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
Why does Metyrapone cause hypertension?
- Deoxycorticosterone accumulates in z. glomerulosa
- It has aldosterone-like (mineralocorticoid) activity
- Leading to salt retention and hypertension
What is Ketoconazole’s mechanism of action?
- Blocks 17a hydroxylase
2. Inhibiting cortisol production
What are the uses of Ketoconazole?
- Treatment and control of symptoms prior to surgery
2. Orally active
What are the unwanted actions of Ketoconazole?
Liver damage (possibly fatal)
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 caused by?
Benign adrenal cortical tumour
zona glomerulosa
What is aldosterone’s action?
Controls BP, sodium and lowers potassium
What can Conn’s syndrome lead to?
- Hypertension
2. Hypokalaemia
How is Conn’s syndrome medically treated?
MR (mineralocorticoid receptor) antagonist
What MR antagonists are used in Conn’s syndrome?
- Spironolactone
2. Epleronone
What is the mechanism of action 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).
What are the pharmacokinetics of Spironolactone?
- Orally active
2. Highly protein bound and metabolised in the liver
What are the unwanted actions of Spironolactone?
- Menstrual irregularities (+ progesterone receptor)
2. Gynaecomastia (- androgen receptor)
Whyi is Epleronone better tolerated than Spironolactone?
Less binding to androgen and progesterone receptors
What are phaeochromocytomas?
Tumours of the adrenal medulla which secrete catecholamines
What are catecholamines?
Adrenaline and nor-adrenaline
What are the clinical features of a phaeo?
- Hypertension in young people
- 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 a phaeo?
- Alpha blockade is first therapeutic step.
- Patients may need intravenous fluid as alpha blockade commences
- Beta blockade added to prevent tachycardia
- Eventually need surgery
Why do phaeo patients need careful preparation for surgery?
Anaesthetic can precipitate a hypertensive crisis
