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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
Salman Razvi Queen Elizabeth Hospital Gateshead, UK
Declared no potential conflict of interest.
www.excemed.org
IMPROVING THE PATIENT’S LIFE THROUGH
MEDICAL EDUCATION
SUBCLINICAL HYPOTHYROIDISM Salman Razvi
Newcastle University
St Petersburg, Russia - April 25, 2015
Format
•TSH reference range and prevalence
•Causes
•Effects
•Impact of treatment (CV risk)
•Summary
‘Normal’ TSH range
Hollowell et al, JCEM 2002
NHANES
Hollowell et al, JCEM 2002
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
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
Effects of SCH
•Progression to overt hypothyroidism
•Symptoms and QoL
•Lipids and BP
•CV risk
•Pregnancy
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
Overall risk of progression??
Diez JJ, JCEM 2004
Stable SCH???
Karmisholt et al JCEM 2008
Symptoms
Canaris GJ et al, Arch Intern Med 2000
SF36 (SCH vs Euthyroid)
Razvi S et al, Eur J Endocrinol 2005
Cholesterol levels
Canaris GJ et al, Arch Intern Med 2000
SCH and BP
Asvold et al, JCEM 2007
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
Rotterdam study
Hak et al, Ann Intern Med 2000
Razvi et al, JCEM 2010
Re-analysis of the Whickham cohort
Leiden 85+ study
Gussekloo et al, JAMA 2004
Incident IHD mortality in SCH
Razvi S et al, JCEM 2008
Surks & Hollowell, 2007
• Median TSH 1.26 in 20s 1.90 in 80+ • 97.5% TSH 3.56 in 20s 7.49 in 80+
Does thyroid function change with aging in the same individual?
Bremner et al, JCEM 2012
Large IPD meta-analysis
Rodondi et al, JAMA 2010
Is LT4 treatment beneficial?
Not everyone agrees that treatment of subclinical hypothyroidism is an unknown.................
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
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
Razvi et al Arch Intern Med 2012
Event rate stratified by age
Razvi et al, Arch Intern Med 2012
• LT4 vs untreated; Fatal + non fatal CV events
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)
ETA Guidelines
Pearce et al, ETJ 2013
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.
Thank you!
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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