hyperplasia
neoplasm
inflammation
disturbance of
blood supply
genitics factors
over-/underproduction
of hormones
biochemical consequences
hyperplasia, hypertrophy or
atrophy 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
Pituitary
1.5×0.9×0.6cm
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 adenoma
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 deficiency
impairment of thyroid hormone synthesis
compensatory rise in the serum TSH level
hypertrophy & 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
than are multiple nodules
• Solid nodules are more likely to be neoplastic than
are cystic nodules
• Nodules in younger patients are more likely to be
neoplastic 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
than are those in females
• Nodules that do not take up radioactive iodine in
imaging studies ( “cold” nodules ) are more likely to
be neoplastic, “hot” nodules are almost benign
Thyroid Adenoma
follicular 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
Mineralocorticoid
Glucocorticoid
Androgen / Estrogen
• Medulla
Catecholamines
(Adrenaline, Noradrenaline)
Disorders of Adrenal Gland
• Hypercortisolism (Cushing Syndrome)
• Adrenocortical Insufficiency
• Adrenocortical Neoplasms
• Pheochromocytoma
Cushing Syndrome
The symptoms and signs are
associated with prolonged inappropriate
elevation of glucocorticoid levels.
Forms of Cushing syndrome
• Endogenous Cushing syndrome
• Exogenous Cushing syndrome
Primary hypothalamicpituitary 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
cells, which synthesize and release
catecholamines
Rule of 10s
• 10% of pheochromocytomas arise in association
with one of several familial syndromes
• 10% of pheochromocytomas are extra-adrenal
• 10% of adrenal pheochromocytomas are bilateral
• 10% of adrenal pheochromocytomas are
biologically malignant
Bilateral pheochromocytoma
Clinic features
Hypertension
an abrupt, precipitous elevation in blood
pressure, associated with tachycardia,
palpitation, 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
childhood/adolescent
1/3
F=M
acute/subacute
thin
ketoacidosis common
plasma insulin absent/low
insulin sensitive
autoimmune mechanism
genetic predisposition
associated with HLA-DR
Type 2
middle-aged/elderly
2/3
F>M(by4:1)
gradual
obese
ketoacidosis rare
normal/raised
insulin insensitive
non-autoimmune
polygenic inheritance
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/l
glucose tolerance
Diabetic 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
aorta, 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