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
Why do you get hypertension with metyrapone?
(11) deoxycorticosterone accumulates in z. glomerulosa and has aldosterone like (mineralcorticoid) activity, leading to salt retention and hypertension
Why do you get hirutism in women with metyrapone?
Increased adrenal androgen production
What are the unwanted actions of ketoconazole?
Liver damage - possibly fatal - monitor liver function weekly, clinically and biochemically
What is the treatment of Cushing’s?
(depends on cause)
- Pituitary surgery (transsphenoidal hypophysectomy)
- Bilateral adrenalectomy
- Unilateral adrenalectomy for adrenal mass
What is Conn’s syndrome? What does it cause?
- Benign adrenal cortical tumour (zona glomerulosa)
- Aldosterone in excess
- Hypertension and hypokalaemia
What is the diagnosis for Conn’s syndrome?
- Primary hyperaldosteronism
2. Renin - angiotensin system should be suppressed (exclude secondary hyperaldosteronism)
What is the mechanism of Spironolactone?
- Converted to several active metabolites, including canrenone, a competitive antagonist of the mineralocorticoid receptor (MR).
- Blocks Na+ resorption and K+ excretion in the kidney tubules (potassium sparing diuretic).
When is spironolactone used?
Primary hyperaldosteronism (Conn’s syndrome)
What is the pharmacokinetics of spironolactone?
- Orally active
* Highly protein bound and metabolised in the liver
What are the unwanted actions of spironolactone?
- Menstrual irregularities (+ progesterone receptor)
2. Gynaecomastia (- androgen receptor)
What is epleronone?
- mineralocorticoid receptor (MR) antagonist
- Similar affinity to the MR compared to spironolactone
- Less binding to androgen and progesterone receptors compared to spironolactone, so better tolerated
What are Phaeochromocytomas?
tumours of the adrenal MEDULLA which secrete catecholamines
adrenaline and nor-adrenaline
What are the clinical features of phaeo?
- Hypertension in young people - intermittent episodes
- Episodic severe hypertension(after abdominal palpation)
•More common in certain inherited conditions - Severe hypertension can cause myocardial infarction or stroke
- High adrenaline can cause ventricular fibrillation + death
- Thus this is a medical emergency
What is the management of phaeo?
- Eventually need surgery, but patient needs careful preparation as anaesthetic can precipitate a hypertensive crisis
- Alpha blockade is first therapeutic step blocks receptor that causes severe hypertension (BP falls when given)
- Patients may need intravenous fluid as alpha blockade commences
- Beta blockade added to prevent tachycardia
- When fully blocked go home, then op
What are some facts about Phaeochromocytoma?
- 10 % extra-adrenal (sympathetic chain) (paragangliomas)
- 10 % malignant
- 10 % bilateral
- Phaeo’s are extremely rare
What do you measure in phaeo?
Not A as changes but breakdown product of A e.g. metanephrine (in blood or urine) as around for a while
