Should We TreatShould We TreatSubclinical Subclinical

Hypothyroidism?Hypothyroidism?

CQCCQC

Alap ShahAlap Shah

Med/Peds PGY-1Med/Peds PGY-1

History / PhysicalHistory / Physical

41 y/o Male with PMHx DM II, HTN, ED presents 41 y/o Male with PMHx DM II, HTN, ED presents for f/ufor f/u Has continued problems with glycemic control with Has continued problems with glycemic control with

sugars 140-160s, problems with ED despite medssugars 140-160s, problems with ED despite meds Had lost 10-15 lbs in 3 months – diet, exercise, but Had lost 10-15 lbs in 3 months – diet, exercise, but

still felt it was “difficult to lose weight”still felt it was “difficult to lose weight”

FHx: “two sisters, one hypothyroid, one FHx: “two sisters, one hypothyroid, one hyperthyroid”hyperthyroid”Meds: Glipizide, Sildenafil, MetforminMeds: Glipizide, Sildenafil, MetforminPE: normal – no edema, no PE: normal – no edema, no thyromegaly/nodularity, no arrhythmia, no thyromegaly/nodularity, no arrhythmia, no obesityobesity

LabsLabs

A1c – 14.5 (11/4/07), 9.6 (8/7/08)A1c – 14.5 (11/4/07), 9.6 (8/7/08)

TSH – 10.29 (8/7/08) (nml 0.4 - 4.4)TSH – 10.29 (8/7/08) (nml 0.4 - 4.4)

Anti TPO Ab – 1673.7 (nml < 9)Anti TPO Ab – 1673.7 (nml < 9)

Free T4 – 1.1 (nml 0.8 – 1.7)Free T4 – 1.1 (nml 0.8 – 1.7)

Testosterone – normalTestosterone – normal

Lipids – Low HDL, High LDL, Normal TGLipids – Low HDL, High LDL, Normal TG

Next StepNext Step

Would you…Would you… A. Start Levothyroxine therapyA. Start Levothyroxine therapy B. Monitor with TSH every 6 – 12 monthsB. Monitor with TSH every 6 – 12 months C. Follow clinicallyC. Follow clinically D. Order additional testsD. Order additional tests

Subclinical HypothyroidismSubclinical Hypothyroidism

State in which TSH is mildly elevated, indicating State in which TSH is mildly elevated, indicating mild thyroid failure, but normal serum levels of mild thyroid failure, but normal serum levels of T3 and T4T3 and T4Most commonly caused by autoimmune Most commonly caused by autoimmune thyroiditis, as in this patientthyroiditis, as in this patientBy most studies, ~ 4 – 18% of patients with SH By most studies, ~ 4 – 18% of patients with SH per year develop overt hypothyroidismper year develop overt hypothyroidism Increased likelihood if Ab+, TSH>20, Hx radiation, Increased likelihood if Ab+, TSH>20, Hx radiation,

chronic Li therapychronic Li therapy

Small amount of patients (not quantified) do Small amount of patients (not quantified) do recover normal thyroid functionrecover normal thyroid function

Etiologies of (Non-Central) Etiologies of (Non-Central) HypothyroidismHypothyroidism

Chronic Autoimmune ThyroiditisChronic Autoimmune ThyroiditisSubacute Postpartum ThyroiditisSubacute Postpartum ThyroiditisIodine Deficiency, ExcessIodine Deficiency, ExcessThyroid surgery, I-131 exposureThyroid surgery, I-131 exposureExternal IrradiationExternal IrradiationInfiltrative DisordersInfiltrative Disorders Sarcoid, Hemochromatosis, Leukemia, Lymphoma, Sarcoid, Hemochromatosis, Leukemia, Lymphoma,

Amyloid, TB, P jiroveciAmyloid, TB, P jiroveci

DrugsDrugs Lithium, Amiodarone, IFN-alpha, IL-2Lithium, Amiodarone, IFN-alpha, IL-2

When to Suspect SHWhen to Suspect SH

SymptomsSymptoms May be asymptomaticMay be asymptomatic Can have vague complaints including fatigue, Can have vague complaints including fatigue,

depression, weakness, sleep disturbance, memory depression, weakness, sleep disturbance, memory problems, constipation, menstrual irregularitiesproblems, constipation, menstrual irregularities

SignsSigns May have no physical abnormalitiesMay have no physical abnormalities Skin/hair changes, reflex delay, ataxia, Skin/hair changes, reflex delay, ataxia,

hyperlipidemia, nonpitting edema, hoarseness, hyperlipidemia, nonpitting edema, hoarseness, bradycardia, hypothermiabradycardia, hypothermia

Initial Lab EvaluationInitial Lab Evaluation

What labs to order for workup and What labs to order for workup and followup for subclinical hypothyroidism?followup for subclinical hypothyroidism? TSH if any of the previously mentioned TSH if any of the previously mentioned

symptoms, or high suspicion with strong symptoms, or high suspicion with strong family historyfamily history

TSH is 98% sensitive and 92% specific for thyroid TSH is 98% sensitive and 92% specific for thyroid diseasediseaseTSH is the definitive screening and monitoring lab TSH is the definitive screening and monitoring lab for (non-central) thyroid diseasefor (non-central) thyroid disease

If abnormal, repeat in 1 month and check Free If abnormal, repeat in 1 month and check Free T4T4

Initial Lab EvaluationInitial Lab Evaluation

Annals of Clinical Biochem (2006)Annals of Clinical Biochem (2006) Indications for Anti TPO Ab:Indications for Anti TPO Ab:

Patients with subclinical hypothyroidismPatients with subclinical hypothyroidism TSH from 4 - 10, normal Free T4TSH from 4 - 10, normal Free T4

Goiter, regardless of TSH or Free T4Goiter, regardless of TSH or Free T4

New onset thyrotoxicosisNew onset thyrotoxicosis No indication to follow Ab once positiveNo indication to follow Ab once positive

TreatmentTreatment

Recommendations vary:Recommendations vary: USPSTF (2004)USPSTF (2004) Consensus Conference Panel on Subclinical Consensus Conference Panel on Subclinical

Thyroid Disease (2004)Thyroid Disease (2004) Endocrinology Clinics (2004)Endocrinology Clinics (2004) American Association of Clinical American Association of Clinical

Endocrinologists Thyroid Task ForceEndocrinologists Thyroid Task Force Various other groups, studiesVarious other groups, studies

TreatmentTreatment

USPSTF (2004)USPSTF (2004) Treatment for subclinical hypothyroidism Treatment for subclinical hypothyroidism

reduces symptoms of patients with history of reduces symptoms of patients with history of Graves’ and TSH > 10Graves’ and TSH > 10

Insufficient evidence for recommendations Insufficient evidence for recommendations from other trialsfrom other trials

Most trials found there was no effect on lipid Most trials found there was no effect on lipid levelslevels

TreatmentTreatment

Consensus Conference Panel on Consensus Conference Panel on Subclinical Thyroid Disease (2004)Subclinical Thyroid Disease (2004) For TSH between 4.5 and 10, no treatmentFor TSH between 4.5 and 10, no treatment

Repeat TSH at 6 – 12 month intervals for changeRepeat TSH at 6 – 12 month intervals for change

For TSH > 10, evidence inconclusive – agreement For TSH > 10, evidence inconclusive – agreement with USPSTFwith USPSTF

TreatmentTreatment

Endocrinology Clinics (2004)Endocrinology Clinics (2004) Good evidence that treatment prevents overt Good evidence that treatment prevents overt

hypothyroidism, but no convincing evidence hypothyroidism, but no convincing evidence that early treatment beneficialthat early treatment beneficial

Improvement in lipid panel, but no hard Improvement in lipid panel, but no hard studies on mortality benefitsstudies on mortality benefits

TreatmentTreatment

National Guideline Clearinghouse (JAMA National Guideline Clearinghouse (JAMA 2004)2004) For TSH between 4.5 and 10, no treatmentFor TSH between 4.5 and 10, no treatment

Follow up with TSH every 6 – 12 monthsFollow up with TSH every 6 – 12 months

Based on no clear cut benefit to these patientsBased on no clear cut benefit to these patients

However, report stated that treatment may prevent However, report stated that treatment may prevent signs and symptoms in those that do progresssigns and symptoms in those that do progress

Treatment ... And FollowupTreatment ... And Followup

AACE Thyroid Task Force (2006) – AACE Thyroid Task Force (2006) – Treatment GuidelinesTreatment Guidelines Start at 25 – 50 micrograms / dayStart at 25 – 50 micrograms / day Repeat TSH 6 – 8 weeks after starting Repeat TSH 6 – 8 weeks after starting

treatmenttreatment Titrate dose to keep TSH between 0.3 – 3Titrate dose to keep TSH between 0.3 – 3 Once TSH stable, check levels and examine Once TSH stable, check levels and examine

patient annuallypatient annually

Next StepNext Step

Would you…Would you… A. Start Levothyroxine at 25-50 mcg/dayA. Start Levothyroxine at 25-50 mcg/day B. Monitor with TSH every 6 – 12 monthsB. Monitor with TSH every 6 – 12 months C. Follow clinicallyC. Follow clinically D. Order additional testsD. Order additional tests

No definitive answer. Most importantly, No definitive answer. Most importantly, remember to treat patient and not just the lab remember to treat patient and not just the lab values.values.

When to Consult EndocrinologyWhen to Consult Endocrinology

AACE recommends endocrine consult if:AACE recommends endocrine consult if: < 18 yrs< 18 yrs Unresponsive to therapyUnresponsive to therapy PregnantPregnant Cardiac historyCardiac history Presence of goiter or nodulesPresence of goiter or nodules Concurrent endocrine diseaseConcurrent endocrine disease

PatientPatient

Due to initial SH, started Synthroid 25mcg Due to initial SH, started Synthroid 25mcg daily x 2 wks, then 50mcg daily until follow daily x 2 wks, then 50mcg daily until follow upup

After TPO was +, called and instructed to After TPO was +, called and instructed to continue regimencontinue regimen

Follow up scheduled, pending…Follow up scheduled, pending…

ReferencesReferences

Devdhar et al.Devdhar et al. Hypothyroidism. Hypothyroidism. Endocrinol Endocrinol Metab Clin N Am. Metab Clin N Am. 2007; 36:595-615.2007; 36:595-615.AACE Thyroid Task Force.AACE Thyroid Task Force. Medical Guidelines Medical Guidelines For Clinical Practice For The Evaluation And For Clinical Practice For The Evaluation And Treatment Of Hyperthyroidism And Treatment Of Hyperthyroidism And Hypothyroidism. Hypothyroidism. Endocrine Practice. Endocrine Practice. 2006; 8:6.2006; 8:6.Herrick.Herrick. Subclinical Hypothyroidism. Subclinical Hypothyroidism. American American Family Physician. Family Physician. 2008; 77:7.2008; 77:7.Surks et al. Surks et al. Subclinical thyroid disease: Subclinical thyroid disease: scientific review and guidelines for diagnosis and scientific review and guidelines for diagnosis and management. management. JAMA.JAMA. 2004; 291(2). 2004; 291(2).

ReferencesReferences

Miller and Rogers. Miller and Rogers. Which Lab Tests Are Best When Which Lab Tests Are Best When You Suspect Hypothyroidism? You Suspect Hypothyroidism? Clinical Inquiries, Family Clinical Inquiries, Family Physicians Inquiries Network. Physicians Inquiries Network. 2008; 57:9.2008; 57:9.Downs and Meyer. Downs and Meyer. How Useful Are Autoantibodies How Useful Are Autoantibodies When Diagnosing Thyroid Disorders? When Diagnosing Thyroid Disorders? Clinical Inquiries, Clinical Inquiries, Family Physicians Inquiries Network. Family Physicians Inquiries Network. 2008; 57:9.2008; 57:9.Sinclair. Sinclair. Clinical And Laboratory Aspects Of Thyroid Clinical And Laboratory Aspects Of Thyroid Antibodies. Antibodies. Ann Clin Biochem.Ann Clin Biochem. 2006; 43: 173-183. 2006; 43: 173-183.USPSTF. USPSTF. Screening For Thyroid Disease: Systematic Screening For Thyroid Disease: Systematic Evidence Review. 2004.Evidence Review. 2004.