Adrenal disorders Flashcards
When should you sample the cortisol of someone when you suspect it to be too high?
At night.
Difficult to get it for those who are night workers as diurnal rhythm has shifted
What is it called if you have too much Cortisol?
Cushing’s syndrome (source is adrenal)
What are the clinical features of Cushing’s syndrome?
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 disease?
Taking too many steroids
Pituitary dependent Cushing’s disease
Ectopic ACTH from lung cancer
adrenal adenoma secreting cortisol
What is the most common cause of Cushing’s Syndrome?
Taking too much steroids
What are the investigations to determine the cause of Cushing’s syndrome?
24 h urine collection for urinary free cortisol
Blood diurnal cortisol levels
Low dose dexamethasone suppression test
How would you carry out a dexamethasone suppression test?
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 9am cortisol - 800nM End of LDDST should be 0 normally, 680nM
What are the pharmacological manipulations for Cushing’s?
Enzyme inhibitors
Receptor blocking drugs
What drugs are inhibitors of steroid biosynthesis?
metyrapone, ketoconazole
What are the actions of Metyrapone?
Inhibition of 11-hydroxylase enzyme.
steroid synthesis in zona fasciculata inhibited at the 11-deoxycortisol stage.
11-deoxycortisol has no negative feedback on the hypothalamus and pituitary gland.
How would you use 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)
Why do you get osteoporosis & thin skin in Cushing’s?
Cortisol suppresses protein synthesis and stimulates fat synthesis.
Why do you get salt retention and hypertension ?
deoxycorticosterone accumulates in z. glomerulosa; it has aldosterone-like (mineralocorticoid) activity, leading to salt retention and hypertension.
What are the unwanted effects of Metyrapone?
Hypertension
Hirsutism
What is the mechanism of action for Ketoconazole?
main use as an antifungal agent – although withdrawn in 2013 due to risk of hepatotoxicity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
What enzyme does ketoconazole inhibit?
17-hydroxylase
What are the unwanted side effects of ketoconazole?
Liver damage - possibly fatal - monitor liver function weekly, clinically and biochemically
What is the treatment for Cushing’s?
Treatment Depends on cause
Pituitary surgery (transsphenoidal hypophysectomy)
Bilateral adrenalectomy
Unilateral adrenalectomy for adrenal mass
What is Conn’s syndrome?
Benign adrenal cortical tumour (zona glomerulosa)
Aldosterone in excess
Hypertension and hypokalaemia
What does Aldosterone do?
Controls blood pressure, sodium and potassium.
What diagnoses Conn’s syndrome?
Primary hyperaldosteronism
Renin - angiotensin system should be suppressed (exclude secondary hyperaldosteronism
What are the drugs for the treatment of Conn’s syndrome?
Spironolactone, epleronone
What is the action of Spironolactone?
Primary hyperaldosteronism (Conn’s syndrome) 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 unwanted side effects of Spironolactone?
Menstrual irregularities (+ progesterone receptor) Gynaecomastia (- androgen receptor)
