Adrenal Disorders

Question 1

where are corticosteroids synthesised?

Answer 1

adrenal cortex

Question 2

examples of corticosteroids

Answer 2

mineralcorticoids (aldosterone)
glucocorticoids (cortisol)
sex steroids (androgens, oestrogen)

Question 3

what is the precursor of a steroid?

Answer 3

cholesterol

Question 4

what is the effect of angiotensin II on the adrenals?

Answer 4

activates:
3-hydroxysteroid dehydrogenase
11, 21, 18-hydroxylase

Question 5

what is the effect of ACTH on the adrenals?

Answer 5

activates: 3-hydroxysteroid dehydrogenase

11, 21 and 17-hydroxylase

Question 6

what is addisons disease?

Answer 6

primary adrenal failure

Question 7

what is the most common cause of Addisons worldwide?

Answer 7

tuberculosis of the adrenal glands

Question 8

what is the most common cause of Addisons in the UK?

Answer 8

autoimmune destruction of the adrenal glands

Question 9

what are the main signs of Addisons disease?

Answer 9

skin and mucous membrane pigmentation
weight loss
vomiting, diarrhoea
low blood pressure

Question 10

what are the physiological consequences of addisons?

Answer 10

low BP
loss of salt in urine
increased plasma potassium 
low blood glucose
increased skin pigmentation

Question 11

why does high ACTH lead to increased pigmentation?

Answer 11

POM-C is cleaved to form ACTH and MSH (and endorphins) so pathologically high ACTH may lead to tanned skin

Question 12

what tests should be performed if Addisons is suspected?

Answer 12

9am cortisol

short synACTHen test

Question 13

what is a short synACTHen test?

Answer 13

give 250ug synACTHen IM

measure cortisol response (should increase)

Question 14

how is Addisons treated?

Answer 14

fludrocortisone 50-100mg

and either hydrocortisone 3x daily(10, 5, 2.5mg) OR prednisolone 3mg daily

Question 15

what is the most common congenital adrenal hyperplasia?

Answer 15

21-hydroxylase deficiency

Question 16

what is complete 21-hydroxylase deficiency?

Answer 16

missing 21-hydroxylase from birth

Question 17

what hormones are absent in complete 21-hydroxylase deficiency?

Answer 17

aldosterone and cortisol

Question 18

which hormones are in EXCESS in complete 21-hydroxylase deficiency?

Answer 18

sex steroids and testosterone

Question 19

what are the signs of someone with complete 21-hydroxylase deficiency?

Answer 19

neonate with salt-losing addisonian crisis

Question 20

what do girls with complete 21-hydroxylase deficiency develop?

Answer 20

ambiguous genitalia, virilised by adrenal testosterone (males usually okay)

Question 21

how do partial and complete 21-hydroxylase deficiency present differently?

Answer 21

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

Question 22

what is virilisation?

Answer 22

development of male physical characteristics in females/precocious boys

Question 23

what hormones are deficient in 11-hydroxylase deficiency?

Answer 23

cortisol and aldosterone

Question 24

what hormones are in excess in 11-hydroxylase deficiency?

Answer 24

sex steroids - testosterone

11-deoxycortisterone

Question 25

what do individuals with 11-hydroxylase deficiency present with?

Answer 25

virilisation, HYPERtension HYPOkalaemia

Question 26

what does 11-deoxycorticosterone act like?

Answer 26

aldosterone - excess can cause hypertension and hypokalaemia

Question 27

what hormones are deficient in 17-hydroxylase deficiency?

Answer 27

cortisol and sex steroids

Question 28

what hormones are in excess in 17-hydroxylase deficiency?

Answer 28

11-deoxycorticosterone and aldosterone (mineralocorticoids)

Question 29

what do individuals with 17-hydroxylase deficiency present with?

Answer 29

``` hypertension, hypokalaemia, infertility, low libido, erectile dysfunction low glucose ```

Question 30

what is cushings syndrome?

Answer 30

high cortisol

Question 31

what are the main signs of cushings disease?

Answer 31

``` centripedal obesity, moon face, buffalo hump proximal myopathy hypertension and hypokalaemia red striae, thin skin, bruising osteoporosis, diabetes ```

Question 32

what is the main cause of cushings syndrome?

Answer 32

taking steroids pituitary adenoma ectopic ACTH lung cancer adrenal adenoma

Question 33

what is cushings disease?

Answer 33

cushings syndrome caused by pituitary adenoma

Question 34

how is cushings syndrome diagnosed?

Answer 34

24hr urine collection for urinary free cortisol blood diurnal cortisol levels low dose dexamethasone suppression test

Question 35

what is a low dose dexamethasone test?

Answer 35

0.5mg 6 hourly doses of artificial steroid for 48hrs | any cause of cushings will fail to suppress cortisol (normal should go to 0)

Question 36

how do you treat cushings?

Answer 36

metyrapone or ketoconazol medication pituitary surgery bilateral or unilateral adrenalectomy

Question 37

what is metyrapone used for?

Answer 37

control of cushings prior to surgery (promotes better wound healing) control of cushings after radiotherapy (while waiting for it to work)

Question 38

what are the side effects of metyrapone?

Answer 38

hirsutism | hypertension if long term

Question 39

what is ketoconazole used for?

Answer 39

mainly an antifungal, | at high doses - control and treatment of cushings syndrome

Question 40

what is ketoconazoles mechanism of action?

Answer 40

inhibits steroidogenesis by 17a-hydroxylase

Question 41

when is a bilateral adrenalectomy typically performed?

Answer 41

for ectopic ACTH lung cancer

Question 42

when is a unilateral adrenalectomy typically performed?

Answer 42

for adrenal masses

Question 43

what is Conns syndrome?

Answer 43

benign adrenal cortical tumour of zona glomerulosa with hyperaldosteronaemia aka primary hyperaldosteronism

Question 44

how does Conns syndrome present?

Answer 44

``` hypertension muscle cramps heart palpitations hypokalaemia anxiety headaches ```

Question 45

how is conns syndrome diagnosed?

Answer 45

``` measuring renin (low) and aldosterone levels (high) low potassium (hypokalaemia) ```

Question 46

what is spironolactone used for?

Answer 46

primary hyperaldosteronism (conns syndrome)

Question 47

how does metyrapone work

Answer 47

blocks 11-hydroxylase therefore no production of cortisol or corticosterone side effects casued by buildup of 11-deoxycorticosterone in zona glomerulosa - hypertension

Question 48

treatment of conns syndrome

Answer 48

spironolactone (or epleronone) | and removal of tumour

Question 49

spironolactone side effects

Answer 49

gynaecomastia | menstrual abnormalities

Question 50

what is a phaeochromocytoma?

Answer 50

``` tumour of adrenal medulla neuroendocrine cells secretes catecholamines (nor/adrenaline) ```

Question 51

how is phaeochromocytoma different to other adrenal tumours?

Answer 51

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

Question 52

signs of phaeochromocytoma

Answer 52

intermittent severe hypertension - especially after abdominal palpation hypertension in young

Question 53

risks due to phaeochromocytomas

Answer 53

``` myocardial infarction stroke ventricular fibrillation sudden death medical emergency! ```

Question 54

management of phaeochromacytoma

Answer 54

alpha adrenoreceptor blocker and give fluids to prevent a bp crash beta blocker to prevent tachycardia then removal of tumour surgically

Question 55

types of phaeochromocytoma

Answer 55

extra-adrenal (somewhere in sympathetic chain) bilateral malignant heritable

Question 56

what is a salt losing addisonian crisis

Answer 56

body unable to retain salt (sodium) as its lost in urine | crash in blood pressure

Question 57

what should you suspect if a baby is born with ambiguous genitalia

Answer 57

21 hydroxylase deficiency - give NaCl fluids just in case of crisis

Question 58

practice drawing the adrenal steroid pathway on paper RN

Answer 58

you better have done it

Question 59

treatment of 21-hydroxylase deficiency

Answer 59

replacement for aldosterone and cortisol so | single morning dose of prednisolone 3mg

Question 60

symptoms of phaechromocytoma

Answer 60

``` severe intermittent hypertension heavy sweating palpitations and tachycardia shortness of breath panic-attack like symptoms ```

Question 61

easy ways to remember CAHs

Answer 61

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)