thyroid disease in pregnancy

Question 1

Should we screen for subclinical thyroid disease

Answer 1

Screening for subclinical hypothyroidism or TPO antibodies, and subsequent treatment with thyroxine is not recommended in pregnancy

Question 2

What are the main causes of hypothyroid disease in NZ

What are other causes

Answer 2

affects 1% of pregnancy woman
Hashimotos thyroiditis
Autoimmune disorder
Associated T1DM / pernicious anaemia / vitiligo

Other causes are post treatment - radioactive iodine, radiation, removal for nodules or malignancy

Question 3

What is the Physiology of thyroid hormone production in pregnancy

Answer 3

ßHCG is structurally similar to TSH and provides weak thyroid stimulating activity , and so the normal
increase in ßHCG in early pregnancy may cause a small transient increase in free T4 (FT4) with
subsequent TSH suppression.

Question 4

When does the fetuses thyroid start working?

Answer 4

The fetus is reliant on transplacental transfer of maternal thyroid hormone until the fetal thyroid
starts to become functional from 12 weeks. The fetus and the fully breastfed infant are dependent on
maternal iodine for thyroid hormone synthesis.

Question 5

How does pregnancy affect normal ranges for thyroid function?

Answer 5

TSH - local pregnancy ranges should be used
If not available 4mU/l upper range for pregnancy
or
T1 0.5 mU/L less then non pregnant range.
T2/3 the same

T4
FT4 concentrations also change with increasing gestation. As there is no single international method
for standardisation of free thyroid hormone tests, method specific reference intervals are necessary
for free thyroid hormone assays.

Question 6

What is overt vs subclinical hypothyroidism

Answer 6

Overt hypothyroidism is defined as increased serum TSH and decreased FT4,
or,
TSH >10mIU/L with FT4 within the normal range.

Subclinical hypothyroidism is defined as serum TSH above the reference range, and FT4 within the
normal range.

Question 7

What does overt hypothyroidism cause?

Answer 7

miscarriage
anovulation

Adverse pregnancy outcomes
PET Abruption
anemia
PPH 
PTB
LBW
perinatal mortality 
reduced IQ and developmental delay 
Adequately tx hypothyroidism is not at increased risk

Question 8

Who should get TFTs to screen for overt hypothyroidism?

Answer 8

Thyroid function testing with serum TSH should be performed in early pregnancy for women with
symptoms of thyroid disease or a personal history of thyroid disease

Question 9

How does dosing for thyroxine change in pregnancy?

How often testing?

Treatment aim?

Answer 9

Often 30-50% increase in dosing from early pregnancy

Levels should be done at least once / trimester to assess adequacy of replacement

Treatment goal should be TSH in lower half of trimester specific ranges

Question 10

does subclinical hypothyroidism need to be treated?

Answer 10

nope
Some suggestive studies but meta analysis didnt agree
no population wide screening

Question 11

Shall we screen for and treat woman with TPO antibodies?

Answer 11

no

There is no substantive evidence to support alteration in TSH
targets or benefits from thyroxine treatment based on TPO antibody status and so universal or
targeted screening for thyroid autoantibodies is not recommended in pregnancy

also not enough evidence it increases the risk of miscarriage and that thyroxine helps so not currently recommended

Question 12

What are the sx of hypothryroidism

Answer 12

Most sensitive in pregnancy
Cold intolerance
slow pulse
delayed relaxation of the tendon

Common
Constipation
weight gain
lethargy
hair loss 
dry skin carpal tunnel
fluid retention
goitre

Question 13

What does severe iodine deficiency cause?

Answer 13

neurological creastinisn
Deaf mutism
Spastic motor disorder
hypothyroid

Question 14

neonatal hypothyroidism

Answer 14

1:180 000
TSH receptor blocking antibodies transplacentally cross to fetus
more with atrophic then hashimotos
suspect if fetal goitre - dx on guthrie card

Question 15

What is the incidence of post partum thyroiditis?

Answer 15

Variable depending on screening and iodine intake

but average 7% (numbers range from 1-17%

Question 16

Who is at risk for post partum thyroiditis

Answer 16

Woman with a family hx of hypothyroid
Woman with thyroid peroxidase (antimicrosomal) antibodies - 50% of whom develop post partum thyroiditis have antibodies
85% of patients have antibodies
more common in T1DM
25% have a FHx of autoimmune thyroid disease

Question 17

When does post partum thyroiditis present?

How does it present?

Answer 17

Many asymptomatic

usually 3-4 months post partum - can be up to 6 months

Question 18

What are the ways post partum thyroiditis can present?

With what sx?

Answer 18

Monophasic or biphasic

monophasic
40% transient hypothyroid (lethary, tired, depression)
40% transient hyperthyroid (palpitations and fatigue)

20% biphasic
Hyperthyroid then hypothyroid lasting 4-8 months

Question 19

What is the pathogenesis of post partum autoimmune thyroiditis ?

What does a FNA show?

any other test to differentiate it?

Answer 19

It is a destructive autoimmune thyroiditis causing first a release of preformed thyroxine from the thyroid (not a hyperfunctional gland)
And then hypothyroid as stores are deplete

FNA shows lymphocytic thyroiditis

It could be a rebound after the immunosuppressive affects of pregnancy

Radioactive iodine will show low uptake (Graves shows high uptake)

Question 20

Management of post partum thyroititis

Who needs managing?
How to manage it?

Answer 20

Most woman recover spontaneously and dont require treatment
need for treatment is determined by symptoms
Hyperthyroid sx should be treated by B blockers (its not a synthesis problems it a release problem)
Hypothyroid with thyroxine
Withdraw threatment after 6-8 months and assess if spont recovery has occurred
96% will not need ongoing treatment

Question 21

Post partum thyroiditis recurrence

Answer 21

10-20% suffer recurrence
20-30% who had + Antibodies have hypothyroidism within 4 years - recommend annual TFTs

Woman with positive thyroid antibodies have increaesed risk of postnatal depression

Question 22

What are the physiological changes of the thyroid in pregnancy

Answer 22

Thyroid binding globulin synthesis in the liver increases
T4 and T3 increase to compensate
T4 levels fall a little in the second and third trimester
TSH rises and falls in T1 - then is higher then normal in T2/3
Levels of Free T3/4 lower in T2/3
Hyperemesis gives high free T4 and suppressed TSH in 60% of cases
(hcg has a TSH like activity)

State of iodine deficiency
fetal requirements
Increased excretion
Uptake in the thyroid increases - it can hypertrophy to trap any iodine there

Question 23

Incidence of thyrotoxicosis

What is the biggest risk factor

Answer 23

1:500 pregnancies

50% of woman have a FHX of autoimmune thyroid disease

Question 24

What are the sx of thyrotoxicosis in pregnancy?

What are the most obvious sx in pregnancy?

Answer 24

head intolerance 
tachycardia
palpitations
palmar erythema
emotional lability
vomiting
goitre

Most discriminatory
weight loss
tremor
tachycardia
lid lag
exophthalmos
50% of people with graves have ophthalmopathy  and can present before hypothyroidism

Question 25

What is the cause of hyperthyroid in pregnancy? How to diagnose?

Answer 25

95% of hyperthyroid in pregnancy is Graves TSH receptor stimulating antibodies Rare other causes are toxic nodular goitre, toxic adenoma subacute thyroiditis, or iodine, amiodarmone or lithium therapy High T4 suppressed TSH

Question 26

How does pregnancy affect graves

Answer 26

As with other autoimmune disease - it often improves in pregnancy in a relative state of immunosuppression There may be a first trimester exacerbation due to hcg affect no change to ophthalmopathy 30% stop meds at end of pregnancy post natal relapses test 3 months post partum

Question 27

How does thyrotoxicosis affect pregnancy

Answer 27

inhibits ovulation and fertility if untreated increased miscarriage, FGR, PTL Perinatal mortality Can leave to AF, SVT, tachycardia If poorly controlled can develop a thyroid storm with heart failure Rarely retrosternal goitre extensions cause tracheal obstruction thyroid stimulating antibodies can cause fetal or neonatal thyrotoxicosis

Question 28

How to manage thyrotoxicosis in pregnancy What are the 2 drugs as proc and cons of each

Answer 28

Onset delayed 3-4 weeks as preformed hormone is depleted. Aggressive tx 4-6 weeks total tx 18 months but relapse high aim to quickly control then maintain on lowest dose possible both cross placenta PTU + carbimazole Typically people stay on what they are on PTU 150-400mg Risk 0.01 % liver failure Less cross into placenta and breast milk First line Carbimazole 15-40 mg Risk of aplasia cutis - loss of skin over fetal skull in T1 no role for block and replace in pregnancy as the anti thyroid is TF across placenta and makes the baby hypothyroid but the thyroxine doesnt cross

Question 29

How to manage relapses?

Answer 29

more medication long term Surgery radioactive iodine

Question 30

SE of anti thyroid drugs

Answer 30

1-5% develop a rash from anti thyroid drugs - should promptly switch Can cause neutropenia and agranulocytosis Should report infection / sore throat liver impairment 1:10 000 on PTU

Question 31

Plan pregnancy management if on anti thyroid drugs

Answer 31

See monthly

Question 32

is breastfeeding safe on anti thyroid mediation?

Answer 32

small amounts are transferred in breast milk so ok to breast feed at ow doses PTU less then 150 mg / day - 0.07% dose TF to baby carbimazole -0.5% of dose TF Check fetal TFT on umbilical blood andat regular intervals / at regular intervals if breastfeeding on high doses

Question 33

What is the role for B blockers?

Answer 33

symptomtic tx of tachycardia Also reduce T4 to T3 conversion Often used short term until the anti thyroid drugs kick in - usually 3 weeks

Question 34

Can you perform a thyroidectomy in pregnancy?

Answer 34

``` Rarely indicated can be done in T2 Usaully if large goitre causing stridor or dysphagia Close FU for hypothyroid Hypocalcaemia in 1-2% of cases ```

Question 35

Can radioactive iodine be used in pregnancy?

Answer 35

nope as also taken up by fetal thyroid Dx radioiodine also contraindicated although can be used in breastfeeding if pump and dump for 24 hours Pregnancy should be avoided for 4 months after treatment- theoretical risk chromosomal damage

Question 36

What are TSIs? Thyroid stimulating antibodies? What is the risk? How to manage that?

Answer 36

antibodies in graves disease can cross the placenta Can cause fetal thyrotoxicosis - Occurs in 1% babies with current or past hx graves - more so with active disease Can predict by TSI levels test in T1 to predict fetal thyrotoxicosis USS - FGR, tachycardia, goitre mortality 25% neonatal TFTs on cord blood In utero treatment - anti thyroid drugs (and thyroxine if needed) Neonatal antibodies last 4 months Maternal treatment can last 1-7 days So can present in first week of life with weight loss, tachycardia, irritability, poor feeding, goitre, hepatospenomegaly Mortality 15%

Question 37

How common is a thyroid nodule in pregnancy?

Answer 37

1-2% of woman | up to 40% are malignant

Question 38

What are concerning features of a thyroid lump in pregnancy ?

Answer 38

``` prev RT to head or neck Fixation of the lump rapid growth lymphadenopathy vice change horners ```

Question 39

What are the first tests to do after finding a thyroid nodule ?

Answer 39

TFT Thyroid antibodies (exclude a toxic nodule or hashimotos) USS (solid or cystic)

Question 40

How does the parathyroid change in pregnancy?

Answer 40

increased demand for Calcium (pregnancy and lactation) Increased urinary loss Calcium absorption is increased X2 Vit D requirements are increased 50-100% Total fall in albumin, calcium and free ionized calcium

Question 41

Hyperparathyroidism | What is the incidence

Answer 41

Nearly 1:10 000 It may be parathyroid adenoma or hyperplasia Can be no sx, or fatigue, thirst, hyperemesis, constipation, depression HTN, pancreatitis, renal calculi Difficult to dx in pregnancy

Question 42

How does pregnancy affect hyperparathyroidism How does hyperparathyroidism affect pregnancy

Answer 42

hypercalcaemia can be improved in pregnancy due to increased Ca demand Increased risk of miscarriage, IUD, PTB, If severe fetal mortality 40% 25% HTN or PET Neonatal risk is hypocalcaemia due to suppression of fetal PTH due to high maternal Ca can be a prompt to dx the mother Tx is surgery OR high fluid, oral phosphate

Question 43

Hypoparathyroid Causes? Diagnosis?

Answer 43

Autoimmune post thyroidectomy 1-2% Dx - low Ca and PTH levels

Question 44

What is the affect of hypoparathyroidism on pregnancy?

Answer 44

Low Ca increases risk T2 miscarriage, fetal hypocalcaemia and secondary hypoparathyroidism bone demineralisation neonatal rickets Can be dx with neonatal seizures

Question 45

How to treat hypoparathyroidism?

Answer 45

Vit D and Ca supplements Vit D doses will need to be increased 2-4 X Check Ca and albumin monthly

Question 46

What is the incidence and risk factors of vitamin D deficiency ?

Answer 46

``` Pigmented skin obesity vegans covered woman several pregnancies with a short interpregnancy interval malabsorption (coeliac) AEDs / highly active ART renal or liver disease alcohol abuse ```

Question 47

What are maternal consequences of Vit D deficiency

Answer 47

``` Bone loss reduces weight gain hypocalcaemia osteomalacia myopathy gestational diabetes HTN PET SGA Increased risk LSCS ```

Question 48

Fetal risks for low vit D

Answer 48

Adverse skeletal development reduces neonatal calcium - seizures subsequent atopy, asthma

Question 49

NICE guideline for Vit D supplementation for all pregnancy woman

Answer 49

400 U / day - part of a pregnancy multivit