Endocrine_CCT (1) Flashcards
What is the other name for hyperaldosteronism?
Hyperaldosteronism - aka Conn’s Syndrome
What happens in Conn’s syndrome?
Hyperaldosteronism (Conn’s)
- Excess production of aldosterone (independent of the renin-angiotensin system) -> an increase in the sodium and water retention
- decrease in the renin release (as compensatory mechanism)
What condition would you suspect in a patient who presents with the following:
- Hypertension
- Hypokalaemia
- Alkalosis
Serum sodium mildly raised or normal
Conn’s syndrome/ hyperaldosteronism
Symptoms of Conn’s
Symptoms of Conn’s:
- often asymptomatic
- signs of hypokalaemia
- weakness
- cramps
- paraesthesia
- polyuria
- polydipsia
- high blood pressure, sometimes but not always
Common causes of Conn’s syndrome
Common causes:
- 2/3 are due to a solitary aldosterone-producing adenoma, and that is linked to mutation in K+ channels
- the rest are due to bilateral adrenocortical hyperplasia
Rare causes of Conn’s syndrome
Rare causes:
- Adrenal carcinoma
- Glucocorticoid-remediable aldosteronism -the ACTH regulatory element of the 11B-hydroxylase gene fuses to the aldosterone synthase gene. This is a genetic condition which should be offered genetic testing.
- Increase aldosterone production and bringing it under the control of ACTH
Investigations in Conn’s
- U&E
- Renin
- Aldosterone
- Adrenal vein sampling
Do not rely on low potassium, and in more than 20% of the patients they are normokalaemic
Treatment for Primary hyperaldosteronism/ Conn’s (depending on cause)
- Conn’s: laparoscopic adrenalectomy
- Spironolactone for 4 weeks pre-op and that is to control BP and K+
- Hyperplasia: treated medically, spironolactone or amiloride
- Adrenal carcinoma: surgery and post operative adrenolytic therapy with mitotance (anti-neoplastic agent) -the prognosis is usually is poor
What happens in Cushing’s syndrome?
Cushing’s syndrome - clinical state where there is a chronic glucocorticoid excess + loss of the normal feedback mechanisms of they hypothalamo-pituitary-adrenal axis and the loss of the circadian rhythm of cortisol secretion
What’s Cushing’s disease?
Pituitary adenoma causing an increase in ACTH
What are the commonest causes of Cushing’s syndrome?
- oral steroids -> the most common
- endogenous causes are rare -> more than 80% are due to an increase of ACTH, of these a pituitary adenoma (Cushing’s disease) is the commonest cause
What conditions may cause ectopic ACTH production?
Ectopic ACTH production: this is due to small cell lung cancer and carcinoid tumours
What happens in Dexamethasone test, when there is an ectopic release of ACTH?
Dexamethasone in high doses fails to supress the cortisol production
What happens in Dexamethasone test in case of pituitary adenoma?
Pituitary adenoma = Cushing’s disease
- low-dose dexamethasone test leads to no change in the plasma cortisol
- 8mg may be enough to halve the morning cortisol
What happens on Dexamethasone test in case of adrenal adenoma?
Adrenal adenoma/cancer: because thetumour is autonomous dextamethasone in any dose will not supress the cotisol
Signs and symptoms of Cushing’s syndrome
- Increase in weight
- Mood change
- Depression
- Lethargy
- Irritability
- Psychosis
- Proximal weakness
- Gonadal dysfunction
- Acne
- Recurrent Achilles tendon rupture
- Central obesity
- Moon face
- Supraclavicular fat distribution
- Skin and muscle atrophy
- Bruises
- Purple striae
- Increased BM
- Increased BP
- poor healing
- osteoporosis
What (2) electrolyte abnormalities may Cushing syndrome present with?
- hypokalaemia
- metabolic alkalosis
Ix for Cushing’s syndrome
- raised plasma cortisol
- overnight dexamethasone suppression test
- 24h urinary free cortisol (an alternative)
What times to perform overnight dexamethasone test?
Dexamethasone 1mg po at midnight -> do serum cortisol at 8am.
Normally, cortisol suppresses to <50nmol/L; no suppression in Cushing’s syndrome.
Result of cortisol testing - what may it mean?
Not suppressed by low-dose dexamethasone
Cushing’s syndrome not due to primary causes, i.e. likely secondary to corticosteroid therapy
Result of cortisol testing - what may it mean?
Not suppressed by low-dose, but suppressed by high-dose dexamethasone
Cushing’s disease (pituitary adenoma)
Result of cortisol testing - what may it mean?
Not suppressed by low- or high-dose dexamethasone
Ectopic ACTH syndrome likely
CRH stimulation results
- if pituitary source
- if ectopic/adrenal source
CRH stimulation
- if pituitary source then cortisol rises
- if ectopic/adrenal then no change in cortisol
Treatment for Cushing’s disease
Cushing’s disease:
- removal of the adenoma
- bilateral adrenalectomy if source unlocatable, or recurrence post-op
Treatment for Cushing’s if adrenal adenoma/carcinoma
Adrenal adenoma or carcinoma:
- adrenalectomy cures the adenomas but never the carcinomas, therefore radio and adrenolytic drugs are done if it is carcinogenic
Treatment for Cushing’s syndrome, in case of ectopic cause
Ectopic:
- surgery if the tumour is able to be located or not have spread
- Metyrapone (inhibiotir of, steroid enzyme), ketoconazole (anti-fungal), and fluconazole ↓cortisol secretion pre-op or if awaiting effects of radiation
- Intubation + mifepristone (competes with cortisol at receptors) + etomidate (blocks cortisol synthesis) may be needed, eg in severeACTH-associated psychosis
What’s Pseudo-Cushing’s?
Pseudo-Cushing’s
- mimics Cushing’s
- often due to alcohol excess or severe depression
- causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
- insulin stress test may be used to differentiate
What’s Addison’s disease?
Addison’s disease = Primary hypoaldosteronism/ adrenal insufficiency
- Autoimmune destruction of the adrenal glands is the commonest cause
- reduced cortisol and aldosterone being produced
Features of Addison’s disease
- lethargy, weakness
- anorexia, nausea & vomiting
- weight loss
- ‘salt-craving’
- hyperpigmentation (especially palmar creases)
- vitiligo
- loss of pubic hair in women
- hypotension
- hypoglycaemia
- crisis: collapse, shock, pyrexia, hypotension, tachycardia
Other causes (than autoimmune destruction) of Addison’s
Primary causes -> adrenal gland destruction
- tuberculosis
- metastases (e.g. bronchial carcinoma)
- meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
- HIV
- antiphospholipid syndrome
Secondary causes
- pituitary disorders (e.g. tumours, irradiation, infiltration)
What electrolyte abnormalities may be seen in Addison’s disease?
- hyperkalaemia
- hyponatraemia
- hypoglycaemia
- metabolic acidosis
What is the Synacthen test used for and what’s its other name?
Synacthen test = short ACTH stimulation test
Used in Addison’s disease (primary adrenal insufficiency)
How Synachten test is performed?
Synachten test (in Addison’s - adrenal insufficiency)
- Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM
- Addison’s is excluded if 30min cortisol >550nmol/L.
*ACTH is injected and the amount of cortisol produced is checked
What are other than Synachten test, Ix in Addison’s (adrenal insufficiency)?
- positive for 21-hydroxylase adrenal autoantibodies
- Plasma renin and aldosterone: and this is to assess the mineralocorticoid status
- XRAY: either chest or abdominal xray -> to check if the patient had any past TB, upper zone fibrosis or adrenal calcification if no autoantibodies, then consider further tests (as these may cause ssecondary destruction to adrenal glands)
Management of Addison’s disease
- Replace the steroids 15-25mg hydrocortisone daily in 2-3 doses
- Mineralocorticoids to correct postural hypotension, low Na and high K+ -fludrocortisone PO 50-200mcg daily.
Steroids in Addison’s disease (administration and advice)
- should be avoided giving late as they might cause insomnia
- advice to wear bracelets that might suggest steroid use
- Give IM if they are unwell
- Do not stop the steroids abruptly and other prescriptions should know that the patient is on steroids
