1. Acute Adrenal Insufficiency
Dr. Sohail Inam FRCP (Ed), FRCP
Consultant & Head, Division of Endocrinology
Armed Forces Hospital
Riyadh

2. CRH
AVP
Renin
substrate
Kidney
Renin
ACTH
Angiotensin I
Angiotensin II
Cortisol
Aldosterone
Androgens

3. X ACTH CRH AVP Renin substrate Kidney Renin Angiotensin I
Angiotensin II
Cortisol
Aldosterone
Androgens

4. X CRH AVP Renin substrate Kidney Renin ACTH Angiotensin I
Angiotensin II
Cortisol
Aldosterone
Androgens

5. Acute Adrenal Insufficiency
Previous adrenal insufficiency
Previous normal adrenal function
Acute adrenal injury
Acute pituitary injury
Drug related effect
Functional adrenal insufficiency
Beware of previous corticosteroid use

6. Acute Adrenal Insufficiency Presentation
Non-specific
Hypotension
Postural
Recumbent
Abdominal pain
Electrolyte disturbances
Hypoglycemia

7. Acute Adrenal Insufficiency Precipitating factors
Omission of corticosteroids
Increased requirements
Infection
Physical stress
Drugs

8. Diagnosis Measurement of adrenal hormones Cortisol
Primary versus central
ACTH
Determine cause

9. Diagnosis Cortisol Random Stimulated 8-9 am level Level during stress
ACTH
Hypoglycemia
CRH
Metyrapone

10. 100
% chance of adrenal insufficiency
<83
650
9 am serum cortisol nmol/l

11. 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

12. Pituitary Stimulation Tests
Insulin tolerance test (ITT)
Gold standard for central disease
Risk from hypoglycemia
CRH
Metyrapone
Other

13. Suspicion of AI Approach
ACTH stimulation test
ACTH measurement on basal sample

14. Acute AI Management
Fluids
Glucocorticoids
Treat underlying cause

15. Fluid Therapy Volume depends upon haemodynamic state & type of AI
Primary AI – hypovolemia (Salt wasting)
Central AI - euvolemia
0.9% Saline
Beware of rapid change in Na
Dextrose to treat hypoglycemia

16. Steroid Therapy Hydrocortisone drug of choice Dose
Natural compound
Mineralocorticoid activity
Dose
No need to use large doses
50 mg 6 hourly (avoid less frequent doses)
Taper dose early
No additional benefit of mineralocorticoids

17. “Low dose regime” Hydrocortisone 50 mg six hourly 1350
Arafah BM, JCEM 2006

18. Electrolyte Disturbance
Hyponatremia
0.9% saline
Glucocorticoid
Beware of rapid change in Na
Hyperkalemia
Fluids & hydrocortisone
Severe cases: NaHCO3, Glucose/insulin

19. Critical Illness
Cortisol is a stress hormone and essential for survival
Metabolic effects
Provision of energy
Haemodynamic effects
Salt & water retention
Increase presser response
Anti-inflammatory effects

20. Cortisol Critical Illness
Cortisol levels are elevated (2-3 times)
Increased secretion
Loss of diurnal variation
Decreased negative feedback
Decreased catabolism

21. Cortisol Critical Illness
Increased availability
Greater increase in Free Cortisol
Decreased Binding (CBG, Albumin)
Increased tissue delivery
Elastase
Increased tissue effect
Up regulation of receptors

22. Cortisol ACTH Neurogenic stimuli Adrenergic stimulation CRH Cytokines
AVP
ACTH
Cortisol
Aldosterone
Androgens
 Tissue action

23. Cortisol in critical illness Dilemmas
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

24. Arafah BM, JCEM 2006

25. Minneci P et al, Ann Intern Med 2004

26. Issues with metanalysis
Small numbers
Measurement of cortisol
Major influence of one study
Almost 80% non-responders
Almost ⅓ had received etomidate
Not designed to test adverse effects
Duration & tapering of steroids

27. 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

28. AI in Critical Illness Approach
Must not miss individuals with true cortisol deficiency
Definitive AI
Relative AI
Treating such individuals could be life saving
Avoid unnecessary steroid therapy

29. Adrenal Insufficiency Critical Illness
Routine testing not recommended
Actively screen those at high risk
ACTH stimulation test
Patients unresponsive to fluids & vasopressors merit trial of steroids

30. Cortisol in critical illness High risk for adrenal insufficiency
Head injury
Known endocrine disease
Previous steroid use
Drugs (etomidate, ketoconazole, Medroxyprogesterone, megestrol)
HIV
Bleeding diathesis

31. Adrenal Insufficiency Critical Illness
Cut off values for cortisol
Basal
Cortisol <400 highly suggestive
Cortisol >810 (930) excludes AI
ACTH stimulation (normal values)
Increase of >250 nmol/l above baseline
Peak cortisol >930 nmol/l?

32. Thank You