A Case of Polyglandular Autoimmune Syndrome - Type II

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A Case of Polyglandular Autoimmune Syndrome - Type II

  1. 1. INTERESTING CASE OF HEPATOMEGALY PROF S.SUNDAR’S UNIT Dr.A.NILAVAN PG
  2. 2. <ul><li>18 year old female was referred from GH for evaluation of hepatomegaly </li></ul><ul><li>H/o abdominal pain </li></ul><ul><li>No h/o fever/ yellowish urine or eyes/ pruritis/clay coloured stools </li></ul><ul><li>No H/o joint pain or rash </li></ul><ul><li>No H/o polyuria /polydipsia </li></ul><ul><li>No h/o vomiting/hemetemesis/melena/loose stools </li></ul><ul><li>No H/o weight loss/ loss of appetite </li></ul><ul><li>No H/o cold or heat intolerance </li></ul><ul><li>No H/o weakness /blurring of vision </li></ul>
  3. 3. <ul><li>Past H/o </li></ul><ul><li>Not a k/c/o hypertension/DM / bronchial </li></ul><ul><li>asthma </li></ul><ul><li>No H/o blood transfusion in the past </li></ul><ul><li>Personal H/o </li></ul><ul><li>Mixed diet </li></ul><ul><li>attained menarche at 17 yrs </li></ul><ul><li>cycles regular 3/28 </li></ul>
  4. 4. <ul><li>Family H/o </li></ul><ul><li>Non consanguinous marriage </li></ul><ul><li>One younger brother and sister- both normal </li></ul>
  5. 5. <ul><li>General examination </li></ul><ul><li>Pt concious, oriented ,afebrile </li></ul><ul><li>no icterus pallor/ cyanosis/ clubbing/lymphadenopathy </li></ul><ul><li>no features of chronic liver disease </li></ul><ul><li>no KF ring </li></ul><ul><li>Alopecia+ </li></ul><ul><li>Hyperpigmentation over forehead, around eyebrows, tongue,palm,buccal mucosa </li></ul><ul><li>BP: 90/70 mmhg </li></ul>
  6. 6. <ul><li>Systemic examination </li></ul><ul><li>CVS: S1 ,S2 + </li></ul><ul><li>No murmur </li></ul><ul><li>RS : NVBS + </li></ul><ul><li>No added sounds </li></ul><ul><li>P/A : soft , firm liver palpable around4cm below RCM , Liver span 20cm </li></ul><ul><li>No free fluid/ splenomegaly </li></ul><ul><li>CNS: NFND </li></ul>
  7. 7. INVESTIGATION Hb 13.5g/dl TC 6300 cells per cu. Mm DC P 62 L34M4 ESR 30 mm/hr PLATLET COUNT 240000 cell per cu.mm HAEMATOCRIT 36 UREA 17mg/dl CREATININE 0.7mg/dl SODIUM 134 meq/l POTTASIUM 5.6meq/ l CHLORIDE 104 meq/l CALCIUM 8.8mg/dl PHOSPHORUS 4.1mg/dl RBS(mg/dl) 356
  8. 8. CONT… 12/12/10 15/12/10 18/12/10 22/12/10 FBS (mg/dl) 440 301 192 148 PPBS( mg/dl) 546 361 355 172
  9. 9. Total bilirubin 0.77mg/dl Direct bilirubin 0.32mg/dl AST 441u/l ALT 348u/l SAP 230u/l GGT 235u/l PT 17sec INR 1.7
  10. 10. <ul><li>Urine routine </li></ul><ul><li>sugar: 3+ </li></ul><ul><li>albumin: nil </li></ul><ul><li>deposits: 2-3 epithelial cells </li></ul><ul><li>Bile salts& Bile pigment : negative </li></ul><ul><li>ketones : negative </li></ul><ul><li>24 hrs urinary protein :120 mg </li></ul>
  11. 11. <ul><li>ECG : NSR, WNL </li></ul><ul><li>Xray chest pa view : normal study </li></ul><ul><li>Echo : normal study </li></ul><ul><li>USG abdomen : hepatomegaly, portal vein normal size, spleen, pancreas normal </li></ul><ul><li>Fundus : normal </li></ul><ul><li>Slit lamp examination : normal </li></ul><ul><li>Viral markers : negative </li></ul><ul><li>HIV ,ELISA : Non reactive </li></ul><ul><li>UGI SCOPY : normal </li></ul>
  12. 12. PROVISIONAL DIAGNOSIS <ul><li>DM? type 1 </li></ul><ul><li>Autoimmune hepatitis </li></ul><ul><li>Haemochromatitis </li></ul><ul><li>Wilson s disease </li></ul>
  13. 13. FURTHER INVESTIGATIONS <ul><li>Serum iron -80micro g/dl </li></ul><ul><li>Serum ferritin -200 ng /ml </li></ul><ul><li>Serum transferrin – 320 mg/dl </li></ul><ul><li>Total iron binding capacity- 300 micro g/dl </li></ul><ul><li>ANA –negative </li></ul><ul><li>Anti LKM-1 -negative </li></ul><ul><li>AntiSLA –negative </li></ul><ul><li>Serum ceruloplasmin- 25 mg/dl </li></ul><ul><li>24 hrs urinary copper- 30 microg/day </li></ul>
  14. 14. <ul><li>T3 -60 ng/dl </li></ul><ul><li>T4 free- 0.4ng/ml </li></ul><ul><li>TSH -23micro Iu/ml </li></ul>
  15. 15. <ul><li>TPO antibody- positive </li></ul><ul><li>GAD antibody- positive </li></ul><ul><li>Islet cell antibody- positive </li></ul><ul><li>Anti mitochondrial antibody- negative </li></ul><ul><li>Anti smooth muscle antibody -positive </li></ul><ul><li>Serum ACTH-92pg/dl </li></ul><ul><li>Serum cortisol-6microgram/dl. After cosyntropin stimulation increased to 14 microgram/dl </li></ul>
  16. 16. FINAL DIAGNOSIS <ul><li>Polyglandular autoimmune syndrome type II (PGA-II) </li></ul>
  17. 17. TREATMENT <ul><li>INSULIN </li></ul><ul><li>ELTROXIN </li></ul><ul><li>FLUDROCORTISONE </li></ul><ul><li>PREDNISONE </li></ul><ul><li>UDCA </li></ul>
  18. 18. Polyglandular autoimmune syndrome type II (PGA-II) <ul><li>Most common of the immunoendocrinopathy syndromes. </li></ul><ul><li>Autoimmune Addison's disease </li></ul><ul><li>Thyroid autoimmune diseases </li></ul><ul><li>Type 1 diabetes mellitus </li></ul><ul><li>Primary hypogonadism, myasthenia gravis, and celiac disease </li></ul><ul><li>The most frequent clinical combination association is Addison's disease and Hashimoto's thyroiditis </li></ul>
  19. 19. Adulthood, usually around the third and fourth decade. Middle-aged women Associated with HLA-DR3 and/or HLA-DR4 haplotypes, Pattern of inheritance is autosomal dominant with variable penatrance.
  20. 20. <ul><li>Type 1 diabetes mellitus </li></ul><ul><ul><li>Symptoms - Polyuria, polydipsia, polyphagia, unexplained weight loss, intermittent blurred vision, and lethargy </li></ul></ul><ul><ul><li>Signs - Depend on the severity; consist of poor skin turgor, orthostasis, and hypotension </li></ul></ul><ul><li>Hashimoto's thyroiditis (chronic lymphocytic thyroiditis) </li></ul><ul><ul><li>Symptoms - cold intolerance, fatigue, somnolence, poor memory, constipation, menorrhagia, myalgias, and hoarseness </li></ul></ul><ul><ul><li>Signs - Slow tendon reflexes, bradycardia, facial and periorbital edema, dry skin and nonpitting edema, carpal tunnel syndromes, deafness, and pericardial or pleural effusions </li></ul></ul><ul><ul><li>Seronegative arthritis </li></ul></ul>
  21. 21. <ul><li>Graves disease </li></ul><ul><ul><li>Symptoms - Heat intolerance, weight loss, weakness, palpitations, oligomenorrhea, and anxiety </li></ul></ul><ul><ul><li>Signs - Brisk tendon reflexes, fine tremor, proximal weakness, stare and eyelid lag, exophthalmos, atrial fibrillation, and sinus tachycardia   </li></ul></ul><ul><li>Addison's disease (primary adrenal insufficiency) </li></ul><ul><ul><li>Symptoms - Anorexia, nausea, vomiting, weight loss, weakness, and fatigue </li></ul></ul><ul><ul><li>Signs - Chronic hyperpigmentation of creases and scars, as well as orthostatic hypotension   </li></ul></ul>
  22. 22. <ul><li>Celiac disease </li></ul><ul><li>Weight loss, steatorrhea, bloating, cramping, and malnutrition </li></ul><ul><li>Pernicious anemia </li></ul><ul><li>Pallor, jaundice, ataxia, glossitis, impaired cognition, impaired vibratory and position sense, and impaired cognition </li></ul>
  23. 23. <ul><li>Other disorders associated with PGA-II  </li></ul><ul><ul><li>Hypogonadism (usually autoimmune oophoritis) and hypopituitarism </li></ul></ul><ul><ul><li>Idiopathic thrombocytopenic purpura </li></ul></ul><ul><ul><li>Myasthenia gravis </li></ul></ul><ul><ul><li>Parkinson's disease </li></ul></ul><ul><ul><li>Vitiligo </li></ul></ul><ul><ul><li>Alopecia </li></ul></ul>
  24. 24. DIFFERENTIAL DIAGNOSIS <ul><li>DiGeorge syndrome </li></ul><ul><li>Kearns – Sayre syndrome </li></ul><ul><li>Wolfram’s syndrome </li></ul><ul><li>Cong . Rubella </li></ul><ul><li>IPEX syndrome </li></ul>
  25. 25. Laboratory Studies <ul><li>Serum autoantibodies screen </li></ul><ul><ul><ul><li>21-hydroxylase </li></ul></ul></ul><ul><ul><ul><li>17-hydroxylase </li></ul></ul></ul><ul><ul><ul><li>Thyroid peroxidase (TPO) </li></ul></ul></ul><ul><ul><ul><li>Thyroid-stimulating immunoglobulins (TSI) </li></ul></ul></ul><ul><ul><ul><li>Glutamic acid decarboxylase and islet cells </li></ul></ul></ul><ul><ul><ul><li>Antitissue transglutaminase antibodies </li></ul></ul></ul><ul><ul><ul><li>Immunoglobulin-A (IgA) endomysial antibodies and antigliadin antibodies. </li></ul></ul></ul><ul><ul><ul><li>Parietal cell and anti-intrinsic factor antibodies </li></ul></ul></ul>
  26. 26. <ul><ul><ul><li>Gonadotropins [FSH], [LH]) and appropriate sex hormones (testosterone, estradiol) </li></ul></ul></ul><ul><ul><ul><li>TSH, free thyroxine (T4), and free triiodothyronine (T3) </li></ul></ul></ul><ul><ul><ul><li>Adrenocorticotropic hormone (ACTH) level and Cortrosyn-stimulation test </li></ul></ul></ul><ul><ul><ul><li>Plasma renin activity and serum electrolytes </li></ul></ul></ul><ul><ul><ul><li>Calcium, phosphorus, magnesium, and albumin </li></ul></ul></ul><ul><ul><ul><li>Fasting blood glucose </li></ul></ul></ul><ul><ul><ul><li>Complete blood count (CBC) with mean cell volume (MCV) and vitamin B-12 levels </li></ul></ul></ul>
  27. 27. Medical Care <ul><li>With the exception of celiac disease and Graves disease, the mainstay of treatment is primarily hormonal replacement therapy </li></ul><ul><li>T4 therapy can precipitate adrenal crisis if adrenal insufficieny is present. So before starting thyroid hormone patient should be screened for adrenal insufficiency and if present should be treated with glucocorticoids. </li></ul><ul><li>A decreasing insulin requirement in patients with type 1 diabetes mellitus can be one of the earliest indications of adrenal insufficiency or renal dysfunction. This can occur before the development of hyperpigmentation or electrolyte abnormalities. </li></ul>
  28. 28. <ul><li>Hashimoto's thyroiditis (Hashimoto's disease) </li></ul><ul><ul><li>aim is to achieve euthyroidism. </li></ul></ul><ul><ul><li>Thyroid-stimulating hormone (TSH) is used to assess the level of euthyroidism. After 6 weeks of therapy, measure plasma TSH. Adjust the dose in increments of 12-25 mcg at intervals of 6-8 weeks until TSH is normal. Thereafter, annual measurements can be taken to ensure compliance and prevent overtreatment. </li></ul></ul><ul><li>Type 1 diabetes mellitus </li></ul><ul><ul><li>It requires lifelong treatment with exogenous insulin. </li></ul></ul><ul><ul><li>A roughly estimated dose for otherwise healthy individuals is approximately 0.6-1.2 U/kg/d (35-50 U/d in adults) </li></ul></ul>
  29. 29. <ul><li>Pernicious anemia </li></ul><ul><ul><li>Replacement with cyanocobalamin is the goal of therapy. </li></ul></ul><ul><ul><li>A typical schedule is 1 mg IM once a day for 7 days, and then weekly for 1-2 months or until the hemoglobin is normalized. Long-term therapy is 1 mg/mo. </li></ul></ul><ul><ul><li>Symptomatic hypokalemia may occur within 48 hours of initiating therapy, and supplemental potassium may be needed </li></ul></ul><ul><li>Graves disease </li></ul><ul><ul><li>Antithyroid medications in older patients (>60 y) or in those with underlying heart disease. When euthyroidism is achieved, radioactive iodine is then administered. </li></ul></ul><ul><ul><li>Ablation by radioactive iodine administration is the therapy of choice by most patients (young and healthy). </li></ul></ul><ul><ul><li>The restoration of euthyroidism using antithyroid drugs takes several months. Patients are evaluated at 6-week intervals by assessing the clinical findings and serum free T4 and free T3. </li></ul></ul>
  30. 30. <ul><li>Addison's disease </li></ul><ul><ul><li>Hydrocortisone and fludrocortisone. </li></ul></ul><ul><ul><li>Adjust the hydrocortisone dose depending on patient's symptoms. Monitor the activity levels of plasma renin to assess the efficacy of treatment with fludrocortisone and serum electrolytes. </li></ul></ul><ul><li>Celiac disease </li></ul><ul><ul><li>Place patients on a gluten-free diet. </li></ul></ul><ul><ul><li>Depending on the degree of malabsorption, patients also may require iron, folate, calcium, or vitamin supplementation. </li></ul></ul><ul><ul><li>In patients whose conditions are severe or refractory, a trial of prednisone (10-20 mg) may be effective. </li></ul></ul>
  31. 31. <ul><li>Screening of patients every 1-2 years, until they are aged 50 years. </li></ul><ul><ul><li>Screening includes an assessment of autoantibodies, electrolytes, thyroid function tests, liver function tests, vitamin B-12 levels, Cortrosyn-stimulation test, fasting blood glucose, plasma renin activity, CBCs, gonadotropins, and testosterone/estradiol. </li></ul></ul><ul><li>Family members should be strongly considered for genetic counseling and should undergo necessary screening for autoimmune diseases. </li></ul>
  32. 32. Polyglandular autoimmune syndrome type I (PGA-I) <ul><li>Childhood. </li></ul><ul><li>Autosomal recessive pattern, with variable inheritance </li></ul><ul><li>No HLA association and, </li></ul><ul><li>Equal sex incidence. </li></ul><ul><li>Mucocutaneous candidiasis </li></ul><ul><li>Hypoparathyroidism </li></ul><ul><li>Primary adrenal insufficiency </li></ul>
  33. 33. <ul><li>Other associated disorders </li></ul><ul><li>hypogonadism </li></ul><ul><li>hypothyroidism </li></ul><ul><li>pernicious anemia </li></ul><ul><li>celiac disease </li></ul><ul><li>autoimmune hepatitis </li></ul><ul><li>alopecia </li></ul><ul><li>vitiligo </li></ul>
  34. 34. <ul><li>THANK YOU </li></ul>

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