Presentation on theme: "UCSF Division of General Internal Medicine"— Presentation transcript:
1 UCSF Division of General Internal Medicine Update on the ThyroidDouglas C. Bauer, MDUCSF Division of General Internal MedicineNo Disclosures
2 Cases68 yr old female with new atrial fibrillation and no other findings except TSH=0.04, normal free T479 yr old man with 1 yr of fatigue and lassitude and no findings except TSH=9.0, anti-TPO positive45 yr old women, enlarged thyroid with dominant nodule since 1999, FNA benign. On T4 suppession ever since, TSH=0.1
6 Are Both sTSH and Free T4 Necessary? American Thyroid Association: YesOthers recommend sTSH firstUCSF outpatient dataResults 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 levels”Subclinical hyperthyroidism “Abnormally low sensitive TSH and normal thyroid hormone levels”
9 Suggested Testing Strategy If sTSH is normal, STOPIf sTSH is low, measure T4, consider T3If sTSH is high, measure T4, consider TPO antibodies
10 Thyroid Antibodies Anti-thyroperoxidase, TPO (titer<100, $78) Similar to “anti-microsomal”Most sensitive thyroid autoantibodySpecificity a problemTSH receptor antibody (absent, $112)Causes Grave’s diseaseRarely found in normal individuals
11 Thyroid Scans Technetium 99 ($450) Low radiation, quick Useful for nodules in some circumstancesUseful to determine cause of hyperthyroidismA. High uptake: Grave’s, toxic noduleB. Low uptake: thyroiditis, thyroxine use
12 Hyperthyroidism: Epidemiology Etiology:IatrogenicA. Over replacement (30-50% given rx)B. Suppression of CA, goiters, and nodulesAutoimmune (Grave’s disease): thyroid stimulating autoantibodiesAutonomous nodule(s). Occasionally T3TSH secreting tumors
13 Hyperthyroidism: Prevalence Population based prevalence of suppressed TSH: Author age men women Bagchi (1990) > % 2.7% Falkenberg (1991) > % Parle (1991) > % Bauer (1993) > %
16 Hyperthyroidism in the Elderly Weight loss, palpitations, and nervousness less commonTachycardia, exophthalmos, tremor less commonAtrial fibrillation more common8-10% are completely asymptomatic
17 Subclinical Hyperthyroidism: Cardiac Effects Systolic time intervals shortenedClinical significance uncertainReduced exercise toleranceIncreased incidence of atrial fibrillationSwain, Prospective cohort, N = RR = 3.1 (1.7, 5.5) if sTSH < 0.1
18 Subclinical Hyperthyroidism: Skeletal Effects Florid hyperthyroidism causes fracturesEffect on BMD, bone loss controversialIncreased 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?
19 Subclinical Hyperthyroidism: Natural History Exogenous: Well establishedEndogenous: Little longitudinal dataParle, untreated individuals >60 1 developed overt hyperthyroidismAfter 1 year, sTSH normal in half!
20 Who Should Be Treated? Exogenous (iatrogenic) Dose reduction unless contraindicatedEndogenous (subclinical)Follow if uncomplicatedConsider treatment if atrial fibrillation or osteoporosis presentEndogenous (overt)Rule out thyroiditisTx everyone else with beta blocker and...
21 Hyperthyroidism: Treatment Anti-thyroid drugs (PTU and methimazole)Remission: 30-50% after moSide effects: rash, fever, arthritis, agranulocytosis (all rare)RadioiodineBest treatment for hot nodulesRemission: everyoneSide effects: transient thyroiditis (rare), hypothyroid (50%), worsening exophthalmous
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 cancerMechanism unknown, clear dose-responseUnable to adjust for other potential confounders
28 Overt Hypothyroidism in the Elderly “Classic” features often missingNeuropsychiatric complaints common: depression, weakness, memory lossOther clues: hypercholesterolemia, elevated CK, pleural effusion
29 Subclinical Hypothyroidism: CV Outcomes Observational studiesTotal cholesterol unchanged, but higher LDL and lower HDL?What about atherosclerosis?Rotterdam population-based study (Hak, 2000)1149 women, mean age 70Subclinical 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 Meta Analysis of Subclinical Hypothyroidism and CHD Summary OR1.65 ( )P for heterogeneity: 0.12
31 Subclinical Hypothyroidism: Other Outcomes Observational studies of neuropsychiatric symptomsConflicting evidenceFour small double blinded trials, sTSH > 5-7Randomized to thyroxine or placeboNo significant change in weight, lipids, other laboratory valuesPsychometric testing: Treated felt better and had better memory scores
32 Subclinical Hypothyroidism: Natural History Many good studiesSpontaneous resolution infrequentAntibodies strongly influence outcomeIf TPO positive, overt hypothyroidism 5%/yr
33 Hypothyroidism: Treatment Replace with thyroxine (T4)T3 + T4 benefit unprovenTypical replacement dose 1.6 mcg/kgElderly or CAD: start low ( mg/d), gradually increase doseMaintain TSH within the normal rangeWait 6 weeks after dose changeMonitor yearly (noncompliance, reduced T4 clearance)
34 What About Treatment of Symptomatic but Euthyroid Patients? Forget It. Symptoms of hypothyroidism commonReal but not detected by usual tests?Double blind RCT (Pollock, 2001)25 “symptomatic”, 18 “controls”All euthyroid3 mo of T4 (0.1/d) or placebo, cross-overTSH 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)90% women over age 60 have one or more thyroid nodules at autopsyRisk factors for cancer: neck irritation, FHEvaluation: FNA first75% benign, 20% suspicious, 5% malignantBest centers: false negative 2% false positive 1%
36 Thyroid Nodules: Treatment Cancer - Histology is important (papillary best) - Surgery and 131I 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 doesn’t prevent new nodules
37 Screening Cost-effectiveness Danese and Sawin, 1995Cost-utility analysis, sTSH-based screeningModeled progression, symptoms and CADScreening every 5 year from 35-65: $9,223 per QALY in women $22,595 per QALY in menSensitivity 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.”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)Published analyses underestimate cost-effectivenessOther unresolved issues:Age to start screening?Optimal frequency?
40 Summary Take Home Points sTSH is best testSubclinical thyroid disease is common, associated with morbidity, and treatableLow threshold to treat subclinical hypoTreatment threshold for subclinical hyper less certainScreening with sTSH is cost-effective
41 Cases68 yr old female with new atrial fibrillation and no other findings except TSH=0.04, normal free T479 yr old man with 1 yr of fatigue and lassitude and no findings except TSH=9.0, anti-TPO positive45 yr old women, enlarged thyroid with dominant nodule since 1999, FNA benign. On T4 suppession ever since, TSH=0.1