Adrenal Disorders Flashcards
Precursor for steroid hormones
Cholesterol
different types of corticosteroid?
mineralocorticoid, glucocorticoid, sex steroids
Made in the adrenal cortex
effect of angiotensin II on adrenal glands?
activation of many metabolic enzymes leading to increased corticosteroid production
aldosterone main actions?
controls blood pressure → increases sodium reabsorption and potassium excretion
effect of ACTH on adrenal cortex?
activates many enzymes including 11-, 21-, 17-hydroxylase → more production of corticosteroids
one lifestyle factor increasing ACTH production?
Stress (cortisol is a stress hormone)
first steps of metabolic pathway for cholesterol?
cholesterol → pregnenolone → progesterone
what is addison’s disease?
primary adrenal failure
mediated by autoimmune adrenal cortex destruction or tuberculosis of adrenal glands
ACTH levels in Addison’s?
high → melanocyte stimulating hormone MSH high too
Symptoms of addisons
hyperpigmentation and possible coexistent autoimmune vitiligo, low blood pressure, weakness, weight loss, nausea, diarrhoea/constipation, vomiting
what is an adrenal crisis?
fever, syncope, convulsions, hypoglycaemia, hyponatraemia, severe vomiting and diarrhoea
why hyperpigmentation?
ACTH and MSH come from the same precursor that is cleaved during formation (pro-opio-melanocortin POMC
- biochemical consequences of adrenal failure?
hyponatraemia, (postural) hypotension, hyperkalaemia, low glucose (glucocorticoid deficiency), high ACTH
- blood → Na+ and K+9am cortisol (at peak so can observe too low), ACTH
Tests for addisons
blood → Na+ and K+ . Sodium would be low and potassium high
9am cortisol (at peak so can observe too low), ACTH
what is a synACTHen test?
inject synACTHen and observe cortisol before and after e.g. 9:00 and 9:30
should be higher in response
Differentiates between primary and secondary adrenal failure
treatment for primary adrenal failure?
replacement of cortisol and aldosterone
- what is used to replace aldosterone and why?
fludrocortisone → longer half-life than aldosterone (has F group)
50-100mcg
What else can replace cortisol to treat adrenal failure
hydrocortisone and prednisolone
(1-2,dehydro hydrocortisone 3-4mg once daily
Hydrocortisone3ntimes daily 10+5+2.5
Prednisolon 2-4mg once daily
most common cause of congenital adrenal hyperplasia?
21-hydroxylase deficiency → complete or partial
Complete deficiency means complete absence of aldosterone and cortisol,excess sex steroids
- how long can you survive with complete 21 hydroxylase deficiency
Less than 24 hours
Present as a neonate with a salt losing crisis
Or before birth while in utero foetus gets steroids across placenta
possible consequence of excess testosterone?
girls may have ambiguous genitalia which is virilised by testosterone
main problem in partial 21-hydroxylase deficiency?
hirsutism and virilisation in girls, precocious puberty in boys
(kind of enough cortisol and aldosterone, excess testosterone)
- not enough cortisol to inhibit ACTH → chronic adrenal overactivity
why might adrenal hyperplasia arise?
not enough cortisol to inhibit ACTH → chronic adrenal overactivity
consequence of 11-hydroxylase deficiency?
accumulation of 11-deoxycortisol/11-deoxycorticosterone
excess of sex steroids
consequence of that? (11 hydroxylase deficiency)
11=deoxycorticosterone behaves like aldosterone → hypertension and hypokalaemia in excess
Can cause virilization hypertension and low k
consequence of 17-hydroxylase deficiency?
can’t produce cortisol or sex steroids, excess aldosterone and 11-deoxycorticosterone
Causes hypertension low k sex steroid deficiency and glucocorticoid deficiency
Cushings symptoms
fat pad, red striae, centripetal obesity, moon face, easy bruising and poor wound healing, thin skin
Hypertension and hypokalaemia
what stops cortisol from activating aldosterone receptors under normal conditions?
11-beta-hydroxysteroid dehydrogenase (11-beta-HSD)
Done via turning it into inactive form of cortisone
Causes of cushings
Too many steroids,pituitary disorder,ectopic ACTH from lung cancer,adrenal adenoma secreting cortisol
Pituitary adenoma
Ectopic acth production
Adrenal adenoma secreting cortisol
Steroids
Investigation for cushings
24hr urine collection, blood diurnal cortisol level, low dose dexamethasone suppression test
Cortisol measured at midnight as that’s the lowest point
what is the dexamethasone suppression test?
artificial steroid taken 6 hourly for 48 hrs
healthy people suppress cortisol to 0, any cause of Cushing’s fails to suppress
measure basal 9am and end of LDDST
functions of hyperadrenal disorder medications?
Enzyme inhibitors
Receptor blockers
what are some inhibitors of steroid biosynthesis? how do they work?
Metyrapone-11 b hydroxylase inhibitor (blocks formation of cortisol),used pre surgery/post radiotherapy cushings control,mean serum cortisol of 150-300. Can control cushings symptoms after radiotherapy Can cause hirsuitism and hypertension as deoxycorticosterone accumulates in z glomerulosa causing aldosterone like activity
Ketoconazole-17 hydroxylase inhibitor. Used for cushings to control prior to surgery,can cause fatal liver damage
Osilodrostat-mainly 11 b hydroxylase and 17 hydroxylase
treatment of cushing’s?
depends on cause, some options are pituitary surgery and bilateral adrenalectomy (unilateral for adrenal mass)
what is conn’s syndrome?
benign adrenal cortical tumour causing aldosterone excess thus primary hyperaldoesteronisn RAS not suppressed
Hypertension,hypokalaemia,renin angiotensin system suppressed
Treat with aldosterone receptor antagonist spironolactone and eplerenone. Can cause gynaecomastia
Spironolactone converted to active metabolite canrenone which is a competitive inhibitor ofMR blocking sodium resorption and potassium excretion
what are pheochromocytomas?
Tumours of adrenal medulla
Create an excess of catecholamines (adrenaline and noradrenaline)
Pheochromocytomas
Hypertension in young people,sever episodic hypertension after abdominal palpating,high adrenaline can cause ventricular fibrillation and death. Severe can cause myocardial infarction or stroke
Management of pheochromocytomas
Surgery needed
An aesthetic can precipitation hypertensive crisis
alpha blockade (eg prazosin) to prevent vasoconstriction, then possible beta blockade to prevent tachycardia (eg propanolol)
Conns syndrome diagnosis
Primary hyperaldosteronism causing Na+ increase and K+ decrease
Or increased renin which causes increased aldosterone levels
Conns syndrome treatment
Mineralcorticoids receptor is targeted
Spironolactone used in primary hyperaldosteronism (conns) and converted to several active metabolites eg canrenone. Blocks Na+ resorption and k+ excretion in kidney tubules. Orally active and highly protein bound. Can cause menstrual irregularities and gynaecomastia in men (androgen receptors are blocked)
Epleronone is a mineralcorticoid receptor antagonist. Less binding to androgen and progesterone compared to spironolactone
Primary adrenal failure bs secondary
Primary
Due to adrenal gland damage
ACTH is high aldosterone is low,
Hyperpigmentation present due to high ACTH
ACTH test cortisol doesn’t increase
Secondary
Pituitary or hypothalamic dysfunction
ACTH is low aldosterone is normal
No hyperpigmentation
Cortisol roses in ACTH test
Metyrapone
Inhibits 11b hydroxylase
Steroid synthesis stops at 11 deoxycortisol stage
Nk negative feedback on hypothalamus and pituitary gland
Cortisol production stopped
Used prior to surgery where the aim is serum cortisol of 150-300. Thus improves post op recovery
Can control cushings symptoms after radiotherapy
However can cause 11 deoxycorticosterone to accumulate in the Z glomerulsoa causing aldosterone like affects eg salt retention and hypertension as well as increasing the risk of hirsituism jn females
Ketoconazole
Inhibits 17a hydroxylase preventing cortisol production
Used prior to surgery to control symptoms
Orally active
Can cause liver damage thus possibly fatal so must monitor function weekly
Osilidrostat
Blocks 17 hydroxylase and 11b hydroxylase
Blocking cortisol and corticosterone
