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Endocrine Pathology Kristine Krafts, M'D' November 18

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Title: Endocrine Pathology Kristine Krafts, M'D' November 18


1
Endocrine PathologyKristine Krafts,
M.D.November 18 19, 2008
2
Endocrine pathology in a nutshell
problem up here
problem down here
3
Endocrine pathology in a nutshell
Problem too much too little
4
Endocrine Pathology
  • Organs
  • Pituitary
  • Thyroid
  • Parathyroids
  • Adrenals
  • Pancreas

Diseases Non-neoplastic ? too much hormone ?
too little hormone Neoplastic ? benign ?
malignant
5
Pituitary
  • Introduction
  • Hyperpituitarism
  • Hypopituitarism

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Pituitary Introduction
  • Anterior pituitary (adenohypophysis)
  • GH, ACTH, TSH, LH, FSH, and prolactin.
  • Controlled by hypothalamus.
  • Most problems happen here.

11
What happens to pituitary hormone output if you
cut off hypothalamic input?
12
? prolactin ? all other hormones
13
Pituitary Introduction
  • Posterior pituitary (neurohypophysis)
  • oxytocin, ADH (vasopressin)
  • hypothalamus makes them
  • posterior pituitary stores them

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Pituitary Introduction
  • Oxytocin
  • labor
  • milk let-down
  • cuddling (after orgasm)
  • monogamy (vole studies)
  • trust (investment experiment)
  • female bonding (UCLA study)

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www.verolabs.com
17
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

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Hyperpituitarism
Growth Hormone Adenoma
  • Produces gigantism or acromegaly
  • Other findings
  • diabetes mellitus
  • hypertension
  • arthritis
  • gastrointestinal carcinoma
  • Lab findings
  • ? GH (spurts)
  • ? IGF-I (better)
  • GH unresponsive to glucose

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Hyperpituitarism
Other Pituitary Adenomas
  • Prolactinoma
  • ACTH-producing
  • FSH-LH-producing
  • TSH-producing
  • Non-functioning

31
Hypopituitarism
  • Definition too little anterior pituitary
    hormone(s)
  • Causes
  • Pituitary destruction
  • Ischemic necrosis
  • Pituitary apoplexy
  • Symptoms usually insidious
  • Dwarfism
  • Loss of libido, menstrual abnormalities
  • Hypothyroidism
  • Adrenal insufficiency

32
Sponge Bob, why is panhypopituitarism so rare?
33
Why, Clucky, its because the pituitary has such
a big reserve!
Sponge Bob, why is panhypopituitarism so rare?
34
Thyroid Pathology
35
Thyroid
  • Introduction
  • Hyperthyroidism
  • Hypothyroidism
  • Non-neoplastic diseases
  • Neoplasms

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3
TRH
2
TSH
hormone synthesis
thyroid growth
1
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  • Most thyroid hormone is bound.
  • Only the free form is active!
  • Thyroid hormone
  • binds to nuclear receptors
  • changes gene expression
  • increases carb and fat breakdown
  • stimulates protein synthesis
  • Result increased basal metabolic rate.

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TSH
T4
46
Endocrine pathology in a nutshell
problem up here
problem down here
47
TSH
low
normal
high
primary hypothyroidism
2 or 3 hypothyroidism
low

subclinical hyperthyroidism
subclinical hypothyroidism
T4
normal
euthyroidism
2 or 3 hyperthyroidism
primary hyperthyroidism
high

48
TSH
low
normal
high
primary hypothyroidism
2 or 3 hypothyroidism
low

subclinical hyperthyroidism
subclinical hypothyroidism
T4
normal
euthyroidism
2 or 3 hyperthyroidism
primary hyperthyroidism
high

49
TSH
low
normal
high
primary hypothyroidism
2 or 3 hypothyroidism
low

subclinical hyperthyroidism
subclinical hypothyroidism
T4
normal
euthyroidism
2 or 3 hyperthyroidism
primary hyperthyroidism
high

50
TSH
low
normal
high
primary hypothyroidism
2 or 3 hypothyroidism
low

subclinical hyperthyroidism
subclinical hypothyroidism
T4
normal
euthyroidism
2 or 3 hyperthyroidism
primary hyperthyroidism
high

51
TSH
low
normal
high
primary hypothyroidism
2 or 3 hypothyroidism
low

subclinical hyperthyroidism
subclinical hypothyroidism
T4
normal
euthyroidism
2 or 3 hyperthyroidism
primary hyperthyroidism
high

52
TSH
low
normal
high
primary hypothyroidism
2 or 3 hypothyroidism
low

subclinical hyperthyroidism
subclinical hypothyroidism
T4
normal
euthyroidism
2 or 3 hyperthyroidism
primary hyperthyroidism
high

53
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

54
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

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  • iodine deficiency or genetic problems.
  • symptoms are mild to severe
  • treatment thyroid hormone replacement
  • prevention better

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Definition Inflammation of the thyroid
  • Hashimoto thyroiditis
  • DeQuervain thyroiditis
  • Lymphocytic thyroiditis
  • Fibrosing thyroiditis

58
Definition Inflammation of the thyroid
  • Hashimoto thyroiditis
  • Commonest cause of hypothyroidism in US!
  • FgtgtM
  • Autoimmune destruction of gland

59
  • Mrs. Potatohead
  • female
  • hash
  • myxedema?

60
Definition Inflammation of the thyroid
  • Hashimoto thyroiditis
  • DeQuervain thyroiditis
  • Recent URI
  • Self-limiting

61
  • Rex
  • looks scary
  • really harmless
  • goes away by itself

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Definition Inflammation of the thyroid
  • Hashimoto thyroiditis
  • DeQuervain thyroiditis
  • Silent thyroiditis
  • Post-partum or middle age
  • Mild symptoms

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  • Bullseye
  • silent
  • doesnt cause problems

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Definition Inflammation of the thyroid
  • Hashimoto thyroiditis
  • DeQuervain thyroiditis
  • Lymphocytic thyroiditis
  • Fibrosing thyroiditis
  • Rock-hard neck mass
  • Can compress trachea

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  • Woody
  • woody.

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  • Common autoimmune disease!
  • Triad
  • Hyperthyroidism
  • Ophthalmopathy
  • Dermopathy
  • Anti-TSH receptor antibodies
  • Stimulate thyroid growth
  • Cause T4 release
  • React with retro-orbital tissues, skin of legs

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  • Goiter general term for a big thyroid gland
  • Latin guttar (throat)
  • Cause defective T4 synthesis.
  • iodine deficiency (endemic)
  • other defects (sporadic)

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  • no iodine

? T4
? TSH
enzyme defects
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  • Most neoplasms present as nodules.
  • Nodules are common!
  • Most are benign.
  • Thyroid carcinoma is uncommon.

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biopsy or FNA
cancer
follicles
thyroiditis
take it out!
treat it!
76
  • Common!
  • Most patients are euthyroid (some are
    hyperthyroid)
  • Radioactive iodine uptake most adenomas are
    cold

77
Thyroid adenoma
78
Thyroid adenoma
79
Thyroid adenoma
80
  • Take it out!
  • Why, if its benign?
  • Need to see the whole tumor (including capsule )
    to make sure its not carcinoma

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  • Papillary thyroid carcinoma
  • Follicular thyroid carcinoma
  • Medullary thyroid carcinoma
  • Anaplastic thyroid carcinoma

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  • Papillary thyroid carcinoma
  • Most common
  • Best prognosis
  • Orphan Annie tumor

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Papillary thyroid carcinoma
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Papillary thyroid carcinoma
85
Papillary thyroid carcinoma
86
Papillary thyroid carcinoma
87
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 Annies eyes
  • has psammoma bodies (from the greek psammos, or
    sand) - Annies dog is named Sandy

88
  • Papillary thyroid carcinoma
  • Follicular thyroid carcinoma
  • 2nd most common
  • Good prognosis

89
Which one is follicular carcinoma?
90
  • Papillary thyroid carcinoma
  • Follicular thyroid carcinoma
  • Medullary thyroid carcinoma
  • Rare
  • Endocrine tumor
  • Bad prognosis

91
Medullary thyroid carcinoma
92
  • Papillary thyroid carcinoma
  • Follicular thyroid carcinoma
  • Medullary thyroid carcinoma
  • Anaplastic thyroid carcinoma
  • Rare
  • Bulky, fast-growing, metastatic at diagnosis
  • Very bad prognosis

93
Medullary thyroid carcinoma
94
Parathyroid Pathology
95
  • Introduction
  • Hyperparathyroidism
  • Hypoparathyroidism

96
  • Four glands in two pairs
  • Upper pair from fourth branchial cleft,
  • descends with the thyroid
  • Lower pair from third branchial cleft,
  • descends with the thymus
  • 3-4 mm, 35 mg each
  • Secrete parathormone (PTH)

97
Parathyroid
98
  • PTH raises serum calcium
  • PTH release controlled by serum calcium
  • Several actions
  • stimulates osteoclasts
  • ? renal reabsorption of calcium
  • ? absorption of dietary calcium.

99
Causes of hypercalcemia
  • Hyperparathyroidism
  • Malignancy
  • mets
  • PTH-related protein
  • Vitamin D overdose
  • Thiazide diuretics
  • Milk-alkali syndrome

100
Causes of hypercalcemia
  • Hyperparathyroidism
  • Malignancy
  • mets
  • PTH-related protein
  • Vitamin D overdose
  • Thiazide diuretics
  • Milk-alkali syndrome

101
  • Causes of hypercalcemia MD PIMPS ME
  • Malignancy
  • Diuretics
  • Parathyroid (hyperparathyroidism)
  • Idiopathic
  • Megadose of vitamin D
  • Pagets disease
  • Sarcoidosis
  • Milk-alkali syndrome
  • Endocrine (thyrotoxicosis)

102
  • Common! (2.5 cases per 1000)
  • Most common cause parathyroid adenoma
  • Symptoms
  • asymptomatic!
  • stone kidney stones, other stones
  • bone pain, brown tumors
  • groan gastrointestinal problems
  • moan mental changes

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Parathyroid adenoma
104
Bone changes in hyperparathyroidism
105
Bone changes in hyperparathyroidism
106
Brown tumor
107
Dental changes in hyperparathyroidism
  • Loss of lamina dura
  • Alveolar bone demineralization
  • Brown tumors

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Demineralized maxillary bone, loss of lamina dura
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Osteitis fibrosa cystica
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  • Uncommon!
  • Causes
  • Iatrogenic
  • Congenital absence
  • Idiopathic atrophy
  • Familial
  • Symptoms
  • tetany (perioral numbness)
  • other changes

111
Enamel hypoplasia
112
Adrenal Pathology
113
  • Introduction
  • Too much stuff
  • Too little stuff
  • Tumors

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  • two glands
  • upper pole of kidneys
  • 4 g each
  • cortex (three zones)
  • medulla

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  • Cortex
  • Zona glomerulosa (mineralocorticoids)
  • Zona fasciculata (glucocorticoids)
  • Zona reticularis (sex steroids)
  • Salt, sugar, sex.
  • The deeper you go, the sweeter it gets.
  • Medulla
  • (epinephrine/norepinephrine)

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Adrenal gland
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  • Too much glucocorticoids
  • Causes
  • Ingested steroids
  • Adrenal adenoma
  • Pituitary adenoma
  • Paraneoplastic syndrome
  • Symptoms
  • Hypertension, weight gain
  • Characteristic habitus
  • Glucose intolerance

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Cushing syndrome
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  • Too little cortisol and mineralocorticoids
  • Primary chronic adrenal insufficiency
  • Cause usually autoimmune
  • Symptoms
  • Slow onset (need to destroy 90 of cortex!)
  • Weakness, fatigue, GI complaints
  • Hypotension
  • Skin hyperpigmentation

121
M.J. 33 y/o female
  • Previously healthy 33 y/o female, who began
    having symptoms fatigue, skin bronzing, weight
    loss, salty food cravings
  • Wednesday
  • Headache
  • Thursday
  • Very fatigued, vomiting
  • Saturday
  • Husband brought to ER
  • Vision loss right eye
  • IV fluids unhelpful

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  • 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

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  • Thursday
  • Different doctor
  • IV Na, hydrocortisone, dextrose
  • Saturday
  • Opened eyes
  • Sunday
  • Started removing IVs
  • Next weeks
  • Removed feeding tube
  • Speech, physical, occupational
  • therapy

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  • Two months later
  • Back to work
  • Feeling normal
  • Cortisol and prednisone
  • daily, for life
  • Carry crisis kit
  • (hydrocortisone)

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M.J. 33 y/o female
  • Previously healthy 33 y/o female, who began
    having symptoms fatigue, skin bronzing, weight
    loss, salty food cravings
  • Wednesday
  • Headache
  • Thursday
  • Very fatigued, vomiting
  • Saturday
  • Husband brought to ER
  • Vision loss right eye
  • IV fluids unhelpful

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  • 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

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  • Thursday
  • Different doctor
  • IV Na, hydrocortisone, dextrose
  • Saturday
  • Opened eyes
  • Sunday
  • Started removing IVs
  • Next weeks
  • Removed feeding tube
  • Speech, physical, occupational
  • therapy

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  • Bacterial infection (N. meningitidis)
  • Hypotension, shock
  • DIC
  • Massive, bilateral adrenal hemorrhage
  • Rapidly progressive

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  • Neoplasm of catecholamine-producing cells
  • Rare cause of hypertension!
  • Urine catecholamines, VMA and metanephrines
  • The 10 tumor!
  • 10 extra-adrenal (paraganglioma)
  • 10 bilateral
  • 10 familial (MEN)
  • 10 bad (malignant)

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Pheochromocytoma
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Pheochromocytoma
133
Pheochromocytoma
134
  • Derived from neural crest cells
  • Relatively common childhood tumor
  • Genetic features
  • 1p deletion
  • N-myc amplification

135
Neuroblastoma
136
Neuroblastoma
137
Diabetes
138
  • 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!

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  • 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

140
  • All have in common

not enough insulin.
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  • Problem not enough ß cells
  • Lots of susceptibility genes, one in MHC II
    region
  • MHC II antigen abnormal
  • T cells attack islets
  • Slow, persistent attack

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  • Problem cant make enough insulin, and tissues
    cant use insulin properly
  • Probably lots of contributory genes
  • Deranged insulin secretion
  • Insulin resistance

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  • 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
  • cells swell, ion pumps get damaged
  • nerves, lens, kidney, vessels injured in this way

advanced glycosylation end-products
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  • Increased infections
  • Microangiopathy
  • Retinopathy
  • Nephropathy
  • Neuropathy

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  • Increased infections
  • Oral (and other) candidiasis
  • Malignant otitis externa

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Oral candidiasis
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Malignant otitis externa
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  • Increased infections
  • Microangiopathy
  • accelerated, severe atherosclerosis
  • increased permeability

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Atherosclerosis aorta
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Atherosclerosis coronary vessels
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Peripheral vascular disease
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  • Increased infections
  • Microangiopathy
  • Retinopathy
  • retinopathy
  • cataracts
  • glaucoma

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  • Increased infections
  • Microangiopathy
  • Retinopathy
  • Neuropathy
  • peripheral neuropathy
  • motor, sensory

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  • Increased infections
  • Microangiopathy
  • Retinopathy
  • Neuropathy
  • Nephropathy
  • glomerular lesions
  • vascular lesions
  • pyelonephritis

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Glomerular lesions
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Fungal bladder infection
159
MEN Syndromes
160
Brad Pitt vs. John Cleese
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No contest!
162
  • genetic disorders
  • predispose to endocrine tumors
  • MEN-1 and MEN-2

163
MEN tumors are worse!
  • younger
  • multiple organs
  • multifocal
  • hyperplasia
  • aggressive

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  • Parathyroid hyperplasia
  • Pancreatic carcinoma
  • Pituitary adenoma
  • Other stuff

167
  • mutation in MEN1 gene
  • MEN1 encodes menin
  • classic tumor suppressor gene

168
MEN-1
  • Pit
  • MEN gene
  • Run-of-the-mill
  • Inactive

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  • Medullary thyroid carcinoma
  • Pheochromocytoma
  • Parathyroid hyperplasia
  • Other stuff

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  • RET mutation
  • Proto-oncogene ? oncogene
  • Tyrosine kinase receptor
  • Constitutively activated
  • Unusual!
  • Genetic testing required

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MEN-2
  • Cleese-cell hyperplasia
  • bRETon gene
  • one-of-a-kind
  • always turned on
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