2 Main Objectives1. To outline the criteria for subclinical thyroid disease.2. To review the evidence for the clinical significance of subclinical thyroid disease.3. To review the management of subclinical thyroid disease.
3 Case50 year old womanTSH = 7 mIU/L ( ) on routine screening, normal free T4/T3Only symptoms = mild fatigue x 10 years, difficulty losing weightNormal physical examAlso serum cholesterol 5.70 mmol/L, LDL 3.62 mmol/LAnti-TPO positiveStart thyroxine???
4 Definition of Subclinical Thyroid Disease Subclinical HypothyroidismTSH elevated (0.27 – 4.20 mIU/L)Free T4/T3 normalRule out other causes of an elevated serum TSHLevothyroxine dosage changes (in process of achieving a steady state)Recovering from severe nonthyroidal illnessRecovery from: postviral subacute thyroiditis, postpartum thyroiditisSubclinical HyperthyroidismTSH low (0.27 – 4.20 mIU/L)Free T4/T3 normalRule out other causes of low serum TSHOveradministration of thyroid hormoneNormal pregnancy, nonthyroidal illnessesAdministration of dopamine, glucocorticoids, etcNormal ThyroidSubclinical ThyroidHypo/Hyper thyroid
5 EpidemiologySubclinical hypothyroidism: 4 – 8.5% of population without known thyroid diseasePrevalence increases with age (esp. women > 60y, up to 20%), also in menElevated TSH levels: 75% values > 10mIU/LFactors that raise likelihood: family history of thyroid disease, postpartum thyroiditis, previous head and neck cancer treated with radiation, DMT1, previous hyperthyroidismIn patients with subclinical hypothyroidism, 2 – 5% per year will progress to overt hypothyroidismRate of progression is higher if + antithyroid antibodiesSerum TSH returns to normal in about 5% of people after 1 year
6 Epidemiology Subclinical hyperthyroidism: much less common If exclude patients with known thyroid disease and lower limit of TSH is 0.4mIU/L, prevalence is 2%More common if: female, elderly, low iodine intakeMore likely if: history thyroid disease, family history thyroid disease, atrial fibrillation, use amiodarone, presence of goiterIf TSH 0.1 – 0.45mIU/L = few progress to overt hyperthyroidism vs. 1 – 2% per year if TSH < 0.1 mIU/L
7 Clinical significance of disease: Why does it matter??? JAMA 2004: Subclinical Thyroid Disease, Scientific review and guidelines for diagnosis and managementRepresentatives from American Thyroid Association, the American Asso. of Clinical Endo, and the Endocrine SocietyReviewed literature and summarized the evidenceRelevant articles found by searching Medline, Embase, Biosis, etc.Examined quality of evidence for strength of association with adverse consequencesPanel rated strength of available evidence as either “good”, “fair” or “insufficient” as it related to the association of treatment and outcomes
9 Subclinical hypothyroidism Cardiac implicationsCardiac disease: decreases in myocardial contractility (echo)Unclear if affects angina, MI, atherosclerosis and cardiovascular deathNo randomized studies have assessed impact of levothyroxine replacement on important clinical cardiac end pointsMany small trials demonstrate improved cardiac function – not clear if clinically importantLipidsSeveral studies suggest thyroid hormone therapy will reduce total and LDL cholesterol levelsHowever, this finding has not been confirmed in RCT’sSystemic symptomsIncreased prevalence of hypothyroid symptoms seen in some studies, not all
10 Evaluation of Subclinical hypothyroidism If TSH is high repeat along with free T4 in the next 2 weeks – 3 monthsEvaluate for signs and symptoms of hypothyroidism, previous tx for hyperthyroidism, thyroid gland enlargement, family hx thyroid diseaseReview lipid profileSpecial consideration if pregnant woman/plans for pregnancyInsufficient evidence to recommend for/against measurement of anti-TPO antibodies
11 Management Serum TSH 4.5 – 10mIU/L Serum TSH > 10mIU/L Repeat TFT’s q 6-12 monthsTreat if symptoms compatible with hypothyroidism (no studies looking at his)Continue therapy of there is clear symptomatic benefitSerum TSH > 10mIU/LLevothyroxine therapy is reasonableRate of progression to hypothyroidism is 5%, may prevent manifestations and consequences of hypothyroidism in those that do progressAim for TSH level in lower half of normal range
12 Subclinical hypothyroidism during pregnancy Evidence rating = “fair” for adverse outcomes for either mother or fetusCheck TSH if family/personal hx of thyroid disease, signs/symptoms of hypothyroidism or goiter, DMT1, personal hx of autoimmune disordersIf TSH elevated = treat, possible association with neuropsychological complications in fetusMonitor TSH levels q 6-8 weeks and modify dose of levothyroxine accordingly (requirements will increase)
14 Subclinical hyperthyroidism Cardiac diseaseSolid evidence for a 3x increased risk of a fib over 10 y in women and men > 60y with TSH < 0.1 mIU/LLimited evidence for a fib if TSH 0.1 – 0.4 mIU/LAlso reported increase in LV mass, cardiac contractility, diastolic dysfunction and atrial arrythmiasSystemic symptomsMore hyperthyroid-type signs and symptoms?Bone health2 meta-analyses reported declines in bone mineral density during prolonged subclinical hyperthyroidism, especially if postmenopausal women (not if premenopausal)Prolonged subclinical hyperthyroidism prior to overt hyperthyroidism may increase risk of fracturesNormalization of bone turnover may take 1 year once treatment started
15 Evaluation/Management of Subclinical hyperthyroidism If TSH 0.1 – 0.45 mIU/L repeat, as well as free T4/T3 (time frame based on clinical circumstances, recommend within 3 months)Repeat within 2 weeks if patient has a fib, cardiac disease, other serious medical conditionIf repeat TSH 0.1 – 0.45 mIU/L, normal free T4/T3 and no s/s cardiac disease, a fib, arrhythmias repeat TFT’s q 3 – 12 monthsMay consider tx of elderly due to possible association with increased cardiovascular mortality
16 Evaluation/Management If TSH < 0.1 mIU/L repeat along with free T4/T3 within 4 weeksSooner if s/s cardiac disease, a fib, arrhythmias, important medical issuesAlso recommend further evaluation, ie. thyroid uptake scan to distinguish between thyroiditis, Graves disease, nodular goiter, etc (treat if Graves or nodular thyroid disease)Consider tx if age > 60y, osteopenia/osteoporosis, people at increased risk for heart disease, symptomaticIf younger individual = offer therapy or follow-up depending in individual considerations
17 Case50 year old womanTSH = 7 mIU/L ( ) on routine screening, normal free T4/T3Only symptom = mild fatigue x 10 years, difficulty losing weightNormal physical examAlso serum cholesterol 5.70 mmol/L, LDL 3.62 mmol/LAnti-TPO positiveStart thyroxine???