Thyroid hormones in health and disease

Dr S RazviEndocrinologist and Senior Lecturer

1st October 2013

Agenda

• Physiology

• Clinical data and evidence

• Some real life cases – interactive

• Summary

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

Reference ranges

2.5th

0.4 mU/L 97.5th

4.0 mU/L

Individual vs population reference range(e.g., serum TSH)

A B

Factors affecting thyroid function (TSH)

• Age

• Gender

• Smoking• Iodine status • Illness • Pregnancy

Surks & Hollowell, 2007

Age group (yrs) Median 97.5th centile

20 – 30 1.26 3.56

> 80 1.90 7.49

Effect of age

Clinical consequences of raised or low TSH

Clinical consequences of raised or low TSH

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

Leiden 85+ study

Gussekloo et al, JAMA 2004

Clinical consequences of raised or low TSH

Clinical consequences of raised or low TSH

Low TSH

• Associated with atrial fibrillation• Osteoporosis• Higher cardiovascular mortality (only if TSH

undetectable <0.1 mU/L)• Dementia

Pregnancy

Every thing changes......

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.

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

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).

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?

Case 2

• 86 yr old man with forgetfulness• TSH 7.4 mU/L FT4 15.4 pmol/L

• Treat?

Case 3

• 34 yr old lady trying to conceive• TSH 5.4 mU/L FT4 12 pmol/L

• Treat?

Case 4

• 32 yr old lady with weight loss, palpitations and tremor.

• TSH<0.01 mU/L, FT4 42 pmol/L

• Next step?

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.

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

Case 6

• 68 yr old woman presents with• Next step?

TFT, TPORefer to endocrinology / ENTUSS +/- FNA (3-5% cancer)

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)

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%

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

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

Thank you!