Adrencortical hypofunction


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Adrencortical hypofunction

  1. 1. Addis Ababa UniversityCollege of Health SciencesDepartment of medical PhysiologyPresentation on Adrenocortical Hypofunction<br />By GIRMAY F.<br />1<br />
  2. 2. Topic out line<br />Objectives<br />Introduction<br />Adrenal insufficiency<br /><ul><li>Primary Adrenal insufficiency
  3. 3. Secondary Adrenal insufficiency</li></ul>Addison's Crisis<br />Treatment modalities<br /> Isolated Hypoadrenalism<br />Adrenal Insufficiency<br />2<br />
  4. 4. learning Objectives<br />At the end of these presentation learners expected to:-<br />Know the pathophysiology of adrenal insufficiency.<br />Identify the cause of adrenal insufficiency.<br />List the clinical manifestation of adrenal insufficiency<br />Explain Addison's crisis<br />Know pathophysiology of isolated hypoadrenalism<br />Know the treatment modalities <br />Adrenal Insufficiency<br />3<br />
  5. 5. Endocrine Abnormalities<br />Endocrine abnormality expressed by hypersecretion or hyposecretion of hormone.<br />Primary disorder-result from the gland it self.<br />Secondary disorder-the problem result from other organ or target tissue.<br />Adrenal Insufficiency<br />4<br />
  6. 6. Cause Of Endocrine Abnormalities<br />Metabolic factors.<br />Physical damage<br />Congenital problems.<br />Genetic abnormalities.<br />Adrenal Insufficiency<br />5<br />
  7. 7. Adrenal Insufficiency<br />Definition<br />Adrenal insufficiencyis 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.<br />Adrenal Insufficiency<br />6<br />
  8. 8. Cont’d<br />According the site of problem<br /><ul><li>primary adrenal insufficiency.
  9. 9. Secondary adrenal insufficiency.
  10. 10. Primary Adrenal insufficiency- The gland it self is </li></ul> damaged.<br /> - Secondary adrenal insufficiency-The gland <br /> healthy but lacks hormonal stimulation <br />Adrenal Insufficiency<br />7<br />
  11. 11. Primary Adrenal insufficiency<br />Addison's disease<br /><ul><li>it occurs when 90% of the adrenal gland is destroyed.
  12. 12. is a relatively uncommon disorder that occurs in people of all ages and both sexes.
  13. 13. characterized by decreased mineralocorticoid, glucocorticoid, and androgen secretion.</li></ul>Adrenal Insufficiency<br />8<br />
  14. 14. cont’d<br />Cause<br /> 1. idiopathic Autoimmune Adrenalitis<br /><ul><li>The most common type.
  15. 15. Atrophy of adrenal cortex due to autoimmune diseases, the adrenal medulla is intact.
  16. 16. Accounts 70% of the Addison’ s disease.
  17. 17. 15% of patients with Addison's disease have an associated autoimmune disease , graves disease being the most common</li></ul>Adrenal Insufficiency<br />9<br />
  18. 18. Cont’d<br />Idiopathic autoimmune Addison disease may occur in isolation or in association with other autoimmune phenomena such as:<br /> - Schmidt syndrome: The association of Addison disease and Hashimoto thyroiditis.<br /> - polyglandular autoimmune syndrome type 1: <br /> The association of Addison disease with hypoparathyroidism and mucocutaneouscandidiasis.<br /><ul><li>It may have an autosomal recessive mode of inheritance. It has no human leukocyte antigen (HLA) associations.</li></ul>10<br />Adrenal Insufficiency<br />
  19. 19. Cont’d<br />- polyglandular autoimmune syndrome type2:<br /> The association of Addison disease with type 1 diabetes mellitus and Hashimoto thyroiditis or Graves disease. <br />11<br />Adrenal Insufficiency<br />
  20. 20. Primary adrenal insufficiency cont’d<br />2.Infections<br /><ul><li>Tuberculosis-most common
  21. 21. AIDS
  22. 22. Fungal infections( histoplasmosis, Cryptococcus)
  23. 23. CMV infection</li></ul>Adrenal Insufficiency<br />12<br />
  24. 24. Cont’d<br />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.<br />Both cortex and adrenal medulla is affected.<br />Fibrosis follows the adrenal become smaller with calcification of 50% evident.<br />Adrenal Insufficiency<br />13<br />
  25. 25. Cont’d<br />Adrenal Insufficiency<br />14<br />
  26. 26. Cont’d<br />3. Miscellaneous-Rare causes Addison's disease<br /><ul><li>Bilateral cancer metastasis-lung ,breastca.</li></ul>Amyloidosis, hemosiderosis (rare)<br />ketoconazole use, macrophage-released cytokines are risk factors<br />Intra adrenal bleeding<br />Bilateral adrenoloctomy<br />Adrenal Insufficiency<br />15<br />
  27. 27. Cont’d<br />Intra adrenal bleeding- cause necrosis of the adrenal may occur in severely sick patient, with underlying infection, trauma, or coagulopathy.<br /> - cause of severe septicemia, particularly in children in whom a common cause is infection with Neisseria Meningitidis.<br /> when caused by meningococci,the association with adrenal insufficiency is know as the Waterhouse Friederichsen syndrome.<br />Adrenal Insufficiency<br />16<br />
  28. 28. WATERHOUSE-FRIDERICHSEN SYNDROME <br /><ul><li>Acute, bilateral hemorrhagic infarction of the adrenals.
  29. 29. Occurs secondary to shock and DIC, in a septicemic infection. Endotoxic hemorrhaging.</li></ul>Tiny fibrin thrombi occlude the vessels going to the adrenal glands ------> infarction.<br />Neisseria Meningitidis is the most common agent causing the infection.<br /> Also Pneumococci, Staph, Strep, Haemophilus, Diphtheria.Herpes Virus can cause it.<br />Complete and sudden collapse of cortical function <br /> SYMPTOMS: like symptoms of shock ,infection and DIC (petechia, thrombocytopenia, increased PT and PTT).<br />Adrenal Insufficiency<br />17<br />
  30. 30. Cont’d<br />Adrenal Insufficiency<br />18<br />
  31. 31. Cont’d<br />4. congenital and genetic abnormalities<br />A.congenital Adrenal Hypoplasia (CAH)<br /><ul><li>It is an X-linked disorder comprising congenital adrenal insufficiency and hypogonadotrophic hypogonadism.
  32. 32. caused by mutations in the NROB1 gene.
  33. 33. DAX-1 gene- a member of the nuclear receptor family that is expressed in the adrenal cortex, gonads, and hypothalamus.</li></ul>Adrenal Insufficiency<br />19<br />
  34. 34. Cont’d<br /><ul><li>Mutations in another transcription factor steroidogenicfactor-1—may also result in adrenal insufficiency due to lack of development of a functional adrenal cortex.
  35. 35. CAH may also occur in association with glycerol </li></ul> kinase deficiency and muscular dystrophy.<br />Adrenal Insufficiency<br />20<br />
  36. 36. Cont’d<br />B.Adrenoleukodystrophy <br /> An inherited metabolic disorder resulting in accumulation of very-long-chain fatty acids (VLCFA) in tissues including the brain and adrenal cortex, resulting in:<br />Progressive demyelination of cerebral white matter<br />Adrenal insufficiency<br /><ul><li> Only males have the fully expressed condition and carrier females are usually normal.</li></ul>Adrenal Insufficiency<br />21<br />
  37. 37. Pathogenesis<br />Accumulation of VLCFA<br />VLCFA esterified to cholesterol, making cholesterol unavailable as a steroid/hormone precursor<br />Adrenocorticalcells with these inclusions have decreased mitochondrial and microsomalenzyme activity<br />Over time these cells atrophy, further deteriorating adrenocorticalfunction<br />Adrenal Insufficiency<br />22<br />
  38. 38. Cont’d<br />C.Familial glucocorticoid deficiency (FGD)<br /><ul><li> inherited unresponsiveness to ACTH.
  39. 39. It is a rare autosomal recessive cause of</li></ul> hypoadrenalism .<br /><ul><li> Usually presents in childhood.
  40. 40. The renin-angiotensin-aldosterone axis is intact.
  41. 41. children usually present either with neonatal hypoglycemia or later with increasing pigmentation, often with enhanced growth velocity.
  42. 42. Two types-type 1 variant-25% of the case.</li></ul> - type 2 variant .<br />Adrenal Insufficiency<br />23<br />
  43. 43. cont’d<br />D.Allgrove syndrome: congenital adrenocortical unresponsiveness to ACTH typically presents in childhood with failure to thrive, features of adrenocortical insufficiency and hypoglycemia.<br />- disease to chromosome 12q13 but the responsible gene is unknown.<br />Adrenal Insufficiency<br />24<br />
  44. 44. Secondary Adrenal insufficiency<br /><ul><li>Loss of hypothalamic-pituitary function and deficiency of ACTH.
  45. 45. Will usually have deficiencies of other gland regulated by hypothalamic-pituitary system.
  46. 46. Aldosterone secretion may continue intact.</li></ul>Adrenal Insufficiency<br />25<br />
  47. 47. Cont’d<br />Problems in hypothalamus or pituitary<br /> ⇓<br />plasma levels of ACTH low.<br />⇓<br /> unable to stimulate the zona fasiculate and zona reticularies of adrenal cortex.<br /> ⇓<br />cortisol levels low.<br /><ul><li>Adrenal cortices do response to exogenous ACTH.</li></ul>Adrenal Insufficiency<br />26<br />
  48. 48. Cont’d<br />Cause<br />Sudden cessation of exogenous glucocorticoid <br /> therapy.<br />Abrupt withdrawal of corticosteroids is a very common cause of secondary acute adrenal insufficiency.<br /><ul><li>chronic exogenous glucocorticoid</li></ul> ⇓<br /><ul><li>Suppresses diurnal CRH/ACTH release</li></ul> both time- and dose-related<br /> reversible<br />recovery may take up to long time<br />Adrenal Insufficiency<br />27<br />
  50. 50. Cont’d<br />2.Pan- Hypopituitarism<br />reflect inadequate ACTH production from the anterior pituitary gland. <br />In many of these, other pituitary hormones are deficient in addition to ACTH, so that the patient presents with partial or complete hypopituitarism.<br />Adrenal Insufficiency<br />29<br />
  51. 51. Cont’d<br />3.Surgical cause<br /> - Selective removal of ACTH-secreting pituitary adenoma<br /> -pituitary surgery.<br />4.Postpartum pituitary infarction (Sheehan's syndrome)<br />Adrenal Insufficiency<br />30<br />
  52. 52. Signs & Symptoms<br /> 1. Hyper Pigmentation of skin & mucous membrane due to excess ACTH secretion because of cortisol deficiency. <br /> - ACTH causes pigmentation by its melanocyte stimulating action. on the sun exposed areas of the skin, extensor surface,knuckles,elbows and knees. <br />2.Vitiligo is also common in auto Immune Addison's disease due to destruction of melanocyte.<br />Adrenal Insufficiency<br />31<br />
  53. 53. Hyperpigmentation<br />Adrenal Insufficiency<br />32<br />
  54. 54. Cont’d<br />2.Electroliyte and acid – base balance abnormalities. <br /><ul><li> Hyponatremia.
  55. 55. Hyperkalemia and metabolic acidosis
  56. 56. Hypercalcemia.</li></ul>Adrenal Insufficiency<br />33<br />
  57. 57. Cont’d<br />3.Dehydretion with loss of sodium <br /> - As ECF becomes depleted.<br /> - plasma volume fall.<br /> - COP decreased.<br />4.Muscle weakness.<br />Adrenal Insufficiency<br />34<br />
  58. 58. Cont’d<br />5. Decreased cardiac output & decreased workload of the heart leading to decrease in size of the heart.<br />6. Hypoglycemia.<br />7. Inability to withstand any type of stress like physical, mental, even exposure to mild stress, trauma.<br />8.Decreased pubic and axillary hair in women.<br />9.Nausea,vomiting and diarrhea.<br />Adrenal Insufficiency<br />35<br />
  59. 59. Cont’d<br />Adrenal Insufficiency<br />36<br />
  60. 60. Cont’d<br />Primary vs. secondaryadrenal hypo function <br /> primary secondary<br />Site=adrenal site=hypothalamus-pituitary<br />↑ACTH ↓ACTH<br />↑pigmentation ↓pigmentation<br />weight loss weight change vary<br />No change in GH and ↓GH and gonadotropins<br />Gonadotropins.<br />Deficient in all corticosteroids other adrenal hormones normal or<br /> slightly↓ <br />No response to exogenous ACTH sluggish response to<br /> exogenousACTH. <br />Adrenal Insufficiency<br />37<br />
  61. 61. Diagnosis<br />1.ACTH stimulation test<br />Blood and/or urine cortisol levels are measured.<br />Administration of synthetic ACTH.<br />Cortisol measurement in blood is repeated 30 to 60 minutes after an IV ACTH injection. <br />In healthy person rise in blood and urine cortisol levels<br />In adrenal insufficiency respond poorly or do not respond at all.<br />Adrenal Insufficiency<br />38<br />
  62. 62. Cont’d<br />2.insulin-induced hypoglycemia test<br />Blood measure of glucose and cortisol level.<br />An injection of fast acting insulin.<br />Blood glucose and cortisol levels are measured at 30,45 and 90 minutes after the insulin injection.<br /><ul><li>The normal response is -↓blood glucose level</li></ul> -↑cortisol level.<br />Adrenal Insufficiency<br />39<br />
  63. 63. Addison’s crisis <br />A life treating emergency of exacerbate adrenal insufficiency of undiagnosed patient during facing stress full conditions.<br />symptoms are intensified. Nausea, vomiting, and abdominal pain may become intractable.<br />In all patients in addisonian’s crisis, a precipitating cause should be identify.<br />Adrenal Insufficiency<br />40<br />
  64. 64. Addison's Crisis<br />Clinical Presentation<br />Life-threatening emergency<br />May be primary or secondary<br />HYPOTENSION<br />Typically resistant to catecholamine and IVF resuscitation<br />Adrenal Insufficiency<br />41<br />
  65. 65. cont’d<br />Abrupt adrenal failure usually from gland hemorrhage or thrombosis<br />Anticoagulation<br />DIC<br />Sepsis<br />Usually have abdominal and flank pain<br />Adrenal Insufficiency<br />42<br />
  66. 66. Cont’d<br />Catastrophic HPA axis failure<br />Head injury<br />Hemorrhage of pituitary adenoma<br />Post-partum herniation (Sheehan syndrome)<br />Usually neurological deficits, headaches, visual field cuts and diabetes insipidus.<br />Adrenal Insufficiency<br />43<br />
  67. 67. Treatment Modalities<br />Different treatment regimes.<br />Emergency treatments<br /> maintenance therapy.<br />Replacement of glucocorticoids and mineralo corticoids.<br />Adrenal Insufficiency<br />44<br />
  68. 68. Treatment of Addison's crisis<br /> hydrocortisone 50-100 mg every 6-8 hours<br />intravenous fluids<br />dextrose<br />search for precipitating cause<br />Adrenal Insufficiency<br />45<br />
  69. 69. Treatment <br />Patients with symptomatic adrenal insufficiency, should be treated with hydrocortisone or cortisone therapy.<br />The usual initial dose is 25 mg of hydrocortisone (divided into doses of 15 and 10 mg) <br /> 37.5 mg of cortisone (divided into doses of 25 and 12.5 mg)<br />The daily dose may be decreased to 20 or 15 mg of hydrocortisone as long as the patient remains asymptomatic.<br />46<br />Adrenal Insufficiency<br />
  70. 70. Treatment chronic AI<br />hydrocortisone 12-15 mg in one or divided doses<br /> titrate to lowest tolerated dose<br /> consider mineralocorticoid ( fludrocortisone ) if primary AI. in a single daily dose of 50 to 200 µg, as a substitute for aldosterone.<br />Adrenal Insufficiency<br />47<br />
  71. 71. Cont’d<br /><ul><li>The dose can be guided by measurements of blood pressure, serum potassium, and plasma renin activity, which should be in the upper-normal .</li></ul>double or triple the dose of hydrocortisone temporarily whenever they have any febrile illness or injury.<br />48<br />Adrenal Insufficiency<br />
  72. 72. Hypoaldosteronism<br /> Secondary hypoaldosteronism (hyporeninism hypoaldosteronism)<br />Inadequate stimulation of the zona gromulesa of the adrenal cortex despite intact adrenal cortex.<br />CAUSE <br />Hyporeninism, as an inherited biosynthetic defect.<br />postoperatively following removal of aldosterone- secreting adenomas.<br />during protracted heparin administration.<br />Renal insufficiency .<br />Adrenal Insufficiency<br />49<br />
  73. 73. pseudohypoaldosteronism<br /> An inherited disease characterized by severe neonatal salt wasting, hyperkalemia, metabolic acidosis, and unresponsiveness to mineralocorticoid hormone action. <br /> The disease can be due to a loss-of-function mutation in<br /> the mineralocorticoid receptor . <br />Adrenal Insufficiency<br />50<br />
  74. 74. References<br />1.Williams text book of endocrinology,11th Edition<br />2.Ganong’s review of medical physiology,23th Edition.<br />3. Harrison’s principles of internal medicine.16th edition.<br />4. Guyton Text book of medical physiology,11th edition<br />5. Internet websites.<br />Adrenal Insufficiency<br />51<br />
  75. 75. Thank you!!!<br />Adrenal Insufficiency<br />52<br />