Use and Interpretation of Thyroid Tests - MCE …

1 Use and Interpretation of Thyroid TestsHerbert L. Muncie, Jr., You diagnosed hyperthyroidism 6 mosago Endocrine consult recommended 131I therapy She completed 131I therapy 6 weeks ago Labs: 1 week ago TSH -< mU/L ( ) Free T4 ng/dL( )Does she have persistent hyperthyroidism requiring additional 131I therapy ?36 Year Old Female(Follow-up Visit) At initial visit gave a history of 3 weeks of mild anterior neck pain, palpitations Mild jitteriness has been noted Thyroid gland was diffusely tender, but not enlarged Labs: 1 week ago TSH mU/L (nl ) Free T4 ng/dL (nl )Should she be started on an anti- Thyroid medication for hyperthyroidism?22 Year Old Female(One Week Follow-up visit) Seen last week for mild fatigue No chest pain or history of CHF Labs: TSH mU/L (nl ) Free T4 ng/dL (nl ) Anti-TPO antibodies positiveShould she be started on Thyroid replacement?

2 66 Year Old Female(Follow-up visit to review labs) Thyroid Gland Normal gland function is secretion of two hormones L-thyroxine (T4) 3,5,3'-triiodo-L-thyroxine (T3) Normal functioning depends on exogenous iodine intake Iodine deficiency rare in developed countryThyroid GlandTwo lobes joined by isthmusLie anterior & caudad to cartilage of larynxThyroid Hormones T4 Only source is Thyroid T3 Thyroid produces 20% Remaining 80% generated in extra glandular tissue by conversion of T4 to T3 Hormones half-life T4 -1 week T3 -1 daySunMonTuesWedThuFriSatXXXXXXXXT hyroid Hormones T4 bound; T3 bound Thyroid hormones bound to: Thyroxine-binding globulin (TBG) T4 binding prealbumin (TBPA)

3 Albumin TBG is dominant binding protein One binding site for T4 or T3 10 fold affinity for T4 Altered Concentrations TBG Increased TBG Pregnancy BCP or estrogen Tamoxifen Hepatitis Biliary cirrhosis Acute intermittent porphyria Decreased TBG Androgens High dose steroids Chronic liver disease Nephrosis Severe systemic illness Active acromegalyAltered Concentrations TBG Abnormalities of binding protein are associated with elevated or decreased totalT4 or T3 However, always accompanied by normal free T4, free T3 & euthyroid state in pregnancy increased TBG leads to less free T4 temporarily Stimulates increased production of total T4 but free T4 level remains normalThyroid Hormone SynthesisT4T3 Thyroid glandOrganic iodinein ThyroglobulinHypothalamusAnt.

4 PituitaryTRHTSHT4T3+TBGTBG + T4 TBG + T3I-I-IPOGI TractIodine to I-T4 Thyroid Test Normal Range* *Confirm normal values for your labAre normal values normal? An individual patient s TSH remains in a much narrower range with repetitive testing Establishment of normal range may have included patients with occult Thyroid disease Results within upper limits of normal range are associated with adverse outcomes TSH mU/L increased risk overt hypothyroidism over next 20 years TSH mU/L associated with increased prevalence heart diseaseAre normal values normal? When corrected for underlying or occult Thyroid disease Mean TSH mU/L Upper limit for mU/L National Academy of Clinical Biochemistry (NACB) recommends TSH normal to be mU/L 95% of TSHs in this range No evidence thyroxine treatment is beneficial for TSH mU/LFollow-up Thyroid Tests Radioisotope Thyroid scan Use for hyperthyroid patient with nodule Can locate extra thyroidal tissue Can identify nodule function Hot nodules < 1% cancer Cold nodules 20% cancer However, FNA best for everyoneFollow-up Thyroid Tests Radioactive iodine uptake (RAIU)

5 Main indication is to differentiate between post-partum, silent & subacute thyroiditis Helps identify Graves disease unless clinically obvious GravesFollow-up Thyroid Tests Ultrasound Determines whether nodule solid or cystic Guides FNA if difficult to palpateFollow-up Thyroid Tests (Rarely required) Antithyroid peroxidase autoantibody (anti-TPO) Antithyroglobulin antibodies TBG level Thyroglobulin level (only produced by Thyroid ) Measure f/u post thyroidectomy for cancer Thyroxine replacement lowers level but not thyrotoxicosis Helps evaluate for thyrotoxicosis factitiaThyroid nodules Obtain ultrasound for all nodules Size is not predictive or risk of malignancy Calcification within the nodule increases likelihood of malignancy Almost all will require FNA Routine measurement of thyroglobulin is not recommended (SOR F)

6 Thyroid Cancer Guidelines American Thyroid Association -2006 Thyroid nodules Benign pathology on FNAB & biochemically normal No treatment is necessary Annual examination & repeat ultrasoundThyroid Cancer Guidelines American Thyroid Association -2006 Reverse T3 What do you do if TSH is normal but Free T4 is below normal? This can occur in medically ill patients with non-thyroidal illness (NTI) Measure reverse T3 to exclude subclinical hypothyroidism Elevated in NTI Low with hypothyroidismCan You Really Exclude Thyroid Dysfunction? If clinically really suspect Thyroid disease Order TSH, free T4, free T3 TSH alone should not be used to make a diagnosis If all three are normal can confidently exclude clinical Thyroid diseaseTSH below normal, Free T4 elevated(Hyperthyroidism) DX: Primary hyperthyroidism Graves disease Multinodular goiter Toxic nodule Gland usually nontender No definitive test to prove which it is If clinically suspect hyperthyroidism & low TSH but normal FT4 Measure FT3 for T3 hyperthyroidismPrimary Hyperthyroidism Probably Graves if.

7 Thyroid scan has homogeneous pattern Positive antithyroid antibodies However, 10% of Graves are negative for antithyroid antibodies 24 hr RAIU normal or elevatedTSH below normal but Free T4 normal(Subclinical hyperthyroidism) No treatment indicated even though Increased risk of atrial fibrillation But no increased mortality or other CVD Repeat TSH, FT4 in 1 3 months Treatment possibly indicated in: Early Graves disease Multinodular goiter Fair evidence beneficial in slowing loss of bone mineral density (BMD)Subclinical hyperthyroidism(Follow-up testing) If the repeat TSH = & FT4 remains normal No treatment is necessary Monitor TSH in 3 12 months If the patient has heart disease , osteoporosis or symptoms of hyperthyroidism Look for endogenous hyperthyroid disease Obtain Thyroid scan, RAIu If endogenous disease treat If no endogenous diesease no treatmentSubclinical hyperthyroidism(Follow-up testing)

8 If the repeat TSH = < & FT4 remains normal Obtain Thyroid scan, RAI uptake to look for endogenous disease If diagnose is Graves disease or nodular goiter Consider treatment for patients with heart disease , osteoporosis, over age > 60 or with estrogen deficiency symptoms Otherwise monitor clinically with treatment optionalTSH Normal but Free T4 below normal Consider pituitary disease with 2ohypothyroidism TSH usually in normal range when it should be elevated Can occur within 2-3 months after treatment of hyperthyroidism with I131 May be hypothyroid phase of transient thyroiditis & will resolve spontaneouslyTSH Elevated and FT4 below normal (Primary hypothyroidism) Common etiologies.

9 Autoimmune thyroiditis Iatrogenic Post radioiodine therapy/thyroidectomy Medications Thyroiditis subacute, postpartum, silentTSH Elevated but Free T4 Normal (Subclinical hypothyroidism) Affects 5-10% of women Transient elevations are common, especially with NTI & medications Consider repeating in 6 8 weeks If TSH > Treatment is indicatedSubclinical hypothyroidism If TSH is , with normal FT4 Clinical stratificationConsider T4 replacementNo benefit to T4 replacementDocumented diastolic dysfunctionNormal cardiac functionDiastolic hypertensionNormal arterial pressureAtherosclerotic risk factorsNo atherosclerotic risk factorsDyslipidemiaNormal lipid profileDiabetes mellitusNormal glucose metabolismSmokerNon-smokerSymptoms of hypothyroidismNo symptomsGoiter No goiterPositive anti-TPO antibodiesNo antibodiesPregnancyNot pregnantInfertility No infertilityVery elderly patient (> age 85)

10 Subclinical hypothyroidism No randomized trials of treatment vs placebo Treatment has not been found to reduce adverse events Treatment can increase risk of hyperthyroidism, osteoporosis & atrial fibrillation (Clinical Evidence) In 70-79 yo well functioning patients, TSH mU/L, no increased risk of mobility problems Show slight functional advantage [Simonsick 2009]Subclinical hypothyroidism In patients > 85 yo condition associated with increased longevity Positive anti-TPO antibodies associated with progression to overt disease However the presence of antibodies does not change managementTSH Normal & FT4 Elevated Rare combination consider: Intermittent T4 therapy or T4 overdose Acute psychiatric illness (first 1-3 weeks) Thyroid hormone receptor mutation and resistance to Thyroid hormoneA 42 female diagnosed with primary hypothyroidism.