Thyroid disease pregnancy
Download
1 / 67

Thyroid Disease & Pregnancy - PowerPoint PPT Presentation


  • 250 Views
  • Uploaded on

2 nd International Endocrine Congress Esfahan, Iran October 10-12, 2012. Thyroid Disease & Pregnancy. Hossein Gharib, MD, MACP, MACE Professor of Medicine, Mayo Clinic College of Medicine President-Elect, American Thyroid Association. Disclosure & Thanks. Nothing to disclose

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Thyroid Disease & Pregnancy' - kolya


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Thyroid disease pregnancy

2nd International Endocrine Congress

Esfahan, IranOctober 10-12, 2012

Thyroid Disease & Pregnancy

Hossein Gharib, MD, MACP, MACEProfessor of Medicine, Mayo Clinic College of MedicinePresident-Elect, American Thyroid Association


Disclosure thanks
Disclosure & Thanks

  • Nothing to disclose

  • My sincere thanks for the invitation to be with you today

  • This presentation is based on clinical evidence, recent guidelines and good clinical judgment


Thyroid pregnancy
Thyroid & Pregnancy

Physiologic changes

  •  TBG

  •  I requirement

  •  urinary I excretion

  •  T4 & T3 synthesis

  •  HCG

  •  immunity


Changes in maternal thyroid function in pregnancy

 E

 TBG

 TSH

 FT4

  • iodine

    TPO Ab

 HCG

 FT4

 TSH

 T4

 TSH

 placental DI III

Changes in maternalThyroid Function in Pregnancy

 goiter

 Tg

 TSH

Modified from JCEM 86:2349, 2001


Presentation of thyroid disease in general
Presentation of Thyroid Disease in General

  • Goiter

  • Symptoms of hyper- or hypothyroidism

    This is also the case in autoimmunethyroid diseases and also the caseduring pregnancy


Hypothyroidism and pregnancy
Hypothyroidism and Pregnancy

  • Hypothyroidism occurs in 0.05% of all pregnancies

  • SCHypo occurs in 2.5-5%

  • Symptoms are masked and diagnosis often overlooked

  • Most common cause worldwide is I deficiency; in U.S. Hashimoto thyroiditis

Endo metab Clin N Am 31:893, 2004


Screening for thyroid disease in pregnancy
Screening for Thyroid Disease in Pregnancy

A 24-year-old woman was just diagnosed withher first pregnancy. She enjoys good generalhealth. There is no h/o thyroid disease or Rx.

Q: Should she have screening TFT?

Thyroid 21:1081-1125, 2011


What are the recommendations for tsh and t4 screening in pregnancy
What are the recommendations forTSH and T4 Screening in Pregnancy

  • Recommendation 72There is insufficient evidence to recommendfor or against universal TSH screening atthe 1st trimester visit

  • Recommendation 73Because no studies to date have demonstrated a benefit to treatment ofisolated maternal hypothyroxinemia,universal FT4 screening of pregnantwomen is not recommended

Thyroid 21:1081, 2011


Screening for thyroid disease in pregnancy1
Screening for Thyroid Disease in Pregnancy

  • Screening for subclinical hypothyroidism in pregnancy will be a cost-effective strategy under a wide range of circumstances. Thung et al: Am J Obstet Gynecol 2009

  • Screening all pregnant women for autoimmune thyroid disease in the 1st trimester is cost-effective compared with not screening. Dosiou et al: EJE, 2008

  • There are few prospective RCTs to substantiate the benefit of screening… the clinical epidemiological evidence does not justify universal screening at the present time. Lazarus J: Thyroid Res 2011

  • Routine TSH screening before pregnancy or during the first trimester in all pregnant women. Gharib et al: Endocr Pract 2002


Screening for thyroid disease in pregnancy2
Screening for Thyroid Disease in Pregnancy

Although the benefits of universal screening for thyroid dysfunction may not be justified at this time, selected screening for the following should be done:

  • Positive FHxthyroid disease

  • Goiter

  • TPOAb+

  • Symptoms

  • Type 1 DM

  • Miscarriage

  • Other autoimmunedisease

  • Infertility

  • Morbid obesity

  • >30 years

Thyroid 2011


Tsh in pregnancy
TSH in Pregnancy

A 28-year-old woman who is 6 weekspregnant has a routine serum TSHlevel of 4.1 mIU/L & FT4 1.3 ng/dL

Q: Is this TSH normal?


Tsh levels in normal pregnancies n 343

3.5

3.5

3.5

3.1

2.3

1.3

1.2

1.2

0.8

1.1

0.13

0.03

0.03

0.4

0.4

TSH Levels in Normal Pregnanciesn=343

Median and 95% TSH

4.5

3.5

2.5

TSH

(mIU/L)

1.5

0.5

0.03

1st trimester

2nd trimester

3rd trimester

10

20

30

40

Weeks gestation

Panesar NS et al: Ann Clin Biochem 32:329, 2001


Guidelines for serum tsh during pregnancy
Guidelines for Serum TSH During Pregnancy

  • Recommendation 1Trimester-specific reference ranges for TSH, as defined in populations with optimal iodine intake,should be applied

  • Recommendation 2If trimester-specific reference ranges for TSH are not available in the laboratory, the following references ranges are recommend:1st trimester, 0.1-2.5 mIU/L; 2nd trimester,0.2-3.0 mIU/L; 3rd trimester, 0.3-3.0 mIU/L


Guidelines for serum ft4 during pregnancy
Guidelines for Serum FT4 During Pregnancy

  • Recommendation 3The optimal method to assess serum FT4 during pregnancyis measurement of T4 in the dialysate or ultrafiltrate of serum samples employing on-line extraction/liquid chromatography/tandem mass spectrometry (LC/MS/MS)

  • Recommendation 4If FT4 measurement by LC/MS/MS is not available, clinicians should use whichever measure or estimate of FT4 is available in their laboratory, being aware of the limitations of each method; serum TSH is a more accurate indication of thyroid status in pregnancy than any of these alternative methods

  • Recommendation 5In view of the wide variation in the results of FT4 assays, method-specific and trimester-specific reference ranges of serum FT4 are required


Hypothyroidism in pregnancy
Hypothyroidism in Pregnancy

  • Thyroid hormone is crucial for fetal brain development

  • Untreated congenital hypothyroidism is associated with low intelligence, impaired growth, cognitive and psychological disturbances (cretinism)

  • Hypothyroidism later in childhood is also associated with impaired growth, behavioral problems, symptoms of ADHD


Thyroid and pregnancy
Thyroid and Pregnancy

Physiologic consequences for the fetus

  • Fetal development – in particular that ofthe brain – is dependent on the thyroid function of the mother

  • The thyroid gland is not developed inthe fetus until 12th week

  • Thyroxine (T4) passes placenta, but relatively poorly


Sch in pregnancy
SCH in Pregnancy

A 26-year-old woman desires pregnancy; serum TSH is 4.5 mIU/L and FT4 1.0 ng/dL

Questions:

  • Should you order TPOAb?

  • Should you Rx with T4 if TPOAbis positive?

  • What if TPOAb is negative?


Increased pregnancy loss in tpoab neg women with tsh 2 5 5 0

4,562

First trimester pregnant women

439

Hyper & TPOAb+

4,123

TPOAb-

642

TSH 2.5-5.0

3,481

TSH <2.5

Pregnancy loss

3.6%

Pregnancy loss

6.1%

P=0.006

Increased Pregnancy Loss in TPOAb-Neg Women with TSH 2.5-5.0

Negro R et al: JCEM 95:E44-8, 2010


Why is it important to diagnose autoimmune thyroid disease in pregnancy
Why is it Important to diagnose Autoimmune Thyroid Disease in Pregnancy?

  • Most thyroid diseases in young women resultingin thyroid dysfunction are due to autoimmunity

  • Maternal thyroid dysfunction has adverse effects on the fetus

  • Improved treatment plan for the mother is beneficial to the fetus


Effects of hypothyroidism on pregnancy outcomes

  • Anemia in Pregnancy?

  • Hypertension

  • Preeclampsia

  • Abruptio placenta

  • Postpartum hemorrhage

  • Miscarriage

  • Low birth weight

  • Stillbirth

  • Psychoneurologic impairment

Effects of Hypothyroidism onPregnancy Outcomes

Maternal

Fetal

JCEM, 2007


Autoimmune thyroidits
Autoimmune Thyroidits in Pregnancy?

  • Hyperthyroidism

    • Graves’ disease

    • Hashitoxicosis

  • Euthyroidism

    • Symptom-free autoimmune thyroiditis

  • Hypothyroidism

    • Hashimoto’s thyroiditis

    • Atrophic thyroiditis


Tsh changes in tpoab pregnant women during gestation

D in Pregnancy?

E

L

I

V

E

R

Y

40

30

20

10

0

10

20

30

40

TSH Changes in TPOAb (+) PregnantWomen During Gestation

TSH 3mIU/I(in % of cases)

Weeks of gestation

Glinoer D et al: JCEM 79:197-204, 1994


Tpoab and hypothyroidism
TPOAb and Hypothyroidism in Pregnancy?

  • Women with thyroid autoimmunity (i.e. positive TPOAb) who are euthyroid in the early stages of pregnancy are at risk of developing hypothyroidism

  • Should be monitored for elevation of TSH above the normal range


Treatment with lt4 in pregnant women with tai effects on obstetrical complications

58 TPOAb + in Pregnancy?No treatment

O

U

T

C

O

M

E

115TPOAb +

984pregnantwomen

57 TPOAb +LT4

869TPOAb-

Treatment with LT4 in Pregnant Women with TAI: Effects on Obstetrical Complications

LT4: 0.5 g/kg.d TSH <1.0 mIU/I

0.75 g/kg.d TSH 1.0-2.0 mIU/I

1 g/kg.d for TSH >2.0 mIU/I orTPOAb >1,500 kIU/L

Negro R et al: JCEM 91:2587-2591, 2006


Treatment with lt4 in pregnant women with tai effects on obstetrical complications1
Treatment with LT4 in Pregnant Women with TAI: Effects on Obstetrical Complications

Miscarriage

Preterm Delivery

%

Negro R et al: JCEM 91:2587-2591, 2006


Study conclusions
Study Conclusions Obstetrical Complications

  • Under powered study

  • Neither placebo controllednor double blind

  • LT4 Rx reduced miscarriageand preterm delivery


Autoimmune thyroid disease and miscarriage
Autoimmune Thyroid Disease Obstetrical Complicationsand Miscarriage

  • Many studies show increased miscarriage in euthyroid women with thyroid antibodies

  • Majority of studies demonstrate an association between thyroid antibodies and recurrent miscarriage

  • A causal relationship not established

  • Should we treat TPOAb+ women?


Thyroid antibodies and spontaneous miscarriage

Ab + Obstetrical Complications

Ab –

Thyroid Antibodies and Spontaneous Miscarriage

Bagis (2001)

Singh (1995)

Glafoor (2006)

Lejeune (1993)

Stagnaro-Green (1990)

Glinoer (1991)

Negro (2006)

Lijima (1997)

Netto (2004)


Recurrent abortion and thyroid antibodies

Ab + Obstetrical Complications

Ab –

Recurrent Abortion and Thyroid Antibodies

Dendrinos (2000)

Bassen (1997)

Bassen (1995)

Esplin (1998)

Pratt (1993)

Kutteh (1999)


30 articles with 31 studies (19 cohort and 12 case-control) involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.Cohort studies: OR 3.90 (95% confidence interval 2.48 to 6.12; P<0.001).Case control studies: OR 1.80 (1.25 to 2.60; P=0.002).

There was a significant doubling in the odds of preterm birth with the presence of thyroid autoantibodies (2.07, 1.17 to 3.68; P=0.01).

Conclusion: The presence of maternal thyroid autoantibodies is strongly associated with miscarriage and preterm delivery. There is evidence that treatment with levothyroxine can attenuate the risks.

Thangaratinam S et al: BMJ 342:d2616, 2011

3162596-30


Schypo pregnancy
SCHypo & Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

  • SCH (serum TSH concentration above the upper limit of the reference range with a normal free T4) has been shown to be associated with an adverse outcome for both the mother and offspring


Perinatal outcomes in hypothyroid pregnancies

% involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

Perinatal Outcomes inHypothyroid Pregnancies

68 women

23 with overt hypo

45 with SCH

Overt

Subclinical

Control

Leung AS et al: Obstet Gynecol 81:349, 1993


Overt and subclinical hypothyroidism complicating pregnancy
Overt and Subclinical Hypothyroidism Complicating Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

51 pregnancies

16 overt hypo

35 subclinical hypo

60% abortion

Rx inadequate

0% abortion

Rx adequate

71% abortion

Inadequate Rx

0% abortion

Adequate Rx

Adequate Rx – TSH <4 mIU/L

Abalovich m et al: Thyroid 12:63, 2002


Hypothyroidism pregnancy
Hypothyroidism & Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

  • 25,216 women with TSH screen retrospectively reviewed

  • All newborn euthyroid at birth

  • IQ scores of children born to mothers with slight TSH elevation were <7 points vs controls

  • Undiagnosed hypothyroidism in pregnancy adversely affects fetuses


21,846 involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.pregnant womenat 11-14 weeks

Control

Screen

TSH >97.5th%FT4 <2.5th%

T4Rx

Follow

IQ test in all children atage 3 were similar

Lazarus et al: N Engl J Med 2012;366:493-501


Guidelines recommendations
Guidelines Recommendations involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

  • Recommendation 8 There is insufficient evidence to recommend for or against universal LT4 Rx in TPOAB negative women with SCHypo

  • Recommendation 9 Women who are positive for TPOAb and have SCHypo should be treated with LT4

    Thyroid, 2011


Schypo and pregnancy to treat or not to treat
SCHypo and Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.To Treat or Not To Treat?

  • Although efficacy of LT4 Rx has not been proved, given that the potential benefits outweigh the potential risks, T4 replacementis recommended


Hypothyroidism pregnancy1
Hypothyroidism & Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

A 28-year-old woman has been on T4 for hypothyroidism for 5 years; she is now pregnant and taking LT4 125 mcg daily

Q: What is optimal T4 dose and TSH level?


Hypothyroidism pregnancy2
Hypothyroidism & Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

  • Recommendation 13Treated hypothyroid women on LT4 who are newly pregnant should increase T4 dose by 30%

  • Recommendation 15Treated hypothyroid women on LT4 who are planning pregnancy should have T4 dose adjusted to TSH <2.5 MIU/L

  • Recommendation 16Maternal serum TSH should be monitored every 4 weeks during 1st half of pregnancy

Thyroid, 2011


Hyperthyroidism pregnancy
Hyperthyroidism & Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

A 32-year-old woman pregnant 10 weeks presents with nausea, vomiting, and a 2 kg weight loss; her first pregnancy 2 years earlier was uncomplicated

On exam she is a bit dehydrated, euthyroid, without a goiter and has normal eyes

TSH 0.01 (<2.5)

FT4 2.1 (0.8-1.8)

FT4I 20 (5-12)

Q: Does she require antithyroid Rx?


Hyperthyroidism pregnancy clinical clues in ddx
Hyperthyroidism & Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.Clinical Clues in DDx


Hyperthyroidism pregnancy conclusions
Hyperthyroidism & Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.Conclusions

  • Hyperemesis gravidarum is HCG-induced, reversible, and rarely requires ATD

  • Measure TSH receptor Ab (TRAb) to distinguish from Graves’ disease


Hyperthyroidism pregnancy1
Hyperthyroidism & Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

  • Recommendation 22When serum TSH is suppressed (<0.1) inthe 1st trimester, FT4 should be obtained;TT3 & TRAb may also be helpful

  • Recommendation 26ATDs are not recommended for Rx of gestational hyperthyroidism


Hyperthyroidism pregnancy2
Hyperthyroidism & Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

A 32-year-old woman is 8 weeks pregnant; she reports palpitations, anxiety, heat intolerance and an 8 lb weight loss for 6 months

On exam she is nervous, slightly hyperthyroid, has lid lag, and thyroid is x2 enlarged

TSH 0.01FT4 2.8

FT4I 16 (5-12)TRAb 75% (<16%)

Q: How do you manage?


TSH receptor involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.antibodies

Stimulating

T4

TSHreceptor

Blocking

T3

Stimulation

Tg

TSH

Spencer CA 2006

3162596-47


Mother involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

Fetus

Placenta

TRH

TRH

TSH

T3

T3

TSH

T4

T4

Stimulate

TSH receptorantibodies

Block

TPOAb & TgAb

Anti-thyroiddrugs

Block

Spencer CA 2006


Hyperthyroidism pregnancy3
Hyperthyroidism & Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

  • Thyroid autoantibodies (TRAb) cross placenta

  • Affect fetal thyroid after week 12

  • Fetus can develop intrauterinemyxedema or hyperthyroidism evenif mother is euthyroid

  • Avoid combination T4/ATD Rx


Hyperthyroidism pregnancy4
Hyperthyroidism & Pregnancy involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage.

  • Recommendation 28PTU is preferred for Rx of hyperthyroidismin the 1st trimester

  • Recommendation 29A combination of ATD and LT4 (block and replace) should not be used in pregnancy

  • Recommendation 30FT4 and TSH should be monitoredevery 2-6 weeks


How to treat the women with graves hyperthyroidism before pregnancy
How to Treat the Women with Graves’ Hyperthyroidism Before Pregnancy

  • Antithyroid drugs

    • PTU

    • MMI

    • Block & replace

  • Radioiodine

  • Total thyroidectomy


Tsh receptor antibodies trab after various types of treatment for graves disease
TSH Receptor Antibodies (TRAb) After Various PregnancyTypes of Treatment for Graves’ Disease

s-TRAB (% inhibition of125-I TSH binding)

Radioiodine

Surgery

Medication

Years

Laurberg et al: EJE 158:69-75, 2008


Postpartum thyroiditis
Postpartum Thyroiditis Pregnancy

A 32-year-old woman who delivered 2 months ago reports depression, excess fatigue and feeling cold

Q: Should she have TFT?

A: TSH is 37 mIU/L, FT4 0.3 ng/dL and TPOAb 580

Q: Should you treat with T4?


Postpartum thyroiditis definition
Postpartum Thyroiditis PregnancyDefinition

  • Autoimmune disorder characterized by lymphocytic infiltration of the thyroid gland and by the occurrence, in the postpartum period, of transient hyperthyroidism and/or transient hypothyroidism

  • Most women return to the euthyroid state by 1 year postpartum


Prevalence of ppt

Denmark 3.3% Pregnancy

Netherlands 7.2%

Sweden 6.5%

Denmark 3.9%

UK 16.7%

Toronto 6.0%

Netherlands 5.2%

Spain 7.8%

NYC 8.8%

Iran 11.4%

Italy 8.7%

Japan 5.5%

India 7%

Thailand 1.1%

Brazil13.3%

Prevalence rate of postpartum thyroiditis is 7.5%

Prevalence of PPT

3162596-55


Clinical course of postpartum thyroiditis
Clinical Course of Postpartum Thyroiditis Pregnancy

Hyper

Euthyroid

Hypo

0 3 6 9 12

Postpartum (months)

Stagnaro-Green A: JCEM 87:4042-7, 2002


Pregnancy and immune function
Pregnancy and Immune Function Pregnancy

  • In a normal pregnancy, the maternal immune system undergoes a remission to allow the maintenance of the fetus

  • Thyroid antibodies, as well as those directed against other tissues suppressed during pregnancy, often increase after delivery

  • The autoimmune rebound after delivery characterize patients with Hashimoto’s and Graves’ disease, who frequently present a worsening of thyroid dysfunction after delivery


Postpartum thyroiditis1
Postpartum Thyroiditis Pregnancy

  • Women with 1 episode of PPT have a 70% chance of recurrence with next pregnancy

  • Patients with TPOAb during pregnancy areat increased risk of developing PPT

  • Selenium, as an antioxidant, is reportedto reduce risk of PPT

  • When TPOAb is positive, TSH and FT4should be checked at 3 and 6 months PP


Conclusions 1
Conclusions (1) Pregnancy

  • Profound physiologic changes of thyroid function occur in pregnancy

  • Serum TSH is the gold standard forthyroid evaluation

  • Targeted thyroid screening is recommended during pregnancy

  • New trimester-specific TSH levels are now available and should be used

  • Both overt and subclinical hypothyroidismcan adversely affect pregnancy


Conclusions 2
Conclusions (2) Pregnancy

  • Hypothyroid patients on T4 Rx oftenrequire  dose in pregnancy

  • Women with SCH and positive TPOAbshould be treated with T4 prior to andduring pregnancy

  • PTU is the drug of choice in early pregnancy

  • PPT is a common and often an overlooked problem after delivery


Thank you! Pregnancy


Thank you! Pregnancy


Title/drp – author: BK – Gharib, Hossein PregnancySub/drp – Job#: BK – 3162596

Subject: Thyroid Disease in Pregnancy

Background: Custom

Plot/brdr: open/BK

Banner/brdr:

232

179

68

102

79

18

53

40

9

109

131

61

Side title: 43-114-149

  • /colhdgs: 43-114-149

PPT shooting instructions

PPT File to Server(64 images)

Text: BK

Highlight: OR108

Subdue: Custom

Artist: mls Due Date: 12-21-2011

Footnotes: 102-79-18

COLOR REFERENCE ONLY


Autoimmune thyroid disease pregnancy

6 Pregnancyth Annual Philippines AACE Endocrine Congress

Cebu, PHAugust 9-12, 2012

Autoimmune Thyroid Disease& Pregnancy

Hossein Gharib, MD, MACP, MACEProfessor of Medicine, Mayo Clinic College of MedicinePast President, American Association of Clinical Endocrinologists


What are the recommendations for tpoab screening in pregnancy
What are the Recommendations for PregnancyTPOAb Screening in Pregnancy?

  • Recommendation 45There is insufficient evidence to recommend foror against screening for thyroid antibodies in the first trimester of pregnancy, or treating TPOAb+ euthyroid women with LT4 to prevent preterm delivery

Thyroid, 2011


Guidelines recommendations1
Guidelines Recommendations Pregnancy

.R 8 There is insufficient evidence to recommend for or against universal LT4 Rx in TPOAb negative women with SCHypo

.R 9 Women who are positive for TPOAb and have SCHypo should be treated with LT4

Thyroid, 2011


Thyroid and pregnancy1
Thyroid and Pregnancy Pregnancy

Consequences of the physiologic changes

  • High risk for false estimation of thyroid function tests

  • Increase goiter size may becomeclinically significant


ad