HYPOTHYROIDISM.& MYXEDEMA CRISIS

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  •  Extensive fungal infection of the finger and toenails (onychomycosis) is often associated with hypothyroidism, a consequence of compromised cardiac contractility, leading to decreased blood flow to the extremities. The resulting low-oxygen state at the tips of the fingers and toes promotes fungal overgrowth.B. Slow capillary refilling, demonstrable by applying firm finger pressure to areas of thin skin, is a manifestation of reduced cardiac inotropy. As thyroid levels decline, cardiac contractility decreases. The worse this condition is, the closer to the heart it will manifest. It usually begins in the extremities, and patient will experience cold hands and feet. By the time it manifests above the knee, the patient has quite serious circulatory compromise.C. Poor capillary refilling, reflective of weak inotropy in the heart, leads to poor circulation at the extremities and facilitates fungal overgrowth in the nails. These signs are typical of longstanding hypothyroidism.D. Fluid leakage into extracellular spaces, a result of reduced glycoaminoglycan production also results in a characteristic swollen, scalloped tongue, which is very common in hypothyroid people.E. Conversion of beta-carotene to vitamin A is dependent on thyroid hormone. Thyroid deficiency will manifest as a yellowish buildup of carotene in the skin of the palms and soles. Poor circulation, also associated with hypothyroidism, facilitates fungal overgrowth between toes.F. Thyroid hormone drives production of glycoaminoglycans, responsible for keeping water inside cells. In hypothyroidism, water tends to leak into extracellular spaces causing significant edema, easily recognized around the legs and ankles.
  • HYPOTHYROIDISM.& MYXEDEMA CRISIS

    1. 1. 2CASES…………!!!!!!!!1)A 38 yr /old lady with generalised paresthesias,pain indiff.joints,generalised weakness, occasional vomiting;cough, she developed symptoms of tremor, irritability ,& shefeels cold even in normal day.Seen by PCP & investigated:CBC-@ Normal,except than Hb-9.5gm/dl,uric acid-7.2mg/dl (N-≤6) ;CPK- 300,2) 65 yoF with confusion brought in by police, Unable to answerquestions95F HR 50 BP 90/70 RR 20 02 85%EKG: low voltage, sinus bradycardia
    2. 2. THINKTHYROIDVAGUE SYMPTOMSMULTIPLE SYMPTOMSOLD AGEPOSTPARTUM PERIODCOLD /HEAT INTOLERANCEDIMENTIAFORGETFULNESSMILD ANEMIAMILD HYPERURICEMIAALTERED LIPID PROFILEELEVT.CPK
    3. 3. HYPOTHYROIDISM&MYXEDEMA CRISISDr.Sajid NomaniMEM (PGT)Peerless Hospital & B.K.Roy Research CenterKolkata
    4. 4. Goals of Discussion…..• THYROID -quick review• HYPOTHYROIDISMDefinitionClinical symptomsTreatment• MYXEDEMA CRISIS
    5. 5. The Thyroid Gland…….Vercelloni 1711: “a bag of worms ” whose eggspass into the esophagus for digestive purposesParry 1825: “a vascular shunt to cushion thebrain from sudden increases in blood flow
    6. 6. Introduction……• Largest endocrine gland• 20 grams in adult• Each lobe• 2-2.5cm in width and thickness• 4cm in height• Isthmus• 0.5cm thick• 2cm height and width
    7. 7. Introduction……• Two principal hormones.• Thyroxine (T4 ) and triiodothyronine (T3).• Required for homeostasis of all cells.• Influence cell differentiation, growth, and metabolism• Considered the major metabolic hormones becausethey target virtually every tissue
    8. 8. In the Thyroid Gland……5 steps in the hormonogenesis1. Trapping of inorganic Iodine from dietary Iodides2. Activation of Iodine to high valance I23. Incorporation of I2 into Tyrosine of Thyroid Globulin4. Coupling of formed MIT and DIT to form T4 & T35. Proteolysis of Thyroglobulin to release T4 & T3
    9. 9. The negative feedback…..
    10. 10. Thyroid gland normally releases 100-125 mcg of thyroxine (T4) daily and small amountsof T3Tri Iodo Thyronine – T310% is from thyroid gland90% derived from conversion of T4 to T3half life 6 hours99.5% protein bound to TBG, TPA, TATetra Iodo Thyronine – T4Is exclusively from thyroid glandhalf life 7 days99.9% protein bound to TBG, TPA, TAFrom the thyroid gland- 80% of hormone secreted is T4- 20% of hormone secreted is T3POTENCY—T3:T4=4:1
    11. 11. Normal……..• TSH :0.5-5.0 mIU/ L……….(Soon -TSH---2.5)• T4 (T) :4.5 - 12.5 µg/dl(F) :0.8 - 1.8 ng/LT4 is 99.9% protein bound to TBG, TPA, TA• T3 (T) :80 -200 ng/dl( F) :2.3- 4.2 pg/mlT3 is 99.5% protein bound to TBG, TPA, TABound hormones are inactive – should not be measuredOnly Free T4 and Free T3 are metabolically active
    12. 12. Thyroid Function Tests• TSH• Free T4• Free T3• Anti-Thyroid Antibodies• Nuclear Scintigraphy• FNAC of nodule
    13. 13. What tests should I order ?As per the Guidelines of the AACE and ATA, ITS• TSH alone if Hypothyroidism is suspected• TSH and Free T4 only if Hyperthyroidism suspected• Free T3 if T3 toxicosis is suspected• For follow-up of treatment only TSH• Don’t order for Total T4 or Total T3• Never order RIU in pregnancy or lactation
    14. 14. HypothyroidismThe Underactive Thyroid
    15. 15. Introduction….• This is the most common pathological hormone deficiency• Results in a slowing down of metabolic processes.• Prevalence 2-3% in the general population• Mean age at diagnosis is mid-40s• Male: Female 1:20
    16. 16. How common is it in India???....• Hypothyroidism :INDIA : 3.9% [Usha menon,A.G.Unnikrishnan,ijem july 2011]WORLDWIDE :2 %• Congenital hypothyroidism:INDIA: 1:2640WORLDWIDE :1 :3800 (vaidya & Pearce,2008)• Subclinical :9.4%M:F=6.2% :11.6%
    17. 17. Introduction…..• Classification:Time of onset: Congenital or acquiredSeverity: Clinical or subclinicalSite of dysfunction: Primary or secondary/tertiary
    18. 18. Interpration…..!!!!!!!!!!LOWNORMALHIGHLOW NORMAL HIGHFREETHYROXINEorFT4THYROID STIMULATING HORMONE - TSHPRIMARYHYPOTHYROIDSECONDARYHYPOTHYROIDSUB-CLINICALHYPOTHYROIDSECONDARYHYPERTHYROIDEUTHYROIDNON THYROIDILLNESS - NTISUB-CLINICALHYPERTHYROIDPRIMARYHYPERTHYROIDNTI or Pt.on ELTROXIN
    19. 19. Sign & symptoms…..Everything from the brain to the skin is affected by thehormone made by the thyroid gland.Hypothyroidism "It slows you down,It makes youlethargic and fatigued Your hair becomes brittle,and your skin becomes dry. You become cold mucheasier than the average person.
    20. 20. Sign & symptoms…..• Depends on degree of hormone deficiency(overt, subclinical)• Depends on speed of development of hormonedeficiency (gradual, better tolerated)
    21. 21. General• Lethargy, Somnalence• Weight gain, Goitre• Cold IntolerenceCardiovascular• Bradycardia, Angina• CHF, Pericardial Effusion• HyperlipIdemia, XanthelsmaHaematological• Iron def. Anaemia,• Normo cytic /chromic AnaemiaReproductive system• Infertility, Menorrhagia• Impotence, Inc. ProlactinNeuromuscular• Aches and pains• Muscle stiffness• Carpel tunnel syndrome• Deafness, Hoarseness• Cerebellar ataxia• Delayed DTR, Myotonia• Depression, PsychosisGastro-intestinal• Constipation, Ileus, AscitesDermatological• Dry flaky skin and hair• Myxoedema, Malar flushes• Vitiligo, Carotenimia, AlopeciaSign&symptoms…..
    22. 22. Clinical Signs of Hypothyroidism Coarse Hair; Dry cool and pale skin Goitre (not in all cases), Hoarseness of voice Non-pitting oedema (myxoedema) Puffiness of eyes and face Delayed relaxation of DTR Slow hoarse speech and slow movements Thinning of lateral 1/3 of eye brows Bradycardia, pericardial effusion
    23. 23. Management……GOAL---keep TSH ,half of upper ref .range.L-Thyroxine 1.6mcg/kg/day in otherwise healthypatientsin patients age>60 or if CAD present, 0.5-1.0mcg/day and slowly increaseT3-controversialrecheck levels in 6 weeks
    24. 24. coming back…to our case 11)A 38 yr /old lady with generalised paresthesias,pain indiff.joints,generalised weakness ,& low mood. cold intolerance,occasional vomiting; coughWHAT FURTHER TO LOOK…..• History• CO-EXISTING FACTORS• Comorbidities• Age• Severity of hypothyroidism• Coexisting drugs
    25. 25. Additional Info generated….• Family H/O hypothyroidism• Delivered 6 mo. back & Brest feeding• Taking Iron & Calcium tabs.• O/P—Small firm goiter• TSH—30 U/ml• FT4--- 0.4ng/ml• FURTHER TESTING ????DIAGNOSISPrimary HypothyroidismPostpartum ThyroiditisAnti TPO antibody(thy.peroxidase)Anti Tg(thyroglobulin)antibodyUSGFNAC
    26. 26. • Started---75mcg /day empty stomach• Called back after 6 weeks.Pt. reports good compliance TSH—20 u/l↑ Doses—100mcgCalled back after 6 weekTSH---15u/l ???……NOT CONTROLLEDWHAT ARE CAUSES FOR HIGH DOSES REQUIRMENT???IS THYROXINE TREATMENT DURING BREASTFEED SAFE TOBABY???
    27. 27. HIGH DOSES REQUIRMENT OF LEVOTHYROXINE• MALABSORPTION• Celiac disease• Small bowel surgery• MEDICATION• Estrogen• Amaidrone• Lithium prepration• Ferrous sulfate• Calcium• PPI• Carbamazepine• Phenytoin• Lovastatin• Bulk laxative• Magnesium prepration• Alumunium hydroxide
    28. 28. High doses requirment of lEVOTHYROXINE MALABSORPTION /↑EXCRETION OF T4Gastrointestinal disorders,Impaired acid secretionCeliac diseaseSmall bowel surgery MEDICATIONIncrease catabolism of T4:RifampinCarbamazepinePhenytoinPhenobarbitolDrugs interfere T4absorption:Cholestyramineorcolestipol,SucralfateFerrous sulfate,Calcium CarbonateAluminum hydroxide gels,SertralineRaloxifene, Omeprazole
    29. 29. What to do???• Space out thyroxine from other offending drugs.• Can be converted in night doses.• No adjustment for Renal / Hepatic diseases.• Safe in Breastfeeding.Our patientSpacing done between medicationCont.same doses; TSH reduced to—2.8Called backed after 3 month for evaluation; TSH—0.1REVERSIBLE HYPOTHYROIDISM20%Autoimmune found to be reversibleSpontaneous disappearance of blocking agent
    30. 30. Maternal Hypothyroidism• AACE recommendations• Carry out TSH assay routinely before pregnancy or during thefirst trimester to rule out thyroid disorder• Avoid complications by administering thyroid hormonereplacement therapy• Both mild as well as overt hypothyroidism are managed byadministering levothyroxine therapy which can be safelyadministered during pregnancy• Assess TSH levels every 6 weeks .• Increase the dose of thyroid hormone in pregnant women withmoderate to severe hypothyroidism
    31. 31. Do you need to treat Subclinical hypothyroidism• 5-8% indivisual have SCH.• 4.3 % progressed to overt hypothyroidism• Treat at all ages if:• Consider treatment, if:2012 European Thyroid AssociationPublished by S. Karger AG, BaselTSH >10.0 mU/lPregnancy (or pre-pregnancy)Age <65 yearsSymptoms or signs of hypothyroidismHigh vascular risk IHD/DM/DL/SMOKER]Positive thyroid peroxidase antibodiesGoitre
    32. 32. In the emerge ncy roomMYXEDEMA CRISISLife-threatening severe hypothyroidism• 80% -100 % mortality rate• Reduced to 15-20% with aggressively managment
    33. 33. MYXEDEMA CRISIS A rare clinical state of insidious onset, in anindividual with pre-existing hypothyroidism End-stage of untreated hypothyroidism. Precipitated by intercurrent illness such as infection,stroke or CNS depressants
    34. 34. Our 2nd patient65 yoF with confusion brought in by police, Unable to answer questions95F HR 50 BP 95/75 RR 20 02 85%EKG: low voltage, sinus bradycardia…CT-WNL, Chest Xray---Pleural effusion• Found wandering in the street• Unable to answer questions• Skin is coarse and waxy• Tranverse surgical scar on neck• Generalized weakness and prolonged DTR
    35. 35. Myxedema Coma: Clinical• OFTEN ELDERLY (but not always!!)• History of hypothyroidism• Levothyroxine replacement, thyroid cancer,• surgery, RAIA• Physical exam• Comatose or decreased mental status• Hypothyroid signs: Cool/dry skin, delayed reflexes,• lid lag, thin hair, hypothermia, ileus, effusionsMyxedema (not always easy to detect)
    36. 36. Myxedema Coma: Risk factor• Cold weather• Elderly women• Undiagnosed or under treated hypothyroidism• Precipitating event
    37. 37. Myxedema Coma: Precipitants• Discontinued thyroid hormone replacement• CVA or MI• Infection (UTI, URI)• Hemorrhage• Narcotics, diarrhea, comorbid illness
    38. 38. Myxedema Coma :FindingsDecrease mental status – from baselineHypothermia/ Hypoglycemia/ HyponatremiaBradycardiaHypoventillationPeri-orbital edemaNon-pitting EdemaDelayed Tendon Reflex
    39. 39. Myxedema Coma :Findings CardiacBradycardia / hypotensionCHFCardiomegalyPericardial effusionLow voltage EKG
    40. 40. Myxedema Coma :Findings NeckThyroidectomy scarGoiter (uncommon) DermatologicDry, scaly, yellow skinLoss of lateral 3rd of eyebrowsNon-pitting waxy edema of face / extremities
    41. 41. Myxedema Coma :Findings
    42. 42. Diagnosis• Diagnosis is clinical• Thyroid panel reflects chronic state
    43. 43. Myxedema Coma: Workup• Basic lab tests and radiology• FT4, TSH• CBC (anemia), electrolytes (hyponatremic),• renal function (increased Cr)• EKG (bradycardia), CXR (effusions)• Evaluate for pituitary disorders• Cortisol, cosyntropin stimulation test• FSH, LH
    44. 44. Managment Supportive careABCsRewarming Treat precipitating causes
    45. 45. Treatment ::Myxedema Coma Rewarming : 0.5celcius/h.,passive rewarming Thyroid hormoneLevothyroxine (T4) @4mcg/kg300 - 500mcg IV Hydrocortisone 100mg IV q8possible unrecognized adrenal or pituitary insufficiency Antibiotics & other supports
    46. 46. RECOMENDATION• The American Thyroid Association recommends screening atage 35 years and every 5 years thereafter, with closer attentionto patients who are at high risk (eg, pregnant women, women>60 y, patients with type 1 diabetes or other autoimmunedisease, patients with history of neck irradiation).• The American College of Physicians recommends screening allwomen older than 50 years who have one or more clinicalfeatures of disease.• The American Association of Clinical Endocrinologistsrecommends TSH measurements of all women of childbearingage before pregnancy or during the first trimester.• The US Preventive Task Force concludes that the evidence isinsufficient to recommend for or against routine screening forthyroid disease in adults (Grade I recommendation).

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