acute adrenal insufficiency
DESCRIPTION
Acute Adrenal Insufficiency. Dr. Sohail Inam FRCP (Ed), FRCP Consultant & Head, Division of Endocrinology Armed Forces Hospital Riyadh. CRH. AVP. Renin substrate. Kidney. Renin. ACTH. Angiotensin I. Angiotensin II. Cortisol. Aldosterone. Androgens. CRH. AVP. Renin substrate. - PowerPoint PPT PresentationTRANSCRIPT
Acute Adrenal Insufficiency
Dr. Sohail Inam FRCP (Ed), FRCPConsultant & Head, Division of Endocrinology
Armed Forces HospitalRiyadh
Kidney
ACTH
Cortisol Aldosterone
Renin
Angiotensin II
Renin substrate
Angiotensin I
Androgens
CRHAVP
Kidney
ACTH
Cortisol Aldosterone
Renin
Angiotensin II
Renin substrate
Angiotensin I
Androgens
CRHAVP
X
Kidney
ACTH
Cortisol Aldosterone
Renin
Angiotensin II
Renin substrate
Angiotensin I
Androgens
CRHAVP
X
Acute Adrenal Insufficiency
Previous adrenal insufficiency
Previous normal adrenal functionAcute adrenal injury
Acute pituitary injury
Drug related effect
Functional adrenal insufficiency
Beware of previous corticosteroid use
Acute Adrenal InsufficiencyPresentation
Non-specific
HypotensionPostural
Recumbent
Abdominal pain
Electrolyte disturbances
Hypoglycemia
Acute Adrenal InsufficiencyPrecipitating factors
Omission of corticosteroids
Increased requirementsInfection
Physical stress
Drugs
Diagnosis
Measurement of adrenal hormones
Cortisol
Primary versus central
ACTH
Determine cause
DiagnosisCortisol
Random8-9 am levelLevel during stress
StimulatedACTH HypoglycemiaCRHMetyrapone
% c
hanc
e of
adr
enal
insu
ffic
ienc
y
9 am serum cortisol nmol/l
<83 650
0
100
ACTH Stimulation Test
Standard (250 mcg) , Low dose (1mcg)
Can be performed any time though preferably 8-9 am.
0, 30, 60 minute
Any value 550 nmol/l excludes adrenal insufficiency in non-critically ill patients
Test is abnormal in almost all patients with primary adrenal insufficiency & 90% individuals with central adrenal insufficiency
Pituitary Stimulation Tests
Insulin tolerance test (ITT)Gold standard for central disease
Risk from hypoglycemia
CRH
Metyrapone
Other
Suspicion of AIApproach
ACTH stimulation test
ACTH measurement on basal sample
Acute AIManagement
Fluids
Glucocorticoids
Treat underlying cause
Fluid Therapy
Volume depends upon haemodynamic state & type of AI
Primary AI – hypovolemia (Salt wasting)
Central AI - euvolemia
0.9% SalineBeware of rapid change in Na
Dextrose to treat hypoglycemia
Steroid Therapy
Hydrocortisone drug of choiceNatural compound
Mineralocorticoid activity
DoseNo need to use large doses
50 mg 6 hourly (avoid less frequent doses)
Taper dose early
No additional benefit of mineralocorticoids
Arafah BM, JCEM 2006
“Low dose regime”
Hydrocortisone 50 mg six hourly
1350
Electrolyte Disturbance
Hyponatremia0.9% saline
Glucocorticoid
Beware of rapid change in Na
HyperkalemiaFluids & hydrocortisone
Severe cases: NaHCO3, Glucose/insulin
Critical Illness
Cortisol is a stress hormone and essential for survival
Metabolic effectsProvision of energy
Haemodynamic effectsSalt & water retention
Increase presser response
Anti-inflammatory effects
CortisolCritical Illness
Cortisol levels are elevated (2-3 times)Increased secretion
Loss of diurnal variationDecreased negative feedback
Decreased catabolism
CortisolCritical Illness
Increased availabilityGreater increase in Free CortisolDecreased Binding (CBG, Albumin)Increased tissue deliveryElastaseIncreased tissue effectUp regulation of receptors
ACTH
Cortisol Aldosterone
Androgens
CRHAVP
Neurogenic stimuli Adrenergic stimulation
Cytokines
Tissue action
Cortisol in critical illnessDilemmas
How much is good?Very high levels – deleterious?
Low levels – deleterious
Cortisol measurement?Changes in free cortisol, hetrophil antibodies
Tissue modulation
No test to measure tissue effect
0100200300400500600700800900
1000
Co
rtis
ol
nm
ol/
l
Basal Stimulated FC Basal FC Stim
Albumin <25 Albumin >25 Normal
Arafah BM, JCEM 2006
Minneci P et al, Ann Intern Med 2004
Issues with metanalysis
Small numbers
Measurement of cortisol
Major influence of one studyAlmost 80% non-responders
Almost ⅓ had received etomidate
Not designed to test adverse effects
Duration & tapering of steroids
CORTICUS study
Non-responders had higher mortality
No difference in mortality between steroid and placebo group
Overall shock reversal rates higher in steroid group- not significant
Rates of super-infection were higher in the steroid group- NS
Hyperglycemia more common on steroids
AI in Critical IllnessApproach
Must not miss individuals with true cortisol deficiency
Definitive AI
Relative AI
Treating such individuals could be life saving
Avoid unnecessary steroid therapy
Adrenal InsufficiencyCritical Illness
Routine testing not recommended
Actively screen those at high riskACTH stimulation test
Patients unresponsive to fluids & vasopressors merit trial of steroids
Cortisol in critical illnessHigh risk for adrenal insufficiency
Head injury
Known endocrine disease
Previous steroid use
Drugs (etomidate, ketoconazole, Medroxyprogesterone, megestrol)
HIV
Bleeding diathesis
Adrenal InsufficiencyCritical Illness
Cut off values for cortisol
BasalCortisol <400 highly suggestive
Cortisol >810 (930) excludes AI
ACTH stimulation (normal values)Increase of >250 nmol/l above baseline
Peak cortisol >930 nmol/l?