thyroid disease in pregnancy Flashcards
Should we screen for subclinical thyroid disease
Screening for subclinical hypothyroidism or TPO antibodies, and subsequent treatment with thyroxine is not recommended in pregnancy
What are the main causes of hypothyroid disease in NZ
What are other causes
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
What is the Physiology of thyroid hormone production in pregnancy
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.
When does the fetuses thyroid start working?
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.
How does pregnancy affect normal ranges for thyroid function?
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.
What is overt vs subclinical hypothyroidism
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.
What does overt hypothyroidism cause?
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
Who should get TFTs to screen for overt hypothyroidism?
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
How does dosing for thyroxine change in pregnancy?
How often testing?
Treatment aim?
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
does subclinical hypothyroidism need to be treated?
nope
Some suggestive studies but meta analysis didnt agree
no population wide screening
Shall we screen for and treat woman with TPO antibodies?
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
What are the sx of hypothryroidism
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
What does severe iodine deficiency cause?
neurological creastinisn
Deaf mutism
Spastic motor disorder
hypothyroid
neonatal hypothyroidism
1:180 000
TSH receptor blocking antibodies transplacentally cross to fetus
more with atrophic then hashimotos
suspect if fetal goitre - dx on guthrie card
What is the incidence of post partum thyroiditis?
Variable depending on screening and iodine intake
but average 7% (numbers range from 1-17%
Who is at risk for post partum thyroiditis
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
When does post partum thyroiditis present?
How does it present?
Many asymptomatic
usually 3-4 months post partum - can be up to 6 months
What are the ways post partum thyroiditis can present?
With what sx?
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
What is the pathogenesis of post partum autoimmune thyroiditis ?
What does a FNA show?
any other test to differentiate it?
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)
Management of post partum thyroititis
Who needs managing?
How to manage it?
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
Post partum thyroiditis recurrence
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
What are the physiological changes of the thyroid in pregnancy
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
Incidence of thyrotoxicosis
What is the biggest risk factor
1:500 pregnancies
50% of woman have a FHX of autoimmune thyroid disease
What are the sx of thyrotoxicosis in pregnancy?
What are the most obvious sx in pregnancy?
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
What is the cause of hyperthyroid in pregnancy?
How to diagnose?
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
How does pregnancy affect graves
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
How does thyrotoxicosis affect pregnancy
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
How to manage thyrotoxicosis in pregnancy
What are the 2 drugs as proc and cons of each
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
How to manage relapses?
more medication long term
Surgery
radioactive iodine
SE of anti thyroid drugs
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
Plan pregnancy management if on anti thyroid drugs
See monthly
is breastfeeding safe on anti thyroid mediation?
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
What is the role for B blockers?
symptomtic tx of tachycardia
Also reduce T4 to T3 conversion
Often used short term until the anti thyroid drugs kick in - usually 3 weeks
Can you perform a thyroidectomy in pregnancy?
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
Can radioactive iodine be used in pregnancy?
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
What are TSIs?
Thyroid stimulating antibodies?
What is the risk?
How to manage that?
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%
How common is a thyroid nodule in pregnancy?
1-2% of woman
up to 40% are malignant
What are concerning features of a thyroid lump in pregnancy ?
prev RT to head or neck Fixation of the lump rapid growth lymphadenopathy vice change horners
What are the first tests to do after finding a thyroid nodule ?
TFT
Thyroid antibodies
(exclude a toxic nodule or hashimotos)
USS (solid or cystic)
How does the parathyroid change in pregnancy?
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
Hyperparathyroidism
What is the incidence
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
How does pregnancy affect hyperparathyroidism
How does hyperparathyroidism affect pregnancy
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
Hypoparathyroid
Causes?
Diagnosis?
Autoimmune
post thyroidectomy 1-2%
Dx - low Ca and PTH levels
What is the affect of hypoparathyroidism on pregnancy?
Low Ca increases risk T2 miscarriage, fetal hypocalcaemia and secondary hypoparathyroidism
bone demineralisation
neonatal rickets
Can be dx with neonatal seizures
How to treat hypoparathyroidism?
Vit D and Ca supplements
Vit D doses will need to be increased 2-4 X
Check Ca and albumin monthly
What is the incidence and risk factors of vitamin D deficiency ?
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
What are maternal consequences of Vit D deficiency
Bone loss reduces weight gain hypocalcaemia osteomalacia myopathy gestational diabetes HTN PET SGA Increased risk LSCS
Fetal risks for low vit D
Adverse skeletal development
reduces neonatal calcium - seizures
subsequent atopy, asthma
NICE guideline for Vit D supplementation for all pregnancy woman
400 U / day - part of a pregnancy multivit
