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Thyroid hormones in health and disease Dr S Razvi Endocrinologist and Senior Lecturer 1st October 2013 Agenda • Physiology • Clinical data and evidence • Some real life cases – interactive • Summary Hypothalamic-Pituitary-Thyroid Axis Clinical Utility Hypothalamus TRH • TSH reflects tissue thyroid hormone actions Pituitary • TSH for diagnosis of hypothyroidism and thyrotoxicosis TSH TSH • TSH as an index of therapeutic success and potential toxicity T4 T3 Thyroid Gland T4 Adapted from Merck Manual of Medical Information. ed. R Berkow. 704:1997. T4 T3 Liver, Muscle T3 Reference ranges Individual vs population reference range (e.g., serum TSH) A 2.5th 0.4 mU/L B 97.5th 4.0 mU/L Factors affecting thyroid function (TSH) • Age • Gender • • • • Smoking Iodine status Illness Pregnancy Effect of age Age group (yrs) Median 97.5th centile 20 – 30 1.26 3.56 > 80 1.90 7.49 Surks & Hollowell, 2007 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...... 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 Children of Mothers with Untreated Hypothyroidism Control 5% Children 0 5 19% (P<0.005) 10 *Full-scale Wechsler Intelligence Scale for Children. Haddow JE, et al. N Engl J Med. 1999;341:549-555. 15 20 25 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 TFTs Possibly increase LT4 to 125 mcg/day Refer her to antenatal endocrine clinic Case 6 • 68 yr old woman presents with • Next step? TFT, TPO Refer to endocrinology / ENT USS +/- 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) How Common Is Suboptimal Thyroxine Therapy? 30% Excessive Thyroxine Therapy 20% Inadequate Thyroxine Therapy 10% 10% 21% 18% 14% 18% 20% 22% Ross, 1990 30% 32% 18% 27% Canaris, 2000 Hollowell, 2002 40% 33% Parle, 1993 48% 15% 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. Conditions and medications affecting thyroid function (including those on LT4) • Iron • Calcium • PPI • Coeliac disease • Pernicious anaemia • Amiodarone • Lithium Consider taking LT4 at a different time prior to increasing the dose Different 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!