Adrenals Flashcards
What are the 3 zones of the adrenals and what do they produce?
GFR
Gets sweeter as you go deeper
Outer zone - zona glomerulus - produces aldosterone
Middle zone - zona fasiculata - produces cortisol
Inner zone - zone reticularis - produces sex steroids
Adrenal hormones are derived from …
Cholesterol
ACTH activates enzyme that converts cholesterol to pregnenolone –> aldosterone, cortisol, testosterone
Low aldosterone results in …
Lose Na+, lose water, hold onto K+ , hold onto hydrogen ions
= Hypovolaemia, hypotension, metabolic acidosis
Low cortisol results in …
Life threatening hypotension
What happens in CAH i.e. 21-hydroxylase deficiency?
21-hydroxylase deficiency –> defective conversion from 17-OHP to 11-deoxycortisol –> high 17-OHP –> high testosterone (shunt production towards testosterone)
How to diagnose CAH i.e. 21-hydroxylase deficiency?
High serum 17-OHP (screening test for suspected CAH)
ACTH stimulation test is gold standard confirmatory test
Give ACTH –> further rise in 17-OHP
What’s the difference between Classic adrenal hyperplasia and Non-classic adrenal hyperplasia?
Both are due to 21-hydroxylase deficiency
Classic adrenal hyperplasia
- More severe form
- 0% 21-hydroxylase activity –> 0 aldosterone and cortisol production. All production shunted towards testosterone.
- Present in infancy with adrenal insufficiency and salt wasting. Females have ambiguous genitalia.
Non-classic adrenal hyperplasia
- Less severe form and more common
- 50% 21-hydroxylase activity –> reduced aldosterone and cortisol production and high testosterone
- No salt wasting
- Present in adolescent/young women as premature puberty, acne, hirsutism, irregular menses/amenorrhoea (similar to PCOS). Females have normal genitalia.
- High serum 17-OHP + testosterone
What happens in 11-hydroxylase deficiency?
11-hydroxylase deficiency –> defective conversion from 11-deoxycorticosterone (weak mineralcorticoid activity) to corticosterone and 11-deoxycortisol (limited activity) to cortisol
Get overproduction of androgens
= females get ambiguous genitalia
= Hypernatraemia, hypokalaemia, hypertension due to increased mineralcorticoid activity from 11-deoxycorticosterone
How to diagnose 11-hydroxylase deficiency?
High serum 11-deoxycortisol
High androgens
If diagnosis is uncertain, can do ACTH stimulation test - would expect both to go up
Rx 11-hydroxylase deficiency
Cortisol replacement
Antihypertensives
Are adrenal masses generally benign?
Yes
Increases with age
Common incidental finding
Usually don’t produce hormones
What do we worry about when we see bilateral adrenal masses?
Metastasis
DDx adrenal masses
Adrenal adenomas - 75% non-functioning
Pheochromocytoma
Adrenal corticoid carcinoma
Metastasis
What characteristics in an adrenal mass point towards it being benign?
Small, usually ≤3cm, ≥6cm needs investigation
Homogenous texture, ≤10 housefield units tend to be benign. >10HU more likely to be ACC, pheo, mets
Round/oval, smooth margins
Usually solitary, unilateral (bilateral suggests mets)
Minimally vascular on CT (ACC, pheo, mets usually vascular)
High washout rate (compaerd to ACC, pheo, mets)
Isointense in relation to liver on MRI (others are hyperintense)
No necrosis, haemorrhage or calcification
Stable or very slow growth
What investigations might you do for an adrenal mass?
Non-contrast CT adrenals
1mg dexamethasone suppression test - give 1mg dex the night before then check cortisol at 8am. If high cortisol, it means the adrenal is producing it without ACTH
Aldosterone renin ratio - high aldosterone and suppressed renin tell us the adrenals are producing aldosterone on their own
Fasting plasma metanephrines - to exlude pheo
Should we biopsy adrenal masses?
No
Due to risk of spread if adrenal corticoid carcinoma
What tests to do in bilateral adrenal hyperplasia?
Serum 17-hydroxyprogesterone
When to do an adrenalectomy when there is an adrenal mass?
Suspect malignancy or if there is cortisol excess
Unilateral >6cm size
If 4-6cm, may choose to monitor growth every 6-12 months and consider surgery if growth is fast.
High aldosterone leads to…
Holds onto Na+, water, loses K+, hydrogen ions
= hypervolemia, hypertension, hypokalaemia, metabolic alkalosis
Causes of primary hyperaldosteronism
Bilateral adrenal hyperplasia (most common)
Adrenal adenoma (Conn syndrome)
Adrenal corticoid carcinoma (rare)
What drugs can affect aldosterone renin ratio?
Any antihypertensives (works by volume depletion or vasodilation) –> increase renin
Low potassium –> decreases aldosterone
High potassium –> increases aldosterone
Aldosterone antagonists e.g. spironolactone, amiloride, epleronone
How does AKI affect aldosterone renin ratio?
AKI –> fluid and salt retention –> decrease renin
What’s the seated saline suppression test?
Give sodium loading –> expect aldosterone to go down –> if it doesn’t, you know its autonomous production = primary aldosteronism
What’s adrenal venous sampling and when do you do it?
Insert catheter through groin –> to left and right adrenal vein –> measure cortisol and aldosterone
Tells us which adrenal gland is the problematic one or whether its both
Right adrenal vein drains into….
Left adrenal vein drains into….
Right adrenal vein drains into IVC
Left adrenal vein drains into left renal vein
Rx primary aldosteronism
Aldosterone antagonist - spironolactone, epleronone, amiloride
Adenomas are usually surgically resected
Prognosis of adrenal corticoid carcinoma
Poor
5 year survival <15%
How does adrenal corticoid carcinoma present?
1) Excess hormones
Usually 2+ hormones
Cortisol > androgens
2) Flank mass/pain
3) Incidental finding on imaging
- Very big - >6cm
- Heterogenous
Rx adrenal corticoid carcinoma
1) Surgical resection
2) Mitotane
- Causes adrenal necrosis
- Improves survival and recurrence
3) Chemotherapy
- Slightly better progression of disease but no effect on survival
Causes of secondary hyperaldosteronism
Renal artery stenosis
Fibromuscular hyperplasia in young people
Atherosclerosis in old people
Renal artery stenosis –> activation of the juxtaglomerular apparatus –> release renin –> converts angiotensinogen to ACEI –> ACEII –> activate adrenal gland to release aldosterone
What would you expect the renin and aldosterone to be in secondary hyperaldosteronism?
High renin and aldosterone
What would you expect the renin and aldosterone to be in primary hyperaldosteronism?
Low renin and high aldosterone
When does cortisol level peak?
Morning
Causes of high cortisol
Stress e.g. infection, trauma
Starvation/anorexic nervosa
Pregnancy
Alzheimer’s
Pseudocushing’s syndrome
Glucocorticoid resistance
Prenatal glucocorticoid excess
Pituitary tumour (Cushing’s disease)
Ectopic ACTH source e.g. small cell carcinoma
Adrenal tumour
Exogenous glucocorticoid
What’s pseudocushing’s syndrome?
High cortisol but no tumour
Related to depression, ETOH excess or can be idiopathic
Lack of progression of Cushing’s features
Clinical features of Cushing’s
Proximal muscle weakness
Moon facies, central adiposity, buffalo hump
Abdominal striae (>1cm pathognomonic for pregnancy or Cushing)
Hypertension + hypokalaemic + metabolic alkalosis (at very high levels, cortisol cross reacts with mineralcorticoid receptors)
Osteoporosis
Immunosuppression (late) especially prone to cellulitis
Diagnostic approach to suspected Cushing’s disease
1) 24h urine cortisol or midnight salivary cortisol level or low dose dexamethasone test
2) Plasma ACTH
If low ACTH –> CT adrenals
If high ACTH
–> do high dose dexamethasone test (will tell us whether ACTH is coming from hypothalamus or ectopic)
–> CRH stimulation test - give CRH then measure ACTH and cortisol. Pituitary adenomas will respond by releasing more ACTH and cortisol. Ectopic source of ACTH and adrenal adenomas will not respond.
–> IPSS if both tests are inconclusive.
What do you expect the adrenal glands to look like in excess exogenous glucocorticoids?
Bilateral adrenal atrophy (due to shut down of ACTH)
What do you expect the adrenal glands to look like in ACTH secreting pituitary adenoma (Cushing’s)?
Bilateral adrenal hyperplasia
What do you expect the adrenal glands to look like in ectopic ACTH secretion?
Bilateral adrenal hyperplasia
What do you expect the adrenal glands to look like in primary adrenal adenoma?
One adrenal has adenoma/carcinoma
The other is atrophied (due to it being shut down by low ACTH)
OR
Bilateral adrenal hyperplasia
Rx persistent Cushing’s
Irreversible options
Surgery
Radiotherapy
Mitotane
Reversible options Pasireotide Cabergoline Ketoconazole Metyrapone IV etomidate (emergency) Mifepristone
What happens in 17-hydroxylase deficiency?
Decreased androgens and cortisol
- Primary amenorrhoea and lack of pubic hair in females
- Pseudohermaphroditism in males
Get increased weak mineralcorticoid (11-DOC) –> hypertension, mild hypokalaemia. Low aldosterone.
Rx for 21-hydroxylase deficiency
Mineralcorticoids
Glucocorticoids
Rx for 17-hydroxylase deficiency
Glucocorticoids
Sex steroids
Causes of adrenal insufficiency
Acute
- Abrupt withdrawal of steroids
- Adrenal haemorrhage
- Pituitary problem (secondary adrenal insufficiency) - pituitary tumour, tumour of the hypothalamic-pituitary region, pituitary radiation, lymphocytic hypophysitis
- Hypothalamus problem (tertiary adrenal insufficiency)
Chronic (Addison’s)
- Autoimmune destruction (associated with other autoimmune disease such as Hashimoto’s thyroiditis)
- TB, HIV
- Metastatic carcinoma e.g. from lung
- Congenital - congenital adrenal hypoplasia, ACTH resistance
Clinical features of adrenal insufficiency
Low cortisol –> hypotension, weakness, diarrhoea, vomiting, abdo pain, hypoglycaemia
Postural hypotension is a very specific sign - drop BP, raised HR on standing
Low mineralcorticoids –> lose water, lose Na+, retain K+, keep hydrogen ions –> hypovolaemia, hyponatraemia, hyperkalaemia, metabolic acidosis
Features of high ACTH –> stimulates melanocytes –> hyperpigmentation (takes time)
What clinical feature helps distinguish primary from secondary adrenal insufficiency?
Hyperpigmentation from too much ACTH (primary insufficiency)
Rx adrenal insufficiency
1) hydrocortisone or cortisone or pred
- Don’t give dex as it doesn’t have mineralcorticoid effect.
2) Fludrocortisone
- Monitor electrolytes, renin
Symptoms of adrenal crisis
Cardinal symptom is hypotension
Anorexia, nausea, vomiting, weakness, fatigue, abdo pain, diarrhoea, confusion, coma, fever
Who gets adrenal crisis?
Undiagnosed people with adrenal insufficiency having an infection
People with adrenal insufficiency who fails to stress dose
Bilateral adrenal infarction/haemorrhage
How much do you stress dose in someone with adrenal insufficiency who is unwell?
Triple dose for 3 days
- Hydrocortisone 100mg stat then 50mg Q6H until stable and tolerating oral intake
Particularly if there is infection, fever
If they can’t take tablet, then IM/SC hydrocortisone 100mg emergency injection kit (tie people over for 12 hours before they can present to ED) or prednisolone/hydrocortisone suppository
Labs in adrenal crisis
Low sodium
High potassium
Low glucose
High calcium
Autoimmune Addison’s disease is often associated with …
T1DM
Adrenal medulla - its main function is …
Produces catecholamines (adrenaline and noradrenaline)
Clinical features of pheochromocytoma
Due to increased serum catecholamines
Episodic HTN Headache Palpitations Tachycardia Sweating
How to diagnose pheochromocytoma?
Serum metanephrine (usually pretty good) or 24h urine metanephrine
If >2 fold elevation above ULN, localise with adrenal/abdominal MRI or CT +/- I-MIBG (nuclear med scan with iodine)
Consider genetic testing
Rx pheochromocytoma
Pre-op preparation
Alpha blockade - phenoxybenzamine, prazosin
Beta blockade - propanolol, atenolol, labetalol
If possible, beta blockade must not be started in patients until alpha blockade has been established.
- Can cause dramatically elevated BP, due to unopposed alpha-adrenoreceptor stimulation
Then… Surgery
What syndrome is pheochromocytoma associated with?
MEN2A and 2B
Neurofibromatosis type 1
Hippel-Lindau disease
Why do we check cortisol in the morning?
Diurnal
Peaks at 8am
Rx adrenal crisis
IV hydrocortisone 100mg then 50mg Q6H until stable + intravascular volume expansion
Hydrocortisone preferred as the 1st line therapy because at higher dose (>60-80mg), it also has mineralcorticoid effect, hence bypass the need to worry about starting fludrocortisone initially
Rx CAH i.e. 21-hydroxylase deficiency
Glucocorticoid
Mineralcorticoid
New: gene therapy (coming)
Adrenal incidentaloma DDx
Cortisol or aldosterone secreting adenoma (14%) - most common
Phaeochromocytoma (7%)
Adrenalcortical carcinoma or metastatic carcinoma (4%)
Do all primary hyperaldosteronism cause hypokalaemia?
NO
30% have normal K
What is the most common cause of primary aldosteronism related hypertension?
Bilateral idiopathic hyperplasia 60%
Aldosterone producing adenoma 30%
