Hyperadrenal disorders Flashcards
Cushing’s syndrome causes
- taking too many oral steroids (determine if patient on cortisol type steroid/testosterone)=most common
- pituitary dependent Cushing’s disease (pituitary adenoma)
- ectopic ACTH from lung cancer cells
- adrenal adenoma or carcinoma secreting cortisol
Cushing’s syndrome clinical features
- excess cortisol
- mental changes (depression)
- moon face
- hirsutism
- acne
- ‘buffalo hump’ (interscapular fat pad)
- centripetal obesity
- osteoporosis
- proximal myopathy
- thin skin
- red striae (stretch marks)
- easy bruising
- hypertension
- hypokalaemia
- impaired glucose tolerance (diabetes)
Cushing’s syndrome investigations
24 hour urine collection for urinary free cortisol
-patients may forget to sample urine
Blood diurnal cortisol levels
-cortisol usually highest in morning(9am) and lowest at midnight/when asleep, so take midnight blood sample
-if cortisol level high in midnight blood sample then Cushing’s syndrome suspicion
Low dose dexamethasone suppression test
-0.5mg, 6 hourly for 48 hours
-dexamethasone is an artificial steroid and should suppress Hypothalamic Pituitary Axis, stopping ACTH release and hence suppressing cortisol to 0
-Cushing’s syndrome patients cortisol levels would be abnormally high
Cushing’s syndrome treatment options
Depends on cause of syndrome
- Pituitary surgery (transsphenoidal hypophysectomy) if Cushing’s disease
- Bilateral/ unilateral adrenalectomy (adrenal gland removal for adrenal mass)
- Drug treatments: Metyrapone and Ketoconazole
Metyrapone
Drug treatment for Cushing’s syndrome
- inhibits 11-beta hydroxylase so blocked cortisol synthesis
- reduced negative feedback on pituitary gland->ACTH secretion increase
- steroid synthesis in zone fasciculata and zona reticularis arrested at 11-deoxycortisol (accumulation of plasma 11-deoxycortisol)
Metyrapone uses
Control Cushing’s syndrome prior to surgery
- adjust oral dose according to cortisol (aim for mean serum cortisol of 150-300nmol/L)
- improve symptoms and promote better post-op recovery (better wound healing, less infection etc as thin skin and easy bruising from syndrome makes patients more prone to surgical complications)
Control Cushing’s symptoms after radiotherapy
-radiotherapy is usually slow to take effect
Metyrapone side effects
- 11-deoxycorticosterone accumulation in zone glomerulosa has mineralocorticoid (aldosterone-like) activity leading to salt retention and hypertension (on long term administration)
- increased adrenal androgen production causing hirsutism in women
Ketoconazole
Drug treatment for Cushing’s syndrome
- inhibits Cytochrome P450scc, blocking production of glucocorticoids, mineralocorticoids and sex steroids
- orally active
Ketoconazole uses
SIMILAR TO METYRAPONE
- Treatment and control of Cushing’s syndrome symptoms before surgery (off label use inhibiting steroidogenesis at high concentrations)
- antifungal agent but withdrawn in 2013 due to hepatotoxicity risk
Ketoconazole side effects
-Hepatotoxicity (chemical-driven liver damage) which could possibly cause death->monitor liver function (LFTs) weekly, clinically and biochemically
Conn’s syndrome causes
Benign adrenal cortical tumour of the zona glomerulosa causing excess aldosterone
Conn’s syndrome clinical features
-Increased sodium retention and potassium excretion leading to hypertension and hypokalaemia
Conn’s syndrome diagnosis
- Primary hyperaldosteronism (high BP and low blood potassium levels)
- Exclude secondary hyperaldosteronism with suppression of renin-angiotensin system (both primary and secondary have high aldosterone levels, but high BP of primary hyperaldosteronism should suppress renin release whilst reduced renal blood flow in secondary hyperaldosteronism should increase renin release)
Epleronone
Drug treatment for Conn’s syndrome
- mineralocorticoid receptor antagonist
- similar mineralocorticoid receptor affinity to spironolactone
- less binding to progesterone and androgen receptors compared to spironolactone (less menstrual irregularities and gynaecomastia so fewer side effects), so better tolerated and more favourable in long term
Spironolactone
Drug treatment for Conn’s syndrome
- mineralocorticoid receptor antagonist
- potassium sparing diuretic blocking sodium resorption and potassium excretion
- converted to several active metabolites, including Canrenone, a competitive antagonist of the mineralocorticoid receptor
