Adrenals Flashcards
Which cells in the adrenal medulla release catecholamines?
Chromaffin cells
What stimulates aldosterone release from the zona glomerulosa?
- potassium (increase in)
- reduced BP (angiotensin II)
- ACTH secretion
What type of receptor is the mineralocorticoid receptor?
Nuclear receptor
What changes occur when aldosterone binds to the mineralocorticoid receptor?
Na/K ATPase stimulated Increased expression of ENaC Additional ENaC Stimulates H+ ATPase - result = loss of H+ = metabolic alkalosis
What are the potential causes of primary hyperaldosteronism?
- Conn’s syndrome
- Aldosterone producing adenoma
- Bilateral adrenal hyperplasia
What are the signs of Conn’s syndrome?
- hypertension
- suppressed plasma renin activity
- increased aldosterone secretion
How can primary hyperaldosteronism be diagnosed?
- aldosterone:renin ratio
- saline suppression test
- CT adrenal
- adrenal venous sampling
- metomide PET
How can primary hyperaldosteronism be treated?
MR antagonists, e.g.:
- spironolactone
- eplerenone
What is Liddle’s syndrome? What are the signs?
It's overexpression of eNaC Signs: - hypertension - hypokalaemia - metabolic alkalosis (increased H+ secretion)
What do glucocorticoids inhibit?
- CRH secretion + RNA transcription
- AVP secretion + RNA transcription
- ACTH secretion
- POMC transcription
What are the main causes of Cushing’s syndrome?
- Iatrogenic - steroid creams/inhalers/tablets
- corticotrophin adenoma of pituitary
- ectopic ACTH secreting neuroendocrine tumour
- cortisol secreting adrenal adenoma
- bilateral adrenal hyperplasia
How is Cushing’s syndrome diagnosed?
- overnight dexamethasone suppression test
- 24 hour urine free cortisol
- LDDST (low dose dexamethasone suppression test): 0.5mg dexamethasone every 6 hours for 2 days
- cortisol day urine and midnight sleeping control
What imaging can be done for Cushing’s syndrome?
- MRI pituitary
- CT adrenals
- Inferior petrosal sinus sampling
- Nuclear medicine: octreotide uptake scan
What is the treatment for Cushing’s syndrome?
Pituitary:
- transsphenoidal surgery
- external beam radiotherapy
- stereotactic radiosurgery
Adrenal:
- adrenalectomy
- metyrapone/ketoconazole/etomidate
What are the main reasons for primary adrenal failure/insufficiency?
- autoimmune
- tuberculosis
What are the symptoms of Addison’s?
- fatigue
- weakness
- myalgia
- anorexia
- weight loss
- hyper pigmentation
What is an Addisonian crisis?
- low BP (can’t respond to hypotension)
- low glucose (can’t respond to hypoglycaemia)
- low Na+ (no/lack of aldosterone)
- high K+ (no/lack of aldosterone)
How is Addison syndrome diagnosed?
- low 9am cortisol
- high ACTH
- short synacthen test (see if corticotrophs react to stimulation with synthetic ACTH)
How is Addison syndrome treated? How is an Addisonian crisis treated?
- replacement steroid (hydrocortison, fludrocortisone)
Addisonian Crisis: IV fluid resuscitation, IM hydrocortisone
What causes congenital adrenal hyperplasia?
due to 21-hydroxylase deficiency
= no conversion to aldosterone and cortisol
What is changes result from congenital adrenal hyperplasia?
- excess ACTH will be secreted (no -ve feedback)
- stimulate cholesterol uptake in adrenal gland –> instead of being converted to cortisol –> converted to testosterone
What are catecholamines made from?
L-tyrosine
What are the different types of chromaffin cell tumours?
- phaeochromacytoma: arising from within the adrenal medulla
- paraganglioma: extra-adrenal tumour
What are alpha 1 receptors responsible for?
vascular and smooth muscle contraction
What are alpha 2 receptors responsible for?
presynaptic, inhibitory to noradrenaline release –> suppress BP
What are beta 1 receptors responsible for?
- positive inotropic and chronotropic in heart
- increase renin
- increase lipolysis
What are beta 2 receptors responsible for?
- bronchodilation
- vascular dilation
- uterine smooth muscle relaxation
- glycogenolysis
What are beta 3 receptors responsible for?
- lipolysis
- energy expenditure
What are D1 receptors responsible for?
cerebral, renal, mesenteric, coronary vasculature dilation
What are D2 receptors responsible for?
presynaptic inhibition of noradrenaline + prolactin release
What are the symptoms of catecholamine excess?
- impending doom
- diaphoresis
- dyspnea
- headache
- hypertension
- palpitation
- tremor
- N+V
- fatigue
- orthostatic hypotension
- hyperglycaemia
- weight loss
- epigastric + chest pain
- congestive heart failure
What are the signs of phaemochromocytoma and paraganglioma (PPGL)?
- hyperadrenergic spells
- resistance hypertension
- familial syndrome
- incidentally discovered adrenal mass
- pressor response during general anaesthesia
- early onset hypertension
- dilated cardiomyopathy
How is PPGL diagnosed?
- 24hour urine metanephrines
- plasma metanephrines
- CT/MRI adrenals and abdomen
- I-MIBG scintigraphy
How is PPGL treated?
- surgical resection
- pre-operative alpha and beta blockade –> phenoxybenzamine and propanolol
- acute crisis: IV phentolamine or nircardipine
- avoid opiates
- I-MIBG therapy for malignant disease
What would happen if you treated a patient with a pheochromocytoma with beta-blockers alone?
will lead to more vasoconstriction –> will block beta-2 receptors causing vasodilation
