1b Adrenal Disorders

Question 1

What hormones are produced in the adrenal cortex?

Answer 1

Corticosteroids

Question 2

What are the corticosteroids?

Answer 2

Mineralcorticosteroids
Glucocorticoids
Sex Steroids

Question 3

What is the precursor for steroid hormones?

Answer 3

Cholesterol

Question 4

What is the effect of angiotensin II on the adrenals?

Answer 4

Activation of the following enzymes
Side Chain Cleavage
3 Beta Hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
18 hydroxylase

Question 5

What is the action of aldosterone?

Answer 5

Increases blood pressure, retains sodium and lowers potassium

Question 6

What is the effect on ACTH on the adrenals:

Answer 6

Activation of the following enzymes
Side Chain Cleavage
3 Beta Hydroxysteroid dehydrogenase
17 hydroxylase
21 hydroxylase
11 hydroxylase

Question 7

Describe the rhythm of cortisol release?

Answer 7

Diurnal secretion

Question 8

What is primary adrenal failure?

Answer 8

Autoimmune disease where the immune system destroys the adrenal cortex, therefore insufficient steroid hormone production

Question 9

What are the symptoms of an adrenal crisis?

Answer 9

Fever
Syncope
Convulsions
Hypoglycaemia
Vomiting
Diarrhea

Question 10

Why do patients with Addison’s have a good tan?

Answer 10

POMC is a large precursor
protein that is cleaved to form
a number of smaller peptides,
including ACTH, MSH and
endorphins
Thus people who have
pathologically high levels of
ACTH may become tanned

Question 11

Describe the changes to the skin in patients with Addisons?

Answer 11

Autoimmune Vitiligo
Hyperpigmentation
Good Tan

Question 12

What are the three causes of adrenocortical failure?

Answer 12

TB - tuberculous Addisons Disease
Autoimmune destruction - Autoimmune Addison’s disease
Born without the necessary enzymes

Question 13

What is POMC?

Answer 13

Pro-opio melanocortin

Question 14

Where is POMC made

Answer 14

Pituitary

Question 15

What is POMC broken down into?

Answer 15

ACTH, MSH, Endorphins and enkephalins

Question 16

What are the consequences of Adrenocortical Failure?

Answer 16

Fall in blood pressure
*Loss of salt in the urine
*Increased plasma potassium
*Fall in glucose due to glucocorticoid
deficiency
*High ACTH resulting in increased
pigmentation

Question 17

Describe the visual symptoms of Addison’s?

Answer 17

Hyperpigmentation
Vitiligo
Mucous Membrane hyperpigmentation - therefore definately not sun tan as these areas are not accessible
Darkening of hair
Muscles weakness

Question 18

What is the test for Addison’s?

Answer 18

SynACTHen test

Question 19

How does the SynACTHen test work?

Answer 19

Measure cortisol at 9am
Administer injection of SynACTHen and remeasure cortisol levels

Question 20

What test results of ACTH suggest Addisons?

Answer 20

Low Cortisol following synACTHen administration

Question 21

Why can aldosterone not be given to patients with Addison’s?

Answer 21

Aldosterone has too short a half life, therefore would have to be given multiple times a day in order to be effective

Question 22

What treatment is given to patients with Addisons?

Answer 22

Fludrocortisone - does not exist in natural steroids, therefore presence slows metabolism

Prednisolone - longer half life and more potent than cortisol, rapidly absorbed with half life suitable for once daily administration

Question 23

What is the dose for prednisolone daily?

Answer 23

3.75mg daily

Question 24

What is the dosage of fludrocortisone?

Answer 24

50 to 100 mcg daily

Question 25

Which hormones will be completely absent in complete 21-hydroxylase deficiency?

Answer 25

Aldosterone and Cortisol

Question 26

How long can you survive without treatment with 21-hydroxylase deficiency?

Answer 26

less than 24 hours

Question 27

Which hormones will be in excess in complete 21-hydroxylase deficiency?

Answer 27

Sex steroids like testosterone

Question 28

What is the youngest age of presentation with Adrenal Disorders?

Answer 28

As a neonate with a salt losing Addisonian Crisis

Question 29

How do female neonates with Addisonian Crises present?

Answer 29

may have ambigious genitalia - look like they have a penis and scrotum, therefore immediately given saline to restore salt balance

Question 30

What happens to hormone levels in Partial 21 hydroxylase deficiency

Answer 30

a bit of aldosterone and cortisol to get by with

Question 31

Which hormones are deficient in partial 21 hydroxylase deficienfy?

Answer 31

Cortisol and Aldosterone

Question 32

What are the main problems in girls with partial 21 hydroxylase deficiency?

Answer 32

Hirsutism and virilisation

Question 33

What are the main problems in boys with partial 21 hydroxylase deficiency?

Answer 33

Precocious puberty due to adrenal testosterone (mature too quickly)

Question 34

Deficiency of what hormone causes male escutcheon?

Answer 34

Partial 21 hydroxylase defiency

Question 35

What builds up with a 11 hydroxylase deficiency?

Answer 35

11-deoxycortiocosterone

Question 36

what is important to note about 11-deoxycorticosterone?

Answer 36

Behaves like aldosterone, therefore excess can cause hypertension and hypokalaemia

Question 37

Which hormones are deficient in 11-hydroxylase deficiency

Answer 37

Cortisol and aldosterone

Question 38

Which hormones are in excess in 11-hydroxylase deficiency

Answer 38

Sex steroids, testosterone and 11-deoxycorticosterone

Question 39

What are the problems associated with 11-hydroxylase deficiency?

Answer 39

virilisation, hypertension and low potassium

Question 40

What hormones are deficient in 17-hydroxylase deficiency?

Answer 40

Cortisol and Sex Steroids

Question 41

What hormones are in excess in 17-hydroxylase deficiency?

Answer 41

11-deoxycorticosterone, aldosterone

Question 42

What are the problems associated with 17-hydroxylase deficiency?

Answer 42

Hypertension, Low K, Sex steroid deficiency and glucocorticoid deficiency

Question 43

What time in the day do cortisol levels peak?

Answer 43

8.32 am

Question 44

What are some of the signs seen in patients with cushings?

Answer 44

Red Striae Buffalo Humps Poor Wound Healing Centripetal Obesity Hyperplasia of the adrenal glands Moon Face Thin Skin Proximal Myopathy Diabetes

Question 45

List the four causes of Cushing's syndrome?

Answer 45

1. Taking too many steroids orally 2. Pituitary dependant Cushing's Disease 9\Pituitary adenoma) 3. Ectopic ACTH from lung cancer 4. Adrenal Adenoma secreting Cortisol

Question 46

What are the two ways to determine the cause of Cushing's Syndrome?

Answer 46

24h urine collection for urinary free cortisol Blood diurnal cortisol levels

Question 47

Describe how the cortisol levels of someone with Cushing's syndrome differs from a normal person?

Answer 47

both have diurnal rhythm - but cushings patient will have a midnight sleeping cortisol which is not zero

Question 48

How does the low dose dexamethasone test work?

Answer 48

Dexamethasone is an artificial steroid which will suppress cortisol levels to zero in normal patients, but with Cushing's patients, the levels will fail to fall to zero

Question 49

Which drugs are used to treat Cushings'?

Answer 49

Steroid biosynthesis inhibitors

Question 50

What are the two steroid biosynthesis inhibitors used to treat cushing's?

Answer 50

Metyrapone and ketoconazole

Question 51

How does Metyrapone work?

Answer 51

Inhibits 11-hydroxylase, so cortisol levels drop as steroid synthesis in the zona fasciulata and zona reticularis are arrested at the 11- hydroxylase level

Question 52

How does the buildup of 11-deoxycortisol as a result of using metyrapone affect the axis?

Answer 52

No effect - does not exert a negative feedback effect

Question 53

What are the two main uses of Metyrapone?

Answer 53

Control of Cushing's before surgery to improve patients post-op healing process (wound healing) Control of Cushing's after radiotherapy

Question 54

What are the side effects of metyrapone?

Answer 54

11-deoxycorticosterone accumulates in the zona glomerulosa and has aldosterone like effects, leading to salt retention and hypertension

Question 55

How does Metyrapone lead to Hirsutism?

Answer 55

Increased androgen production due to the lack of 11-hydroxylase leads to hirsutism in women as there is more testosterone produced

Question 56

Describe the mechanism of action for ketoconazole?

Answer 56

Mainly blocks 17 hydroxylase, which inhibits cortisol production

Question 57

What are the side effects of ketoconazole?

Answer 57

Liver damage - monitor liver function weekly

Question 58

Describe the mechanism of Osilidrostat?

Answer 58

Blocks 11 hydroxylase, therefore no cortisol produced

Question 59

What is Conn's syndrome?

Answer 59

Where a benign adrenal cortical tumour causes an excess of aldosterone

Question 60

What are the effects of Conn's syndrome?

Answer 60

Hypertension and hypokalaemia

Question 61

What is used to treat Conn's syndrome?

Answer 61

Spironolactone

Question 62

How does Spironolactone work?

Answer 62

Converted into several active metabolites, including canrenone which is a competitive antagonist of the mineralcorticoid receptor which reverses the effects of aldosterone Also blocks Na+ reabsorption and K+ excretion in the kidney tubules

Question 63

Where is Spironolactone metabolised?

Answer 63

it is highly protein bound and metabolised in the liver

Question 64

What are the side effects of spironolactone?

Answer 64

Menstrual irregularities Gynaecomastia

Question 65

What are the two drugs used to treat Conn's syndrome?

Answer 65

Spironolactone Epleronone

Question 66

Why is epleronone prefered over spironolactone?

Answer 66

Binds less to androgen and progesterone receptors, therefore less gynaecomastia

Question 67

What are phaeochromocytomas?

Answer 67

Tumours of the adrenal MEDULLA which secrete catecholamines liek Adrenaline and Nor Adrenalline

Question 68

What are the clinical features of a phaeocytochromocytoma?

Answer 68

Hypertension in young people Episodic severe hypertension (after abdominal palpitations)

Question 69

Why is a phaeocytochromocytoma considered a medical emergency?

Answer 69

High blood pressure can cause MI or stroke High Adrenaline = cause ventricular fibrillation

Question 70

Why must you be careful when performing surgery for a phaeo?

Answer 70

Surgery - but have to be careful as anaesthetic can precipitate a hypertensive crisis

Question 71

How are Phaeo's managed?

Answer 71

Alpha Blockade - give IV fluid while this Beta Blockade - added to prevent tachy cardia