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1、Evaluation and Management of Hypothyroidism in the Primary Care SettingChristopher P.Paulson,Maj,USAF,MCChristopher P.Paulson,Maj,USAF,MCFaculty,Eglin AFB Family Medicine ResidencyFaculty,Eglin AFB Family Medicine Residency 1 1Case Scenario n nWhile precepting residents the following case is While p
2、recepting residents the following case is presented for your reviewpresented for your reviewn n45 yo female with abnormal thyroid labs 45 yo female with abnormal thyroid labs discovered during an evaluation of mild fatigue discovered during an evaluation of mild fatigue of several months durationof
3、several months duration2 2Case Scenario n nPast Med Hx:negative for diabetes,autoimmune Past Med Hx:negative for diabetes,autoimmune disorders,radiation exposure,and known thyroid disorders,radiation exposure,and known thyroid disease or thyroid surgerydisease or thyroid surgeryn nMedications:noneMe
4、dications:nonen nFamily Hx:negative for autoimmune disorders Family Hx:negative for autoimmune disorders and thyroid dysfunctionand thyroid dysfunction3 3Case Scenario n nLabs:Labs:TSH (0.46-4.68)mIU/mlTSH (0.46-4.68)mIU/mlFT4 1.32 (0.71 2.19)ng/dlFT4 1.32 (0.71 2.19)ng/dln nRepeat labs in 6 weeksRe
5、peat labs in 6 weeksTSH TSH 4 4Case Scenario n nThe patient desires thyroid replacement therapyThe patient desires thyroid replacement therapyn nThe resident inquires about treatment guidelines The resident inquires about treatment guidelines for subclinical hypothyroidismfor subclinical hypothyroid
6、ismn nHow do you respond?How do you respond?5 5Learning Objectivesn nIdentify common risk factors and etiologies of Identify common risk factors and etiologies of hypothyroidismhypothyroidismn nBe able to evaluate and initiate appropriate Be able to evaluate and initiate appropriate treatment for hy
7、pothyroidismtreatment for hypothyroidismn nUse an evidence-based approach for population Use an evidence-based approach for population screening and sub-clinical disease managementscreening and sub-clinical disease managementn nApply management guidelines to your patient Apply management guidelines
8、to your patient populationpopulation6 6Overview of Hypothyroidismn nEpidemiologyEpidemiologyn nEtiologyEtiologyn nEvaluation and TreatmentEvaluation and Treatmentn nSubclinical Disease and Screening GuidelinesSubclinical Disease and Screening Guidelinesn nConclusion/Key PointsConclusion/Key Points7
9、7Epidemiology n nIncidence of Hypothyroidism1%in areas with adequate iodine(U.S.)1%in areas with adequate iodine(U.S.)Female to Male ratio 8:1Female to Male ratio 8:1Incidence increases with ageIncidence increases with ageVanderpump,MP,Tunbridge,WM.The epidemiology of thyroid disease.In:The Thyroid:
10、A Fundamental and Clinical Text,8th ed,Braverman,LE,Utiger,RD(eds).Lippincott Williams and Wilkins,Philadelphia,2000.p.467.8 8Epidemiology n nRisk FactorsRisk Factors Downs SyndromeDowns Syndrome Turners SyndromeTurners Syndrome Head and neck Head and neck radiation exposureradiation exposure Type 1
11、 DiabetesType 1 Diabetes Family history of Family history of autoimmune diseaseautoimmune disease History of previous History of previous thyroid disorderthyroid disorder Presence of other Presence of other autoimmune disordersautoimmune disorders Postpartum statePostpartum state Family history of F
12、amily history of thyroid disordersthyroid disordersLarsen PR,Kronenberg HM,Melmed S,Polonsky KS,editors.Williams textbook of endocrinology.10th edition.Philadelphia:Saunders,2003;423-55.9 9Epidemiology n nSymptomsSymptoms FatigueFatigue Weight gainWeight gain HeadacheHeadache Dry SkinDry Skin Hoarse
13、ness of voiceHoarseness of voice Irregular mensesIrregular menses Decreased appetiteDecreased appetite MyalgiasMyalgias ParasthesiasParasthesias SomnolenceSomnolence LethargyLethargy DepressionDepression Cold intoleranceCold intoleranceLarsen PR,Kronenberg HM,Melmed S,Polonsky KS,editors.Williams te
14、xtbook of endocrinology.10th edition.Philadelphia:Saunders,2003;423-55.1010Epidemiology n nSymptomsSymptoms Fatigue 90%Fatigue 90%Weight gainWeight gain HeadacheHeadache Dry SkinDry Skin Hoarseness of voiceHoarseness of voice Irregular mensesIrregular menses Decreased appetiteDecreased appetite Myal
15、giasMyalgias ParasthesiasParasthesias SomnolenceSomnolence LethargyLethargy Depression Depression Cold intoleranceCold intoleranceLarsen PR,Kronenberg HM,Melmed S,Polonsky KS,editors.Williams textbook of endocrinology.10th edition.Philadelphia:Saunders,2003;423-55.1111Epidemiology n nSignsSigns Nonp
16、itting edemaNonpitting edema ConstipationConstipation Memory defectsMemory defects Coarse skinCoarse skin Dry skinDry skin Brittle nailsBrittle nails BradycardiaBradycardia AtaxiaAtaxia Diminished libidoDiminished libido Bleeding tendenciesBleeding tendencies AlopeciaAlopecia MacroglossiaMacroglossi
17、a Slowed speechSlowed speech DementiaDementia PsychosisPsychosis Slowed reflexesSlowed reflexesLarsen PR,Kronenberg HM,Melmed S,Polonsky KS,editors.Williams textbook of endocrinology.10th edition.Philadelphia:Saunders,2003;423-55.1212Etiologyn nPrimary hypothyroidism(95 99%)Chronic autoimmune thyroi
18、ditisChronic autoimmune thyroiditis (Hashimotos)(Hashimotos)n nGoitrousGoitrousn nAtrophicAtrophicIatrogenicIatrogenicn nThyroidectomyThyroidectomyn nRadioiodine treatmentRadioiodine treatmentn nExternal beam radiationExternal beam radiationFarwell,AP,Ebner,SA,editors.Hypothyroidism.In:Noble:Textboo
19、k of Primary Care Medicine,3rd ed,Mosby 2001.1313Etiologyn nPrimary hypothyroidism Iodine deficiencyIodine deficiency(most common world-wide)(most common world-wide)DrugsDrugsn nLithium,amiodarone,etcLithium,amiodarone,etcInfiltrative disease-rareInfiltrative disease-raren nFibrous thyroiditis(Reide
20、ls thyroiditis)Fibrous thyroiditis(Reidels thyroiditis)n nHemochromatosisHemochromatosisn nSclerodermaScleroderman nOthersOthersFarwell,AP,Ebner,SA,editors.Hypothyroidism.In:Noble:Textbook of Primary Care Medicine,3rd ed,Mosby 2001.1414Etiologyn nPrimary hypothyroidism CongenitalCongenitalTransient
21、HypothyroidismTransient Hypothyroidismn nPostpartumPostpartumn nSubacute(granulomatous)thyroiditisSubacute(granulomatous)thyroiditisn nSubtotal thyroidectomySubtotal thyroidectomyFarwell,AP,Ebner,SA,editors.Hypothyroidism.In:Noble:Textbook of Primary Care Medicine,3rd ed,Mosby 2001.1515Etiologyn nSe
22、condary and Tertiary hypothyroidism TumorTumorPostpartum pituitary necrosis(Sheehans)Postpartum pituitary necrosis(Sheehans)HypophysitisHypophysitisInfiltrating diseaseInfiltrating diseaseTSH or TRH deficiencyTSH or TRH deficiencyTraumaTraumaRadiation therapy Radiation therapy Farwell,AP,Ebner,SA,ed
23、itors.Hypothyroidism.In:Noble:Textbook of Primary Care Medicine,3rd ed,Mosby 2001.1616Etiologyn nOther Thyroid hormone resistance very rareThyroid hormone resistance very rareFarwell,AP,Ebner,SA,editors.Hypothyroidism.In:Noble:Textbook of Primary Care Medicine,3rd ed,Mosby 2001.1717Evaluationn nWhen
24、 to evaluateSigns or symptoms suggestive of Signs or symptoms suggestive of hypothyroidismhypothyroidismPeriodic assessment for high risk medications Periodic assessment for high risk medications(amiodarone,lithium,etc.)(amiodarone,lithium,etc.)Screening at risk populations?Screening at risk populat
25、ions?n nControversial addressed in screening sectionControversial addressed in screening section1818Evaluationn nAssess risk factors for hypothyroidismMedications(lithium,amiodarone,etc)Medications(lithium,amiodarone,etc)History of head or neck radiation exposureHistory of head or neck radiation exp
26、osurePresence of Downs or TurnersPresence of Downs or TurnersFamily or personal history of autoimmune or Family or personal history of autoimmune or thyroid disordersthyroid disordersType 1 diabetesType 1 diabetes1919EvaluationTSHFT4Primary HypothyroidismSubclinical HypothyroidismSecondary or Tertia
27、ry HypothyroidismThyroid Hormone Resistance(pt is clinically hypothyroid)Basic Thyroid Labs2020Evaluationn nPrimary hypothyroidismProceed to treatmentProceed to treatmentFurther evaluation generally not indicatedFurther evaluation generally not indicatedFor postpartum hypothyroidism,serial TSH For p
28、ostpartum hypothyroidism,serial TSH and FT4,treat only if significantly and FT4,treat only if significantly symptomaticsymptomatic2121Evaluationn nSecondary or tertiary hypothyroidismImage the sellar and suprasellar regions with Image the sellar and suprasellar regions with MRI to evaluate for massM
29、RI to evaluate for massScreen for other hypothalamic or pituitary Screen for other hypothalamic or pituitary diseasediseasen nAdrenocortical,posterior pituitary,and gonadal Adrenocortical,posterior pituitary,and gonadal dysfunctiondysfunctionConsider consultationConsider consultation2222Evaluationn
30、nThyroid hormone resistanceExceedingly rareExceedingly rareIf suspected consultation is appropriateIf suspected consultation is appropriaten nSubclinical hypothyroidismAddressed in later sectionAddressed in later section2323Treatment Guidelinesn nStandard Replacement TherapySynthetic thyroxine(T4)Sy
31、nthetic thyroxine(T4)1.6 mcg/kg/day lean body mass1.6 mcg/kg/day lean body mass112 mcg in 70kg adult112 mcg in 70kg adultFull dose recommended regardless of degree Full dose recommended regardless of degree of hypothyroidismof hypothyroidismReassess after 6 weeks with TSHReassess after 6 weeks with
32、TSHRoos,A,Linn-Rasker,SP,van Domburg,RT,et al.The starting dose of levothyroxine in primary hypothyroidism treatment:a prospective,randomized,double-blind trial.Arch Intern Med 2005;165:1714.2424Treatment Guidelinesn nSpecial situationsElderly patientsElderly patientsn nStart at 50 mcg/day and incre
33、ase by 25 mcg/day Start at 50 mcg/day and increase by 25 mcg/day every 6 weeks until TSH is normalizedevery 6 weeks until TSH is normalizedKnown CADKnown CADn nStart at 25 mcg/day and increase by 25 mcg/day Start at 25 mcg/day and increase by 25 mcg/day every 6 weeks until TSH is normalizedevery 6 w
34、eeks until TSH is normalizedLarsen PR,Kronenberg HM,Melmed S,Polonsky KS,editors.Williams textbook of endocrinology.10th edition.Philadelphia:Saunders,2003;423-55.2525Treatment Guidelinesn nSpecial situationsPostpartum hypothyroidismPostpartum hypothyroidismn nTreat based on moderate or severe clini
35、cal Treat based on moderate or severe clinical symptoms not based on labssymptoms not based on labsn nOnly 1 in 4 will require treatmentOnly 1 in 4 will require treatmentn n50 to 100 mcg per day x 12 weeks50 to 100 mcg per day x 12 weeksn nDiscontinue and recheck thyroid labs 6 wks laterDiscontinue
36、and recheck thyroid labs 6 wks laterStuckey,BG,Kent,GN,Allen,JR.The biochemical and clinical course of postpartum thyroid dysfunction:the treatment decision.Clin Endocrinol(Oxf)2001;54:377.2626Treatment Guidelinesn nWhat about liothyronine(T3)replacement?Physiologically active Physiologically active
37、 20%from thyroid directly and 80%from 20%from thyroid directly and 80%from peripheral conversion of T4peripheral conversion of T4Early studies indicated possible beneficial Early studies indicated possible beneficial effects on mood,quality of life,and effects on mood,quality of life,and psychometri
38、c functioningpsychometric functioning2727Treatment Guidelinesn nSystematic review of the literature published in 2005Levothyroxine(T4)compared with Levothyroxine(T4)compared with levothyroxine+liothyronine(T3)levothyroxine+liothyronine(T3)9 controlled trials included 9 controlled trials included Ben
39、eficial results in only a single studyBeneficial results in only a single studyn nQuality of life,mood,psychometric performanceQuality of life,mood,psychometric performanceEscobar-Morreale,HF.Treatment of Hypothyroidism with Combinations of Levothyroxine plus Liothyronine.Journal of Clinical Endocri
40、nology and Metabolism.Vol 90,number 8.Aug 2005.2828Treatment Guidelinesn nSystematic review of the literature published in 2005Increased incidence of side effects with T3 Increased incidence of side effects with T3 including palpitations,irritability,including palpitations,irritability,nervousness,d
41、izziness,and tremornervousness,dizziness,and tremorOverall patient preference for T3Overall patient preference for T3n nNot explained by outcome measuresNot explained by outcome measuresNo clear clinical benefitNo clear clinical benefitEscobar-Morreale,HF.Treatment of Hypothyroidism with Combination
42、s of Levothyroxine plus Liothyronine.Journal of Clinical Endocrinology and Metabolism.Vol 90,number 8.Aug 2005.2929Subclinical Hypothyroidismn nGenerally defined as few or no symptoms of hypothyroidism with an elevated TSH and normal FT4Historically unclear recommendations in the Historically unclea
43、r recommendations in the literatureliterature3030Subclinical Hypothyroidismn nPossible benefits of treatmentSymptom improvementSymptom improvementPrevent progression to overt hypothyroidismPrevent progression to overt hypothyroidismReduce lipid levels and subsequently lower Reduce lipid levels and s
44、ubsequently lower risk of cardiovascular events risk of cardiovascular events Prevent poor developmental outcomes in Prevent poor developmental outcomes in children born to women with subclinical children born to women with subclinical diseasedisease3131Subclinical Hypothyroidismn nPossible risk of
45、unnecessary treatmentDevelopment of osteoporosisDevelopment of osteoporosisIncreased incidence of atrial fibrillationIncreased incidence of atrial fibrillationCost Cost 3232Subclinical Hypothyroidismn nWhat does the literature show?USPSTF review in 2004USPSTF review in 2004n nNo clear difference in
46、lipid levels or No clear difference in lipid levels or cardiovascular outcomes for subclinical diseasecardiovascular outcomes for subclinical disease Except for patients with known thyroid diseaseExcept for patients with known thyroid diseasen nNo significant symptom improvement with No significant
47、symptom improvement with treatmenttreatment Except for patients with known thyroid diseaseExcept for patients with known thyroid disease 3333Subclinical Hypothyroidismn nWhat does the literature show?USPSTF review in 2004USPSTF review in 2004n nPoor neurodevelopmental outcomes in children Poor neuro
48、developmental outcomes in children born to women with elevated TSH values in their born to women with elevated TSH values in their first trimesterfirst trimester Increase in fetal demise rateIncrease in fetal demise rate Average IQ at age 7 to 9 was 7 points less(significant)Average IQ at age 7 to 9
49、 was 7 points less(significant)No studies on whether screening or treatment would No studies on whether screening or treatment would impact outcomeimpact outcome 3434Subclinical Hypothyroidismn nWhat does the literature show?USPSTF review in 2004USPSTF review in 2004n nNo increased risk of fracture
50、or diminished bone No increased risk of fracture or diminished bone density with levothyroxine treatmentdensity with levothyroxine treatment Except in those patients on suppressive therapyExcept in those patients on suppressive therapyn nNo increased risk of atrial fibrillation with No increased ris