Adrenals Flashcards
What does the adrenal cortex do
Produced steroids -
Glucocorticoids e.g. cortisol, which affect carbohydrate, lipid, and protein metabolism
Mineralocorticoids - aldosterone, which control sodium and potassium balance
Androgens - sex hormones which have a weak effect until peripheral conversion to testosterone and dihydrotestosterone
Layers of the adrenal cortex
G - glomerulosa - mineralocorticoids
F - fasiculata - glucocorticoids
R - reticularis - androgens
How does the adrenal cortex become stimulated
Corticotropin releasing factor - from hypothalamus stimulates ACTH release from ant pit
That stimulates cortisol and androgen production
How is cortisol excreted
Urinary free cortisol various 17-oxogenic steroids
What is Cushing’s syndrome
Clinical state produced by chronic glucocorticoid excess and loss of normal feedback mechanisms of the HPA axis And loss of the circadian rhythm of cortisol release - inc release on waking
What are the main causes of Cushing’s syndrome
Exogenous steroids - iatrogenic and used by patient for other purposes
The other main type is ACTH producing pituitary adenoma -
Cushings disease
Rarer: adrenal adenoma, carcinoma producing cortisol
Cancers such as small cell lung ca and carcinoid tumours producing ACTH which acts on the adrenals inc cortisol
What are the symptoms of Cushing’s syndrome
Weight gain, mood change (depression, lethargy, irritability, psychosis), proximal weakness, gonadal dysfunction (irregular menses, hirsutism, erectile dysfunction), acne, recurrent Achilles’ tendon rupture, occasionally virilisation if female - become more masculine looking
Signs of cushings
Central obestity, plethoric, moon face, buffalo hump, supraclavicular fat distribution, skin and muscle atrophy, bruises, purple abdominal striae, osteoporosis, inc glucose, infection prone , poor healing,
Tests not done in cushings
Random cortisol as it affected by many things
Such as time of day, illness, stress
Also imaging cannot be relied upon and adrenal incidentalomas do not cause any problems in many but many have them and same with some pituitary adenomas and some ACTH producing micro adenomas are too small to be seen on scans
Tests done in investigating suspected Cushing’s syndrome
1) find a raised cortisol
Then you do tests that localise where the cortisol is coming from
1st line tests
-Overnight dexamethasone suppression test
1mg dexamethasone PO midnight do serum cortisol at 8 am
Normally cortisol would be suppressed below 50 but in Cushing’s syndrome it is not
- 24 hr urinary free cortisol alternative
2nd line tests
-48hr dexamethasone suppression test
Give measure cortisol at 0 and 48 hr- no suppression seen so still high
-48hr high dose dexamethasone suppression test
Pituitary (there would be suppression) from other ectopic (no suppression)
-midnight cortisol - blood or saliva at midnight cortisol should be lowest but in cushings the circadian rhythm is lost therefore may still be high
Localisation tests
If 1st and 2nd line +ve then do plasma ACTH- if undetectable = adrenal adenoma - CT/MRI adrenals
If ACTH detectable distinguish pituitary from ectopic - high dose suppression or CRH test - cortisol rises with pit disease not ectopic
What to do if cushings disease found as the pituitary is implicated
MRI/CT of the pituitary and consider bilateral inferior petrosal blood sampling
What to do if an ectopic cause is indicated as the reason for the Cushing’s syndrome
Hunt for the source
CT chest abdo pelvis
MRI neck thoracand abdo
Hunting small cell lung and small carcinoid tumours
What is Addison’s disease
Primary adrenocortical insufficiency
Rare can be fatal
There is destruction of the adrenal cortex leading to glucocorticoid and mineralocorticoid deficiency
Causes of Addison’s disease
In the Uk autoimmune Other causes TB - commonest worldwide Adrenal mets Lymphoma Opportunity infections in HIV Adrenal haemorrhage Anti-phospholipid syndrome Congenital - late onset CAH
What is the cause of secondary adrenal insufficiency
Commonest cause is iatrogenic due to long term steroid use
Which suppresses the HPA
Only becomes apparent on steroid withdrawal
Rare - HP disease leading to dec ACTH
Symptoms of Addisons disease
Lean Tanned Tired Tearful \+/-weakness, anorexia, dizzy, faint, flu-like, myalgia, arthralgia Mood depressed GI N/V abdo pain diarrhoea, constipation
Signs of Addison’s disease
Hyperpigmented palmar creases and bucks mucosa
Inc ACTH, cross reacts with melanin receptors postural hypotension
Vitilogo
Biochemistry of Addison’s disease
Low Na+ High K+ - due to low mineralocorticoid - aldosterone Low glucose - due to cortisol Uraemia Inc Ca2+ Eosinophilia Anaemia
What test doe you do for Addison’s disease
Short synacthen test
Do plasma cortisol half hour before synacthen given if 30 min cortisol over 550 Addison’s can be excluded
9am ACTH inappropriately high >300
How to assess mineralocorticoid status
Plasma renin and aldosterone
Tx Addison’s
Replace the steroids
15-25mg daily
Fludrocortisone to correct the mineralocorticoid
Adjust on clinical grounds
What should steroid users wear
Bracelet declaring steroids use
Advice when sick in Addison’s disease
Double dose
What is hyperaldosteronism
Excess production of aldosterone, independent of the renin-angiotensin system
What does hyperaldosteronism cause
Inc sodium and water retention and dec renin release
When to consider hyperaldosteronism
High BP, hypokalaemia, or alkalosis in someone who is not on diuretics
Symptoms of hyperaldosteronism
Often asymptomatic o signs of hypokalaemia
Weaknesss cramps, parasthesia, polyuria, polydipsia, inc BP but not always
Causes of hyperaldosteronism
Solitary aldosterone producing adenoma linked to mutations in K+ channels this is conns syndrome
Bilateral adrenocortical hyperplasia
Rare- carcinoma, GRA hereditary where aldosterone gene becomes under the control of ACTH
Syndrome associated with hyperaldosteronism
Conns syndrome
Tests in hyperaldosteronism
U&E Renin aldosterone Adrenal vein sampling Genetic - GRA
Tx conn’s
Laparoscopic adrenalectomy
Spironolactone for 4 weeks pre-op controls BP and K+
Tx of hyperplasia
Treated medically spironolactone or amiloride
Tx of GRA
Dexamethasone normalises biochemistry but not alway BP if high use spironolactone as an alternative.
Tx adrenal carcinoma
Surgery +/- post-op adrenolytic therapy with mitotane - prognosis is poor
What is secondary hyperaldosteronism
Due to high renin from dec renal perfusion e.g. renal artery stenosis, accelerated hypertension, diuretics, CCF or hepatic renal failure
What is Bartters syndrome
This is a major cause of congenital (autosomal recessive) salt wasting - via sodium and chloride leak into the loop of henle via mutations in channels and transporters.
Presents in childhood with failure to thrive, polyuria, polydipsia
Sodium loss leads to volume depletion, causing inc renin and inc aldosterone production. Leading to hypokalaemia, and metabolic acidosis
Tx - k+ replacement, NSAIDS (to inhibit prostaglandins) and ACEi
What is a phaeochromocytoma
Rare catecholamine producing tumour
arise from sympathetic para ganglia cells
Which are collections of chromaffin cells
Usually found in the adrenal medulla
Are phaeochromocytoma not found in the adrenals
No Xtra adrenal They are rare Often found in the formation of the aorta the organs of zuckerkandl 10% extra adrenal
Can phaeochromocytoma metastasise
Yes 10% do
Are phaeochromocytoma familial
10% are
FHx crucial can be offered genetic testing as some gene mutations have been shown to inc risk
What is the classic triad iof phaeochromocytoma
Episodic headache, sweating,and tachycardia
+/- deranged up down or normal BP
Tests for phaeochromocytoma
24hr urine metanephrines
Plasma metanephrines
Inc WCC
Imaging MRI/CT abdo pelvis
Tx of phaeochromocytoma
Surgery
Remove
Need to prep with an alpha blockade and then beta blockade
This is to prevent crisis from unopposed alpha adrenergic stimulation
