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
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Acute Adrenal Insufficiency
Dr. Sohail Inam FRCP (Ed), FRCPConsultant & Head, Division of Endocrinology
Armed Forces HospitalRiyadh
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Kidney
ACTH
Cortisol Aldosterone
Renin
Angiotensin II
Renin substrate
Angiotensin I
Androgens
CRHAVP
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Kidney
ACTH
Cortisol Aldosterone
Renin
Angiotensin II
Renin substrate
Angiotensin I
Androgens
CRHAVP
X
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Kidney
ACTH
Cortisol Aldosterone
Renin
Angiotensin II
Renin substrate
Angiotensin I
Androgens
CRHAVP
X
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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
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Acute Adrenal InsufficiencyPresentation
Non-specific
HypotensionPostural
Recumbent
Abdominal pain
Electrolyte disturbances
Hypoglycemia
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Acute Adrenal InsufficiencyPrecipitating factors
Omission of corticosteroids
Increased requirementsInfection
Physical stress
Drugs
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Diagnosis
Measurement of adrenal hormones
Cortisol
Primary versus central
ACTH
Determine cause
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DiagnosisCortisol
Random8-9 am levelLevel during stress
StimulatedACTH HypoglycemiaCRHMetyrapone
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% c
hanc
e of
adr
enal
insu
ffic
ienc
y
9 am serum cortisol nmol/l
<83 650
0
100
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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
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Pituitary Stimulation Tests
Insulin tolerance test (ITT)Gold standard for central disease
Risk from hypoglycemia
CRH
Metyrapone
Other
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Suspicion of AIApproach
ACTH stimulation test
ACTH measurement on basal sample
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Acute AIManagement
Fluids
Glucocorticoids
Treat underlying cause
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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
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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
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Arafah BM, JCEM 2006
“Low dose regime”
Hydrocortisone 50 mg six hourly
1350
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Electrolyte Disturbance
Hyponatremia0.9% saline
Glucocorticoid
Beware of rapid change in Na
HyperkalemiaFluids & hydrocortisone
Severe cases: NaHCO3, Glucose/insulin
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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
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CortisolCritical Illness
Cortisol levels are elevated (2-3 times)Increased secretion
Loss of diurnal variationDecreased negative feedback
Decreased catabolism
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CortisolCritical Illness
Increased availabilityGreater increase in Free CortisolDecreased Binding (CBG, Albumin)Increased tissue deliveryElastaseIncreased tissue effectUp regulation of receptors
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ACTH
Cortisol Aldosterone
Androgens
CRHAVP
Neurogenic stimuli Adrenergic stimulation
Cytokines
Tissue action
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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
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0100200300400500600700800900
1000
Co
rtis
ol
nm
ol/
l
Basal Stimulated FC Basal FC Stim
Albumin <25 Albumin >25 Normal
Arafah BM, JCEM 2006
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Minneci P et al, Ann Intern Med 2004
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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
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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
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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
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Adrenal InsufficiencyCritical Illness
Routine testing not recommended
Actively screen those at high riskACTH stimulation test
Patients unresponsive to fluids & vasopressors merit trial of steroids
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Cortisol in critical illnessHigh risk for adrenal insufficiency
Head injury
Known endocrine disease
Previous steroid use
Drugs (etomidate, ketoconazole, Medroxyprogesterone, megestrol)
HIV
Bleeding diathesis
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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?
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