HPA axis and adrenal hormones Flashcards

1
Q

What is the adrenal axis (hypothalamic-pituitary-adrenal axis)?

A

Complex set of interaction and feedback loops between the hypothalamus, pituitary, and adrenal glands. It regulates the body’s response to stress, immune function, energy expenditure, mood, emotions and libido.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where are the adrenal glands located?

A

Just above each kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the hormones released from the adrenal glands?

A

Cortisol, aldosterone, adrenaline and noradrenaline.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are adrenal glands composed of?

A

Outer cortex and an inner medulla

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are 3 classes of steroid hormones produced and released into the circulation by the adrenal cortex?

A

Mineralocorticoids – mainly aldosterone
Glucocorticoids – mainly cortisol (hydrocortisone)
Androgens – sex hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What does the adrenal inner medulla produce?

A

Adrenaline and noradrenaline through direct control of the hypothalamus.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the effects of adrenaline and noradrenaline?

A

Fight or flight response. Increased heart rate, blood pressure and muscle perfusion.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What ions do steroids have an effect on?

A

Increased Na reabsorption

Increased K secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Aldosterone regulation half-life?

A

20 mins (short)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the two effects that aldosterone is regulated by?

A
Direct
 Indirect (most important)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is direct effects on aldosterone stimulated by?

A

Stimulated by low plasma Na or K (action on zona glomerulosa cell of adrenal cortex)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is indirect effects on aldosterone stimulated by?

A

Stimulated by angiotensin II (renin angiotensin system)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Aldosterone regulation (5)

A
  1. Low blood volume stimulates the release of angiotensin II.
  2. Angiotenis II stimulates the adrenal cortex to produce aldosterone.
  3. Aldosterone has a number of different action including: sodium reabsorption, water reabsorption, potassium excretion]
  4. Aldosterone, therefore, causes a net increase in blood volume
  5. Increased blood volume inhibits the production of angiotensin II via negative feedback.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is aldosterone?

A

A mineralocorticoids that regulates Na and K.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does aldosterone act on to regulate Na and K?

A

Mineralocorticoid receptors in distal tubules increase Na reabsorption and K secretions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the effects of no aldosterone?

A
Low Na and High K
 Leads to depolarization of plasma membrane
 Cardiac arrythmia
 Muscle weakness
 Hypotension
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does adrenal hypersecretion cause?

A

Conn’s syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Symptoms of aldosterone hypersecretion (Conn’s syndrome)

A

Hypertension
High Na
Low K
Oedema (water retention)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Treatment of aldosterone hypersecretion?

A

MR (Mineralocorticoid receptors) antagonist/aldosterone antagonist

  • spironolactone – lack of selectivity leads to side effects
  • Eplerenone – fewer side effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What does adrenal hyposecretion cause?

A

Addison’s syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Symptoms of aldosterone hyposecretion (Addison’s syndrome)

A
Hypotension and vascular collapse
 Low NA dehydration
 High K
 Cardiac arrythmias 
 Potentially fatal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Treatment of aldosterone hyposecretion?

A

Mineralocorticoid agonist

Fludrocortisone – longer half-life than aldosterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Why is aldosterone inappropriate for treatment for hyposecretion?

A

Short aldosterone half-life means it is not used for drug treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What other things use fludrocortisone as treatment?

A

Postural hypotension or symptomatic hypotension treatment involves fludrocortisone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Cortisol half life

A

90 minutes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the three effects that cortisol is regulated by?

A
  • Metabolic (physiological)
  • Anti-inflammatory (supraphysiological)
  • Immunosuppressive (supraphysiological)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What does cortisol act on?

A

Glucocorticoid receptors to regulate transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are the metabolic effects of cortisol?

A
  • Liver - Glucose production (gluconeogenesis)
  • Skeletal muscle - Increase in protein degradation (Increased a.a.)
  • Adipose tissue - Increased lipolysis (Increased free fatty acids and glycerol for gluconeogenesis)
  • Bone - Matrix protein breakdown (Increased a.a. for gluconeogenesis)
  • Mobilisation of energy stores in time of stress
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Where are the metabolic effects of cortisol? (5)

A
  • Liver
  • Skeletal muscle
  • Adipose tissue
  • Bone
  • Mobilisation of energy stores in time of stress
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the metabolic effect in the Liver?

A
  • Glucose production (gluconeogenesis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the metabolic effect in the Skeletal muscle?

A
  • Increase in protein degradation (Increased a.a.)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is the metabolic effect in the Adipose tissue?

A
  • Increased lipolysis (Increased free fatty acids and glycerol for gluconeogenesis)
33
Q

What is the metabolic effect in the Bone?

A
  • Matrix protein breakdown (Increased a.a. for gluconeogenesis)
34
Q

What effects does cortisol have at supraphysiological level?

A

Inhibits chronic and acute inflammation (immunosuppressed)

35
Q

What increases cortisol?

A
Stress as it activates the HPA axis.
 Illness
 Trauma
 Burns
 Surgery
36
Q

When is the most cortisol naturally produced?

A

Morning when you wake up to get you through the day.

37
Q

What does hypercortisolemia cause?

A

Cushing’s syndrome

38
Q

How does Cushing’s syndrome occur?

A

Excess cortisol, usually exogenous corticosteroid use. Endogenous causes include, adrenal or pituitary tumors (Cushing’s disease).

39
Q

What is Cushing’s syndrome?

A
Set of symptoms resulting from exposure 
 to increased levels of cortisol 
 -Endogenous or exogenous sources 
 -Chronic excess 
 -Loss of normal feedback mechanisms 
 -Loss of circadian rhythm of cortisol secretion
40
Q

Diagnosis of Cushing’s syndrome

A

Overnight dexamethasone suppression tests

  • Give dexamethasone at midnight
  • Serum cortisol in morning
  • If normal – dex dose will cause negative feedback/suppression and reduce cortisol level
  • In Cushing’s there is no cortisol suppression
41
Q

Why can you not use a random plasma cortisol?

A

Time, stress and illness can impact level.

42
Q

Cushing’s syndrome 4 effects that cause symptoms

A

Anti-inflammatory and immunosuppressive effects
Mineral corticoid effects
Mood effect
Metabolic Effects

43
Q

Cushing’s syndrome Anti-inflammatory and immunosuppressive effects

A
  • risk of infection

- poor wound healing

44
Q

Cushing’s syndrome Mineral corticoid effects

A
  • hypertension

- oedema

45
Q

Cushing’s syndrome Mood effect

A
  • depression

- Euphoria

46
Q

Cushing’s syndrome Metabolic Effects

A
Lipolysis and fat redisposition
 - Centripedal obesity 
 - Shoulder fat 
 - Moon face 
 Muscle protein degradation - Weakness 
 - Skin transparency 
 Bone protein degradation - Osteoporosis 
 Gluconeogenesis 
 - Diabetes mellitus
47
Q

Latrogenic Cushing’s treatment

A

stop causative medications

48
Q

Tumour Cushing’s treatment

A

surgical removal/radiotherapy

49
Q

Cushing’s treatment Metyrapone (3)

A
  • Inhibitor in adrenal cortex
  • blocks the synthesis of cortisol, can be used pre-op
  • specialist use
50
Q

Cushing’s treatment Ketoconazole

A

May have a direct effect on corticotropic tumour cells in patients with Cushing’s disease

51
Q

What does hypocortisolemia cause?

A

Addison’s Disease

52
Q

How does Addison’s Disease occur?

A

Destruction of the adrenal cortex

53
Q

What is Addison’s Disease?

A

-Reduced production of glucocorticoids such as cortisol), mineralocorticoids (such as aldosterone), and adrenal androgens (such as dehydroepiandrosterone).
The absence or cortisol leads to increased production of adrenocorticotrophic hormone (ACTH) because negative feedback to the pituitary gland is reduced.

54
Q

Diagnosis of Addison’s Disease

A
  • Low Na, high K (due to reduced mineralocorticoid)
  • Low glucose
  • Serum cortisol
  • Short ACTH stimulation test
55
Q

Addison’s - Classification

A
  • Primary – adrenal failure
  • Secondary – pituitary problem with ACTH synthesis
  • Tertiary – hypothalamic problem
56
Q

Addison’s Disease treatment

A
  • Replace steroids

- Specialist input

57
Q

List some symptoms of Addison’s Disease

A
Persistent, non-specific 
 Fatigue 
 Hyperpigmentation 
 Weight loss 
 Loss of appetite 
 Premature satiety 
 Nausea and vomiting 
 Abdominal pain 
 Cravings for salt
 Muscle weakness/cramps 
 Joint pain
 Postural dizziness/hypotension
 Headache 
 Low grade fever 
 Thirst 
 Anxiety and depression
58
Q

When is the highest dose of cortisol replacement (steroids) given?

A

In the morning then reduced throughout the day

59
Q

Why should you not take cortisol replacement (steroids) before bed?

A

It keeps you awake

60
Q

List some symptoms of Adrenal insufficiency

A
Fatigue
 Weight loss
 Failure to thrive (in children)
 Anorexia
 Skin crease hyperpigmentation
 Buccal pigmentation
 Low blood pressure
 Postural hypotension
 Abdominal discomfort
61
Q

List some symptoms of Adrenal crisis

A
Nausea and vomiting
 Severe weakness
 Tachycardia
 Reduced consciousness
 Syncope
 Confusion
 Fever/unexplained pyrexia
 Hypovolemic shock 
 Abdominal guarding/pain
62
Q

What is the physiological level of steroids produced by the body?

A

About 7.5mg a day

63
Q

What happens to the normal adrenal response when steroids are given?

A

It suppresses the adrenal response as the body has been given steroids. About 2-3 weeks of use will completely turn drive off.

64
Q

What happens if steroids stopped abruptly?

A

Adrenal crisis as the body can no longer make own steroids as the mechanism has been switched off.

65
Q

How are steroids weaned?

A

Around 5mg off prednisolone dropped every week to help turn back on natural adrenal production.
For long term users, when they reach 7.5mg you may need to wean slower.

66
Q

Who is at risk of adrenal crisis?

A

People with Addison’s
People on steroids
They are steroid dependent.

67
Q

When may a patient require higher doses of steroids?

A

Patients with adrenal insufficiency that before acutely ill, or trauma/surgery as they body is under more stress.

68
Q

What is the blanket rule for acutely unwell patients that have adrenal insufficiencies?

A

Sick days = double steroids

69
Q

What corticosteroid does not put you into adrenal crisis?

A

Fludrocortisone, as it regulates sodium and water for BP.

70
Q

What is important for steroid users?

A

Steroid emergency card so it is known in emergency situations.

71
Q

What is the hormone that stimulates the cortisol release?

A

ACTH

72
Q

Short Synacthen test (SST)

A

Chemically similar drug to ACTH administered at night
Plasma cortisol measured in the morning.
A normal function will show a rise

73
Q

Why does a normal function will show a rise in cortisol (SST)?

A

Stimulated ACTH, stimulated adrenal cortex to release cortisol.

74
Q

What can make it hard to interpret SST?

A

Someone who is on steroids as their cortisol level will already be up.

75
Q

What other drugs may be considered for someone who is on steroids?

A

Bone pretension and GI protection

76
Q

What dose of tablet are usually used to give steroid users who are weaning?

A

5mg as you can easily change dose, and not a risk of over/under dose. (5 tablets -> 4 tablets etc)

77
Q

What are the anti-inflammatory effects of cortisol used for?

A
  • Asthma
  • Topical inflammatory conditions
  • Autoimmune disease/ transplants
  • Neoplastic disease of lymphocytes (e.g.Hodgkins disease)
  • Transplant rejection
78
Q

What receptor do the steroids act on for anti-inflammatory effect for conditions such as asthma?

A

Glucocorticoids receptor (GR), drugs with high affinity to GR are effective anti-inflammatory and immunosuppressive agents.