ADRENAL INSUFFICIENCY

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 adrenalitiseither 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; • Waterhouse-friderichsen syndrome • 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, <100nmol/l is suggestive, >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;todiagnose 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 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. • Increased CRH • Increased ACTH • reduced cortisol • reduced aldosterone • Hyponatremia • Hyperkalemia • Increased renin • hyperpigmentation • Glucocorticoid and mineralocorticoid replacement

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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