Adrenal Disorders

Question 1

Precursor for steroid hormones

Answer 1

Cholesterol

Question 2

different types of corticosteroid?

Answer 2

mineralocorticoid, glucocorticoid, sex steroids
Made in the adrenal cortex

Question 3

effect of angiotensin II on adrenal glands?

Answer 3

activation of many metabolic enzymes leading to increased corticosteroid production

Question 4

aldosterone main actions?

Answer 4

controls blood pressure → increases sodium reabsorption and potassium excretion

Question 5

effect of ACTH on adrenal cortex?

Answer 5

activates many enzymes including 11-, 21-, 17-hydroxylase → more production of corticosteroids

Question 6

one lifestyle factor increasing ACTH production?

Answer 6

Stress (cortisol is a stress hormone)

Question 7

first steps of metabolic pathway for cholesterol?

Answer 7

cholesterol → pregnenolone → progesterone

Question 8

what is addison’s disease?

Answer 8

primary adrenal failure

mediated by autoimmune adrenal cortex destruction or tuberculosis of adrenal glands

Question 9

ACTH levels in Addison’s?

Answer 9

high → melanocyte stimulating hormone MSH high too

Question 10

Symptoms of addisons

Answer 10

hyperpigmentation and possible coexistent autoimmune vitiligo, low blood pressure, weakness, weight loss, nausea, diarrhoea/constipation, vomiting

Question 11

what is an adrenal crisis?

Answer 11

fever, syncope, convulsions, hypoglycaemia, hyponatraemia, severe vomiting and diarrhoea

Question 12

why hyperpigmentation?

Answer 12

ACTH and MSH come from the same precursor that is cleaved during formation (pro-opio-melanocortin POMC

Question 13

• biochemical consequences of adrenal failure?

Answer 13

hyponatraemia, (postural) hypotension, hyperkalaemia, low glucose (glucocorticoid deficiency), high ACTH

• blood → Na+ and K+9am cortisol (at peak so can observe too low), ACTH

Question 14

Tests for addisons

Answer 14

blood → Na+ and K+ . Sodium would be low and potassium high

9am cortisol (at peak so can observe too low), ACTH

Question 15

what is a synACTHen test?

Answer 15

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

Question 16

treatment for primary adrenal failure?

Answer 16

replacement of cortisol and aldosterone

Question 17

• what is used to replace aldosterone and why?

Answer 17

fludrocortisone → longer half-life than aldosterone (has F group)
50-100mcg

Question 18

What else can replace cortisol to treat adrenal failure

Answer 18

hydrocortisone and prednisolone

(1-2,dehydro hydrocortisone 3-4mg once daily
Hydrocortisone3ntimes daily 10+5+2.5
Prednisolon 2-4mg once daily

Question 19

most common cause of congenital adrenal hyperplasia?

Answer 19

21-hydroxylase deficiency → complete or partial
Complete deficiency means complete absence of aldosterone and cortisol,excess sex steroids

Question 20

• how long can you survive with complete 21 hydroxylase deficiency

Answer 20

Less than 24 hours

Present as a neonate with a salt losing crisis
Or before birth while in utero foetus gets steroids across placenta

Question 21

possible consequence of excess testosterone?

Answer 21

girls may have ambiguous genitalia which is virilised by testosterone

Question 22

main problem in partial 21-hydroxylase deficiency?

Answer 22

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

Question 23

why might adrenal hyperplasia arise?

Answer 23

not enough cortisol to inhibit ACTH → chronic adrenal overactivity

Question 24

consequence of 11-hydroxylase deficiency?

Answer 24

accumulation of 11-deoxycortisol/11-deoxycorticosterone

excess of sex steroids

Question 25

consequence of that? (11 hydroxylase deficiency)

Answer 25

11=deoxycorticosterone behaves like aldosterone → hypertension and hypokalaemia in excess Can cause virilization hypertension and low k

Question 26

consequence of 17-hydroxylase deficiency?

Answer 26

can’t produce cortisol or sex steroids, excess aldosterone and 11-deoxycorticosterone Causes hypertension low k sex steroid deficiency and glucocorticoid deficiency

Question 27

Cushings symptoms

Answer 27

fat pad, red striae, centripetal obesity, moon face, easy bruising and poor wound healing, thin skin Hypertension and hypokalaemia

Question 28

what stops cortisol from activating aldosterone receptors under normal conditions?

Answer 28

11-beta-hydroxysteroid dehydrogenase (11-beta-HSD) Done via turning it into inactive form of cortisone

Question 29

Causes of cushings

Answer 29

Too many steroids,pituitary disorder,ectopic ACTH from lung cancer,adrenal adenoma secreting cortisol Pituitary adenoma Ectopic acth production Adrenal adenoma secreting cortisol Steroids

Question 30

Investigation for cushings

Answer 30

24hr urine collection, blood diurnal cortisol level, low dose dexamethasone suppression test Cortisol measured at midnight as that’s the lowest point

Question 31

what is the dexamethasone suppression test?

Answer 31

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

Question 32

functions of hyperadrenal disorder medications?

Answer 32

Enzyme inhibitors Receptor blockers

Question 33

what are some inhibitors of steroid biosynthesis? how do they work?

Answer 33

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

Question 34

treatment of cushing’s?

Answer 34

depends on cause, some options are pituitary surgery and bilateral adrenalectomy (unilateral for adrenal mass)

Question 35

what is conn’s syndrome?

Answer 35

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

Question 36

what are pheochromocytomas?

Answer 36

Tumours of adrenal medulla Create an excess of catecholamines (adrenaline and noradrenaline)

Question 37

Pheochromocytomas

Answer 37

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

Question 38

Management of pheochromocytomas

Answer 38

Surgery needed An aesthetic can precipitation hypertensive crisis alpha blockade (eg prazosin) to prevent vasoconstriction, then possible beta blockade to prevent tachycardia (eg propanolol)

Question 39

Conns syndrome diagnosis

Answer 39

Primary hyperaldosteronism causing Na+ increase and K+ decrease Or increased renin which causes increased aldosterone levels

Question 40

Conns syndrome treatment

Answer 40

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

Question 41

Primary adrenal failure bs secondary

Answer 41

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

Question 42

Metyrapone

Answer 42

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

Question 43

Ketoconazole

Answer 43

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

Question 44

Osilidrostat

Answer 44

Blocks 17 hydroxylase and 11b hydroxylase Blocking cortisol and corticosterone