The Adrenal Gland _PV Flashcards
Describe the organization of the adrenal gland in terms of its functional layers and the principal hormones secreted from them.
LO1
Adrenal Cortex
1) Zona Glomerulosa
- mineralcorticoids (aldosterone)
2) Zona fasciculata
- glucocorticoids (cortisol)
- androgens (DHEA)
3) Zona reticularis
- glucorticoids (cortisol)
- androgens (DHEA)
Adrenal Medulla
- Catecholamines ( Epi and NE)
What does steroidogenesis start with?
cholesterol
Describe the pathways that control steroid hormone production?
LO2
Cholesterol-> Prenganglone via desmolase-> progesterone -> 11b deoxycorticosterone via 21 hydroxylase and 17a hydroxyprogesterone via 17 hydroxylase -> androgens via 17,20 lyase
HPA axis is under what type of control?
- stimulated by
- target organs and effects (4)
negative feedback
stimulatory factors: stress and circadian rhythm
Target Organs
1) immune system- immune suppression
2) liver- gluconeogenesis
3) muscle- protein catabolism
4) adipose tissue- lipolysis
Circadian rhythm of cortisol
high in morning
low in late evening
Glucocorticoids
- what type of control?
- examples
negative feedback
- cortisone
- prednisone
- methylprednisone
- dexamethasone
21 hydroxylase deficiency
- describe
- symptoms
LO2a
CYP21A2
- most common
- decrease cortisol
- decrease mineralcorticoid
- increase sex hormones
Symptoms
- hypotension
- decrease aldosterone
- sodium and volume loss (salt wasting)
- hyperkalemia
- elevated renin
- Female: virilization and sexual ambiguity
- Male: phenotypically normal, precocious psuedo-puberty, premature epiphyseal plate closure
11B hydroxylase deficiency
- describe
- symptoms
LO2a
CYP11B1
- increased androgens
- virilization of female fetuses
- increase 11 deoxycorticosterone
Symptoms
- HTN
- hypokalemia
- suppressed renin secretion
17a hydroxylase deficiency
- describe
- symptoms
LO2a
CYP17A1
- extremely rare
- decreased androgens and cortisol
- excess mineralocorticoids
- diagnosed at puberty
Symptoms
- HTN
- hypokalemia
- hypogonadism
- male: undescended testes
- female: lack of secondary sexual development
Actions of mineralcorticoids
LO3
influence sodium and potassium levels
aldosterone
- kidney fxn
- secreted in response to low BP or blood volume
- controlled by RAAS
Actions of Corticosteroids
LO3
influence glucose metabolism and immune system
ACTH
- stimulated by stress and mediates glucose metabolism
Actions of Androgens
LO3
- influence secondary sex characteristics
Cortisol
- describe
- target organ
- action
- diseases
target tissue: body wide
Actions: numerous
- glucocorticoid response elements (GRE)
- non-genomic actions( endocannabinoids)
Glucocorticoid excess= Cushing syndrome or disease
Glucocorticoid defiency= Addison disease
Effects of cortisol on:
Liver
increases gluconeogenesis
Effects of cortisol on:
muscle
breakdown of muscle protein
Effects of cortisol on:
fat
promotes lipolysis in extremities
promotes central fat deposition
Effects of cortisol on:
cutaneous
skin thins
fragile blood vessels
Effects of cortisol on:
immune system
increase infection
Effects of cortisol on:
endocrine
insulin resistant
glucose intolerant
Effects of cortisol on:
GI
interferes with calcium absorption
- risk of osteoporosis
Describe the regulation of cortisol secretion
-steps
LO5
1) CRF (CRH)
2) release from PVN
3) brinds CRF1 receptor (GPCR)
4) stimulates release of ACTH
Describe the pattern of ACTH and cortisol release.
- produced where
- derived from
- component
- type of control
LO4
produced in anterior pituitary (PEPTIDE HORMONE)
principle hormone that stimulates adrenal glucocorticoids
derived from POMC
contains MSH activity (excess ACTH= hyperpigmentation)
negative feedback
- glucocorticoid exert negative feedback onto CTH adn ACTH secretion
- GC inhibit POMC
- GC inhbit mRNA synthesis of CRH and ACTH
Dexamethasone suppression test
-types and describe
1) Low dose
- determines whether a problem is present
- overnight
- differentiates pts with Cushing of any cause from patients who do not have Cushing
- no ACTH suppression= Cushing
- normal response= suppression of ACTH and cortisol secretion
2) High Dose
- distinguishes patients with Cushing
- help determine source of the problem
Cosyntropin (synthetic ACTH) stimulation tests
- test for what
- steps
for adrenal gland insufficiency
1) adminster ACTH
2) results
- healthy= cortisol should increase from baseline
- adrenal unresponsive and cortisol remains the same= adrenal insuffiency
- adrenal responds dramatically and cortisol increases too= secondary adrenal insufficiency
Etiologies of Cushing’s syndrome
1) exogenous glucocorticoid excess
- latrogenic
- decrease cortisol but symptoms of excess
2) psuedo cushing syndrome
- major depression
- anxiety
- acute/chronic illness
- alcoholism
3) ACTH dependent
- cushing disease
- ectopic acth- secreting tumors
- CRH secreting tumors
4) ACTH- independent
- adrenal adenoma/carcinoma
Primary action of aldosterone
- steps
Renal sodium absorption
- Aldosterone combines with cytoplasmic receptor
- hormone-receptor complex initiates transcription in nucleus
- translation and protein synthesis makes new protein channels and pumps
- aldosterone-induced proteins modulate existing channels and pump
- increase Na reabsorption and K secretion
Symptoms and signs of Cushing’s syndrome
LO7
- truncal obestity
- moon face
- buffalo hump
- easy bruising
- HTN
- edema
- osteoporosis
- hirsutism
- acne
- virilization
- diabetes
Cushing Syndrome
- describe
- clinical lab results
LO7
hypercortisolism
hypersecretion of CORTISOL
- adrenal neoplasm
elevated cortisol but LOW ACTH
- Adrenal problem
Test
- if inject exogenous glucocorticoid (dexamethasome)-> ACTH undetectable and dexamathasone FAILS to suppress cortisol secretion (negative feedback works but hypercortisolism still persist)
Cushing Disease
- descrive
- clinical lab results
LO7
Hypercortisolism
*pituitary problem
hypersecretion of ACTH
- pituitary gland tumor
- can be non-pituitary neoplasm (cell carcinoma)
overstimulates adrenal cortex and excess cortisol is secreted
HIGH ACTH HIGH CORTISOL
Test
- if inject exogenous glucocorticoid (dexamethasome)-> ACTH normal or slightly elevated and SUCCESSFULLY suppresses cortisol secretion (abnormal negative feedback)
Addison Disease
- describe
- clinical lab results
LO7
primary adrenal insufficiency
* adrenal problem
chronic, progressive destruction of adrenal gland
HIGH ACTH LOW CORTISOL
- adrenal response is blocked from signal
Test
- if inject synthetic ACTH (cosyntropin)-> no change in plasma cortisol level (bc adrenals can’t respond to ACTH)
Secondary Adrenal Insufficiency
- describe
- clinical lab results
LO7
- pituitary problem
- caused by exogenous glucocorticoid administration
ACTH deficiency
LOW ACTH LOW CORTISOL
Test
- if inject synthetic ACTH (cosyntropin)-> increase in plasma cortisol level (bc adrenals are functional)
Primary vs Secondary/ Tertiary adrenal insuffiency
Primary
- both cortisol and aldosterone DECREASES
- RAAS damafed
Secondary/Tertiary
- cortisol decreases
- but RAAS STILL exists
Causes of Primary adrenal insufficiency
- Symptoms
Addison’s disease
- autoimmune disease
Adrenal hemmorhage
- can be caused by anticoagulant
infection
- tuberculosis
- meningitidis
Tumor metastases to adrenal gland
Symptoms:
- hyperpigmentation
- hypoglycemia
- weight loss
- muscle weakness
- hypotension
- hyponatremia
- hyperkalemia
Treatment for Adrenal insufficiency
cortisol is replaced with corticosteroid
aldosterone in replaced with mineralcorticoid hormone (fludrocortisone)
- people with secondary adrenal insufficiency normally maintain aldosterone production-> do NOT require mineralcorticoid replacement therapy
Primary excess (adrenal)
- cortisol
- CRF
- ACTH
- hyperpigmentation?
- cortisol: increase
- CRF: decrease
- ACTH: decrease
- hyperpigmentation: No
Secondary excess (pituitary )
- cortisol
- CRF
- ACTH
- hyperpigmentation?
- cortisol: increase
- CRF: decrease
- ACTH: increase
- hyperpigmentation: Yes
Primary excess (adrenal)
- cortisol
- CRF
- ACTH
- hyperpigmentation?
- cortisol: decrease
- CRF: increase
- ACTH: increase
- hyperpigmentation: yes
Secondary deficiency (pituitary)
- cortisol
- CRF
- ACTH
- hyperpigmentation?
- cortisol: decrease
- CRF: increase
- ACTH: derease
- hyperpigmentation: no
Exogenous glucocorticoid treatment
- cortisol
- CRF
- ACTH
- hyperpigmentation?
- cortisol: decrease
- CRF: derease
- ACTH: decrease
- hyperpigmentation: no
Aldosterone
- describe
- regulator
- overall results
LO9
principal mineralcorticoid controlling Na/K exchange in distal nephrin
Major regulator of K body storage
increases synthesis and activity of :
- Na channels in APICAL membrane
- Na/K ATPAse in basolateral membrane in distal tubule
Overall result: increase in Na reabsorption and increase in K excretion
Actions of aldosterone in kidney (3)
- increases Na reabsorption
- Increases K+ secretion
- Increases H+ secretion
Aldosterone pathologies
- Hyperaldosteronism
- Hypoaldosteronism
LO10
Hyperaldosteronism
- Primary
- excessive release of aldosterone from adrenal cortex
- exm. Conn’s syndrome: adenoma in adrenal cortex - Secondary
- excessive renin secretion by juxtaglomerular cells in kidney
Hypoaldosteronism
- destruction of adrenal cortex
- defects in aldosterone synthesis
- inadequate stimulation of aldosterone secretion
High-dose dexamethaosone
- two paths
1) decrease ACTH-> pituitary tumor
- effect mediated by negative feedback on pituitary
2) no change in ACTH-> ectopic tumor
- no negative feedback effect on ectopic source of ACTH
All congenital adrenal enzyme deficiencies are characterized by what?
enlargement of both adrenal gland
bc increase ACTH stimulation due to low cortisol
Cortisol-cortisone shunt
11B HSD2 metabolizes cortisol to cortisone in kidney
protects the MR from cortisol binding
keeps MR available for aldosterone
11B HSD2 is inhibited by glcyrrhizic acid (licorice)
- cortisol has free access to MR
- MR is overwhelemed by cortisol, especially in hypercortisomelic conditions (Cushing)
Primary Hyperaldosteronism
- describe
aka Conn Syndrome
- hypersecretion of aldosterone
- adrenal neoplasm
- adrenal problem
Secondary Hyperaldosteronism
- describe
LO10
hypersecretion of rennin
excess renin from juxtaglomerular cells of the kidney
KIDNEY problem
Primary hypoaldosteronism
- describe
LO10
hyposecretion of aldosterone
destruction of adrenal cortex
defects in aldosterone synthesis
ADRENAL problem
Secondary hypoaldosteronism
- describe
LO10
hyposecretion of renin
deficient renin from juxtaglomerular cells of kidney
inadequate stimulation of aldosterone
KIDNEY problem
Primary adrenal failure
-general characteristics
deficient cortisol AND aldosteron
ACTH deficiency
- general characterisitc
cortisol deficiency but NOT change in Aldosterone
Adrenal androgen
- hormone
- precursor
DHEA
precursor to human sex steroids
relies on 3B hsd superfamily to exert androgenic and estrogenic activities
adrenal carcinomas that secrete androgens
- females may feature virilization, hirsutism, clitoromegaly, acne
Cathecholamines
- produced where
- breakdown
produced in adrenal medulla
80% epinephrine
- responder to stress (hypoglycemia/exercise)
-influence energy metabolism and cardiac output
20% noepinephrine
Epi and NE pathway
- SNS release Ach
- Ach binds nicotinic receptor
- ACH increases synthesis of tyrosine hydroxylase and activity of dopamine
- VMAT moves EPi into specialized storage vesicles in chromaffin cells
Synthesis of catecholamines
-controlled by
under the control of CRH-ACTH-cortisol axis
- ACTH stimulate synthesis of DOPA
- Cortisol increase PNMT enzyme
- release is triggered by CNS control
Rate limiting step of NE/E synthesis
tyrosine hydroxylase
degradation of catecholamines
- describe enzymes
1) monoamine oxidase
-oxidizes stuff
- used to treat neuropsychiatric disorders
NE or E=> dihydroxymandelic acid
2) COMT
- methylates
- primary enzymes that inactivates catecholamines released from the adrenal gland
both enzymes located in CNS and peripheral tissue
Pheochromocytoma
- describe
- symptoms
- receptors
benign, unilateral tumor on chromaffin tissue
-produces excess catecholamines
Symptoms
- HTN
- orthostatic hypotension
- headaches, sweat, palpitation, chest pain
- anxiety
Catecholamines secreted by pheochromocytoma stimulate both a & B adrenergic receptors
Adrenergic receptors
- which one responds better to NE than E? vice versa? same?
a receptors and B3 respond better to NE than E
B1 receptors respond equally to NE and E
E is more potent than EN for B2 receptors
a1 receptor
- primary mechanism
- action
ip3/ca/dag
increase vascular SM contraction
a2 receptor
- primary mechanism
- action
decrease camp
inhibit NE and insulin
b1 receptor
- primary mechanism
- action
increase camp
increase CO
b2 receptor
- primary mechanism
- action
increase camp
increase hepatic glucose output
dilation for bronchioles,, uterus, vessels
b3 receptor
- primary mechanism
- action
increase camp
increase hepatic glucose output
increase lipolysis
Stress Response and HPA axis
- short term
- long term
1) short term nerve impulse catecholamines (Epi/NE) - increase HR, BP - dilate bronchioles - BMR increase - glycogen to glucose
2) long term mineralocorticoid and glucocorticoid - sodium and h2o retentin - increase BP, BV - immune system suppressed - blood glucose increase
