The Adrenal Gland Flashcards
What is the origin of the adrenal cortex? Hormones?
What is the origin of the adrenal medulla? Hormones?
Epidermal (intermediate mesoderm); corticoids and androgens
Ectodermal; catecholamines
What are the three regions of the adrenal gland and what do they secrete?
Zona glomerulosa: mineralocorticoids (aldosterone)
Zona fasiculata: glucocorticoids (cortisol) androgens
Zona reticularis: glucocorticoids and androgens
Adrenal medulla: catecholamines (N/NE)
*more pronounced
What hormones are produced in the adrenal cortex?
Mineralocorticoids (aldosterone)
Glucocorticoids (cortisol)
Sex steroids (DHEA, DHEAS)
Adrenal enzyme deficiency: 21-hydroxylase causes what symptoms?
Treatment?
Decreased cortisol and mineralocorticoid, increased sex hormones
Hypotension (decreased aldosterone), Na and volume loss, hyperkalemia, elevated renin, female virilization (secondary’s male characteristics) of fetus and sexual ambiguity, male precoscious puberty and premature epiphyseal plate closure
Replace glucocorticoids and mineralocorticoids
Adrenal enzyme 11 beta-hydroxylase deficiency causes what symptoms?
Decreased cortisol and mineralocorticoids, and increased androgens
Virilization of female fetus, increases 11-deoxycorticosterone (builds up because lacks enzyme to convert it to corticosterone)
Hypertension, hypokalemia, suppressed renin secretion
Adrenal enzyme 17 alpha-hydroxylase deficiency causes what symptoms?
Decreased androgens and cortisol, excess mineralocorticoids
Hypertension, hypokalemia, hypogonadism
Describe the genomic and non-gemomic actions of cortisol
Glucocorticoid excess causes what?
Glucocorticoid deficiency causes what?
Glucocorticoid response elements (GRE) lead to genomic: glucocorticoid binding to its steroid hormone and affecting GRE directly or indirectly through secondary messenger signaling and affecting transcription or translation
AND
non-genomic actions (endocannabinoids): binding of glucocorticoid to its receptor in a neuron, neuron releases neurotransmitter (glutamate) into synaptic cleft and causes depolarization to nearby neuron
Cushing syndrome/disease
Addison disease
What are the effects of cortisol on the liver, muscle, fat, cutaneous, immune system, endocrine, GI?
Liver: increase gluconeogenesis
Muscle: breakdown of muscle protein
Fat: promotes lipolysis in extremities, promotes central fat deposition
Cutaneous: skin thins, fragile blood vessels
Immune system: increase infection
Endocrine: insulin resistant or glucose intolerant
GI: interferes with Ca absorption
Describe the regulation of cortisol:
What is released from the hypothalamus?
What are stressors that cause this to be released?
What does it bind to?
What does it do?
Stressors induce: hypoglycemia, hypotension, fever, trauma, surgery
CRF (CRH) is release from paraventricular nucleus in the hypothalamus
Binds to CRH1 receptor (G-protein receptor)
Stimulates the release of ACTH from the anterior pituitary gland
Stimulates the release of cortisol from the adrenal gland
ACTH is derived/cleaved from ____ that is produced in the anterior pituitary.
ACTH can be broken down into ____.
Excess ACTH can lead to disease of _____.
POMC
MSH (melanocytes stimulation hormone)
Hyperpigmentation
Describe the feedback loops of ACTH
Long loop: cortisol inhibiting release of CRH in hypothalamus
Short loop: ACTH inhibits CRH
Ultrashort loop: CRH inhibits itself from being secreted from the hypothalamus
ACTH and cortisol is normally released in a _____.
Highest levels of cortisol are in the ____.
Rhythm
Morning (arouses you)
Describe the negative feedback of cortisol
___ can stimulate the stress response and therefore cortisol pathway
___ is also involved in negative feedback.
Glucocorticoids (GC) exert a negative feedback onto CRH and ACTH by inhibiting POMC transcription and mRNA synthesis of CRH and ACTH
Amygdala
Hippocampus
What does the dexamethasone suppression test (DST) do? (Exogenous glucocorticoid)
Effects of low dose?
High does?
Determines if there is a glucocorticoid problem; give a high does of dexamethasone; ACTH and cortisol secretion should decrease due to the negative feedback
Cushing disease has no suppression
Helps determine which type of Cushing disease
What is the cosyntropin (synthetic ACTH) stimulation tests (CST)?
Effects?
Tests adrenal gland insufficiency
Administer synthetic ACTH
Normal person, cortisol should increase from baseline
If adrenals are unresponsive, cortisol remains the same or rises in small amount (adrenal insufficiency)
If adrenal respond dramatically and cortisol increases substantially, consider secondary adrenal insufficiency
Four cortisol related pathologies
Cushing syndrome
Cushing disease
Addison disease
Secondary adrenal insufficiency
Hypercortisolism causes what two diseases?
Explain
Cushing syndrome: hypersecretion of cortisol; usually adrenal neoplasm; HIGH cortisol but LOW ACTH (negative feedback from cortisol); adrenal problem because primary endocrine disorder
Cushing disease: hypersecretion of ACTH; usually pituitary gland tumor; can be non-pituitary neoplasm like a non-small cell carcinoma; overstimulates the adrenal cortex and excess cortisol is secreted; HIGH ACTH and HIGH cortisol; pituitary problem because secondary endocrine disorder
If a pt with Cushing syndrome was injected with exogenous glucocorticoids (dexamethasone), what would happen to their ACTH levels and cortisol suppression?
Why?
ACTH would be undetectable and dexamethasone fails to suppress cortisol secretion
Negative feedback loop is functional yet hypercortisolism continues (abnormal feedback at level of adrenal gland)
If a pt with Cushing disease was injected with exogenous glucocorticoids (dexamethasone), what would happen to their ACTH levels and cortisol suppression?
Why?
ACTH would be normal or slightly elevated and dexamethasone would successfully suppress cortisol secretion
Abnormal negative feedback at level of pituitary
Hypercortisolism
Symptoms of moon face, hirsutism, bruising, abdomen adiposity, stretch marks, buffalo hump
Cushing’s
Hypocorticolism causes what two diseases?
Explain
Addison disease: primary adrenal insufficiency; chronic; progressive destruction of adrenal gland; HIGH ACTH but LOW cortisol; adrenal response is blocked from signal; adrenal problem
Secondary adrenal insufficiency: caused by exogenous glucocorticoid administration; ACTH deficiency; LOW ACTH, LOW cortisol; pituitary problem
If a pt with Addison disease (primary adrenal insufficiency) is injected with synthetic ACTH (cosyntropin) what would happen to plasma cortisol levels?
If a pt with secondary adrenal insufficiency is injected with synthetic ACTH (cosyntropin) what would happen to plasma cortisol levels?
No change (adrenals can’t respond to ACTH)
Increase cortisol (adrenals are functional)
Causes of Addison disease
Addison disease causes hyposecretion of all ______.
What is an adrenal crisis?
Autoimmune disease of adrenal gland
Adrenal hemorrhage (secondary to infection, secondary to anticoagulant treatment)
Infection (TB, N. menigitidis)
Tumor
Adrenal steroids
Acute change in hypocortisolism (more profound effects)
Signs and symptoms of Addison disease
Hyperpigmentation (MSH) if elevated ACTH
Weight loss
Muscle weakness
Hypoglycemia
Hypotension
Hyponatremia and hyperkalemia (because loss of aldosterone)
Actions of aldosterone
What does a lack of aldosterone cause?
Principle mineralocorticoid controlling Na and K exchange in distal nephron
Major regulator of body stores of K
Increase synthesis and activity of Na channels in apical membrane
Increases synthesis and activity of Na/K ATPase in the basolateral membrane of the distal tubule
Increases Na reabsorption and increases K secretion and H secretion
Hyponatremia and hyperkalemia
Cortisol-cortisone shunt:
MR has equal affinities for ____ and _____.
____ metabolizes the conversion of cortisol to cortisone
Protects the mineralocorticoid receptor (MR) from binding to ____ and keeps MR available for ____.
This enzyme is inhibited by ______ causing _____.
Aldosterone; glucocorticoids
11 beta-HSD2
Cortisol; Aldosterone
Glycyrrhizic acid (licorice); cortisol to have free access to the MR, MR becomes overwhelmed by cortisol especially in hypercortisolemic conditions like Cushings
Two diseases caused by hyperaldosteronism
Explain
Primary (Conn syndrome): hypersecretion of aldosterone usually from an adrenal neoplasm; adrenal problem (primary endocrine disorder)
Secondary: hypersecretion of renin; excess renin from juxtaglomerular cells of the kidney; kidney problem (secondary endocrine disorder)
Two disease caused from hypoaldosteronism
Explain
Primary: hyposecretion of aldosterone, destruction of the adrenal cortex, or defects in aldosterone synthesis; adrenal problem (primary endocrine disorder)
Secondary: hyposecretion of renin; deficient renin from juxtaglomerular cells of the kidney; therefore inadequate stimulation of aldosterone; kidney problem (secondary endocrine disorder)
How does ACTH affect aldosterone?
ACTH had a modest effect on aldosterone secretion
Primary adrenal failure -> deficient cortisol and aldosterone
ACTH deficiency -> cortisol deficiency but no change in aldosterone
What are adrenal androgens?
What enzyme do they rely on?
What do adrenal carcinomas that secrete androgens cause?
DHEA (dehydroepiandrosterone) and DHEAS (DHEA sulfate)
Precursors to human sex steroids
Relies on 3beta-HSD superfamily to exert androgens and estrogenic activities
Females: virilization, hirsutism, clitoromegaly, breast atrophy, deepening of voice, temporal recession, severe acne
E and NE are from sympathetic nerve terminals that release ____.
ACh binds to ____ receptors.
ACh increases synthesis of ____ and activity of ____.
ACh
Nicotinic
Tyrosine hydroxylase; dopamine
Describe the pathway from L-tyrosine to epinephrine
Begin with L-tyrosine -> L DOPA by tyrosine hydroxylase (Rate limiting step)
L-DOPA -> dopamine: dopamine gets stored in secretory vesicles called chromaffin granules by VMAT
Dopamine -> NE by dopamine beta-hydroxylase
NE diffuses out of the granules
NE -> Epi in the cytosol
Epi gets stored in vesicles by VMAT
How does sympathetic stimulation affect the conversion of tyrosine to epinephrine?
How does cortisol affect it?
Sympathetic terminals release ACh which binds to nicotinic receptors
Nicotinic receptor cell signaling increases expression of tyrosine hydroxylase (RLS) and activity of dopamine beta hydroxylase
Cortisol stimulates the conversion of norepinephrine to epinephrine
What is contained in a chromaffin granule?
Epinephrine can be re-shunted back into the chromaffin granule; combines with leftover NE, and chromogranins (contain Ca and ATP), and create a storage complex
NE, E, Ca, ATP
Chromogranins are released when catecholamines are stimulated during fight or flight
Two enzymes involved in the metabolism of catecholamines
Function?
Location?
What is VMA? (vanillylmandelic acid, metanephrines, catecholamines)
MAO (monoamine oxidase): oxidizes; treat neuropsychiatric disorders
COMT (catechol-O-methyltransferase): primary enzyme that inactivates catecholamines released from the adrenal gland
Both in CNS and peripheral tissues
VMA: measurement of breakdown products that are used to determine catecholamines production (elevated VMA = elevated catecholamines)
What is pheochromocytoma?
Symptoms?
Tumor of the chromaffin tissue; produces excess catecholamines
Hypertension, orthostatic hypotension, HA, sweating, palpitations, CP, flushing, anxiety
Stress response and the hypothalamus-pituitary-adrenal axis:
Short-term
Long-term stress
HR increases, BP increass, bronchioles dilates, liver converts glycogen to glucose and releases glucose to blood, blood flow changes and reduces digestive system activity and urine output, metabolic rate increase
Kidneys retain Na and water, blood volume and BP rise, protein and fat converted to glucose and broken down for energy, blood glucose increases, immune system suppressed
What is the function of renin?
Where is it secreted from?
When is it secreted?
What inhibits it?
Converts angiotensinogen to angiotensin I
Kidneys
During times of decreased renal arterial pressure, increased beta-adrenergic action, increased prostaglandins
ANP, dopamine
What are the catecholamines?
What do they come from?
Where are they produced?
Epinephrine and norepinephrine
L-tyrosine
Adrenal medulla
