Hyperadrenal disorders Flashcards
What is Cushing’s syndrome due to?
Too much cortisol
Clinical features of Cushing’s
Synthesize too much fat and break down too much protein
Get really obese with weak muscles - centripetal obesity
Thin skin that tears so red marks - striae
Buffalo hump
Proximal myopathy
Bruising
Moon face
Osteoporosis
Diabetes
What causes Cushing’s
Taking too many steroids
Pituitary dependent Cushing’s disease
Ectopic ACTH from lung cancer
Adrenal adenoma secreting cortisol
Investigations for Cushing’s syndrome
24h urine collection for urinary free cortisol
Blood diurnal cortisol levels
Low dose dexamethasone
When is cortisol usually highest and lowest?
cortisol usually highest at 9am and lowest at midnight if asleep. Follows circadian rhythm.
What is dexamethasone
Artificial cortisol that lasts a long time
How is dexamethason suppression test administrated
0.5mg every 6 hours for 48 hours
What shows cushing’s syndrome in a dexamethason supression test?
Normally will suppress cortisol to zero as that is a lot of steroid but ANY cause of Cushing’s will fail to suppress
How would you approach too much cortisol medically?
Inhibitors of steroid biosynthesis: metyrapone, ketoconazole
Why do you really want to lower cortisol before a surgery to remove the source permanently
Patients have thin skin, easy bruising and there is a lot of bleeding. Cortisol suppresses the immune system and increases risk of infection.
How does metyrapone work?
It inhibits 11 beta hydroxylase which stops corticosterone and cortisol production from cholesterol
What are uses of metyrapone?
Control of Cushing’s syndrome prior to surgery - improve patient symptoms and promotes better post op recovery
Control Cushing’s syndrome after radiotherapy (which is usually slow to take effect)
What are the issues with metyrapone?
Hypertension on long term administration
Hirsutism
How does metyrapone cause salt retention and hypertension
It would lead to a build up of the product before the use of 11 beta hydroxylase - such as 11 deoxycorticosterone which has a mineralocorticoid activity which leads to salt retention and hypertension
How does metyrapone cause hirsutism
Due to the other two brances of cholesterol conversion being blocked, funnels it into sex steroid production so more androgen production so causes hirsutism in women
What is hirsutism
condition of unwanted, male-pattern hair growth in women. Hirsutism results in excessive amounts of dark, course hair on body areas where men typically grow hair — face, chest and back
What is the main use of ketoconazole?
Antifungal agent that was withdrawn in 2013 because of risk of hepatotoxicity
How does ketoconazole work?
It blocks 17 alpha hydroxylase which is higher up than metyrapone
What is the unwanted action of ketoconazole?
Liver damage that is possibly fatal therefore must monitor liver function weekly, clinically and biochemically
What are ways of curing Cushing’s?
Depends on cause:
Pituitary surgery - transsphenoidal hypophysectomy
Bilateral adrenalectomy
Unilateral adrenalectomy for adrenal mass
What is Conn’s syndrome?
Benign adrenal cortical tumour of outer zone of adrenal gland - zona glomerulosa leading to XS aldosterone
What are symptoms of Conns
Hypertension and hypokalaemia
How do you diagnose Conn’s
If aldosterone very high but renin surpressed - conns
Just measure them
What is the treatment of Conn’s syndrome?
Block the receptor that the hormone works by - MR antagonist eg spironolactone or eplerenone
What is the mechanism of action of Spironolactone?
It is converted into several active metabolites including cenrenone, a competitive antagonist of the mineralocorticoid receptor that blocks Na+ resorption and K+ excretion in the kidney tubules (potassium sparing diuretic)
What are the unwanted actions of spironolactone?
Menstrual irregularities (+ progesterone receptor) Gynaecomastia (- androgen receptor) bc not very specific
What is a phaeochyromocytomas
A tumour of adrenal medulla which secretes catecholamines that leads to episodic release of adrenaline or noradrenaline that is more common in certain inherited condition
What are clinical features of phaeochyromocytomas
Blood pressure shoots up crazy numbers Sweating Headache Sick Sudden dizziness Sudden anxiety Hypertension in young people Episodic severe hypertension after abdominal palpation
How can phaeochyromocytomas cause sudden death
The severe hypertension can cause myocardial infarction or stoke and the high adrenaline can cause ventricular fibrillation and death THUS is a MEDICAL EMERGENCY
What is the management for phaeochyromocytomas
Alpha blockade is the first therapy step, patients may need intravenous fluid as alpha blockade commence - may have very severe drop on BP. The beta blockade added to prevent tachycardia
What percentage of phaeochyromocytomas are malignant? What percentage bilateral? how common are they? What percentage extra adrenal?
10% extra adrenal - sympathetic chain
10% malignant
10% bilateral
Phaeos are v. rare
