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GP LECTURE NOV 2009

GP LECTURE NOV 2009. INTERPRETATION OF BIOCHEMISTRY RESULTS POTENTIAL PITFALLS (with short cases) & FREQUENT ADVICE TOPICS. TFT AUTOIMMUNE TESTS IRON / FERRITIN / PORPHYRIN HYPERCALCAEMIA PROTEINURIA TUMOUR MARKERS TEST REPETOIRE ICE. THYROID FUNCTION TESTS. CAN BE MISLEADING !

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GP LECTURE NOV 2009

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  1. GP LECTURE NOV 2009 INTERPRETATION OF BIOCHEMISTRY RESULTS POTENTIAL PITFALLS (with short cases) & FREQUENT ADVICE TOPICS

  2. TFT • AUTOIMMUNE TESTS • IRON / FERRITIN / PORPHYRIN • HYPERCALCAEMIA • PROTEINURIA • TUMOUR MARKERS • TEST REPETOIRE • ICE

  3. THYROID FUNCTION TESTS CAN BE MISLEADING ! SOME ATYPICAL PATTERNS

  4. CLINICAL PRESENTATION: TACHYCARDIA INVESTIGATIONS 07/08 FT4 26.7 (9.5-22) FT3 7.8 (<6.5) DIAGNOSIS ENDOCRINE REFERRAL 09/08 FT4 25.3 FT3 7.2 CARDIAC SYMPTOMS: TACHYCARDIA HYPERTHYROIDISM REVIEW ENDOCRINOLOGIST 2 CHANGE FROM CBZ TO PTU MONITORING 01/09 FT4 19.7 TSH 7.45 FT4 20.2 TSH 11.09 FEMALE 67Y

  5. CLINICAL PRESENTATION INVESTIGATIONS 07/08 FT4 26.7 (9.5-22) FT3 7.8 (<6.5) DIAGNOSIS ENDOCRINE REFERRAL 09/08 FT4 25.3 FT3 7.2 CARDIAC SYMPTOMS HYPERTHYROIDISM DIAGNOSED REVIEW ENDOCRINOLOGIST 2 CHANGE FROM CBZ TO PTU MONITORING 01/09 FT4 19.7/20.2 TSH 7.45/11.09 TSH 4.73 (0.3-5.5) TSH 1.41 ?? REVIEW DIAGNOSIS ?? FEMALE 67Y

  6. DIFFERENTIAL DIAGNOSIS • FURTHER INVESTIGATION (20/04/09) • DCH FT4 22.3 TSH 3.23 FT3 8.5 REF LAB FT4 26.0 TSH 4.18 FT3 7.4 • HETEROPHILIC ANTIBODIES – NEGATIVE FOR FT4, TSH, FT3 • THYROID HORMONE ANTIBODIES – NEGATIVE FOR FT4, TSH • FAMILIAL DYSALBUMINAEMIC HYPERTHYROXINAEMIA – NEG • THYROID HORMONE RECEPTOR - POSITIVE

  7. THYROID HORMONE RESISTANCE Heterozygous for TRbeta mutation c.728G.A (p.Arg243Gln) Fluorescent sequencing analysis of exon 7 has detected a single base change c.728G>A. This mutation is predicted to result in an abnormal TBbeta protein (p.Arg243Gln) and has been previously associated with thyroid hormone resistance (HGMD database). Screening can be offered to Jennifer's first degree relatives, IF APPROPRIATE. Relatives having thyroid hormone tests should be aware of this condition and the importance of a normal TSH

  8. CASE 2 MALE 43Y PRESENTED TO ENDOCRINE CLINIC GOITRE AT AGE 19Y SUBTOTAL THYROIDECTOMY / CARBIMAZOLE 5Y FREE T4 61.3 (9.5-22.5) TSH 0.95 ( .3-5.5) CLINICALLY EUTHYROID POSSIBILITIES 1 EUTHYROID HYPERTHYROXINAEMIA (Unlikely / T3) 2 ASSAY INTERFERENCE (AUTOANTIBODIES TO THYROXINE) 3 THYROID HORMONE RESISTANCE

  9. FAMILY STUDIES / THYROID HORMONE RESISTANCE PATIENT AGE GOITRE FT4 TSH TREATMENT INDEX 43 + 61.3 1.9 Partial thyroidectomy / carbimazole BROTHER 1 51 + 41.8 1.95 Partial thyroidectomy 1 22 - 67.8 1.3 2 21 - 17.1 2.2 3 19 - 59.0 1.3 4 14 - 16.7 1.4 BROTHER 2 46 + 30.5 1.9 Partial thyroidectomy / carbimazole / I131 1 24 + 48.0 1.3 Carbimazole

  10. CASE 1 26 Y CAUCASIAN LADY EIGHT WEEKS PREGNANT WITH HYPEREMESIS SINGLETON PREGNANCY Free T4 = 60 pmol/L ( 9.5 - 22.0) TSH = < 0.1 mu/L Free T3 = 15 pmol/L (3.5 - 7.5) IS ANTITHYROID TREATMENT INDICATED ?

  11. TRANSIENT HYPERTHYOXINAEMIA ASSOCIATED WITH PREGNANCY

  12. CLASSIFICATION OF THYROIDITIS TYPE AETIOLOGY PAIN ESR TH Ab %RESOLVED 1Y CHRONIC AUTOIMMUNE - N/ ^ +++ 0 (Transient variant) - 100 ACUTE BACTERIAL ++++ HIGH - 100 SUBACUTE VIRAL +++ HIGH - 95 P/PARTUM AUTOIMMUNE - N/ ^ +++ 80 (Painless postpartum thyroiditis may occur in 5 - 9 % unselected women)

  13. TFT’S AND TRANSIENT THYROIDITIS

  14. CASE 6 48Y FEMALE PRESENTATION WITH WT LOSS / HEAT INTOLERANCE FREE T4 = 16.5 (9.5 - 22.0) TSH = < 0.02 (0.3-5.5) FREE T3 = 8.5 (3.5-6.5) COMMENTS ?

  15. CASE 6 48Y FEMALE PRESENTATION WITH WT LOSS / HEAT INTOLERANCE FREE T4 = 16.5 (9.5 - 22.0) TSH = < 0.02 (0.3-5.5) FREE T3 = 8.5 (3.5-6.5) COMMENTS “ T3 THYROTOXICOSIS “ THYROID EXTRACT PURCHASED OVER INTERNET.

  16. CASE 3 FEMALE 28WEEKS GESTATION TATT FREE T4 8.8 (9.5-22.0) TSH 1.2 (0.3 - 5.5) IS THYROXINE INDICATED ?

  17. FREE T4 IN PREGNANCY

  18. CASE 4 TFT REFERRAL FROM GP 28Y FEMALE CLINICAL INFORMATION TIREDNESS / LOW BP FREE T4 12.2 (9.5-22) TSH 0.21 (0.3-5.5) POSSIBLE CAUSES ?

  19. CASE 4 TFT REFERRAL FROM GP 28Y FEMALE: CLINICAL INFORMATION TIREDNESS / LOW BP FREE T4 12.2 (9.5-22)TSH 0.21 (0.3-5.5) POSSIBLE CAUSES 1 NON THYROIDAL ILLNESS 2 STEROIDS /DRUGS 3 HYPOPITUITARISM INFERTILITY PROFILE / CONSULTANT REFERRAL PARTIAL HYPOPITUITARISM

  20. DRUGS AFFECTING TSH TSH DECREASE TSH INCREASE Bromocryptine Clomiphene Carbamazepine * Iodides Corticosteroids ** Lithium Cyproheptadine Metoclopramide Dopamine Morphine Heparin Phenothiazines Levodopa Amiodarone *** Thyroxine, tri-iodothyronine 

  21. CASE 5 CLINICAL INFORMATION 68Y MALE SVT / TIREDNESS FREE T4 28.3 (9.5 - 22.0) TSH 1.12 (0.3 - 5.5) FREE T3 4.5 (3.5 - 6.5) IS PATIENT HYPERTHYROID ? WHY IS FT4 RAISED ?

  22. CASE 5 CLINICAL INFORMATION 68Y MALE SVT / TIREDNESS FREE T4 28.3 (9.5 - 22.0) TSH 1.12 (0.3 - 5.5) FREE T3 4.5 (3.5 - 6.5) IS PATIENT HYPERTHYROID ? - BIOCHEMISTRY NOT SUPPORTIVE WHY IS FT4 RAISED ? 1 ANALYTICAL 2 ? THYROID HORMONE REPLACEMENT 3 EUTHYROID HYPERTHYROXINAEMIA 4 IMPAIRED CONVERSION OF T4 TO T3 AMIODARONE INDUCED CHANGES

  23. AMIODARONE / THYROID FUNCTION

  24. AMIODARONE INDUCED THYROID DISORDERS Iodine deficientIodine sufficient

  25. Thyroxine Replacement Therapy in Primary Hypothyroidism • TSH Level This Indicates • < 0.01 miu/L Over Replacement • 0.01-0.3 miu/L Indicates Possible Over Replacement • Normal Sufficient Replacement • > 3.5 miu/L Likely under • Clinical symptomatology and TSH are the major parameters used in assessing the adequacy of replacement therapy. • T4 level is an index of recent patient compliance. • TSH may take up to 4-6 weeks to stabilise. Thus, repeat TFT following alteration of dose should only be performed after this period.

  26. PATHOLOGY HANDBOOKhttp://www.pathologydch.co.ukSpecial Test Guidelines • Rheumatic Diseases • SLE Monitoring • Eye Disorders • Vasculitic Diseases • Respiratory Disorders • Renal Disease • Antiphospholipid Disorder’s • Liver Disorders • GI Disorders • Dermatological Disorders • Endocrine Disorders • Addison’s • Primary Ovarian failure • Polyendocrinopathy • Muscle Disorders • Idiopathic Cardiomyopathy, Myocarditis • Allergic Disorders

  27. IMMUNOLOGY TESTS • Weak positives • Connective tissue ANA • Coeliac TTG • PBC M2 Ab • Thyroid Anti TPO antibodies are present in most patients with Hashimoto's thyroiditis (95%), primary myxoedema (90%) and in some patients with Grave's disease (18%). They are also present in low levels in patients with colloid goitre, thyroid carcinoma, transiently in de Quervain's thryoiditis and in normal elderly females. (This is relatively non specific test)

  28. Thyroid Peroxidase Ab (TPO)

  29. TPO: RISK FACTOR FOR HYPOTHYROIDISM North England - Whickham Survey • Positive thyroid microsomal antibodies were present in 21% of women aged 55-65 years and these women have an annual risk of developing hypothyroidism of 2.6% • Annual incidence of hypothyroidism was 3.5/1000 women. • The odds ratio for developing hypothyroidism were: 8 for women and 44 for men with an isolated increase in TSH 8 for women and 25 for men with positive anti-thyroid antibodies 38 for women and 173 for men with an increase in TSH and positive antibodies

  30. INCIDENCE OF THYROID CARCINOMA

  31. FEMALE 49Y 10/09 FT4 53.0 pmol/L (8-20) TSH <0.02 mu/L (0.3-5.5) Other Feb 2008 FEMALE 49Y 09/09 FT4 24.8 pmol/L (8-20) TSH <0.02 mu/L (0.3-5.5) ? OK for monitoring THYROID CARCINOMA: POST ABLATION

  32. FEMALE 49Y 10/09 FT4 53.0 pmol/L (8-20) TSH <0.02 mu/L (0.3-5.5) Other Feb 2008 FEMALE 49Y 09/09 FT4 24.8 pmol/L (8-20) TSH <0.02 mu/L (0.3-5.5) ? OK for monitoring THYROGLOBULIN < 0.2 ug/L ([<1.0 post thyroid ablation] ? OK for monitoring THYROID CARCINOMA: POST ABLATION

  33. FEMALE 49Y 10/09 FT4 53.0 pmol/L (8-20) TSH <0.02 mu/L (0.3-5.5) Other Feb 2008 FEMALE 49Y 09/09 FT4 24.8 pmol/L (8-20) TSH <0.02 mu/L (0.3-5.5) ? OK for monitoring THYROGLOBULIN < 0.2 ug/L ([<1.0 post thyroid ablation] ? OK for monitoring THYROGLOBULIN Ab 2362 (< 20) THYROID CARCINOMA: POST ABLATION

  34. ANTI CYCLIC CITRULLINATED PEPTIDE Ab • Rheumatoid factor = Positive “Interpret with reference to clinical symptoms as this is non specific marker which may also be raised in response to infection and other autoimmune conditions”. • Anti CCP antibodies • Improved specificity (98%) and sensitivity (80%) for the detection of Rheumatoid Arthritis • Differentiate rheumatoid from similar conditions (polymyalgia, Sjogren’s, lupus – RhF can be +ve) • High initial titres are prognostic for subsequent structural damage (target patients requiring early aggressive therapy)

  35. TSH RECEPTOR Ab (TSH-RAb) • GESTATIONAL HYPERTHYROIDISM / GRAVE’S ANTENATAL BOOKING Very high titre predictive of intrauterine or neonatal thyrotoxicosis Negative / low need not be measured again POST THYROIDECTOMY FOR GRAVE’S High titres TSH-RAb results in concomitant risk of neonatal Grave’s • EUTHYROID GRAVE’S OPTHALMOPATHY • NEONATAL TRANSIENT HYPOTHYROIDISM / TSH BLOCKING Ab

  36. Iron deficiency: Iron or ferritin ?? CAUSES OF IRON DEFICINCY BLOOD LOSS DECREASED IRON ABSORPTION Refractive to oral iron therapy OTHER Intravascular haemolysis Pulmonary haemosiderosis Response erythropoeitin Gastric bypass /obesity Peripheral smear from a patient with iron deficiency shows pale small red cells with just a scant rim of pink haemoglobin; occasional "pencil" shaped cells are also present. Normal red cells are similar in size to the nucleus of a small lymphocyte (arrow); thus, many microcytic cells are present in this smear. Thalassaemia can produce similar findings.

  37. RELIABLE BIOCHEMISTRY !! MALE 76Y: RENAL REVIEW Hb 10.2 g/dL (13.5-17.5) Iron 2.0 umol/L (10-28) UIBC 32 umol/L (28-64) Iron Sat 6 % (15-40) ?? Iron deficient

  38. RELIABLE BIOCHEMISTRY !! MALE 76Y: RENAL REVIEW Hb 10.2 g/dL (13.5-17.5) Iron 2.0 umol/L (10-28) UIBC 32 umol/L (28-64) Iron Sat 6 % (15-40) ?? Iron deficient MCV 98.5 fL

  39. RELIABLE BIOCHEMISTRY !! MALE 76Y: RENAL REVIEW Hb 10.2 g/dL (13.5-17.5) Iron 2.0 umol/L (10-28) UIBC 32 umol/L (28-64) Iron Sat 6 % (15-40) ?? Iron deficient MCV 98.5 fL Ferritin 514 ug/L (15-300) ??

  40. RELIABLE BIOCHEMISTRY !! MALE 76Y: RENAL REVIEW Hb 10.2 g/dL (13.5-17.5) Iron 2.0 umol/L (10-28) UIBC 32 umol/L (28-64) Iron Sat 6 % (15-40) ?? Iron deficient MCV 98.5 fL Ferritin 514 ug/L (15-300) ?? CRP 34.9 mg/L ( < 6) Neutrophils 17.6 x 109 (1.8-7.7)

  41. FACTORS AFFECTING IRON INDICES IRON TIBC FERRITIN Inflammatory states Pregnancy / OCP N N Anaemia chronic disease N

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