Adrencortical hypofunction


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Adrencortical hypofunction

  1. 1. College of Health SciencesDepartment of medical PhysiologyPresentation on Adrenocortical Hypofunction robel abay 1
  2. 2. Topic out line Objectives Introduction Adrenal insufficiency  Primary Adrenal insufficiency  Secondary Adrenal insufficiency Addisons Crisis Treatment modalities Isolated Hypoadrenalism Adrenal Insufficiency 2
  3. 3. learning ObjectivesAt the end of these presentation learners expected to:- Know the pathophysiology of adrenal insufficiency. Identify the cause of adrenal insufficiency. List the clinical manifestation of adrenal insufficiency Explain Addisons crisis Know pathophysiology of isolated hypoadrenalism Know the treatment modalities Adrenal Insufficiency 3
  4. 4. Endocrine Abnormalities Endocrine abnormality expressed by hypersecretion or hyposecretion of hormone. Primary disorder-result from the gland it self. Secondary disorder-the problem result from other organ or target tissue. Adrenal Insufficiency 4
  5. 5. Cause Of Endocrine Abnormalities Metabolic factors. Physical damage Congenital problems. Genetic abnormalities. Adrenal Insufficiency 5
  6. 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. 7. Cont’dAccording 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 Insufficiency 7
  8. 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 Insufficiency 8
  9. 9. cont’d Cause1. idiopathic Autoimmune Adrenalitis The most common type. Atrophy of adrenal cortex due to autoimmune diseases, the adrenal medulla is intact. Accounts 70% of the Addison’ s disease. 15% of patients with Addisons disease have an associated autoimmune disease , graves disease being the most common Adrenal Insufficiency 9
  10. 10. Cont’d Idiopathic autoimmune Addison disease may occur in isolation or in association with other autoimmune phenomena such as: - Schmidt syndrome: The association of Addison disease and Hashimoto thyroiditis. - polyglandular autoimmune syndrome type 1: The association of Addison disease with hypoparathyroidism and mucocutaneouscandidiasis.o It may have an autosomal recessive mode of inheritance. It has no human leukocyte antigen (HLA) associations. Adrenal Insufficiency 10
  11. 11. Cont’d- polyglandular autoimmune syndrome type2: The association of Addison disease with type 1diabetes mellitus and Hashimoto thyroiditis orGraves disease. Adrenal Insufficiency 11
  12. 12. Primary adrenal insufficiency cont’d2.Infections Tuberculosis-most common AIDS Fungal infections( histoplasmosis, Cryptococcus) CMV infection Adrenal Insufficiency 12
  13. 13. Cont’d Hematogenous spread of the M.tuberculosis from else 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 with calcification of 50% evident. Adrenal Insufficiency 13
  14. 14. Cont’dAdrenal Insufficiency 14
  15. 15. Cont’d3. Miscellaneous-Rare causes Addisons disease • Bilateral cancer metastasis  Amyloidosis, hemosiderosis (rare)  ketoconazole use, macrophage-released cytokines are risk factors  Intra adrenal bleeding  Bilateral adrenoloctomy Adrenal Insufficiency 15
  16. 16. Cont’dIntra 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. 17. WATERHOUSE-FRIDERICHSEN SYNDROME• Acute, bilateral hemorrhagic infarction of the adrenals.• Occurs secondary to shock and DIC, in a septicemic infection. Endotoxic hemorrhaging. Tiny fibrin thrombi occlude the vessels going to the adrenal glands ------> infarction. Neisseria Meningitidis is the most common agent causing the infection. Also Pneumococci, Staph, Strep, Haemophilus, Diphtheria. Herpes Virus can cause it. Complete and sudden collapse of cortical function SYMPTOMS: like symptoms of shock ,infection and DIC (petechia, thrombocytopenia, increased PT and PTT). Adrenal Insufficiency 17
  18. 18. Cont’dAdrenal Insufficiency 18
  19. 19. Cont’d4. congenital and genetic abnormalities A. congenital Adrenal Hypoplasia (CAH) It is an X-linked disorder comprising congenital adrenal insufficiency and hypogonadotrophic hypogonadism. caused by mutations in the NROB1 gene. DAX-1 gene- a member of the nuclear receptor family that is expressed in the adrenal cortex, gonads, and hypothalamus. Adrenal Insufficiency 19
  20. 20. Cont’d Mutations in another transcription factor steroidogenic factor-1—may also result in adrenal insufficiency due to lack of development of a functional adrenal cortex. CAH may also occur in association with glycerol kinase deficiency and muscular dystrophy. Adrenal Insufficiency 20
  21. 21. Cont’dB.Adrenoleukodystrophy An inherited metabolic disorder resulting in accumulation of very-long-chain fatty acids (VLCFA) in tissues including the brain and adrenal cortex, resulting in: Progressive demyelination of cerebral white matter Adrenal insufficiencyo Only males have the fully expressed condition and carrier females are usually normal. Adrenal Insufficiency 21
  22. 22. Pathogenesis Accumulation of VLCFA VLCFA esterified to cholesterol, making cholesterol unavailable as a steroid/hormone precursor Adrenocorticalcells with these inclusions have decreased mitochondrial and microsomalenzyme activity Over time these cells atrophy, further deteriorating adrenocorticalfunction Adrenal Insufficiency 22
  23. 23. Cont’dC.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 hypoglycemia or later with increasing pigmentation, often with enhanced growth velocity. Two types-type 1 variant-25% of the case. - type 2 variant . Adrenal Insufficiency 23
  24. 24. cont’dD. 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. 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 Insufficiency 25
  26. 26. Cont’d Problems in hypothalamus or pituitary ⇓ plasma levels of ACTH low. ⇓ unable to stimulate the zona fasiculate and zona reticularies of adrenal cortex. ⇓ cortisol levels low. Adrenal cortices do response to exogenous ACTH. Adrenal Insufficiency 26
  27. 27. Cont’d Cause1. Sudden cessation of exogenous glucocorticoid therapy. Abrupt withdrawal of corticosteroids is a very common cause 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 Insufficiency 27
  29. 29. Cont’d2. Pan- Hypopituitarismreflect inadequate ACTH production from the anterior pituitary 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 Insufficiency 29
  30. 30. Cont’d3.Surgical cause - Selective removal of ACTH-secreting pituitary adenoma -pituitary surgery.4. Postpartum pituitary infarction (Sheehans syndrome) Adrenal Insufficiency 30
  31. 31. Signs & Symptoms 1. Hyper Pigmentation of skin & mucous membrane due to excess ACTH secretion because of cortisol deficiency.- ACTH causes pigmentation by its melanocyte stimulating action. on the sun exposed areas of the skin, extensor surface,knuckles,elbows and knees.2.Vitiligo is also common in auto Immune Addisons disease due to destruction of melanocyte. 31 Adrenal Insufficiency
  32. 32. Hyperpigmentation Adrenal Insufficiency 32
  33. 33. Cont’d2.Electroliyte and acid – base balance abnormalities. Hyponatremia. Hyperkalemia and metabolic acidosis Hypercalcemia. Adrenal Insufficiency 33
  34. 34. Cont’d3.Dehydretion with loss of sodium- As ECF becomes depleted. - plasma volume fall. - COP decreased.4.Muscle weakness. Adrenal Insufficiency 34
  35. 35. Cont’d 5. Decreased cardiac output & decreased workload of the heart 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 Insufficiency 35
  36. 36. Cont’dAdrenal Insufficiency 36
  37. 37. Cont’d Primary vs. secondary adrenal hypo functionprimary secondarySite=adrenal site=hypothalamus-pituitary↑ACTH ↓ACTH↑pigmentation ↓pigmentationweight loss weight change varyNo change in GH and ↓GH and gonadotropinsGonadotropins.Deficient in all corticosteroids other adrenal hormones normal or slightly↓No response to exogenous ACTH sluggish response to exogenousACTH. 37 Adrenal Insufficiency
  38. 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 60 minutes after an IV ACTH injection.In healthy person rise in blood and urine cortisol levelsIn adrenal insufficiency respond poorly or do not respond at all. Adrenal Insufficiency 38
  39. 39. Cont’d2.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. 40. Addison’s crisis A life treating emergency of exacerbate adrenal insufficiency of undiagnosed patient during facing stress full conditions. symptoms are intensified. Nausea, vomiting, and abdominal pain may become intractable. In all patients in addisonian’s crisis, a precipitating cause should be identify. Adrenal Insufficiency 40
  41. 41. Addisons CrisisClinical Presentation Life-threatening emergency May be primary or secondary HYPOTENSION  Typically resistant to catecholamine and IVF resuscitation Adrenal Insufficiency 41
  42. 42. cont’dAbrupt adrenal failure usually from gland hemorrhage or thrombosis  Anticoagulation  DIC  Sepsis  Usually have abdominal and flank pain Adrenal Insufficiency 42
  43. 43. Cont’dCatastrophic HPA axis failure  Head injury  Hemorrhage of pituitary adenoma  Post-partum herniation (Sheehan syndrome)  Usually neurological deficits, headaches, visual field cuts and diabetes insipidus. Adrenal Insufficiency 43
  44. 44. Treatment Modalities Different treatment regimes. Emergency treatments maintenance therapy. Replacement of glucocorticoids and mineralo corticoids. Adrenal Insufficiency 44
  45. 45. Treatment of Addisons crisis hydrocortisone 50-100 mg every 6-8 hours intravenous fluids dextrose search for precipitating cause Adrenal Insufficiency 45
  46. 46. Treatment Patients with symptomatic adrenal insufficiency, should be treated with hydrocortisone or cortisone therapy. The usual initial dose is 25 mg of hydrocortisone (divided into 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 of hydrocortisone as long as the patient remains asymptomatic. Adrenal Insufficiency 46
  47. 47. Treatment chronic AI hydrocortisone 12-15 mg in one or divided doses titrate to lowest tolerated dose consider mineralocorticoid ( fludrocortisone ) if primary AI. in a single daily dose of 50 to 200 µg, as a substitute for aldosterone. Adrenal Insufficiency 47
  48. 48. Cont’do 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. 49. Hypoaldosteronism Secondary hypoaldosteronism (hyporeninism hypoaldosteronism)Inadequate stimulation of the zona gromulesa of the adrenal 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 Insufficiency 49
  50. 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 Insufficiency 50
  51. 51. References1.Williams text book of endocrinology,11th Edition2.Ganong’s review of medical physiology,23th Edition.3. Harrison’s principles of internal medicine.16th edition.4. Guyton Text book of medical physiology,11th edition5. Internet websites. Adrenal Insufficiency 51
  52. 52. Adrenal Insufficiency 52