Acute Adrenal Insufficiency Dr. Sohail Inam FRCP (Ed), FRCP Consultant & Head, Division of Endocrinology Armed Forces Hospital Riyadh AVP CRH Kidney ACTH Renin substrate Renin Angiotensin I Angiotensin II Cortisol Aldosterone Androgens AVP CRH Kidney ACTH Renin substrate Renin Angiotensin I X Cortisol Angiotensin II Aldosterone Androgens AVP CRH Kidney X ACTH Renin substrate Renin Angiotensin I Angiotensin.
Download ReportTranscript Acute Adrenal Insufficiency Dr. Sohail Inam FRCP (Ed), FRCP Consultant & Head, Division of Endocrinology Armed Forces Hospital Riyadh AVP CRH Kidney ACTH Renin substrate Renin Angiotensin I Angiotensin II Cortisol Aldosterone Androgens AVP CRH Kidney ACTH Renin substrate Renin Angiotensin I X Cortisol Angiotensin II Aldosterone Androgens AVP CRH Kidney X ACTH Renin substrate Renin Angiotensin I Angiotensin.
Acute Adrenal Insufficiency Dr. Sohail Inam FRCP (Ed), FRCP Consultant & Head, Division of Endocrinology Armed Forces Hospital Riyadh AVP CRH Kidney ACTH Renin substrate Renin Angiotensin I Angiotensin II Cortisol Aldosterone Androgens AVP CRH Kidney ACTH Renin substrate Renin Angiotensin I X Cortisol Angiotensin II Aldosterone Androgens AVP CRH Kidney X ACTH Renin substrate Renin Angiotensin I Angiotensin II Cortisol Aldosterone Androgens 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 Acute Adrenal Insufficiency Presentation Non-specific Hypotension Postural Recumbent Abdominal pain Electrolyte disturbances Hypoglycemia Acute Adrenal Insufficiency Precipitating factors Omission of corticosteroids Increased requirements Infection Physical stress Drugs Diagnosis Measurement of adrenal hormones Cortisol Primary versus central ACTH Determine cause Diagnosis Cortisol Random 8-9 am level Level during stress Stimulated ACTH Hypoglycemia CRH Metyrapone % chance of adrenal insufficiency 100 0 <83 650 9 am serum cortisol nmol/l ACTH Stimulation Test Standard (250 mcg) , Low dose (1mcg) Can be performed any time though preferably 89 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 AI Approach ACTH stimulation test ACTH measurement on basal sample Acute AI Management 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% Saline Beware of rapid change in Na Dextrose to treat hypoglycemia 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 “Low dose regime” 1350 Hydrocortisone 50 mg six hourly Arafah BM, JCEM 2006 Electrolyte Disturbance Hyponatremia 0.9% saline Glucocorticoid Beware of rapid change in Na Hyperkalemia Fluids & hydrocortisone Severe cases: NaHCO3, Glucose/insulin 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 Cortisol Critical Illness Cortisol levels are elevated (2-3 times) Increased secretion Loss of diurnal variation Decreased negative feedback Decreased catabolism 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 Neurogenic stimuli CRH AVP Adrenergic stimulation Cytokines ACTH Cortisol Tissue action Aldosterone Androgens 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 Cortisol nmol/l Albumin <25 Albumin >25 Normal 1000 900 800 700 600 500 400 300 200 100 0 Basal Arafah BM, JCEM 2006 Stimulated FC Basal FC Stim Minneci P et al, Ann Intern Med 2004 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 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 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 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 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 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?