Adrenal disorders Flashcards
What is cushing’s syndrome?
A condition in which the patient with the disease produces excess cortisol
What are the clinical features of cushing’s?
- Too much cortisol (check bloods)
- Centripetal obesity
- Moon face and buffalo hump
- Proximal myopathy (thin arms and legs)
- Hypertension and hypokalaemia
- Red striae, thin, shiny skin and bruising
- osteoporosis, diabetes
- peripheral oedema
What are the causes for Cushing’s disease?
- The main cause of Cushing’s is taking too may steroids (as drugs or by actual medication).
- Pituitary dependent Cushing’s disease. Disease is to do the pituitary gland
- Ectopic ACTH released from lung cancer
- Adrenal adenoma secreting cortisol
What is the first investigation you would do to diagnose cushings?
24 hour urine collection for urinary free cortisol
What is the second test you would do to diagnose Cushing’s?
Blood diurnal (varying times of the day) cortisol analysis.
You lose the rhythm of cortisol if you have Cushing’s. Normally, cortisol at 9am will be very high but will drop at midnight. Therefore, you need to take (a blood) sample from patients at night. Every so often so observe normal changes. People who have Cushing’s will have a high level of cortisol all the time.
What is the final diagnostic test you would do to diagnose Cushing’s?
Low dose dexamethasone suppression test:
Give them a steroid (dexamethasone)- for example 0.5mg 6-hourly for 48 hours.
Normal people will be able to suppress cortisol to zero due to feedback inhibition. People with Cushing’s will not be able to supress the steroids.
What are the 2 methods of treatment of Cushing’s?
- Surgery is the main method of treatment.
You want to prevent cortisol production (keep it low) before surgery. You want them to recover well from the operation. With Cushing’s it’s about the post-operative care.
- These 2 drugs lower cortisol: metyrapone and ketoconazole.
What does Metyrapone do?
Inhibits 11 beta- hydroxylase
This enzyme catalyses the last step of producing cortisol and corticosterone.
There will be a rise in ATCH secretion (feedback- because there is no cortisol around)
There will therefore be a rise of 11-deoxycortisol and 11-deoxycorticosterone too. There is no negative feedback for 11-deoxycortisol.
What are the unwanted side effects of metyrapone?
- HYPERTENSION- 11- deoxycorticosterone increases and acts like aldosterone. Increases water and mineral reabsorption. It accumulates in zona glomerulosa.
- HIRSUTISM-All of the precursors that accumulate are funnelled into the sex steroid arm- leads to hirsutism in women (as they will make excess testosterone)
What is ketoconazole?
Antifungal agent that can block cortisol production. It can be used in select patients (with healthy livers).
At high concentrations, it inhibits steroidogenesis.
It blocks 17 alpha- hydroxylase (blocking reactions further up the chain).
Why do you need to be careful when using ketoconazole?
It is tablet that is taken orally and it will reduce the cortisol.
However, patients that take it need to have sufficient liver function otherwise, it can cause damage.
Suggest some cures for Cushing’s
- Remove the pituitary gland (pituitary surgery)- also known as a transsphenoidal hypophysectomy
- Remove the adrenal galnds (one or both)- if you remove both, it is known as a bilateral adrenalectomy.
What is Conn’s syndrome?
A condition in which you make too much aldosterone (because you have a neign tumour in the zona glomerulosa)
Characteristics of people with Conn’s syndrome
People with Conn’s syndrome have hypertension and hypokalaemia- due to water retention (aldosterone increases sodium reabsorption) and potassium secretion in the kidneys.
You need to measure the aldosterone in the blood, as well as the renin. If the renin is supressed and the aldosterone is high, then the patient has Conn’s syndrome
How can Conn’s syndrome (primary hyperaldosteronism) be treated?
It is treated by blocking the mineralocorticoid receptor that the hormone works through
- a mineralcorticoid antagonist.
