Acute Adrenal Insufficiency

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?