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Thyroid Disease in Pregnancy
Abdelrahman Al-daqqa
Physiologic Changes in Thyroid
Function During Pregnancy
 Thyroid binding globulin (TBG) increases
due to reduced hepatic clearance and
estrogenic stimulation of TBG synthesis
 The test results that change in pregnancy
are influenced by changes in TBG
concentration
 Plasma iodide levels decrease due to fetal
iodide use and increased maternal
clearance -> leads to notable increase in
gland size in 15% of women (without
abnormal TFTs)
Physiologic Changes in Thyroid
Function During Pregnancy
Maternal
Status
TSH
**initial
screening
test**
Free T4 Free
Thyroxine
Index
(FTI)
Total T4 Total T3 Resin
Triiodo-
thyronine
Uptake
(RT3U)
Pregnancy No
change
No
change
No
change
Increase Increase Decrease
Hyperthyroidism Decrease Increase Increase Increase Increase
or no
change
Increase
Hypothyroidism Increase Decrease Decrease Decrease Decrease
or no
change
Decrease
The Fetal Thyroid
 Begins concentrating iodine at 10-
12 weeks
 Controlled by pituitary TSH by
approximately 20 weeks
Hyperthyroidism
 Occurs in 0.2% of
pregnancies; Graves’
disease accounts for
95% of cases
Look for:
-Nervousness
-Tremor
-Tachycardia
-Frequent stools
-Sweating
-Heat intolerance
-Weight loss
-Goiter
-Insomnia
-Palpitations
-Hypertension
-Lid lag/lid retraction
-Pretibial myxedema
Fetal & Neonatal Effects of
Hyperthyroidism
 Associated with preterm delivery, low
birth weight, fetal loss
 Fetal thyrotoxicosis (related to disease
itself or treatment)
 Risk of immune-mediated
hypo/hyperthyroidism (due to antibodies
crossing the placenta, esp. in Graves or
chronic autoimmune thyroiditis)
 Antibodies in Graves’ disease can be either
stimulatory or inhibitory
 Neonates of women with Graves’ who have
been surgically/radioactively treated are at
higher risk, b/c not taking suppression
Causes & Diagnosis of
Hyperthyroidism
 Most common cause of hyperthyroidism is
Graves’ disease
 Document elevated FT4 or elevated FTI with
suppressed TSH, in absence of goiter/mass
 Most patients have antibodies to TSH receptor,
antimicrosomal, or antithyroid peroxidase
antibodies, but measurement of these is not
required (though some endocrinologists
recommend measuring TSI, which are
stimulatory antibodies to TSH receptor)
 Other causes:
 Excess TSH production, gestational
trophoplastic disease, hyperfunctioning thyroid
adenoma, toxic goiter, subacute thyroiditis,
extrathyroid source of TH
Treatment of Hyperthyroidism
 Goal is to maintain FT4/FTI in high normal
range using lowest possible dose
(minimize fetal exposure)
 Measure FT4/FTI q2-4 weeks and titrate
 Thioamides (PTU/methimazole) ->
decrease thyroid hormone synthesis by
blocking organification of iodide
 PTU also reduces T4->T3 and may work more
quickly
 PTU traditionally preferred (older studies found
that methimazole crossed placenta more
readily and was associated with fetal aplasia
cutis; newer studies refute this)
Treatment of Hyperthyroidism
 Effect of treatment on fetal thyroid
function:
 Possible transient suppression of thyroid
function
 Fetal goiter associated with Graves’ (usually
drug-induced fetal hypothyroidism)
 Fetal thyrotoxicosis due to maternal antibodies
is rare -> screen for growth and normal FHR
 Neonate at risk for thyroid dysfunction; notify
pediatrician
 Breastfeeding safe when taking
PTU/methimazole
Treatment of Hyperthyroidism
 Beta-blockers can be used for
symptomatic relief (usually Propanolol)
 Reserve thyroidectomy for women in
whom thioamide treatment unsuccessful
 Iodine 131 contraindicated (risk of fetal
thyroid ablation especially if exposed after
10 weeks); avoid
pregnancy/breastfeeding for 4 months
after radioactive ablation
Hypothyroidism
 Symptoms: fatigue, constipation, cold
intolerance, muscle cramps, hair loss, dry
skin, slow reflexes, weight gain,
intellectual slowness, voice changes,
insomnia
 Can progress to myxedema and coma
 Subclinical hypothyroidism: elevated TSH,
normal FTI in asymptomatic patient
 Associated with other autoimmune
disorders
 Type 1 DM -> 5-8% risk of hypothyroidism;
25% postpartum thyroid dysfunction
Hypothyroidism: Fetal & Neonatal
Effects
 Higher incidence of LBW (due to
medically indicated preterm
delivery, pre-eclampsia, abruption)
 Iodine deficient hypothyroidism ->
congenital cretinism (growth failure,
mental retardation, other
neuropsychological deficits)
Causes & Diagnosis of
Hypothyroidism
 Causes:
 Hashimoto’s (chronic thyroiditis; most common
in developed countries) & iodine deficiency ->
both associated with goiter
 Subacute thyroiditis -> not associated with
goiter
 Thyroidectomy, radioactive iodine treatment
 Iodine deficiency (most common worldwide;
rare in US)
Treatment of Hypothyroidism
 Treat with Levothyroxine in
sufficient dose to return TSH to
normal
 Adjust dosage every 4 weeks
 Check TSH every trimester
ACOG Recommendations
 Screening of all pregnant women
with a personal history, physical
examination, or symptoms of a
thyroid disorder.
Rheumatoid Arthritis
Rheumatoid Arthritis in Pregnancy
Affects 1-2% of the general population
More common in women
RA in pregnancy is a common challenge
Sex hormones have effects on disease
activity
70-80% of cases improve during pregnancy
Post-partum flare common
Minimal effects on fetal morbidity and
mortality
Steroids may increase risk of IUGR and
PPROM
Active disease correlates with lower
birth
weights
Effect of Pregnancy on RA
Avoid NSAIDS and high dose aspirin
Low-dose aspirin safe
Use lowest doses of prednisone
Sulfasalazine, hydroxychloroquine in
refractory cases
Treatment of RA in Pregnancy
Aspirin
Azathioprine
Cyclosporin
Cyclophosphamide
Methotrexate
Chlorambucil
High dose prednisone
RA Medications and Breast-feeding –
Avoid:
Immune Thrombocytopenic
Purpura
ITP
Immune thrombocytopenic purpura
(ITP)
 is a clinical syndrome in which a decreased
number of circulating platelets
(thrombocytopenia) manifests as a
 bleeding tendency,
 easy bruising (purpura), or extravasation of blood
from capillaries into skin and mucous membranes
(petechiae). Although most cases of acute ITP,
particularly in children, are mild and self-limited,
intracranial hemorrhage may occur when the
platelet count drops below 10 × 109/L (< 10 ×
103/µL);[1] this occurs in 0.5-1% of children, and
half of these cases are fatal.[2]
Isolated thrombocytopenia
No drugs or other conditions that
may
affect platelet count
Exclude HIV, Hep C, SLE
ITP – Diagnostic Criteria:
Increased platelet destruction
Inhibition of platelet production at
megakaryocyte level
Mediated by IgG Abs against platelet
membrane glycoproteins
Usually a chronic condition
ITP – Pathology:
Petechiae, purpura, easy bruising
Epistaxis, menorrhagia, bleeding from gums
GIT bleeding, hematuria: rare
Intracranial hemorrhage – very rare
ITP – Clinical Features:
May affect fetus in up to 15% of cases
Neonatal count may drop sharply several days after
birth
Difficult to differentiate from gestational
thrombocytopenia
Epidurals safe if count > 50000
Prednisone +/- IVIG if count < 50000
Manage delivery according to standard obstetric
practice
Avoid NSAIDS post-partum
ITP and Pregnancy
Incidence about 5%
Occurs late in pregnancy
Mild (>70 000)
No fetal neonatal
thrombocytopenia
Postpartum resolution
Gestational Thrombocytopenia
Myasthenia Gravis
Typically presents with fluctuating skeletal
muscular weakness
May be ocular or generalised
May have antibodies to the AChR
10-15% have a thymoma
Respiratory muscle involvement may lead
to respiratory failure
Myasthenia Gravis:
Pregnancy has a variable effect on the
course of MG
Post-partum exacerbations in 30%
Infections can trigger exacerbations
Steroids can cause transient worsening
MgSO4 is contraindicated
Myasthenia Gravis in Pregnancy:
Transplacental passage of IgG anti-AChR
Neuromuscular junction disorders
Transient neonatal MG in 10-20%
Decreased FM’s and breathing
Polyhydramnios
Arthrogryposis multiplex congenita
Myasthenia Gravis – Effect on the Fetus
First stage of labour not affected
Second stage: expulsive efforts may
weaken
Assisted vaginal delivery may be indicated
Pre-labour anaesthetic assessment
indicated
Myasthenia Gravis – Labour & Delivery
Systemic Lupus Erythematosus
Severe pulmonary hypertension
Restrictive lung disease
Heart failure
History of severe HELLP or PET
Stroke within previous 6/12
Lupus flare within previous 6/12
SLE features associated with high maternal and fetal risks –
pregnancy relatively contraindicated
Disease exacerbation
Miscarriage, stillbirth
IUGR, preterm labour
Neonatal lupus
Drugs and breast-feeding
SLE complications in pregnancy:
Occurs in up to 2% of mothers with SLE
Targets skin and cardiac tissue,rarely other tissues
Congenital partial or complete heart block
Heart block detected in utero
Complete heart block: PNM of 44%
Rash: erythematous annular lesions
Rash clears within 6/12
Maternal dexamethasone may prevent progression
of heart block
Neonatal pacemaker if HR<55
Neonatal Lupus:

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Thyroid disease in pregnancy

  • 1. Thyroid Disease in Pregnancy Abdelrahman Al-daqqa
  • 2. Physiologic Changes in Thyroid Function During Pregnancy  Thyroid binding globulin (TBG) increases due to reduced hepatic clearance and estrogenic stimulation of TBG synthesis  The test results that change in pregnancy are influenced by changes in TBG concentration  Plasma iodide levels decrease due to fetal iodide use and increased maternal clearance -> leads to notable increase in gland size in 15% of women (without abnormal TFTs)
  • 3. Physiologic Changes in Thyroid Function During Pregnancy Maternal Status TSH **initial screening test** Free T4 Free Thyroxine Index (FTI) Total T4 Total T3 Resin Triiodo- thyronine Uptake (RT3U) Pregnancy No change No change No change Increase Increase Decrease Hyperthyroidism Decrease Increase Increase Increase Increase or no change Increase Hypothyroidism Increase Decrease Decrease Decrease Decrease or no change Decrease
  • 4. The Fetal Thyroid  Begins concentrating iodine at 10- 12 weeks  Controlled by pituitary TSH by approximately 20 weeks
  • 5. Hyperthyroidism  Occurs in 0.2% of pregnancies; Graves’ disease accounts for 95% of cases Look for: -Nervousness -Tremor -Tachycardia -Frequent stools -Sweating -Heat intolerance -Weight loss -Goiter -Insomnia -Palpitations -Hypertension -Lid lag/lid retraction -Pretibial myxedema
  • 6. Fetal & Neonatal Effects of Hyperthyroidism  Associated with preterm delivery, low birth weight, fetal loss  Fetal thyrotoxicosis (related to disease itself or treatment)  Risk of immune-mediated hypo/hyperthyroidism (due to antibodies crossing the placenta, esp. in Graves or chronic autoimmune thyroiditis)  Antibodies in Graves’ disease can be either stimulatory or inhibitory  Neonates of women with Graves’ who have been surgically/radioactively treated are at higher risk, b/c not taking suppression
  • 7. Causes & Diagnosis of Hyperthyroidism  Most common cause of hyperthyroidism is Graves’ disease  Document elevated FT4 or elevated FTI with suppressed TSH, in absence of goiter/mass  Most patients have antibodies to TSH receptor, antimicrosomal, or antithyroid peroxidase antibodies, but measurement of these is not required (though some endocrinologists recommend measuring TSI, which are stimulatory antibodies to TSH receptor)  Other causes:  Excess TSH production, gestational trophoplastic disease, hyperfunctioning thyroid adenoma, toxic goiter, subacute thyroiditis, extrathyroid source of TH
  • 8. Treatment of Hyperthyroidism  Goal is to maintain FT4/FTI in high normal range using lowest possible dose (minimize fetal exposure)  Measure FT4/FTI q2-4 weeks and titrate  Thioamides (PTU/methimazole) -> decrease thyroid hormone synthesis by blocking organification of iodide  PTU also reduces T4->T3 and may work more quickly  PTU traditionally preferred (older studies found that methimazole crossed placenta more readily and was associated with fetal aplasia cutis; newer studies refute this)
  • 9. Treatment of Hyperthyroidism  Effect of treatment on fetal thyroid function:  Possible transient suppression of thyroid function  Fetal goiter associated with Graves’ (usually drug-induced fetal hypothyroidism)  Fetal thyrotoxicosis due to maternal antibodies is rare -> screen for growth and normal FHR  Neonate at risk for thyroid dysfunction; notify pediatrician  Breastfeeding safe when taking PTU/methimazole
  • 10. Treatment of Hyperthyroidism  Beta-blockers can be used for symptomatic relief (usually Propanolol)  Reserve thyroidectomy for women in whom thioamide treatment unsuccessful  Iodine 131 contraindicated (risk of fetal thyroid ablation especially if exposed after 10 weeks); avoid pregnancy/breastfeeding for 4 months after radioactive ablation
  • 11. Hypothyroidism  Symptoms: fatigue, constipation, cold intolerance, muscle cramps, hair loss, dry skin, slow reflexes, weight gain, intellectual slowness, voice changes, insomnia  Can progress to myxedema and coma  Subclinical hypothyroidism: elevated TSH, normal FTI in asymptomatic patient  Associated with other autoimmune disorders  Type 1 DM -> 5-8% risk of hypothyroidism; 25% postpartum thyroid dysfunction
  • 12. Hypothyroidism: Fetal & Neonatal Effects  Higher incidence of LBW (due to medically indicated preterm delivery, pre-eclampsia, abruption)  Iodine deficient hypothyroidism -> congenital cretinism (growth failure, mental retardation, other neuropsychological deficits)
  • 13. Causes & Diagnosis of Hypothyroidism  Causes:  Hashimoto’s (chronic thyroiditis; most common in developed countries) & iodine deficiency -> both associated with goiter  Subacute thyroiditis -> not associated with goiter  Thyroidectomy, radioactive iodine treatment  Iodine deficiency (most common worldwide; rare in US)
  • 14. Treatment of Hypothyroidism  Treat with Levothyroxine in sufficient dose to return TSH to normal  Adjust dosage every 4 weeks  Check TSH every trimester
  • 15. ACOG Recommendations  Screening of all pregnant women with a personal history, physical examination, or symptoms of a thyroid disorder.
  • 17. Rheumatoid Arthritis in Pregnancy Affects 1-2% of the general population More common in women RA in pregnancy is a common challenge Sex hormones have effects on disease activity 70-80% of cases improve during pregnancy Post-partum flare common
  • 18. Minimal effects on fetal morbidity and mortality Steroids may increase risk of IUGR and PPROM Active disease correlates with lower birth weights Effect of Pregnancy on RA
  • 19. Avoid NSAIDS and high dose aspirin Low-dose aspirin safe Use lowest doses of prednisone Sulfasalazine, hydroxychloroquine in refractory cases Treatment of RA in Pregnancy
  • 22. Immune thrombocytopenic purpura (ITP)  is a clinical syndrome in which a decreased number of circulating platelets (thrombocytopenia) manifests as a  bleeding tendency,  easy bruising (purpura), or extravasation of blood from capillaries into skin and mucous membranes (petechiae). Although most cases of acute ITP, particularly in children, are mild and self-limited, intracranial hemorrhage may occur when the platelet count drops below 10 × 109/L (< 10 × 103/µL);[1] this occurs in 0.5-1% of children, and half of these cases are fatal.[2]
  • 23. Isolated thrombocytopenia No drugs or other conditions that may affect platelet count Exclude HIV, Hep C, SLE ITP – Diagnostic Criteria:
  • 24. Increased platelet destruction Inhibition of platelet production at megakaryocyte level Mediated by IgG Abs against platelet membrane glycoproteins Usually a chronic condition ITP – Pathology:
  • 25. Petechiae, purpura, easy bruising Epistaxis, menorrhagia, bleeding from gums GIT bleeding, hematuria: rare Intracranial hemorrhage – very rare ITP – Clinical Features:
  • 26. May affect fetus in up to 15% of cases Neonatal count may drop sharply several days after birth Difficult to differentiate from gestational thrombocytopenia Epidurals safe if count > 50000 Prednisone +/- IVIG if count < 50000 Manage delivery according to standard obstetric practice Avoid NSAIDS post-partum ITP and Pregnancy
  • 27. Incidence about 5% Occurs late in pregnancy Mild (>70 000) No fetal neonatal thrombocytopenia Postpartum resolution Gestational Thrombocytopenia
  • 29. Typically presents with fluctuating skeletal muscular weakness May be ocular or generalised May have antibodies to the AChR 10-15% have a thymoma Respiratory muscle involvement may lead to respiratory failure Myasthenia Gravis:
  • 30. Pregnancy has a variable effect on the course of MG Post-partum exacerbations in 30% Infections can trigger exacerbations Steroids can cause transient worsening MgSO4 is contraindicated Myasthenia Gravis in Pregnancy:
  • 31. Transplacental passage of IgG anti-AChR Neuromuscular junction disorders Transient neonatal MG in 10-20% Decreased FM’s and breathing Polyhydramnios Arthrogryposis multiplex congenita Myasthenia Gravis – Effect on the Fetus
  • 32. First stage of labour not affected Second stage: expulsive efforts may weaken Assisted vaginal delivery may be indicated Pre-labour anaesthetic assessment indicated Myasthenia Gravis – Labour & Delivery
  • 34. Severe pulmonary hypertension Restrictive lung disease Heart failure History of severe HELLP or PET Stroke within previous 6/12 Lupus flare within previous 6/12 SLE features associated with high maternal and fetal risks – pregnancy relatively contraindicated
  • 35. Disease exacerbation Miscarriage, stillbirth IUGR, preterm labour Neonatal lupus Drugs and breast-feeding SLE complications in pregnancy:
  • 36. Occurs in up to 2% of mothers with SLE Targets skin and cardiac tissue,rarely other tissues Congenital partial or complete heart block Heart block detected in utero Complete heart block: PNM of 44% Rash: erythematous annular lesions Rash clears within 6/12 Maternal dexamethasone may prevent progression of heart block Neonatal pacemaker if HR<55 Neonatal Lupus: