La diagnostica di laboratorio delle malattie tiroidee e il caso del TSH reflex

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Erico Maggi
7 anni fa
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1 Romolo M. Dorizzi, CoreLab, Laboratorio Unico di AvR La diagnostica di laboratorio delle malattie tiroidee e il caso del TSH reflex 1

2 When the TSH concentration is elevated, clinicians should consider that serum TSH levels may become normal with time in more than half of patients. In the appropriate clinical setting, a second serum TSH measurement should be made after several months. If the concentration remains elevated for 1 to 3 years, mild hypothyroidism may be considered permanent 2

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4 Furthermore, increased levels of TSH and low levels of FT4 have been associated with a better survival in elderly subjects (mean age, 85 and 78 yr, respectively). Based on these studies, it has been argued that the treatment of elderly subjects with elevated TSH levels may be of very limited clinical benefit or may even be unfavorable. 4

5 There is evidence that a low activity of thyroid hormone might be beneficial in the elderly, whereas sub- clinical hyperthyroidism is a predictor of mortality. It has been demonstrated that subjects with exceptional longevity (centenarians; median age, 98 yr) have higher levels of TSH compared with controls. 5

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7 Different set-points in different subjects 100 TSH (mui/l) A B REFERENCE INTERVAL 0.01 ft4 (ng/l)

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10 Glucose 5 mmol/l Total T4 150 nmol/l Total T4 Glucose 10

11 Total T4 150 nmol/l ft4 5 nmol/l ft4 Total T4 11

12 All of the methods that we examined had a functional sensitivity 0.02 miu/l except for the ADVIA Centaur. The ARCHITECT i2000 and Vitros ECi demonstrated the lowest functional sensitivities, but the ARCHITECT i2000 was the most precise of the methods 12

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15 Lower TSH reference limit There is general agreement that it lies between mu/l Canaris 2000 Parle 2001 Warren

16 2.5 mu/l 16

17 3 mu/l 17

18 4.2 mu/l 18

19 TSH value between 2 and 4 mu/l as abnormal, is probably doing more harm than good. 19

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21 In general, there is a poor agreement between reference intervals quoted by different laboratories, even for those laboratories supposedly quoting intervals supplied by Chiron Diagnostics 21

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28 TSH ALL Observations: Outliers 1355 Class width: Mean: SD: Regr. distr. Class width: Mean: SD: Mode: Underl. distr. SD left side: SD right side: Lower ref. limit: Underl. percentile: % Upper ref. limit: Underl. percentile: % 28

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30 FT4 F Observations: Outliers 526 Class width: Mean: SD: Regr. distr. Class width: Mean: SD: Mode: Underl. distr. SD left side: SD right side: Lower ref. limit: 8.95 Underl. percentile: % Upper ref. limit: Underl. percentile: %

31 FT4 M Observations: 9000 Outliers 157 Class width: Mean: SD: Regr. distr. Class width: Mean: SD: Mode: Underl. distr. SD left side: SD right side: Lower ref. limit: 8.64 Underl. percentile: % Upper ref. limit: Underl. percentile: % 31

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33 FT3 F Observations: Outliers 215 Class width: Mean: SD: Regr. distr. Class width: Mean: SD: Mode: Underl. distr. SD left side: SD right side: Lower ref. limit: 2.00 Underl. percentile: % Upper ref. limit: 3.61 Underl. percentile: %

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37 The time of phlebotomy is important, (TSH varies throughout the day, with early morning values greater than later ones, and is accentuated by sleep deprivation, strenuous exercise, or working during the night or evening shifts). Repeated measurements vary considerably over months. 37

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41 Take home messages Il TSH è rock Il T4 libero è lento Il T3 libero è molto lento Gli Ab anti-tpo sono rock 41

42 Take home messages Gli Ab anti-tg sono molto lenti La Tg è ferma La CT è rock 42

43 Ab anti-tpo sono rock TPOAb più sensibili per patologia autoimmune TgAb non aggiungono informazioni NHANES III: 3 % presentano TgAb senza TPOAb e senza tireopatia 43

44 Tg è ferma mass of thyroid tissue inflammation/injury release Tg the amount of stimulation of the TSH receptor 44

45 CT: rock higher sensitivity/specificity than FNAC (bct >20; sct >60 ng/l) screening: earlier diagnosis and treatment, better outcome of MTC 45

46 CT: lenta se non è usato il metodo ELSA (CIS) è eseguito il test pentagastrina è disponibile risultato prima dell intervento chirurgico è eseguito follow up con lo stesso metodo 46

47 I. L esame più importante è il TSH. II. Preferire gli anti-tpo agli anti-tg. Una volta diagnosticata una tireopatia autoimmune, non è necessario monitorare gli anti-tpo. III. Chiedere gli anti-tg, insieme alla Tg, solo nel follow-up del cancro della tiroide. 47

48 IV. Chiedere la CT una volta. Nel follow up dell MTC inserire CT (+CEA) V. Chiedere FT3 eccezionalmente (l 80% deriva dall FT4). Un aumento dell FT3 con FT4 nei limiti è praticamente sempre un artefatto di laboratorio. 48

49 VI. Monitorare terapia ormonale sostitutiva con solo TSH (target: TSH entro l IR). VII. Monitorare (dopo 2-3 mesi) la terapia ormonale soppressiva con TSH e FT4 (target:tsh < 0.1 mu/l e FT4 entro l IR) e solo con TSH dopo target:tsh < 0.1 mu/l). 49

50 VIII.In terapia sostitutiva con L-T4 non assumere il farmaco nelle 8 ore prima prelievo. IX.Nei primi mesi di terapia con farmaci antitiroidei l esame più utile è l ft4. X.Richiedente e laboratorista devono collaborare strettamente per interpretare alcuni esami tiroidei. 50

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53 TSH < mu/l >5 ft4 >17 ng/l ft4 ft3 53

54 Cascade/Reflex TSH Automated algorithm Single patient access All the test with a single sample The patient/nhs will pay only the carried out tests (EMR?) No delay in report 54

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