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Thyroid Disease During Pregnancy

Thyroid Disease During Pregnancy. h. D elshad m.d Endocrinologist Research Institute for Endocrine Sciences Shahid Beheshti University Of Medical Sciences. Thyroid Auto-antibodies and Pregnancy Complications. Thyroid Auto-antibodies And Pregnancy Complications.

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Thyroid Disease During Pregnancy

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  1. Thyroid Disease During Pregnancy h. Delshadm.d Endocrinologist Research Institute for Endocrine Sciences ShahidBeheshti University Of Medical Sciences

  2. Thyroid Auto-antibodiesandPregnancy Complications

  3. Thyroid Auto-antibodiesAnd Pregnancy Complications The prevalence of thyroid autoantibodies in pregnant women • Anti-TPO or Anti-Tgthyroid autoantibodies are present in 2% to 17% of unselected pregnant women. • The prevalence of antibodies varies with ethnicity. • In U.S. populations, TAs are most frequent in Caucasian and Asian women and least frequent in African Americans. • A recent study from Belgium in women seeking fertility treatment: 8% = TPO-Ab + Tg-Ab 5% = isolated Tg-Ab 4% = isolated TPO-Ab

  4. Thyroglobulin and thyroid peroxidase in thyroid hormone biosynthesis

  5. The Natural History Of Antithyroid Antibodies In Pregnant Women In women with thyroid autoimmunity, hypothyroidism may occur. #Glinoer et al. 1994 ; prospective study of 87 euthyroid (TSH<4 mU/L) women with TPO-Ab, Tg-Ab, or both: ●20% developed a serum TSH >4 mU/L during gestation ● Anti-thyroid Ab titers were highest in the first trimester, ● They decreased by about 60% over the course of gestation. # Twelve years later, in a prospective study, Negro et al. demonstrated similar results: ● TSH: 1.7mIU/L (12th week) to 3.5mIU/L (term). ●19% = supra normal TSH value at delivery.

  6. The Natural History Of Antithyroid Antibodies In Pregnant Women • TPO-Ab are able to cross the placenta. • At the time of delivery, cord blood TPO-Ab levels strongly correlate with third-trimester maternal TPO-Ab concentrations. • However, maternal passage of either TPO-Ab or Tg-Ab is not associated with fetal thyroid dysfunction. • RECOMMENDATION 11 (ATA.2017) • Euthyroid pregnant women who are TPO-Ab or Tg-Ab positive should have measurement of serum TSH concentration performed at time of pregnancy confirmation and every 4 weeks through mid-pregnancy.

  7. Should Euthyroid Women With ThyroidAutoimmunity Be Treated With Selenium? • Some studies evaluating non-pregnant women have shown that selenium can diminish TPO-Ab concentrations 1- Gartner R, et al. 2002; J ClinEndocrinolMetab 87:1687–1691. 2- Duntas LH, et al. 2003 EurJ Endocrinol 148: 389–393. 3- MazokopakisEE , et al. 2007 ;Thyroid 17:609–612. 4- Fan Y, et al. 2014 IntJ Endocrinol 90:45-73 • Negro et al: Euthyroid TPO-Ab positive pregnant women randomized to treatment with 200 mg/d selenium had a significant decrease in the frequency of postpartum thyroid dysfunction (p<0.01) and also had lower TPO-Ab concentrations during pregnancy compared to those in the untreated group.

  8. Should Euthyroid Women With ThyroidAutoimmunity Be Treated With Selenium? • A recent RCT performed in mildly iodine-deficient British pregnant women, treatment with 60 mg of selenium daily did not affect TPO concentrations or TPO-Ab positivity. Mao J, et al. 2016; Eur J Nutr 55:55–61. • Patients treated with Selenium could be at higher risk for developing type 2 diabetes mellitus. StrangesS,et al. Ann Intern Med 2007;147: 217–223. • For these reasons, the risk-to-benefit comparison does not presently support routine selenium supplementation of TPO-Ab positive women during pregnancy. RECOMMENDATION 12 (ATA 2017) • Selenium supplementation is not recommended for the treatment of TPO-Ab positive women during pregnancy.

  9. Association Between Thyroid Antibodies and Sporadic Spontaneous Pregnancy Loss inEuthyroid Women • Spontaneous pregnancy loss (miscarriage), occurs in 17% - 31% of all gestations. • The individual risk varies according to clinical factors including maternal age, family history, environmental exposures, and medical comorbidities. • Patients with poorly controlled diabetes mellitus may have up to a 50% risk of loss. Thyroid dysfunction has similarly been associated with increased pregnancy loss. • Stagnaro-Green, first demonstrated an association between pregnancy loss and thyroid antibodies in a prospective observational study. Stagnaro-Green A, et al. 1990; JAMA 264:1422–1425.

  10. Association Between Thyroid Antibodies and Sporadic Spontaneous Pregnancy Loss inEuthyroid Women Stagnaro-Green A, et al. study: • Patients who were positive for TPO-Ab, Tg-Ab, or both, demonstrated a 2-fold increase in the risk for pregnancy loss (17% vs. 8.4%, p=0.01). • Since that time, numerous other studies have examined the association between maternal anti-thyroid Ab. status and pregnancy loss risk, showing similar findings. • In a recent meta-analysis of eight case–control studies, the pooled OR for pregnancy loss in women with thyroid autoimmunity versus women without anti-thyroid antibodies was 2.55 [95% CI 1.42–4.57] • Meta-analysis of 14 cohort studies showed a similar increased OR of 2.31 [95% CI 1.90–2.82] Chen L, Hu R 2011; ClinEndocrinol (Oxf) 74:513–519.

  11. Thangaratinam et al. British Medical Journal, vol. 342, no. 7806, 2011. Relationship between thyroid antibodies and Miscarriages. There is an increased prevalence of women positive for thyroid autoantibodies in individuals with subfertility and with recurrent miscarriages.

  12. The Underlying Mechanisms for Such an Association Remain Unclear Several mechanistic hypotheses have been proposed, including: • Ab-mediated mild thyroid hypofunction. • Cross-reactivity of anti-thyroid antibodies with hCGreceptors on the zonapellucida. • Presence of concurrent non–organ-specific autoimmunity. • Increased levels of endometrial cytokines in women with thyroid autoimmunity. Twig G, et al. 2012 ; J Autoimmun 38: J275–J281.

  13. Association Between Thyroid Antibodies and Recurrent Spontaneous Pregnancy Loss in Euthyroid Women • Recurrent pregnancy loss : two consecutive spontaneous losses or three or more spontaneous losses, ( up to 1% of all women) • Parental chromosomal anomalies, immunologic derangements, uterine pathology, endocrine dysfunction • Iravani AT, et al. 2008; EndocrPract14:458–464. Patients with primary recurrent pregnancy losses (three or more) had a higher incidence of Tg-Ab and/or TPO-Ab positivity (OR 2.24 [95% CI 1.5–3.3]) • KuttehWH, et al. 1999 ; FertilSteril 71: 843–848 Positivity rate for Tg-Ab, TPO-Ab, or both in 700 women with recurrent pregnancy loss compared to 200 healthy controls (22.5% vs. 14.5%, p=0.01)

  14. Association Between Thyroid Antibodies and Recurrent Spontaneous Pregnancy Loss in Euthyroid Women • Esplin and colleagues : No difference in positivity for Tg-Ab, TPO-Ab, or both between patients with recurrent pregnancy loss and healthy controls. • Rushworth and colleagues : No significant difference in live birth rates between women with recurrent losses who were Tg-Ab or TPO-Ab positive and those who were not. • Thus, the data for an association between thyroid anti- bodies and recurrent pregnancy loss are less robust than for sporadic loss. • This finding may be because recurrent pregnancy loss has many potential causes, and endocrine dysfunction may only account for 15%–20% of all such cases

  15. J Nat Sci Biol Med. 2015 Jul-Dec; 6(2): 402–405.

  16. Does treatment with LT4 therapy decrease the risk for pregnancy loss in euthyroid women with thyroid autoimmunity? • Negro and colleagues : prospective RCT of LT4 in euthyroid patients who were TPOAbpositive: - a significantly decreased rate of pregnancy loss in the LT4-treated group (3.5% vs. 13.8%, p<0.05) • Lepoutre and colleagues : Randomized, retrospective study analyzed data from 65 TPO-Ab-positive pregnant women : - 34of these women were treated with 50 µg LT4 daily , while 31 women were not treated. None of the LT4-treated women miscarried, but 5 of 31 untreated women (16%) experienced pregnancy loss.

  17. Impact of treatment with LT4 on TPO Ab (+) Pregnancy Miscarriage % Negro et al 2006 Preterm Delivery %

  18. Does treatment with Intravenous Immunoglobulin therapy decrease the risk for pregnancy loss in euthyroid women with thyroid autoimmunity? • Three small nonrandomized case series have been published on the use of IVIG therapy for the prevention of recurrent pregnancy loss in women with anti-thyroid antibodies. Kiprov DD, et al, 1996 ; Am J ReprodImmunol36: 228–234. StrickerRB, et al. 2000; FertilSteril73: 536–540. Vaquero E, et al. 2000; Am J ReprodImmunol43: 204–208. • The live birth rates ranged from 80% to 95% in IVIG group • Comparison of a LT4 intervention to an IVIG intervention in one study demonstrated a higher rate of term delivery in the LT4-treated group

  19. conclusion • Nonetheless, intervention trials with LT4 (and less so IVIG) in euthyroidTPOAb-positive women with recurrent abortion appear to show a possible decrease in miscarriage rates. Further randomized trials are needed to better understand the effectiveness of both LT4 and IVIG intervention. • Two randomized clinical trials are currently on going: - The Thyroid AntiBodiesand LEvoThyroxinestudy (TABLET) trial in the United Kingdom - The T4Lifetrial in the Netherland • At present, however, the cost, complexity, and side effect profile associated with IVIG infusion must be noted and make its use undesirable. • In contrast, LT4 administration in low dosage (25–50 µg/d) is safe. RECOMMENDATION 13, 14 ( ATA, 2017)

  20. Is thyroid autoimmunity in euthyroid pregnant women associated with adverse obstetric or child outcomes other than pregnancy loss and premature birth? • Anti-thyroid antibodies have been associated with perinatal death in some but not all studies. • Postpartum depression • Neonatal respiratory distress syndrome • Lower motor and intellectual development at age 25–30 months • Lower perceptual performance and motor scores • Sensory-neural hearing loss • Autism

  21. RaghunathBhattacharyya et al. J Nat Sci Biol Med. 2015 Jul-Dec; 6(2): 402–405.

  22. Thyroid antibody levels throughout pregnancy. In pregnancy there is a marked fall in both TPO-Ab and Tg-Ab levels followed by an increase in the postpartum

  23. Testing For Thyroid Dysfunction In Pregnancy (ATA 2017)

  24. TSH + TPO-Ab as soon as pregnancy confirmed TSH < 0.1 mU/L TSH > 10 mU/L TSH < 0.1 – 2.5 mU/L Thyrotoxicosis Treatment : LT4 No further workup Testing For Thyroid Dysfunction In Pregnancy (ATA 2017)

  25. TSH = 2.5 - 10 mU/L TPO-Ab Positive TPO-Ab Negative TSH= 2.5-4.0 TSH= 4.0 - 10 TSH= 2.5-4.0 TSH= 4.0 - 10 Consider treatment With LT4 Consider treatment With LT4 Treatment with LT4 No Treatment Testing For Thyroid Dysfunction In Pregnancy (ATA 2017)

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