1.College of Health SciencesDepartment of medical PhysiologyPresentation on AdrenocorticalHypofunctionrobel abay 1

2. Topic out line Objectives Introduction Adrenal insufficiencyPrimary Adrenal insufficiency Secondary Adrenal insufficiency Addisons Crisis Treatment modalities Isolated Hypoadrenalism Adrenal Insufficiency2 3. learning ObjectivesAt the end of these presentation learners expectedto:- Know the pathophysiology of adrenal insufficiency. Identify the cause of adrenal insufficiency. List the clinical manifestation of adrenalinsufficiency Explain Addisons crisis Know pathophysiology of isolated hypoadrenalism Know the treatment modalitiesAdrenal Insufficiency 3 4. Endocrine Abnormalities Endocrine abnormality expressed by hypersecretion orhyposecretion of hormone. Primary disorder-result from the gland it self. Secondary disorder-the problem result from otherorgan or target tissue.Adrenal Insufficiency4 5. Cause Of Endocrine Abnormalities Metabolic factors. Physical damage Congenital problems. Genetic abnormalities. Adrenal Insufficiency 5 6. Adrenal InsufficiencyDefinition Adrenal insufficiency is a condition in which the adrenal gland is not able to function well enough to produce the amount of all corticosteroid hormones which the body needs.Adrenal Insufficiency 6 7. ContdAccording the site of problem primary adrenal insufficiency. Secondary adrenal insufficiency.- Primary Adrenal insufficiency- The gland it self is damaged.- Secondary adrenal insufficiency-The glandhealthy but lacks hormonal stimulation Adrenal Insufficiency7 8. Primary Adrenal insufficiencyAddisons disease- it occurs when 90% of the adrenal gland is destroyed.- is a relatively uncommon disorder that occurs in people of all ages and both sexes.- characterized by decreased mineralocorticoid, glucocorticoid, and androgen secretion. Adrenal Insufficiency8 9. contd Cause1. idiopathic Autoimmune Adrenalitis The most common type. Atrophy of adrenal cortex due to autoimmunediseases, the adrenal medulla is intact. Accounts 70% of the Addison s disease. 15% of patients with Addisons disease have anassociated autoimmune disease , graves disease beingthe most commonAdrenal Insufficiency9 10. Contd Idiopathic autoimmune Addison disease may occur in isolationor in association with other autoimmune phenomena such as: - Schmidt syndrome: The association of Addison disease andHashimoto thyroiditis. - polyglandular autoimmune syndrome type 1: The association of Addison disease with hypoparathyroidism andmucocutaneouscandidiasis.o It may have an autosomal recessive mode of inheritance. It hasno human leukocyte antigen (HLA) associations.Adrenal Insufficiency10 11. Contd- polyglandularautoimmune syndrome type2: The association of Addison disease with type 1diabetes mellitus and Hashimoto thyroiditis orGraves disease.Adrenal Insufficiency 11 12. Primary adrenal insufficiency contd2.Infections Tuberculosis-most common AIDS Fungal infections( histoplasmosis, Cryptococcus) CMV infection Adrenal Insufficiency 12 13. Contd Hematogenous spread of the M.tuberculosis fromelse where in the body to the adrenal gland cause- initial enlarged with extensive epitheloid granulomas then followed by degeneration of the adrenal gland. Both cortex and adrenal medulla is affected. Fibrosis follows the adrenal become smaller withcalcification of 50% evident.Adrenal Insufficiency13 14. ContdAdrenal Insufficiency 14 15. Contd3. Miscellaneous-Rare causes Addisons disease Bilateral cancer metastasis Amyloidosis, hemosiderosis (rare) ketoconazole use, macrophage-releasedcytokines are risk factors Intra adrenal bleeding Bilateral adrenoloctomyAdrenal Insufficiency15 16. ContdIntra adrenal bleeding- cause necrosis of the adrenal may occur in severely sick patient, with underlying infection, trauma, or coagulopathy. - cause of severe septicemia, particularly in children in whom a common cause is infection with Neisseria Meningitidis.when caused by meningococci,the association with adrenal insufficiency is know as the Waterhouse Friederichsen syndrome.Adrenal Insufficiency 16 17. WATERHOUSE-FRIDERICHSEN SYNDROMEAcute, bilateral hemorrhagic infarction of the adrenals.Occurs secondary to shock and DIC, in a septicemicinfection. Endotoxic hemorrhaging. Tiny fibrin thrombi occlude the vessels going to the adrenalglands ------> infarction. Neisseria Meningitidis is the most common agent causingthe infection.Also Pneumococci, Staph, Strep, Haemophilus,Diphtheria. Herpes Virus can cause it. Complete and sudden collapse of cortical functionSYMPTOMS: like symptoms of shock ,infection and DIC(petechia, thrombocytopenia, increased PT and PTT).Adrenal Insufficiency17 18. ContdAdrenal Insufficiency 18 19. Contd4. congenital and genetic abnormalities A. congenital Adrenal Hypoplasia (CAH) It is an X-linked disorder comprising congenitaladrenal insufficiency and hypogonadotrophichypogonadism. caused by mutations in the NROB1 gene. DAX-1 gene- a member of the nuclear receptor familythat is expressed in the adrenal cortex, gonads, andhypothalamus.Adrenal Insufficiency19 20. Contd Mutations in another transcription factorsteroidogenic factor-1may also result inadrenal insufficiency due to lack of developmentof a functional adrenal cortex. CAH may also occur in association with glycerolkinase deficiency and muscular dystrophy.Adrenal Insufficiency20 21. ContdB.Adrenoleukodystrophy An inherited metabolic disorder resulting inaccumulation of very-long-chain fatty acids(VLCFA) in tissues including the brain and adrenalcortex, resulting in: Progressive demyelination of cerebral white matter Adrenal insufficiencyo Only males have the fully expressed condition andcarrier females are usually normal. Adrenal Insufficiency 21 22. Pathogenesis Accumulation of VLCFA VLCFA esterified tocholesterol, makingcholesterol unavailable as asteroid/hormone precursor Adrenocorticalcells withthese inclusions havedecreased mitochondrial andmicrosomalenzyme activity Over time these cells atrophy,further deterioratingadrenocorticalfunction Adrenal Insufficiency 22 23. ContdC.Familial glucocorticoid deficiency (FGD) inherited unresponsiveness to ACTH. It is a rare autosomal recessive cause of hypoadrenalism . Usually presents in childhood. The renin-angiotensin-aldosterone axis is intact. children usually present either with neonatal hypoglycemiaor later with increasing pigmentation, often with enhancedgrowth velocity. Two types-type 1 variant-25% of the case.- type 2 variant .Adrenal Insufficiency23 24. contdD. Allgrove syndrome: congenital adrenocortical unresponsiveness to ACTH typically presents in childhood with failure to thrive, features of adrenocortical insufficiency and hypoglycemia.- disease to chromosome 12q13 but the responsible gene is unknown. Adrenal Insufficiency 24 25. Secondary Adrenal insufficiency Loss of hypothalamic-pituitary function and deficiency of ACTH. Will usually have deficiencies of other gland regulated by hypothalamic-pituitary system. Aldosterone secretion may continue intact. Adrenal Insufficiency25 26. Contd Problems in hypothalamus or pituitary plasma levels of ACTH low. unable to stimulate the zona fasiculate and zonareticularies of adrenal cortex. cortisol levels low. Adrenal cortices do response to exogenous ACTH. Adrenal Insufficiency 26 27. Contd Cause1. Sudden cessation of exogenous glucocorticoid therapy. Abrupt withdrawal of corticosteroids is a very commoncause of secondary acute adrenal insufficiency. chronic exogenous glucocorticoid Suppresses diurnal CRH/ACTH release both time- and dose-related reversible recovery may take up to long time Adrenal Insufficiency27 28. STEROID THERAPY STEROID LEVELSPITUITARY GLAND IS INHIBITED TO REALEASEACTHENDOGENOUS CORTISOLPRODUCTION &ADRENAL ATROPHYRELEASE BY ADRENAL CORTEXAdrenal Insufficiency28 29. Contd2. Pan- Hypopituitarismreflect inadequate ACTH production from the anteriorpituitary gland. In many of these, other pituitary hormones are deficient in addition to ACTH, so that the patient presents with partial or complete hypopituitarism.Adrenal Insufficiency29 30. Contd3.Surgical cause- Selective removal of ACTH-secreting pituitaryadenoma -pituitary surgery.4. Postpartum pituitary infarction (Sheehans syndrome)Adrenal Insufficiency30 31. Signs & Symptoms 1. Hyper Pigmentation of skin & mucous membranedue to excess ACTH secretion because of cortisoldeficiency.- ACTH causes pigmentation by its melanocytestimulating action. on the sun exposed areas of the skin,extensor surface,knuckles,elbows and knees.2.Vitiligo is also common in auto Immune Addisonsdisease due to destruction of melanocyte. 31 Adrenal Insufficiency 32. Hyperpigmentation Adrenal Insufficiency 32 33. Contd2.Electroliyte and acid base balanceabnormalities. Hyponatremia. Hyperkalemia and metabolic acidosis Hypercalcemia.Adrenal Insufficiency33 34. Contd3.Dehydretion with loss of sodium- As ECF becomes depleted. - plasma volume fall. - COP decreased.4.Muscle weakness. Adrenal Insufficiency34 35. Contd 5. Decreased cardiac output & decreased workload of theheart leading to decrease in size of the heart. 6. Hypoglycemia. 7. Inability to withstand any type of stress like physical,mental, even exposure to mild stress, trauma. 8.Decreased pubic and axillary hair in women. 9.Nausea,vomiting and diarrhea. Adrenal Insufficiency35 36. ContdAdrenal Insufficiency 36 37. Contd Primary vs. secondary adrenal hypo functionprimarysecondarySite=adrenal site=hypothalamus-pituitaryACTHACTHpigmentationpigmentationweight lossweight change varyNo change in GH and GH and gonadotropinsGonadotropins.Deficient in all corticosteroidsother adrenal hormones normal or slightlyNo response to exogenous ACTHsluggish response to exogenousACTH. 37Adrenal Insufficiency 38. Diagnosis1.ACTH stimulation testA. Blood and/or urine cortisol levels are measured.B. Administration of synthetic ACTH.C. Cortisol measurement in blood is repeated 30 to 60minutes after an IV ACTH injection.In healthy person rise in blood and urine cortisol levelsIn adrenal insufficiency respond poorly or do notrespond at all. Adrenal Insufficiency38 39. Contd2.insulin-induced hypoglycemia testA. Blood measure of glucose and cortisol level.B. An injection of fast acting insulin.C. Blood glucose and cortisol levels are measured at 30,45 and 90 minutes after the insulin injection. The normal response is -blood glucose level-cortisol level. Adrenal Insufficiency 39 40. Addisons crisis A life treating emergency of exacerbate adrenalinsufficiency of undiagnosed patient during facingstress full conditions. symptoms are intensified. Nausea, vomiting, andabdominal pain may become intractable. In all patients in addisonians crisis, a precipitatingcause should be identify.Adrenal Insufficiency 40 41. Addisons CrisisClinical Presentation Life-threatening emergency May be primary or secondary HYPOTENSION Typically resistant to catecholamine and IVF resuscitation Adrenal Insufficiency 41 42. contdAbrupt adrenal failure usually from gland hemorrhage or thrombosis Anticoagulation DIC Sepsis Usually have abdominal and flank pain Adrenal Insufficiency42 43. ContdCatastrophic HPA axis failure Head injury Hemorrhage of pituitary adenoma Post-partum herniation (Sheehan syndrome) Usually neurological deficits, headaches, visual fieldcuts and diabetes insipidus. Adrenal Insufficiency 43 44. Treatment Modalities Different treatment regimes. Emergency treatments maintenance therapy. Replacement of glucocorticoids and mineralo corticoids. Adrenal Insufficiency44 45. Treatment of Addisons crisis hydrocortisone 50-100 mg every 6-8 hours intravenous fluids dextrose search for precipitating cause Adrenal Insufficiency 45 46. Treatment Patients with symptomatic adrenal insufficiency, should betreated with hydrocortisone or cortisone therapy. The usual initial dose is 25 mg of hydrocortisone (dividedinto doses of 15 and 10 mg) 37.5 mg of cortisone (divided into doses of 25 and 12.5 mg) The daily dose may be decreased to 20 or 15 mg ofhydrocortisone as long as the patient remainsasymptomatic.Adrenal Insufficiency46 47. Treatment chronic AI hydrocortisone 12-15 mg in one or divided doses titrate to lowest tolerated dose consider mineralocorticoid ( fludrocortisone ) ifprimary AI. in a single daily dose of 50 to 200 g, asa substitute for aldosterone. Adrenal Insufficiency 47 48. Contdo The dose can be guided by measurements of blood pressure, serum potassium, and plasma renin activity, which should be in the upper-normal . double or triple the dose of hydrocortisone temporarily whenever they have any febrile illness or injury.Adrenal Insufficiency 48 49. Hypoaldosteronism Secondary hypoaldosteronism (hyporeninismhypoaldosteronism)Inadequate stimulation of the zona gromulesa of theadrenal cortex despite intact adrenal cortex.CAUSE Hyporeninism, as an inherited biosynthetic defect. postoperatively following removal of aldosterone-secreting adenomas. during protracted heparin administration. Renal insufficiency .Adrenal Insufficiency49 50. pseudohypoaldosteronism An inherited disease characterized by severe neonatal salt wasting, hyperkalemia, metabolic acidosis, and unresponsiveness to mineralocorticoid hormone action.The disease can be due to a loss-of-function mutation in the mineralocorticoid receptor .Adrenal Insufficiency50 51. References1.Williams text book of endocrinology,11th Edition2.Ganongs review of medical physiology,23thEdition.3. Harrisons principles of internal medicine.16thedition.4. Guyton Text book of medical physiology,11thedition5. Internet websites. Adrenal Insufficiency 51 52. Adrenal Insufficiency 52