Hyperadrenal disorders Flashcards
10.10.2019
What are the clinical feature of Cushing’s?
- Too much cortisol
- Centripetal obesity
- Moon face
- buffalo hump
- Proximal myopathy
- Hypertension and hypokalaemia
- Red striae
- thin skin
- 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
Investigations to determine the cause of Cushing’s Syndiome
- 24 h urine collection for urinary free cortisol
- Blood diurnal cortisol levels
- (cortisols usually highest at 9am and lowest at midnight, if asleep)
- low dose dexamethasone suppression test
How does the low dose dexamethasone suppression test work?
- 0.5 mg 6 hourly for 48 hrs
- Dexamethasone = artificial steroid
- Normals will suppress cortisol to zero
- Any cause of Cushing’s will fail to suppress
What are pharmacological manipulations of steroids?
- Enzyme inhibitors
- Receptor blocking drugs
What is the diurnal rhythm of cortisol in Cushing’s syndrome like?
- constantly high
(usually it is highest in the morning, drops throughout the day and ‘‘recharges’’ at night.
Name 2 inhibitors of steroid synthesis
- Metyrapone
- Ketonazole
What drugs can you treat Cushing’s with?
Inhibitors of steroid biosynthesis
- metyrapone
- ketonazole
What drugs can you treat Conn’s syndrome with?
MR antagonists
- spironolactone
- epleronone
Name 2 MR antagonists
- spironolactone
- epleronone
Metyrapone - mechanism of action and effects
- inhibits 11-beta-hydroxylase
- cortisol synthesis blocked
- ACTH secretion increased
- plasma deoxycortisol increased
- steroid synthesis in the zona fasciculata [and reticularis] is arrested at the 11-deoxycortisol stage
What are the zones if the adrenal gland and what is produced where?
Medulla - catecholamines (A, NA)
Zona reticularis - sex steroids
Zona fasciculata - glucocorticoids (cortisol)
Zona glomerulosa - mineralcorticoids (aldosterone)
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 some side effects/unwanted actions of metyrapone?
- Increased adrenal androgen production HIRSUTISM
in women - Hypertension on long term admin. Deoxycorticosterone accumulates in z. glomerulosa; it has aldosterone-like (mineralocorticoid) activity, leading to salt retention and hypertension.
What is the mechanism of action of ketoconazole?
- main use as an antifungal agent – although withdrawn in 2013 due to risk of hepatotoxicity
- Blocks production of glucocorticoids, mineralocorticoids& sex steroids
- at higher concentrations, inhibits steroidogenesis – off-label use in Cushing’s syndrome
When is ketoconazole used?
Cushing’s syndrome
- treatment and control of symptoms prior to surgery
- orally active
What are unwanted actions of ketoconazole?
- Liver damage
- possibly fatal
- monitor liver function weekly, clinically and
biochemically
How do you treat Cushing’s?
- Depends on cause
- Pituitary surgery (transsphenoidal hypophysectomy)
- Bilateral adrenalectomy
- Unilateral adrenalectomy for adrenal mass
Drugs for medical treatment of Cushing’s
- Metyrapone
- Ketoconazole
What are the features of Conn’s syndrome?
- Benign adrenal cortical tumour (zona glomerulosa)
- Aldosterone in excess
- Hypertension and hypokalaemia
Drugs for medical treatment of Conn’s Syndrome
- spironolactone
- epleronone
OR surgery
Uses of spironolactone
- primary hyperaldosteronism (Conn’s syndrome)
Spironolactone: Mechanism of action
- 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).
Diagnosis of Conn’s syndrome
Measure in Blood:
- if aldoserone is high and
- RAS is suppressed (exclude secondary hyperaldosteronism)
=> the person has Conn’s syndrome
What are some unwanted actions of spironolactone?
- Menstrual irregularities (+ progesterone receptor)
- Gynaecomastia (- androgen receptor)
Properties of 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?
- tumors of the adrenal medulla
- secrete catecholamines (A and NA)
What are features of phaeochromocytoma?
- Hypertension in young people
- Episodic severe hypertension (after abdominal palpation)
- More common in certain inherited conditions
- Severe hypertension can cause MI or stroke
- High adrenaline can cause ventricular fibrillation + death
= medical emergency
What are some dangerous things that can happen in pheochromocytoma?
- Severe hypertension: can cause MI or stroke
- High adrenaline: can cause V-fib + death
=> medical emergency
Management of Phaeochromocytoma
- first therapeutic step: alpha blockade
- patients may need i.v. fluid as alpha blockade commences
- beta-blockade added to prevent tachycardia
=> then they will need surgery
Key facts about phaeochromocytoma
- 10 % extra-adrenal (sympathetic chain)
- 10 % malignant
- 10 % bilateral
- more than 10% is genetic
- Phaeo’s are extremely rare
(House loves rare…)
Why do you block alpha receptors first in phaeochromocytoma?
- BP goes down
this is why you should also give i.v. fluid before
What is known to be the 10% tumor disease?
- Phaeochromocytoma
10% malignant, 10% extra-aderenal, 10% bilateral
