La tiroide: il decalogo proposto dal medico di Laboratorio

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Cornelio Graziano
7 anni fa
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1 1 When the TSH concentration is elevated, clinicians should consider that seum 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 1

2 Nevertheless, the FT4 level was measured in 98% of our patients with elevated TSH concentrations and was within normal limits in almost all of these patients, which strongly suggests that hypothyroidism in this group of patients could be considered subclinical 3 When the TSH is normal and there are no new clinical indications for a thyroid disorder, there is only a 2% probability that another TSH determination obtained within 5 years will be abnormal we suggest additional. TSH measurement only if warranted by the clinical evaluation. In patients with abnormal serum TSH levels after full clinical evaluation, we suggest obtaining, at least 2 TSH measurements before considering treatment. 4 2

3 Patients: Forty patients (32 women, mean age yr) with spontaneous subclinical hypothyroidism (TSH 5 mu/liter and normal free T4) participated in the study. Each patient normalize their TSH values without T4 therapy throughout the follow-up. 5 However, two recent meta-analyses suggest that increased risk for adverse cardiovascular outcomes occurs in patients younger than 65 yr of age, but not in those more than 65 yr old (19, 20). Until these issues are settled by further research, it seems prudent not to treat routinely elderly patients with levothyroxine because they are found to have a minimal increase in serum TSH. 6 3

4 Furthermore, increased levels of TSH (7) and low levels of FT4 (8) 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 (7). 7 There is evidence that a low activity of thyroid hormone might be beneficial in the elderly (1, 7, 8), whereas subclinical hyperthyroidism is a predictor of mortality (9). It has been demonstrated that subjects with exceptional longevity (centenarians; median age, 98 yr) have higher levels of TSH compared with controls (1). 8 4

5 9 100 Different set-points in different subjects TSH (mui/l) A B REFERENCE INTERVAL ft4 (ng/l)

7 Glucose Total T4 5 mmol/l 150 nmol/l 13 Total T4 Glucose Total T4 ft4 150 nmol/l 5 nmol/l 14 ft4 Total T4 7

8 EQUILIBRIUM DIALYSIS to be dialysed dialysed 15 binding protein free hormone bound hormone 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 16 8

10 2.5 mu/l 19 3 mu/l 20 10

11 21 TSH value between 2 and 4 mu/l as abnormal, is probably doing more harm than good. 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 22 11

13 25 La tiroide: il 5.5 decalogo proposto dal medico di Laboratorio

15 TSH ALL 4.24 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: %

16 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: %

834 751 666 584 499 417 334 249 167 82 FT3 F Observations: 15307 Outliers 215 Class width: 0.

6741 Underl. distr. SD left side: 0.3527 SD right side: 0.4586 Lower ref. limit: 2.00 Underl.

17 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: %

18 Laboratorians should appreciate that the cutoffs quoted in guidelines often arise from historical data using assays with poorly defined bias that may no longer be available for routine use 35 Clinicians should appreciate that the TSH cutoffs quoted in guidelines are subject to uncertainty and should be regarded as typical rather than an absolute target figures and thus can be applied with some degree of flexibility

20 Time of phlebotomy The average decline between 0730 and 0900 and 1030 and 1200 h was 26.4% 10 of 15 with fasting early morning TSH between 3.0 and 4.5 mu/l had a late morning nonfasting TSH level <3.0 mu/l. 39 Take home messages Il TSH è rock Il T4 libero è lento Il T3 libero è molto lento Gli Ab anti-tpo sono rock 40 20

21 Take home messages Gli Ab anti-tg sono molto lenti La Tg è ferma La CT è rock 41 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 42 21

22 Tg è ferma mass of thyroid tissue inflammation/injury release Tg the amount of stimulation of the TSH receptor 43 CT: rock higher sensitivity/specificity than FNAC (bct >20; sct >60 ng/l) 44 screening: earlier diagnosis and treatment, better outcome of MTC 22

23 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 45 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

24 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. 47 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 (obiettivo < 0.1 mu/l TSH con FT4 entro l IR)

25 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

26 51 TSH < mu/l >5 ft3 ft4 >17 ng/l ft

27 53 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 27

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