Brigitte VelkeniersBrigitte Velkeniers

Kris PoppeKris Poppe

Free University of BrusselsFree University of Brussels

Thyroid & PregnancyThyroid & Pregnancy

Classification

• Thyroid function &– Normal reproduction

• dysfunction and menstruations

– Changes during pregnancy

• Thyroid disorders BEFORE pregnancy– In association with

• infertility / COH

• Thyroid disorders DURING pregnancy– Thyroid Autoimmunity –without dysfunction-

– Hypothyroidism / Hyperthyroidism

• Thyroid disorders AFTER pregnancy– Post Partum Thyroiditis / Graves’-Basedow

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Woman (23 years)

She stopped 6 m before the consultation with thiamazol

for a Graves’ disease

She consulted to « talk » about the relationship between

thyroid disorders and pregnancy

Next visit 6 months later

unless pregnancy or relapse of the Graves’ disease

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Q

Does hyperthyroidism influence fertility ?

• direct effects– T3-receptors are present on

» theca cells

» corpus luteum

» throphoblast

• indirect effects– GnRH secretion

– PRL secretion

– SHBG levels

– Coagulation factors

» In hypoT: decreased levels of factors VII, VIII, IX, and

XI

Poppe K et al. Clinical Endocrinology 2007

46/214 = 22 % 18/124 = 15 %

46/214 = 22 % 18/124 = 15 %

The prevalence of infertility due to these

menstrual irregularities

is however unknown

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One month before the planned consultation,

the patient came with symptoms of hyperthyroidism,

biologically confirmed

PTU 3*1

was started

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No symptoms, but

she had a pregnancy wish

PTU 3*1 – LT4 50 ug/d

continued

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Q

What would you propose in general and

would you modify the treatment ?

PTU Methimazole

Protein Binding 75 % 0

Half-life 75 min 4-6 h

Duration of action 12-24 h > 24 h

Transplacental

passageLower Higher

Breast milk levels Lower Higher

PTU was historically preferred over MMI (especially in the US), with the rationale that the former was more water soluble and more extensively bound to albumin than MMI (limiting the trans-placental passage)

– this seems however to be unlikely …

Krassas et al. Endocrine Review 2010 in press

Side-effects of ATD in pregnancy

‘MMI embryopathy’ includes aplasia cutis and choanal or esophageal atresia

– Aplasia cutis is the absence of skin and accessory structures over the scalp.

Skin defects are estimated to occur in 1 out of ~4,000 to ~10,000 pregnancies and, from the scarce data available, it is considered that this incidence is not above background in pregnant women who have received MMI.

– Choanal or esophageal atresia is a severe congenital anomaly requiring

major surgery to repair and is considered to have a higher incidence than expected in fetuses exposed to MMI in the first trimester. The relative risk of choanal atresia in pregnant women receiving MMI was estimated to be ~17-fold greater than in the general population, although it should be noted that such congenital birth defects could also be attributed to thyrotoxicosis per se rather than to the administration of MMI.

Krassas et al. Endocrine Review 2010 in press

Aplasia cutis

- Available evidence suggests that MMI may be associated with congenital

anomalies, PTU should be used as a first line drug especially during 1st

trimester’s organogenesis.

- MMI may be prescribed if PTU is not available, or in case of intolerance

- T4 is not recommended with ATD during pregnancy

Graves’ treatment

Mortimer RH, et al. 1997 Methimazole and propylthiouracil equally cross the perfused

human term placental lobule. JCEM 82:3099-3102

Bournaud C, Orgiazzi J 2003 Antithyroid agents and embryopathies. Ann Endo (Paris) 64:366-369

• With regard to PTU, a controversy has recently come to light following the

alarming report that the use of PTU for treatment of pediatric GD was

associated with a significant risk of liver failure

– the Endocrine Society recommended that PTU stopped being used in the

pediatric population.

In the context of the first trimester of pregnancy, however, PTU remains the

drug of choice with a switch to MMI treatment thereafter. Finally, pregnant

women under PTU should monitor their liver function tests regularly.

- Rivkees SA, Mattison DR 2009 Ending propylthiouracil-induced liver failure in children.

NEJM 360:1574-1575

- FDA Statement (Medwatch Online) 2009 Information for healthcare

professionals PTU induced liver failure.

- The Endocrine Society Statement on the NEJM Letter to the Editor on PTU use in children (2009)

Side-effects of ATD in pregnancy

• Surgery

– may be necessary in women who cannot tolerate thionamides

because of allergy or agranulocytosis or have a huge goiter

• It is however associated with an increased risk of spontaneous

abortion or premature delivery. These risks are minimized by

operating during the second trimester.

Mother Placental barrierPlacental barrier FetusFetus

AntiAnti--TSH receptorTSH receptor

antibodies antibodies

with stimulating and/orwith stimulating and/or

blocking activityblocking activity

ThionamideThionamide

antithyroid drugsantithyroid drugs

(PTU, MMI )(PTU, MMI )

Hyperthyroidism ?Hyperthyroidism ?

Hypothyroidism ?Hypothyroidism ?

TSH-Rec Abs freely cross the placenta and can stimulate the fetal thyroid.

These antibodies should be measured before pregnancy or by the

end of the 2nd trimester in mothers with current GD, or with a history

of GD and treatment with I-131 or thyroidectomy, or with a previous

neonate with GD.

Women who have negative TRAb and do not require ATD have a

very low risk of fetal or neonatal thyroid dysfunction.

131-I should not be given to a woman who is pregnant.

If inadvertently treated, the patient should be promptly informed of

the radiation danger to the fetus, including thyroid destruction if treated

after the 12th week of gestation.

no pregnancy < 6 months after I*

MATERNAL HYPERTHYROIDISM

FETAL ASPECTS

Kamijo K 2007

TSH-receptor antibodies determined by the first, second and third generation assay and thyroid stimulating

antibody in pregnant patients with Graves’ disease. Endocr J 54:619–624

In women with elevated TRAb or in women treated with ATD, fetal ultrasound should

be performed to look for evidence of fetal thyroid dysfunction

- lgrowth restriction, hydrops, presence of goiter or cardiac failure.

Umbilical blood sampling should be considered only if the diagnosis of fetal thyroid

disease is not reasonably certain from the clinical data and if the information gained

would change the treatment.

All newborns of mothers with GD should be evaluated by the medical care

provider for thyroid dysfunction and treated if necessary.

MATERNAL HYPERTHYROIDISM:

FETAL ASPECTS

Eisenstein Z et al. Intellectual capacity of subjects exposed to

methimazole or propylthiouracil in utero. Eur J Ped 1992 151:558-9.

Krassas et al. Endocrine Review 2010 in press

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We advised :

To STOP LT4

To continue PTU 2*1

To continue her contraception

until thyroid function was normalized

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No symptoms

PTU 2*1

Miscarriage at the end of 2003

(contraception ??)

Next visit in 2 months

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Q

Is Graves-Basedow associated with

an adverse pregnancy outcome ?

Prevalence

• The prevalence of hyperthyroidism has been estimated

to range between 0.1% and 1%

• 0.4% clinical and 0.6% subclinical

– The most common cause is GD (85% of overt hyperthyroidism in pregnant women).

– A second common aetiology is gestational transient

thyrotoxicosis (GTT) or non-autoimmune hyperthyroidism.

• differentiation of GD from GTT is supported by presence of evidence of autoimmunity and/or a goiter

Krassas et al. Endocrine Review 2010 in press

GD – pregnancy morbidity and mortality

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No symptoms

PTU 2*1

8 weeks pregnant !

Q

What would you do now ?

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Treatment was stopped

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Normal pregnancy

No treatment

Next visit 6 weeks after pregnancy

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6w PP

Symptomatic hyperthyroidism

- 2*1 thiamazol

- Propanolol

- Next visit 2 weeks later

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Q

DD ?

DD GD – PPT

Stagnaro-Green A. Postpartum thyroiditis.

JCEM. 2002 Sep;87(9):4042-7.

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2-3 months PP

TSI –

Scintigraphy: no uptake

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Q

Is PPT frequent ?

PPT

– Prevalence between 3-17%

• 50 % in women with TPO-Ab

• 25 % in women with DM-1

– Recurrence in subsequent pregnancies (70%)

• The pathologic findings in the two disorders are similar and both are

associated with particular HLA-B and HLA-D haplotypes, suggesting

that inherited risk factors are important.

Stagnaro-Green A. Postpartum thyroiditis.

JCEM. 2002 Sep;87(9):4042-7.

Stagnaro-Green A. Postpartum thyroiditis.

JCEM. 2002 Sep;87(9):4042-7.

20-40%

20-30%

40-50%

20-30%

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-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

Q

How would you treat ?

Transient thyrotoxicosis No therapy or beta-blockers

Transient

hypothyroidism

T4 for 12-18 months; then discontinue

& check TSH

Permanent

hypothyroidismIndefinite T4 replacement

Treatment of PPT

Stagnaro-Green, Best Practice in Clinical Endocrinology 2004

PREVENTION of PPT ?

– Selenium supplementation may decrease inflammatory activity in pregnant

women with AITD and may reduce the risk of PPT in women who are

positive for TPO-abs.

• This was illustrated in a trial of 151 TPO-positive women randomly assigned to

receive selenium (200 mcg daily) or placebo (beginning at about the 12th week of

gestation). PPT occurred in 22 of 77 women (29 percent) in the selenium group,

compared to 36 of 74 (49 percent) in the placebo group.

– The routine clinical application of this supplementation requires further study.

Negro R et al. The influence of selenium supplementation on postpartum thyroid status in

pregnant women with thyroid peroxidase autoantibodies. JCEM 2007 Apr;92(4):1263-8.

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

- Methimazol STOPPED

- Propanolol not supported

- Diltiazem started

-Next visit 1 month later

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

4-10 months PP

TSI –

LT4 25 ug/d

- PP depression

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

Q

PPT & PP depression ?

PPT - PD

Lucas A et al. Postpartum thyroid dysfunction and postpartum depression:

are they two linked disorders? Clin Endo (Oxf). 2001 Dec;55(6):809-14.

PPT - PD

PPT - PD

• The general PD incidence rate of 1,7 % was not higher

in women with hormone abnormalities caused by PPTD.

– Women with a past history of depression present a higher risk of

PD while those who breast fed did not have an increased risk.

Stagnaro-Green, Best Practice in Clinical Endocrinology 2004

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

4-10 months PP

TSI –

LT4 25 ug/d

- PP depression (SSRI)

- next visit in 6 months

unless pregnant

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

Routine control

No symptoms

Treatment: LT4 25 ug/d

next visit in 6 months,

unless pregnant

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

Symptomatic

Hyperthyroidism

…

Q

What would

you propose ?

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

All posibilities were

proposed and the

patient wanted

a « definitive »

treatment with I*

…

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

After I*, increase in TSH

New pregnancy wanted

(6m after I*)

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

75 ug LT4 started to keep

serum TSH < 2.5 mIU/L

Abalovich M et al. J Clin Endocrinol Metab. 2007 Aug

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

> 6 months later,

still not pregnant

with an optimal TSH …

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

Idiopathic infertility

Q

Is this associated with

a higher prevalence of AITD ?

Poppe K et al. Nat Clin Pract Endocrinol Metab. 2008

Cause of

infertilityn (%) Age# TSH° FT4° TPO-Abs^

Female 197 (45) 34 6 1.3 (0.9) * 12 (2) 18 % *

Male 168 (38) 31 5 * 1.3 (0.9) * 12 (2) 11 %

Idiopathic 73 (17) 32 5 1.2 (1.1) * 12 (2) 7 %

All 438 (100) 32 5 1.3 (0.9) * 12 (2) 14 %

Controls 100 33 4 1.1 (0.8) 11 (2) 8 %

# mean SD ° median (interquartile) ^ % positive

* p < 0.05 against controls

Poppe et al. Thyroid 2002

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

Idiopathic infertility

COH started and ICSI planned

Q

What do you expect,

concerning

the TSH evolution ?

(R= 0.5; p < 0.0001)

Muller et al. JCEM 2000

------- before ART _______ after ART

p < 0.0001 p < 0.0001

Conclusion

• Serum TSH significantly increased and FT4

decreased after COH

• Remaining Q

– TAI status in relation to TSH, FT4 after COH ?

– Only one time point that TSH and FT4 was measured

– Outcome of ART ?

1

TSH

0.0

2.0

4.0

6.0

8.0

0 20 40 60 80 100

Time (days)

mU

/ L

FT4

10.0

11.0

12.0

13.0

14.0

15.0

16.0

0 20 40 60 80 100

Time (days)

ng

/ L

FT4

TSH TSH

TPO +

TPO -

TPO -

TPO +

Serum TSH and FT4 according to TAI status

p< 0.001

p=0.005

Poppe et al. JCEM 2004

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

Idiopathic infertility

COH started and ICSI planned

LT4 increased to 125 ug/d

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

Pregnant !

LT4 increased to 125 ug/d

1

1513 13

97

3 3 2 1 1 1 14

6

40

36

15

2 2 1 10.01

1.01

2.01

3.01

4.01

5.01

Aug

-02

Jan-03

Mar-0

3

May

-03

Jul-0

3

Oct-0

3

Jan-04

Apr-0

4

May

-04

Jul-0

4

Jan-05

Jan-05

Feb

-05

Feb

-05

Mar-0

5

Apr-0

5

Jun-05

Jul-0

5

Oct-0

5

Apr-0

6

Aug

-06

Sep

-06

Nov-06

Jan-07

May

-07

Jul-0

7

Dec-07

Feb

-08

Aug

-08

Oct-0

8

Jan-09

May

-09

Sep

-09

Seru

m F

T4 &

TS

I

0

10

20

30

40

50

60

70

80

Seru

m T

SH

TSH (mIU/l)

FT4 (ng/l)

TSI (U/L)

6 months PP

LT4 kept at 125 ug/d, without problems