Current Concept in the Treatment of Hypothyroidism in Pregnancy

							Current Concept in the Treatment of
  Hypothyroidism in Pregnancy

       國立成功大學醫學院附設醫院
        內科部內分泌新陳代謝科
           吳達仁 醫師
  Thyroid Problems in Pregnancy
• Autoimmune thyroid diseases:
  – Infertility : immune or metabolic
• Hyperthyroidism / Hypothyroidism during
  Pregnancy
• Anti-thyroid Drug during Pregnancy
• Levothyroxine Therapy during Pregnancy
TPO(+)而甲狀腺正能之懷孕婦女不論有無甲狀腺素治療
受孕率並未減少。但是沒有甲狀腺素治療者流產率增加




                                               輔


                                               助


                                               受


                                               孕




 Negro R, et al. Hum Reprod 2005 20:1529-33;
 甲狀腺素治療甲狀腺正能之自體甲狀腺
  疾病懷孕婦女對產科併發症之影響
• 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 2006;91:2587-91
TPO(+)而甲狀腺正能之懷孕婦女早期就顯示TSH
雖仍在正常範圍內，但是比TPO(-)懷孕婦女較高




Negro R, et al. JCEM 2006; 91:2587-91
    甲狀腺素治療有助TPO(+)而甲狀腺正能之懷孕婦女

    25
                                             22.4
%                                                         相對風險       流產   早產
    20

                                                          Group A    1.72 1.66
    15             13.8
                                                          (n= 57)
    10                                              8.2
                                                          Group B    4.95 12.18
                                        7
                                                          (n= 58)
     5       3.5                                          Group C
                          2.4                                        1    1
                                                          (n= 869)
     0
             流產                          早產
         Negro R, et al. JCEM 2006; 91:2587-91
甲狀腺素治療有助TPO(+)而甲狀腺正能之懷孕婦女
• 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; 91:2587-91
The week at which the levothyroxine dose was first increased in
women with primary hypothyroidism (the dose was increased
when TSH > 5.0 µU/mL) and with a history of thyroid cancer (the
dose was increased when the TSH> 0.5 µU/mL)




Alexander EK, et al. Engl J Med 2004;351:241-249
             懷孕婦女甲狀腺素治療劑量之調整




Panel A shows TSH levels in early Panel B shows changes in a subject in
pregnancy at the time of the first the levothyroxine dose and in
levothyroxine adjustment.                          serum estradiol levels during her two
  Alexander EK, et al. Engl J Med 2004;351:241-249 pregnancies.
       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.
       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.
                            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 2006;91:2587-2591
• 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 2005:20:1529–1533
• 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 2005;90:6093-9.
• 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 2004;351:241-
  249