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Endocrine > Lec 12 Adrenal gland > Flashcards

Lec 12 Adrenal gland Flashcards

1
Q

What does the adrenal cortex produce?

A
  • outer zona glomerulosa –> aldosterone
  • zona fasciculata –> cortisol
  • zona reticularis –> androgens that get converted peripherally to major androgens, testosterone, and DHT
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2
Q

What is the origin of adrenal cortex?

A

mesoderm

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3
Q

What is the origin of adrenal medulla?

A

neural crest tissue

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4
Q

What is structure of the fetal adrenal cortex?

A
  • fetal zone –> produces DHEA and DHEA-sulfate [DHEA-S]
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5
Q

What does the zona glomerulosa make?

A

aldosterone

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6
Q

What does the zona fasciculata make?

A

cortisol

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7
Q

What does the zona reticularis make?

A

androgens

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8
Q

What is starting point for all adrenal hormones?

A

cholesterol

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9
Q

Where does the adrenal vein empty on L and R sides?

A

right –> into vena cava

left –> into left renal vein

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10
Q

What is the first step in steroid hormone synthesis? enzyme? 2 things that regulate it?

A
  • cholesterol desmolase catalyzes cholesterol –> pregnenolone in the inner mitochondrial membrane
  • activated by ACTH
  • inhibited by ketoconazole
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11
Q

What 3 reactions are catalyzed by 3B-hydroxysteroid dehydrogenase?

A

zona glomerulosa: pregnenolone –> progesterone

zona fasciculata: 17-hydroxypregnenolone –> 17-hydroxyprogesterone

zona reticularis: dehydroepiandrosterone [DHEA] –> androstenedione

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12
Q

What is function of StAR [steroidogenic acute regulator protein]?

A

mediates reaction of cholesterol to pregnenolone; induced by high cAMP after binding of ACTH

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13
Q

What parts of adrenal cotex have 21-hydroxylase activity?

A
  • zona glomerulosa [aldosterone]

- zona fasciuclata [cortisol]

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14
Q

What parts of adrenal cortex have 11B-hydoxylase activity?

A
  • zona glomerulosa [aldosterone]

- zona fasciculata [cortisol]

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15
Q

What parts of adrenal cortex have 17a-hydroxylase activity?

A

just the zona glomerulosa

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16
Q

What regulates cortisol and androgen secretion from the adrenal gland?

A

ACTH from pituitary

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17
Q

What regulates aldosterone secretion from zona glomerulosa?

A

JG apparatus in kidney that produces renin –> angiotensin II stimulates adrenal aldosterone secretion

thus high Na; high K; volume depletion increase aldosterone

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18
Q

Where does ACTH come from?

A

synthesized from POMC in pituitary

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19
Q

What 3 proteins are created from POMC in anterior pituitary?

A
  • beta-lipoprotein
  • ACTH
  • melanocyte stimulating hormone [MSH]
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20
Q

What is action of cortisol?

A 
stimulates conversion of AA to glucose = gluconeogenesis
lipolysis
proteolysis
increased BP
increased insulin resistance
21
Q

Is cortisol anabolic or catabolic?

A

catabolic

22
Q

What is effect of high levels of cortisol?

A
  • central weight gain
  • Na and H2O retention
  • suppression of inflammation and immune responses
  • inhibition of fibroblasts
  • loss of connective tissue
  • thin skin
  • easy bruising
  • impaired wound healing
  • growth failure in kids
  • decreased Ca absorption
  • osteoblast inhibition
  • bone loss
23
Q

When is cortisol highest?

A

has a circadian rhythm –> highest amount in early AM; lowest in late PM

24
Q

What are three sources of cholesterol for adrenal steroid hormone synthesis?

A
  • LDL from blood that is internalized
  • cholesterol generated de novo in cortex from acetyl CoA
  • HDL
25
Q

What causes the increased pigmentation in Addison’s disease?

A

ACTH binding to melanocortin-2 receptor

26
Q

What are some things that stimulate cortisol secretion?

A
  • stress
  • circadian rhythm
  • inflammatory cytokines
27
Q

What are the main actions of aldosterone?

A
  • increases Na reabsorption
  • excretes K and H
  • increased intravascular volume
28
Q

What stimulates secretion of aldosterone?

A
  • RAAS by high vascular volume or high Na
  • increased sympathetic activity
  • hyperkalemia
  • ACTH = very minor effect
29
Q

What is path of action of cortisol/aldosterone?

A

bind receptor –> translocate to nucleus –> bind cofactors and hormone-response elements in promotors of target genes –> enhance transcription

30
Q

What is the difference hormone-response elements [HREs] of aldosterone vs coritsol?

A

they are identical

31
Q

What determines specificity of cortisol vs aldosterone effects since they have such similar structure?

A

aldosterone receptors [mineralocorticoid receptors = MR] = expressed heavily in kidney

MR-expressing cells in kidney express high levesl of 11-beta-hdroxysteroid-dehydrogenase [11-beta-HSD] so they convert cortisol to cortisone which cannot bind the MR

32
Q

What adrenal androgens are produces?

A
  • DHEA, DHEA-S, and delta-4-androstenedione

= weak androgens; converted peripherally to more potent androgens

33
Q

What is effects of high adrenal androgens in males vs females?

A

males = insignificant b/c have more potent androgens

females: can cause hirsuitism or virilization at high level

34
Q

What is cushings disease?

A

ACTH-secreting pituitary adenoma causing overproduction of cortisol

35
Q

What is cushings syndrome?

A

syndrome of excess cortisol; can be exogenous or endogenous cause

36
Q

What are clinical manifestations of cushings syndrome?

A
  • hypertension
  • obesity
  • moon facies
  • truncal obesity
  • buffalo hump
  • hyperglycemia
  • skin changes [thinning/striae]
  • osteoporosis
  • amenorrhea
  • immune suppression
  • muscle weakness
  • hirsuitism
37
Q

What are two major classes of cause of cushings disease?

A

ACTH dependent = include pituitary tumors, ectopic ACTH production

ACTH independent = adrenal cortical neoplasm, exogenous glucocorticoid administration

38
Q

What are 2 most common sources of ectopic ACTH production?

A

carcinoid tumors and small cell cancers of lung

39
Q

What are the four screening tests for cushings syndrome?

A
  • 24 hours urinary free cortisol
  • midnight salivary or serum cortisol [should be low]
  • dexamethasone suppression test
  • CRH stimulation test
40
Q

What happens to ectopic ACTH in dexamethasone suppression test?

A

ectopic secretion will not increase with CR b/c pituitary ACTH is suppressed

41
Q

What does high dose dexamethasone suppression test tell you?

A

give dexamethasone at bedtime and check AM coritsol the next morning

if its not suppressed –> ectopic ACTH secretion

if its suppressed –> cushings disease [pituitary adenoma]

42
Q

What does low vs high ACTH with cushings symptoms tell you?

A

low ACTH = tells you probably adrenal tumor

high ACTH = either cushing disease or other ectopic ACTH secretion

43
Q

What does CRH stimulation test tell you?

A

increase in ACTH/cortisol with CRH –> cushing disease [pituitary adenoma]

no increase in ACTH/cortisol with CRH –> ectopic ACTH secretion

44
Q

What is petrosal vein sampling?

A

compare levels of ACTH in the petrosal veins vs periphery

if source is pituitary –> higher ACTH in petrosal than periphery

but be bilateral and simultaneous

> 3:1 central: peripheral to establish pituitary source of ACTH

> 2:1 from one side to other to lateralize pituitary tumor

45
Q

What is treatment for cushings syndrome?

A

if adrenal tumor: remove
if pituitary tumor: try removal or treat with focused radiation

medical: give ketoconazole [glucocorticoid synthesis inhibitor] or glucocorticoid receptor antagonist [mifepristone]

46
Q

What is problem with doing adrenalectomy for cushings?

A

cures cushings but causes addisons

47
Q

What is problem with radiation therapy for pituitary tumor?

A

has delayed therapeutic effects and may cause panhypopoituitarism

48
Q

What is mech of action mifespristone?

A

glucocorticoid receptor antagonist; to treat cortisol excess

49
Q

What is mech of action ketoconazole?

A

inhibits glucocorticoid synthesis

Endocrine (21 decks)

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