Primary adrenal insufficiency Flashcards
Definition
Destruction of adrenal cortex resulting in aldosterone (mineralocorticoid), cortisol (glucocorticoid) & androgen (DHEA converted to testosterone) deficiency
- in Addison’s disease there is 21-alpha-hydroxylase autoantibody mediated destruction
Aldosterone - production site & function
Secreted from zona glomerulosa of adrenal cortex. Stimulates Na+ reabsorption & K+ excretion & H+ excretion by: increasing activity of basolateral Na+/K+ ATPase & increasing transcription of ENaC in principal cells of collecting ducts. In alpha intercalated cells, aldosterone increases H+ excretion by increasing activity of H+ ATPase pumps in apical membrane.
Cortisol - functions & production site
Secreted from zona fasciculata of adrenal cortex in response to ACTH secretion from anterior pituitary.
- Increases blood glucose by directly stimulating hepatic gluconeogenesis & indirectly stimulating glycogenolysis
- Increases BP by increasing sensitivity of alpha-1 adrenergic receptors in VSM to catecholamines
- increases proteolysis in muscles to release AA as gluconeogenic substrates
Which androgens does adrenal gland produce? Implication of this for adrenal insufficiency
DHEA (dihydroepiandosterone) which is converted to testosterone. In men, the main source of testosterone is from Leydig cells in the testes therefore primary adrenal insufficiency doesn’t affect gonadal development or body hair. In women, primary adrenal insufficiency results in loss of pubic & axillary hair & body hair.
Causes
Most common in UK = autoimmune adrenalitis (Addison’s disease) - 21 alpha hydroxylase autoantibodies destroy adrenal cortex.
Most common worldwide = TB (+sarcoidosis)
Other causes: adrenal metastases & adrenal haemorrhage due to meningococcal septicaemia- known as Waterhouse-Friderichsen syndrome
What is Waterhouse-Friderichsen syndrome?
Bacterial infection, most commonly meningococcal septicaemia due to Neisseria meningiditis, causes adrenal haemorrhage (rupture of adrenal BV) resulting in primary adrenal insufficiency.
Signs and symptoms
SIGNS:
- bronze skin pigmentation, especially in palmar creases & joints = KEY
- hypoglycaemia (cortisol important for raising blood glucose)
- postural hypotension (low aldosterone & fluid depletion)
- loss of pubic & axillary hair (reduced androgens- DHEA)
- often associated with vitiligo
SYMPTOMS
- depression
- fatigue & lethargy
- salt cravings (due to low Na+ due to low aldosterone)
Non-specific symptoms:
- weight loss & anorexia
- abdominal pain
- nausea & vomiting
Pathophysiology
Low cortisol results in high ACTH release from anterior pituitary due to lack of negative feedback. ACTH & MSH (melanocyte-stimulating hormone) are both cleaved from POMC (proopiomelanocortinn) precursor. High ACTH means high MSH resulting in bronze skin pigmentation in palmar creases & joints. This is a KEY sign not present in secondary adrenal insufficiency (since low ACTH causes low cortisol).
1st line Investigations & gold standard test
1st line:
- Morning 9AM serum cortisol- low
- Plasma ACTH- high (due to lack of negative feedback)
- U & E- low Na+ & high K+ (due to low aldosterone), may show raised urea & creatinine due to volume depletion
- Serum aldosterone = low & plasma renin = high (due to hypotension, JGA cells are stimulated to release renin)
- 21 hydroxylase antibodies- high sensitivity, if +ve indicate, autoimmune adrenalitis (Addison’s disease)
Gold standard for PAI = short Synacthen test:
Measure basal cortisol at 9AM, administer IM Syancthen, measure plasma cortisol again at 30 mins. Failure of cortisol levels to rise to at least double the baseline indicates primary adrenal insufficiency. Exclude PAI if 30 mins post-Synacthen cortisol > 550nmol/L (adrenal glands still working).
Consider:
- Blood glucose- check for hypoglycaemia (Adrenal insufficiency can cause this)
- CXR if TB suspected
Treatment + principles of this
Hydrocortisone (corticosteroid for cortisol replacement) + Fludrocortisone (mineralocorticoid replacement, will correct postural hypotension by increasing Na+ & water reabsorption)
- During intercurrent illness, double hydrocortisone dose to prevent adrenal crisis (as cortisol needed for stress response).
- after 3 weeks of steroids DON’T stop as risk of adrenal crisis
- sick day rules - double dose
- treatment card
- osteoporosis- give bisphosphonates
- peptic ulcers risk - use PPI
Complications
Adrenal/Addisonian crisis-
- precipitated by infection/intercurrent illness or poor compliance with hydrocortisone therapy or abruptly stopping long-term exogenous steroids (suppress CRH & ACTH so zona fasciculata atrophies & endogenous cortisol production decreases)
Tx:
- give** IV /IM (in community)hydrocortisone 100mg**
- then IV 0.9% NaCl + dextrose if hypoglycaemic
- then 200mg hydrocortisone over next 24 hours
