 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
 Unremarkable examination apart from vitiligo
over arms
 βhCG confirm pregnancy
 Pregnancy screen (CBC normal, Gp and Ab
screen, Rubella immune, Hep B/C/HIV/Syphilis –)
 Electrolytes, Creatinine, LFT’s normal

 Other tests?
 TSH
 Anti – thyroid Ab (TPO/Tg)
 Consider others if indicated wrt possible
autoimmune background
(Cortisol/Celiac/Reproductive hormones)
 TSH: 6.0 (0.4-4) mU/L
 fT4: 15 (10-20) pmol/L
 fT3: 4.0 (2.8-6.8) pmol/L

 Is this normal for pregnancy?

 TSH: 6.0 (0.4-4) mU/L
 fT4: 15 (10-20) pmol/L
 fT3: 4.0 (2.8-6.8) pmol/L

 Anti Thyroperoxidase Antibody 500 (<9)IU/ml

 Anti Thryroglobulin Antibody 60 (<40)IU/ml
 TSH: 6.0 (0.4-4) mU/L
 fT4: 15 (10-20) pmol/L
 fT3: 4.0 (2.8-6.8) pmol/L

 Anti Thyroperoxidase Antibody 500 (<9)IU/ml

 Anti Thryroglobulin Antibody 60 (<40)IU/ml

Subclinical Hypothyroidism likely secondary

to Hashimotos Thyroiditis
Thyroid in Pregnancy
 Huge increase in workload
 What are the causes?
 Huge increase in workload
 Indirect:
1. Increase in thyroxine binding globulin (TBG)
2. Reduction in maternal serum thyroid
hormone
3. Reduction in plasma iodide
 Direct:
1. hCG effect
1. Increased TBG
 Oestrogen related
 Increase synthesis/reduced hepatic clearance (2-3 fold)

 Expands the extra-thyroidal pool triggering:

 Increase in maternal thyroid hormone synthesis
 Elevation of total T4 & T3

LeBeau and Mandel, Endocrinol Metab Clinics N Am 2006 35:117

2. Depletion of the maternal circulation of
thyroid hormone
 Transplacental passage of T4
 Placental production of monodeiodinase

3. Reduction in plasma iodide

 Increased maternal GFR
 Transplacental passage
 Increased thyroid uptake
LeBeau and Mandel, Endocrinol Metab Clinics N Am 2006 35:117
1. Increased hCG

 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
0.1mU/L for every 10,000 IU/L increment in hCG)
 Increased total T4 and T3 (usually within the normal
reference range)
 Small goitre
 Usually resolves by mid second trimester

LeBeau and Mandel, Endocrinol Metab Clinics N Am 2006 35:117

 TBG

Gestation

The shaded area represents the normal range in

non pregnant
 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?
Implications
 Estimated prevalence in pregnancy
 Overt hypothyroidism 0.3-0.5%
 Subclinicial hypothyroidism 2-3%
 Thyroid autoantibodies present in approx
5-15% of women of childbearing age
 In an iodine sufficient environment, most
common cause is Hashimoto’s thyroiditis
 Worldwide most common cause is iodine
deficiency (1.2 billion individuals)
 Few women develop symptoms and
diagnosis often overlooked as symptoms
attributed to pregnancy
 T4 critical for normal fetal brain development

 High TSH, isolated low total and free T4 and

raised Anti TPO antibodies ALL
independently associated with
developmental and motor delay with
demonstrable reduction in IQ
• Fetus dependent on
maternal thyroid
hormone, especially the
first trimester
• Production of fetal T4
begins approx. 12 - 14
weeks gestation
•Thyroid hormone
crucial to fetal and
neonatal
neuropsychological
development
 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’ gestation 1
 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

 Impaired psychomotor development at 10 months, 1 year and 2

years of age in infants born to mothers who had isolated low T 4 at
least until 24 weeks of gestation 2,3
 A reduction in the orientation index (as m’ment of
neurodevelopment) at 3 weeks of age
in infants born to mothers with isolated 1. Haddow et al. NEJM 1999; 341(8):549
low T4 4 2. Pop et al. Clin Endocrinol 1999; 50(2):149
3. Pop et al. Clin Endocrinol 2003; 59(3):282
4. Kooistra et al. Pediatrics 2006;117:161
 Increase in rate of gestational hypertension (overt hypothyroidism
36% vs. subclinical 25% vs. gen. pop. 8%)1
 Increased incidence of low birth weight neonates (overt
hypothyroidism 22% vs. subclinical hypothyroidism 9% vs. gen. pop.
7%)1
 Increased use of LSCS due to fetal distress (severe hypothyroidism at
first antenatal visit 56% vs. mild hypothyroidism or euthyroid 3%) 2
 Increased risk of placental abruption, anemia, postpartum
haemorrhage, miscarriage, pre-eclampsia, placental abruption, IUGR,
prematurity and stillbirth 3,4,5
1. Leung et al. Obstet Gynecol 1993; 81:349
2. Wasserstrum et Nania. Clin Endocrinol 1995;42:353
 High TSH in third trimester 3. Davis et al. Obstet Gynecol 1988; 72:108
4. Casey et al. Obstet Gynecol 2005;105:239
associated with breech 6 5. Stagnaro-Green et al. Thyroid 2005;15:351
6. Kooistra et al. Clin Endocrinol 2010;73:661
 Would you treat her?
 Yes – to reduce the risk of impaired foetal
neurodevelopment
 And…
Implications
 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
 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;91:2587
 After discussion of the risks, started
Thyroxine replacement
 100mcg daily
 One empty stomach and prior to her prenatal
vitamins
 Repeat TFT’s at 10 weeks:
 TSH: 1.3 (0.4-4) mU/L
 fT4: 15 (10-20) pmol/L
 fT3: 4 (2.8-6.8) pmol/L
 Repeat thyroid function tests at 20/40

 TSH : 0.8 (0.4-4) mU/L

 fT4: 6 (10-20) pmol/L
 f T3: 3.5 (2.8-6.8) pmol/L

 Interpretation and management?

Interpretation in Pregnancy
 TSH generally considered the primary test for evaluating
thyroid status during pregnancy
 Use of non Pregnant ranges may result in misdiagnosis

Dashe et al. Obstet Gynecol 2005;106:753–7)

 Ensure you interpret TSH with
pregnancy/trimester specific ranges
 Check with your local laboratory for specific
ranges
 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
pregnant)

 More recently rely on free T4 and T3

 Expected free T4/T3 trends:
 Increases first trimester (response to elevated
hCG)
 Subsequent decline (nadir third trimester)

 But multiple studies have reported

higher/lower/unchanged values compared
with non pregnant levels
Limitations to currently used free T4 immunoassays
 Sensitive to alterations in binding proteins
 High TBG and reduction in albumin state of pregnancy may
lower fT4 values and may result in misdiagnosis
 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
TSH Total vs. free T4

Lee et al, Am J Obstet Gynecol 2009;200:260e1 – e6

 Interpret with caution the serum free T4
levels in pregnancy
 If free T4 value seems out of keeping with the TSH
and clinical picture, the serum total T4 may
provide a more reliable answer
 Talk to the laboratory about whether their
reference ranges quoted are pregnancy
specific
 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 9,10)
Asks:
1. Continue her thyroid replacement?
2. Any future concerns?
3. What to do in her next pregnancy?
Asks:
1. Continue her thyroid replacement?
2. Any future concerns?
3. What to do in her next pregnancy?
 After delivery reduce thyroxine to pre-
pregnancy levels and repeat TFT in 4-6 weeks.
 Reasonable to cease thyroxine and repeat TFT’s
 If TFT within normal range - 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
 But, over next 3 years became overtly
hypothyroid
 Restarted thyroxine 100mcg daily
 Would like to try to fall pregnant again.
 What are your recommendations?
 Preconception TSH aims?
 Management of thyroxine dose periconception?
Management Periconception
 If on thyroxine preconception
 Adjust dose to reach a pre-pregnancy TSH <2.5 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%)
 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, JCEM 2007;92(8): S1
 Two schools of thought:
 1. 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
• 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, may miss a significant period of
neurodevelopment
During
pregnancy,
thyroid function
merits regular
monitoring, fine-
tuning of
treatment
 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