The document summarizes thyroid disorders in pregnancy. Some key points: - Thyroid disorders are among the most common endocrine conditions affecting 1-2% of pregnancies. Proper management is important for pregnancy outcomes. - Hypothyroidism can cause complications for both mother and fetus like preeclampsia, preterm birth, and developmental delays. Treatment is levothyroxine. - Hyperthyroidism in pregnancy is usually Graves' disease and may improve during pregnancy due to immunosuppressive effects but often worsens postpartum. Treatment focuses on maintaining normal thyroid levels. - Postpartum thyroiditis is an autoimmune condition causing transient thyroid dysfunction after delivery

1. DR RAJEEV SOOD
DR RASHMI VOHRA
DEPT. OF O.B.G. IGMC SHIMLA

2.  Most common endocrine disorder in pregnancy.
 1-2% pregnant women.
 Pregnancy may modify course of thyroid disease.
 Pregnancy outcome can depend on optimal management of thyroid
disorders.
 The Himalayan goiter belt - word’s largest belt from Kashmir to
Naga Hills.

3.  Thyroid; derived from Greek
word – means shield gland.
 Highly vascular organ.
 Brownish red, 2 lobes (4x2cm),
one isthmus(2x2cm).
 30% have pyramidal lobe.
 Weight: 15-20g

4.  Hypothalamic-Pituitary axis governs thyroid physiology.
HYPOTHALAMUS
TRH
PITUITARY
3,5,3’,5’ tetra-iodo-L-thyronine
(levothyroxine,L-thyroxine,T4)
TSH
3,5,3’-tri-iodo-L-
THYROID thyronine (liothyronine,
triiodothyronine;T3)

5. iodine
reduced iodide
transported Thyroid
 in gut to
Iodide
incorporated
into gp
thyroglobulin
MIT DIT
 T4 enters circulation by direct glandular secretion.
 T3 is produced by mono-deiodination of T4 in periphery.

6.  T4 bound to circulating transport proteins –
 Thyroxine binding globulin (TBG),
 Thyroxine binding prealbumin or transthyretin,
 Albumin.

7. Serum Units 1st trimester 2nd 3rd
TSH mU/L 0.03-2.3 0.03-3.7 0.13-3.4
FT4 ng/dl 0.86-1.77 0.63-1.29 0.66-1.12
FT3 pmol/L 3-5.7 2.8-4.2 2.4-4.1
ratio FT4:FT3 :: 4:1

8.  Increased thyroxine requirement in pregnancy:
(1) TBG Free thyroid hormones H-P-T axis stimulation
(2) hCG stimulates TSH rp
(3) peripheral metabolism. ?
placental type II deiodinase
T4 T3 (fetus is dependent on type II conversion)
pl type III deiodinase
T4 rT3 3,3’diiodothyronine(T2)

9. PHYSIOLOGIC CHANGE CLINICAL IMPORTANCE
Increased TBG Need for T4 production
TT3 & TT4 levels
Interference with FT4 assay accuracy
Placental de-iodination of T4 T3 & T4 metabolism
Need for T4 production
Increased iodine clearance iodine requirement
(renal clearance and fetal transfer) Risk of maternal and fetal hypothyroidism and goiter
B HCG elevation 1st TM FT4 & TSH
Transient mild thyrotoxicosis
Reduction in TSHRAb during Graves’ disease improvement
pregnancy
Postpartum increase in thyroid Exacerbation of Graves’ disease
antibodies Precipitation of postpartum thyroiditis

10. organization Thyroid screening Goal TSH(mIU/L) Treatment of
with TSH subclinical
hypothyroidism
ACOG Case finding Not specified Not recommended
oct 2007
USPSTF(United Case finding Not specified Not specified
States Preventive
Services Task Force)
TES(The Endocrine Case finding 2.5 in Ist TM Recommended
Society) 3 in IInd &IIIrd TM
AACE( American Routine 0.3-3.0 Recommended
Association of Clinical
Endocrinologists)
BTA(British thyroid Case finding 0.4-2.0 Recommended
association)

11.  Sign/symptoms of hypo or hyperthyroidism
 Goiter
 h/o hyperthyroid or hypothyroid disease, postpartum thyroiditis or thyroid surgery
 Previous therapeutic head or neck irradiation
 Autoimmune disorder
 Family history of thyroid disease
 Infertility
 History of miscarriage or preterm delivery
 Thyroid antibodies
 Unexplained anemia or hyponatremia
 Increased cholesterol level

12. Events in
fetus
Maternal thyroxine in coelomic fluid 6 weeks
THR gene expression in human brain 8 weeks
Fetal iodine uptake 10-14 weeks
Fetal thyroxine secretion 18 weeks

13.  Hypothyroidism
 Autoimmune thyroid disease
 Hyperthyroidism
 Postpartum thyroiditis

14.  Incidence: 1 - 3 per 1000 pregnancies.
 Types:
 Primary - inadequate thyroid hormone production despite pituitary
gland stimulation(including iodine deficiency).
 Central - insufficient stimulation of the thyroid by the pituitary or
hypothalamus.
 Subclinical – Elevated TSH levels normal FT4 in absence of clinical
symptoms.
 Overt – increased TSH with low thyroxine levels with clinical
symptoms.

15. PRIMARY HYPOTHYROIDISM SECONDARY
HYPOTHYROIDISM
 Hashimoto thyroiditis  Hypothalamic or pituitary
 Subacute thyroiditis tumor
 Endemic iodine deficiency  Surgery
 Suppurative thyroiditis  Radiation
 Previous thyroidectomy  Sheehan syndrome
 Previous radioablation  Lymphocytic hypophysitis
 Medication exposure
SUBCLINICAL
HYPOTHYROIDISM
ISOLATED
HYPOTHYROXINEMIA

16.  Lymphadenoid thyroiditis ; chronic lymphocytic thyroiditis.
 Most common cause in iodine sufficient population.
 Incidence: 4 per 1000.
 female: male : 5:1
 Antithyroid antibodies damage the gland.
 Transient hyperthyroidism hypothyroidism(90% gland
destroyed)

17. SUBACUTE GRANULOMATOUS SUBACUTE LYMPHOCYTIC
THYROIDITIS
THYROIDITIS
 Subacute painful thyroiditis  Subacute painless thyroiditis
 Viral infection  Postpartum thyroiditis
 Sudden onset  Painlessly enlarged thyroid
gland.
 Fever, myalgia, neck pain
L/E
 Painfully enlarged thyroid

18. Subacute granulomatous thyroiditis Subacute lymphocytic thyroiditis
Transient hyperthyroidism
Transient hypothyroidism
90% 10%
recover persistent goiter
 Lasts 4-6 weeks; may be 9 months
 Differentiated from Graves disease by lack of radioiodine uptake on
thyroid scan
 Symptomatic treatment.

19.  Leading cause of preventable mental retardation worldwide.
 Mean IQ loss of 13.5 points.
 Iodine sufficiency determined through measuring median Urinary
Iodine excretion.
 Insufficient urinary iodine:
 Pregnancy : <150mcg/L
 Lactation : <100mcg/L
renal clearance
 Iodine needs increase in pregnancy
fetal and placental uptake

20. Recommended iodine Excessive iodine (μg/d)
intake (μg/d)
Pregnant women 250 500
Lactating women 250 500
Children 0-5 years 90 180
6 to 12 years 120 180
>12 years 150 180

21.  Iodised salt : 46–76 mg/kg
 Shrimp (85 grams) : 35mcg
 Egg, boiled : 12mcg
 Navy beans, cooked – ½ cup : 32mcg
 Potato with peel, baked – 1 medium : 60mcg
 Seaweed (7 grams) dried – 4,500mcg (highest).
Iodine should be added after cooking of food. ?

22.  Secondary hypothyroidism
 Pituitary necrosis from vascular hypoperfusion
 Spectrum varies from failure of lactation or resume menses to acute
panhypopituitarism
 90% develop secondary hypothyroidism.

23.  Secondary hypothyroidism
 Peripartum period
 Autoimmune disorder
 Anterior pituitary destruction
 Panhypopituitarism to single hormone deficiency
 Imaging: enhancing sella turcica mass
 Mass effects (headache and visual field changes)

24.  TSH ; N FT4 & FT3
 Prevalence in pregnancy- 2-5%
 31% +ve for TPO antibodies.
 More commonly seen with autoimmune diseases
 Associated with gestational hypertension, preterm
delivery, stillbirths, abruption.

25.  N TSH FT4
 Prevalence: 1-2% of pregnancies.
 No adverse affects on pregnancy outcome
 No benefit of levothyroxine treatment.

26.  Fatigue,  Insomnia,
 Constipation,  Periorbital oedema,
 Cold intolerance,  Myxedema,
 Weight gain,  Prolonged relaxation of DTRs.
 Carpal tunnel syndrome,
 Hair loss,
 Voice changes,
 Reduced memory; slowed thinking,
 Muscle cramps,
 Dry skin,
 Goiter.

27. ON PREGNANCY ON FETUS
 early pregnancy failure,  neurodevelopmental delay,
 pre-eclampsia(5-10%),  deafness,
 placental abruption(1%),
 stunted growth ,
 Preterm delivery(10-15%)
 Peripartum hypoxia and
 Malpresentation,
 low birthweight,  increased risk of neonatal
mortality
 Stillbirth,
 PPH.

28.  TSH
 Low FT4
?
 Low FT4I(4.5-12.5mcg/dl)
 Antithyroid antibodies (anti-TPO and
antithyroglobulin)

29. Goal
 To return thyroid hormone levels to within the
reference range. ?

30.  Euthyroidism at the time of conception.
 If on treatment- delay pregnancy until TSH is normal.
 do not take levothyroxine and multivitamins at the same time
(interference with absorption of thyroxine)
 adequate iodine intake (250mcg/d).
 Dietary goitrogens : cabbage, cauliflower, broccoli and even water
purifying agents should be avoided. Boiled water is recommended.

31. >/=1 risk Euthyroid:no
 factor for S.TSH 0.08-<3 further work
thyroid ds up
Repeat TSH,FT4, TPO
>/=3 Levothyroxine
started
TSH>/=3
Normal TSH>/=3 Low FT4
results N FT4, +/-TPO
+/- TPO
SUBCLINICAL HYPOTHYROIDISM HYPOTHYROIDISM
EUTHYROID:
Stop
levothyroxine

32.  Levothyroxine sodium - most widely prescribed treatment
 Safe for both mother and fetus. Category A.
 Available dosages - 25–300 mcg.
 Dose : 30% increase from non pregnant value, if already
hypothyroid.
 If newly diagnosed in pregnancy : 1.0–2.0 mcg/kg/day or
approximately 100 – 150 mcg of levothyroxine daily.
 TSH measured 4-6 weeks following dose change with TSH goal
between 0.5-2.5mIU/L
 Once stable, TSH checked every 8 weeks.

33.  Bioavailability affected by medications or food: taken empty
stomach.
 Absorption: Carafate, cholestyramine, ferous sulphate & calcium
carbonate.
 Clearance: phenytoin, carbamazepine.
 Postpartum:
 Decrease dose by 30% (diagnosed in pregnancy)
 Prepregnancy dose (hypothyroid before pregnancy)
 TSH reassessed 6 week postpartum.

34. ON MOTHER ON FETUS
 Related to Overtreatment  smaller head circumference
and LBW.
 hyperthyroidism.
 transient hair loss.
 BMD

35.  Women should be clinically and biochemically euthyroid
prior to labor.
 Obstetric complications including increased risk of
stillbirth, preterm delivery, pre-eclampsia and placental
abruption should be kept in mind.

36. Causes:
 Thyroid dysgenesis
 Thyroid apasia
 Thyroid hypoplasia
 Thyroid ectopy
 Drug induced (thioamides ,amiodarone , lithium , potassium iodide)
 Dyshormogenesis
 TSH receptor mutations
 Thyorid hormone resistance
 Pendred’s syndrome: defect in iodine organification and sensorineural
deafness.

37. In utero therapy:
Fetus effectively absorbs T4 from amniotic fluid.
3rd trimester fetal T4 requirement : 6 ug / kg /day.
Intraamniotic administration of 250 – 500 ug of thyroxine done at 7 –
10 days interval.
In term infants :
Requirement : 10 – 15 ug /kg /day.
TSH levels kept below 5 mU /l and T4 levels at 10-16 ug /dl.
Tab thyroxine crushed and fed directly to the infant.

38. Thyroid antibodies:
 directed towards cytoplasmic antigens-
 thyroid peroxidase (TPOAb) and
 thyroglobulin (TgAb) antibodies.
 directed to the TSH receptor-
 TSH receptor antibody (TSHRAb).
 TPOAB present in 10-15% normal population.

39.  Thyroid autoimmunity increased miscarriage rates.
 Causes :
 subtle maternal thyroid dysfunction
 autoimmune imbalance; rejection of the fetus
 thyroid antibodies affecting fetal thyroid gland ; fetal loss
 Associated increased maternal age

40. Trophoblast secrete immunosuppressant factors
antibody titers
graves disease improvement
antibody titer post partum
postpartum flare up
postpartum thyroiditis.

41.  Incidence: 0.1 to 0.4 %
 Types:
 Subclinical hyperthyroidism-suppressed TSH, normal FT4 and FT3
 Overt-suppressed TSH and elevated FT4 and/or FT3
 Gestational- detected in pregnancy.

42. Intrinsic thyroid disease
 Graves’ disease (most common)
 Toxic nodule – single or multiple
 Subacute or silent thyroiditis
Excessive, exogenous thyroid hormone
 Factitious
 Therapeutic(amiodarone)
Gestational thyrotoxicosis
 Hyperemesis
 Gestational trophoblastic disease
 Hydatidiform mole
 Multiple gestations
 Hydrops
Rare
 TSH producing pituitary tumour
 Iodine induced
 Struma ovaii.

43.  Cause: cross reactivity between hcg and TSH at thyroid receptor
 Nausea and vomiting leading to dehydration, electrolyte
imbalance and weight loss.
 Spontaneous resolution by 18 weeks.
 Antithyroid medications avoided.

44.  Autoimmune disorder.
 Incidence: 0.5%
 Most common cause of hyperthyroidism in pregnancy
 Symptoms antecedent pregnancy
 Physiology: antibodies stimulate thyroid receptors; thyroid
hypertrophy and hyperfunction.
 Antibodies:
 TPO
 Thyroglobulin
 Microsomal
 Thyroid receptor antibodies.

45.  Immunoglobulins, ( IgG subclass).
 2 types:
 Stimulating – thyroid stimulating immunoglobulins(TSI); Graves'
disease.
 Blocking – thyrotropin binding inhibitory immunoglobulins(TBII);
Hashimoto's thyroiditis.

46.  Cross the placental barrier affect fetal thyroid function.
 TSI fetal tachycardia, goiter, IUGR, craniosynostosis,
premature skeletal maturation, CHF, hydrops.
 TBII fetal bradycardia, goiter, IUGR.

47. 1st and 2nd trimester
 Previous radio-active iodine or thyroidectormy for Graves’ disease
 New-onset thyrotoxicosis to differentiate Graves’ disease from
gestational thyrotoxicosis
 Previous pregnancy complicated by fetal or neonatal
hyperthyroidism
3rd trimester
 Woman requiring antithyroid drugs for Graves’ disease into third
trimester

48.  Nervousness,Agitation,Fatigue  Eye signs (distinct from
Graves’ ophthalmopathy)
 Tachycardia/palpitations
 Heat intolerance  Lid lag
 Increased appetite, Weight loss  Lid retraction
 Change in bowel habits
 Proptotis
 Skin/hair/nail changes; Skin is soft
and moist
 Onycholysis (separation of the distal
nail from its bed)
 Hair soft, fine and thin

49.  Graves' orbitopathy:
 Chemosis (swelling of the conjunctiva),
 Proptosis (exophthalmos or bulging orbit),
 Dysconjugate gaze (double vision on looking to the extremes of the visual
field)
 Pretibial myxedema ( thyroid dermopathy)
 bilateral, firm, nonpitting, asymmetric plaques or nodules, most often
confined to the pretibial area ; may occur anywhere
 Thyroid bruit
 Clubbing

50. ON PREGNANCY ON FETUS
 Spontaneous abortion,  Congenital malformations of
 Preterm birth, heart, kidney or brain.
 Pre-eclampsia,  Fetal Graves’ disease
 Abruption,  fetal tachycardia,
 Fetal growth restriction,  high output cardiac failure,
 Perinatal morbidity and  NIHF,
mortality,  craniosynostosis,
 Congestive heart failure,  LBW,
 Thyroid storm.  fetal goiter,
 Fetal demise.

51.  Hyperthyroidism can be diagnosed on the basis of
 Clinical presentation
 Thyroid examination
 Thyroid function tests
 Thyroid antibody tests

52.  Graves disease- a diffuse, symmetric, soft goiter, which
may have an audible bruit.
 Nodular thyroid disease- A palpable nodule (usually 3 cm)
 Subacute thyroiditis- generalized thyroid tenderness.

53. Goals
 To normalize thyroid hormone levels(keeping FT4 in upper normal
range <0.85-1.9ng/dl),
 To treat bothersome adrenergic symptoms of hyperthyroidism.

54. Clinical situations:
 Hyperthyroidism under treatment
 Potential side effects of antithyroid drugs on the fetus discussed.
 wait 6 months after radioablation.
 euthyroid at the time of conception.
 Previous ablation treatment for Graves' disease
 The dose of thyroid replacement therapy needs to be increased soon after conception.
 In spite of euthyroidism, high maternal titers for TSI may be present; fetus at risk.
 Previous treatment for thyroid carcinoma
 wait 1 year after completion of radioactive treatment before conception.
 Inadequately treated hyperthyroidism
 impaired maturation of the fetal hypothalamic-pituitary-thyroid axis - central congenital
hypothyroidism in the infant.

55. PROPYLTHIOURACIL (PTU)
 Inhibits conversion of T4 to T3
 Crosses placenta less readily.  Improvement seen in 3-4
 Dose- 300-450mg in 3 divided weeks; full response 8 weeks.
doses of 100-150mg each.
 Category D ?  Tapered as pregnancy
progresses.
 Side effects:
 Iatrogenic fetal hypothyroidism
 Transient leukopenia (10%)
 Agranulocytosis (0.3-0.4%)
 Hepatotoxicity (0.1-0.2%)
 Vasculitis

56. METHIMAZOLE  Side effects:
 Dose- 5–20 mg b.i.d
 Crosses placenta more readily.
 Transient leukopenia (10%)
 Category D
 Agranulocytosis (0.3-0.4%)
 Methimazole embryopathy –  Hepatotoxicity (0.1-0.2%)
 Esophageal atresia  Vasculitis
 Choanal atresia
 Cutis aplasia.
 Dose monitored with 3-4 weekly FT4 or FT4I levels.
 Improvement seen in 3-4 weeks; full response 8 weeks.
 Tapered as pregnancy progresses.

57.  10% fetus exposed to drugs develop fetal or neonatal
hypothyroidism
Monitoring:
 Clinical examination for fetal growth
 Ultrasonography :
 FHR (bradycardia)
 Growth parameters
 Fetal goiter(symmetric paratracheal mass, neck hyperextension,
polyhydramnios)
 Cordocentesis.

58.  Routine fetal blood sampling for thyroid indices is recommended if –
 previous I131 ablation,
 Abnormal TSIs or TBII,
 FGR, heart failure or goiter, with or without tachycardia.

59. Other drugs in hyperthyroidism
 Beta adrenergic blockers: propranolol.
inhibits
 MOA: T4 T3
 20-40mg orally every 8-12 hours

60.  Management
 Antithyroid medications,
 beta-blockers and
 Supportive Care.
 fetal thyrotoxicosis suspected in labor aggressive treatment of
maternal thyrotoxicosis
 fetus with a large goiter consideration of the best route of delivery
 Elective cesarean to avoid dystocia
 management of the fetal airway.

61. ex utero intrapartum treatment (EXIT) procedure
 Candidates: Fetuses with neck masses large enough to cause airway
obstruction ; to manage airway obstruction after fetal surgery.
 It involves securing the neonatal airway (usually with endotracheal
intubation often guided by laryngoscopy or bronchoscopy) while the
umbilical cord and maternal-fetal circulation remain intact in the
hopes of avoiding difficult emergency intubations in the delivery
room.
 Usually perfomed with cesarean deliveries; described with vaginal
deliveries too.

62.  Most commonly diagnosed endocrine malignancy.
 Incidence: 14 / 1,00,000 pregnant women.
 Histologic types: papillary, follicular, medullary, Hurthle cell, anaplastic
 Papillary thyroid cancer : most common type in pregnancy.
 Excellent long term prognosis
 Surgey delayed postpartum; depending upon histology.
 S.thyroglobulin : predictive of recurrent disease.
 Postsurgical I131 whole body scintigraphy and radioiodine remnant
ablation : contraindicated in pregnancy & lactation.

63. PRECIPITATING FACTORS
CLASSIC FEATURES
 Fever,  Preeclampsia,
 Tachycardia with atrial fibrillation,  Anemia,
 Nausea/vomiting/diarrhoea/  Sepsis,
dehydration,  surgery.
 Agitation/delirium/coma, LAB VALUES
 T4 & T3
 High-output cardiac failure,
 TLC
 Jaundice,
 Transaminases
 Abdominal pain.  hypercalcemia

64. STEP 1. START THIONAMIDES & CONTROL HEART RATE
beta-blockers - control tachycardia (maintain
THIONAMIDES- 1 g PTU (orally or through HR<90bpm)- propranolol 1-2 mg i/v over 5 min to total
NG tube) 200 mg every 6 hours of 6-10mg 60–80 mg every 4 hours orally or
NG tube.
STEP 2.CORTICOSTEROIDS
Dexamethasone 1-2mg PO/IV/IM 6 hourly
Or
Hydrocortisone 100mg IV 8 hourly
Or
Prednisone 60mg PO a day
STEP 3.IODINE(after 1-2 hour of thionamide therapy.)
SSKI 5 drops orally 8 hourly.
Or
500-1000mg sodium iodide i.v. 8 hourly
Or
Lugol’s solution 10 drops orally 8 hourly
Or
Lithium carbonate 300mg PO 6 hourly
Or
Iodinated radiocontrast agents iopodate and iopanoic acid
0.5–1.0 g orally daily.

65.  immunosuppression postpartum relapse(70%)
disappears (within first 3 months)
 TSH and free T4 done 6 weeks post partum.
 T4 levels must be controlled prior to the next pregnancy.
Drugs in lactating mother:
 Both PTU and methimazole excreted in breast milk; PTU is largely protein bound;
does not seem to pose a significant risk to the breastfed infant.
 Methimazole safe only at low doses (10–20 mg/day).
 AAP and WHO support compatibility of breatfeeding and all antithyroid
medications

66.  Postpartum Rebound in thyroid autoimmunity
lymphocytic infiltration of the thyroid gland
 The likelihood of developing postpartum thyroidis is related to serum levels of
thyroid autoantibodies.
 Anti-TPO antibodies are present in 90% of women with PPT.
 Women with high antibody titers in early pregnancy have 40–50% chance of
developing PPT.
 Women with type 1 diabetes have a significantly higher incidence, ranging from
18% to 25% due to the high prevalence of TPO antibodies.

67. HYPERTHYROID PHASE HYPOTHYROID PHASE
 Autoimmune destruction of the  immune destruction loss of
gland - release of stored hormone functioning thyrocytes
 1 - 4 months postpartum  3 - 8 months postpartum (usually at 6
months)
 self-limiting (1–2 months).
 lasts much longer (4–6 months)
 Abrupt onset
 fatigue, palpitations, sleep  fatigue, weight gain, loss of
deprivation, nervousness / irritability. concentration, depression
 small, painless goiter may be
present.
 Antithyroid medications not
beneficial.

68.  Patients identified with PPT should be screened regularly since 20–
50% of women will develop permanent hypothyroidism within 2–10
years.
 A TSH level should be done annually and prior to conception.

69. EVALUATION OF THYROID NODULE IN PREGNANCY
Abnormal TSH
Work up N
& treat
Solid lesion>2cm USG
Cystic lesion>4cm Solid lesion<2cm
Cystic lesion<4cm
<24
weeks
>24
weeks
FNAC Postpartum
Levothyroxine follow up
Non
malignant malignant
surgery