1. ADRENAL INSUFFICIENCY NONSO EMEGOAKOR ENDOCRINOLOGY UNIT

2. Discuss the aetiology, clinical presentation, investigation and treatment of adrenal insufficiency

3. Outline INTRODUCTION HPA AXIS Renin angiotensin, aldosterone axis Aetiology Clinical presentation Investigations Treatment Summary

4. INTRODUCTION Is a condition that results from inadequate production of steroid hormones from the adrenal glands The adrenal hormones include glucocorticoids, mineralocorticoids and androgens AI may be primary, secondary or tertiary

5. Hypothalamo-pituitary-adrenal axis

7. Primary adrenal insufficiency Called Addison's disease Results from destruction and dysfunction of the entire adrenal cortex Hence both glucocorticoids, mineralocorticoids and adrenal androgens are affected May be acute(addisonian crises) or chronic

8. Aetiology of chronic primary AI Autoimmune adrenalitis either isolated or as part of APS types 1 and 2 Adrenal infections; TB, histoplasmosis, HIV blastomycosis, cryptococcosis, coccidiodomycosis Infiltrative disorders; amyloidosis, sarcoidosis, haemochromatosis, metastasis,lymphoma

9. DRUGS; ketoconazole, aminoglutethimide, mitotane, methadone, busulphan Abdominal irradiation Surgical removal Congenital adrenal hyperplasia Adrenal dysgenesis adrenoleukodystrophy

10. Causes of acute primary AI Stress ; infection, infarction, surgery, trauma, emotional turmoil Sudden withdrawal of long term steroids Bilateral adrenal haemorrhage; 1.Waterhouse-friderichsen syndrome 2.Complication of anticoagulant therapy, coagulopathies, pregnancy Bilateral adrenal artery emboli/vein thrombosis

11. Causes of secondary/tertiary AI Exogenous steroid use Pituitary tumors Pituitary irradiation Autoimmune hypophysitis Pituitary apoplexy Sheehans syndrome Pituitary infiltrations Pituitary surgery Craniopharyngioma Meningioma Metastasis to the pituitary or hypothalamus Hypothalamic tumors Head injury

12. Clinical presentation Gradual onset with non specific features Hyperpigmentation especially of sun exposed areas, extensor surfaces, knuckles, elbows, knees, scars, palm creases, nail beds, mucous membranes of oral cavity Chronic, worsening fatigue Muscle weakness Weight loss

13. Clinical features Poor appetite Nausea, vomiting and occasional diarrhea Dizziness, syncope Flaccid muscle paralysis Salt craving Impotence Joint and back pains Confusion/depression Abdominal pains Loss of axillary/pubic hair Dry itchy skin vitiligo

14. Physical findings Generalised wasting Dehydration Loss of body hair Pigmentation as already described/ vitiligo Postural hypotension

15. Hyperpigmentation in buccal mucosa of a patient

17. Pointers to secondary hypoadrenalism Absence of hyperpigmentation Alabaster colored pale skin(POMC def) Features of panhypopituitarism e.g, reduced thyroid and gonadal functions Neurological features e.g headaches, blurring of vision, bitemporal hemianopia Lack of features of aldosterone def such as salt craving, abdominal pains

18. Presentation of addisonian crises Severe vomiting/diarrhea Severe lethargy Dehydration Hypotension or may be in shock Sudden, severe pain in back, belly or legs Confusion, fits, loss of consciousness Abdominal features may present as an acute abdomen Fever/hyperpyrexia Features of precipitating factor

19. Investigations ACTH STIMULATION TEST Gold standard assay for adrenal insufficiency May distinguish primary from secondary AI Measures cortisol response to injection of synthetic ACTH IM Tetracosactide 250mcg is given. Take sample for cortisol at 0, 30 and 60mins

20. Serum cortisol doubles after one hour of injection of synecthen in normal people Impaired response in adrenal insufficiency Stress,recent radioisotope scans, spironolactone, contraceptives may affect the result. c/I in people on glucocorticoid therapy Random plasma cortisol, 550nmol/l is unlikely

21. Investigations 9am Plasma ACTH and cortisol; high level (>80ng/l) of ACTH with low cortisol confirms primary insufficiency Insulin tolerance test;to diagnose or exclude ACTH deficiency measures ACTH stress response via cortisol to hypoglycaemia Cortisol rises above 550nmol/l in normal people CRH stimulation test; i.v 100mcg of CRH is given Plasma ACTH rises by 30-40pg/ml in normal.

22. INVESTIGATIONS Serum electrolyte, urea Adrenal antibodies Plasma rennin FBC Blood glucose Urine and sweat Na Chest and abdominal x-ray Abdominal USS/CT Brain MRI

23. Treatment Is with replacement therapy for life except for treatable causes like TB Glucocorticoid replacement is with tabs hydrocortisone 20-30mg/day Mimic circadian rhythm Thin patients require lower doses while obese patients may need higher doses Dose should be adjusted in times of stress

24. Treatment ctd Patients on medications that induce cytochrome p-450 need higher doses Those with decreased cortisol clearance like in liver disease are placed on lower doses Tabs prednisolone and dexamethasone are alternative medications used Adequacy of treatment is monitored with improved clinical wellbeing and serum cortisol

25. Treatment Mineralocorticoids are replaced with fludrocortisone Only in primary hypoadrenalism Daily dose is titrated to maintain normal BP and serum Na and K level Dose adjustments are not needed in stressful situations, however dose should be increased in hot weather Adrenal androgen replacement is with DHEA 25- 50mg/day

27. OUTPATIENT CARE Monitor for signs of inadequate replacement e.g headaches, dizziness, weakness Suppression of plasma rennin activity indicate adequate mineralcorticoid replacement Monitor BP, weight and cushingoid features which may indicate over replacement Periodic bone mineral density evaluation.

28. Treatment Ctd Patients are taught how to increase steroid dose during intercurrent illness Advised to wear a medic-alert bracelet Keep at least an ampoule of hydrocortisone at home Other treatment is dependent on aetiology e.g anti TB Patients with secondary AI may also need T4 replacement

29. Mgt of acute hypoadrenalism IVF N/S over 30-60mins Subsequent liters of N/S is dependent on degree of dehydration I.V. hydrocortisone 100mg bolus I.M. hydrocortisone 100mg 6hrly until patient is clinically stable IV dextrose for hypoglycemia Tabs hydrocortisone 20mg 8hourly when patient can take orally Fludrocortisone not required in the acute period

30. Primary versus secondary adrenal insufficiency primary Increased CRH Increased ACTH reduced cortisol reduced aldosterone Hyponatremia Hyperkalemia Increased renin hyperpigmentation Glucocorticoid and mineralocorticoid replacement secondary Increased CRH Reduced ACTH Reduced cortisol Normal aldosterone Normal or reduced Na Normal or reduced K Normal renin No hyperpigmentation Only glucocorticoid replacement needed.

31. Conclusion AI is a great pretender. It’s a potentially life threatening condition Autoimmune destruction of the adrenals is the commonest cause Primary and secondary are differentiated by ACTH levels amongst other features Acute insufficiency is a medical emergency and is treated with IV hydrocortisone and IV fluids

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