Flashcards in Adrenal structure and function Deck (52):
Where are the adrenal glands located?
Above the kidneys
What are the layers of the adrenal gland (5)?
Zone reticularis (cortex)
Zone fasciculata (cortex)
Zona glomerulosa (cortex)
What adrenohormones are produced in the cortex?
Zona gomerulosa=mineralocorticoids (aldosterone)
Zona fasciculata=glucocorticoids (cortisol)
Zona reticularis= androgens
What adrencortical hormones are produced in the medulla?
Catecholamines (adrenaline and noradrenaline)
What is the function and control of the zona glomerulosa?
What is the function and control of the zona fasciculata?
What is the function and control of the zona reticulata?
Sex steroids (DHEA, DHEAS)
What is the function and control of the medulla?
Function=fight or flight
Control=sympathetic nervous system
What is adrenocorticotropic hormone (ACTH)?
Hormone produced in the anterior, or front pituitary Gland in the brain. Regulates levels of cortisol
Describe the structure of steroid hormones
All derived from cycopetanoperhydrophenanthrene (all have 3 cyclohexane rings and a single cyclopentane ring)
What is the purpose of the HPA axis?
Regulation of glucocorticoid secretion
Describe the HPA axis
CRH (from hypothalamus) -> ACTH release (anterior pituitary) -> cortisol release (from adrenal cortex) -> cortisol -ve feedback on CRH and ACTH.
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
What are the systemic effects of cortisol release?
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
How is aldosterone regulated?
Aldosterone can be increased due to: increased ang II, increased potassium, increased ACTH, decreased sodiu
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
What are the functions of aldosterone?
Increased Na+ and H2O reabsorption to increase blood vol.
Increase K+ and H+ secretion
What are the effects of aldosterone?
Increase renal tubular re-absorption of sodium and secretion of potassium
Increases ECF volume
Increases arterial pressure
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
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
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
Give examples of
1. Active steroids
2. Inert steroids
1. Cortisol, corticosterone, prednisolone
2. Cortisone, 11-dehydrocorticosterone, prednisone
What are the effects of glucocorticoids?
Gluconeogenesis (type II diabetes)
Inhibit protein synthesis
Increase protein breakdown (muscle wasting in Cushing’s sydrome)
Immunologic and inflammatory responses (delayed wound healing)
What are corticosteroids?
Refers to both glucocorticoids and mineralocorticoids but often used as a synonym for glucocorticoid
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
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
Describe the fight or flight response?
What is Addison’s disease?
Primary adrenal insufficiency/hypoadrenaism-insufficient cortisol
What is Conn’s syndrome?
Primary aldosteronism/hyperaldosteronism-excess aldosterone
What is Cushing’s disease?
Benign tumour (adenoma) forms in pituitary glands causing excessive release of ACTH and elevated cortisol production (excess cortisol)
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
Give an example of primary adrenal insufficiency
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)
What are the signs and symptoms of Addison’s disease?
Hyperpigmentation in gums
What are the signs and symptoms of adrenal crisis?
Severe vomiting and diarrhoea
What are the causes of Addison’s disease?
Infection (TB, fungal, CMV)
Infiltration (metastasis, lymphoma, amyloidosis)
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
What is Adrenal crisis/addisonian crisis?
Hormonal factor precipitating adrenal crisis is mineralocorticoid not glucocorticoid
Manifests as hypotensive shock
Total loss of adrenocortical function causes death in 3 days-2 weeks
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
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
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
What is secondary adrenal insufficiency?
HPA axis suppression due to long term steroid use
Clinical presentations similar but no hyperpigmentation, no dehydration or hyperkalaemia, hypoglycaemia is more common
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
What are the symptoms of Cushing’s syndrome?
More body and facial hair
Slow wound healing
Thin skin and subcutaneous tissue
Thin extremities with muscle atrophy
Supraclavicular fat pad
Thinning of hair
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
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%)
What is a differential diagnosis for Cushing’s
Pseudo Cushing’s states
What can cause high CRH
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)
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
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
Describe the overnight dexamethasone suppression test?
1mg dexamethasone at 11pm
9am measure cortisol
Increased dexamethasone clearance (anti-convulsants)
Increase in CBG (oestrogen)