Current Concept in the Treatment of Hypothyroidism in Pregnancy

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Current Concept in the Treatment of
Hypothyroidism in Pregnancy

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Thyroid Problems in Pregnancy

• Autoimmune thyroid diseases
• Infertility immune or metabolic
• Hyperthyroidism / Hypothyroidism during Pregnancy
• Anti-thyroid Drug during Pregnancy
• Levothyroxine Therapy during Pregnancy

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Negro R, et al. Hum Reprod 2005 201529-33
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• Aim to determine whether these women suffer from
  a higher rate of obstetrical complications and
  whether levothyroxine (LT4) treatment exerts
  beneficial effects.
• Design This was a prospective study.
• Intervention TPOAb patients were divided into
  two groups group A (n 57) was treated with
  LT4, and group B (n 58) was not treated. The
  869 TPOAb patients (group C) served as a normal
  population control group.
• Main Outcome Measures Rates of obstetrical
  complications in treated and untreated groups
  were measured.

Negro R, et al. JCEM 2006912587-91
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Negro R, et al. JCEM 2006 912587-91
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Negro R, et al. JCEM 2006 912587-91
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• The prevalence of TAI (thyroid autoimmunity) in
  our population was 11.7, a percentage that is in
  agreement with the data found in other studies.
• The average age of women affected by TAI was
  slightly, but significantly, older than the
  unaffected group this finding indirectly
  confirms that the presence of thyroid antibodies
  is associated with reduced fertility.
• At the beginning of their pregnancy, women with
  TAI showed a higher TSH level compared with those
  who were TPOAb, although the mean TSH level was
  still within the normal range.
• We noted that after parturition, about half of
  the patients in this study had FT4 values below
  the minimal limit.
• The LT4 treatment turned out to be extremely
  effective in reducing the number of miscarriages
  when given during the early stages of pregnancy,
  because miscarriages generally occurred within
  the first trimester.

Negro R, et al. JCEM 2006 912587-91
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The week at which the levothyroxine dose was
first increased in women with primary
hypothyroidism (the dose was increased when TSH gt
5.0 µU/mL) and with a history of thyroid cancer
(the dose was increased when the TSHgt 0.5 µU/mL)
Alexander EK, et al. Engl J Med 2004351241-249
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Panel A shows TSH levels in early pregnancy at
the time of the first levothyroxine adjustment.
Panel B shows changes in a subject in the
levothyroxine dose and in serum estradiol levels
during her two pregnancies.
Alexander EK, et al. Engl J Med 2004351241-249
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Thyroid Function and Pregnancy

• Changes in TFT total T4, T3, fT4, TSH
• increased synthesis of TBG
• thyroid-stimulating effect of HCG
• The fetal thyroid begins to develop at 5-6 weeks'
  gestation, with follicles and colloid production
  at 10-12 weeks. Adverse effects on fetal thyroid
  function are thus unlikely unless treatment
  begins after 10 weeks' gestation.
• By 20 weeks gestational age, the fetal thyroid
  is fully responsive to TSI and to ATDs.
• Maternal T4 and T3 and TSH pass across the
  placenta in small and decreasing amounts as
  gestation progresses, but TRH,TSI, ATDs, iodides,
  and beta-blockers are readily transferred to the
  fetus from the mother.

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Hypothyroidism in Pregnancy

• Overt hypothyroidism complicates up to 3 of 1,000
  pregnancies
• An adequate serum concentration of T4 is
  necessary for foetal brain development.
• If the hypothyroidism is apparent prior to
  pregnancy, it should be corrected before
  conception (target TSH value of 1 mU/l). If
  discovered during pregnancy, treatment with
  levothyroxine should be started as soon as
  possible.
• In the case of a pre-existing hypothyroidism a
  25-50 increase in the levothyroxine dosage is
  often needed during the first trimester of
  pregnancy.
• Postpartum thyroiditis requiring thyroxine
  replacement has been reported in 2 to 5 of
  women. Most women will return to the euthyroid
  state within 12 months.

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References

• Roberto Negro, Gianni Formoso, Tiziana Mangieri,
  Antonio Pezzarossa, Davide Dazzi and Haslinda
  Hassan. Levothyroxine Treatment in Euthyroid
  Pregnant Women with Autoimmune Thyroid Disease
  Effects on Obstetrical Complications. J Clin
  Endocrinol Metab 2006912587-2591
• Negro R, Mangieri T, Coppola L, Presicce G,
  Caroli Casavola E, Gismondi R, Locorotondo G,
  Caroli P. Pezzarossa A, Dazzi D, Hassan H.
  Levothyroxine treatment in thyroid peroxidase
  antibody-positive women undergoing assisted
  reproduction technologies a prospective study.
  Hum Reprod 20052015291533
• Luton D, Le Gac I, Vuillard E, Castanet M,
  Guibourdenche J, Noel M, Toubert ME, Leger J,
  Boissinot C, Schlageter MH, Garel C, Tebeka B,
  Oury JF, Czernichow P, Polak M. . Management of
  Graves Disease during Pregnancy The Key Role of
  Fetal Thyroid Gland Monitoring. J Clin Endocrinol
  Metab 2005906093-9.
• Alexander EK, Marqusee E, Lawrence J, Jarolim P,
  Fischer GA, Larsen PR. Timing and Magnitude of
  Increases in Levothyroxine Requirements during
  Pregnancy in Women with Hypothyroidism. N Engl J
  Med 2004351241-249