Adrenal Gland Flashcards
Embryological origin of adrenal cortex vs. adrenal medulla
Adrenal cortex is of mesodermal origin
Adrenal medulla is of ectodermal origin
What types of hormones are secreted by adrenal cortex vs. adrenal medulla?
Adrenal cortex = corticoids and androgens
Adrenal medulla = catecholamines (NE and E)
What are the zones of the adrenal cortex?
[capsule] Zona glomerulosa Zona fasciculata Zona reticularis [adrenal medulla]
What is the primary hormone secreted from zona glomerulosa of adrenal cortex?
Mineralocorticoid = aldosterone
What is the primary hormone secreted from zona fasciculata of adrenal cortex?
Gluococorticoid = cortisol
[also some androgen secretion]
What is the primary hormone secreted from zona reticularis of adrenal cortex?
Androgens
[some cortisol as well]
What is the most common adrenal enzyme deficiency?
21-hydroxylase deficiency
A deficiency in 21-hydroxylase results in what changes in hormone production?
Decreased cortisol
Decreased mineralocorticoid
Increased sex hormones
What are signs/symptoms of 21-hydroxylase deficiency?
Hypotension (decreased aldosterone)
Sodium and volume loss
Hyperkalemia
Elevated renin
Female = virilization of fetus and sexual ambiguity at birth
Male = phenotypically normal, precocious pseudopuberty, premature growth plate closure
Tx for 21-hydroxylase deficiency
Replace glucocorticoids and mineralocorticoids
A deficiency in what adrenal enzyme leads to increased androgens, virilization of female features, and increased 11-deoxycorticosterone?
11b-hydroxylase deficiency
Signs and symptoms of 11b-hydroxylase deficiency
Hypertension
Hypokalemia
Suppressed renin secretion
A 17-alpha hydroxylase deficiency is extremely rare. What changes in hormone secretion occur with this deficiency?
Decreased androgens and cortisol
Excess mineralocorticoids
[patients typically diagnosed at puberty]
Signs/symptoms of 17-alpha hydroxylase deficiency
Hypertension
Hypokalemia
Hypogonadism
Do the following increase or decrease in a 17-alpha hydroxylase deficiency?
Mineralocorticoids Cortisol Sex hormones Blood pressure Plasma [K]
Mineralocorticoids increase Cortisol decrease Sex hormones decrease Blood pressure increase Plasma [K] decrease
Do the following increase or decrease in a 21-beta hydroxylase deficiency?
Mineralocorticoids Cortisol Sex hormones Blood pressure Plasma [K]
Mineralocorticoids decrease Cortisol decrease Sex hormones increase Blood pressuredecrease Plasma [K] increase
Do the following increase or decrease in an 11-beta-hydroxylase deficiency?
Mineralocorticoids Cortisol Sex hormones Blood pressure Plasma [K]
Mineralocorticoids decrease (aldosterone) Cortisol decrease Sex hormones increase Blood pressure increase Plasma [K] decrease
The target tissues of cortisol are body wide and the actions numerous. Genomic actions occur via ______, and non-genomic actions occur via _____
Glucocorticoid response elements (GREs)
Endocannabinoids
What conditions occur with glucocorticoid excess?
Cushing syndrome or cushing disease
What conditions occur with glucocorticoid deficiency?
Addison disease
What effect does cortisol have on the liver?
Increased gluconeogenesis
What effect does cortisol have on the muscle?
Breakdown of muscle protein
What effect does cortisol have on fat?
Promotes lipolysis in extremities, promotes central fat deposition
What effect does cortisol have on skin?
Skin thins, fragile blood vessels
What effect does cortisol have on the immune system?
Increased risk of infection (diminished immune response)
What effect does cortisol have on the endocrine system?
Insulin resistance or glucose intolerance
[also decreased LH, FSH release, decreased TSH release, decreased GH secretion
What effect does cortisol have on the GI system?
Increased risk of osteoporosis d/t interference with calcium absorption
Cortisol release begins with stimulationg by ____ from the ______ nucleus in the hypothalamus
This binds the CRF1 receptor (GPCR) and stimulates the release of ______, which acts on the adrenals and stimulates release of cortisol
CRF aka CRH; paraventricular
ACTH
ACTH is produced in the anterior pituitary and is the principle hormone that stimulates adrenal glucocorticoids
The precursor to ACTH is ______; it also contains ____ activity responsible for stimulation of melanocytes
POMC; MSH
Excess ACTH can lead to ______ due to increased alpha-MSH activity
Hyperpigmentation
Differentiate between long, short, and ultrashort HPA axis feedback loops
Long = from adrenal glands back up to anterior pituitary and hypothalamus
Short = from anterior pituitary back to hypothalamus
Ultrashort = hormone from hypothalamus inhibits itself
When do we experience the largest spike in cortisol release? How does this compare to the rhythm of ACTH?
Largest spike in cortisol upon awakening, around sun-up
ACTH tends to stay around the same levels with a slight drop off in early evening
Glucocorticoids exert negative feedback onto CRH and ACTH
What is the mechanism for this?
GCs inhibit POMC transcription
GCs also inhibit mRNA synthesis of CRH and ACTH
What is the dexamethasone suppression test?
Administration of exogenous glucocorticoid to determine if ACTH and cortisol will be suppressed
[normally they will be suppressed, but if no suppression occurs - indicative of Cushing]
What is the difference in low dose vs. high does dexamethasone suppression tests?
Both are supraphysiologic doses; low dose is used to detect if problem is present.
High dose determines source of problem - pituitary cushing if high dose suppresses ACTH, adrenal or ectopic cushing if no suppresion
What test is used for adrenal gland insufficiency?
Cosyntropin (synthetic ACTH) stimulation test [CST]
What is a postive vs. negative result for cosyntropin stimulation test?
Normal = cortisol increases from baseline
If adrenals are undresponsive and crotisol remains the same or only rises a small amount - consider adrenal insufficiency
If adrenals respond dramatically and cortisol increases substantially, consider secondary adrenal insufficiency
Hypercortisolism characterized by hypersecretion of cortisol, usually an adrenal neoplasm, and low serum ACTH
Cushing syndrome
Hypercortisolism characterized by hypersecretion of ACTH, pituitary gland tumor overstimulating adrenal cortex leading to excess cortisol secretion
Cushing disease
Which is associated with adrenal problem and which is a pituitary problem: cushing syndrome vs. cushing disease?
Syndrome = adrenal problem
Disease = pituitary problem
Why is ACTH low in cushing syndrome, while it is high in cushing disease?
Cushing syndrome is a primary condition d/t adrenal problem - and negative feedback ends up inhibiting ACTH release
Cushing disease is affecting the pituitary leading to excess ACTH release
If a patient with Cushing syndrome was injected with exogenous glucocorticoids like dexamethasone, what do you predict would happen to their ACTH levels and cortisol suppression?
ACTH would be undetectable and dexamethasone fails to suppress cortisol secretion
This occurs bc negative feedback loop itself is functional yet hypercortisolism continues
If a patient with Cushing disease was injected with exogenous glucocorticoids like dexamethasone, what do you predict would happen to their ACTH levels and cortisol suppression?
ACTH would be normal or slightly elevated, and dexamethasone would successfully suppress cortisol secretion because abnormal negative feedback is occurring at level of pituitary
Symptoms of Cushing’s
Moon face Hirsutism Bruising Abdominal adiposity Stretch marks Buffalo hump
Hypocortisolism characterized by primary adrenal insufficiency d/t chronic, progressive destruction of adrenal gland resulting in high ACTH but low cortisol
Addison disease
Hypocortisolism characterized by ACTH deficiency and low cortisol, caused by exogenous glucocorticoid administration
Secondary adrenal insufficiency
Differentiate between addison and secondary adrenal insufficiency - which one is adrenal problem and which one is a pituitary problem?
Addison is adrenal problem
Secondary is pituitary problem
Addison disease is a form of hypocortisolism in which there is hyposecretion of ALL adrenal steroids (primary adrenal insufficiency). What are some causes of Addison?
Autoimmune disease of adrenal gland
Adrenal hemorrhage (d/t infection, AC tx)
Infection (d/t Tb, meningitis)
Tumor
Signs/symptoms of addisons
HYPERPIGMENTATION (d/t MSH activity) Weight loss Muscle weakness HYPOGLYCEMIA Hypotension Hyponatremia and hyperkalemia d/t loss of aldosterone!!
Which of the following is characteristic of primary cortisol deficiency?
A. Increased cortisol, decreased CRF, decreased ACTH, no hyperpigmentation
B. Increased cortisol, decreased CRF, increased ACTH, hyperpigmentation present
C. Decreased cortisol, increased CRF, increased ACTH, hyperpigmentation present
D. Decreased cortisol, increased CRF, decreased ACTH, no hyperpigmentation
E. Decreased cortisol, decreased CRF, decreased ACTH, no hyperpigmentation
C. Decreased cortisol, increased CRF, increased ACTH, hyperpigmentation present
Which of the following is characteristic of primary cortisol excess?
A. Increased cortisol, decreased CRF, decreased ACTH, no hyperpigmentation
B. Increased cortisol, decreased CRF, increased ACTH, hyperpigmentation present
C. Decreased cortisol, increased CRF, increased ACTH, hyperpigmentation present
D. Decreased cortisol, increased CRF, decreased ACTH, no hyperpigmentation
E. Decreased cortisol, decreased CRF, decreased ACTH, no hyperpigmentation
A. Increased cortisol, decreased CRF, decreased ACTH, no hyperpigmentation
Which of the following is characteristic of secondary cortisol deficiency?
A. Increased cortisol, decreased CRF, decreased ACTH, no hyperpigmentation
B. Increased cortisol, decreased CRF, increased ACTH, hyperpigmentation present
C. Decreased cortisol, increased CRF, increased ACTH, hyperpigmentation present
D. Decreased cortisol, increased CRF, decreased ACTH, no hyperpigmentation
E. Decreased cortisol, decreased CRF, decreased ACTH, no hyperpigmentation
D. Decreased cortisol, increased CRF, decreased ACTH, no hyperpigmentation
Which of the following is characteristic of exogenous glucocorticoid treatment?
A. Increased cortisol, decreased CRF, decreased ACTH, no hyperpigmentation
B. Increased cortisol, decreased CRF, increased ACTH, hyperpigmentation present
C. Decreased cortisol, increased CRF, increased ACTH, hyperpigmentation present
D. Decreased cortisol, increased CRF, decreased ACTH, no hyperpigmentation
E. Decreased cortisol, decreased CRF, decreased ACTH, no hyperpigmentation
E. Decreased cortisol, decreased CRF, decreased ACTH, no hyperpigmentation
[actual endogenous cortisol may be low, but symptoms of hypercortisolism may be present]
Which of the following is characteristic of secondary cortisol excess?
A. Increased cortisol, decreased CRF, decreased ACTH, no hyperpigmentation
B. Increased cortisol, decreased CRF, increased ACTH, hyperpigmentation present
C. Decreased cortisol, increased CRF, increased ACTH, hyperpigmentation present
D. Decreased cortisol, increased CRF, decreased ACTH, no hyperpigmentation
E. Decreased cortisol, decreased CRF, decreased ACTH, no hyperpigmentation
B. Increased cortisol, decreased CRF, increased ACTH, hyperpigmentation present
Principle mineralocorticoid controlling Na and K exchange in distal nephron and major regulator of body stores of K
Aldosterone
What are the specific actions of aldosterone on apical vs. basolateral membrane in distal nephron?
What is the overall result?
Apical = increases synthesis/activity of Na channels
Basolateral = increases synthesis/activity of Na/K ATPase
Overal result = increase in Na reabsorption and increase in K excretion, also increases H+ secretion
MR, or mineralocorticoid receptor, has equal affinities for _____ and _____
Aldosterone; glucocorticoids
_____ is responsible for metabolizing cortisol to cortisone (inactive form)
11beta-HSD2
Since 11beta-HSD2 typically protects the MR from cortisol binding, leaving it available for aldosterone, what would a defect in this enzyme cause?
Cortisol would have free access to MR and MR would become overwhelmed by cortisol, especially in things like Cushing’s
2 types of hyperaldosteronism
Primary = Conn syndrome (adrenal problem)
Secondary hyperaldosteronism (kidney problem)
Primary hyperaldosteronism (Conn syndrome) involves hypersecretion of ____
Secondary hyperaldosteronism involves hypersecretion of ____
Aldosterone
Renin
Primary vs. secondary hypoaldosteronism
Primary = hyposecretion of aldosterone, destruction of adrenal cortex, defects in aldosterone synthesis — an ADRENAL problem
Secondary =hyposecretion of renin, deficient renin from JG cells in kidney, inadequate stim of aldosterone — a KIDNEY problem
The effect of ACTH on aldosterone secretion is modest at best
Primary adrenal failure —> deficient ____ and ____
ACTH deficiency —> _____ deficiency, but no change in ______
Cortisol; aldosterone
Cortisol; aldosterone
____ and ____ are adrenal androgens - precursors to human sex steroids that rely on 3beta-HSD superfamily to exert androgenic or estrogenic activities
DHEA; DHEAS
Adrenal carcinomas that secrete androgens lead to what signs/symptoms?
Female virilization, hirsutism, clitoromegaly, breast atrophy, deepening of the voice, temporal recession, severe acne
Catecholamines are proced in the adrenal medulla
80% = _____
20% = ______
Epinephrine
Norepinephrine
Epinephrine and NE are released upon release of _______ from sympathetic nerve terminals, which binds to _____ receptors
This NT increases synthesis of ______and the activity of _____
Acetylcholine; nicotinic
Tyrosine hydroxylase; dopamine
What is the rate limiting step of epinephrine synthesis? Where in the cell does this step take place?
L-tyrosine converted to L-DOPA by tyrosine hydroxylase
Takes place in cytosol
L-DOPA is converted to dopamine, which gets stored in special secretory vesicles called _______ and converted into ______, which later diffuses out of the granules
Chromaffin granules; NE
After NE diffuses out of the granules, it is converted to _____ in the _____
Epinephrine; cytosol
[epinephrine is then stored in different vesicles]
Epinephrine is stored in chromaffin granules as a complex with ___, ____, and _____
ATP; NE; Calcium
What some various receptor types for catecholamine signaling?
Alpha 1 and 2
Beta 1, 2, and 3
What are some mechanisms of action of catecholamine signaling?
Increased IP3, Ca, and DAG (alpha 1 receptors)
Decreased cAMP (alpha 2 receptors)
Increased cAMP (beta 1, 2, and 3 receptors)
Examples of tissue distribution for receptors involved in catecholamine signaling
Alpha 1 = sympathetic postsynaptic nerve terminals
Alpha 2 = sympathetic presynaptic nerve terminals, beta cells of pancreatic islets
Beta 1 = heart
Beta 2 = liver; smooth muscle of vasculature, bronchioles, and uterus
Beta 3 = liver; adipose tissue
Examples of action of alpha 1 catecholamine receptors, distributed in sympathetic postsynaptic nerve terminals
Increased vascular smooth muscle contraction
Examples of action of alpha 2 catecholamine receptors, distributed in sympathetic presynaptic nerve terminals and beta cells of pancreatic islets
Inhibits NE release, inhibist insulin release
Examples of action of beta 1 catecholamine receptors, distributed in heart
Increases cardiac output
Examples of action of beta 2 catecholamine receptors, distributed in liver; smooth muscle of vasculature, bronchioles, and uterus
Increased hepatic glucose output, decreased contraction of blood vessels, bronchioles, and uterus
Examples of action of beta 3 catecholamine receptors, distributed in liver; adipose tissue
Increased hepatic glucose output; increased lipolysis
2 major enzymes for the metabolism of catecholamines
MAO
COMT
[both are located in CNS and peripheral tissues]
Tumor of the chromaffin tissue resulting in excess production of catecholamines
Pheochromocytoma
Symptoms of pheochromocytoma
Symptoms wax and wane:
HTN Orthostatic hypotension Headaches Sweating Palpitations Chest pain Flushing Anxiety
Short-term stress response to catecholamines
Increased HR Increased BP Dilation of bronchioles Glucose release from liver Reduction in digestive blood flow Increased metabolic rate
Long-term stress response to catecholamines
Kidneys retain Na and H2O
Blood volume and BP rise
Proteins and fats converted to glucose for energy
BG increases
Immune system suppressed
