Transcript Aldosterone as a Risk Factor for Metabolic Syndrome

Thyroid Disease in
Pregnancy
2011 Update
Endocrinology Rounds
February 16, 2011
Selina Liu
PGY5 Endocrinology
Objectives
 To briefly review thyroid anatomy and physiology in
pregnancy and fetal thyroid physiology
 To review causes of thyroid disease in pregnancy
 To review the maternal and fetal outcomes of
thyroid disease in pregnancy
 To discuss the controversy surrounding screening
for thyroid disease in pregnancy
Objectives
 To review special considerations in management of
thyroid disease in pregnancy
 To highlight recent 2009-2011 articles published on
thyroid disease in pregnancy
Thyroid in Pregnancy
 non-pregnant: 10-30 g (North America)
 in pregnancy,
 increased vascularity
 thyroid gland hyperplasia
 if enlargement noted incidentally on exam, may lead
to lab evaluation of thyroid function
 normal pregnancy - significant but reversible
changes in maternal thyroid physiology
Total T4: 150 % above
normal non-pregnant
reference interval
Casey BM & Leveno KJ. Obstet Gynecol 2006;1081283-9
Clinical Importance of Physiological Changes
 Increased TBG
 Need for  T4 production
  total T4, T3
 interference with fT4 assay
 Placental de-iodination of T4
 Need for  T4 production
  T4 and T3 metabolism
 Increased iodine clearance
(renal clearance and fetal
transfer)
  need for iodine
supplementation
 risk of maternal & fetal
hypothyroidism and goitre
Keely E & Casey BM (2010). Thyroid disease in pregnancy. In RO Powrie, MF Greene, W Camann (Eds)
deSwiet’s Medical Disorders in Obstetric Practice (5th Edition pp322-34). West Sussex, Wiley-Blackwell
Clinical Importance of Physiological Changes
  bhCG (1st trimester)
  fT4 and  TSH
 may have mild transient
thyrotoxicosis
  TSH-R Abs (TSI/TBII)
 Graves’ disease may improve
during pregnancy
  thyroid antibodies
(post-partum)
 exacerbation of Graves’
disease
 precipitation of postpartum
thyroiditis
Keely E & Casey BM (2010). Thyroid disease in pregnancy. In RO Powrie, MF Greene, W Camann (Eds)
deSwiet’s Medical Disorders in Obstetric Practice (5th Edition pp322-34). West Sussex, Wiley-Blackwell
Fetal Thyroid Physiology
 12 weeks gestational age:
 embryogenesis of fetal thyroid gland is complete
 synthesis of thyroid hormone
 fetal TSH also detectable
 Mid-gestation:
 negative feedback control of thyroid hormone synthesis
develops
 Throughout gestation:
 pituitary-thyroid axis continues to develop
Fetal Thyroid Physiology
What crosses the placenta?
 iodine
 T3, T4 (poorly) – but large maternal–fetal gradient
 maternal TRH – but negligible amount in maternal circulation
 TSH-R antibodies (TSI/TBII)
 anti-thyroid medication – methimazole, PTU
Maternal TSH does NOT cross the placenta
Fetal Thyroid Physiology
Prior to 12 weeks gestation,
 fetus dependent on maternal thyroid hormone
production
 critical time for fetal neural development
(as well as later in gestation)
Throughout pregnancy,
 T4 and iodine supplied by mother to fetus
 maternal iodine supply very important throughout
 unclear role of maternal T4 after fetal T4 production
begins
Thyroid Disease in Pregnancy
 Hyperthyroidism
 Hypothyroidism
 Post-partum Thyroiditis
 Thyroid Nodules
Hyperthyroidism in Pregnancy
 ~ 0.2% of pregnancies complicated by hyperthyroidism
 Causes:
 Graves’ Disease
 toxic nodule/MNG
 thyroiditis
 exogenous iodine
 TSHoma
 struma ovarii
non hCG-mediated
 gestational transient thyrotoxicosis
 hyperemesis gravidarum
 gestational trophoblastic disease
 familial gestational thyrotoxicosis
hCG-mediated
Hypothyroidism in Pregnancy
 overt hypothyroidism ~ 0.1-0.3% of pregnancies
 subclinical hypothyroidism ~ 3-5% of pregnancies
 Causes:
 Hashimoto’s Thyroiditis (developed world)
 iodine deficiency
(worldwide)
 prior RAI ablation/thyroidectomy
 medications (lithium, amiodarone)
 central hypothyroidism (rare)
? genetic susceptibility
Subclinical Hypothyroidism
 TSH variable
~ 40-60% of TSH variability under genetic control?
 Genome Wide Association Scanning:
 SNP in PDE 8B gene associated with circulating TSH levels
 PDE 8 B – catalyzes hydrolysis of cAMP
 responsible for 2.3% of variance in TSH
 each copy of allele present – associated with an increase in
TSH concentration of 0.13 mIU/L
Arnaud-Lopez L et al. 2008 Am J Hum Genet 82:1270-80
Subclinical Hypothyroidism – PDE8B
Arnaud-Lopez L et al. 2008 Am J Hum Genet 82:1270-80
 1014 healthy pregnant women at 28 wks
 TFTs, anti-TPO, PDE8B genotype (AA, AG, GG)
 developed reference range (based on anti-TPO – subjects)
 TSH 0.49-4.21 mIU/L
 AA group had highest, GG group had lowest TSH
 AA group - greater proportion with TSH >4.21 mIU/L (ULN)
 SNP in PDE8B associated with  TSH - AA highest, GG lowest
 no difference in fT3, fT4 or prevalence of anti-TPO + Abs
Post-partum Thyroiditis (PPT)
 due to rebound autoimmunity post-partum
 lymphocytic infiltration, transient changes in thyroid
function
 + anti-TPO in >90% women with PPT
 those with high titres in early pregnancy more likely to be
affected (50-60%)
 high incidence in T1DM (18-25%)
 (high prevalence anti-TPO)
Post-partum Thyroiditis (PPT)
Pearce EN et al. 2003 N Engl J Med 348:2646-55
Thyroid Nodules in Pregnancy
 nodule > 1cm – FNAB
 if 1st or early 2nd trimester
and malignant OR rapid growth,
offer surgery in 2nd trimester
J Clin Endocrinol Metab 2007, 92(8):Suppl:S1-47
 if follicular or papillary, no advanced disease – can defer
surgery until post-partum
 can suppress TSH if: previously treated thyroid cancer,
FNAB suspicious or positive for malignancy, or if delaying
surgery until post-partum
 to detectable levels (keep fT4 in normal range)
Thyroid Nodules in Pregnancy
 RAI with I131 should NOT be
given to pregnant women or
those breastfeeding
 women with thyroid cancer
treated with therapeutic doses of RAI should avoid
pregnancy for 6-12 months post-ablation
J Clin Endocrinol Metab 2007, 92(8):Suppl:S1-47
Maternal Outcomes - Hyperthyroidism
 increased risk of:
 spontaneous pregnancy loss
 CHF
 thyroid storm
 preterm birth
 preeclampsia
 perinatal morbidity & mortality
Fetal Outcomes – Maternal Hyperthyroidism
 depends on degree of thyrotoxicosis, cause, and
treatment of mother
 in most cases, fetus is euthyroid
 but, transplacental transfer of TSH-R Abs (TSI/TBII) can
cause fetal Graves’ disease
 1-10% of neonates of affected women
 risk directly related to maternal Ab titre in 3rd trimester
 manifestations:
 fetal tachycardia
 high output heart failure
 hydrops fetalis
 craniosynostosis
 IUGR
 fetal goitre
Fetal Outcomes – Maternal Hyperthyroidism
Endocrine Society Clinical Practice Guidelines 2007
 measure TSH-R Abs prior to pregnancy or before
end of 2nd trimester in women with:
 current Graves’ Disease
 prior history of Graves’ Disease and I131 treatment or
thyroidectomy
 previous neonate with Graves’ Disease
 if – TSH-R Abs and don’t require anti-thyroid Rx
 low risk of fetal/neonatal thyroid dysfunction
J Clin Endocrinol Metab 2007, 92(8):Suppl:S1-47
Fetal Outcomes – Maternal Hyperthyroidism
 if + TSH-R Abs, need close fetal monitoring:
 fetal heart rate at each OB visit - ?tachycardia
 fetal ultrasound – assess growth, ?goitre – especially if mother
on anti-thyroid medication
 consider serial U/S q2-4 wks in 3rd trimester – if very high
TSH-R Abs titres
 ? fetal blood sampling for thyroid indices – not routine
 if high maternal TSH-R Abs, evidence of IUGR, fetal CHF, or
fetal goitre
J Clin Endocrinol Metab 2007, 92(8):Suppl:S1-47
ACOG Practice Bulletin Obstet Gynecol 2002, 100(2):387-396
Maternal Outcomes - Hypothyroidism
 increased risk of:
 early pregnancy failure
 preeclampsia
 placental abruption
 treatment of women with overt hypothyroidism
associated with improved pregnancy outcomes
Fetal Outcomes – Maternal Hypothyroidism
 increased risk of:
 low birthweight
 stillbirth
 intellectual impairment
 especially if overt maternal hypothyroidism in 1st
trimester
Outcomes – Subclinical Thyroid Disease
 less clear effect of:
 subclinical hypo/hyperthyroidism
 euthyroid thyroid autoimmunity (+ autoantibodies)
 maternal hypothroxinemia
 normal TSH but low fT4
on both maternal and fetal outcomes
 population-based cohort - Netherlands
 3659 children and their mothers (Apr/02-Jan/06)
 examined association between early pregnancy thyroid
function and cognitive function in early childhood
 maternal TFTs (mean 13.3 wk GA)
 verbal/nonverbal cognitive development – as per mailed
parent-report measures (18 and 30 months)
 specifically looked at maternal hypothyroxinemia
(normal TSH, but fT4)
TSH range 0.35-2.5
fT4 11-25 (non-preg)
Hypothyroid
TSH>2.5, fT4 <11
Hyperthyroid
TSH <0.03, fT4>25
Mild hypothyroxinemia
Normal TSH
fT4 <11.76 (10th %ile)
Severe hypothyroxinemia
Normal TSH
fT4 < 10.96 (5th %ile)
 mild hypothyroxinemia significantly related to
expressive language delay across ages
 severe hypothyroxinemia predicted  likelihood of
expressive language delay at 18m, 30m, and across ages
 severe hypothyroxinemia predicted  likelihood of
nonverbal cognitive delay at 30m
Conclusions:
 maternal hypothyroxinemia predicted a higher risk of
verbal and nonverbal cognitive delay in early childhood
 maternal TSH did not predict cognitive outcomes
 need more studies assessing potential benefit of iodine
or T4 supplementation in early pregnancy before can
justify implementation of fT4 screening in early
pregnancy
Screening in Pregnancy ?
 What is a normal TSH in pregnancy?
 Gestational age-specific TSH reference range?
 several studies, in variety of populations
 reference ranges in non-pregnant
populations are not applicable to pregnancy
Gestational Age-Specific TSH Range
 Dashe JS et al. 2005 Obstet Gynecol 106:753-7
 13 731 pregnancies
 13 599 singleton and
132 twin pregnancies
 measured TSH
 assay reference 0.4 – 4
 created nomogram based
on gestational age
342 women (singleton) with TSH above 97.5%ile
95 (28%) would not have been identified with TSH
elevation as per assay reference value
340 women (singleton) with TSH below 2.5%ile
1448 (11%) euthyroid women would have been
incorrectly characterized as abnormal as per assay
reference value
Dashe JS et al. 2005 Obstet Gynecol 106:753-7
Gestational Age-Specific TSH Range
 Gestational-age specific normal TSH range
 converted TSH
values to MoM
“multiples of median”
to facilitate use in
other populations
Dashe JS et al. 2005 Obstet Gynecol 106:753-7
 goal – to calculate gestational age-specific TSH, fT4 and
fT3 reference intervals in an iodine sufficient, thyroid
antibody-negative population
 also – to establish association between BMI and fT4, fT3
 prospective population-based cohort
 Northern Finland Birth Cohort 1986 (9632 singleton births)
Thyroid 2011 Jan 22 epub ahead of print
0.35
Assay reference range TSH 0.35-4.94
Thyroid 2011 Jan 22 epub ahead of print
19
Assay reference range
fT4 9-19
5.7
Assay reference range
fT3 2.62-5.7
Thyroid 2011 Jan 22 epub ahead of print
 95%ile selected as upper limit
 therefore, upper limit of 2.7-3.1 mU/L in 1st trimester
and 2.8-3.5 mU/L in early 2nd trimester
Thyroid 2011 Jan 22 epub ahead of print
 TSH increases
and fT4 decreases
with increasing
BMI
 fT3 increases
with increasing
BMI
Thyroid 2011 Jan 22 epub ahead of print
Screening in Pregnancy?
 YES - ? potential harm to fetus if undiagnosed
thyroid disease
 NO – ? unclear benefits of screening in preventing
adverse events
 screening of only high-risk women failed to detect
30% of hypothyroid and 69% of hyperthyroid women
Vaidya B et al. 2007 J Clin Endocrinol Metab 92:203-7
 4562 women, 2 centres in Italy
 randomized to universal screening or case-finding
 stratified as high risk or low risk
 all women in universal screening group, and high risk
women in case-finding group, had TSH, fT4, antiTPO
 low risk women in case-finding group:
 serum frozen, tested post-partum
 Rx LT4 if TSH >2.5 if +anti-TPO, or Rx antithyroid
medication if hyperthyroid
J Clin Endocrinol Metab 2010 95(4):1699-707
J Clin Endocrinol Metab 2010 95(4):1699-707
 No difference in total number of adverse outcomes in case finding vs screening
 Majority of adverse outcomes in euthyroid groups
J Clin Endocrinol Metab 2010 95(4):1699-707
Interaction between
thyroid status and trial
arm:
 low risk women:
adverse outcomes less
likely in screening vs case
finding
 inferred NNT = 1.8
36/39 had
at least 1
adverse
outcome
19/51 had
at least 1
adverse
outcome
J Clin Endocrinol Metab 2010 95(4):1699-707
J Clin Endocrinol Metab 2010 95(4):1699-707
 universal screening vs case-finding did not result in less
adverse outcomes
 BUT - low risk women in universal screening group
with abnormal thyroid function (who were treated)
avoided adverse outcomes more often than low risk
women in case finding group with abnormal thyroid
function (not detected, so not treated)
J Clin Endocrinol Metab 2010 95(4):1699-707
Screening in Pregnancy?
 CATS study – Controlled Antenatal Thyroid Screening
 multicentre, prospective randomized trial in UK from
2002-2010
 ~ 22 000 women, blood drawn prior to 16 wks GA
 before testing, randomized to “screening” or “control”
 screening group – tested, and if TSH or  fT4 – Rx LT4
 control group – tested post-partum, and if TSH or  fT4 – Rx
LT4 post-partum
 1o outcome: children’s IQ at 38-40 months - no difference
J Clin Endocrinol Metab 2007, 92(8):Suppl:S1-47
Management – Special Considerations
Hyperthyroidism
 goal – fT4 in upper limit normal range using lowest
possible dose, monitor q4 weeks
 PTU vs. methimazole ? – both equally effective
 benefits of PTU:
 crosses placenta less readily, less excreted in breastmilk
 decreased conversion fT4 to fT3
 methimazole – risk of aplasia cutis, esophageal/choanal
atresia (or is it due to hyperthyroidism itself?)
Management – Special Considerations
 Endocrine Society Clinical Practice Guidelines – 2007
 PTU is first line, especially during 1st trimester (organogenesis)
J Clin Endocrinol Metab 2007, 92(8):Suppl:S1-47
 However – concern re: PTU and hepatotoxicity
 2009 – meeting between American Thyroid Association and U.S.
FDA reviewing role of PTU vs. methimazole in pregnancy
 consider changing to methimazole in 2nd trimester?
Cooper DS & Rivkees SA. 2009 J Clin Endocrinol Metab, 94(6):1881-2
 systematic review to assess the effects of interventions for
preventing or treating hyperthyroidism in pregnant women
 criteria – RCTs (or “quasi-randomized” trials), including abstracts,
comparing antithyroid treatments in pregnant women
 unable to identify any eligible studies….
Cochrane Database Syst Rev 2010 (9):CD008633
Conclusions:
 unable to comment on implications for practice
 early identification of hyperthyroidism before pregnancy may
allow a woman to choose RAI or surgery before planning to
have a child
Cochrane Database Syst Rev 2010 (9):CD008633
PTU in Pregnancy
Br J Clin Pharmacol 2009, 68(4):609-17
 prospective observational controlled cohort study – 1994-2004
 115 PTU-exposed pregnancies and 1141 controls
 1o outcome – rate of major structural anomalies
 PTU exposure between weeks 4-13 GA
 2o outcomes – rate of fetal/neonatal thyroid dysfunction +/- goitre
 PTU exposure beyond 13 weeks GA
 other – pregnancy outcomes, pre-term delivery, birth weight
PTU in Pregnancy
 median daily dose of PTU 150 mg
Rosenfeld et al. 2009 Br J Clin Pharmacol, 68(4):609-17
PTU in Pregnancy
 data on neonatal thyroid function in 87 cases and fetal
thyroid ultrasound in 89 cases
 16/87 had thyroid dysfunction:
 hypothyroidism - 7/74 (9.5%) pregnancies with PTU
exposure after 13wks resulting in live birth
 dose range 150-300 mg/day – dose constant until goitre found
 3 without goitre, 4 with goitre
 hyperthyroidism – 9/87 (10.3%)
 dose range 25-200 mg/day – 50% dose constant, 50% dose had
been decreased
 7 without goitre, 2 with goitre
Rosenfeld et al. 2009 Br J Clin Pharmacol, 68(4):609-17
PTU in Pregnancy
Conclusions:
 no increased risk of major anomalies with PTU
exposure from 4-13 weeks GA
 PTU exposure after 13th week GA:
 9.5% neonatal hypothyroidism
 10.3% neonatal hyperthyroidism
 <50% goitre in neonates with thyroid dysfunction
 role of directed fetal thyroid ultrasound in prenatal
diagnosis of thyroid dysfunction, and for modification
of PTU dosing ?
Rosenfeld et al. 2009 Br J Clin Pharmacol, 68(4):609-17
PTU in Pregnancy
 started PTU 1st trimester for Graves’ Disease
 at 30 wks GA, fever, sore throat, malaise, cough, dyspnea
 WBC 0.7 x109/L (3-10 x109/L), neutrophils 0.1x109/L (1.5-8
x109/L), lymphocytes 0.5 x109/L (1-3.5 x109/L)
 PTU stopped, Rx antibiotics & bB, expectant management
 required thyroidectomy at 35 wks GA
Obstet Gynecol 2010, 116 Suppl 2:485-7
Management – Special Considerations
Hypothyroidism – LT4
 if diagnosed pre-pregnancy, target TSH <2.5 prior to
pregnancy
 if diagnosed during pregnancy, normalize TFTs as rapidly
as possible
 goal – TSH < 2.5 mIU/L in 1st trimester
< 3.0 mIU/L in 2nd and 3rd trimesters
or to trimester-specific normal TSH range
J Clin Endocrinol Metab 2007, 92(8):Suppl:S1-47
Management – Special Considerations
Hypothyroidism – LT4
 thyroid hormone requirements  by 20-40% in
pregnancy
 ? best way to meet these increased requirements in
women with pre-existing hypothyroidism already on
replacement
Management – Special Considerations
 Endocrine Society guidelines do not specify how
J Clin Endocrinol Metab 2007, 92(8):Suppl:S1-47
 prospective randomized trial
 enrolled 60 pregnant women with 1o hypothyroidism on LT4,
either seeking pregnancy or newly pregnant (<11wks GA)
 on stable dose of LT4 for at least 6 wks prior, with normal baseline TSH
within 6 months of conception
 after pregnancy confirmed, randomized to either:
 group A – increase by 2 tablets/week (extra tablet Sat, W)
 29% dose increase
 group B – increase by 3 tablets/week (extra tablet M, W, Fri)
 43% dose increase
 repeat TSH, total T4, thyroid hormone binding ratio
2 weeks until 20 wks GA, then at 30 wks
 LT4 dose adjusted q 4 wks as per protocol
 wks 4, 8, 12, 16, 20, 30
 on other weeks, LT4 changed only if TSH >10 or <0.1
 wks 6, 10, 14, 18
q
10 miscarriages (16.6%)
1 stillbirth (20 wks – incompetent cervix)
1 molar pregnancy
 initial LT4 dose increase normalized TSH <5 in all
patients for the remainder of the 1st trimester
 initial LT4 increase caused TSH suppression <0.5 (or
<0.1 in thyroid cancer patients) in:
 8/25 = 32% in Group A
P <0.01
 15/23 = 65% in Group B
18/29
20/32
13/20
P=0.02
 also investigated optimal frequency of TSH evaluation
 in 25 patients in Group A:
 if tested every 4 wks, 24/26 (92%) of abnormal TSH values
would have been detected
 if tested every 6 wks, 19/26 (73%) of abnormal TSH values
would have been detected
Conclusions:
 a 29% LT4 dose increase (2 tablets extra/week)
significantly decreased risk of maternal hypothyroidism
throughout 1st trimester
 q4 week TSH required to detect further changes in
dose requirements
 predictors of suppression: pre-pregnancy LT4 dose, prepregnancy TSH and etiology of hypothyroidism
 retrospective study
 53 pregnant women on LT4, with pre-conception
(within 6 months) TSH <2.5, but within normal range
 stable LT4 dose pre-conception as at first visit
 divided into:
 Group 1 – women who required LT4 dose increase
 Group 2 – women who did not require dose increase
2010 Thyroid 20(10):1175-8
 pre-conception TSH higher in Group 1 vs. Group 2
1.55 + 0.62 mU/L vs. 0.98 + 0.67 mU/L (p<0.005)
 when pre-conception TSH 1.2-2.4 – 50% needed 
 when pre-conception TSH 0.1-1.2 – 17.2% needed 
(p<0.02)
2010 Thyroid 20(10):1175-8
Management – Special Considerations
Subclinical Hypothyroidism
 recall: ~3-5% of pregnancies
 does this require treatment?
 is there any evidence showing benefit in treating?
 what about euthyroid women with + antibodies?
 to identify interventions used in management of clinical and
subclinical hypothyroidism in pregnancy
 to ascertain the impact of these interventions on important
maternal, fetal, neonatal and childhood outcomes
Cochrane Database Syst Rev 2010 (7):CD007752
 1o outcomes:
Maternal – pre-eclampsia (variously defined)
Infant – pre-term delivery (<37 weeks GA)
Infant as child – neurodevelopmental delay (variously defined)
Cochrane Database Syst Rev 2010 (7):CD007752
 2o outcomes:
Maternal
PP hemorrhage
miscarriage
PP depression
anemia
maternal death
gestational HTN
excessive weight gain QOL
infertility
placental abruption
preterm labour
symptomatic hypothyroidism
Infant
Fetal
lethargy
IUFD
SGA
cretinism macroglossia
hypotonia
goitre
admission to special care nursery
jaundice requiring Rx
poor feeding
hoarse cry
constipation
Cochrane Database Syst Rev 2010 (7):CD007752
 3 trials involving 314 women, all in Italy
 moderate iodine-deficient area
 compared:
 levothyroxine vs. no treatment
 selenomethionine (selenium) vs. placebo
 levothyroxine adjusted dose vs. no adjusted dose
 all at moderate risk of bias
Cochrane Database Syst Rev 2010 (7):CD007752
Cochrane Database Syst Rev 2010 (7):CD007752
Results - LT4 vs. none:
 euthyroid women with
+anti-TPO
  risk of pre-term
birth
 non-significant trend
towards fewer
miscarriages (1st
trimester)
Cochrane Database Syst Rev 2010 (7):CD007752
Results - selenium:
  risk of PP thyroid
dysfunction w/in 12
months post delivery
 non-significant trend
towards less overt
hypothyroidism 12
months post delivery
Conclusions:
 LT4 in overt hypothyroidism – standard practice
 “Whether levothyroxine should be utilised in autoimmune and
subclinical hypothyroidism remains to be seen, but it may prove
worthwhile, given a possible reduction in preterm birth and
miscarriage.”
 selenium – promising, but needs further study
Cochrane Database Syst Rev 2010 (7):CD007752
Management – Special Considerations
Endocrine Society Clinical Practice Guidelines – 2007
 LT4 treatment recommended in all pregnant women
with subclinical hypothyroidism
 not proven to modify long-term neurological
development in offspring, but improvement in obstetrical
outcomes
 potential benefits outweigh potential risks
J Clin Endocrinol Metab 2007, 92(8):Suppl:S1-47
Objectives
 To briefly review thyroid anatomy and physiology in
pregnancy and fetal thyroid physiology
 To review causes of thyroid disease in pregnancy
 To review the maternal and fetal outcomes of
thyroid disease in pregnancy
 To discuss the controversy surrounding screening
for thyroid disease in pregnancy
Objectives
 To review special considerations in management of
thyroid disease in pregnancy
 To highlight recent 2009-2011 articles published on
thyroid disease in pregnancy
References
 Casey BM & Leveno KJ. Obstet Gynecol 2006;1081283-9
 Keely E & Casey BM (2010). Thyroid disease in pregnancy. In RO Powrie, MF
Greene, W Camann (Eds) de Swiet’s Medical Disorders in Obstetric Practice (5th Edition
pp322-34). West Sussex, Wiley-Blackwell
 Arnaud-Lopez L et al. 2008 Am J Hum Genet 82:1270-80
 Shields BM et al. 2009 J Clin Endocrinol Metab 94(11):4608-12
 Pearce EN et al. 2003 N Engl J Med 348:2646-55
 J Clin Endocrinol Metab 2007, 92(8):Suppl:S1-47
 Cooper DS & Rivkees SA. 2009 J Clin Endocrinol Metab, 94(6):1881-2
 Earl R et al. 2010 Cochrane Database Syst Rev, (9):CD008633
 Rosenfeld H et al. 2009 Br J Clin Pharmacol, 68(4):609-17
 Murji A et al. 2010 Obstet Gynecol, 116 Suppl 2:485-7
 ACOG Practice Bulletin Obstet Gynecol 2002, 100(2):387-396
 Yassa L et al. 2010 J Clin Endocrinol Metab, 95:3234-41
 Abalovich M et al. 2010 Thyroid 20(10):1175-8
 Reid SM et al. 2010 Cochrane Database Syst Rev, (7):CD007752
References
 Negro R et al. 2006 J Clin Endocrinol Metab 91(7):2587-91
 Negro R et al. 2007 J Clin Endocrinol Metab 92(4):1263-8
 Rotondi M et al. 2004 Eur J Endocrinol 151:695-700
 Dashe JS et al. 2005 Obstet Gynecol 106:753-7
 Männistö T et al. 2011 Thyroid Jan 22 epub ahead of print
 Vaidya B et al. 2007 J Clin Endocrinol Metab 92:203-7
 Negro R et al. 2010 J Clin Endocrinol Metab 95(4):1699-707
 Henrichs J et al. 2010 J Clin Endocrinol Metab 95(9):4227-34
Negro R. et al. 2006 J Clin Endocrinol Metab 91(7):2587-91
 115 euthyroid anti-TPO+ women randomized to LT4 vs. no
treatment
 0.5 ug/kg/d if TSH <1 mIU/L, 1.0 ug/kg/d if TSH 1-2 mIU/L,
1.5 ug/kg/d if TSH >2 mIU/L or anti-TPO > 1500 kIU/L
 euthyroid anti-TPO- women were controls
 gestational HTN, severe pre-eclampsia, pre-term birth,
TSH, fT4, miscarriage, abruption, neonatal characteristics
Cochrane Database Syst Rev 2010 (7):CD007752
Negro R. et al. 2007 J Clin Endocrinol Metab 92(4):1263-8
 169 euthyroid anti-TPO+ women randomized to selenium 200
ug/d) at or after 12 wks GA vs. placebo
 anti-TPO- women were controls
 permanent hypothyroidism, PP thyroid dysfunction,
fT4, anti-TPO Ab levels
Cochrane Database Syst Rev 2010 (7):CD007752
TSH,
Rotondi M. et al. 2004 Eur J Endocrinol 151:695-700
 25 women with 1o hypothyroidism (Hashimotos or
thyroidectomy) on LT4 who were anticipating pregnancy within
next 1 yr, randomized to “modified” (target low-normal TSH) vs.
“non-modified” (same dose), then seen at <12 wks GA
 TFTs pre-conception and post-conception
Cochrane Database Syst Rev 2010 (7):CD007752