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28 year old woman Presents with positive urine pregnancy test 
Gestation (based on LNMP) 6/40

Medical History: 
Vitiligo

Family history: 
Sister and Mother with Hashimoto s

hypothyroidism

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Unremarkable examination apart from vitiligo over arms

hCG confirm pregnancy Pregnancy screen (CBC normal, Gp and Ab screen, Rubella immune, Hep B/C/HIV/Syphilis ) ƒ Electrolytes, Creatinine, LFT s normal
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Other tests?

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TSH Anti thyroid Ab (TPO/Tg) Consider others if indicated wrt possible autoimmune background (Cortisol/Celiac/Reproductive hormones)

8) pmol/L Is this normal for pregnancy? .0 (2.4-4) mU/L 15 (10-20) pmol/L 4.ƒ ƒ ƒ ƒ TSH: fT4: fT3: 6.8-6.0 (0.

4-4) mU/L 15 (10-20) pmol/L 4.8) pmol/L Anti Thyroperoxidase Antibody 500 (<9)IU/ml Anti Thryroglobulin Antibody 60 (<40)IU/ml .0 (2.0 (0.ƒ ƒ ƒ ƒ ƒ TSH: fT4: fT3: 6.8-6.

8-6.8) pmol/L Anti Thyroperoxidase Antibody 500 (<9)IU/ml Anti Thryroglobulin Antibody 60 (<40)IU/ml Subclinical Hypothyroidism likely secondary to Hashimotos Thyroiditis .0 (2.0 (0.ƒ ƒ ƒ ƒ ƒ TSH: fT4: fT3: 6.4-4) mU/L 15 (10-20) pmol/L 4.

Thyroid in Pregnancy .

ƒ ƒ Huge increase in workload What are the causes? .

Reduction in plasma iodide ƒ Direct: 1. . hCG effect 2. Increase in thyroxine binding globulin (TBG) Reduction in maternal serum thyroid hormone 3.ƒ Huge increase in workload ƒ Indirect: 1.

Endocrinol Metab Clinics N Am 2006 35:117 .1. Increased TBG ƒ Oestrogen related  Increase synthesis/reduced hepatic clearance (2-3 fold) ƒ Expands the extra-thyroidal pool triggering:  Increase in maternal thyroid hormone synthesis  Elevation of total T4 & T3 LeBeau and Mandel.

2. Reduction in plasma iodide  Increased maternal GFR  Transplacental passage  Increased thyroid uptake LeBeau and Mandel. Endocrinol Metab Clinics N Am 2006 35:117 . Depletion of the maternal circulation of thyroid hormone  Transplacental passage of T4  Placental production of monodeiodinase 3.

000 IU/L increment in hCG)  Increased total T4 and T3 (usually within the normal reference range)  Small goitre ƒ Usually resolves by mid second trimester LeBeau and Mandel.1mU/L for every 10. Increased hCG ƒ ƒ Peak around 10/40. declines to nadir 20/40 Weak but direct activator of the TSH receptor  Mild suppression of TSH (reduction in basal TSH by 0. Endocrinol Metab Clinics N Am 2006 35:117 .1.

TBG Gestation The shaded area represents the normal range in non pregnant .

ƒ Potential increased demands on thyroid will worsen her subclinical hypothyroidism /unmask overt hypothyroidism Who would treat her? What are the implications for pregnancy of :  A) Hypothyroidism?  B) Positive anti-thyroid antibodies? ƒ ƒ .

Implications .

2 billion individuals) ƒ Few women develop symptoms and diagnosis often overlooked as symptoms attributed to pregnancy .ƒ Estimated prevalence in pregnancy  Overt hypothyroidism 0.5%  Subclinicial hypothyroidism 2-3% Thyroid autoantibodies present in approx 5-15% of women of childbearing age ƒ In an iodine sufficient environment.3-0. most common cause is Hashimoto s thyroiditis ƒ  Worldwide most common cause is iodine deficiency (1.

isolated low total and free T4 and raised Anti TPO antibodies ALL independently associated with developmental and motor delay with demonstrable reduction in IQ .ƒ ƒ T4 critical for normal fetal brain development High TSH.

especially the first trimester ‡ Production of fetal T4 begins approx. 12 .14 weeks gestation ‡Thyroid hormone crucial to fetal and neonatal neuropsychological development .‡ Fetus dependent on maternal thyroid hormone.

NEJM 1999. 1 year and 2 years of age in infants born to mothers who had isolated low T4 at least until 24 weeks of gestation 2.ƒ Low IQ scores in the offspring at 7 to 9 yrs of age was correlated with elevated maternal TSH levels at less than 17 weeks gestation1  Children born to untreated hypothyroid women had IQ 7 points lower than those of healthy or thyroxine treated women  3x increase in learning disabilities  3x as many with IQ s 2SD below controls ƒ Impaired psychomotor development at 10 months. 50(2):149 3. 341(8):549 low T4 4 2.117:161 ƒ . Pop et al. Pediatrics 2006. Clin Endocrinol 1999. Haddow et al. 4. Pop et al.3 A reduction in the orientation index (as m ment of neurodevelopment) at 3 weeks of age in infants born to mothers with isolated 1. Clin Endocrinol 2003. 59(3):282 Kooistra et al.

Leung et al. Obstet Gynecol 1988. pre-eclampsia. Obstet Gynecol 1993.4.5 High TSH in third trimester associated with breech 6 1. Thyroid 2005.42:353 Davis et al. 4. IUGR. Obstet Gynecol 2005. 81:349 Wasserstrum et Nania.15:351 Kooistra et al. pop. postpartum haemorrhage. prematurity and stillbirth 3. 3. 6.105:239 Stagnaro-Green et al. anemia. 8%)1 Increased incidence of low birth weight neonates (overt hypothyroidism 22% vs. gen. 72:108 Casey et al. subclinical 25% vs. miscarriage. placental abruption. 7%)1 Increased use of LSCS due to fetal distress (severe hypothyroidism at first antenatal visit 56% vs. gen.ƒ Increase in rate of gestational hypertension (overt hypothyroidism 36% vs. 2.73:661 ƒ ƒ ƒ ƒ . Clin Endocrinol 2010. Clin Endocrinol 1995. 5. mild hypothyroidism or euthyroid 3%) 2 Increased risk of placental abruption. subclinical hypothyroidism 9% vs. pop.

ƒ Would you treat her?  Yes to reduce the risk of impaired foetal neurodevelopment  And .

Implications .

ƒ Presence of anti-thyroid autoantibodies associated with poorer pregnancy outcomes  Number of studies shown association with pregnancy loss in women with autoantibodies and hyper/hypo/euthyroid status  Increase in preterm delivery 1  One intervention study reduced the risk of prematurity and miscarriage with thyroxine replacement1 1.Negro et al. JCEM 2006.91:2587 .

91:2587 .ƒ ƒ Women with +TPO antibodies but no treatment had a higher rate of miscarriage (largely 1st trimester) and preterm delivery Treatment with thyroxine reduced the risk to that of the control group rate Negro et al. JCEM 2006.

started Thyroxine replacement  100mcg daily  One empty stomach and prior to her prenatal vitamins ƒ Repeat TFT s at 10 weeks:  TSH:  fT4:  fT3: 1.ƒ After discussion of the risks.3 (0.4-4) mU/L 15 (10-20) pmol/L 4 (2.8-6.8) pmol/L .

8-6.8 (0.4-4) mU/L  fT4:  f T3: 6 (10-20) pmol/L 3.5 (2.8) pmol/L ƒ Interpretation and management? .ƒ Repeat thyroid function tests at 20/40  TSH : 0.

Interpretation in Pregnancy .

Obstet Gynecol 2005.TSH generally considered the primary test for evaluating thyroid status during pregnancy ƒ Use of non Pregnant ranges may result in misdiagnosis ƒ Dashe et al.106:753±7) .

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ƒ Ensure you interpret TSH with pregnancy/trimester specific ranges  Check with your local laboratory for specific ranges .

ƒ However isolated hypothyroxinaemia may also be associated with impaired fetal psychomotor development and reduced IQ Previously used:  Total T4 and T3  Free thyroxine index (pregnancy range = approx 1.5x non ƒ pregnant) ƒ More recently rely on free T4 and T3 .

ƒ Expected free T4/T3 trends:  Increases first trimester (response to elevated hCG)  Subsequent decline (nadir third trimester) ƒ But multiple studies have reported higher/lower/unchanged values compared with non pregnant levels .

Limitations to currently used free T4 immunoassays ƒ Sensitive to alterations in binding proteins  High TBG and reduction in albumin state of pregnancy may lower fT4 values and may result in misdiagnosis ƒ Manufacturer reference ranges established using pools of non pregnant normal sera thus not valid in pregnancy  Limited method specific and trimester specific data for current direct immunoassays  No consensus on reference range .

Am J Obstet Gynecol 2009.TSH Total vs. free T4 Lee et al.200:260e1 ± e6 .

the serum total T4 may provide a more reliable answer ƒ Talk to the laboratory about whether their reference ranges quoted are pregnancy specific .ƒ Interpret with caution the serum free T4 levels in pregnancy  If free T4 value seems out of keeping with the TSH and clinical picture.

10) .ƒ ƒ ƒ ƒ ƒ ƒ Feeling well Pregnancy progressing normally TSH and fT3 normal No change to dose of thyroxine replacement Had an otherwise uncomplicated pregnancy Spontaneous vaginal delivery at term of 3.6 kg baby (APGARS 9.

. What to do in her next pregnancy? 1.ƒ Asks: Continue her thyroid replacement? 2. Any future concerns? 3.

ƒ Asks: Continue her thyroid replacement? 2. Any future concerns? 3. What to do in her next pregnancy? 1. .

stay off treatment  Discuss future risk: Increased risk of hypothyroidism Likely need for thyroxine replacement Repeat TFT (6-12 monthly) TFT if considering another pregnancy or ASAP if unplanned pregnancy Discuss contraception .  Reasonable to cease thyroxine and repeat TFT s  If TFT within normal range .ƒ After delivery reduce thyroxine to prepregnancy levels and repeat TFT in 4-6 weeks.

What are your recommendations?  Preconception TSH aims?  Management of thyroxine dose periconception? .ƒ But. over next 3 years became overtly hypothyroid  Restarted thyroxine 100mcg daily ƒ ƒ Would like to try to fall pregnant again.

Management Periconception .

ƒ ƒ If on thyroxine preconception  Adjust dose to reach a pre-pregnancy TSH <2. JCEM 2007.92(8): S1 .5 mU/L Increase in dose needed early in pregnancy to maintain euthyroid status  85% women will need increase in thyroxine dose during pregnancy (av. dose increase 48%) ƒ Thyroxine dose requirement mirrors rising TBG  By 10 wks need average increase of 29% LT4 dose  By 20 wks need average increase of 48% LT4 dose  Usually no increase of dose beyond 20 wks required Abalovich et al.

Increase dose by 30% as soon as fall pregnant Woman can do this herself after + home pregnancy test Pre-empt increased needs Reduce risk of first trimester underreplacement  2. Wait until review by doctor Do TFT and adjust dose accordingly Relies on patient to see physician in timely manner .ƒ Two schools of thought:  1.

may miss a significant period of neurodevelopment .‡ Increased thyroxine needed irrespective of cause of hypothyroidism ‡ Dose increase required early (~ week 8) ‡ If wait for first prenatal visit to check TFT and increase thyroxine dose.

thyroid function merits regular monitoring.During pregnancy. finetuning of treatment .

ƒ ƒ Adjusted dose until TSH <2.5 preconception Advised that when confirms pregnancy on home test  Increase dose by 30%  See you ASAP for: Confirmation of pregnancy TFT to further guide dose adjustment .