Clinical Aspects of the Adrenal Gland Flashcards
The common approach to assessing a clinical suspicison to the adrenal gland
Testing for assessing functional status - is it functioning? - it is primary or secondary? What is the cause? If it is a tumour - can it be removed? - is additional chemo or radiotherapy required?
An abnormality of cortisol, aldosterone, insulin and vasopressin can cause what?
HTN
Endocrine causes of HTN
Primary hyperaldosteronism (unilateral adenoma, bilateral hyperplasia) Phaechromocytoma Cushings syndrome Acromegaly Hyperparathyroidism Hypothyroidism Congenital adrenal hyperplasia
Most common cause of endocrine cause of HTN
Primary hyperaldosteronism
Presentation of Cushing’s syndrome
Central obesity HTN Glucose intolerance Hirsutism Amenorrhea / impotence Purple striae Plethoric facies Easily bruise Osteoporosis Personality changes Acne Oedema Headache Poor wound healing Thin skin ulcers Pendulous breasts and abdomen Moon face
Why do people put on weight in cushing’s disease?
Muscle atrophy is replaced by fat
Causes of cushing’s syndrome
Corticosteriod Tx for e.g. asthma, IBD
ACTH-dependent
- 75% pituitary tumour (disease)
- 5% ectopic ACTH secretion (e.g. lung carcinoid)
ACTH-independent
- 20% of cases; adrenal tumour (adeno or carcinoma)
What tests are done to screen for hypercortisolism?
Overnight Dex test
24 hour urine Free cortisol
What is a DEX test?
Dexamethasone Suppression test
Measures how cortisol levels change in response to an injection of dexamethasone.
Dexamethasone provides negative feedback to the pituitary gland to suppress ACTH
How is hypercortisolism confirmed?
24 urine free cortisol
Low dose dexamethasone suppression test
Low dose vs high dose Dex Tests
Low dose suppresses cortisol in individuals who have no pathology in endogenous cortisol production
A high dose exerts negative feedback on pituitary neoplastic ACTH producing cells (cushing’s disease) but not on ectopic ACTH producing cells or adrenal adenoma (cushing’s syndrome)
How would you test if the hypercortisolism is ACTH dependent or not?
Paired morn-midnight ACTH cortisol
How would you localise where the hypercorticolism was coming from?
MRI sella turnica
CT adrenal glands
BIPSS
CT chest
How would you know if the ACTH had to do with the pituitary or not in hypercorticolism?
High dose dex test
What is conn’s syndrome?
Primary hyperaldosteronism
What does conn’s syndrome result in?
Decreased renin
Retention of sodium and loss of potassium, leading to HTN
What tests are used to screen for Conn’s syndrome?
PAC
PA/PRA Ratio
If the PA/PRA ratio = > 20, what does this indicate?
Primary hyperaldosteronism (conns syndrome)
If the PA/PRA ratio = <20, what could this indicate?
(Less reliable)
Secondary hyperaldosteronism
Essential hypertension
What does PRA stand for?
Plasma renin activity
What does PAC stand for?
Plasma aldosterone concentration
Confirmatory tests for Conns syndrome
24 hour urine aldosterone > 12 ug/day
Urinary sodium > 200mEq/day during 4 days of salt loading
How do you establish the aldosterone source in conns syndrome?
CT scan of adrenal glands
Upright posture test
Plasma 18-hydroxycorticosterone
Adrenal venous sampling if CT scan inconclusive of discordant with posture test
Presentation of phaemochromocytoma
Hypertension (persistent in 70%) Headache Sweating Palpitations Tremor Pallor Anxiety/fear
How much of phaemochromocytoma is inherited and what genes are implicated?
30%
Genes - RET
Familial syndromes - MEN-2, VHL, NF1, PGL
How would you test if clinical suspicion of phaemochromocytoma?
24 hour urine
- total metanephrines
- catecholamines
- plasma metanephrines
How would you localise a phaemochromocytoma?
Adrenal/abdominal MRI/CT scan
Causes of addisons disease
Autoimmune destruction Invasion Infiltration Infection Infarction Iatrogenic
What is addisons disease?
Primary adrenal insufficiency - hypocortiolsim and hypoaldosteronism
Pathology of autoimmune Addison’s disease
+ve adrenal autoantibodies (to 21-OHase) in 70%
lymphocytic infiltrate of adrenal cortex
Assosiated diseases with autoimmune addison’s
Thyroid disease (20%) T1DM (15%) Premature ovarian failure (15%)
Presentation of primary adrenal failures
Weakness Fatigue Anorexia Weight loss Nausea and vomiting Hyperpigmentation/Skin pigmentation (especially palmar creases) or vitiligo Loss of pubic hair in women Hypotension Hypoglycaemia Hyponatraemia and hyperkalaemia may be seen Unexplained vomiting or diarrhoea Salt craving Postural symptoms
Causes of primary adrenal insufficiency
Addison’s disease
Adrenal enzyme defects - congenital adrenal hyperplasia
What is vitiligo?
Pale white patches develop on the skin
Clues to the diagnosis of adrenal failure
Disproportion between severity of illness and circulatory collapse/hypotension/dehydration Unexplained hypoglycaemia Other endocrine features - hypothyroidism - body hair loss - amenorrhoea Previous depression or weight loss
Investigations to diagnose adrenal insufficiency
U + Es, glucose, FBC
Random cortisol
Synacthen test and basal ACTH
What value of random cortisol shows that it is not addisons?
> 700 nmol/l
What is synacthen?
Synthetic ACTH
What would be ideal in a synacthen test If all is working?
A rise in cortisol level
> 500 = reassuring
What would happen in a synacthen test to diagnose primary adrenal failure?
If impaired cortisol response and ACTH > 200ng/l
If plasma ACTH is fine, what does this show?
Adrenal problem
Pituitary response is fine
If plasma ACTH is low, what does this show?
A problem with the pituitary response
Examples of glucocorticoid replacements
Hydrocortisone
Prednisolone
Dexamethasone
Doses of glucocorticoid replacements
Given in doses to mimic normal diurnal variation
What synthetic steroid is given in mineralocorticoid replacement?
Fludrocortisone
What circumstances should treatment be altered when on steroid treatment?
Minor short lived illness or stress (double glucocorticoid dose)
Major illness or operation (IV medications)
Self care rules for patients on steriods
Never miss steroid doses
Double the hydrocortisone dose in the event of intercurrent illness (e.g. flu, UTI)
If severe vomiting or diarrhoea call for help without delay (may need IM)
What are over 90% of the cases of congenital adrenal hyperplasia due to?
21-hydroxylase deficiency
Results of 21-hydroxylase deficiency
Congenital adrenal hyperplasia Neonatal salt losing crisis Ambiguous genitalia Pseudo-precocious puberty (boys) Hirsutism (women)
Investigations for conns syndrome
Random aldosterone:renin ratio
Saline suppression test
Scan the adrenals
Adrenal vein sampling
What is conns syndrome?
Hyperaldosteronism
What is a saline suppression test?
The patient is given saline IV, after which the measures of renin and aldosterone are measured
If have conns syndrome, what would be the result of the saline suppression test?
Aldosterone high
Renin is low
What is deficient in congenital adrenal hyperplasia?
21 hydroxylase
What type of inheritance is congenital adrenal hyperplasia?
Autosomal recessive
Symptoms of congenital adrenal hyperplasia
Virilising
Salt wasting
How is congenital adrenal hyperplasia measured for?
Precursors can be measured from a heel prick test
Treatment of congenital adrenal hyperplasia
Stop ACTH
Bring androgens down
- hydrocortisone
- sometimes fludrocortisone
Why could congenital adrenal hyperplasia be late onset?
Autosomal recessive
Hirsituism - men wouldn’t be found or would just go unnoticed
What medicine can be used in PCOS that is also used in DM?
Metformin
What is spironolactone?
Aldosterone antagonist
Anti-androgen
S/Es of spironolactone
Gynaecomastia
Erectile dysfunction
What is hirsituism a result of?
Increased androgen production
Examples of causes of hirsituism
PCOS
Adrenal carcinoma
Causes of purple abdominal striae
Cushings syndrome
Pregnancy
Anyone putting on weight quickly
When should cortisol be measured to get the most accurate reading?
At midnight to see when it should be lowest - sleeping midnight cortisol (serum)
What can cortisol be measured from?
Urine
Serum
Saliva
When would a dexamethasone suppression test be done?
When you suspect overproduction of ACTH from the pituitary
What does a dexamethasone suppression test do?
Switches off pituitary ACTH
When is dexamethasone given and when thereafter is the cortisol measured?
Given at night
Cortisol measured in morning
What is the normal response to a dexamethasone suppression test and to what level?
Cortisol should drop
< 50
If the dexamethasone test is higher than normal, what should be done next?
A higher dose
Causes of Cushings syndrome
Steroids
Cushings disease
Ectopic ACTH production
Adrenal adenomas
Effects of hypercortisolaemia
Impaired insulin tolerance
Hyperglycaemia
T2DM
What are cortisol readings often?
Unhelpful
What would you measure if you suspected the problem was coming from the pituitary?
ACTH
Why can CRH still be tested even in Cushings disease?
Still has a slight sensitivity to CRH
What size are the pituitary adenomas often in cushings disease?
Tiny
What is BIPSS?
Gradient between venous drainage and the peripheral blood +/- CRH injection
What ratio does BIPSS look at?
Central ACTH : Peripheral ACTH
What is the cut off for BIPSS?
> 2.0
Treatment of cushings disease
Metyrapone
Pituitary transphenoidal microadenomectomy
Hydrocortisone post op
What does metyrapone do?
Reduces enzymes in the adrenal gland to decrease glucocorticoid production
Why is hydrocortisone given post op?
In case there has been damage to surrounding tissue as could get adrenal crisis post op
What is the initial remission rate of cushings disease?
70 - 80%
What is the permanent cure rate of cushings disease?
60-70%
What could be done if a pituitary adenoma causing cushings disease came back?
Bilateral adrenalectomy
Causes of leg cramping at night
Calcium problems
Iron deficiency
Exercise
Circulatory problems
Cause of conns syndrome
Adenoma of adrenal cortex (aldosterone producing unilateral adenoma)
Who gets conns syndrome?
Younger women
Causes of secondary hyperaldosteronism
Increased levels of renin
HF
Liver failure etc
If serum bicarbonate is high, what does this indicate?
Alkalosis
What is another name for the saline suppression test?
Salt loading test
What should happen after the saline suppression test?
Aldosterone should decrease
If after a saline suppression test aldosterone has failed to be suppressed, what is the diagnosis?
Primary hyperaldosteronism
What test is used to exclude renal artery stenosis?
Renal USS
What happens before a tumour develops in any gland?
Hyperplasia
Over production
Causes of primary hyperaldosteronism
Acquired bilateral adrenal hyperplasia
Conns syndrome
Glucocorticoid suppressive hyperplasia
Who gets acquired bilateral adrenal hyperplasia?
Older men and women
What is the purpose of adrenal venous sampling?
To demonstrate the source of aldosterone
How does adrenal venous sampling work?
Put catheter into adrenal veins and put in ACTH
Cortisol and adrenaline responses are looked at
Right versus left are looked at
Peripheral vs inside the gland are looked at
Tells us if bilateral or unilateral
Treatment of conns syndrome
Spironolactone
or
Epllerelone
Why is epperelone a good alternative to spironolactone?
Does not have anti androgen effects
What is amiloride?
A K+ sparing diuretic `
What does POMC stimulate?
MSH
ACTH
What does excess MSH result in?
Scar pigmentation
What is a decreased cortisol effect on POMC?
POMC decreases
What treatment should be done immediately before diagnosis when suspect addisons crisis?
IV hydrocortisone
Causes of primary hypoaldosteronism
Autoimmune adrenalitis (addisons) TB Adrenal haemorrhage Adrenal metastases Fungal infections Others e.g. CAH, iatrogenic
What is the most common cause of primary hypoaldosteronism?
Addisons (autoimmune adrenalitis)
What is the most common cause of primary hypoaldosteronism worldwide?
TB
What gets pigmented in Addisons?
Gums
Scars
Hands
Skin (tanned)
Treatment of addisons
Steroids; hydrocortisone, fludrocortisone
What is hydrocortisone replacing?
Glucocorticoids
What is fludrocortisone replacing?
Mineralcorticoids
What must be done to the dose of steroids treating addisons if ill?
Dosage doubled 24 or 48 hours
Injection available if vomiting
Why can short syncathen test be used in both primary and secondary hypoaldosteornism?
As adrenal atrophy occurs in 2ndry
What happens in the long term for people with secondary hypoaldosteronism?
Adrenal atrophy
What is the level of Na in secondary hypoaldosteronism? Why?
Decreased
Increased levels of vasopressin (due to increased CRH) - which is an ACTH releaser - causing H20 retention and dilutional hyponatraemia
How to distinguish between primary and secondary?
ACTH levels
Causes of hypercalcaemia
Metastatic disease Sarcoidosis Primary hyperthyroidism Hyperparathyroidism Myeloma Addisons
What is the effect of decreased Ca on PTH?
Increased PTH
Causes of decreased Ca
Vit D deficient
Malabsorption
What can too much calcium in the kidneys lead to?
Kidney stones
What can you check for calcium to monitor the kidneys?
Urine calcium
What do gastrinomas lead to?
Gastric duodenal ulceration
Features of Addisonian crisis
Collapse
Shock
Pyrexia
Causes of hypoadrenalism
Addisons (autoimmune) TB Metastases (e.g. bronchial carcinoma) Meningococcal septicaemia (waterhouse friederichsen syndrome) HIV Antiphosopholipid syndrome Pituitary disorders - tumours - irridation - infiltration Exogenous glucocorticoid therapy
1ry vs 2ndry addisons hyperpigmentation
1ry yes
2ndry no
3 features of conns syndrome
- HTN
- Alkalosis
- Hypokalaemia (muscle weakness)
Features of Addisonian crisis
Hyponatraemia
Hypoglycaemia
Hyperkalaemia
Treatment of phaeochromocytoma
- Phenoxybenzamine FIRST (non selective a blocker)
2. BBs
What is NOT required in the treatment of Addisonian crisis?
IV fludrocortisone
Treatment of Addisonian crisis
IV hydrocortisone
What is nelsons syndrome?
Occurs due to rapid enlargement of pituitary corticotroph adenoma (ACTH producing adenoma) that occurs after the removal of both adrenal glands (bilateral adrenalectomy)
Pathology of nelsons syndrome
Removal of both adrenals leads to the elimination of production of cortisol, and the lack of cortisols -ve feedback can allow any pre existing adenomas to grow unchecked.
What can spironolactone cause?
Gynaecomastia
How to treat an Addisonian patient if they are unwell
Double hydrocortisone dose
Fludrocortisone dose can stay the same
