IHP StressVoice
Transcript of IHP StressVoice
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Lightheadness
Low blood pressure
Rapid heart rate
Salt craving
High blood potassium
Low blood sugar
Poor appetite
Weight loss
Tanned
Death if untreated
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Low blood pressure
Rapid heart rate
High blood potassium
Low blood sugar
Poor appetite
Weight loss
Ambiguous genitalia
Death if untreated
Newborn
Child
Lightheadness
Low blood pressure
Rapid heart rate
Salt craving
High blood potassium
Low blood sugar
Poor appetite
Weight loss
Tanned
Death if untreated
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Circadian Rhythm in ACTH and
Cortisol
6am 6pm 6am
ACTH(pg/mL)
Cortisol( g/dL)
1
15
5
20
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The Stress AxisHormonal[Hypothalamic-Pituitary-Adrenal]
Maintain bloodpressure
Preventahypoglycemia
Loss ofareproductiveabehavior and fxn
Loss of growth
Behavioral
Acute Fear Clarity of thought
Anorexia
Loss of libido
Fight or flight
Chronic Loss of reproductive
behavior
Autonomic[Sympathetic NervousSystem]
Dilate eyes
Raise heart rate Raise cardiac output
Maintain bloodpressure
Raise breathing rate Bronchodilate
Prevent hypoglycemia
Increase blood to brain,muscle
Decrease blood to skin
gut
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The Stress Axis
Amygdala
Stress-inducedbehaviors
Behavioral
Brainstem
Catecholamines
AutonomicSympatheticNervous
System
effects
HormonalHypothalamic-Pituitary-Adrenal
CRHVP III
CRH
PVN
Pituitary
ACTH
CortisolEpinephrine effects
pregangionic
postgangionic
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CRH
VP III
CRH
PVN
Ant PitACTH
The Hypothalamic-Pituitary-Adrenal Axis
Mineralocorticoid
Effects
Suppress Growth
Suppress Fertility
GlucocorticoidEffects
C i l i hibi d i f i b bl ki
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Stress
Lulu Wang,PhD
01020304050
Unstressed 5h restraintCorticosterone(ug
/dL) Corticosterone after
5h restraint
Cortisol inhibits reproductive function by blocking
kisspeptin gene expression
0
2
4
68
Unstressed 5h restraint
T(ng/mL)
Testosterone after 5h
restraintUnstressed 5h restraint
Kisspeptin mRNA
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CRH
VP III
CRH
PVN
Ant PitACTH
The Hypothalamic-Pituitary-Adrenal Axis
Mineralocorticoid
Effects
Suppress Growth
Suppress Fertility
GlucocorticoidEffects
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N-terminal
Glycopeptide
(1-76)
Joining
Peptide
(79-108)
-MSH
(112-124)
CLIP
(130-150)
-LPH
(153-207)
-END
(210-240)
ACTH(112-150)
-LPH
(153-240)
-KR
-KR
-KKRR
-KR
-KR
Pro-opiomelanocortin (POMC)
Anterior Pituitary
PC1 PC = proconvertase
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Genetic Deficiency of Human POMC
Krude and Gruters Nat Genetics 19:155, 1998
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Human Adrenal from Organ Transplant Donor
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Structure of Adrenal Cortex
Aldosterone
Cortisol
Adrenal Androgens
Epinephrine
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CRH
VP III
CRH
VP
PVHpc
Ant PitACTH
GlucocorticoidEffects
The Hypothalamic-Pituitary-Adrenal Axis
Development
Metabolism
Immune
Vascular
Mineralocorticoid
Effects
Suppress GrowthSuppress Fertility
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Fetal Lung Development Requires Glucocorticoid
Normal Crh KO Crh KO +
Glucocorticoid
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CRH
VP III
CRH
VP
PVHpc
Ant PitACTH
GlucocorticoidEffects
The Hypothalamic-Pituitary-Adrenal Axis
Development
Metabolism
Immune
Vascular
Mineralocorticoid
Effects
Suppress GrowthSuppress Fertility
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Cortisol Maintains Blood Sugar
during Fasting
FAT
LIVER
MUSCLE
Amino Acids
Fatty Acids, Glycerol GLUCOSE
Cortisol
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Adrenal Insufficiency
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Lightheadness Hypotension
Tachycardia
Salt craving
Hyperkalemia Hypoglycemia
Anorexia
Weight loss
Hyperpigmentation
Death if untreated
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III
CRH
PVN
Pituitary
ACTH
Glucocorticoid
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Abnormal lytes 90 Hypotension 90
Salt craving 50
Weakness 100
Anorexia 100
Weight loss 100
Hyperpigmentation 95% Death (untreated) 100
Clinical Findings in
Addison s Disease
??????
Aldosterone
ACTH
T f Ad l I ffi i
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Anterior Pituitary
ACTH
Cortisol,Aldosterone
Types of Adrenal Insufficiency
Hypothalamus
Adrenal
Primary Autoimmune
Genetic (Adrenoleuko-dystrophy, DAX-1, CAH)
Hemorrhage
Infectious
Secondary Steroid Rx-Withdrawal
Structural Genetic (POMC, MCR2)
Tertiary Steroid Rx-Withdrawal
Structural
CRH
AII K+
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Hypotension
Tachycardia
Hyperkalemia Hypoglycemia
Anorexia
Weight loss
Ambiguous genitalia
Death if untreated
Newborn
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HO
HO
HO
OH
HO
O
OH OHOH
O
zonaglomerulosa
zonafasciculata
zonareticularis
medulla
OH
CHOH
CH2
NH-CH3
PNMT
Testosterone
Cholesterol
Pregnenolone
17OH-Pregnenolone
Dehydroepiandrosterone
17OH-Progesterone
Androstenedione
Corticosterone Aldosterone
11Deoxy-Cortisol
Cortisol
Norepi-nephrine
Epinephrine
DeoxycorticosteroneProgesterone
3HSD 21OHase
17-
OHase
17-20
Lyase
11OHase
Aldosterone Synthase
(11OHase, 18OHase,
18HSD)
20-22
Desmolase
OH17Ketosteroid
Reductase
OH
CHOH
CH2
NH2
OH
HOEstradiol
Aromatase
GONAD
Adrenal Hormone Synthesis
P i Ad l I ffi i i CAH
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Anterior Pituitary
ACTH
Cortisol,Aldosterone
Primary Adrenal Insufficiency in CAH
Hypothalamus
Adrenal
Adrenal Androgen Excess Females: virilization
Males: ??
Aldosterone Deficiency Hyperkalemia
Hypotension
Tachycardia
Cortisol Deficiency Hypotension
Tachycardia Hypoglycemia
Anorexia?
Weight loss?
CRH
AdrenalAndrogens
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Cushing Syndrome
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Hypertension
Hypokalemia Hyperglycemia
Hyperphagia
Obesity
Poor growth
Death if untreated
Cushing Syndrome: Violaceous Striae
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Joe EK. Dermatology Online J.9:16, 2003
Cushing Syndrome: Violaceous Striae
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Cli i l Fi di i C hi S d
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Weight gain 90%
Facial plethora 95 Moon facies 90
Poor growth (children) 90
Hirsutism 80
Hypertension 75
Hypokalemia 50
Osteoporosis/fractures 50 Bruising 50
Striae 50
Weakness 30
Clinical Findings in Cushing Syndrome
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CRH
AnteriorPituitaryACTH
Cortisol,Aldosterone
Types of Cushing SyndromeHypothalamus
Adrenal
ACTH-Independent
ACTH-Dependent
Steroid Rx Adrenal Tumors
Cushing s Disease Ectopic ACTH
Diagnostic studies?
Cushing syndrome
ACTH-dependent vs.
-independent
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Anterior Pituitary
ACTH
Steroid Treatment:Cushing Syndrome + Adrenal Insufficiency
Hypothalamus
Adrenal
CRH
Prednisone
from CVS
Cushing syndrome
cortisol
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Nicholas, James A., M.D., Philip D. Wilson, M.D., and Charles J.Umberger, Ph. D., "Induced Hypoadrenalism in Patients
Requiring Orthopedic Surgery," Journal of the American Medical
Association, May 18, 1957, vol. 164, No. 3, pp. 261-265.
Nichols, John, M.D., "President Kennedy's Adrenals," Journal
of the American Medical Association, July 10, 1967, vol. 201, No.
2, pp. 115-116.