Cortisol normally produced from adrenal cortex - zona fasciculata

Mineralocorticoids

• similarity to aldosterone

• influence salt and water balance

• fludrocortisone

Glucocorticoids

• hydrocortisone = natural glucocorticoid

  • normal unstressed: 10-20mg/day

  • increase to 300mg in stressed, ill patient

• Synthetic:

  • hydrocortisone

  • prednisone

  • triamcilone

  • dexamethasone

• Effects:

  • anti-inflammatory

  • immunosuppressant

  • metabolic effects

    • protein/lipid metabolism

    • inc. gluconeogenesis

    • inc. glycogen deposition

Prednisone

• readily absorbed from GI tract

• converted to active metabolite prednisolone in liver

  • takes \~60min

  • conversion not diminished by liver disease

• Excreted in urine as free and conjugated metabolites

• plasma half-life 2-4 hours

• 4x anti-inflammatory effect cf. hydrocortisone

• 0.8x sodium retaining properties cf. hydrocortisone

• Dexamethasone = 40x anti-inflam effect cf. hydrocortisone

• (fludrocortisone = 150x sodium retaining cf. hydrocortisone)

Pregnancy:

Benefits generally outweigh risks

• increased IUGR with long term use (not short term)

• no increase cleft palate

• adrenal suppression in neonate rarely clinically significant

• appears in breast milk:

  • \<40mg/day unlikely to causee systemic effects in infant

Hypothalamic-pituitary-adrenal suppression:

• Inhibition may lead to adrenal insufficiency when steroids are ceased after long term use

• treatment for \<3 weeks or with less than 10mg of prednisone unlikely to suppress h-p-a axis - unless clinically cushingoid

• Low early morning cortisol levels after omitting therapy for 24 hours suggest suppression

• Evening doses of steroids inc. risk of suppression

• Alternate day therapy probably doesn’t reduce the risk

• Some evidence that adrenal gland is suppressed during inhaled corticosteroid use

  • unlikely to be clinically signifiant but consider if addisonian presentation

• Addisononian crisis:

  • anorexia, nausea/vomiting

  • hypotension

  • sudden pain - abdominal, legs, lower back

  • Syncope

  • Hypoglycaemia

  • Confusion

  • Electrolyte disturbance

  • Seizure

  • Fever

Stress dose steroids:

• controversial

• traditional:

  • double dose for major illness (defined as fever present) if adrenal suppressed and stress dose for surgery.

• However; lack of evidence to support this.

  • Cochrane, Marick et al. (2008) recommend to continue usual daily dose

  • Adrenal testing too sensitive and doesn’t predict addisonian crisis

Adverse effects (not exhaustive list) - Cushing’s

• Psychiatric disturbance

  • change mood (up and down)

  • psychosis

  • emotional lability

• HTN

  • mineralocorticoid effect

  • salt and h2o retention

• Suppression of response to infection/injury

• Osteoporosis

  • increased calcium excretion

  • dec. osteoblast and inc. osteoclast

  • greatest rate of bone loss occurs first 6-12 months

  • @ risk if >7.5mg prednisone/day for >3/12

  • Should be on Vit D

    • consider calcium supplementation if dietary calcium not sufficient

      • ?inc. cardiovascular risk with calcium

      • Calcium carbonate 1.5g daily

  • bisphosphonate recommended if using steroid and:

    • >65yo

    • \< 65yo and previous fragility # or T-score \<= -1

    • if doesn’t meet special authority criteria

      • etidronate 400mg daily on empty stomach for 14/7

        • repeated every 3 months

        • significantly “weaker” cf. alendronate/zolendronic acid

  • Note avascular necrosis of head of femur due to altered blood supply and assoc. with corticosteroid use

• Hyperglycaemia

  • inc. gluconeogensis, inc. glycolysis

  • dec. glucose utilisation/uptake

  • Recommend screening if long term steroid and >25yo for T2DM

• Muscle wasting and proximal muscle weakness

• Skin: striae,thinning, bruising

• Hirsutism

• Glaucoma

• Cataracts

• GI upset/peptic ulceration

  • consider co-prescription with PPI

• inc. intracranial pressure

• Children:

  • inhibition of growth if used >6 months

Tapering corticosteroids

• Tapering may not be required if \<40mg prednisone for less than 3 weeks

• Should not be abrupt if >3 weeks

  • Taper to allow HPA axis to recover (over weeks or months)

• Number of methods (BPAC):

  • dec. 2.5-5mg every 1-3 days

    • or 10% every 2-4 weeks

  • once dose @ 10mg reduce more slowly:

    • 1mg/week

  • reduce more slowly if likely disease will relapse

  • longer term treatment:

    • more gradual rate