Abnormal Thyroid Function tests

1. Abnormal Thyroid Function tests

2. Thyroid hormone release hypothalamus -ve TRH +ve, Somatostatin -ve -ve pituitary TSH thyroid T4 - 90% T3 - 10% • thyroid hormones: • directly inhibit TSH release • inhibit the effects of TRH on pituitary • promote somatostatin release

3. Thyroid hormone metabolism 5’deiodinase type 1; liver, kidney, decreased in illness/starvation T4 5 deiodinase; 5’deiodinase type 2; pituitary, brain T3 rT3 thyroid hormone receptor binding DNA transcription

4. TFTs

5. TSH

7. TFTs in the sick

8. Hyperthyroidism • High t4/t3, suppressed TSH • Differential diagnosis: • Graves’ • Autonomous nodules, toxic MNG • Hyperemesis • thyroiditis • factitious/ectopic

9. Causes of hyperthyroidism

10. Multisystem Skin sweating onycholysis hyperpigmentation pruritis vitiligo / alopecia hair loss Eyes lid lag (100% - sympathetic activity opthalmopathy in Graves’ Clinical features of hyperthyroidism

11. Dermopathy in Graves’

12. Multisystem GI weight loss (inc calorigenesis, gut motility hyperphagia dysphagia (goitre) vomiting LFTs GU system urinary frequency polydipsia oligomanorrhoea (inc SHBG) gynaecomastia, erectile dysfunction, loss of libido (T-E conversion) Clinical features of hyperthyroidism

13. Multisystem Skeleton loss in cortical bone density increase in bone resorption increased calcium Neuromuscular tremor hyperactive reflexes emotional lability anxiety prox muscle weakness hypokalemic periodic paralysis myaesthenia Clinical features of hyperthyroidism

14. Pathogenesis of Graves’ • An autoimmune condition • characterised by stimulating antibodies to the TSHR

15. HLA and Graves

16. TSH receptor

17. TSHRab

18. Antithyroid antibodies……..

19. Treatment options for Graves’

20. PTU vs Carbimazole

21. Thionamide dosage…..

22. Predicting relapse ….

23. Radioiodine and TAO

24. Subclinical hyperthyroidism • Low TSH normal fT4 (and fT3) • common and controversial • 1210 subjects >60y - 6.3% men and 5.5% women had TSH <0.5 • Persistent in 88% of subjects with TSH<0.05 (20% TSH 0.05-0.5)

25. Subclinical hyperthyroidism

26. Subclinical hyperthyroidism

27. Subbclinical hyperthyroidism • Associated with increased mortality • 1200 subjects >60y • 65% mortality with suppressed TSH • 55% mortality with normal TSH

28. Thyroid storm

29. Thyroiditis……..

30. Thyroiditis………..

32. Hypothyroidism

33. Hypothyroidism - the cause • Important to determine the cause: • usually primary autoimmune….but.. • May be transient • subacute lymphocytic or postpartum thyroiditis • drug induced (eg lithium or iodine containing) • OR • maybe manifestation of pituitary/hypothalamic disease

34. Hypothyroidism - clinical manifestations • Generalised slowing of metabolic processes • fatigue • slow movement • slow speech • cold intolerance • constipation • weight gain • bradycardia • slow relaxation of reflexes

35. Hypothyroidism - clinical manifestations • Accumulation of matrix GAGs • coarse hair • coarse skin • puffy facies • macroglossia • hoarse voice

36. Hypothyroidism

37. Hypothyroidism - problems • My TFTs are normal but I still feel awful • temptation is to increase T4 but low TSH is bad for you • check other causes of fatigue and consider CFS • rarely can try combination T4+T3 • not really proven in RCT • difficult to monitor

38. Subclinical hypothyroidism • Normal fT4, high (5-25) TSH • Vague and non specific symptoms • Prevalence: 7-8% women, 3-4% men • More common in patients with other AI • High TSH and high anti TPO abs develop overt hypothyroidism at 4.5% per year

39. Subclinical hypothyroidism • Do we need to treat with T4 • 4 RCTs suggest benefit • improvement in symptom scores and psychometric test results • improvement in lipid profile • improvement in myocardial function

40. Subclinical hypothyroidism • Do we need to treat with T4 • risk factor for impaired development in pregnancy - lower IQ at age 7 (103 vs 107, p<0.006)

41. Subclinical hypothyroidism • Do we need to treat with T4 • concensus view 1998 (ACP) - not enough data!! • General view - because of theoretical reduction in CVS risk factors, prevention of goitre growth and improvement in wellbeing - TREAT - but care in the elderly and avoid suppressing TSH

43. Interpretation of abnormal TFTS Usually straightforward……...

44. Case 1: 30 year old woman who felt anxious and shaky and had a pulse of 94/min Reference ranges fT4 9.1-23.8 pmol/L fT3 2.5-5.3 pmol/L TSH 0.49-4.67 mIU/L • fT4 37.0, fT3 12.6, TSH <0.05 interpret these results • treated with I131 and carbimazole 2/12 later: fT4 21.0, fT3 4.6, TSH <0.05 comment on these results • 2/12 later: fT4 7.2, fT3 2.2, TSH <0.05 comment on these results • 2/12 later: fT4 6.9, fT3 2.2, TSH 1.90

45. Case 1 - use of TFT’s in treatment of hyperthyroidism • Thyrotroph cells may remain suppressed for several months after thyrotoxicosis • TSH is not a useful marker for monitoring the initial efficacy of treatment for hyperthyroidism

46. Case 2 - 49 year old woman c/o tiredness & weakness Reference ranges fT4 9.1-23.8 pmol/L fT3 2.5-5.3 pmol/L TSH 0.49-4.67 mIU/L • fT4 14.5 pmol/L • TSH 6.5 mIU/L • no medication • interpret these results

47. TSH normal range frequency 0.35 1.5 5.5 TSH (mIU/L)

48. Probability of developing hypothyroidism over 20 years (BMJ 1997; 314: 1175)

49. Compensated (subclinical) hypothyroidism • Low normal fT4 maintained by increased pituitary drive • Gradual deterioration in thyroid function • Recent recommendations state such patients should receive T4 if microsomal (thyroid peroxidase) Ab +ve • If Ab -ve and TSH <10 mIU/L then watch and wait • Benefits of treatment: symptomatic improvement, slight reduction in cholesterol, reduced progression of atherosclerotic disease (DTB January 1998, BMJ 1996; 313: 539)

50. Case 3 - 80 year old woman with breast cancer and liver secondaries • TFT requested as a screening test: fT4 16.9 pmol/L fT3 1.1 pmol/L TSH 2.3 mIU/L • Interpret these results Reference ranges fT4 9.1-23.8 pmol/L fT3 2.5-5.3 pmol/L TSH 0.49-4.67 mIU/L