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www.excemed.org
IMPROVING THE PATIENT’S LIFE THROUGH
MEDICAL EDUCATION
Diabetes and thyroid disorders in clinical practice today
St Petersburg, Russia - April 25, 2015
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Salman Razvi Queen Elizabeth Hospital Gateshead, UK
Declared no potential conflict of interest.
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www.excemed.org
IMPROVING THE PATIENT’S LIFE THROUGH
MEDICAL EDUCATION
SUBCLINICAL HYPOTHYROIDISM Salman Razvi
Newcastle University
St Petersburg, Russia - April 25, 2015
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Format
•TSH reference range and prevalence
•Causes
•Effects
•Impact of treatment (CV risk)
•Summary
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‘Normal’ TSH range
Hollowell et al, JCEM 2002
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NHANES
Hollowell et al, JCEM 2002
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Subclinical hypothyroidism (SCH)
•Elevated serum TSH level in presence of normal serum thyroid hormone levels
•Affects 5-10% of the population
•More than 85% of patients with SCH have TSH levels < 10mIU/L
•It is controversial whether SCH affects atherosclerosis/ CV risk/hypothyroid symptoms
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Causes of SCH
Autoimmune hypothyroidism Positive thyroid autoantibodies and/or hypo-
echogenic on ultrasound.
Treated thyroid or neck disease History of radioiodine or surgical treatment
Drugs Lithium, amiodarone, anticonvulsants (due to increased T4 metabolism), interferon, sunitinib.
Inadequately treated thyroid disease Non-compliance, under treatment with LT4, malabsorption, other substances (iron, calcium); overtreatment with antithyroid drugs
Transiently raised TSH levels Non-thyroidal illness (recovery phase)
Systemic diseases with thyroid involvement
Sarcoidosis, amyloidosis, lymphoproliferative disorders, haemochromatosis
TSH receptor gene mutations Several loss of function gene mutations have been found in non-autoimmune SHypo
Rare conditions Pituitary tumours secreting low bioactivity TSH
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Effects of SCH
•Progression to overt hypothyroidism
•Symptoms and QoL
•Lipids and BP
•CV risk
•Pregnancy
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Copyright ©2010 The Endocrine Society
Predicted odds of hypothyroidism from a logistic regression model split at a baseline TSH of 2.5 mU/liter (vertical dotted line)
Progression to overt hypothyroidism
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Overall risk of progression??
Diez JJ, JCEM 2004
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Stable SCH???
Karmisholt et al JCEM 2008
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Symptoms
Canaris GJ et al, Arch Intern Med 2000
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SF36 (SCH vs Euthyroid)
Razvi S et al, Eur J Endocrinol 2005
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Cholesterol levels
Canaris GJ et al, Arch Intern Med 2000
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SCH and BP
Asvold et al, JCEM 2007
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Uncertainty about IHD/mortality in SCH
• Vanderpump et al,1996 No difference
• Hak et al, 2000 Increased in women more than 55 yrs
• Parle et al, 2001 No increased mortality
• Imaizumi et al, 2004 Increased in men
• Gussekloo et al, 2004 Protective in those aged >85 years
• Walsh et al, 2005 Increased prevalent and incident IHD
• Rodondi et al, 2005 Increased risk of CHF but not IHD
• Cappola et al, 2006 No increased risk of IHD or mortality
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Rotterdam study
Hak et al, Ann Intern Med 2000
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Razvi et al, JCEM 2010
Re-analysis of the Whickham cohort
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Leiden 85+ study
Gussekloo et al, JAMA 2004
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Incident IHD mortality in SCH
Razvi S et al, JCEM 2008
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Surks & Hollowell, 2007
• Median TSH 1.26 in 20s 1.90 in 80+ • 97.5% TSH 3.56 in 20s 7.49 in 80+
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Does thyroid function change with aging in the same individual?
Bremner et al, JCEM 2012
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Large IPD meta-analysis
Rodondi et al, JAMA 2010
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Is LT4 treatment beneficial?
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Not everyone agrees that treatment of subclinical hypothyroidism is an unknown.................
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2001
L-Thyroxine n=31) Placebo (n=32)
Before After Before After p value
TSH (mIU/L) 12.8 3.1 10.7 9.9 <0.001
FT4 (pmol/L) 11.6 17.8 12.0 12.3 <0.001
T3 (nmol/L) 2.0 1.7 1.9 1.9 <0.001
TC (mmol/L) 6.3 6.1 6.1 6.0 0.01
LDLc (mmol/L) 4.0 3.7 3.8 3.7 0.004
HDLc (mmol/L) 1.7 1.7 1.6 1.6 0.47
Trigs (mmol/L) 1.3 1.3 1.5 1.5 0.77
Apo A1 (g/L) 1.82 1.76 1.71 1.73 0.1
Apo B (g/L) 1.25 1.15 1.22 1.17 0.04
Meier et al, JCEM
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2007
L-Thyroxine (n=50) Placebo (n=50)
Before After Before After p value
TSH (mIU/L) 5.3 0.5 5.3 5.2 <0.001
FT4 (pmol/L) 13.6 20.5 13.7 13.5 <0.001
FT3 (pmol/L) 4.7 5.3 4.7 4.7 <0.001
TC (mmol/L) 6.0 5.7 6.0 6.0 <0.001
LDLc (mmol/L) 3.6 3.4 3.6 3.7 0.008
HDLc (mmol/L) 1.7 1.6 1.6 1.7 0.02
Trigs (mmol/L) 1.2 1.3 1.2 1.3 0.26
Apo A1 (g/L) 1.52 1.51 1.47 1.56 0.02
Apo B (g/L) 1.04 1.02 1.04 1.08 0.01
Razvi et al, JCEM
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Razvi et al Arch Intern Med 2012
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Event rate stratified by age
Razvi et al, Arch Intern Med 2012
• LT4 vs untreated; Fatal + non fatal CV events
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Risks/benefits of treatment
• Risk of overtreatment ≈ 10-33% (AF, osteoporosis)
• A proportion will revert to euthyroidism
• In some individuals (e.g. very elderly), slightly high TSH may be normal and possibly beneficial (Hollowell et al, 2002; Gussekloo et al, 2005)
• Relevance of some ‘benefits’ unclear (e.g. Echo parameters)
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ETA Guidelines
Pearce et al, ETJ 2013
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Summary
• Good evidence that SCH is associated with CVD in younger individuals.
• Moderate evidence that SCH may be “protective” in very elderly individuals.
• LT4 treatment is beneficial in alleviating symptoms and some CV risk factors in the right patient.
• Younger patients with sustained SCH should be offered a trial of treatment.
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Thank you!
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www.excemed.org
IMPROVING THE PATIENT’S LIFE THROUGH
MEDICAL EDUCATION
Diabetes and thyroid disorders in clinical practice today
St Petersburg, Russia - April 25, 2015