Adrenal insufficiency

medicine undergraduate

1. ADRENAL INSUFFICIENCY NUR FARRA NAJWA BINTI ABDUL AZIM 082015100035

2. LEARNING OBJECTIVES What is adrenal insufficiency Features/clinical findings Investigation Making diagnosis Treatment and follow-up Addisonian crisis

3. Primary adrenocortical insufficiency Secondary adrenocortical insufficiency

4. PRIMARY ADRENOCORTICAL INSUFFICIENCY (ADDISON’S DISEASE) Rare (~0.8/100 000) Can be fatal Destruction of the adrenal cortex Glucocorticoid (cortisol) Mineralocorticoid (aldosterone) deficiency

5. Cont. It is ‘ the unforgiving master of non-specificity and disguise ’. Suspected in : UNEXPLAINED FATIGUE, HYPONATRAEMIA OR HYPOTENSION Misdiagnose a viral infection or anorexia nervosa, chronic fatigue syndrome or depression

6. Causes 80% are due to autoimmunity in the UK. Other causes: TB (commonest cause worldwide) Adrenal metastases (from lung, breast, renal cancer) Lymphoma Opportunistic infections in HIV ( eg CMV, mycobacterium avium ) Adrenal haemorrhage ( waterhouse – friderichsen syndrome) Antiphospholipid syndrome SLE Congenital (late-onset congenital adrenal hyperplasia).

7. SECONDARY ADRENAL INSUFFICIENCY Commonest cause Iatrogenic Due to long term steroid therapy leading to suppression of the pituitary–adrenal axis . Symptoms apparent on withdrawal of the steroids. Mineralocorticoid production remains intact, and there is no hyperpigmentation as decreased ACTH Other causes are rare and include Hypothalamic–pituitary disease leading to decreased ACTH production.

8. Symptoms (often diagnosed late) Lean Tanned Tired Tearful ± weakness Anorexia Dizzy Faints Flu-like myalgias / arthralgias . Mood: depression, psychosis. GI : nausea/ vomiting, abdominal pain, diarrhoea/constipation. ( Think of A ddison’s in all with unexplained abdominal pain or vomiting. ) Pigmented palmar creases & buccal mucosa. Postural hypotension. Vitiligo .

9. Signs of Critical Deterioration Addisonian crises Hypoglycaemia Hypercalcaemia . Muscle cramps Nausea Vomiting Diarrhoea Unexplained fever High temperature Shock Coma

10. TESTS Low N a+ & high K+ (due to decreased mineralocorticoid) Low glucose (due to decreased cortisol) Uraemia High Ca2+ Eosinophilia Anaemia.

11. ASSESSMENT OF GLUCOCORTICOIDS Random plasma cortisol is low in patients with adrenal insufficiency it may be within the reference range, yet inappropriately low, for a seriously ill patient. Random measurement of plasma cortisol cannot therefore be used to confirm or refute the diagnosis, unless the value is above 500 nmol /L (> 18 µg/ dL ), which effectively excludes adrenal insufficiency. More useful is the short ACTH stimulation test

12. Short ACTH stimulation test ( Synacthen ® test ) DO PLASMA CORTISOL ADDISON’S IS EXCLUDED Before and ½h after tetracosactide ( Synacthen ®) 250mcg IM If 30min cortisol >550nmol/L.

13. ACTH IN ADDISON’S (high) IN SECONDARY CAUSES (low) 9AM ACTH is high (>300ng/L: inappropriately high). 21-Hydroxylase adrenal autoantibodies: + ve in autoimmune disease in >80% Plasma renin & aldosterone: to assess mineralocortocoid status.

14. AXR/CXR Any past TB, Upper zone fibrosis Adrenal calcification If no autoantibodies, consider further tests Adrenal CT TB, histoplasma , or metastatic disease.

15. Assessment of Mineralocorticoids CANNOT BE ADEQUATELY ASSESSED BY ELECTROLYTE MEASUREMENTS IS Since hyponatraemia occurs in both aldosterone and cortisol deficiency HYPERKALAEMIA MEASUREMENT Finding is common, but not universal ALDOSTERONE DEFICIENCY. Plasma renin and aldosterone should be measured in the supine position MINERALOCORTICOID DEFICIENCY Plasma renin activity is high, with plasma aldosterone being either low or in the lower part of the reference range.

16. TREATMENT

17. Steroid Use Advise wearing a bracelet declaring steroid use. Add 5–10mg hydrocortisone to daily intake before strenuous activity/exercise . Double steroids in febrile illness, injury, or stress. Give out syringes and in-date IM hydrocortisone , and show how to inject 100mg IM if vomiting prevents oral intake

18. Follow-up Yearly (BP, U&E) Watch for autoimmune diseases (pernicious anaemia).

19. Prognosis (Treated) adrenal crises and infections do cause excess deaths Mean age at death for Men is ~65yrs (11yrs <estimated life expectancy Women lose ~3yrs).

20. EXOGENOUS STEROID USE Replacement steroids are vital in those taking long-term steroids when acutely unwell. Adrenal insufficiency may develop with deadly hypovolaemic shock, if additional steroid is not given. Warn against abruptly stopping steroids . Give steroid card. Emphasize that prescribing doctors/dentists/surgeons must know of steroid use

21. ADDISONIAN CRISIS

22. Signs and Symptoms Patients may present in shock (low HR; vasoconstriction; postural hypotension; oliguria; weak; confused; comatose) High temperature Shock Coma

23. Precipitating Factors Infection , trauma, surgery, missed medication In a patient with known Addison’s oral steroid has not been increased to cover stress such as pneumonia Remember Bilateral adrenal haemorrhage ( eg meningococcaemia ) hypoglycaemia.

24. Management If suspected, treat before biochemical results. Bloods for cortisol and ACTH (this needs to go straight to laboratory, call ahead !) U&ES can have high K + (check ECG and give calcium gluconate if needed) Low Na + (salt depletion, should resolve with rehydration and steroids). Hydrocortisone 100mg IV stat. IV fluid bolus eg 500mL 0.9% saline to support BP, repeated as necessary. Monitor blood glucose : the danger is hypoglycaemia. Blood , urine, sputum for culture , then antibiotics if concern about infection

25. Continuing Treatment HYPOGLYCAEMIC. Glucose IV CLINICAL STATE AND U&E IMBALANCE. IV fluids STEROIDS Continue hydrocortisone, eg 100mg/8h IV or IM. Change to oral steroids after 72h if patient’s condition good. ADRENAL DISEASE: ASK AN EXPERT. Fludrocortisone may well be needed FIND UNDERLYING CAUSE. Get endocrinological help Search for (and vigorously treat)

26. SUMMARY What is adrenal insufficiency Features/clinical findings Investigation Making diagnosis Treatment and follow-up Addisonian crisis, diagnosis, investigation, management and follow-up

27. REFERENCES Clinical Medicine, Oxford Handbook Davidson, Medicine

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