hypothyroidism thyroid club亚临床甲状腺功能减退甲状腺俱乐部课件

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 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 AuthorNumberCardiovascular events Cardiovascular mortality All cause mortality Singh 2008 13,2671.53 (1.311.79)1.28 (1.021.60)1.12 (0.99-1.26) Ochs 2008 14,4491.20 (0.97-1.49)1.18 (0.98-1.42)1.12 (0.99-1.26) Haentjens 2008 14,619NINI1.22 (0.95-1.57) Razvi 2008 29,0221.23 (1.02 1.48)1.09 (0.84 1.41)NI Rodondi 2010 55,2871.18 (0.99- 1.42)1.14 (0.99- 1.32)1.09 (0.96-1.24) Thvilum 2012 35,740NINI1.17 (1.00-1.37) Relative risks (5-95% confidence intervals) Meta-summary of meta-analyses AuthorNumberCardiovascular events Cardiovascular mortality All cause mortality Singh 2008 13,2671.53 (1.311.79)1.28 (1.021.60)1.12 (0.99-1.26) Ochs 2008 14,4491.20 (0.97-1.49)1.18 (0.98-1.42)1.12 (0.99-1.26) Haentjens 2008 14,619NINI1.22 (0.95-1.57) Razvi 2008 29,0221.23 (1.02 1.48)1.09 (0.84 1.41)NI Rodondi 2010 55,2871.18 (0.99- 1.42)1.14 (0.99- 1.32)1.09 (0.96-1.24) Thvilum 2012 35,740NINI1.17 (1.00-1.37) Relative risks (5-95% confidence intervals) M Thvilum, F Brandt, TH Brix 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 Hazard Ratio for vascular events P value for trend TSH 6.6 or lessTSH 6.6 40-70 yrs0.62 (0.39-0.96)0.41(0.26-0.81)0.007 70 yrs1.02 (0.66-1.82)1.19 (0.74-1.80)NS Median serum TSH 6.6 mU/l Reference group (HR=1) is untreated patients Razvi et al. Arch Intern Med; 2012 Atrial fibrillation Hazard Ratio for AF/ month L-T4 exposure 5-95% CI 40-70 yrs0.9980.995- 1.001 70 yrs1.0000.999- 1.001 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? Mariotti et al. JCEM 1993 Age-related decline in median TSH levels (ill people excluded) What is normal in extreme old age? Mariotti et al. JCEM 1993 Age related decline in T3 levels (ill people excluded) FT4 (and TT4) levels remain constant Magri et al. 2002 Change to function of HPT axis Reduced hepatic thyroid hormone clearance -glucuronidation, sulfation Reduced T4 to T3 conversion Reduced type 1 deiodinase activity Blunted diurnal TSH secretion Flattened TSH response to TRH Subclinical Hyperthyroidism Degrees of hyperthyroidism Degrees of hyperthyroidism 87% remained 5.0 0.4- 5.0 TSH (mU/l) Cardiovascular Health Study 3233 US community dwelling individuals over 65, mean age 73 AF rate 2.0 (CI 1.3-3.0) in Sub Hyper Cappola et al. JAMA 2006 Overall survival “Circulatory” survival Parle et al. Lancet 2001 Community-living 60 year olds; overt thyroid disease excluded Gussekloo et al. JAMA 2004; 292:2591 TSH4.8mU/l Normal TSH TSH 50%) will have subsequently normalised TSH levels during follow up How to interpret adverse outcome of low TSH/ Subclinical hyperthyroidism group? Formulation 1 Low TSH represents true endogenous hyperthyroidism Adverse cardiac events & AF are an expected consequence of excess thyroid hormones Need to treat for hyperthyroidism Formulation 2 Low TSH represents an effect of ageing and reduced turnover of pituitary-thyroid axis (biomarker for age) Decreased hepatic thyroid hormone clearance, blunted diurnal TSH secretion & flattened TSH response to TRH with ageing Adverse cardiac events & AF (+ OP & dementia) simply are consequences of “biological age” No need to treat for hyperthyroidism Formulation 1.5 Both the previous suggestions are true Adverse cardiac effects are due to excess thyroid hormones in some In others, low TSH is a biomarker for aging & hence associated with poor outcome Need to distinguish between these two groups to treat some for hyperthyroidism Cardiovascular Health Study AF rate little different between grade I and grade II SH TSH mU/l NAF rate/1000 pt yrs Hazard ratio (5-95% CI) Euthyroid 2502311.00 (ref) 75 No symptoms Below median FT3, FT4 -ve Antibodies, scan No complications Algorithm Mitchell & Pearce. Clin Endo 2010 * Rare causes Pituitary disease Tumour hCG Repeat testing May need investigations Maybe yearly re-testing Maybe never re-test “There is no reason to treat a patient with subclinical hyperthyroidism for thyrotoxicosis, provided they are in sinus rhythm” Vaidya B et al. Clin Endo 2008 27% agree 55% disagree Peer opinion: BTA Survey