Adrenal Disorders Flashcards
where are corticosteroids synthesised?
adrenal cortex
examples of corticosteroids
mineralcorticoids (aldosterone) glucocorticoids (cortisol) sex steroids (androgens, oestrogen)
what is the precursor of a steroid?
cholesterol
what is the effect of angiotensin II on the adrenals?
activates:
3-hydroxysteroid dehydrogenase
11, 21, 18-hydroxylase
what is the effect of ACTH on the adrenals?
activates: 3-hydroxysteroid dehydrogenase
11, 21 and 17-hydroxylase
what is addisons disease?
primary adrenal failure
what is the most common cause of Addisons worldwide?
tuberculosis of the adrenal glands
what is the most common cause of Addisons in the UK?
autoimmune destruction of the adrenal glands
what are the main signs of Addisons disease?
skin and mucous membrane pigmentation
weight loss
vomiting, diarrhoea
low blood pressure
what are the physiological consequences of addisons?
low BP loss of salt in urine increased plasma potassium low blood glucose increased skin pigmentation
why does high ACTH lead to increased pigmentation?
POM-C is cleaved to form ACTH and MSH (and endorphins) so pathologically high ACTH may lead to tanned skin
what tests should be performed if Addisons is suspected?
9am cortisol
short synACTHen test
what is a short synACTHen test?
give 250ug synACTHen IM
measure cortisol response (should increase)
how is Addisons treated?
fludrocortisone 50-100mg
and either hydrocortisone 3x daily(10, 5, 2.5mg) OR prednisolone 3mg daily
what is the most common congenital adrenal hyperplasia?
21-hydroxylase deficiency
what is complete 21-hydroxylase deficiency?
missing 21-hydroxylase from birth
what hormones are absent in complete 21-hydroxylase deficiency?
aldosterone and cortisol
which hormones are in EXCESS in complete 21-hydroxylase deficiency?
sex steroids and testosterone
what are the signs of someone with complete 21-hydroxylase deficiency?
neonate with salt-losing addisonian crisis
what do girls with complete 21-hydroxylase deficiency develop?
ambiguous genitalia, virilised by adrenal testosterone (males usually okay)
how do partial and complete 21-hydroxylase deficiency present differently?
partial may present much later in life as is not fatal without treatment. males may present with precocious puberty and females with hirsutism and virilisation
what is virilisation?
development of male physical characteristics in females/precocious boys
what hormones are deficient in 11-hydroxylase deficiency?
cortisol and aldosterone
what hormones are in excess in 11-hydroxylase deficiency?
sex steroids - testosterone
11-deoxycortisterone
what do individuals with 11-hydroxylase deficiency present with?
virilisation,
HYPERtension
HYPOkalaemia
what does 11-deoxycorticosterone act like?
aldosterone - excess can cause hypertension and hypokalaemia
what hormones are deficient in 17-hydroxylase deficiency?
cortisol and sex steroids
what hormones are in excess in 17-hydroxylase deficiency?
11-deoxycorticosterone and aldosterone (mineralocorticoids)
what do individuals with 17-hydroxylase deficiency present with?
hypertension, hypokalaemia, infertility, low libido, erectile dysfunction low glucose
what is cushings syndrome?
high cortisol
what are the main signs of cushings disease?
centripedal obesity, moon face, buffalo hump proximal myopathy hypertension and hypokalaemia red striae, thin skin, bruising osteoporosis, diabetes
what is the main cause of cushings syndrome?
taking steroids
pituitary adenoma
ectopic ACTH lung cancer
adrenal adenoma
what is cushings disease?
cushings syndrome caused by pituitary adenoma
how is cushings syndrome diagnosed?
24hr urine collection for urinary free cortisol
blood diurnal cortisol levels
low dose dexamethasone suppression test
what is a low dose dexamethasone test?
0.5mg 6 hourly doses of artificial steroid for 48hrs
any cause of cushings will fail to suppress cortisol (normal should go to 0)
how do you treat cushings?
metyrapone or ketoconazol medication
pituitary surgery
bilateral or unilateral adrenalectomy
what is metyrapone used for?
control of cushings prior to surgery (promotes better wound healing)
control of cushings after radiotherapy (while waiting for it to work)
what are the side effects of metyrapone?
hirsutism
hypertension if long term
what is ketoconazole used for?
mainly an antifungal,
at high doses - control and treatment of cushings syndrome
what is ketoconazoles mechanism of action?
inhibits steroidogenesis by 17a-hydroxylase
when is a bilateral adrenalectomy typically performed?
for ectopic ACTH lung cancer
when is a unilateral adrenalectomy typically performed?
for adrenal masses
what is Conns syndrome?
benign adrenal cortical tumour of zona glomerulosa
with hyperaldosteronaemia
aka primary hyperaldosteronism
how does Conns syndrome present?
hypertension muscle cramps heart palpitations hypokalaemia anxiety headaches
how is conns syndrome diagnosed?
measuring renin (low) and aldosterone levels (high) low potassium (hypokalaemia)
what is spironolactone used for?
primary hyperaldosteronism (conns syndrome)
how does metyrapone work
blocks 11-hydroxylase
therefore no production of cortisol or corticosterone
side effects casued by buildup of 11-deoxycorticosterone in zona glomerulosa - hypertension
treatment of conns syndrome
spironolactone (or epleronone)
and removal of tumour
spironolactone side effects
gynaecomastia
menstrual abnormalities
what is a phaeochromocytoma?
tumour of adrenal medulla neuroendocrine cells secretes catecholamines (nor/adrenaline)
how is phaeochromocytoma different to other adrenal tumours?
neuroendocrine cells
it stores the adrenaline then suddenly releases it unlike a steady release of hormones
therefore symptoms can come on very suddenly - blood pressure rises etc
signs of phaeochromocytoma
intermittent severe hypertension - especially after abdominal palpation
hypertension in young
risks due to phaeochromocytomas
myocardial infarction stroke ventricular fibrillation sudden death medical emergency!
management of phaeochromacytoma
alpha adrenoreceptor blocker and give fluids to prevent a bp crash
beta blocker to prevent tachycardia
then removal of tumour surgically
types of phaeochromocytoma
extra-adrenal (somewhere in sympathetic chain)
bilateral
malignant
heritable
what is a salt losing addisonian crisis
body unable to retain salt (sodium) as its lost in urine
crash in blood pressure
what should you suspect if a baby is born with ambiguous genitalia
21 hydroxylase deficiency - give NaCl fluids just in case of crisis
practice drawing the adrenal steroid pathway on paper RN
you better have done it
treatment of 21-hydroxylase deficiency
replacement for aldosterone and cortisol so
single morning dose of prednisolone 3mg
symptoms of phaechromocytoma
severe intermittent hypertension heavy sweating palpitations and tachycardia shortness of breath panic-attack like symptoms
easy ways to remember CAHs
If the enzyme deficiency starts with 1 (eg. 11 or 17 hydroxylase) → it causes hypertension.
If the enzyme deficiency ends with 1 (eg. 11 or 21 hydroxylase) → it causes virilisation in females and precocious puberty in males
- In each of these conditions, the absence of an enzyme results in decreased cortisol, which causes:
- Hyperpigmentation (due to decreased negative feedback → elevated ACTH → increased MSH from POMC breakdown)
- Hypoglycaemia (because one of the functions of cortisol is to promote gluconeogenesis)
- Nausea and vomiting (mechanism unclear but this is a classic symptom of adrenal insufficiency)
