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Gabe's Endocrinology > Adrenocortical function and dysfunction > Flashcards

Adrenocortical function and dysfunction Flashcards

1
Q

What constitutes the adrenal glands?

A

Adrenal cortex and medulla - 2 endocrine glands of different embryological origin that fused during development.

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2
Q

What is the adrenal medulla?

A

A modified sympathetic ganglion the secretes catecholamines - neurohormones.

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3
Q

What is the adrenal cortex?

A

A true endocrine gland; secretes steroids - classical hormones.

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4
Q

What are the 3 different layers to the adrenal cortex?

A

Zona glomerulosa, fasciculata and reticularis.

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5
Q

What do each of the different zones of the adrenal cortex secrete?

A
  • Glomerulosa: aldosterone
  • Fasciculata: glucocorticoids
  • Reticularis: sex hormones
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6
Q

Where are sex hormones secreted from?

A

Zona reticularis and fasciculata

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7
Q

Which sex hormones are secreted from the adrenal cortex?

A

Androgens, estrogens, dehydroepiandosterone (DHEA)

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8
Q

Where are glucocorticoids secreted from?

A

Zona fasciculata and reticularis

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9
Q

Which glucocorticoids are secreted from the adrenal cortex?

A

Cortisol, stimulated by: HPAA, ACTH tropic to ZF&ZR

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10
Q

Where are the mineralocorticoids secreted from the adrenal cortex?

A

Glomerulosa only

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11
Q

Which mineralocorticoids are secreted from the adrenal cortex?

A

Aldosterone

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12
Q

What is aldosterone secreted stimulated by?

A

RAAS & plasma K+

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13
Q

Why do cells produce different steroids?

A

Because they have different enzymes

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14
Q

What is the precursor to corticosteroid?

A

Progesterone

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15
Q

What is the precursor to oestradiol?

A

Testosterone and estrone

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16
Q

Why can steroids have crossover effects?

A

Because different steroids are chemically related

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17
Q

What is the HPA pathway for the control of cortisol secretion?

A

CRH from hypothalamus stimulates anterior pituitary to release ACTH which stimulates adrenal cortex to release cortisol.

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18
Q

What stimulates the hypothalamus to release CRH?

A

Circadian rhythm and stress

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19
Q

Where does cortisol act? What does it do at these sites?

A
  • Immune system (suppression)
  • Liver (gluconeogenesis)
  • Muscle (protein catabolism)
  • Adipose tissue (lipolysis).
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20
Q

How is cortisol release inhibited?

A

By cortisol negatively feeding back to anterior pituitary and hypothalamus.

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21
Q

What is CRH?

A

Corticotropin releasing hormone

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22
Q

What is ACTH?

A

Adrenocorticotropic hormone

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23
Q

What does CRH mediate other than release of ACTH?

A
  • Effects on inflammation and immune responses
  • Inhibition of appetite
  • Signals the onset of labour
  • Appears linked to several mood disorders
  • Urocortin: brain neuropeptide ↓ appetite
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24
Q

What is POMC?

A

Pro‐opiomelanocortin: a large protein that yields several bioactive peptides by proteolysis

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25
Q

What are some of the peptides produced by proteolysis of POMC?

A
  • ACTH and beta‐endorphin in the anterior pituitary
  • Alpha-MSH outside the pituitary
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26
Q

What is beta-endorphin?

A

Pain perception blocker

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27
Q

What is alpha-MSH?

A

Melanocyte‐stimulating hormone: ↓ food intake & ↑ skin melanin

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28
Q

What are the melanocortins?

A
  • Family name for the MSH hormones and ACTH
  • The effects of the peptides depend on which melanocortin receptor subtypes are stimulated
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29
Q

What does cortisol help the body cope with?

A

Long-term stress

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30
Q

How does cortisol protect against hypoglycaemia?

A

By stimulating catabolism of energy stores

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31
Q

What is cortisol permissive for?

A

For glucagon & catecholamine actions

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32
Q

When are the peaks and troughs of the diurnal rhythm?

A
  • Peaks morning
  • Low night
33
Q

What does cortisol promote in the liver?

A

Gluconeogenesis

34
Q

What does cortisol cause in the muscle?

A

Breakdown of skeletal muscle proteins - substrate for gluconeogenesis.

35
Q

What effect does cortisol have on adipose tissue?

A

Enhances lipolysis – FA for energy

36
Q

What effect does cortisol have on the immune system?

A

Suppresses the immune system

37
Q

What effect does cortisol have on calcium?

A
  • Causes negative calcium balance
    • ↓absorption, ↑excretion, bone breakdown
38
Q

What effect does cortisol have on the brain?

A

Influences brain function –mood, memory, learning

39
Q

What are the effects of cortisol being used as a therapeutic drug?

A
  • Suppresses the immune system
  • Inhibits the inflammatory response
  • Some specific uses
    • Bee stings, poison ivy, and pollen allergies
    • Prevents rejection of transplanted organs
40
Q

What does long-term use of cortisol result in?

A

Inhibition of ACTH secretion and atrophy of cortisol‐secreting cells - taper doses gradually.

41
Q

Is cholesterol made on demand or stored?

A

Made on demand.

42
Q

What is the half-life of cortisol?

A

60-90 minutes

43
Q

What factors affect the release of cortisol?

A

Circadian rhythm of tonic secretion; stress enhances release

44
Q

Where is the receptor for cortisol located?

A

Intracellularly

45
Q

What is the action of cortisol at the molecular level?

A

Initiates transcription, translation and new protein synthesis.

46
Q

What are the 3 major adrenal cortex disorders resulting from hypersecretion?

A
  • Hyperaldosteronism
  • Excess Cortisol (Cushing’s syndrome)
  • Excess Androgen & Estrogen (adrenogenital syndrome)
47
Q

What are the 2 types of hyperaldosteronism?

A
  • Primary hyperaldosteronism (Conn’s syndrome)
  • Secondary hyperaldosteronism (RAS)
48
Q

What do the 2 types of hyperaldosteronism cause?

A

Cause hypernatremia, hypokalaemia, hypertension

49
Q

What are the different causes of excess cortisol (Cushing’s syndrome)?

A
  • Primary adrenal cortex tumors that autonomously secretes cortisol
  • Secondary pituitary tumor that autonomously secretes ACTH (Cushing’s disease)
  • Hyperstimulation (CRH, ACTH)
  • Iatrogenic (physcian caused) hypercortisolism – treat with cortisol therapy
50
Q

What does excess cortisol (Cushing’s syndrome) cause?

A

Glucose excess, protein shortage, abnormal fat distribution

51
Q

What causes excess Androgen & Estrogen (adrenogenital syndrome)?

A
  • Lack enzyme in cortisol steroidogenic pathway
  • Inappropriate masculinisation in all but adult males
52
Q

How is excess Androgen & Estrogen (adrenogenital syndrome) treated?

A

With glucorticoids - repairs glucorticoid deficit and inhibits ACTH (reducing steroid secretion)

53
Q

What are the signs and symptoms of Cushing’s syndrome (hypercortisolism)?

A
  • Excess gluconeogenesis causes hyperglycemia; mimics diabetes
  • Muscle protein breakdown, lipolysis causes wasting
  • Paradoxical fat deposits in trunk & face due to ↑appetite
    • Thin arms & legs, trunk obesity, “moon face”
    • Stretched skin due to fat depots causes reddish purple striae
  • Mineralocortocoid action of excess glucocorticoid
    • Salt & water retention, “moon face”, weakness, hypertension
  • Osteoporosis
  • Mood elevation then depression, difficult learning & memory
54
Q

What is the primary pathology that can lead to hypercortisolism (Cushing’s syndrome)?

A

Primary secretion due to problem with adrenal cortex: CRH and ACTH low (due to cortisol inhibitory feedback) Cortisol levels high.

55
Q

What are the secondary pathologies that can lead to hypercortisolism (Cushing’s syndrome)?

A
  • Secondary secretion due to hypothalamic or pituitary problem.
  • Hypothalamic: high CRH, ACTH and cortisol.
  • Pituitary: low CRH, high ACTH and cortisol.
56
Q

What is cortisol hyposecretion due to?

A

Adrenocortical insufficiency

57
Q

What is Addison’s disease?

A

Primary adrenal insufficiency - autoimmune destruction of adrenal cortex.

58
Q

What happens in Addison’s disease?

A
  • Autoimmune destruction of adrenal cortex
  • Hyposecretion of all adrenal steroid hormones
  • ↓Aldosterone
  • K+ retention → Cardiac arrhythmias
  • Na+ depletion → hypotension
  • ↓Cortisol
  • ↓stress response & hypoglycaemia
59
Q

What hereditary problems can cause cortisol hyposecretion?

A

Adrenal steroid enzyme defects - lack of cortisol & aldosterone causes ↑ androgens & adrenogenital syndrome

60
Q

What happens in secondary cortisol hyposecretion?

A
  • Deficient cortisol only:
    • Abnormal hypothalamus or pituitary
    • ↓ACTH & ↓cortisol only (normal aldosterone)
61
Q

What is the embryological origin of the adrenal medulla?

A

Modified part of SNS

62
Q

What happens in the adrenal medulla?

A

Modified postganglionic sympathetic neurons (chromaffin cells) secrete neurohormones (catecholamines).

63
Q

What are the 3 catecholamines?

A
  • Adrenaline (only made in adrenal medulla)
  • Noradrenaline
  • Dopamine
64
Q

What are secretions from the adrenal medulla stimulated by?

A

Preganglionic sympathetic neurons.

65
Q

What is the precursor to dopamine?

A

DOPA

66
Q

What converts tyrosine to DOPA?

A

Tyrosine hydroxylase

67
Q

What converts DOPA to dopamine?

A

Amino acid decarboxylase

68
Q

What converts dopamine to noradrenaline?

A

Dopamine-beta-hydroxylase

69
Q

What converts noradrenaline into adrenaline?

A

PNMT

70
Q

Where is PNMT found outside of the CNS?

A

In the adrenal medulla

71
Q

What are the adrenomedullary hormone actions on flight-or-fight responses?

A

↑cardiac rate and contractility, ↑TPR, ↑BP

72
Q

What are the adrenomedullary hormone actions on metabolic effects?

A

↑glucose & FFA, ↑BMR

73
Q

What are the adrenomedullary hormone actions on central effects?

A

↑arousal & alertness

74
Q

What are the adrenomedullary hormone actions on stress responses?

A
  • Physical
  • Psychological
75
Q

Have there been any recognised hyposecretion disorders of the adrenal medulla?

A

No

76
Q

What is adrenomedullary hypersecretion disorder?

A
  • Pheochromocytomas (tumor)
  • Rare
  • Potentially deadly (hypertension)
  • Treatment: removal
77
Q

What role does stress play in cortisol secretion?

A
  • Nonspecific stimuli (“stressors”) disrupt homeostasis
  • Two types of stress elicit two responses
    • Acute stress results in the fight‐or‐flight reaction
    • Chronic stress elevates cortisol levels, which suppresses immune responses
78
Q

What is the MoA of stress on the hypothalamus?

A

See image.

Gabe's Endocrinology (17 decks)

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