Transcript Endocrine - bloodhounds Incorporated

Endocrine Pathology
Endocrine pathology in a nutshell
problem up here
problem down here
Endocrine pathology in a nutshell
Problem:
too much
too little
Endocrine Pathology
Organs
Diseases
•
•
•
•
Non-neoplastic
Pituitary
Thyroid
Adrenals
Pancreas


too much hormone
too little hormone
Neoplastic


benign
malignant
Pituitary
Introduction
Hyperpituitarism
Hypopituitarism
Pituitary gland
Anterior and posterior pituitary
Anterior pituitary
Posterior pituitary
Pituitary Introduction
Anterior pituitary (adenohypophysis)
• GH, ACTH, TSH, LH, FSH, and prolactin.
• Controlled by hypothalamus.
• Most problems happen here.
Pituitary Introduction
Posterior pituitary (neurohypophysis)
• oxytocin, ADH (vasopressin)
• hypothalamus makes them
• posterior pituitary stores them
Pituitary Introduction
Oxytocin
• labor
• milk let-down
• cuddling (after orgasm)
• monogamy (vole studies)
• trust (investment experiment)
• female bonding (UCLA study)
www.verolabs.com
Hyperpituitarism
• Definition: too much anterior pituitary hormone(s)
• Most common cause: pituitary adenoma
• Pituitary adenoma symptoms:
• None, for a while
• Endocrine abnormalities
• Mass effects
• Many types
Pituitary adenoma
Hyperpituitarism
Growth Hormone Adenoma
• Produces gigantism or acromegaly
• Other findings
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•
•
•
diabetes mellitus
hypertension
arthritis
gastrointestinal carcinoma
• Lab findings
•  GH (spurts)
•  IGF-I (better)
• GH unresponsive to glucose
Adult male with gigantism
12 year old male with gigantism
Tallest man in the world in 2008
Tallest man in the world in 2009
Tallest man in the world for 2010 Guinness Book
Fezzik, Inigo Montoya, and Vizzini
Andre the Giant
Andre the Giant
Acromegalic facial features
Acromegaly: development over time
Hyperpituitarism
Other Pituitary Adenomas
• Prolactinoma
• ACTH-producing
• FSH-LH-producing
• TSH-producing
• Non-functioning
Surgical removal of pituitary adenoma
Hypopituitarism
• Definition: too little anterior pituitary hormone(s)
• Causes
• Pituitary destruction
• Ischemic necrosis
• Pituitary apoplexy
• Symptoms usually insidious
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•
•
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Dwarfism
Loss of libido, menstrual abnormalities
Hypothyroidism
Adrenal insufficiency
Thyroid Pathology
Thyroid
Introduction
Hyperthyroidism
Hypothyroidism
Non-neoplastic diseases
Neoplasms
Normal thyroid follicles
thyroid
growth
TRH
3°
TSH
2°
hormone
synthesis
1°
Thyroid Hormone
• Most thyroid hormone is bound.
• Only the free form is active!
• Thyroid hormone
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•
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binds to nuclear receptors
changes gene expression
increases carb and fat breakdown
stimulates protein synthesis
• Result: increased basal metabolic rate.
Thyroid Lab Tests
Thyroid Lab Tests
TSH
T4
Endocrine pathology in a nutshell
problem up here
problem down here
Endocrine pathology in a nutshell
problem up here
problem down here
Thyroid Lab Tests
TSH
low
low
T4
2° or 3°
hypothyroidism
subclinical
normal hyperthyroidism
high
primary
hyperthyroidism
normal
*
euthyroidism
*
high
primary
hypothyroidism
subclinical
hypothyroidism
2° or 3°
hyperthyroidism
Thyroid Lab Tests
TSH
low
low
T4
2° or 3°
hypothyroidism
subclinical
normal hyperthyroidism
high
primary
hyperthyroidism
normal
*
euthyroidism
*
high
primary
hypothyroidism
subclinical
hypothyroidism
2° or 3°
hyperthyroidism
Thyroid Lab Tests
TSH
low
low
T4
2° or 3°
hypothyroidism
subclinical
normal hyperthyroidism
high
primary
hyperthyroidism
normal
*
euthyroidism
*
high
primary
hypothyroidism
subclinical
hypothyroidism
2° or 3°
hyperthyroidism
Thyroid Lab Tests
TSH
low
low
T4
2° or 3°
hypothyroidism
subclinical
normal hyperthyroidism
high
primary
hyperthyroidism
normal
*
euthyroidism
*
high
primary
hypothyroidism
subclinical
hypothyroidism
2° or 3°
hyperthyroidism
Thyroid Lab Tests
TSH
low
low
T4
2° or 3°
hypothyroidism
subclinical
normal hyperthyroidism
high
primary
hyperthyroidism
normal
*
euthyroidism
*
high
primary
hypothyroidism
subclinical
hypothyroidism
2° or 3°
hyperthyroidism
Thyroid Lab Tests
TSH
low
low
T4
2° or 3°
hypothyroidism
subclinical
normal hyperthyroidism
high
primary
hyperthyroidism
normal
*
euthyroidism
*
high
primary
hypothyroidism
subclinical
hypothyroidism
2° or 3°
hyperthyroidism
Hyperthyroidism
A hypermetabolic state caused by  thyroid hormones.
cardiac: rapid pulse, arrythmias
neuromuscular: tremor, emotional lability
eye: lid lag
skin: warm, moist
gastrointestinal: diarrhea
skeletal: osteoporosis
thyroid storm:  thyroid hormone
Lid lag
Hypothyroidism
A hypometabolic state caused by ↓ thyroid hormones.
slowing of mind and body
myxedema: deepened voice
cardiac: slow pulse
gastrointestinal: constipation
skin: dry, cool, pale
cold intolerance
delayed reflexes
myxedema coma
Hypothyroidism with myxedema: before and after treatment
Congenital Hypothyroidism
• iodine deficiency or
genetic problems.
• symptoms are mild to
severe
• treatment: thyroid
hormone replacement
• prevention better
Thyroiditis
Definition: Inflammation of the thyroid
• Hashimoto thyroiditis
• Lymphocytic thyroiditis
• DeQuervain thyroiditis
• Fibrosing thyroiditis
Thyroiditis
Definition: Inflammation of the thyroid
• Hashimoto thyroiditis
• Commonest cause of hypothyroidism in US!
• F>>M
• Autoimmune destruction of gland
Hashimoto
Thyroiditis
• Female
• Myxedema
•TPO Antibodies
Hashimoto thyroiditis: Hϋrthle cells
Thyroiditis
Definition: Inflammation of the thyroid
• Hashimoto thyroiditis
• DeQuervain thyroiditis
• Recent URI
• Self-limiting
DeQuervain
Thyroiditis
• Looks scary
• Really harmless
• Goes away by itself
Rex
De Quervain thyroiditis: Multinucleated giant cell
Thyroiditis
Definition: Inflammation of the thyroid
• Hashimoto thyroiditis
• DeQuervain thyroiditis
• Silent thyroiditis
• Post-partum or middle age
• Mild symptoms
Silent
Thyroiditis
• Swelling of the
thyroid gland
•Person
alternates
between hyper
and
hypothyroidism
Silent thyroiditis: lymphoid infiltrate
Thyroiditis
Definition: Inflammation of the thyroid
• Hashimoto thyroiditis
• DeQuervain thyroiditis
• Lymphocytic thyroiditis
• Fibrosing thyroiditis
• Rock-hard neck mass
• Can compress trachea
Riedel’s Fibrosing
Thyroiditis
•Rarest form of
thyroiditis
•Dense fibrosis invades
thyroid parenchyma and
even beyond the capsule
Woody
•Woody
Reidel thyroiditis
Graves Disease
• Common autoimmune disease!
• Triad
• Hyperthyroidism
• Ophthalmopathy
• Dermopathy
• Anti-TSH receptor antibodies
• Stimulate thyroid growth
• Causes T4 release
• Reacts with retro-orbital tissues, skin of legs
Graves Dermopathy
Marty Feldman as Igor in Young Frankenstein
Exophthalmos
Pretibial myxedema
Goiter
• Goiter: general term for a big thyroid gland
• Latin “guttar” (throat)
• Cause: defective T4 synthesis.
• iodine deficiency (endemic)
• other defects (sporadic)
Goiter
Goiter
Goiter
no iodine
 T4
enzyme defects
 TSH
Thyroid Neoplasms
Most neoplasms present as nodules.
• Nodules are common!
• Most are benign.
• Thyroid carcinoma is uncommon.
Incidence of thyroid carcinoma vs. adenoma
carcinoma
adenoma
Thyroid Neoplasms
biopsy or FNA
cancer
follicles
take it out!
thyroiditis
treat it!
• http://www.youtube.com/watch?v=CN5yFGa
MDCs
Thyroid Adenoma
• Common!
• Most patients are euthyroid
(some are hyperthyroid)
• Radioactive iodine uptake:
most adenomas are “cold”
Thyroid adenoma
Thyroid adenoma
Thyroid adenoma
Thyroid Adenoma
• Take it out!
• Why, if it’s benign?
• Need to see the whole tumor
(including capsule ) to make
sure it’s not carcinoma
Thyroid Carcinoma
• Papillary thyroid carcinoma
• Follicular thyroid carcinoma
• Medullary thyroid carcinoma
• Anaplastic thyroid carcinoma
Incidence of different types of thyroid carcinoma
medullary (5%)
anaplastic (<5%)
follicular (10%)
papillary
(80%)
Thyroid Carcinoma
• Papillary thyroid carcinoma
• Most common
• Best prognosis
• “Orphan Annie” tumor
Papillary thyroid carcinoma
Papillary thyroid carcinoma
Papillary thyroid carcinoma
Papillary thyroid carcinoma
Papillary Carcinoma: The Little Orphan Annie Tumor
• often affects younger women
• tends to stay around for years
without getting any bigger
• is usually well-behaved; seldom
kills people
• has nuclei that resemble Orphan
Annie’s eyes
• has psammoma bodies (from the
greek psammos, or sand) Annie’s dog is named Sandy
Thyroid Carcinoma
• Papillary thyroid carcinoma
• Follicular thyroid carcinoma
• 2nd most common
• Good prognosis
Papillary/Follicular Carinoma
Which one is follicular carcinoma?
Thyroid Carcinoma
• Papillary thyroid carcinoma
• Follicular thyroid carcinoma
• Medullary thyroid carcinoma
• Rare
• Endocrine tumor
• Bad prognosis
Medullary thyroid carcinoma
Thyroid Carcinoma
• Papillary thyroid carcinoma
• Follicular thyroid carcinoma
• Medullary thyroid carcinoma
• Anaplastic thyroid carcinoma
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Rare
Bulky, fast-growing, metastatic at diagnosis
Invades surrounding tissue
Very bad prognosis
Medullary thyroid carcinoma
Adrenal Pathology
Adrenal Pathology
• Introduction
• Too much stuff
• Too little stuff
• Tumors
Introduction
• two glands
• upper pole of kidneys
• 4 g each
• cortex (three zones)
• medulla
Adrenal gland anatomy
Capsule
Zona
glomerulosa
Zona
fasiculata
Medulla
Zona
reticularis
Adrenal gland histology
Salt, sugar, sex.
The deeper you go, the sweeter it gets.
Glomerulosa, fasiculata, reticularis =
GFR (glomerular filtration rate)
Cushing Syndrome
• Too much glucocorticoids
• Causes
• Ingested steroids
• Adrenal adenoma
• Pituitary adenoma
• Paraneoplastic syndrome
• Symptoms
• Hypertension, weight gain
• Glucose intolerance
• Bone aches
• Buffalo hump
• Moon face
Cushing syndrome
Addison Disease
• Too little cortisol and mineralocorticoids
• Low Aldosterone
• Primary chronic adrenal insufficiency
• Cause: usually autoimmune
• Symptoms
• Slow onset (need to destroy 90% of cortex!)
• Weakness, fatigue, GI complaints
• Hypotension
• Skin hyperpigmentation
M.J. 33 y/o female
Previously healthy 33 y/o
female, who began having
symptoms: fatigue, weight
loss, craving potato chips
Wednesday
• Headache
Thursday
• Very fatigued, vomiting
Saturday
• Husband brought to ER
• Vision loss right eye
• IV fluids unhelpful
Sunday
• Right side paralyzed
• Oxygen levels dropping
• CT: brain swelling
• Coma
• BP 70/33
• Given IV fluids, respirator
• 40 pound weight gain
Tuesday
• No brain activity, kidneys
shutting down
• “Nothing else can be done”
Thursday
• Different doctor
• IV Na+, hydrocortisone, dextrose
Saturday
• Opened eyes
Sunday
• Started removing IVs
Next weeks
• Removed feeding tube
• Speech, physical, occupational
therapy
Two months later
• Back to work
• Feeling normal
• Cortisol and prednisone
daily, for life
• Carry crisis kit
(hydrocortisone)
M.J. 33 y/o female
Previously healthy 33 y/o
female, who began having
symptoms: fatigue, weight
loss, craving potato chips
Wednesday
• Headache
Thursday
• Very fatigued, vomiting
Saturday
• Husband brought to ER
• Vision loss right eye
• IV fluids unhelpful
Sunday
• Right side paralyzed
• Oxygen levels dropping
• CT: brain swelling
• Coma
• BP 70/33
• Given IV fluids, respirator
• 40 pound weight gain
Tuesday
• No brain activity, kidneys
shutting down
• “Nothing else can be done”
Thursday
• Different doctor
• IV Na+, hydrocortisone, dextrose
Saturday
• Opened eyes
Sunday
• Started removing IVs
Next weeks
• Removed feeding tube
• Speech, physical, occupational
therapy
Waterhouse-Friderichsen Syndrome
• Bacterial infection (N. meningitidis)
• Hypotension, shock
• Massive, bilateral adrenal hemorrhage
• Rapidly progressive
Pheochromocytoma
• Neoplasm of catecholamine-producing cells
• Rare cause of hypertension!
• Urine: catecholamines, VMA and metanephrines
• The 10% tumor!
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10% extra-adrenal (“paraganglioma”)
10% bilateral
10% familial (MEN)
10% bad (malignant)
Pheochromocytoma
Pheochromocytoma
Pheochromocytoma
Neuroblastoma
• Derived from neural crest cells
• Relatively common childhood tumor
• Prognosis better in:
• Children < 18 months
• Lower stage tumors
• Lower grade tumors
• Hyperdiploid tumors
• Fewer copies of N-myc
Neuroblastoma
Neuroblastoma
Diabetes
Diabetes
Common, common, common!
• 100 million worldwide have it (3% of the world)!
• 13 million in US have it (only half diagnosed)!
• 54,000 die in US each year (#7 cause of death)!
• Lifetime risk of getting diabetes: up to 5%!
Diabetes
• A disease in which the body does not
produce or properly use insulin
• Primary vs. secondary
• Primary: type 1 vs. type 2
• Pathogenesis different, but end result same
Diabetes
All have in common:
not enough insulin.
Type I Diabetes
• Problem: not enough β cells
• Lots of susceptibility genes,
one in MHC II region
• MHC II antigen abnormal
• T cells attack islets
• Slow, persistent attack
Type II Diabetes
• Problem: can’t make enough insulin,
and tissues can’t use insulin
properly
• Probably lots of contributory genes
• Deranged insulin secretion
• Insulin resistance
Diabetes pathophysiology
Non-enzymatic glycosylation
• glucose attaches itself to proteins, forming AGEs *
• AGEs crosslink, trap stuff
• AGEs bind to receptors, do nasty stuff
Intracellular hyperglycemia
• some cells take up the glucose without insulin
• glucose activates protein kinase C
• …which induces production of pro-angiogenic and
pro-fibroblastic molecules
* advanced glycosylation end-products
Hemoglobin A1C
Diabetes complications
• Increased infections
• Microangiopathy
• Retinopathy
• Nephropathy
• Neuropathy
Diabetes complications
• Increased infections
• Oral (and other) candidiasis
• “Malignant” otitis externa
Oral candidiasis
Malignant otitis externa
Diabetes complications
• Increased infections
• Microangiopathy
• accelerated, severe atherosclerosis
• increased permeability
Atherosclerosis: aorta
Atherosclerosis: coronary vessels
Peripheral vascular disease
Diabetes complications
• Increased infections
• Microangiopathy
• Retinopathy
• retinopathy
• cataracts
• glaucoma
Diabetes complications
• Increased infections
• Microangiopathy
• Retinopathy
• Neuropathy
• peripheral neuropathy
• motor, sensory
Diabetes complications
• Increased infections
• Microangiopathy
• Retinopathy
• Neuropathy
• Nephropathy
• glomerular lesions
• vascular lesions
• pyelonephritis
Glomerular lesions
Fungal bladder infection
MEN Syndromes
Brad Pitt vs. John Cleese
No contest!
MEN Syndromes
• genetic disorders
• predispose to endocrine tumors
• MEN-1 and MEN-2
MEN Syndromes
MEN tumors are worse!
• younger
• multiple organs
• multifocal
• hyperplasia
• aggressive
MEN Syndromes
ORGAN
MEN-1
medullary
carcinoma
thyroid
other endocrine
organs
MEN-2
hyperplasia,
adenoma,
carcinoma
MEN Syndromes
ORGAN
MEN-1
medullary
carcinoma
thyroid
other endocrine
organs
MEN-2
hyperplasia,
adenoma,
carcinoma
MEN-1 Lesions
• Parathyroid hyperplasia
• Pancreatic carcinoma
• Pituitary adenoma
• Other stuff
MEN-1 Genetics
• mutation in MEN1 gene
• MEN1 encodes menin
• classic tumor suppressor gene
MEN-1
• Pit
• MEN gene
• Run-of-the-mill
• Inactive
MEN Syndromes
ORGAN
MEN-1
medullary
carcinoma
thyroid
other endocrine
organs
MEN-2
hyperplasia,
adenoma,
carcinoma
MEN-2 Lesions
• Medullary thyroid carcinoma
• Pheochromocytoma
• Parathyroid hyperplasia
• Other stuff
Parafollicular C cells and medullary thyroid carcinoma
MEN-2 Genetics
• RET mutation
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Proto-oncogene → oncogene
Tyrosine kinase receptor
Constitutively activated
Unusual!
• Genetic testing required
MEN-2
• Cleese-cell hyperplasia
• bRETon gene
• one-of-a-kind
• always turned on