Subclinical thyroid disorders: still a matter of controversy,Simon HS Pearce,Plan, Background Subclinical hypothyroidism-Vascular risk Subclinical hyperthyroidism-Understand the pathophysiology-Approach to Management,What is normal?,Andersen et al. JCEM 2002, 16 healthy individuals, having monthly TFTs for 1 year People stick to their own “reference” interval Extrapolating to Free T4 values -setpoint +/- 2.5 pmol/l “My normal range is different from yours”,TSH in centenarians and offspring,Atzmon et al. JCEM 2009, 232 Ashkenazim, age 97 o 366 of offspring, age 69 177 age-matched controls,Lancet 1971; I: 203,Possible mechanisms, Dyslipidaemia Cardiac systolic & diastolic dysfunction Hypertension Endothelial dysfunction Hypercoagulability,Hard outcomes,Rotterdam Heart Study Community-based cross sectional survey 1149 women (mean age 69 +/-7 yrs) 10.8% had “subclinical hypothyroidism” (TSH4.0, N FT4)Odds ratio for MI= 2.3 (CI; 1.3-4.0) OR for aortic atherosclerosis 1.7 (1.1-2.6) Population attributable risk of TSH to MI estimated to be 14% N.B. Diabetes 14%, Smoking 15%,Hak et al. Ann Intern Med 2000;132: 270,Meta-summary of meta-analyses, Relative risks (5-95% confidence intervals),Meta-summary of meta-analyses, Relative risks (5-95% confidence intervals),M Thvilum, F Brandt, TH Brix & L Hegedus. Nat Rev Endocrinol 2012,All cause mortality in SCH,Janus response: Age,Thanks to Stefano Mariotti & David Cooper,Meta-analysis,Performed by Salman Razvi/ Abdul Shakoor Longitudinal or cross sectional studies of independent community-based subjects 14 studies fitted stringent criteria 2,531 SCH participants 26,491 euthyroid individuals Divided studies according to age of inclusion 40 yrs with TSH 5.0- 10.0 mU/l, normal FT4Excluded individuals on L-T4, ATDs, previous thyroid disease, previous IHD, stroke, other vascular disease,Razvi S et al. Arch Intern Med 2012,UK General Practice Research Database,Participants followed until March 2008 (median 7.6 yrs)People aged 40- 70 yrs (n=3093) and 70 yrs (n=1642) 52.9% and 49.9% were treated with L-thyroxine during follow up (Primary Care decision) Analysed outcomes for incident IHD, vascular and all cause mortality over follow up period (Cox regression MVA),L-Thyroxine treated group, 94% of people continued to take L-T4 Median dose 75g (12.5-175 g) daily,Untreated group, 1.3% developed overt hypothyroidism -(TSH 10, or FT4) 58% remained with elevated TSH 38% reverted to euthyroidism 2.5% developed low TSH,Baseline characteristics,Fatal & non-fatal vascular events 40-70 yrs,HR 0.61 (0.39- 0.95); p=0.02,All cause mortality 40-70 yrs,HR= 0.36 (0.19 0.66) ; p70 yrs,HR 0.99 (0.59- 1.33); p=0.56,All cause mortality 70 yrs,HR= 0.71 (0.56 1.08) ; p=0.11,Event rate stratified by age, LT4 vs untreated; Fatal + non fatal CV events,Degree of serum TSH elevation, Median serum TSH 6.6 mU/l Reference group (HR=1) is untreated patients,Razvi et al. Arch Intern Med; 2012,Atrial fibrillation,Summary, L-T4 treatment of SCH was associated with a lower CV mortality and CV event rate in patients 10.0 mU/l,Who should we consider treating?, Symptoms or signs of hypothyroidism Age less than 70 yrs TSH 7.0 mU/l Goitre High vascular risk including Ischaemic heart disease Diabetes Dyslipidaemia, 380 attendees at ITC 2010 Electronic voting system Female, serum TSH 6.8,Pearce, Wemeau, Vaisman. Eur Thyroid J 2012,Subclinical hyperthyroidism,What is normal in extreme old age?,