Management of Adrenal Dysfunction Flashcards
What are the clinical features of Cushing’s?
- Too much cortisol
- Centripetal obesity
- Moon face and buffalo hump
- Proximal myopathy
- Hypertension and hypokalaemia
- Red striae, thin skin and bruising
- osteoporosis, diabetes
- Fat retention, protein loss
What are the causes of Cushing’s?
- Taking too many steroids
- Pituitary dependent Cushing’s disease
- Ectopic ACTH from lung cancer
- Adrenal adenoma secreting cortisol
What are the investigations to determine cause of Cushing’s syndrome?
- 24 h urine collection for urinary free cortisol
- Blood diurnal cortisol levels
- Low dose dexamethasone (artificial steroid) suppression test
(•0.5 mg 6 hourly for 48 hrs
When is cortisol highest and lowest?
Highest at 9am and lowest at midnight, if asleep (don’t tell them incase stay up) - in Cushing’s or awake won’t be down at midnight
What will the result be for non Cushing’s in the low dose dexamethasone suppression test?
suppress cortisol to zero (any cause of Cushing’s fail to suppress)
What are the results for diagnosis of Cushing’s?
- Basal (9am) cortisol 800 nM
* End of LDDST (low dose suppression test): 680 nM
What is the pharmacological manipulation of steroids?
- Enzyme inhibitors
* Receptor blocking drugs
What are the inhibitors of steroid biosynthesis?
- metyrapone
2. ketoconazole
What is Conn’s syndrome?
Excess aldosterone
What are the MR antagonists for Conn’s syndrome?
- spironolactone
2. epleronone
What is the mechanism of Metyrapone?
- Inhibition of 11b-hydroxylase
- steroid synthesis in the zona fasciculata [and reticularis] is arrested at the 11-deoxycortisol stage
- 11-deoxycortisol has no negative feedback effect on the hypothalamus and pituitary gland - excess of this but deficient in cortisol
What are the uses of metyrapone?
- Control of Cushing’s syndrome prior to surgery.
- adjust dose (oral) according to cortisol (aim for mean serum cortisol 150-300 nmol/L)
- improves patient’s symptoms and promotes better post-op recovery (better wound healing, less infection etc) - Control of Cushing’s symptoms after radiotherapy (which is usually slow to take effect)
What are the unwanted actions of metyrapone?
- Hypertension on long-term administration
* Hirsutism (bit more testosterone made)
What is the mechanism of ketoconazole?
Blocks 17 alpha hydroxylase, inhibiting cortisol production
What are the main uses to ketoconazole?
- Cushing’s syndrome
- treatment and control of symptoms prior to surgery
- orally active - Main use as an antifungal agent – although withdrawn in 2013 due to risk of hepatotoxicity
•at higher concentrations, inhibits steroidogenesis – off-label use in Cushing’s syndrome