THYROID DISEASES IN PREGNANCY, grave's disease, hypothyroidism, hyperthyroidism, thyroid storm, thyroid nodule, thyroid cancer, iodine deficiency, goiter, neonatal hypothyroidism, management of hypothyroidism, thyroid gland, maternal and fetal risks

1. THYROID IN
PREGNANCY
DR. PREKSHA JAIN
DR. BHAVNA KUMARE

2. CONTENTS
 Introduction & incidence
 Physiological changes in
pregnancy
 Normal values in pregnancy
 Events in fetus
 Interpretation of tests
 Hypothyroidism
 Hashimoto thyroiditis
 Subacute thyroiditis
 Subclinical hypothyroidism
 Neonatal hypothyroidism
 Autoimmune diseases
 Hyperthyroidism
 Grave’s disease
 Thyrotoxicosis
 Thyroid cancer
 Postpartum management &
postpartum thyroiditis
 Thyroid nodule in
pregnancy
REFERENCE: de Swiet’s, Fogsi, William’s

3. INTRODUCTION
 Highly vascular organ
 15-20 gm
 Isthmus cross 2nd to 4th cartilage
 Follicle, C cells/parafollicular cells
 Produce T4 & T3
 Synthesis- Iodide trapping, Oxidation & iodination,
Coupling, Release
 Transport (TBG, TTR, Albumin)
 Free hormone levels- T4 (0.03%) < T3 (0.3%)

4. INCIDENCE
 M/c endocrine disorder in pregnancy
 1-2% pregnant women
 Overt Hypothyroidism- 0.05%
 Subclinical hypothyroidism- 2%
 Hyperthyroidism- 0.05-0.2% (Grave’s – 90%)
 Postpartum thyroiditis- 5-10%

5. NORMAL CHANGES IN PREGNANCY
PHYSIOLOGICAL CHANGE IMPACT
Iodine clearance
(renal & transplacental)
Relative iodine deficiency state
Risk of fetal & maternal hypothyroidism
Placental deiodination of T4 T4 Reverse T3
TBG TT3 & TT4 levels
FT4 same
1st trimester HCG
(Weak TSH effect)
FT4 & TSH
Fetal & placental devp
3rd trimester - placenta enlarge,
preparation for delivery
FT4 & TSH
Mild hypothyroidism
TSHR Ab reduced Grave’s disease improvement
Postpartum increase in thyroid Ab Postpartum thyroiditis
Grave’s disease exacerbation

7. NORMAL VALUES IN PREGNANCY
SERUM UNITS 1ST trimester 2nd 3rd
TSH mU/L 0.03-2.3 0.03-3.7 0.13-3.4
FT4 Ng/dl
pmol/L
0.86-1.77
11.1-22.9
0.63-1.29
8.1-16.7
0.66-1.12
8.5-14.4
FT3 pmol/L 3-5.7 2.8-4.2 2.4-4.1

8. EVENTS IN FETUS
 Maternal thyroxine in coelomic fluid @ 6 weeks
 T3 is present in fetal brain @ 7 weeks
 THR gene expression in brain @ 8 weeks
 Fetal iodine uptake @ 10-14 weeks
 Fetal thyroxine secretion @ 18 weeks
 30% Maternal thyroxine in fetal serum at birth

9. INTERPRETATION OF TESTS
TSH
NORMAL
TSH
INCREASED
TSH
DECREASED
FT4
NORMAL
Normal ,
Euthyroid Sick
Syndrome
Subclinical
hypothyroidism
Subclinical
Hyperthyroidism
FT4
INCREASED
Consider TSH high Hyperthyroidism
(TSH producing
pituitary
adenoma)
Hyperthyroidism
(Grave’s, toxic
nodule)
FT4
DECREASED
Consider TSH low Hypothyroidism
(primary thyroid
failure)
Hypothyroidism
(primary pituitary
failure),
T3 toxicosis

10. HYPOTHYROIDISM
 Nonspecific insidious clinical findings like weight gain, fatigue,
cold intolerance & muscle cramps
 1-3 per 1000 pregnancies
 Types-
1. PRIMARY
2. SECONDARY/CENTRAL
3. SUBCLINICAL
4. OVERT

11. CAUSES OF HYPOTHYROIDISM
PRIMARY HYPOTHYROIDISM SECONDARY HYPOTHYROIDISM
 Endemic iodine deficiency
 Hashimoto thyroiditis
 Subacute thyroiditis
 Suppurative thyroiditis
 Previous thyroidectomy
 Previous radioablation
 Medication exposure
 Hth/ pituitary tumor
 Surgery
 Radiation
 Sheehan’s
 Lymphocytic hypophysitis
Subclinical hypothyroidism
Isolated hypothyroxinemia

12. IODINE DEFICIENCY GOITER
 Leading cause of preventable Mental retardation
(developing countries)
 Mean IQ loss 13.5points
 Median Urinary Iodine Excretion determine iodine
sufficiency
 Iodine requirement
 Non pregnant 150μg
 Pregnancy 175μg
 Lactation 200μg

13. SPECTRUM OF IDD
 FETUS
• Stillbirth
• Perinatal & infant mortality
• Neurological Cretinism
• Myxedematous cretinism
• Mental deficiency
• Mutism, spastic diplegia
• Squint
• Dwarfism, psychomotor
defects
• Hypothyroidism
 NEONATE
• Neonatal hypothyroidism
 CHILD & ADOLESCENT
• Mental & physical development
 ADULT
• Goiter & its complications
• Iodine induced hypothyroidism
 ALL AGES
• Goiter
• Susceptibility to nuclear radiation

14. HASHIMOTO THYROIDITIS
 M/c cause of hypothyroidism in pregnancy (developed countries)
 Lymphadenoid thyroiditis; chronic lymphocytic thyroiditis
 Autoimmune destruction of thyroid cells
 Transient hyperthyroidism hypothyroidism (90% destroyed)

15.  Painful
SUBACUTE THYROIDITIS
 Viral infection
 Sudden onset
 Fever, myalgia, neck pain
 Painfully enlarged thyroid
 Painless
 Postpartum thyroiditis
 Painlessly enlarged gland
SUBACUTE GRANULOMATOUS
THYROIDITIS
SUBACUTE LYMPHOCYTIC
THYROIDITIS

16. Subacute thyroiditis
 4-6weeks
Transient hyperthyroidism
Transient hypothyroidism
90% 10%
Recover Persistent goiter
 Symptomatic treatment

17. LYMPHOCYTIC HYPOPHYSITIS
 Secondary hypothyroidism
 Peripartum period
 Autoimmune
 Ant pituitary destruction
 Panhypopituitarism to single hormone deficiency
 Mass effects (headache & visual changes)
 Imaging: enhancing sella turcica mass

18. SUBCLINICAL HYPOTHYROIDISM
 TSH & Normal FT4 & FT3
 2-5% in pregnancy
 31% positive for TPO Ab
 Associated with Gest HTN, preterm deliveries, stillbirths,
abruption.
 Fetal psychomotor development may be impaired
 Routine screening not recommended

19. ISOLATED HYPOTHYROXINEMIA
 Normal TSH FT4
 1-2% pregnancies
 No adverse effects in pregnancy
 No benefit of levothyroxine t/t

20. SYMPTOMS & SIGNS OF HYPOTHYROIDISM
 Fatigue
 Constipation
 Cold intolerance
 Weight gain
 Carpel tunnel syndrome
 Hair loss
 Voice changes
 Slow thinking
 Dry skin
 Goiter
 Insomnia
 Periorbital edema
 Myxedema
 Prolonged relaxation of DTRs
 PR slow

22. EFFECTS OF HYPOTHYROIDISM
 ON PREGNANCY
• Prolonged infertility t/t
• Recurrent abortions
• Preeclampsia 5-10%
• Placental abruption 1%
• Preterm delivery 10-15%
• Anemia
• Myxedema coma
• Malpresentation
• LBW
• PPH
• Stillbirth
 ON FETUS
• Neurodevelopmental delay
• Deafness
• Stunted growth
• Peripartum hypoxia
• Neonatal mortality

23. LAB TESTS & SCREENING
 TSH
 FT4
 Antithyroid ab (Anti TPO & antithyroglobulin)
 Case finding approach rather than universal screening
 TSH should be done ideally before pregnancy
 If not done, high risk women should be screened –
• Strong family history
• Autoimune disorder
• Presence of goiter
• Personal history of thyroid disease
• Therapeutic neck irradiation
• Medications

24. MANAGEMENT
 Prepregnancy: 1.7μg/kg levothyroxine started
 During pregnancy:
4-6wks
TSH normalized
Pregnancy
• If TSH > 5μU/ml start t/t
• If TSH 2.5-5μU/ml & AMA positive start t/t
• If TSH 2.5-5μU/ml & AMA negative monitor
closely

25. PREGNANCY
BLOOD VOLUME & TBG INCREASED
FREE T4 DECREASED
EUTHYROID HYPOTHYROID
COMPENSATE THYROXINE DOSE INCREASED
25-40%
4-6 WEEKS
REPEAT TSH (GOAL 0.5-2.5mIU/L)
ADJUST DOSE
REPEAT TSH EVERY 8WEEKS

26. LEVOTHYROXINE SODIUM
 Most widely prescribed t/t
 Category A
 25-300 mcg
 If newly diagnosed in pregnancy started @ 1-2μg/kg/d
or approx 100-150μg/d
 If previously hypothyroid dose increased by 25-40%
 Taken empty stomach
 Separated from multivitamins, calcium, iron, soy
products by 4hrs
 Postpartum:
• Decrease dose by 30% (if newly diagnosed)
• Prepregnancy dose (known case)
• Reassess after 6 weeks

27.  Adverse effect
On mother – Hyperthyroidism
Transient hair loss
BMD
Myocardial effects
On Fetus – LBW
Smaller HC
 LABOR & DELIVERY-
• Should be euthyroid clincally & biochemically
• Stillbirth, preterm, preeclampsia, abruption
 POSTPARTUM-
• Return to prepregnant dose
• Breast feeding is not contraindicated

28. NEONATAL HYPOTHYROIDISM
 M/c endocrinopathies
 Causes: Primary, secondary, tertiary.
 Cord blood at birth OR heel prick on 3rd day
 Symptoms & Signs
 Goal – To normalize TSH(<5mU/l) & T4 (10-16μg/dl) as quickly as
possible.
 3rd trim fetal T4 req : 6μg/kg/d
 M/m-
• In utero: Intraamniotic 250-500μg thyroxine 7-10d interval
• In term infants: 10-15μg/kg/d

29. AUTOIMMUNE THYROID DISEASE
 Thyroid antibodies-
• TPOab (TMA, 10-15% normal population)
• TgAb
• TSHRAb (types- stimulating, inhibiting, blocking)
 Increased miscarriage, postpartum thyroid dysfunction
 Causes :
• Increased maternal age
• Autoimmune imbalance
• Fetal to maternal cell trafficking

30. TSH RECEPTOR ANTIBODIES
 IgG type
 Cross placenta
 2 types:
• Stimulating – TSI in Grave’s disease
• Blocking – TBII in Hashimoto thyroiditis

31. Trophoblast secrete immunosuppressant factors
Antibody titres
Grave’s disease improvement
Ab increase post partum
Postpartum flare up
POSTPARTUM THYROIDITIS

32. HYPERTHYROIDISM
 0.05-0.2% pregnancies
 Types :
• Subclinical- TSH normal FT3, FT4
• Overt- TSH FT4, FT3
• Gestational- detected in pregnancy
 Symptoms: Palmar erythema, emotional lability,
vomiting, goiter, heat intolerance, exophthalmos, fail to
gain weight.

33. CAUSES OF THYROTOXICOSIS
 INTRINSIC THYROID
DISEASE
• Grave’s
• Toxic nodule
• Subacute thyroiditis
 EXOGENOUS THYROID
HORMONE
• Factitious
• Therapeutic
 GESTATIONAL THYROTOXICOSIS
• Hyperemesis
• GTD
• Hydatidiform mole
• Multiple gestations
• Hydrops
 RARE
• Tsh producing pituitary tumour
• Iodine deficiency
• Struma ovarii

34. GESTATIONAL TRANSIENT THYROTOXICOSIS
 Cross reactivity between HCG & TSH at receptor
 TSHR ab negative, rarely symptomatic
 Nausea & vomiting, dehydration, electrolyte imbalance
& weight loss.
 Spontaneous resolution by 18 weeks.
 Antithyroid medications avoided.

35. GRAVE’S DISEASE
 Autoimmune. Incidence 0.5%
 M/c cause hyperthyroidism in pregnancy
 Triad – hyperthyroidism, exophthalmos, pretibial myxedema
 Others- Clubbing, thyroid bruit, chemosis,
 Physiology
 Ab: TPO, Tg, TSHR

36.  MATERNAL RISKS
• Heart failure
• Thyroid storm
• Preeclampsia(11%)
• Anemia
• Infection
• Fever
• Psychosis, seizure, coma
• Diarrhea, pain, vomiting
• Atrial fibrillation
• Preterm
• Spontaneus loss
 FETAL RISKS
• Fetal tachycardia
• IUGR
• Fetal goiter
• IUFD
• Stillbirth
• Non immune hydrops
• Craniosynostosis
• Mental deficiency
• Poor wt gain, feeding, jaundice,
hepatospleenomegaly

37. PRESENTATION OF HYPERTHYROIDISM
 Nervousness, agitation
 Tachy, palpitation
 Wt loss, increased appetite
 Change in bowel habits
 Skin moist & soft
 Onycholysis
 Hair soft, thin, fine
 Eyes signs (lid retraction, lag, proptosis)

39. TREATMENT OF THYROTOXICOSIS
 MATERNAL
• DOC Propylthiouracil 50-100mg TDS
• Carbimazole 5-20mg BD
• Thyroid studies 4weekly
• Dose adjusted based on T4
 FETAL/NEONATAL
• 50% mortality of thyrotoxicosis
• Carbimazole 10mg/kg
• Lugol’s iodine
• Propanolol 2mg/kg/d
• Digoxine & diuretics

40. DIAGNOSIS
 Clinical presentation
 Thyroid examination –
• Grave’s- diffuse, symmetric, soft
• Nodular
• Subacute thyroiditis- Generalised tenderness
 TFT
 Thyroid Ab test

41. ANTENATAL MANAGEMENT
 Detected in 1st trim- observe
 Persists in 2nd trim- t/t
 THIONAMIDES:
1. Propylthiouracil
• Less readily crosses placenta
• 50-150mg TDS
• Category D
• Side effects-m/
c rash
Fetal hypothyroidism
Transient leukopenia (10%)
Agranulocytosis (0.3-0.4%) discontinue t/t
Hepatotoxicity (0.1-0.2%)
Vasculitis

42. 2. Methimazole:
• 5-20mg BD
• Crosses placenta readily
• Category D
• Methimazole embryopathy- Esophageal atresia, choanal
atresia, cutis aplasia
 FETAL MONITORING:
• 10% hypothyroidism
• Clinical exam
• USG
• Cordocentesis
• Selective Fetal blood sampling
 Subtotal thyroidectomy rarely
 Radioactive iodine ablation is contraindicated

43. LABOR & DELIVERY
 Antithyroid drugs
 Beta blockers
 Supportive care
 Fetal thyrotoxicosis T/t of maternal thyrotoxicosis
 Fetal goiter consider mode of delivery
 EXIT procedure:
• Ex utero intrapartum treatment
• Fetus with large neck masses causing airway obstruction

44. POSTPARTUM MANAGEMENT
 Immunosupression disappears
 Relapse in 70 %
 TSH & freeT4 done 6weeks post partum
 Lactating mother-
• PTU & methimazole excreted in breast milk
• PTU protein bound. Safer
• Methimazole only at low doses (10-20mg/d)

45. THYROID STORM
 Acute exacerbation of hyperthyroidism, life threatening,
hypermetabolic state
 Rare in pregnancy
 Pregnant women with thyrotoxicosis has minimal
cardiac reserve
 Decompensation precipitated by sepsis, preeclampsia &
anemia
 Features
 Lab tests- increased T4 & T3, TLC, Transaminases,
calcium
 Management..

46. START THIONAMIDES & CONTROL HEART RATE(<90bpm)
PTU 1g PO or NGT
100mg 6hrly
PROPRANOLOL 1-2mg IV over
5min to total 6-10mg
60-80mg 4hrly PO/NGT
CORTICOSTEROIDS
Dexa 1-2mg PO/IV/IM 6hrly
Or
Hydrocort 100mg IV 8hrly
Or
Prednisone 60mg/d PO
IODINE (after 1-2hrs of thionamide)
Sodium iodide 500-1000mg IV 8hrly
Or
SSKI 5drops PO 8hrly
Or
Lugol’s solution 10 drops PO 8hrly
Or
Lithium carbonate 300mg PO 6hrly
Or
iodinated radiocontrast agents iopodate 0.5-1g PO per day

47. THYROID CANCER IN PREGNANCY
 Types: Papilllary (m/c in pregnancy), follicular,
medullary, Hurthle cell, anaplastic
 Excellent long term prognosis
 Surgery delayed postpartum
 Sr. thyroglobulin- tumor marker
 Postsurgical whole body scintigraphy & radioiodine
remnant ablation – contraindicated in pregnancy &
lactation

48. PRECONCEPTIONAL COUNSELLING
 Clinical situations
 Hyperthyroidism under t/t-
• Side effects of antithyroid drugs on fetus
• Wait 6mth after radioablation (4mth at least)
• Euthyroid at time of conception
 Previous ablation for Grave’s disease-
• The dose needs to be increased soon after conception
• High maternal titers of TSI may be present in spite of euthyroid ; fetus at risk
 Previous t/t for thyroid carcinoma
• Wait 1 yr after completion of radioactive t/t for conception.
 Inadequate t/t
• Central congenital hypothyroidism in infant

49. POSTPARTUM THYROIDITIS
 Rebound autoimmunity lymphocytic infilteration of gland
 High chances(40-50%) if high titers of ab in early pregnancy
 Anti- TPO 90% with PPT
 Type 1 diabetics- 18-25% chances
 20-50% will develop permanent hypothyroidism within 2-10yrs
 Phases-
 Hyperthyroid
 Hypothyroid

50.  HYPERTHYROID PHASE
• Release of stored
hormone
• 1-4mth postpartum
• Self limiting
• Abrupt onset
• Fatigue,palpitation,
insomnia,nervousness
• Small painless goiter
 HYPOTHYROID PHASE
• Loss of functioning
thyrocytes
• 3-8mth
• Lasts longer
• Fatigue, wt gain,
depression, loss of conc.

51. THYROID NODULE IN PREGNANCY
 95% of solitary thyroid nodule benign
 Malignant- >4cm, firm to hard, lymph nodes, local invasion
 Investigations-
• TSH
• FNAC
• USG
• Thyroid scan(contraindicated in pregnancy)