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Hypothyroidism in Pregnancy

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Jessica Gray MSIV April 13, 2011 Casey and Leveno Fig. 1. The pattern of changes in serum concentrations of thyroid function studies and hCG according to gestational age. – PowerPoint PPT presentation

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Title: Hypothyroidism in Pregnancy


1
Hypothyroidism in Pregnancy
  • Jessica Gray MSIV
  • April 13, 2011

2
Clinic Case
  • 34 yo F with Hx Graves Disease s/p ablation and
    surgery on levothyroxine
  • Patient wants to get pregnant
  • What effect does hypothyroidism have on pregnancy
    and how should it be managed?

3
Presentation Outline
  • Thyroid physiology in pregnancy
  • Overt hypothyroidism
  • Presentation, complications, diagnosis, and
    management
  • Subclinical hypothyroidism
  • Definition prevalence, current research,
    recommendations, future possibilities
  • Universal Screening?
  • Take home points

4
Thyroid Physiology in Pregnancy
5
Physiologic Changes in Pregnancy
  • hCG stimulation of TSH-Receptors
  • Serum hCG concentrations increase soon after
    fertilization and peak at 10 to 12 weeks.
  • Serum free T4 and T3 concentrations increase
    slightly, usually within the normal range, and
    serum TSH concentrations are appropriately
    reduced
  • In 10 to 20 percent of normal women, serum TSH
    concentrations are transiently low
  • Estrogen-mediated increase in circulating levels
    of TBG
  • major transport protein for thyroid hormone
  • Increase in total serum T4 and Total T3 but
    no/minimal change in free T3 or T4

6
Hormonal Changes in Pregnancy
7
Fetal Thyroid Physiology
  • The fetal thyroid gland begins concentrating
    iodine and synthesizing thyroid hormone after 10-
    12 weeks of gestation.
  • Little hormone synthesis occurs until the 18-20th
    week, when fetal thyroid secretion increases
    gradually.
  • Any requirement for thyroid hormones before this
    time is supplied by the mother, and it is during
    this time that maternal thyroid hormones are most
    important to fetal brain development

8
Overt Hypothyroidism in Pregnancy
9
Causes of Hypothyroidism
  • PRIMARY
  • (thyroid dysfunction)
  • SECONDARY
  • (pituitary dysfunction)
  • Hashimoto thyroiditis
  • Iodine sufficient areas
  • Autoimmune destruction of thyroid (thyroid
    peroxidase and thyroglobulin antibodies)
  • Antithyroid antibodies are found in approximately
    10 of women in second trimester.
  • Endemic iodine deficiency
  • Central Africa, South America, northern Asia
  • History of ablative radioiodine therapy or
    thyroidectomy.
  • Sheehans syndrome
  • Lymphocytic hypophysitis
  • history of a hypophysectomy.

10
Signs Symptoms of HypothyroidismSimilar to
symptoms of pregnancy Vague and nonspecific
  • Fatigue
  • Constipation
  • Cold intolerance
  • Muscle cramps
  • Insomnia,
  • Weight gain,
  • Carpal tunnel syndrome,
  • Hair loss,
  • Voice changes
  • Intellectual slowness
  • /- goiter
  • Periorbital edema
  • Dry skin
  • Prolonged DTR relaxation phase

11
Prevalence of Overt Hypothyroidism in Pregnancy
  • 3-5/1000 pregnant women
  • Less common because
  • Some hypothyroid women are anovulatory and have
    difficulty conceiving
  • New or inadequately treated hypothyroidism
    complicating pregnancy is associated with a high
    rate of first trimester spontaneous abortion

12
Untreated HypothyroidismAssociated with
Increased Risk of
  • MOM
  • BABY
  • Preeclampsia
  • gestational hypertension
  • Placental abruption
  • NRFHT
  • Preterm delivery, very preterm delivery (lt32
    weeks)
  • Increased rate of caesarean section
  • Postpartum hemorrhage
  • Preterm birth
  • Low birth weight
  • Perinatal morbidity and mortality
  • Increased NICU admission
  • Neuropsychological and cognitive impairment
  • Congenital cretinism growth restriction,
    deafness, neuropsych impairment from severe
    Iodine deficiency or untreated congenital
    hypothyroidism

13
Identifying Clinical hypothyroidism
  • Thyroid testing should be performed on
    symptomatic women or those with a personal
    history of thyroid disease
  • Serum TSH is more sensitive than free T4 for
    detecting hypo and hyperthyroidism.

14
Normal values for TSH in Pregnancy?
  • Laboratories use 4.5-5.0 mU/L as the upper limit
    of normal for TSH.
  • However, some current data suggests that that the
    upper limit of normal in pregnancy for TSH should
    be 2.5 mU/L
  • A study in anti-TPO-Ab negative women found a
    higher rate of pregnancy loss in those women
    with first trimester serum TSH 2.5 to 5.0 mU/L
    compared to women with normal free T4 and TSH
    below 2.5 mU/L (6.1 versus 3.6). There was no
    difference in the rates of preterm delivery.
  • Limited data suggest that women undergoing IVF
    with pre-conception TSH above 2.5mU/L may have
    babies with lower gestational age and birth
    weight than those with TSH below 2.5mU/L.

15
Pregnant women have increased thyroid hormone
requirement
  • Approximately 75 -85 of women with preexisting
    hypothyroidism need more T4 during pregnancy
  • T4 requirements are increased due to
  • Weight gain and increased T4 pool size
  • High serum TBG concentrations
  • Placental de-iodinase activity (increases T4
    clearance)
  • Transfer of T4 to fetus
  • Reduced GI absorption of levothyroxine due to
    iron in prenatal vitamins
  • Levothyroxine dose requirements may increase by
    as much as 50 percent during pregnancy, and the
    increase occurs as early as the fifth week of
    gestation

16
Levothyroxine titration for women with known
hypothyroidism
  • Check TSH at initiation of prenatal care
  • Adjust levothyroxine in 25-50mcg increments with
    goal TSH 0.5-2.5mU/L
  • if treatment naïve, begin at 100-125mU/L or
    1-2mcg/kg/day
  • Check TSH 4-6 weeks after each dose adjustment
  • Repeat TSH during each trimester
  • After delivery return to pre-pregnancy dose and
    recheck TSH in 6-8 weeks postpartum

17
Levothyroxine Drug Facts
  • Pregnancy Category A
  • Breastfeeding Safe
  • Not contraindicated. Levothyroxine is excreted
    into breastmilk in small quantities
  • Drug interactions
  • Interfere w/absorption Iron salts,
    Antacids, Calcium salts
  • Separate ingestion by gt4 hours.

18
Subclinical Hypothyroidism
  • - Definition and prevalence
  • Evidence for maternal and fetal harm
  • Current recommendations for universal screening
    treatment?

19
Subclinical Hypothyroidism
  • Definition Elevated TSH with normal thyroid
    hormone in an asymptomatic patient
  • Prevalence 2-5 pregnant women
  • Concern Women with thyroid hypofunction in
    pregnancy may have subtle hormone abnormalities
    that may be asymptomatic but suboptimal for
    obstetric outcomes and for the developing fetal
    brain

20
Evidence for Maternal Fetal Harm
  • Several older studies have reported
    neuropsychological impairment in offspring of
    women with subclinical hypothyroidism.
  • 1969 study reported that mild maternal
    hypothyroidism alone was associated with lower IQ
    levels in the offspring (Man 1969)
  • 1999 prospective study of children born to women
    with elevated TSH during the midtrimester of
    pregnancy had a slight but significant reduction
    in IQ scores between 7-9 years of age when
    compared with infants of euthyroid women.
    (Haddow, NEJM 1999)
  • 1999 study found that during pregnancy maternal
    free thyroxine levels lt10th percentile at 12
    weeks gestation (but not 32 weeks) were
    associated with a 5.8 fold risk for impaired
    psychomotor development in infants evaluated at
    10 months of age. (Pop 1999)

21
2 recent studies on Subclinical Hypothyroidism
and Pregnancy Outcomes
  • 2005 prospective screening study in the Journal
    of Obstetrics and Gynecology evaluated pregnancy
    outcomes in women with subclinical hypothyroidism
    and found that in the cohort with subclinical
    hypothyroidism
  • placental abruption was 3 x as likely,
  • preterm birth was 2x higher
  • The authors speculate that the previously
    reported reduction in intelligence quotient of
    offspring of women with subclinical
    hypothyroidism may be related to effects of
    prematurity
  • (Obstet Gynecol 2005 105 239-245)

22
Maternal Thyroid Hypofunction and Adverse
Obstetric Outcomes
  • 2008 study reported in Journal of Obstetrics and
    Gynecology looked at whether subclinical
    hypothyroidism in the first two trimesters of
    pregnancy was associated with obstetric
    complications.
  • They concluded that maternal thyroid hypofunction
    is not associated with a consistent pattern of
    adverse pregnancy outcomes (as reported below)
    and routine screening is not indicated.
  • T1 hypothyroxinemia was associated with preterm
    labor (aOR 1.62 95 CI 1.0-2.62) and macrosomia
    (aOR 1.7, 95 CI 1.02-2.84)
  • T2 hypothyroxinemia was associated with
    gestational DM (aOR 1.7, 95 CI 1.37-2.83)
  • Obstet Gynecol 2008 11285-92

23
Universal Screening for Thyroid Disease in
Pregnancy is controversialANTI-UNIVERSAL
SCREENING ARGUMENT insufficient evidence
  • USPTF 2004 Grade I The evidence is insufficient
    to recommend for or against routinely providing
    screening.
  • Subclinical hypothyroidism is associated with
    poor obstetric outcomes and poor cognitive
    development in children
  • No trials of treatment of subclinical
    hypothyroidism in pregnant women were identified
  • ACOG Practice Bulletin 37 2002 There are
    insufficient data to warrant routine screening of
    asymptomatic pregnant women for hypothyroidism
  • Current data are observational. There have been
    no intervention trials to demonstrate the
    efficacy of screening and treatment to improve
    neuropsychologic performance in the offspring of
    hypothyroid women
  • It would be premature to recommend universal
    screening for hypothyroidism during pregnancy
  • Indicated testing of thyroid function may be
    performed in women with a personal history of
    thyroid disease or symptoms of thyroid disease
  • Cochrane Review 2010
  • There is a particular need to determine whether
    subclinical hypothyroidism significantly
    increases the risk of fetal neurological damage
    and childhood disability.
  • The Endocrine Society clinical practice
    guidelines also recommend targeted case finding
    rather than universal screening

24
Universal Screening for Thyroid Disease in
Pregnancy is controversialPRO-UNIVERSAL
SCREENING ARGUMENT we may miss cases
  • A 2007 study of 1560 consecutive pregnancies
    demonstrated that targeted screening (women with
    a personal or family history of thyroid disease
    or another autoimmune disorder) found only
    two-thirds of the women with TSH gt4.2 mU/I an
    accompanying editorial suggests that case finding
    is no longer an acceptable approach, and
    advocates universal screening (Vaidya 2007)
  • Limited data suggest that universal screening may
    be more cost-effective than not screening
  • A 2009 decision analysis model presented in
    Journal of Obstetrics Gynecology compared the
    two approaches and estimated that for every
    100,000 pregnant women screened, over 8 million
    dollars would be saved due to improved neonatal
    outcomes (reduced risk of neurodevelopmental
    impairment). (Thung 2009)
  • UpToDate.Com
  • Professional societies recommend testing
    pregnant women for thyroid dysfunction only if
    they are symptomatic or have a family history of
    thyroid disease. However, this approach may miss
    up to one-third of women with hypothyroidism, and
    preliminary data suggest that universal screening
    is cost-effective. Therefore, we suggest
    universal screening for thyroid dysfunction in
    pregnant women or those hoping to become
    pregnant.

25
Summary and recommendations
  • Untreated hypothyroidism is associated with
    significant risks to mom and baby
  • Treatment with levothyroxine is standard of care
    for overt hypothyrodisim in pregnancy
  • Preconception and early pregnancy counseling
    regarding the importance of thyroid control is
    recommended (especially for preterm birth).
  • Currently the upper limit of normal for TSH is
    4.5-5mU/L but some studies indicate that it
    should be lower in early pregnancy
  • Current recommendations are against universal
    thyroid screening in pregnant women given limited
    evidence for treatment of subclinical
    hypothyroidism at this time. However, targeted
    thyroid hormone testing could potentially miss a
    significant number of women with subclinical
    disease
  • In the coming years we must determine whether
    subclinical hypothyroidism significantly
    increases the risk of fetal neurological damage
    and childhood disability as this may prompt a
    universal thyroid screening program in pregnancy.

26
References
  • American College of Obstetricians and
    Gynecologists. ACOG practice bulletin. No. 37
    August 2002. Thyroid Disease in Pregnancy.
    (Replaces Practice Bulletin Number 32, November
    2001). Obstet Gynecol 2002 100387
  • Casey, Brian. Leveno, K.J. Thyroid Disease in
    Pregnancy. Journal of Obstetrics Gynecology.
    Vol 108 No 5 Nov 2006
  • Casey, Brian et al. Subclinical Hypothyroidism
    and Pregnancy Outcomes. Journal of Obstetrics and
    Gynecology Vol 105 No 2 Feb 2005
  • Cleary-Goldman et al Thyroid Hypofunction and
    Pregnancy Outcome Journal of Obstetrics and
    Gynecology. Vol 112 No 1, July 2008
  • Negro R. et al. Increased pregnancy loss rate in
    thyroid antibody negative women with TSH levels
    between 2.5 and 5.0 in the first trimester of
    pregnancy. J Clin Endocrinol Metab 2010 95E44.

27
References
  • Reid SM,Middleton P, Cossich MC, Crowther CA.
    Interventions for clinical and subclinical
    hypothyroidism in pregnancy. Cochrane Database of
    Systematic Reviews 2010, Issue 7. Art. No.
    CD007752. DOI 10.1002/14651858.CD007752.pub2.
  • Ross, et al. Overview of Thyroid Disease in
    Pregnancy Uptodate.com, Last updated September
    15, 2010. Visited April 5, 2011.
  • Thung SF et al. The cost effectiveness of
    universal screening in pregnancy for subclinical
    hypothyroidism. Am J Obstet Gynecol 2009
    200267.e1.
  • US Preventive Task Force. Recommendation
    statement. Screening for Thyroid Disease 2004.
  • Vaidya B et al. Detection of thyroid dysfunction
    in early pregnancy universal screening or
    targeted high-risk case finding? J Clin
    Endocrinol Metab 2007 92203.
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