Thyroid disease in primary careThyroid disease in primary care

OutlineOutline

Thyroid anatomy and physiologyThyroid anatomy and physiologyHypothyroidismHypothyroidism

Etiologies and work upEtiologies and work upTreatmentTreatmentSubclinicalSubclinical hypothyroidismhypothyroidism

HyperthyroidismHyperthyroidismRole of the radioactive iodine uptake (RAIU)Role of the radioactive iodine uptake (RAIU)Etiologies and work upEtiologies and work upTreatment optionsTreatment optionsSubclinicalSubclinical hypothyroidismhypothyroidism

Thyroid noduleThyroid noduleWork upWork up

Thyroid glandThyroid gland

Thyroid hormone physiologyThyroid hormone physiology

Most T4 and T3 Most T4 and T3 bound to bound to thyroxinethyroxinebinding globulin binding globulin (TBG) in serum(TBG) in serumUnbound T4 (Unbound T4 (““free free T4T4””) is active) is activeVery small changes in Very small changes in free T4 will affect free T4 will affect TSHTSHT4 is made T4 is made exclusively in the exclusively in the thyroidthyroid

Hypothyroidism Hypothyroidism –– clinical featuresclinical features

GoiterWt gain, high cholesterol

Depression

Constipation

Hypothyroidism Hypothyroidism -- EtiologiesEtiologies

Autoimmune: #1 cause in iodine sufficient areasAutoimmune: #1 cause in iodine sufficient areasHashimotoHashimoto’’s (aka Chronic autoimmune s (aka Chronic autoimmune thyroiditisthyroiditis))

IodineIodineDeficiency is #1 cause worldwideDeficiency is #1 cause worldwideExcess can also cause hypothyroidismExcess can also cause hypothyroidism

IatrogenicIatrogenicDrugs Drugs –– Lithium, Lithium, amiodaroneamiodaroneRadioactive Iodine therapy / other radiationRadioactive Iodine therapy / other radiation

Transient (Transient (thyroiditisthyroiditis))

Antibodies in thyroid diseaseAntibodies in thyroid diseaseGroupGroup Anti TSHRAnti TSHR Anti Anti TgTg Anti TPOAnti TPO

General populationGeneral population 00 55--2020 88--2727

GravesGraves’’ diseasedisease 8080--9595 5050--7070 5050--8080

Autoimmune Autoimmune thyroiditisthyroiditis 1010--2020 8080--9090 9090--100100

Relatives of people with Relatives of people with autoimmune autoimmune thyroiditisthyroiditis

00 3030--4040 3030--5050

Type 1 diabetesType 1 diabetes 00 3030--4040 3030--4040

Pregnant womenPregnant women 00 About 14About 14 About 14About 14

TSHR: thyrotropin (TSH) receptor; Tg: thyroglobulin; TPO: thyroid peroxidase

HashimotoHashimoto’’s s thyroiditisthyroiditis

DiagnosisDiagnosisAppropriate clinical setting (often goiter is present)Appropriate clinical setting (often goiter is present)Antibodies presentAntibodies presentRule out Graves disease, cancerRule out Graves disease, cancer

Biopsy shows lymphocytic infiltration of thyroidBiopsy shows lymphocytic infiltration of thyroid

Disease courseDisease courseUsually painless (as compared to other Usually painless (as compared to other thyroiditisthyroiditis))Initially may have transient hyperthyroidismInitially may have transient hyperthyroidismGradually progresses to overt hypothyroidismGradually progresses to overt hypothyroidismUsually permanently hypothyroidUsually permanently hypothyroid

Treatment Treatment –– different formulationsdifferent formulationsGeneric nameGeneric name CompositionComposition Brand namesBrand names

LevothyroxineLevothyroxine T4T4 SynthroidSynthroidLevoxylLevoxyl

EuthyroxEuthyroxLevothroidLevothroidUnithroidUnithroid

LiothyronineLiothyronine T3T3 CytomelCytomel

LiotrixLiotrix 4:1 mixture T4 4:1 mixture T4 and T3and T3

ThyrolarThyrolar

Thyroid USPThyroid USP Thyroid extract Thyroid extract of pork or beefof pork or beef

ArmourArmour thyroidthyroidSS--PP--TTThyrarThyrar

Thyroid strongThyroid strong

Treatment Treatment –– overt hypothyroidismovert hypothyroidism

Average replacement dose: 1.6 mcg/kg/day (~125 mcg Average replacement dose: 1.6 mcg/kg/day (~125 mcg a day)a day)Initiate treatment with T4 Initiate treatment with T4 –– full dose in youngfull dose in young

Start low go slow in elderly (particularly those with CAD / Start low go slow in elderly (particularly those with CAD / angina)angina)T3 has short half life and may cause swings between low and T3 has short half life and may cause swings between low and high T3 levels, causing varied symptomshigh T3 levels, causing varied symptoms

Recheck TSH, T4 in 6 weeks, Recheck TSH, T4 in 6 weeks, redoseredose accordingly (T4 accordingly (T4 half life ~1 week)half life ~1 week)Continue until TSH returns to normal levelsContinue until TSH returns to normal levelsMonitor TSH q yearly once dose stableMonitor TSH q yearly once dose stable

T4 pearlsT4 pearls

Must be taken on an empty Must be taken on an empty stomachstomachBe consistent with brand Be consistent with brand names or generic names or generic formulations (different formulations (different preparations act differently)preparations act differently)

Subclinical hypothyroidismSubclinical hypothyroidism

Mildly elevated TSH, normal T4Mildly elevated TSH, normal T4Often due to HashimotoOften due to Hashimoto’’ssUsually progresses to overt hypothyroidism if Usually progresses to overt hypothyroidism if left untreatedleft untreatedLinked with atherosclerosis and increased risk of Linked with atherosclerosis and increased risk of MI in elderly womenMI in elderly women11

May be related to May be related to dyslipidemiasdyslipidemias

1. Hak A et al. Ann Intern Med 2000 Feb 15;132(4):270-8

TxmtTxmt –– subclinical hypothyroidismsubclinical hypothyroidism

ProsProsUnrecognized vague symptoms may improveUnrecognized vague symptoms may improvePossible correction of lipids may be cardio protectivePossible correction of lipids may be cardio protectiveWill prevent progression to overt hypothyroidismWill prevent progression to overt hypothyroidism

ConsConsExpensive (medication and monitoring)Expensive (medication and monitoring)May exacerbate angina or arrhythmiaMay exacerbate angina or arrhythmia11

Benefit of treatment is not supported with data and is Benefit of treatment is not supported with data and is controversialcontroversial

1. Chu JW et al. J Clin Endocrinol Metab 2001 Oct;86(10):4591-9.

““GuidelinesGuidelines””

RecommendationsRecommendations1 1 (2004 clinical consensus (2004 clinical consensus group):group):

Initiate treatment with T4 if TSH >10Initiate treatment with T4 if TSH >10Goal TSH is to return to normal levelsGoal TSH is to return to normal levelsConsider treatment also if pt pregnant, has Consider treatment also if pt pregnant, has ovulatoryovulatoryproblems, having behavioral problemsproblems, having behavioral problems

1. Sirks MI et al. JAMA 2004 Jan 14;291(2):228-38

Special considerationsSpecial considerations

Surgical patientsSurgical patientsUrgent surgeries should not be postponedUrgent surgeries should not be postponedIf NPO no need for IV thyroid hormone until ~1 If NPO no need for IV thyroid hormone until ~1 week week

Pregnant patientsPregnant patientsThyroid needs go up (fetus, T4 clearing, Thyroid needs go up (fetus, T4 clearing, incrincr TBG)TBG)TSH must be measured once every trimesterTSH must be measured once every trimester

Screening for hypothyroidismScreening for hypothyroidismNHANES IIINHANES III11

~13,000 people had thyroid function tests~13,000 people had thyroid function tests4.6% found to have hypothyroidism (0.3 overt, 4.3 4.6% found to have hypothyroidism (0.3 overt, 4.3 subclinical)subclinical)

Q 5Q 5--year screening in everyone found to be NOT cost year screening in everyone found to be NOT cost effectiveeffective22

Recommendations of various groups conflictRecommendations of various groups conflictOnly screening in elderly is somewhat recommendedOnly screening in elderly is somewhat recommended

Insurance companies will not pay for screening TSH in Insurance companies will not pay for screening TSH in asymptomatic patientasymptomatic patient

1. Hollowell JG et al. J Clin Endocrinol Metab 2002 Feb;87(2):489-99

2. Danese MD et al. JAMA 1996 Jul 24-31;276(4):285-92.

High TSH

Low free T4 Normal free T4 (subclinical hypothyroidism)

- TPO antibody+ TPO antibody

Yes to any of above No

Yearly follow upStart T4 therapy

Check fT4

Check TPO, TG, TSHR Ab

Probable Hashimoto’s

?pregnant, ovulatorydysfunction, hyperlipidemia, behavior problem, goiter?

If TSH becomes >10

Hypothyroidism – flowsheet review

OutlineOutline

Thyroid anatomy and physiologyThyroid anatomy and physiologyHypothyroidismHypothyroidism

Etiologies and work upEtiologies and work upTreatmentTreatmentSubclinical hypothyroidismSubclinical hypothyroidism

HyperthyroidismHyperthyroidismRole of the radioactive iodine uptake (RAIU)Role of the radioactive iodine uptake (RAIU)Etiologies and work upEtiologies and work upTreatment optionsTreatment optionsSubclinical hypothyroidismSubclinical hypothyroidism

Thyroid noduleThyroid noduleWork upWork up

Hyperthyroidism Hyperthyroidism –– clinical featuresclinical features

GoiterBone thinning

Weight loss

Atrial fibrillation

Radioactive Iodine Uptake (RAIU)Radioactive Iodine Uptake (RAIU)

Radioactive iodine given to patient to ingestRadioactive iodine given to patient to ingestDetector placed over thyroid in 24h Detector placed over thyroid in 24h

% of dose taken up reported% of dose taken up reportedNo pretty pictures!No pretty pictures!

NOT THE SAME AS RADIONUCLIDE NOT THE SAME AS RADIONUCLIDE THYROID SCANTHYROID SCAN

RAIURAIU

High RAIU High RAIU Thyroid is making a lot of thyroid hormone Thyroid is making a lot of thyroid hormone (requiring uptake of large amounts of iodine)(requiring uptake of large amounts of iodine)

Low RAIU Low RAIU Thyroid gland is not making extra hormoneThyroid gland is not making extra hormoneThyroid saturated with iodineThyroid saturated with iodine

Etiologies of hyperthyroidismEtiologies of hyperthyroidism

HIGH RAIUHIGH RAIUGraves DiseaseGraves Disease

#1 cause of hyperthyroidism#1 cause of hyperthyroidism

Toxic (Toxic (““hothot””) nodules: ) nodules: #2 cause#2 causeHyperplasia of follicular cells, Hyperplasia of follicular cells, independent of TSH regulationindependent of TSH regulation

Tumors:Tumors:Germ cell tumors, Germ cell tumors, choriocarcinomachoriocarcinoma, , hydatidiformhydatidiform moles stimulate moles stimulate TSH receptorTSH receptor

LOW RAIULOW RAIUThyroiditisThyroiditis: Inflammation of : Inflammation of thyroid causes release of thyroid causes release of preformed thyroid hormonepreformed thyroid hormoneExogenous thyroid hormoneExogenous thyroid hormoneIodine excess: Iodine excess:

Uncommon; usually from Uncommon; usually from medications (IV contrast, medications (IV contrast, amiodaroneamiodarone))

GravesGraves’’ DiseaseDisease

Autoimmune diseaseAutoimmune diseaseAssoc with thyroid Assoc with thyroid autoantibodiesautoantibodies5x more common in women, usually 5x more common in women, usually 3030--50 50 y/oy/o

TSH receptor stimulating TSH receptor stimulating IgGIgGClinical triad:Clinical triad:

Goiter (70% of cases)Goiter (70% of cases)OpthalmopathyOpthalmopathyDermopathyDermopathy ((pretibialpretibial myxedemamyxedema))

Antibodies in thyroid diseaseAntibodies in thyroid diseaseGroupGroup Anti TSHRAnti TSHR Anti Anti TgTg Anti TPOAnti TPO

General populationGeneral population 00 55--2020 88--2727

GravesGraves’’ diseasedisease 8080--9595 5050--7070 5050--8080

Autoimmune Autoimmune thyroiditisthyroiditis 1010--2020 8080--9090 9090--100100

Relatives of people with Relatives of people with autoimmune autoimmune thyroiditisthyroiditis

00 3030--4040 3030--5050

Type 1 diabetesType 1 diabetes 00 3030--4040 3030--4040

Pregnant womenPregnant women 00 About 14About 14 About 14About 14

TSHR: thyrotropin (TSH) receptor; Tg: thyroglobulin; TPO: thyroid peroxidase

ThyroiditisThyroiditis

PAINFULPAINFULSubacuteSubacute granulomatousgranulomatous (aka de (aka de QuervainsQuervains))

Pain radiates to the earPain radiates to the earInfectious: viral or bacterialInfectious: viral or bacterial

Viral much more common, usually Viral much more common, usually after URIafter URI

RadiationRadiation77--10 d after starting radioactive 10 d after starting radioactive iodine treatmentiodine treatment

PAINLESSPAINLESSHashimotoHashimoto’’ss

Usually leads to permanent Usually leads to permanent hypothyroidismhypothyroidism

Silent (aka Silent (aka ““painlesspainless”” aka aka subacutesubacutelymphocytic)lymphocytic)

Variant of HashimotoVariant of Hashimoto’’ssPostpartumPostpartumDrug inducedDrug induced

IFN IFN alfaalfa, IL, IL--22AmiodaroneAmiodaroneLithiumLithium

Fibrous (aka RiedelFibrous (aka Riedel’’s)s)Adjacent tissue invasion causes Adjacent tissue invasion causes neck painneck pain

-Wide spectrum of diseases that overlap with each other

-Usually cause transient hyperthyroidism hypothyroidism resolution within 8-10 weeks

AmiodaroneAmiodarone and thyroid diseaseand thyroid disease

37% iodine37% iodineHalf life is 100 daysHalf life is 100 daysRAIU is always low (thyroid is always saturated with iodine RAIU is always low (thyroid is always saturated with iodine already)already)HyperthyroidismHyperthyroidism

ThyroiditisThyroiditis (unclear mechanism)(unclear mechanism)Iodine excess can cause hyperthyroidismIodine excess can cause hyperthyroidism

HypothyroidismHypothyroidismIodine excess can cause hypothyroidismIodine excess can cause hypothyroidismBlocks T4 to T3 conversion Blocks T4 to T3 conversion

Check TSH before starting, q3 months when on medicationCheck TSH before starting, q3 months when on medication

Treatment Treatment –– GravesGraves’’ DiseaseDisease

Beta blocker to help autonomic symptomsBeta blocker to help autonomic symptoms3 options to treat thyroid 3 options to treat thyroid –– radioactive iodine, surgery, or radioactive iodine, surgery, or medicationsmedications

1 trial comparing 3 methods, each were equally effective in norm1 trial comparing 3 methods, each were equally effective in normalizing alizing TSH within 6 weeksTSH within 6 weeks11

Radioactive Iodine (IRadioactive Iodine (I131131))Most popular treatment in US (less popular in Europe / Japan)Most popular treatment in US (less popular in Europe / Japan)Doses sufficient to cure hyperthyroidism usually lead to permaneDoses sufficient to cure hyperthyroidism usually lead to permanent nt hypothyroidism within 12 weeks (3% a year)hypothyroidism within 12 weeks (3% a year)

Surgery (remove thyroid)Surgery (remove thyroid)Unpopular for GraveUnpopular for Grave’’s Disease; recommended if large goiters Disease; recommended if large goiter

1. Torring O et al. J Clin Endocrinol Metab 1996 Aug;81(8):2986-93

Treatment Treatment –– GravesGraves’’ DiseaseDisease

Medication Medication -- thionamidesthionamides ((PropylthiouracilPropylthiouracil or or MethimazoleMethimazole))

Inhibit iodine processing by thyroidInhibit iodine processing by thyroidPTU also blocks T4 to T3 conversion (PTU also blocks T4 to T3 conversion (give for give for prethyroidectomyprethyroidectomy prophylaxis if neededprophylaxis if needed))Often used for symptom relief prior to surgery or radioactive Often used for symptom relief prior to surgery or radioactive iodineiodineMethimazoleMethimazole is preferred (fewer side effects, ease of dosing) is preferred (fewer side effects, ease of dosing) except for pregnant patientsexcept for pregnant patients (harmful to fetus) and pre (harmful to fetus) and pre surgical prophylaxissurgical prophylaxis30% people can achieve long term remission30% people can achieve long term remission

Treatment Treatment –– Toxic nodular diseaseToxic nodular disease

Radioactive iodineRadioactive iodineExtremely effective and localizes to nodulesExtremely effective and localizes to nodulesPatients often do NOT become hypothyroidPatients often do NOT become hypothyroid

SurgerySurgeryIndicated if large goiter is present, recommended if co Indicated if large goiter is present, recommended if co existing cold nodules presentexisting cold nodules present

MedicationsMedicationsRarely achieve remission with these alone (unlike Graves)Rarely achieve remission with these alone (unlike Graves)Usually used to achieve Usually used to achieve euthyroideuthyroid state before more definitive state before more definitive therapytherapy

Subclinical hyperthyroidismSubclinical hyperthyroidism

Low TSH, normal T4 and T3Low TSH, normal T4 and T3Same etiologies of overt hyperthyroidism (endogenous causes)Same etiologies of overt hyperthyroidism (endogenous causes)

Progression to overt hyperthyroidism is uncommon (4% a year)Progression to overt hyperthyroidism is uncommon (4% a year)11

Also caused by too high of a T4 dose (exogenous)Also caused by too high of a T4 dose (exogenous)Clinical manifestations similar to overt hyperthyroidismClinical manifestations similar to overt hyperthyroidism

Higher risk for Higher risk for AFibAFib (13% of patients in one study as opposed to 14% (13% of patients in one study as opposed to 14% of patients with overt hyperthyroidism and 2% of of patients with overt hyperthyroidism and 2% of euthyroideuthyroid ptpt’’s)s)22

Decreased LDLDecreased LDLDecreased bone densityDecreased bone density

1. Sandrock D et al. Acta Endocrinol (Copenh) 1993 Jan;128(1):51-5

2. Auer J et al. Am Heart J 2001 Nov;142(5):838-42.

TxmtTxmt –– subclinical hyperthyroidismsubclinical hyperthyroidism

Little data to guide treatmentLittle data to guide treatmentRecommendationsRecommendations11 (2004 clinical consensus group):(2004 clinical consensus group):

High risk patients (elderly or post menopausal not on HRT)High risk patients (elderly or post menopausal not on HRT)If TSH <0.1, evaluate and treatIf TSH <0.1, evaluate and treatIf 0.1 to 0.5, treat if bone density is low or thyroid radionuclIf 0.1 to 0.5, treat if bone density is low or thyroid radionuclide scan ide scan has focal hot area; observe if all studies are negativehas focal hot area; observe if all studies are negative

Low risk patientsLow risk patientsIf TSH <0.1, consider treatment if bone density low or thyroid If TSH <0.1, consider treatment if bone density low or thyroid radionuclide scan has hot arearadionuclide scan has hot areaIf TSH 0.1 to 0.5, monitorIf TSH 0.1 to 0.5, monitor

1. Surks MI et al. JAMA 2004 Jan 14;291(2):228-38

Low TSH

Normal (subclinical hyperthyroidism)Elevated

High RAIU

-Graves’

-Toxic nodule(s)

-Tumor (rare)

Low RAIU

-Thyroiditis

-Iodine excess

-Amiodarone

High risk pt (elderly, post menopausal)

Consider treatment if TSH <0.1 with bone disease; otherwise monitor yearly

Treat underlying causeTreat (medication vs

I131 vs surgery)

Low risk pt

Treat if TSH <0.1, consider treatment if <0.5 with bone dz

Check free T4

RAIURisk stratify

Hyperthyroidism – flowsheet review

OutlineOutline

Thyroid anatomy and physiologyThyroid anatomy and physiologyHypothyroidismHypothyroidism

Etiologies and work upEtiologies and work upTreatmentTreatmentSubclinical hypothyroidismSubclinical hypothyroidism

HyperthyroidismHyperthyroidismRole of the radioactive iodine uptake (RAIU)Role of the radioactive iodine uptake (RAIU)Etiologies and work upEtiologies and work upTreatment optionsTreatment optionsSubclinical hypothyroidismSubclinical hypothyroidism

Thyroid noduleThyroid noduleWork upWork up

Work up of thyroid noduleWork up of thyroid nodule

FNA and FNA and biopsy as biopsy as initial test of initial test of thyroid thyroid nodulesnodulesSome patients Some patients with larger with larger benign benign FNAFNA’’ssmay receive may receive T4 to try to T4 to try to shrink noduleshrink nodule

Radionuclide thyroid scansRadionuclide thyroid scans

HOT COLD

Take home pointsTake home points

Screening for hypothyroidism is controversialScreening for hypothyroidism is controversialConsidered q5 years especially in the elderlyConsidered q5 years especially in the elderly

Name brand Name brand vsvs generic thyroid hormone replacement generic thyroid hormone replacement can be differentcan be differentCheck TSH ~4Check TSH ~4--6 weeks after changing doses6 weeks after changing doses#1 cause of hypothyroidism = Hashimoto#1 cause of hypothyroidism = Hashimoto’’s s #1 cause of hyperthyroidism = Graves#1 cause of hyperthyroidism = GravesLow RAIU = Low RAIU = thyroiditisthyroiditis and iodine excess (e.g. and iodine excess (e.g. amiodaroneamiodarone))Treat subclinical thyroid disease when appropriate!Treat subclinical thyroid disease when appropriate!