5/28/2013 Pesky Thyroid Problems UCSF Internal Medicine Updates May 20 th , 2013 Case • 45 yow comes to see you complaining of fatigue, depressive symptoms and weight gain over the past year. Exam: 80 kg, BMI 32, dry skin Would you screen for thyroid disease? A) Yes B) No 1
5/28/2013 Cooper and Biondi, Lancet , 379:1142; 2012. 3 Case for Routine Screening 65 yow followed in endocrine for primary hyperparathryoidism and DM2. Date TSH 6/2002 1.30 10/2004 1.37 11/2005 1.31 12/2006 1.63 5/2007 1.78 5/2008 1.65 2/2009 1.37 7/2009 1.16 5/2010 1.12 3/2011 1.55 9/2011 1.17 4 2
5/28/2013 Screening for Thyroid Disease • If you do check a TSH and it’s completely normal, there is no need to recheck for 5 years unless there is a clinical change • “ Screening” is recommended for Newborns • DM1, Down Syndrome, Turner’s Syndrome, • Addision’s disease Amiodarone, lithium • New onset a.fib. • History of neck irradiation • • Consider screening prior to pregnancy 5 Case • 45 yow comes to see you complaining of fatigue, depressive symptoms and weight gain over the past year. Exam: 80 kg, BMI 32, dry skin • TSH 8.9 H (0.45-4.20) What now? a) Treat with levothyroxine b) Order thyroid peroxidase antibody (TPO) c) Recheck a TSH d) Recheck a TSH and Free T4 6 3
5/28/2013 Factors Altering TSH • Diurnal variation (nocturnal surge resulting in highest values in the morning and lower values in the afternoon) • Non-thyroidal illness • Assay Issues o Heterophile antibodies o Assay variability 7 Case • 45 yow comes to see you complaining of fatigue, depressive symptoms and weight gain over the past year. Exam: 80 kg, BMI 32, dry skin • TSH 8.9 H (0.45-4.20) • TSH 12 H (0.45-4.20) FT4 0.63 L (0.65-1.78) Hypothyroid - Treat 8 4
5/28/2013 Case 45 yow comes to see you complaining of fatigue, depressive symptoms and weight gain over the past year. Exam: 80 kg, BMI 32, dry skin Thyroid: firm, normal size TSH 8.9 H (0.45-4.20) TSH 9.2 H (0.45-4.20) FT4 1.1 (0.65-1.78) Subclinical Hypothyroidism 9 Case 45 yow comes to see you complaining of fatigue, depressive symptoms and weight gain over the past year. Exam: 80 kg, BMI 32, dry skin Thyroid: firm, normal size TSH 8.9 H (0.45-4.20) TSH 9.2 H (0.45-4.20) FT4 1.1 (0.65-1.78) – Normal for the population A given individual will have a narrower normal range. 10 5
5/28/2013 Relationship of TSH to Free T4 Quest Diagnostics, D. Fisher, J. Nelson 11 Case 45 yow comes to see you complaining of fatigue, depressive symptoms and weight gain over the past year. Exam: 80 kg, BMI 32, dry skin Thyroid: firm, normal size TSH 8.9 H (0.45-4.20) TSH 9.2 H (0.45-4.20) FT4 1.1 (0.65-1.78) What now? a) Treat with levothyroxine b) Order thyroid peroxidase antibody (TPO), treat if positive c) Recheck a TSH in 6 months d) Recheck a TSH and Free T4 in 6 months 12 6
5/28/2013 Subclinical Hypothyroidism • Prevalence in US o 4.3% NHANES III o 9.5% Colorado Mall Study • Prevalence o Increased in iodine sufficient areas o Increases with age o Increased in women o Decreased in African Americans • Only 25% of people with subclinical hypothryoidism have TSH > 10 13 Race and Ethnicity Specific TSH Distributions – NHANES III Hollowell J G et al. JCEM 2002;87:489-499 14 7
5/28/2013 Subclinical Hypothyroidism Deciding When to Treat • There is no clear right or wrong answer • Consensus Statement 2004 1 Routine treatment for TSH 4.5-10 mIU/L is not warranted as there is no evidence of benefit. Treat for TSH > 10 mIU/L. • Subsequently societies took issue with this recommendation as lack of evidence is not the same as evidence against • Newest data is causing a push for more treatment • There is no clear right or wrong answer 1 JAMA 2004; 291:228-238 15 Subclinical Hypothyroidism Deciding When to Treat • Reasons to treat o Prevent progression to frank hypothyroidism o Improve symptoms o Improve lipids o Pregnant/considering pregnancy o Associated with increased mortality and/or morbidity • Reasons not to treat o Treatment has not yet been shown to improve mortality in a prospective trial o Expense o Could do harm 16 8
5/28/2013 Progression to Hypothyroidism Increased likelihood for the development of overt hypothyroidism : o Female, older, antibody positive, higher TSH Approximately 2.5% of antibody negative individuals per year progress to overt hypothryoidism and 4.5% of TPO antibody positive individuals Women with +TPO antibodies have a 38 fold increased risk of hypothyroidism TSH normalizes in about 5% of individuals at one year Almost half of patients with subclinical hypothyroidism (43%) will have progressed in 10 years Tunbridge et al., Clinical Endocrinology 7:481, 1977; Vanderpump et al., Clinical Endocrinology 17 43:55, 1995; Walsh et al., JCEM 95:1095, 2010 Progression to Hypothyroidism Increased likelihood for the development of overt hypothyroidism : o Female, older, antibody positive, higher TSH Approximately 2.5% of antibody negative individuals per year progress to overt hypothryoidism and 4.5% of TPO antibody positive individuals Women with +TPO antibodies have a 38 fold increased risk of hypothyroidism TSH normalizes in about 5% of individuals at one year The majority of patients with subclinical hypothyroidism (57%) will not have progressed in 10 years Tunbridge et al., Clinical Endocrinology 7:481, 1977; Vanderpump et al., Clinical Endocrinology 18 43:55, 1995; Walsh et al., JCEM 95:1095, 2010 9
5/28/2013 Subclinical Hypothyroidism Deciding When to Treat • Reasons to treat o Prevent progression to frank hypothyroidism o Improve symptoms o Improve lipids o Pregnant/considering pregnancy o Associated with increased mortality and/or morbidity • Reasons not to treat o Treatment has not yet been shown to improve mortality in a prospective trial o Expense o Could do harm 19 Subclinical Hypothyroidism Deciding When to Treat • Reasons to treat o Prevent progression to frank hypothyroidism o Improve symptoms o Improve lipids o Pregnant/considering pregnancy o Associated with increased mortality and/or morbidity • Reasons not to treat o Treatment has not yet been shown to improve mortality in a prospective trial o Expense o Could do harm 20 10
5/28/2013 Subclinical Hypothyroidism Deciding When to Treat • Reasons to treat o Prevent progression to frank hypothyroidism o Improve symptoms o Improve lipids o Pregnant/considering pregnancy o Associated with increased mortality and/or morbidity • Reasons not to treat o Treatment has not yet been shown to improve mortality in a prospective trial o Expense o Could do harm 21 Maternal Thyroid and Kid IQ • Studied children of women with undiagnosed hypothryoidism (TSH 13) 1 Offspring IQ Age 7 Haddow et al, NEJM , 341:549; 1999. 22 11
5/28/2013 Maternal Thyroid and Kid IQ Antenatal screening at 12w3d gestation, 21,800 • women, TSH 3-4. Treatment for hypothryoidism didn’t improve cognitive function at age 3 1 Study Flaws • Fetal thyroid develops at wk 12 o Median TSH 3.8/3.1 o Half of those enrolled had a low FT4 o Age 3 might be to early to study o Guidelines don’t recommend antenatal screening • however, prenatal screening is likely more beneficial 1 Lazarus et al, NEJM , 366:493; 2012. 23 Subclinical Hypothyroidism Deciding When to Treat • Reasons to treat o Prevent progression to frank hypothyroidism o Improve symptoms o Improve lipids o Pregnant/considering pregnancy o Associated with increased mortality and/or morbidity • Reasons not to treat o Treatment has not yet been shown to improve mortality in a prospective trial o Expense o Could do harm 24 12
5/28/2013 Subclinical Hypothyroidism Long Term Effects – CVD • CHD o Good prospective studies give discordant results for CHD o Meta-analysis suggests significant increased CHD risk 1 - Age < 65 OR 1.51 (1.09-2.09); age > 65 OR 1.05 NS - TSH > 10 OR 1.69 (0.64-4.45); TSH > 4.5 OR 1.06 NS • CV Dysfunction o Diastolic and systolic dysfunction o Small trials shows improvement when made euthyroid • CHF Events o Health ABC 2 increased events if TSH > 7 o CV Health Study 3 RR for events 1.9 if TSH > 10 1 Osch Ann Intern Med, 2008; 2 Rondondi Arch Int Med 2005; 3 Rondondi JACC 2008 25 Subclinical Hypothyroidism and the Risk of Coronary Heart Disease and Mortality By Degree of TSH Elevation Patient level metananalysis of individual patient data from 11 prospective cohort studies Bodondi et al., JAMA . 2010;304:1365-1374. 13
5/28/2013 Subclinical Hypothyroidism and the Risk of Coronary Heart Disease and Mortality By Age Bodondi et al., JAMA . 2010;304:1365-1374. Subclinical Hypothyroidism Deciding When to Treat • Reasons to treat o Prevent progression to frank hypothyroidism o Improve symptoms o Improve lipids o Pregnant/considering pregnancy o Associated with increased mortality and/or morbidity • Reasons not to treat o Treatment has not yet been shown to improve mortality in a prospective trial o Expense o Could do harm 28 14
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