1. RECOGNITION AND MANAGEMENT OF ACUTE ADRENAL CRISES Dr Rohit Rajagopal Staff Specialist Endocrinologist August 2016

2. OUTLINE Basic Physiology and Terminology Clinical Presentation Management

3. OUTLINE Basic Physiology and Terminology Clinical Presentation Management

4. HYPOTHALAMIC-PITUITARY-ADRENAL AXIS Primary Adrenal Failure Secondary Adrenal Failure Tertiary Adrenal Failure Autoimmune adrenalitis (Addison’s disease) TB, HIV, Cryptococcus Bilateral adrenal haemorrhage/infarct Congenital Drugs – eg ketoconazole Hypothalamic/Pituitary mass Pituitary apoplexy Irradiation Trauma Long-term steroid use

5. OTHER PITUITARY HORMONES LH, FSH – sex hormones, reproductive function GH – linear growth, metabolic effects, body composition Prolactin – lactation TSH – thyroid hormones ADH – regulation of osmolality and water balance

6. OTHER ADRENAL HORMONES Aldosterone Regulation of salt and water balance and hence volume and BP by acting on the renal distal tubule to facilitate K excretion and Na/H2O reabsorbtion Main stimulus is serum K level and the Renin-Angiotensin system (not ACTH) Sex steroids

7. OUTLINE Basic Physiology and Terminology Clinical Presentation Management

8. ADRENAL CRISES A life-threatening emergency related to acute adrenal insufficiency (usually primary) although may also occur with secondary/tertiary especially if acute or following sudden withdrawal of long- term steroid therapy Majority of manifestations are due to aldosterone deficiency although cortisol is also important for BP maintenance

9. ADRENAL CRISES Incidence: 5-10 cases per 100 patient years annually and a recent Australian study suggests an increasing trend 1 in 200 patients die from an adrenal crisis Early recognition of the clinical features and prompt institution of treatment is vital!

10. ADRENAL CRISES – CLINICAL FEATURES Predominant manifestation is shock usually out of proportion to the severity of the presenting illness Other symptoms include: Nausea, vomiting and anorexia Abdominal pain – may mimic an “acute abdomen” Unexplained fever Lethargy, fatigue, weakness, confusion, coma May have a background history of long-standing lethargy, anorexia, weight loss and fatigue May carry a “Sick day plan” or MedicAlert tag

11. ADRENAL CRISES – CLINICAL FEATURES Other symptoms/signs may also be present that may point to an aetiology of the underlying disease or precipitant: Increased pigmentation – suggests chronic ACTH excess Vitiligo and other autoimmune diseases Headaches and visual field disturbances Source of infection or history of missed steroid doses

12. ADRENAL CRISES - LABORATORY FEATURES Hyponatraemia Hyperkalaemia (usually primary) Hypoglycaemia (ACTH deficiency) Increased urea Anaemia, eosinophilia Increased ESR Mild hypercalcaemia High TSH

13. ADRENAL CRISES – OTHER INVESTIGATIONS Should be directed at possible precipitant: Blood and urine cultures, CXR, ECG etc IF FEBRILE, PATIENT HAS AN INFECTION TILL PROVEN OTHERWISE Collect blood for ACTH, Cortisol, Aldosterone and Renin BUT DO NOT WAIT FOR RESULTS PRIOR TO INITIATING TREATMENT!

14. 51 yo female with 7 yr history of known Addison’s disease On Hydrocortisone 20 mg mane, 10 mg nocte and Fludrocortisone 0.1 mg bd Had a MedicAlert bracelet and aware of sick day management Developed viral gastroenteritis with a 24 hour history of vomiting and diarrhoea Tripled usual hydrocortisone but unable to keep pills down Called ambulance as directed Found to have BP of 80/60 at scene; given 1L Hartmann’s and transferred to ED Gargya, IMJ - 2016

15. On arrival, BP was 101/62. Labelled as ‘normotensive’ and triaged to be reviewed in 60 min IV fluids and steroids not given although requested by family 3 hours later, patient had a cardiorespiratory arrest and found to have a pH of 7.06 Resuscitated, intubated and transferred to ICU Treating endocrinologist informed 5 hours later Total LOS 16 days and admission complicated by stress-induced cardiomyopathy and a broken tooth Gargya, IMJ - 2016

17. OUTLINE Basic Physiology and Terminology Clinical Presentation Management

18. ADRENAL CRISES – ACUTE MANAGEMENT Establish IV access – preferably 2 large bore cannulas (collect bloods as per previously) IV Fluids: 1-3 litres of N/Saline as quickly as possible 5% dextrose via second line if hypoglycaemic Regular monitoring of haemodynamic status including urine output and electrolytes/glucose to prevent fluid overload Glucocorticoid replacement: 100 mg iv hydrocortisone bolus followed by 50 mg q 8 hourly

19. ADRENAL CRISES – SUBACUTE MANAGEMENT Contact Endocrinology service Ongoing IV N/Saline for next 24-48 hours Search for and treat possible precipitant eg infection Taper IV steroids over next 24-48 hours and commence oral replacement Oral fludrocortisone if required once IV fluids ceased

20. ADRENAL CRISES – LONG-TERM MANAGEMENT If no previous diagnosis, establish cause of adrenal insufficiency A low cortisol (<100 nmol/L) with an elevated ACTH is diagnostic of primary adrenal failure Borderline cortisol levels or inappropriately normal ACTH levels may require further dynamic testing Lifelong hormone replacement Hydrocortisone 18-30 mg daily in divided doses or Prednisolone 4.5-7.5 mg daily Fludrocortisone or other pituitary hormone replacement as indicated Sick day plans, script for IM Solu-Cortef and instructions on how to use, MedicAlert tags, Addison’s society

21. SICK DAY PLANS Gargya, IMJ - 2016

24. WHAT DO AMBULANCES CARRY? Gargya, IMJ - 2016

25. ANY QUESTIONS?