Adrenal Disorders (Hyper) 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
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 investigations are used to determine the cause of Cushing’s syndrome?
- 24 h urine collection for urinary free cortisol
- Blood diurnal cortisol levels - in normal circumstances, is lowest at midnight
- Low dose dexamethasone suppression test
What is dexamethasone?
Artificial steroid
How does a low dose dexamethasone suppression test?
0.5 mg 6 hourly for 48 hrs
- Normal people will suppress cortisol to zero
- Any cause of Cushing’s will fail to suppress
What does the pharmacological manipulation of steroids encompass?
- Enzyme inhibitors
2. Receptor blocking drugs
What two syndromes are caused from hypersecretion of hormones of the adrenal cortex
- Cushing’s syndrome
2. Conn’s syndrome
What is Cushing’s syndrome?
Excess cortisol
What is Conn’s Syndrome?
Excess aldosterone
How is Cushing’s syndrome medically treated?
Inhibition of steroid biosynthesis
What drugs are used for inhibition of steroid biosynthesis in Cushing’s syndrome?
- Metyrapone
2. Ketaconazole
What is Metyrapone’s mechanism of action?
- 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.
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 of long-term administration
2. Hirsutism in women
Why does Metyrapone cause hirsutism?
Increased adrenal androgen production