1b Adrenal Disorders Flashcards
What hormones are produced in the adrenal cortex?
Corticosteroids
What are the corticosteroids?
Mineralcorticosteroids
Glucocorticoids
Sex Steroids
What is the precursor for steroid hormones?
Cholesterol
What is the effect of angiotensin II on the adrenals?
Activation of the following enzymes
Side Chain Cleavage
3 Hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
18 hydroxylase
What is the action of aldosterone?
Increases blood pressure, retains sodium and lowers potassium
What is the effect on ACTH on the adrenals:
Activation of the following enzymes
Side Chain Cleavage
3 Hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
17 hydroxylase
Describe the rhythm of cortisol release?
Diurnal secretion
What is primary adrenal failure?
Autoimmune disease where the immune system destroys the adrenal cortex, therefore insufficient steroid hormone production
What are the symptoms of an adrenal crisis?
Fever
Syncope
Convulsions
Hypoglycaemia
Vomiting
Diarrhea
What are the symptoms of an adrenal crisis?
Fever
Syncope
Convulsions
Hypoglycaemia
Vomiting
Diarrhea
Why do patients with Addison’s have a good tan?
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
Describe the changes to the skin in patients with Addisons?
Autoimmune Vitiligo
Hyperpigmentation
Good Tan
What are the three causes of adrenocortical failure?
TB - tuberculous Addisons Disease
Autoimmune destruction - Autoimmune Addison’s disease
Born without the necessary enzymes
What is POMC?
Pro-opio melanocortin
Where is POMC made
Pituitary
What is POMC broken down into?
ACTH, MSH, Endorphins and enkephalins
What are the consequences of Adrenocortical Failure?
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
Describe the visual symptoms of Addison’s?
Hyperpigmentation
Vitiligo
Mucous Membrane hyperpigmentation - therefore definately not sun tan as these areas are not accessible
Darkening of hair
Muscles weakness
What is the test for Addison’s?
SynACTHen test
How does the SynACTHen test work?
Measure cortisol at 9am
Administer injection of SynACTHen and remeasure cortisol levels
What test results of ACTH suggest Addisons?
Low Cortisol following synACTHen administration
Why can aldosterone not be given to patients with Addison’s?
Aldosterone has too short a half life, therefore would have to be given multiple times a day in order to be effective
What is give to patients with Addisons?
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
What is the dose for prednisolone daily?
3.75mg daily
What is the dosage of fludrocortisone?
50 to 100 mcg daily
Which hormones will be completely absent in complete 21-hydroxylase deficiency?
Aldosterone and Cortisol
How long can you survive without treatment with 21-hydroxylase deficiency?
less than 24 hours
Which hormones will be in excess in complete 21-hydroxylase deficiency?
Sex steroids like testosterone
What is the youngest age of presentation with Adrenal Disorders?
As a neonate with a salt losing Addisonian Crisis
How do female neonates with Addisonian Crises present?
may have ambigious genitalia - loo like they have a penis and scrotum, therefore immediately given saline to restore salt balance
What happens to hormone levels in Partial 21 hydroxylase deficiency
a bit of aldosterone and cortisol to get by with
Which hormones are deficient in partial 21 hydroxylase deficienfy?
Cortisol and Aldosterone
Which hormones are in excess in partial 21 hydroxylase deficiency?
Sex steroids and testosterone
What are the main problems in girls with partial 21 hydroxylase deficiency?
Hirsutism and virilisation
What are the main problems in boys with partial 21 hydroxylase deficiency?
Precocious puberty due to adrenal testosterone
Deficiency of what hormone causes male escutcheon?
This is where the female pubic hair grows in a pattern similar to that of a male
Partial 21 hydroxylase defiency
What builds up with a 11 hydroxylase deficiency?
11-deoxycortiocosterone
what is important to note about 11-deoxycorticosterone?
Behaves like aldosterone, therefore excess can cause hypertension and hypokalaemia
Which hormones are deficient in 11-hydroxylase deficiency
Cortisol and aldosterone
Which hormones are in excess in 11-hydroxylase deficiency
Sex steroids, testosterone and 11-deoxycorticosterone
What are the problems associated with 11-hydroxylase deficiency?
virilisation, hypertension and low potassium
What hormones are deficient in 17-hydroxylase deficiency?
Cortisol and Sex Steroids
What hormones are in excess in 17-hydroxylase deficiency?
11-deoxycorticosterone, aldosterone
What are the problems associated with 17-hydroxylase deficiency?
Hypertension, Low K, Sex steroid deficiency and glucocorticoid deficiency
What time in the day do cortisol levels peak?
8.32 am
What are some of the signs seen in patients with cushings?
Red Striae
Buffalo Humps
Poor Wound Healing
Centripetal Obesity
Hyperplasia of the adrenal glands
Moon Face
Thin Skin
Proximal Myopathy
Diabetes
List the four causes of Cushing’s syndrome?
- Taking too many steroids orally
- Pituitary dependant Cushing’s Disease 9\Pituitary adenoma)
- Ectopic ACTH from lung cancer
- Adrenal Adenoma secreting Cortisol
What are the two ways to determine the cause of Cushing’s Syndrome?
24h urine collection for urinary free cortisol
Blood diurnal cortisol levels
Describe how the cortisol levels of someone with Cushing’s syndrome differs from a normal person?
both have diurnal rhythm - but cushings patient will have a midnight sleeping cortisol which is not zero
How does the low dose dexamethasone test work?
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
Which drugs are used to treat Cushings’?
Steroid biosynthesis inhibitors
What are the two steroid biosynthesis inhibitors used to treat cushing’s?
Metyrapone and ketoconazole
How does Metyrapone work?
Inhibits 11-hydroxylase, so cortisol levels drop as steroid synthesis in the zona fasciulata and zona reticularis are arrested at the 11- hydroxylase level
How does the buildup of 11-deoxycortisol as a result on using metyrapone affect the axis?
No effect - does not exert a negative feedback effect
What are the two main uses of Metyrapone?
Control of Cushing’s before surgery to improve patients post-op healing process (wound healing)
Control of Cushing’s after radiotherapy
What are the side effects of metyrapone?
11-deoxycorticosterone accumulates in the zona glomerulosa and has aldosterone like effects, leading to salt retention and hypertension
How does Metyrapone lead to Hirsutism?
Increased androgen production due to the lack of 11-hydroxylase leads to hirsutism in women as there is more testosterone produced
Describe the mechanism of action for ketoconazole?
Mainly blocks 17 hydroxylase, which inhibits cortisol production
What are the side effects of ketoconazole?
Liver damage - monitor liver function weekly
Describe the mechanism of Osilidrostat?
Blocks 11 hydroxylase, therefore no cortisol produced
What is Conn’s syndrome?
Where a benign adrenal cortical tumour causes an excess of aldosterone
What are the effects of Conn’s syndrome?
Hypertension and hypokalaemia
What is used to treat Conn’s syndrome?
Spironolactone
How does Spironolactone work?
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
Where is Spironolactone metabolised?
it is highly protein bound and metabolised in the liver
What are the side effects of spironolactone?
Menstrual irregularitie
Gynaecomastia
What are the two drugs used to treat Conn’s syndrome?
Spironolactone
Epleronone
Why is epleronone prefered over spironolactone?
Binds less to androgen and progesterone receptors, therefore less gynaecomastia
What are phaeochromocytomas?
Tumours of the adrenal MEDULLA which secrete catecholamines liek Adrenaline and Nor Adrenalline
What are the clinical features of a phaeochromocytoma?
Hypertension in young people
Episodic severe hypertension (after abdominal palpitation
Why is a phaeochromocytoma considered a medical emergency?
High blood pressure can cause MI or stroke
High Adrenaline = cause ventricular fibrillation
Why must you be careful when performing surgery for a phaeo?
Surgery - but have to be careful as anaesthetic can precipitate a hypertensive crisis
How are Phaeo’s managed?
Alpha Blockade - give IV fluid while this
Beta Blockade - added to prevent tachy cardia
