Adrenal glands Flashcards
Where are the adrenal glands located?
Above the kidneys
What are the three major layers of the adrenal gland?
Capsule
Adrenal cortex
Adrenal medulla
What are the three zones of the adrenal cortex (list from out to in).
Zona glomerulosa
Zona fasciculata
Zona Reticularis
What does the zona glomerulosa produce?
Mineralocorticoids such as aldosterone
What does the zona fasciculata produce?
Glucocorticoids such as cortisol
What does the zona reticularis produce?
Adrenal androgens such as testosterone
What is the precursor for all products of the adrenal cortex?
Cholesterol
How does cholesterol proceed through the metabolism?
Straight down to aldosterone
Diverted off to cortisol precursors
Cortisol precursors to cortisol or androgen precursors
Androgen precursors to androgens
How is cortisol and androgen release regulated?
By ACTH release from the anterior pit
What is the negative feedback for cortisol release?
Cortisol inhibits hypothalamus and ant pit
What effects does cortisol have on circulation and renal efficiency?
Increase CO and BP
Increase renal blood flow and GFR
What effects does cortisol have on metabolism?
Increase blood sugar
Increase lipolysis and central redistribution
Increase proteolysis
What effects does cortisol have on the CNS?
Mood lability
Euphoria/psychosis
Decrease libido
What effects does cortisol have of bone and connective tissue?
Increase osteoporosis
Decrease serum Ca
Decrease collagen formation
Decrease wound healing
WHat effects does cortisol have on the immune system?
Decrease cap dilation
Decrease leukocyte migration
Decrease macrophage activity
Decrease inflammatory cytokine production
What are the clinical uses of cortisol?
Suppress inflammation
Suppress immune system
Replacement therapy
How much cortisol is used in replacement therapy?
Enough to restore normal levels
How much cortisol is used in suppression therapy?
> 10x dose used in replacement
How should you give steroids?
PO if well
IV/IM if unwell
How is aldosterone release regulated?
RAAS
Describe RAAS
Drop in BP stim renin release
Renin converts angiotensinogen to angiotensin I
ACE converts angiotensin I to angiotensin II
Angiotensin II stim aldosterone release
What effect does aldosterone have?
Increases Na retention in kidneys therefore increasing BP
What are the two broad categories of adrenal dysfunction?
Hypo and hyper production
What two areas of the adrenal gland are affected by adrenal insufficiencies?
Cortex and medulla
What are some common causes for primary adrenal insufficiencies?
Infection- TB/HIV Autoimmune Tumours Haemorrhage- Waterhouse-Friderichsen syndrome Genetic defects
What two forms of adrenal insufficiency affect the adrenal cortex?
Primary
Secondary
What is an adrenal insufficiency of the adrenal MC producing area of the adrenal gland called?
Addison’s disease
What is the most common cause of Addison’s disease?
Autoimmune destruction
What other autoimmune diseases is Addison’s disease linked with?
T1DM
Autoimmune thyroiditis
How does Addison’s disease present?
Anorexia/weight loss Fatigue DIzziness Low BP Abdo pain Vomiting Diarrhoea Skin pigmentation (due to elevated ACTH levels)
How do you treat Addison’s disease?
Fludrocortisone- if suspect Addison’s treat as such until proven otherwise.
How does adrenal insufficiency tend to present?
Anorexia/weight loss Fatigue DIzziness Low BP Abdo pain Vomiting Diarrhoea Skin pigmentation (due to elevated ACTH levels)
What blood chemistry would you see in Addison’s disease?
Low Na High K Hypotension Raised renin Low aldosterone
What blood chemistry would you see in adrenal insufficiency?
Low Na High K Hypotension Hypoglycemia Raised renin Low aldosterone Raised ACTH levels
How do you diagnose Addison’s disease/adrenal insufficiency?
Synacthen test
How do you do a synacthen test?
Give ACTH and check cortisol levels at: 0, 30, 60 and 90 mins. Baseline should be >250nmol/l. Should rise to >550nmol/l
Give a genetic cause of adrenal insufficiency
Congenital adrenal hyperplasia (CAH)
What are some causes of secondary causes of adrenal insufficiency?
Excessive exogenous steroid
Pit problems resulting in lack of ACTH
What is the most common cause of secondary adrenal insufficiency?
Exogenous steroids
How does secondary adrenal insufficiency present?
Weight loss/ Anorexia Fatigue Dizziness Abdo pain Vomiting Diarrhoea
How do you treat secondary adrenal insufficiency?
Treat underlying cause
Hydrocortisone
How should you administer hydrocortisone?
Large does in morning
Small does at lunch
Nothing after as will cause sleep problems
What is an excess of cortisol called?
Cushing’s syndrome
What can cause Cushing’s syndrome?
Pit adenoma- Cushing’s disease (too much ACTH)
Ectopic ACTH/CRH production
Adrenal adenoma/carcinoma
Nodular hyperplasia
Iatrogenic- too much exogenous steroid atrophying adrenal glands.
How can Cushing’s present?
Interscapular fat pad Thin skin/ bruising Proximal muscle wasting/thin arms and legs Central obesity Moon face Striae- dark colour/purple
What signs can you get in Cushing’s?
Hypertension Osteoporosis- rare in obesity Hyperglycemia Poor wound healing Infections Eye problems
How do you diagnose Cushing’s?
Overnight dexamethasone suppression test
Low dose dexamethasone suppression test
Urine free cortisol test
How do you do an overnight dexamethasone suppression test?
1mg dexa at midnight and cortisol test at 8am
<50 is normal and >100 is abnormal
What is the best test for diagnosis Cushing’s?
Low dose dexa suppression test
How do you do a low dose dexa suppression test?
0.5mg dexa every 6 hours
<40 is normal
What is a normal result in a urine free cortisol test?
<250
How do you differentiate between primary and secondary Cushing’s?
Primary ACTH<1
Secondary pit origine <300
Secondary ectopic origine >300
How do you treat Cushing’s?
Treat underlying cause
Metyrapone
Ketoconazole
What is Cushing’s disease?
Pit adenoma producing too much ACTH leading to Cushing’s syndrome
What two forms of hyperaldosteronism can you have?
Primary/Conn’s syndrome
Secondary
What causes secondary hyperaldosteronism?
Decrease blood flow to the kidneys increasing aldosterone release.
What causes primary hyperaldosteronism?
Adenoma or hyperplasia of adrenal glands.
Remember not all nodules are significant!!!
What is primary hyperaldosteronism?
Autonomous production of aldosterone
What is another term for primary hyperaldosteronism?
Conn’s syndrome
How does primary hyperaldosteronism present?
Hypertension
Hyperkalemia
Alkalosis
Raised BP
How do you diagnose hyperaldosteronism?
Confirm aldosterone excess by doing:
Ratio of plasma aldosterone and renin. If ratio raised diagnose subtype
How do you diagnose the subtype of hyperaldosteronism?
CT imaging
Adrenal vein sampling (use cortisol as a control)
How do you treat primary hyperaldosteronism?
Remove underlying cause (only in the young)
Spironolactone
What causes Congenital Adrenal Hyperplasia?
The loss of an enzyme in the metabolism of cholesterol to steroids
What is the most commonly lost enzyme in CAH?
12alpha hydroxylase
What does the loss of 12alpha hydroxylase do?
Inability to produce aldosterone or cortisol so direct metabolites down testosterone route
What are some symptoms of CAH?
Addison’s style symptoms
Early puberty in males
Ambiguous female genitalia
Poor weight gain
How do you diagnose CAH?
Genetic testing
Synacthen test but look for 17-OH progesterone
How do you treat CAH?
Give GC and MC replacement
Correct physical abnormalities
Is the loss of the adrenal medulla much of a problem?
No as catecholamines (adrenaline etc) are made elsewhere too.
What is a major cause of adrenal medulla overaction?
Phaeochromocytoma
What is pheochromocytoma?
Tumour derived from chromaffin cells in the adrenal medulla
What is another name for the pheochromocytoma?
10% tumour
What is a common triad of symptoms in pheochromocytoma?
Hypertension- labile or postural
Paroxysmal (fast on/off) sweating
Headaches
What are some of the symptoms of pheochromocytoma?
Hypertension- labile or postural Paroxysmal (fast on/off) sweating Headaches Pallor Tachycardia Hyperglycemia Low K Lactic acidosis
How do you diagnose pheochromocytoma?
24h urine catecholamines
Plasma catecholamines at time of symptoms
What do you have to do once you’ve diagnosed pheochromocytoma?
ID the source- MRI or MIBG (radio uptake) to do this
How do you ID where a pheochromocytoma is?
MRI or MIBG (radio uptake)
How do you treat pheochromocytoma?
Treat underlying cause
Alpha and beta blockers
Always give alpha first
What is pheochromocytoma often associated with?
MEN2
VHL
Succinate dehydrogenase B and D mutations
Neurofibromatosis
What is an extra adrenal gland source of excessive catecholamine production?
Extra adrenal paraganglioma
Where can extra adrenal paragangliomas be found?
Anywhere in the sympathetic chain
In panhypopituitarism what is the most important hormone to replace?
Cortisol
Why does ACTH not tend to be measured directly?
Needs to be sent to lab on ice and processed ASAP
What time of day and how often should cortisol replacement be given?
Large dose in morning
Smaller dose at lunch
Nothing in evening or won’t sleep
What do you need to monitor when taking fludrocortisone and why?
Blood chemistry and BP to check not retaining too much salt
What is an Addisonian crisis?
Symptomatic Addison’s- especially with low BP
How do you treat an Addisonian crisis?
Fluid and hydrocortisone
Why can you use hydrocortisone to treat and Addisonian crisis?
Because GC have a degree of efficacy at MCR.
What should you do to their medication if a patient receiving cortisol replacement therapy is ill?
Minor illness- double dose and keep doubled for 24hrs after illness
Major illness- Double dose and wean off after
How do you treat Conn’s disease?
Spironolactone
What is Conn’s disease?
Primary hyperaldosteronism
How does Conn’s disease present?
Raised BP and Na
Low K
What does Metyrapone do?
Block GC production
What two kind of steroids can the adrenal gland produce?
Glucocorticoids
Mineralocorticoids
How do GCs work?
Bind to nuclear receptors which can then form a dimer with the help of +Glucocorticoid Recognition Element or bind to nGRE remain as a monomer
Are GC monomers and dimers active?
Monomer inactive
Dimer active
Are GCs restricted to acting on just their own receptors?
No, they can act on MCR too
What negative effects can activation of the GCR have?
Increase feeding
Increase alcohol cravings
What negative effects can actions of the GC on the MCR have?
Skin atrophy and poor wound healing
How can you mitigate GCR effects on alcohol cravings?
By giving the morning after pill
What does a solid mass in the adrenal gland suggest?
Metastasis- lung met most common
