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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

2004

Monzani et al, JCEM 2004

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