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Flashcards in Adrenal structure and function Deck (52):
1

Where are the adrenal glands located?

Above the kidneys

2

What are the layers of the adrenal gland (5)?

Medulla
Zone reticularis (cortex)
Zone fasciculata (cortex)
Zona glomerulosa (cortex)
Capsule

3

What adrenohormones are produced in the cortex?

Zona gomerulosa=mineralocorticoids (aldosterone)
Zona fasciculata=glucocorticoids (cortisol)
Zona reticularis= androgens

4

What adrencortical hormones are produced in the medulla?

Catecholamines (adrenaline and noradrenaline)

5

What is the function and control of the zona glomerulosa?

Outer layer
Minerolocorticoid (aldosterone)
Function: salt
Control: renin

6

What is the function and control of the zona fasciculata?

Middle layer
Glucocorticoid (cortisol)
Function=sweet
Control=ACTH

7

What is the function and control of the zona reticulata?

Inner layer
Sex steroids (DHEA, DHEAS)
Function=sex
Control ACTH

8

What is the function and control of the medulla?

Adrenaline/ noradrenaline
Function=fight or flight
Control=sympathetic nervous system

9

What is adrenocorticotropic hormone (ACTH)?

Hormone produced in the anterior, or front pituitary Gland in the brain. Regulates levels of cortisol

10

Describe the structure of steroid hormones

All derived from cycopetanoperhydrophenanthrene (all have 3 cyclohexane rings and a single cyclopentane ring)

11

What is the purpose of the HPA axis?

Regulation of glucocorticoid secretion

12

Describe the HPA axis

CRH (from hypothalamus) -> ACTH release (anterior pituitary) -> cortisol release (from adrenal cortex) -> cortisol -ve feedback on CRH and ACTH.

13

1. How does stress affect HPA axis?
2. What effect does cortisol have on the immune system

1. People who are stressed have overactive HPA axis
2. Decreases immune response

14

What are the systemic effects of cortisol release?

Gluconeogenesis
Protein mobilisation
Fat mobilisation
Decreased inflammation

15

1. How does cortisol levels affect sleep
2. How may this be affected

1. Cortisol levels are low at night to promote sleep
2. Cushing’s disease (excess cortisol), cortisone treatment, chronic stress, diurnal variation lost in Cushing syndrome (test for high midnight cortisol), night shifts, jet lag, exogenous steroids

16

How is aldosterone regulated?

RAAS
Aldosterone can be increased due to: increased ang II, increased potassium, increased ACTH, decreased sodiu

17

Describe the process of aldosterone regulation

Dehydration/Na+ deficiency/haemorrhage -> decreased blood vol. and pressure -> juxtagomerular cells increase renin -> angiotensinogen converted to ang I -> ACE (lungs) converts Ang I to Ang II -> adrenal cortex increases aldosterone (also vasoconstriction of arterioles) -> kidneys increase Na+ and H2O reabsorption and increased H+ and K+ secretion -> blood vol and pressure return to normal

18

What are the functions of aldosterone?

Increased Na+ and H2O reabsorption to increase blood vol.
Increase K+ and H+ secretion

19

What are the effects of aldosterone?

Increase renal tubular re-absorption of sodium and secretion of potassium
Increases ECF volume
Increases arterial pressure

20

What is the significance of the structures of glucocorticoids and mineralocorticoids?

They look similar due to ring structure
Cortisol can act as a mineralocorticoid and bind to these receptors and cause similar effects to aldosterone

21

1. What prevents cortisol binding to mineralocorticoid receptors
2. What are the issues with this
3. Why is this clinically important

1. 11 beta-HSD2 inactivates cortisol to cortisone so prevents it binding to mineralocorticoid receptors
2. Serum conc of cortisol is 2000X of aldosterone so if too much cortisol it can escape the effects of 11 beta-HSD2
3. In adrenal insufficiency don’t give mineralocorticoid if giving corticosteroids

22

1 What food in high concentrations can cause apparent mineralocorticoid excess?
2. What condition may apparent mineralocorticoid excess be seen in?

1. Liquorice as it can inhibit 11 beta-HSD2
2. Cushing’s

23

Give examples of
1. Active steroids
2. Inert steroids

1. Cortisol, corticosterone, prednisolone
2. Cortisone, 11-dehydrocorticosterone, prednisone

24

What are the effects of glucocorticoids?

Gluconeogenesis (type II diabetes)
Inhibit protein synthesis
Increase protein breakdown (muscle wasting in Cushing’s sydrome)
Stimulate lipolysis
Immunologic and inflammatory responses (delayed wound healing)

25

What are corticosteroids?

Refers to both glucocorticoids and mineralocorticoids but often used as a synonym for glucocorticoid

26

What is phaeochromocytoma?

Rare tumour of adrenal gland that results in too much adrenaline and noradrenaline being produced. Difficult to detect due to short half live of adrenaline and noradrenaline. Urine catecholamines or metanephrins are measured instead

27

What is the role of the adrenal medulla?

Catecholamines released in response to exercise or imminent danger
Adrenaline 80% / noradrenaline 20%
These have a half life of 2 minutes
Fight or flight response

28

Describe the fight or flight response?

Increased HR
Vasoconstriction
Bronchiole dilation
Increased metabolism

29

What is Addison’s disease?

Primary adrenal insufficiency/hypoadrenaism-insufficient cortisol

30

What is Conn’s syndrome?

Primary aldosteronism/hyperaldosteronism-excess aldosterone

31

What is Cushing’s disease?

Benign tumour (adenoma) forms in pituitary glands causing excessive release of ACTH and elevated cortisol production (excess cortisol)

32

What is
1. Primary adrenal insufficiency
2. Secondary adrenal insufficiency
3. Tertiary adrenal insufficiency

1. Problem with adrenal gland
2. Lack of ACTH
3. Lack of CRH

33

Give an example of primary adrenal insufficiency

Addison’s disease
120 per million
80% due to auto-immune adrenalitis
75% have positive antibodies
50% have other autoimmune conditions (pernicious anaemia, Grave’s disease, type I diabetes)

34

What are the signs and symptoms of Addison’s disease?

Hyperpigmentation in gums
Skin creases
Low BP
Weakness
Weight loss
Nausea/diarrhoea/vomiting/constipation/abdominal pain
Vitiligo

35

What are the signs and symptoms of adrenal crisis?

Fever
Syncope
Convulsions
Hypoglycaemia
Hyponatraemia
Severe vomiting and diarrhoea

36

What are the causes of Addison’s disease?

Autoimmune
Infection (TB, fungal, CMV)
Infiltration (metastasis, lymphoma, amyloidosis)
Infarction (thrombophilia)
Haemorrhage (meningococcal septicaemia, pseudomonas, anticoagulants (Waterhouse-Frederichsen syndrome=meningococcal sepsis with bilateral adrenal haemorrhage)
Adrenoleukodystrophy (ALD)=inherited, affects genes responsible for peroxisome activation so damage adrenal gland, brain, myelin

37

What is Adrenal crisis/addisonian crisis?

Hormonal factor precipitating adrenal crisis is mineralocorticoid not glucocorticoid
Manifests as hypotensive shock
Rarely hypoglycaemic
Total loss of adrenocortical function causes death in 3 days-2 weeks

38

What is the immediate treatment for adrenal crisis?

Fluids 1-3L of 0.9% saline in first 12-24 hours
Hypoglycaemia: IV dextrose
Glucocorticoids: hydrocortisone 100mg stat, 100mg IV 6 hourly
Precipitating cause should be treated

39

What is the long term treatment of adrenal crisis?

Hydrocortisone-10mg morning, 5mg lunch, 5mg evening (difficult to mimic circadian rhythm)
Fludrocortisone 100mcg daily
Androgen replacement: DHEA 25-50mg daily
In secondary adrenal insufficiency HPA axis suppression means dose should be reduced gradually

40

What is the sick day rules for adrenal crisis?

Never stop steroids
Double dose during illness/infection
If unable to take PO hydrocortisone, need IM/IV hydrocortisone
Carry steroid card/medicAlert bracelet

41

What is secondary adrenal insufficiency?

HPA axis suppression due to long term steroid use
Pituitary/hypothalamic disease
Clinical presentations similar but no hyperpigmentation, no dehydration or hyperkalaemia, hypoglycaemia is more common

42

What is Cushing’s syndrome/

Prolonged exposure to elevated levels of glucocorticoids
Most commonly due to exogenous corticosteroid use
Suppression of HPA axis which can las years

43

What are the symptoms of Cushing’s syndrome?

Acne
Moon face
More body and facial hair
Weight gain
Purple striae
Pendulous abdomen
Slow wound healing
Ecchymosis
Thin skin and subcutaneous tissue
Thin extremities with muscle atrophy
Supraclavicular fat pad
Buffalo hump
Red cheeks
Thinning of hair

44

What is the difference between Cushing’s sydrome and Cushing’s disease?

Sydrome=due to any cause of hypercortisolism
Disease=ACTH producing pituitary adenoma causing hypercortisolaemia

45

What are the types of Cushing’s syndrome?

ACTH dependent (pituitary adenoma, 60-70%, ectopic ACTH production)

ACTH independent (majority due to exogenous steroids 80-90%, adrena adenomas/carcinomas 10-20%)

46

What is a differential diagnosis for Cushing’s

Pseudo Cushing’s states

47

What can cause high CRH

Stress
Alcoholism
Depression
Obesity
Anorexia
Bulimia

48

How do you make a diagnosis of Addison’s disease?

Random cortisol-levels are variable through day so may miss it

9am cortisol- cortisol <100nmol=insufficiency

Short syncathen / ACTH stimulation tests (definitive test used)

49

What is short synacthen test?

0 mins-sample for cortisol at baseline then give synthetic ACTH (synacthen) injection IM of IV
30 mins-take sample for cortisol
Normal response is 30 min cortisol >540 nmol/L

50

How is Cushing’s screened for?

24 hr urine rest, measuring free cortisol
1mg overnight dexamethasone suppression test
Midnight serum cortisol (not really used)
Late night salivary cortisol

51

Describe the overnight dexamethasone suppression test?

1mg dexamethasone at 11pm
9am measure cortisol
Normal=<50nmol/L
Sensitivity 98%
False positives
Decreased absorption
Increased dexamethasone clearance (anti-convulsants)
Increase in CBG (oestrogen)
Pseudo-Cushing’s states

52

What are other associated laboratory abnormalities with adrenal disease?

Raised WBC
Hyperglycaemia
Hypokalaemia metabolic alkalosis