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

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Presentation on theme: "Acute Adrenal Insufficiency Dr. Sohail Inam FRCP (Ed), FRCP Consultant & Head, Division of Endocrinology Armed Forces Hospital Riyadh."— Presentation transcript:

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

2 Kidney ACTH CortisolAldosterone Renin Angiotensin II Renin substrate Angiotensin I Androgens CRH AVP

3 Kidney ACTH CortisolAldosterone Renin Angiotensin II Renin substrate Angiotensin I Androgens CRH AVP X

4 Kidney ACTH CortisolAldosterone Renin Angiotensin II Renin substrate Angiotensin I Androgens CRH AVP X

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 8-9 am level Level during stress Stimulated ACTH Hypoglycemia CRH Metyrapone

10 % chance of adrenal insufficiency 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 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 Arafah BM, JCEM 2006 “Low dose regime” Hydrocortisone 50 mg six hourly 1350

18 Electrolyte Disturbance Hyponatremia 0.9% saline Glucocorticoid Beware of rapid change in Na Hyperkalemia Fluids & hydrocortisone Severe cases: NaHCO 3, 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 ACTH Cortisol Aldosterone Androgens  CRH  AVP Neurogenic stimuli Adrenergic stimulation Cytokines  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?

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