Thyroid Lecture 2007 USAFP.ppt

Evaluation and Management of Evaluation and Management of Hypothyroidism in the Primary Hypothyroidism in the Primary

Care SettingCare Setting

Christopher P. Paulson, Maj, USAF, MCChristopher P. Paulson, Maj, USAF, MC

Faculty, Eglin AFB Family Medicine ResidencyFaculty, Eglin AFB Family Medicine Residency

Case Scenario Case Scenario

While precepting residents the following case is While precepting residents the following case is presented for your reviewpresented for your review

45 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 several months duration


Past 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 surgery

Medications: noneMedications: none

Family Hx: negative for autoimmune disorders Family Hx: negative for autoimmune disorders and thyroid dysfunctionand thyroid dysfunction


Labs:Labs:– TSH TSH 6.736.73 (0.46 - 4.68) mIU/ml (0.46 - 4.68) mIU/ml– FT4 1.32 (0.71 – 2.19) ng/dlFT4 1.32 (0.71 – 2.19) ng/dl

Repeat labs in 6 weeksRepeat labs in 6 weeks– TSH TSH 6.826.82– FT4 1.27FT4 1.27


The patient desires thyroid replacement therapyThe patient desires thyroid replacement therapy

The resident inquires about treatment guidelines The resident inquires about treatment guidelines for subclinical hypothyroidismfor subclinical hypothyroidism

How do you respond?How do you respond?

Learning ObjectivesLearning Objectives

Identify common risk factors and etiologies of Identify common risk factors and etiologies of hypothyroidismhypothyroidism

Be able to evaluate and initiate appropriate Be able to evaluate and initiate appropriate treatment for hypothyroidismtreatment for hypothyroidism

Use an evidence-based approach for population Use an evidence-based approach for population screening and sub-clinical disease managementscreening and sub-clinical disease management

Apply management guidelines to your patient Apply management guidelines to your patient populationpopulation

Overview of HypothyroidismOverview of Hypothyroidism

EpidemiologyEpidemiology

EtiologyEtiology

Evaluation and TreatmentEvaluation and Treatment

Subclinical Disease and Screening GuidelinesSubclinical Disease and Screening Guidelines

Conclusion/Key PointsConclusion/Key Points

Epidemiology Epidemiology

Incidence of HypothyroidismIncidence of Hypothyroidism

– 1% in areas with adequate iodine (U.S.)1% in areas with adequate iodine (U.S.)

– Female to Male ratio 8:1Female to Male ratio 8:1

– Incidence increases with ageIncidence increases with age

Vanderpump, MP, Tunbridge, WM. The epidemiology of thyroid disease. In: The Thyroid: A Fundamental and Clinical Text, 8th ed, Braverman, LE, Utiger, RD (eds). Lippincott Williams and Wilkins, Philadelphia, 2000. p. 467.


Risk FactorsRisk Factors

– Downs SyndromeDowns Syndrome

– Turners SyndromeTurners Syndrome

– Head and neck Head and neck radiation exposureradiation exposure

– Type 1 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 Family history of thyroid disordersthyroid disorders

Larsen PR, Kronenberg HM, Melmed S, Polonsky KS, editors. Williams textbook of endocrinology. 10th edition. Philadelphia: Saunders, 2003; 423-55.


SymptomsSymptoms

– FatigueFatigue

– Weight gainWeight gain

– HeadacheHeadache

– Dry SkinDry Skin

– Hoarseness of voiceHoarseness of voice

– Irregular mensesIrregular menses

– Decreased appetiteDecreased appetite

– MyalgiasMyalgias

– ParasthesiasParasthesias

– SomnolenceSomnolence

– LethargyLethargy

– DepressionDepression

– Cold intoleranceCold intolerance



SymptomsSymptoms

– Fatigue – 90%Fatigue – 90%

– Weight gainWeight gain

– HeadacheHeadache

– Dry SkinDry Skin

– Hoarseness of voiceHoarseness of voice

– Irregular mensesIrregular menses

– Decreased appetiteDecreased appetite

– MyalgiasMyalgias

– ParasthesiasParasthesias

– SomnolenceSomnolence

– LethargyLethargy

– Depression Depression

– Cold intoleranceCold intolerance



SignsSigns– Nonpitting edemaNonpitting edema

– ConstipationConstipation

– Memory defectsMemory defects

– Coarse skinCoarse skin

– Dry skinDry skin

– Brittle nailsBrittle nails

– BradycardiaBradycardia

– AtaxiaAtaxia

– Diminished libidoDiminished libido

– Bleeding tendenciesBleeding tendencies

– AlopeciaAlopecia

– MacroglossiaMacroglossia

– Slowed speechSlowed speech

– DementiaDementia

– PsychosisPsychosis

– Slowed reflexesSlowed reflexes


EtiologyEtiology

Primary hypothyroidism Primary hypothyroidism (95 – 99%)(95 – 99%)– Chronic autoimmune thyroiditisChronic autoimmune thyroiditis

(Hashimoto’s)(Hashimoto’s) GoitrousGoitrous AtrophicAtrophic

– IatrogenicIatrogenic ThyroidectomyThyroidectomy Radioiodine treatmentRadioiodine treatment External beam radiationExternal beam radiation

Farwell, AP, Ebner, SA, editors. Hypothyroidism. In: Noble: Textbook of Primary Care Medicine, 3 rd ed, Mosby 2001.

EtiologyEtiology

Primary hypothyroidism Primary hypothyroidism – Iodine deficiencyIodine deficiency (most common world-wide) (most common world-wide)– DrugsDrugs

Lithium, amiodarone, etcLithium, amiodarone, etc

– Infiltrative disease - rareInfiltrative disease - rare Fibrous thyroiditis (Reidel’s thyroiditis)Fibrous thyroiditis (Reidel’s thyroiditis) HemochromatosisHemochromatosis SclerodermaScleroderma OthersOthers


EtiologyEtiology

Primary hypothyroidism Primary hypothyroidism

– CongenitalCongenital

– Transient HypothyroidismTransient Hypothyroidism PostpartumPostpartum Subacute (granulomatous) thyroiditisSubacute (granulomatous) thyroiditis Subtotal thyroidectomySubtotal thyroidectomy


EtiologyEtiology

Secondary and Tertiary hypothyroidism Secondary and Tertiary hypothyroidism – TumorTumor– Postpartum pituitary necrosis (Sheehan’s)Postpartum pituitary necrosis (Sheehan’s)– HypophysitisHypophysitis– Infiltrating diseaseInfiltrating disease– TSH or TRH deficiencyTSH or TRH deficiency– TraumaTrauma– Radiation therapy Radiation therapy


EtiologyEtiology

OtherOther

– Thyroid hormone resistance – very rareThyroid hormone resistance – very rare


EvaluationEvaluation

When to evaluateWhen to evaluate– Signs or symptoms suggestive of Signs or symptoms suggestive of

hypothyroidismhypothyroidism– Periodic assessment for high risk medications Periodic assessment for high risk medications

(amiodarone, lithium, etc.)(amiodarone, lithium, etc.)

– Screening at risk populations?Screening at risk populations? Controversial – addressed in screening sectionControversial – addressed in screening section


Assess risk factors for hypothyroidismAssess risk factors for hypothyroidism

– Medications (lithium, amiodarone, etc)Medications (lithium, amiodarone, etc)– History of head or neck radiation exposureHistory of head or neck radiation exposure– Presence of Downs or TurnersPresence of Downs or Turners– Family or personal history of autoimmune or Family or personal history of autoimmune or

thyroid disordersthyroid disorders– Type 1 diabetesType 1 diabetes


TSH FT4

Primary Hypothyroidism

Subclinical Hypothyroidism

Secondary or Tertiary Hypothyroidism

Thyroid Hormone Resistance

(pt is clinically hypothyroid)

Basic Thyroid Labs


Primary hypothyroidismPrimary hypothyroidism– Proceed to treatmentProceed to treatment– Further evaluation generally not indicatedFurther evaluation generally not indicated

– For postpartum hypothyroidism, serial TSH For postpartum hypothyroidism, serial TSH and FT4, treat only if significantly and FT4, treat only if significantly symptomaticsymptomatic


Secondary or tertiary hypothyroidismSecondary or tertiary hypothyroidism

– Image the sellar and suprasellar regions with Image the sellar and suprasellar regions with MRI to evaluate for massMRI to evaluate for mass

– Screen for other hypothalamic or pituitary Screen for other hypothalamic or pituitary diseasedisease

Adrenocortical, posterior pituitary, and gonadal Adrenocortical, posterior pituitary, and gonadal dysfunctiondysfunction

– Consider consultationConsider consultation


Thyroid hormone resistanceThyroid hormone resistance

– Exceedingly rareExceedingly rare– If suspected – consultation is appropriateIf suspected – consultation is appropriate

Subclinical hypothyroidismSubclinical hypothyroidism– Addressed in later sectionAddressed in later section

Treatment GuidelinesTreatment Guidelines

Standard Replacement TherapyStandard Replacement Therapy

– Synthetic thyroxine (T4) Synthetic thyroxine (T4) – 1.6 mcg/kg/day – lean body mass1.6 mcg/kg/day – lean body mass– 112 mcg in 70kg adult112 mcg in 70kg adult– Full dose recommended regardless of degree Full dose recommended regardless of degree

of hypothyroidismof hypothyroidism– Reassess after 6 weeks with TSHReassess after 6 weeks with TSH

Roos, 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.


Special situationsSpecial situations

– Elderly patientsElderly patients Start at 50 mcg/day and increase 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 normalized

– Known CADKnown CAD Start 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 weeks until TSH is normalized



Special situationsSpecial situations

– Postpartum hypothyroidismPostpartum hypothyroidism Treat based on moderate or severe clinical Treat based on moderate or severe clinical

symptoms not based on labssymptoms not based on labs Only 1 in 4 will require treatmentOnly 1 in 4 will require treatment 50 to 100 mcg per day x 12 weeks50 to 100 mcg per day x 12 weeks Discontinue and recheck thyroid labs 6 wks laterDiscontinue and recheck thyroid labs 6 wks later

Stuckey, BG, Kent, GN, Allen, JR. The biochemical and clinical course of postpartum thyroid dysfunction: the treatment decision. Clin Endocrinol (Oxf) 2001; 54:377.


What about liothyronine (T3) What about liothyronine (T3) replacement?replacement?

– Physiologically active Physiologically active – 20% from thyroid directly and 80% from 20% from thyroid directly and 80% from

peripheral conversion of T4peripheral conversion of T4– Early studies indicated possible beneficial Early studies indicated possible beneficial

effects on mood, quality of life, and effects on mood, quality of life, and psychometric functioningpsychometric functioning


Systematic review of the literature Systematic review of the literature published in 2005published in 2005– Levothyroxine (T4) compared with Levothyroxine (T4) compared with

levothyroxine + liothyronine (T3)levothyroxine + liothyronine (T3)– 9 controlled trials included 9 controlled trials included – Beneficial results in only a single studyBeneficial results in only a single study

Quality of life, mood, psychometric performanceQuality of life, mood, psychometric performance

Escobar-Morreale, HF. Treatment of Hypothyroidism with Combinations of Levothyroxine plus Liothyronine. Journal of Clinical Endocrinology and Metabolism. Vol 90, number 8. Aug 2005.


Systematic review of the literature Systematic review of the literature published in 2005published in 2005– Increased incidence of side effects with T3 Increased incidence of side effects with T3

including palpitations, irritability, including palpitations, irritability, nervousness, dizziness, and tremornervousness, dizziness, and tremor

– Overall patient preference for T3Overall patient preference for T3 Not explained by outcome measuresNot explained by outcome measures

– No clear clinical benefitNo clear clinical benefit

Escobar-Morreale, HF. Treatment of Hypothyroidism with Combinations of Levothyroxine plus Liothyronine. Journal of Clinical Endocrinology and Metabolism. Vol 90, number 8. Aug 2005.

Subclinical HypothyroidismSubclinical Hypothyroidism

Generally defined as few or no symptoms Generally defined as few or no symptoms of hypothyroidism with an elevated TSH of hypothyroidism with an elevated TSH and normal FT4and normal FT4

– Historically unclear recommendations in the Historically unclear recommendations in the literatureliterature


Possible benefits of treatmentPossible benefits of treatment

– Symptom improvementSymptom improvement– Prevent progression to overt hypothyroidismPrevent progression to overt hypothyroidism– Reduce lipid levels and subsequently lower Reduce lipid levels and subsequently 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 diseasedisease


Possible risk of unnecessary treatmentPossible risk of unnecessary treatment

– Development of osteoporosisDevelopment of osteoporosis

– Increased incidence of atrial fibrillationIncreased incidence of atrial fibrillation

– Cost Cost


What does the literature show?What does the literature show?– USPSTF review in 2004USPSTF review in 2004

No clear difference in 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 disease

No significant symptom improvement with No significant symptom improvement with treatmenttreatment

– Except for patients with known thyroid diseaseExcept for patients with known thyroid disease

www.ahrq.gov/clinic/uspstf/uspsthyr.htm



Poor neurodevelopmental outcomes in children Poor neurodevelopmental 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 was 7 points less (significant)– No studies on whether screening or treatment would No studies on whether screening or treatment would

impact outcomeimpact outcome




No increased risk of fracture 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 therapy

No increased risk of atrial fibrillation with No increased risk of atrial fibrillation with treatmenttreatment



What does the literature show?What does the literature show?– Other considerationsOther considerations

Annual rate of progression to overt diseaseAnnual rate of progression to overt disease

– No autoimmunity <2%No autoimmunity <2%– No prior thyroid disease - < 2%No prior thyroid disease - < 2%

– Thyroid antibodies – 5-7%Thyroid antibodies – 5-7%– Elderly with thyroid antibodies – 20-24%Elderly with thyroid antibodies – 20-24%


Case Scenario - revisitedCase Scenario - revisited

Initial labs:Initial labs:– TSH TSH 6.736.73 – FT4 1.32FT4 1.32

Repeat labs in 6 weeksRepeat labs in 6 weeks– TSH TSH 6.826.82– FT4 1.27FT4 1.27

Case Scenario - revisited Case Scenario - revisited

The patient desires thyroid replacement therapyThe patient desires thyroid replacement therapy

The resident inquires about treatment guidelines The resident inquires about treatment guidelines for subclinical hypothyroidismfor subclinical hypothyroidism

Now, how do you respond? Now, how do you respond? What is the What is the evidence based answer?evidence based answer?

Case Scenario - revisited Case Scenario - revisited

The evidence-based answerThe evidence-based answer

– There is no clear indication to treatThere is no clear indication to treat

– Likelihood of progressing on to overt Likelihood of progressing on to overt hypothyroidism in this case is very lowhypothyroidism in this case is very low

Screening GuidelinesScreening Guidelines

The American Thyroid AssociationThe American Thyroid Association– Screen Screen ALLALL adults at age 35 and then every 5 adults at age 35 and then every 5

years; more frequent for high risk or years; more frequent for high risk or symptomssymptoms

The American College of PhysiciansThe American College of Physicians– Screen women older than 50 with at least one Screen women older than 50 with at least one

symptomsymptom



The American Association of Clinical The American Association of Clinical EndocrinologistsEndocrinologists

– Screen women of childbearing age or during Screen women of childbearing age or during the first trimesterthe first trimester



The American College of Obstetricians and The American College of Obstetricians and GynecologistsGynecologists

– Be aware if signs and symptoms of Be aware if signs and symptoms of postpartum thyroid dysfunction and evaluate postpartum thyroid dysfunction and evaluate when indicatedwhen indicated



AAFPAAFP

– Recommends Recommends AGAINSTAGAINST routine screening in routine screening in asymptomatic patients younger than age 60asymptomatic patients younger than age 60

No recommendation for those over 60No recommendation for those over 60



USPSTFUSPSTF– Evidence is insufficient (I) to recommend for Evidence is insufficient (I) to recommend for

or against routine screening for thyroid or against routine screening for thyroid disease in adultsdisease in adults

Fair evidence that TSH is useful in detecting Fair evidence that TSH is useful in detecting subclinical diseasesubclinical disease

Poor evidence that treatment improves clinically Poor evidence that treatment improves clinically important outcomesimportant outcomes



USPSTF – Clinical ConsiderationsUSPSTF – Clinical Considerations

– Clinicians should be aware of subtle thyroid Clinicians should be aware of subtle thyroid dysfunction particularly in high risk groupsdysfunction particularly in high risk groups

ElderlyElderly Down SyndromeDown Syndrome Post-partum womenPost-partum women Radiation exposure (>20 mGy)Radiation exposure (>20 mGy)



USPSTF – Clinical ConsiderationsUSPSTF – Clinical Considerations

– Subclinical hypothyroidismSubclinical hypothyroidism Is associated with poor obstetric outcomes and Is associated with poor obstetric outcomes and

poor cognitive development in childrenpoor cognitive development in children Evidence for dyslipidemia, atherosclerosis, and Evidence for dyslipidemia, atherosclerosis, and

decreased quality of life is inconsistent and less decreased quality of life is inconsistent and less convincingconvincing



USPSTF – DiscussionUSPSTF – Discussion

– No controlled studies showing whether routine No controlled studies showing whether routine screening improved symptoms or health outcomesscreening improved symptoms or health outcomes

– 2 of 3 small randomized studies demonstrated no 2 of 3 small randomized studies demonstrated no benefit in treating subclinical diseasebenefit in treating subclinical disease

– No trials of treatment of subclinical disease for No trials of treatment of subclinical disease for pregnant womenpregnant women



USPSTF – DiscussionUSPSTF – Discussion

– No clear benefit demonstrated on systematic No clear benefit demonstrated on systematic review of the literature for either screening review of the literature for either screening asymptomatic adults or treating subclinical asymptomatic adults or treating subclinical thyroid diseasethyroid disease



Hypothyroidism is commonly encountered in the Hypothyroidism is commonly encountered in the primary care settingprimary care setting

Be aware of signs and symptoms of Be aware of signs and symptoms of hypothyroidism particularly in populations at riskhypothyroidism particularly in populations at risk

There is insufficient evidence to recommend There is insufficient evidence to recommend treatment with liothyronine (T3) over treatment with liothyronine (T3) over levothyroxine (T4)levothyroxine (T4)


There is insufficient evidence for screening There is insufficient evidence for screening asymptomatic patients without a history of asymptomatic patients without a history of thyroid diseasethyroid disease

There is no clear benefit in treating subclinical There is no clear benefit in treating subclinical hypothyroidismhypothyroidism– Treatment is indicated in pregnancy due to Treatment is indicated in pregnancy due to

known risk without treatmentknown risk without treatment

Thyroid Lecture 2007 USAFP.ppt

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Transcript of Thyroid Lecture 2007 USAFP.ppt