thyroid hormones in health and disease dr s razvi endocrinologist and senior lecturer 1 st october...
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Thyroid hormones in health and disease
Dr S RazviEndocrinologist and Senior Lecturer
1st October 2013
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Agenda
• Physiology
• Clinical data and evidence
• Some real life cases – interactive
• Summary
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TRHHypothalamus
Pituitary
TSH TSH
Thyroid Gland
T4
T3
Hypothalamic-Pituitary-Thyroid Axis
Clinical Utility
• TSH reflects tissue thyroid hormone actions
• TSH for diagnosis of hypothyroidism and thyrotoxicosis
• TSH as an index of therapeutic success and potential toxicity
Adapted from Merck Manual of Medical Information. ed. R Berkow. 704:1997.
T4 T3 Liver, Muscle
T4 T3
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Reference ranges
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2.5th
0.4 mU/L 97.5th
4.0 mU/L
Individual vs population reference range(e.g., serum TSH)
A B
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Factors affecting thyroid function (TSH)
• Age
• Gender
• Smoking• Iodine status • Illness • Pregnancy
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Surks & Hollowell, 2007
Age group (yrs) Median 97.5th centile
20 – 30 1.26 3.56
> 80 1.90 7.49
Effect of age
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Clinical consequences of raised or low TSH
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Clinical consequences of raised or low TSH
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Raised TSH
• Cholesterol increases with TSH• Associated with heart disease in younger
(<65/70 yr olds)• Higher risk of progression to overt
hypothyroidism (particularly if TPO +ve)• Associated with heart failure
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Leiden 85+ study
Gussekloo et al, JAMA 2004
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Clinical consequences of raised or low TSH
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Clinical consequences of raised or low TSH
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Low TSH
• Associated with atrial fibrillation• Osteoporosis• Higher cardiovascular mortality (only if TSH
undetectable <0.1 mU/L)• Dementia
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Pregnancy
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Every thing changes......
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5%
19%
0 5 10 15 20 25
Consequences of Mild Hypothyroidism Fetal Brain Development• Children of women with untreated hypothyroidism during
pregnancy:– Averaged 7 points lower on IQ testing*– Had a significant percentage (19%) of IQ 85
IQ Scores of 85
Control
Children
Children of Mothers withUntreated Hypothyroidism
(P<0.005)
*Full-scale Wechsler Intelligence Scale for Children. Haddow JE, et al. N Engl J Med. 1999;341:549-555.
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Guidelines for raised TSH
• If TSH > 10 consistently then treat.• For consistently raised TSH in younger people
(70 – 75 yrs) with symptoms – a trial of treatment is recommended for 3 – 6 months.
• For consistently raised TSH in older people (> 75 yrs) – wait and watch policy.
• Pregnancy: should be treated with aim for low normal TSH
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Guidelines for low TSH
• If TSH consistently < 0.1 (suppressed) AND if other risk factors (AF, osteoporosis) or symptoms – treat.
• If TSH mildly low and asymptomatic - wait and watch policy.
• In pregancy, low TSH is of no consequece (normal in 1st trimester).
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Case 1• 45 year old woman• Seen by GP for tiredness• Examination and all other Ix normal• TSH 6.6 mIU/L (0.4 – 4.0)• FT4 15.6 pmol/L (9 – 22)• TPO positive
• What is the diagnosis?• Is treatment beneficial?
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Case 2
• 86 yr old man with forgetfulness• TSH 7.4 mU/L FT4 15.4 pmol/L
• Treat?
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Case 3
• 34 yr old lady trying to conceive• TSH 5.4 mU/L FT4 12 pmol/L
• Treat?
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Case 4
• 32 yr old lady with weight loss, palpitations and tremor.
• TSH<0.01 mU/L, FT4 42 pmol/L
• Next step?
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Case 4 cont
• Tc uptake thyroid scan – 0% uptake• TSH receptor and TPO antibody – negative
• Diagnosis?
• Thyroiditis• TSH 3.5 mU/L four months later.
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Case 5
• 20 yr old lady• 8/40 pregnant. On LT4 100 mcg/day
• What would you do next?Check TFTsPossibly increase LT4 to 125 mcg/dayRefer her to antenatal endocrine clinic
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Case 6
• 68 yr old woman presents with• Next step?
TFT, TPORefer to endocrinology / ENTUSS +/- FNA (3-5% cancer)
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Case 7
• 34 yr old man on LT4 (150 mcg/day) after thyroidectomy for Graves’ disease
• TSH 13.5 mU/L FT4 12.6 pmol/L
• Next step?Intermittent compliance (mainly)
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Excessive Thyroxine Therapy
Inadequate Thyroxine Therapy
30%
20%
10%
Ross, 1990 Parle,
1993
Canaris, 2000 Hollowell, 2002
27%
21%
14%
18% 18%
22%
15%
18%
10%
20%
30%
Ross DS, et al. JCEM.1990;71:764-769. Parle JV, et al. Br J Gen Pract. 1993;43:107-109. Canaris GJ, et al. Arch Intern Med. 2000;160:526-534. Hollowell J, et al. JCEM. 2002;87:489-499.
How Common Is Suboptimal Thyroxine Therapy?
32% 48% 40% 33%
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Conditions and medications affecting thyroid function (including those on
LT4)• Iron• Calcium• PPI• Coeliac disease• Pernicious anaemia• Amiodarone• LithiumConsider taking LT4 at a different time prior to
increasing the doseDifferent formulations may have varying strengths
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Take home messages
• Thyroid function is affected by multiple processes.
• Slightly high TSH in elderly may not have an adverse impact.
• In pregnancy, high TSH should always be treated.• Overt hyperthyroidism should always be referred
to endocrinologists for further assessment.• Thyroid nodules need specialist assessment with
USS and ?FNA
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Thank you!