The Adrenal Gland

Question 1

What is the origin of the adrenal cortex? Hormones?

What is the origin of the adrenal medulla? Hormones?

Answer 1

Epidermal (intermediate mesoderm); corticoids and androgens

Ectodermal; catecholamines

Question 2

What are the three regions of the adrenal gland and what do they secrete?

Answer 2

Zona glomerulosa: mineralocorticoids (aldosterone)

Zona fasiculata: glucocorticoids (cortisol) androgens

Zona reticularis: glucocorticoids and androgens

Adrenal medulla: catecholamines (N/NE)

*more pronounced

Question 3

What hormones are produced in the adrenal cortex?

Answer 3

Mineralocorticoids (aldosterone)

Glucocorticoids (cortisol)

Sex steroids (DHEA, DHEAS)

Question 4

Adrenal enzyme deficiency: 21-hydroxylase causes what symptoms?

Treatment?

Answer 4

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

Question 5

Adrenal enzyme 11 beta-hydroxylase deficiency causes what symptoms?

Answer 5

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

Question 6

Adrenal enzyme 17 alpha-hydroxylase deficiency causes what symptoms?

Answer 6

Decreased androgens and cortisol, excess mineralocorticoids

Hypertension, hypokalemia, hypogonadism

Question 7

Describe the genomic and non-gemomic actions of cortisol

Glucocorticoid excess causes what?

Glucocorticoid deficiency causes what?

Answer 7

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

Question 8

What are the effects of cortisol on the liver, muscle, fat, cutaneous, immune system, endocrine, GI?

Answer 8

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

Question 9

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?

Answer 9

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

Question 10

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 _____.

Answer 10

POMC

MSH (melanocytes stimulation hormone)

Hyperpigmentation

Question 11

Describe the feedback loops of ACTH

Answer 11

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

Question 12

ACTH and cortisol is normally released in a _____.

Highest levels of cortisol are in the ____.

Answer 12

Rhythm

Morning (arouses you)

Question 13

Describe the negative feedback of cortisol

___ can stimulate the stress response and therefore cortisol pathway

___ is also involved in negative feedback.

Answer 13

Glucocorticoids (GC) exert a negative feedback onto CRH and ACTH by inhibiting POMC transcription and mRNA synthesis of CRH and ACTH

Amygdala

Hippocampus

Question 14

What does the dexamethasone suppression test (DST) do? (Exogenous glucocorticoid)

Effects of low dose?

High does?

Answer 14

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

Question 15

What is the cosyntropin (synthetic ACTH) stimulation tests (CST)?

Effects?

Answer 15

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

Question 16

Four cortisol related pathologies

Answer 16

Cushing syndrome

Cushing disease

Addison disease

Secondary adrenal insufficiency

Question 17

Hypercortisolism causes what two diseases?

Explain

Answer 17

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

Question 18

If a pt with Cushing syndrome was injected with exogenous glucocorticoids (dexamethasone), what would happen to their ACTH levels and cortisol suppression?

Why?

Answer 18

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)

Question 19

If a pt with Cushing disease was injected with exogenous glucocorticoids (dexamethasone), what would happen to their ACTH levels and cortisol suppression?

Why?

Answer 19

ACTH would be normal or slightly elevated and dexamethasone would successfully suppress cortisol secretion

Abnormal negative feedback at level of pituitary

Question 20

Hypercortisolism

Symptoms of moon face, hirsutism, bruising, abdomen adiposity, stretch marks, buffalo hump

Answer 20

Cushing’s

Question 21

Hypocorticolism causes what two diseases?

Explain

Answer 21

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

Question 22

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?

Answer 22

No change (adrenals can’t respond to ACTH)

Increase cortisol (adrenals are functional)

Question 23

Causes of Addison disease

Addison disease causes hyposecretion of all ______.

What is an adrenal crisis?

Answer 23

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)

Question 24

Signs and symptoms of Addison disease

Answer 24

Hyperpigmentation (MSH) if elevated ACTH

Weight loss

Muscle weakness

Hypoglycemia

Hypotension

Hyponatremia and hyperkalemia (because loss of aldosterone)

Question 25

Actions of aldosterone What does a lack of aldosterone cause?

Answer 25

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

Question 26

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 _____.

Answer 26

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

Question 27

Two diseases caused by hyperaldosteronism Explain

Answer 27

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)

Question 28

Two disease caused from hypoaldosteronism Explain

Answer 28

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)

Question 29

How does ACTH affect aldosterone?

Answer 29

ACTH had a modest effect on aldosterone secretion Primary adrenal failure -> deficient cortisol and aldosterone ACTH deficiency -> cortisol deficiency but no change in aldosterone

Question 30

What are adrenal androgens? What enzyme do they rely on? What do adrenal carcinomas that secrete androgens cause?

Answer 30

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

Question 31

E and NE are from sympathetic nerve terminals that release ____. ACh binds to ____ receptors. ACh increases synthesis of ____ and activity of ____.

Answer 31

ACh Nicotinic Tyrosine hydroxylase; dopamine

Question 32

Describe the pathway from L-tyrosine to epinephrine

Answer 32

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

Question 33

How does sympathetic stimulation affect the conversion of tyrosine to epinephrine? How does cortisol affect it?

Answer 33

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

Question 34

What is contained in a chromaffin granule?

Answer 34

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

Question 35

Two enzymes involved in the metabolism of catecholamines Function? Location? What is VMA? (vanillylmandelic acid, metanephrines, catecholamines)

Answer 35

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)

Question 36

What is pheochromocytoma? Symptoms?

Answer 36

Tumor of the chromaffin tissue; produces excess catecholamines Hypertension, orthostatic hypotension, HA, sweating, palpitations, CP, flushing, anxiety

Question 37

Stress response and the hypothalamus-pituitary-adrenal axis: Short-term Long-term stress

Answer 37

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

Question 38

What is the function of renin? Where is it secreted from? When is it secreted? What inhibits it?

Answer 38

Converts angiotensinogen to angiotensin I Kidneys During times of decreased renal arterial pressure, increased beta-adrenergic action, increased prostaglandins ANP, dopamine

Question 38

What are the catecholamines? What do they come from? Where are they produced?

Answer 38

Epinephrine and norepinephrine L-tyrosine Adrenal medulla