28- Addison's Disease Flashcards
what is Addison’s disease?
a progressive condition of primary adrenal insufficiency, characterised by lack of cortisol and aldosterone from the adrenal glands
distinguish primary and secondary adrenal insufficiency
primary adrenal insufficiency - Addison’s disease:
- insufficient production of cortisol and aldosterone from autoimmune destruction of the adrenal cortex, leads to adrenal failure
- low cortisol and aldosterone
secondary adrenal insufficiency:
- pituitary or hypothalamic disease leading to insufficient cortisol production
- adrenal gland is still functional = low cortisol
- aldosterone/ mineralocorticoid production is regulated by RAAS
how does the lack of cortisol affect the HPA axis in both primary and secondary adrenal insufficiency? what is the consequence of this?
lack of cortisol = negative feedback to HPA axis = increased/elevated CRH and ACTH production
consequence is higher levels of ADH secretion - though it’s stimulated by changes in plasma osmolarity, the absence of cortisol negative feedback further increases its secretion
symptoms commonly associated with Addison’s disease (4)
anorexia
fatigue, weakness
GI symptoms - constipation, diarrhoea, abdominal pain
hyperpigmentation
diagnostic signs observed in Addison’s disease (5)
hypotension
low/normal plasma Na+
normal/high plasma K+
high ACTH
high plasma renin
what contributes to hypotension in Addison’s disease?
the lack of cortisol and aldosterone - aldosterone is important for blood volume regulation, absence contributes to volume depletion
how does hyperpigmentation occur in Addison’s disease?
caused by high levels of ACTH
prolonged high ACTH stimulates melanocyte receptors due to cross-reactivity = causes a characteristic pattern of hyperpigmentation
why are plasma sodium levels typically normal to low in Addison’s disease?
absence of cortisol = lack of cortisol negative feedback increases ADH levels
ADH promotes pure water reabsorption, diluting electrolytes in the extracellular fluid
hyponatremia tends to develop later in Addison’s disease
why doesn’t aldosterone contribute to hyponatremia in Addison’s disease?
lack of aldosterone can lead to salt wasting and higher urinary sodium excretion
however, aldosterone affects Na+ reabsorption, which brings an osmotic equivalent of water with it - aldosterone affects volume depletion, has very little effect on plasma Na+ conc
what contributes to the elevation of plasma renin in Addison’s disease?
elevated plasma renin from lack of aldosterone - RAAS is activated to compensate for volume depletion, but the adrenal glands can’t produce aldosterone due to their dysfunction
how is Addison’s disease diagnosed?
hallmarked by high ACTH and low cortisol
dynamic tests - e.g. ACTH stimulation/ syancthen test - used to assess the adrenal glands’ ability to produce cortisol in response to ACTH
what is the purpose of the ACTH stimulation test?
evaluates the adrenal glands’ ability to produce cortisol in response to ACTH
diagnoses adrenal insufficiency, differentiates between primary and secondary causes
what is the short synacthen test?
baseline cortisol levels are measured in the morning, then synthetic ACTH (synacthen) is given
cortisol levels are measured at 30 and 60 minutes post-injection
criteria for a normal response in the short synacthen test?
normal response:
- increase in cortisol above 200nmol/L from baseline
- cortisol at 30 minutes greater than 550 nmol/L
when is the long synacthen test used, and why? what test is more preferred?
used to diagnose secondary adrenal insufficiency, assesses adrenal responsiveness over an extended period of time
ACTH assay used instead, it’s sufficient for distinguishing between primary and secondary causes
