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Update on the Thyroid Douglas C. Bauer, MD UCSF Division of General Internal Medicine No Disclosures.

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Presentation on theme: "Update on the Thyroid Douglas C. Bauer, MD UCSF Division of General Internal Medicine No Disclosures."— Presentation transcript:

1 Update on the Thyroid Douglas C. Bauer, MD UCSF Division of General Internal Medicine No Disclosures

2 Cases 68 yr old female with new atrial fibrillation and no other findings except TSH=0.04, normal free T468 yr old female with new atrial fibrillation and no other findings except TSH=0.04, normal free T4 79 yr old man with 1 yr of fatigue and lassitude and no findings except TSH=9.0, anti-TPO positive79 yr old man with 1 yr of fatigue and lassitude and no findings except TSH=9.0, anti-TPO positive 45 yr old women, enlarged thyroid with dominant nodule since 1999, FNA benign. On T4 suppession ever since, TSH=0.145 yr old women, enlarged thyroid with dominant nodule since 1999, FNA benign. On T4 suppession ever since, TSH=0.1

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4 Thyroid Tests: sTSH Very sensitive to circulating thyroid hormone levelsVery sensitive to circulating thyroid hormone levels Excellent correlation with TRH stimulation (sTSH < 0.1)Excellent correlation with TRH stimulation (sTSH < 0.1) Requires intact pituitary-hypothalamic axis; 4-6 weeks to equilibrateRequires intact pituitary-hypothalamic axis; 4-6 weeks to equilibrate Falsely low: severe illness, corticosteriods, dopamineFalsely low: severe illness, corticosteriods, dopamine Normal range mU/L; $58Normal range mU/L; $58

5 Thyroid Tests: Free Thyroxine Measures unbound hormoneMeasures unbound hormone Replacing index assaysReplacing index assays Gold standard: Equilibrium dialysisGold standard: Equilibrium dialysis Other immunoassays: ImprovingOther immunoassays: Improving Normal range, 9-24 pmol/L; $64Normal range, 9-24 pmol/L; $64

6 Are Both sTSH and Free T4 Necessary? American Thyroid Association: YesAmerican Thyroid Association: Yes Others recommend sTSH firstOthers recommend sTSH first UCSF outpatient dataUCSF outpatient data – Results when both tests ordered on the same specimen (N=3143) – Each test classified as low, normal or high

7 Diagnostic Redundancy of sTSH and Free T4 sTSH (mU/L) 5.5 < > Free T4 (pmol/L)

8 Subclinical Thyroid Disease Subclinical hypothyroidism Abnormally high sensitive TSH and normal thyroid hormone levelsSubclinical hypothyroidism Abnormally high sensitive TSH and normal thyroid hormone levels Subclinical hyperthyroidism Abnormally low sensitive TSH and normal thyroid hormone levelsSubclinical hyperthyroidism Abnormally low sensitive TSH and normal thyroid hormone levels

9 Suggested Testing Strategy If sTSH is normal, STOPIf sTSH is normal, STOP If sTSH is low, measure T4, consider T3If sTSH is low, measure T4, consider T3 If sTSH is high, measure T4, consider TPO antibodiesIf sTSH is high, measure T4, consider TPO antibodies

10 Thyroid Antibodies Anti-thyroperoxidase, TPO (titer<100, $78)Anti-thyroperoxidase, TPO (titer<100, $78) –Similar to anti-microsomal –Most sensitive thyroid autoantibody –Specificity a problem TSH receptor antibody (absent, $112)TSH receptor antibody (absent, $112) –Causes Graves disease –Rarely found in normal individuals

11 Thyroid Scans Technetium 99 ($450)Technetium 99 ($450) –Low radiation, quick –Useful for nodules in some circumstances –Useful to determine cause of hyperthyroidism A. High uptake: Graves, toxic noduleA. High uptake: Graves, toxic nodule B. Low uptake: thyroiditis, thyroxine useB. Low uptake: thyroiditis, thyroxine use

12 Hyperthyroidism: Epidemiology Etiology:Etiology: –Iatrogenic A. Over replacement (30-50% given rx)A. Over replacement (30-50% given rx) B. Suppression of CA, goiters, and nodulesB. Suppression of CA, goiters, and nodules –Autoimmune (Graves disease): thyroid stimulating autoantibodies –Autonomous nodule(s). Occasionally T3 –TSH secreting tumors

13 Hyperthyroidism: Prevalence Population based prevalence of suppressed TSH: Author age men women Bagchi (1990) >55 1.8%2.7% Falkenberg (1991) >601.9% Parle (1991) > % Bauer (1993) >555.8%Population based prevalence of suppressed TSH: Author age men women Bagchi (1990) >55 1.8%2.7% Falkenberg (1991) >601.9% Parle (1991) > % Bauer (1993) >555.8%

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15 Crooks Index*

16 Hyperthyroidism in the Elderly Weight loss, palpitations, and nervousness less commonWeight loss, palpitations, and nervousness less common Tachycardia, exophthalmos, tremor less commonTachycardia, exophthalmos, tremor less common Atrial fibrillation more commonAtrial fibrillation more common 8-10% are completely asymptomatic8-10% are completely asymptomatic

17 Subclinical Hyperthyroidism: Cardiac Effects Systolic time intervals shortenedSystolic time intervals shortened – Clinical significance uncertain Reduced exercise toleranceReduced exercise tolerance Increased incidence of atrial fibrillationIncreased incidence of atrial fibrillation Swain, 1994 Prospective cohort, N = 2000 RR = 3.1 (1.7, 5.5) if sTSH < 0.1

18 Subclinical Hyperthyroidism: Skeletal Effects Florid hyperthyroidism causes fracturesFlorid hyperthyroidism causes fractures Effect on BMD, bone loss controversialEffect on BMD, bone loss controversial Increased fracture risk (Bauer, 2001) - Prospective study, 9407 older women - TSH < 0.1 vs. normal - Hip fracture: RR = 3.6 (1.0, 12. 9) - Vertebral fracture: RR = 4.5 (1.3, 15.6)Increased fracture risk (Bauer, 2001) - Prospective study, 9407 older women - TSH < 0.1 vs. normal - Hip fracture: RR = 3.6 (1.0, 12. 9) - Vertebral fracture: RR = 4.5 (1.3, 15.6) Effect of accelerated bone turnover?Effect of accelerated bone turnover?

19 Subclinical Hyperthyroidism: Natural History Exogenous: Well establishedExogenous: Well established Endogenous: Little longitudinal dataEndogenous: Little longitudinal data Parle, untreated individuals >60 1 developed overt hyperthyroidism After 1 year, sTSH normal in half!

20 Who Should Be Treated? Exogenous (iatrogenic)Exogenous (iatrogenic) –Dose reduction unless contraindicated Endogenous (subclinical)Endogenous (subclinical) –Follow if uncomplicated –Consider treatment if atrial fibrillation or osteoporosis present Endogenous (overt)Endogenous (overt) –Rule out thyroiditis –Tx everyone else with beta blocker and...

21 Hyperthyroidism: Treatment Anti-thyroid drugs (PTU and methimazole)Anti-thyroid drugs (PTU and methimazole) –Remission: 30-50% after mo –Side effects: rash, fever, arthritis, agranulocytosis (all rare) RadioiodineRadioiodine –Best treatment for hot nodules –Remission: everyone –Side effects: transient thyroiditis (rare), hypothyroid (50%), worsening exophthalmous

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23 Radioiodine and Mortality Franklyn, hyperthyroid pts, 15 yr follow-up - All cause mortality: 13% higher than age and sex matched populations - CV deaths increased, but not cancerFranklyn, hyperthyroid pts, 15 yr follow-up - All cause mortality: 13% higher than age and sex matched populations - CV deaths increased, but not cancer Mechanism unknown, clear dose-responseMechanism unknown, clear dose-response Unable to adjust for other potential confoundersUnable to adjust for other potential confounders

24 Hypothyroidism: Epidemiology EtiologyEtiology –Autoimmune (Hashimotos) –Iodine deficiency –Iatrogenic A. Radioiodine/ surgery B. Drugs (lithium, amiodarone) –Pituitary/ hypothalamic disease

25 Hypothyroidism: Prevalence Population based prevalence of elevated TSH:Population based prevalence of elevated TSH: Authoragemenwomen Tunbridge(1977)>65 6.0% 10.9% Bagchi(1990)>55 1.8% 2.7% Parle(1991)>60 2.9% 11.6% Bauer(1993)>55 5.4%

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27 Billewicz Index*

28 Overt Hypothyroidism in the Elderly Classic features often missingClassic features often missing Neuropsychiatric complaints common: depression, weakness, memory lossNeuropsychiatric complaints common: depression, weakness, memory loss Other clues: hypercholesterolemia, elevated CK, pleural effusionOther clues: hypercholesterolemia, elevated CK, pleural effusion

29 Subclinical Hypothyroidism: CV Outcomes Observational studiesObservational studies –Total cholesterol unchanged, but higher LDL and lower HDL? What about atherosclerosis?What about atherosclerosis? Rotterdam population-based study (Hak, 2000)Rotterdam population-based study (Hak, 2000) – 1149 women, mean age 70 – Subclinical hypo (TSH > 4, nl T4) in 10.8% – Aortic atherosclerosis RR = 1.7 (1.1, 2.6) – History of MI RR = 2.3 (1.3, 4.0)

30 Summary OR 1.65 ( ) P for heterogeneity: 0.12 Meta Analysis of Subclinical Hypothyroidism and CHD

31 Subclinical Hypothyroidism: Other Outcomes Observational studies of neuropsychiatric symptomsObservational studies of neuropsychiatric symptoms – Conflicting evidence Four small double blinded trials, sTSH > 5-7Four small double blinded trials, sTSH > 5-7 –Randomized to thyroxine or placebo –No significant change in weight, lipids, other laboratory values –Psychometric testing: Treated felt better and had better memory scores

32 Subclinical Hypothyroidism: Natural History Many good studiesMany good studies Spontaneous resolution infrequentSpontaneous resolution infrequent Antibodies strongly influence outcomeAntibodies strongly influence outcome –If TPO positive, overt hypothyroidism 5%/yr

33 Hypothyroidism: Treatment Replace with thyroxine (T4)Replace with thyroxine (T4) –T3 + T4 benefit unproven Typical replacement dose 1.6 mcg/kgTypical replacement dose 1.6 mcg/kg –Elderly or CAD: start low ( mg/d), gradually increase dose Maintain TSH within the normal rangeMaintain TSH within the normal range –Wait 6 weeks after dose change Monitor yearly (noncompliance, reduced T4 clearance)Monitor yearly (noncompliance, reduced T4 clearance)

34 What About Treatment of Symptomatic but Euthyroid Patients? Forget It. Symptoms of hypothyroidism commonSymptoms of hypothyroidism common –Real but not detected by usual tests? Double blind RCT (Pollock, 2001)Double blind RCT (Pollock, 2001) –25 symptomatic, 18 controls –All euthyroid –3 mo of T4 (0.1/d) or placebo, cross-over –TSH fell with T4 tx but no difference in cognitive or psychological function

35 Thyroid Nodules: Epidemiology and Evaluation Nodules are common (and cancer is rare)Nodules are common (and cancer is rare) –90% women over age 60 have one or more thyroid nodules at autopsy Risk factors for cancer: neck irritation, FHRisk factors for cancer: neck irritation, FH Evaluation: FNA firstEvaluation: FNA first –75% benign, 20% suspicious, 5% malignant –Best centers: false negative 2% false positive 1%

36 Thyroid Nodules: Treatment Cancer - Histology is important (papillary best) - Surgery and 131 I ablation - Suppression with T4? TSH = Cancer - Histology is important (papillary best) - Surgery and 131 I ablation - Suppression with T4? TSH = Benign nodules - Many shrink spontaneously - Meta analysis of T4 suppression Smaller: 26% vs. 12% (NNT=7) Larger: 8% vs. 17% (NNT=11) - T4 doesnt prevent new nodulesBenign nodules - Many shrink spontaneously - Meta analysis of T4 suppression Smaller: 26% vs. 12% (NNT=7) Larger: 8% vs. 17% (NNT=11) - T4 doesnt prevent new nodules

37 Screening Cost-effectiveness Danese and Sawin, 1995Danese and Sawin, 1995 – Cost-utility analysis, sTSH-based screening – Modeled progression, symptoms and CAD – Screening every 5 year from 35-65: $9,223 per QALY in women $22,595 per QALY in men – Sensitivity analysis: cost of TSH key ($25)

38 Screening for Subclinical Thyroid Disease US Preventive Task Force, 1996 Routine screening is not recommended. Insufficient evidence for high risk patients, including elderly.US Preventive Task Force, 1996 Routine screening is not recommended. Insufficient evidence for high risk patients, including elderly. ACP, 1998 It is reasonable to screen women older than 50 years of age for unsuspected but symptomatic thyroid disease.ACP, 1998 It is reasonable to screen women older than 50 years of age for unsuspected but symptomatic thyroid disease.

39 Screening Cost-effectiveness Effects on HDL, fractures not included. Cost of testing overestimated ($3/TSH)Effects on HDL, fractures not included. Cost of testing overestimated ($3/TSH) Published analyses underestimate cost-effectivenessPublished analyses underestimate cost-effectiveness Other unresolved issues:Other unresolved issues: – Age to start screening? – Optimal frequency?

40 Summary Take Home Points sTSH is best testsTSH is best test Subclinical thyroid disease is common, associated with morbidity, and treatableSubclinical thyroid disease is common, associated with morbidity, and treatable Low threshold to treat subclinical hypoLow threshold to treat subclinical hypo Treatment threshold for subclinical hyper less certainTreatment threshold for subclinical hyper less certain Screening with sTSH is cost-effectiveScreening with sTSH is cost-effective

41 Cases 68 yr old female with new atrial fibrillation and no other findings except TSH=0.04, normal free T468 yr old female with new atrial fibrillation and no other findings except TSH=0.04, normal free T4 79 yr old man with 1 yr of fatigue and lassitude and no findings except TSH=9.0, anti-TPO positive79 yr old man with 1 yr of fatigue and lassitude and no findings except TSH=9.0, anti-TPO positive 45 yr old women, enlarged thyroid with dominant nodule since 1999, FNA benign. On T4 suppession ever since, TSH=0.145 yr old women, enlarged thyroid with dominant nodule since 1999, FNA benign. On T4 suppession ever since, TSH=0.1


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