1. Thyroid disorders in pregnancy
Dr.K.Saravanan
ECG & ECHO Club of Trichy

2. Control of thyroid function

3. Thyroid Disorders & Pregnancy
Specific to Pregnancy : Transient hyperthyroidism of HG Postpartum thyroiditis Neonatal & fetal hyperthyroidism Neonatal & fetal hypothyroidism Not specific to Pregnancy : Thyrotoxicosis , Hypothyroidism Thyroid nodules , Thyroid neoplasia

4. Physiological adaptation in pregnancy

5. Clinical presentation - 1
A 19 year old primi with H/o 54 days amenorrhea was referred by obstetrician with C/o palpitations, weight loss of 2-3 months duration (8 kg), Her haemoglobin was 9.8 g/dl, HR  120/mt with prominent eye sign.

6. Q1
In a background of clinical suspicion of Graves disease, the preferred investigation of choice :
TSH, T3, T4
TSH, FT4, FT3
TSH, FT4
4. TSH, FT4, Anti-TPO antibodies

7. Thyroid Function Tests in Pregnancy-hyperthyroidism
TSH
Low
FT4
Normal
High
Hyper
thyroidism
FT3
Subclinical
Hyperthyroidism
Normal

8. Q2
Her TSH was < (n mIU/L)and FT (n ng/dl). Her TPO antibodies were positive. Drug of choice is Propanolol +
Carbimazole
Methimazole
PTU

9. TSH  low FT4 ,FT3normal Subclinical hyperthyroidismobserve
FT4  high
Clinical  hyperemesis
Observe , fluid therapy
TSH  low
FT4  high
Clinical  thyrotoxicosis
Anti-TPO antibodies +ve
Treat with PTU
TSH  low FT4 ,FT3normal Subclinical hyperthyroidismobserve

10. Thyrotoxicosis & Pregnancy
Causes:
Graves’ disease
TMNG, toxic adenoma
Thyroiditis
Hydatiform mole
Gestational hCG-asscociated Thyrotoxicosis
Hyperemesis gravidarum   hCG
60%  TSH, 50%  FT4
Resolves by 20 wks gestation
Only Rx with ATD if persists > 20 wk

11. Hyperthyroidism & Pregnancy
Useful Physical Signs :
Inappropriately low weight gain for gest. age Goiter
Lid lag
Muscle weakness
Heart rate >100
Onycholysis

12. Thyrotoxicosis & Pregnancy
Risks:
Maternal:
stillbirth, preterm labor, preeclampsia, CHF, thyroid storm during labor
Fetal:
SGA, possibly congenital malformation (if 1st trimester thyrotoxicosis), fetal tachycardia, hydrops fetalis, neonatal thyrotoxicosis

13. Approach in Pregnant & Suppressed TSH
Recheck in 5 wks
FT4, FT3, T4, T3
Thyroid Ab’s
Examine
Still suppressed
Normalizes
Hyperemesis Gravidarum
Very High TFT’s:
TSH undetectable
very high free/total T4/T3
hyperthyroid symptoms
no hyperemesis
TSH-R ab +
orbitopathy
goitre, nodule/TMNG
pretibial myxedema
Don’t treat with PTU
Abnormal TFT’s past 20 wk
Treat Hyperthyroidism (PTU)

14. Thyrotoxicosis & Pregnancy: Rx
No RAI ever (destroy fetal thyroid)
PTU
Start 100 mg tid, titrate to lowest possible dose
Monitor dose by: FT4, TSH
TSH alone is less useful (lags, hCG suppression)
Aim for high-normal to slightly elevated hormone levels
FT ng/dl and TSH 0.5 – 2.5mIU/L
3rd trimester: titrate PTU down & decrease prior to delivery if TFT’s permit
Consider fetal U/S wk to R/O fetal goitre
If allergy/neutropenia on PTU: 2nd trimester thyroidectomy
Propranolol

15. TO summarize…. Arrive at the diagnosis. Correlate clinically
Rule out hyperemesis
Treat with PTU and propranolol in hyperthyroidism
Watch for neutropenia and infections
Monitor FT4 to assess control

16. Points to ponder……. Target FT4 is 0.85-1.9 ng/dl
TSH alone not helpful in monitoring PTU dose.
PTU dose adjusted every 3-4 weeks.
Symptoms improve in 3-4 wk but full response only after 8 weeks.
Block and replace therapy avoided in pregnancy due to risk to fetus.
Fetal monitoring is important
Subclinical hyperthyroidism-no intervention .

17. Q4 Clinical Presentation - 2
Known hypothyroidism on 150 mcg Eltroxin with H/o 3 months amenorrhea comes with TSH,T3,T4 results. TSH-2.5(n 0.3 – 4.5 mIU/L) T4 – 16.4 (n ug/dl) T3 – 3.2 (n ng/dl).
Eltroxin should be stopped.
Eltroxin dose should be increased in pregnancy
Check FT4 alone
Check FT4 ,FT3

18. Thyroid Function Tests in Pregnancy-hypothyroidism
TSH
High
FT4
Normal
Low
Subclinical Hypothyroidism
Primary Hypothyroidism

19. Thyroid & Pregnancy: Hypothyroidism
85% will need increase in LT4 dose during pregnancy due to increased TBG levels (ave dose increase 48%)
Risks:
increased spont abort, HTN/preeclampsia, abruption, anemia, postpartum hemorrhage, preterm labour, baby SGA
Fetal neuropsychological development (NEJM, 341(8): , Aug 31, 2001):
Cognitive testing of children age 7-9
Untreated hypothyroid mothers vs. normal mothers:
Average of 7 IQ points less in children
Increased risk of IQ < 85 (19% vs. 5%)

20. Causes & Diagnosis of Hypothyroidism
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)

21. Symptoms Fatigue Constipation Cold intolerance Weight gain
Muscle cramps
CTS
Insomnia , lethargy

22. Points to ponder ….. Known hypothyroid, eltroxin is increased by
30-50% in first trimester.
First time diagnosed start eltroxin at 1-2 mcg/kg /day
Target TSH is 0.5 – 2.5mU/L
TSH checked initially at 4-6 weeks and later 8 weeks
Space eltroxin and vitamin tablets to avoid interaction.
Postpartum-dose is reduced
Recommended iodide salt avg 250 mcg/day

23. Q5 Clinical Presentation - 3
27 year old female and 3 MA with clinical features suggestive of hypothyroidism has a TSH  6.8 and FT4  1.2 ng. This is
Overt Hypothyroidism
Subclinical Hypothyroidism
Subacute Thyroiditis
Overt Hyperthyroidism

24. Recommended approach in this patientQ6
Recommended approach in this patient
Start eltroxin
Repeat TSH every 4 weeks until weeks and atleast once between weeks
Repeat TSH & FT4 every 4 weeks until weeks and atleast once between weeks
No Intervention at all.

25. Pregnancy: screen for thyroid dysfn ?
Universal screening not currently recommended:
ACOG, AACE, Endo Society, ATA
Controversial!
Definitely screen:
Goitre, FHx thyroid dysfn., prior postpartum thyroiditis, T1DM
Ideally, check TSH preconception:
mU/L: recheck TSH during 1st trimester
mU/L: do not need to recheck during preg
If TSH not done preconception do at earliest prenatal visit:
mU/L: hCG effect (9% preg), recheck in 5wk
< 0.1 mU/L: recheck immediately with FT4, FT3, T4, T3

26. Takeaways……..
Thyroid is second commonest endocrine disorder in pregnancy.
Untreated hypothyroidism-fetus more affected
Untreated hyperthyroidism-mother more affected
Subclinical hypothyroidism- treat
Subclinical hyperthyroidism-followup
Routine screening- not recommended

28. Management…..
LT4  1-2 mcg/kg/day
Dose adjustments by mcg

29. Hyperthyroidism & Pregnancy
TPO antibodies are increased in (80–90%) of patients with Graves disease
+ Other autoimmune disorders
(TRAbs) are increased in >80% of patients with Graves disease

30. Endo consult FT3, rT3 MRI, α-SU TSH Low High FT4 & FT3 FT4 Low High
Central Hypothyroid
1° Thyrotoxicosis
1° Hypothyroid If
equivocal
2° thyrotoxicosis
RAIU
TRH Stim.
Endo consult
FT3, rT3
MRI, α-SU
MRI, etc.

31. EFFECTS OF PREGNANCY ON THYROID PHYSIOLOGY
Physiologic Change
Thyroid-Related Consequences
↑ Serum thyroxine-binding globulin
↑ Total T4 and T3; ↑ T4 production
↑ Plasma volume
↑ T4 and T3 pool size; ↑ T4 production; ↑ cardiac output
D3 expression in placenta and (?) uterus
↑ T4 production
First trimester ↑ in hCG
↑ Free T4; ↓ basal thyrotropin; ↑ T4 production
↑ Renal I- clearance
↑ Iodine requirements
↑ T4 production; fetal T4 synthesis during second and third trimesters
↑ Oxygen consumption by fetoplacental unit, gravid uterus, and mother
↑ Basal metabolic rate; ↑ cardiac output

32. Thyroid function in mother and foetus

33. No TSH & FTI at end of 1st trimester as expected from hCG effect
Requirement to increase LT4 dose occurred between weeks 4 -20
Despite exponential rise in estradiol throughout pregnancy (note y-axis units) TBG levels plateau at 20 wks

35. 6. Women with type I diabetes.
7. Women with other autoimmune disorders.
8. Women with infertility who should have screening with TSH as part of their infertility work-up.
9. Women with previous therapeutic head or neck irradiation.
10. Women with a history of miscarriage or preterm delivery.

36. Why treat hypothyroidism in preg?
To prevent:
Premature birth
LBW
Abruption,PPH
Impaired neuropsychological development in child

37. Physiologic thyroid adaptations in pregnancy
TBG
FT4, FT3
hCG
TSH
Plasma iodide

38. Thyrotoxicosis & Pregnancy
Diagnosis difficult:
hCG effect:
Suppressed TSH (9%) +/-  FT4 (14%) until 12 wks
Enhanced if hyperemesis gravidarum: 50-60% with abnormal TSH & FT4, duration to 20 wks
FT4 assays reading falsely low
T4 elevated due to TBG (1.5x normal)
NO RADIOIODINE
Measure:
TSH, FT4, FT3, T4, T3, thyroid antibodies?
Examine: goitre? orbitopathy? pretibial myxedema?

39. Hyperthyroidism & Pregnancy
Complications
First-trimester spontaneous abortions.
High rates of still births and neonatal deaths.
low birth weight infants : ↑ 2-3 folds.
Premature delivery.
Fetal or neonatal hyperthyroidism.
Intrauterine growth retardation .

40. Case Presentation - 2
A 19 year old primi with H/o 54 days amenorrhea was referred by obstetrician for C/o palpitations, weight loss of 2-3 months duration (8 kg), Her hemaglobin was 9.8 g/dl, HR  120/mt with prominent eye sign.

41. Q1
In a background of clinical suspicion of Graves disease, the preferred investigation of choice :
TSH, T3, T4
TSH, FT4, FT3
TSH, FT4
TSH, Anti-TPO antibodies

42. Q2
Her TSH was < and FT Her TPO antibodies were positive. Drug of choice:
Carbimazole
Methimazole
Betablockers
PTU

43. Q3 Restart LT4 in preconception dose Wait for 4 weeks and recheck TSH
Known hypothyroidism on 150 kg LT4 lost following and came 2 years later with H/o 3 months amenorrhea. She had stopped LT4 since conception and has checked TSH now which was 2.8
Restart LT4 in preconception dose
Wait for 4 weeks and recheck TSH
Restart LT4 in low dose
Wait till delivery and then restart LT4

44. The Fetal Thyroid Begins concentrating iodine at 10-12 weeks
Controlled by pituitary TSH by approximately 20 weeks

45. 10-12 wks of gestation: Fetal thyroid concentrates iodine, synthesize T3 and T4. The fetal pituitary differentiates. Prior to 12 weeks the mother is the sole source of thyroid hormone to the fetus. Fetal thyroid function is at low basal level till wks At birth TSH 70uU/ml. Day 2max. TSH 12uU/ml

46. Treatment indicated if FT4>2.0ng/dl
PTU mg q12 hours in pt. with minimal symptoms (doses>200 mg of PTU can result in fetal goiter & Hypothyroidism
Pt with large goiters & long disease duration may require larger initial doses mg tid
Clinical improvement (weight gain & ↓in HR) is noted in the first 2-6 wks, with FT4 improvement in the first 2 wks
Once clinical improvement occurs the dose of PTU is ↓by half. Goal to keep FT4 at the upper limit of normal, with least amt of medication
In 30% of pt PTU may be D/C’ed in the last 4 - 8wks of pregnancy (Mestman. Best Practice & Research clin endoMetb.,200,vol 18,no. 2,27-88)

47. CENTRAL CONGENITAL HYPOTHYROIDISM
Uncontrolled maternal hyperthyroidism
High levels of serum T4 in maternal circulation cross placental barrier
Feed back to the fetal pituitary with suppression of fetal pituitary TSH
Diagnosis : Neonatal serum FT4 is low & serum TSH is low normal or inappropriate for the level of FT4. In majority of infants there is a return to euthyroidism in a few weeks to months.
Rx with LT4 and long term follow up

48. 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
Increase
Decrease
Hyperthyroidism
Increase or no change
Hypothyroidism
Decrease or no change

49. Physiologic adaptation during pregnancy
increase in thyroid-binding globulin
secondary to an estrogenic stimulation of TBG synthesis and reduced hepatic clearance of TBG ;two to threefold
levels of bound proteins, total thyroxine, and total triiodothyronine are increased and resin triiodothyronine uptake (RT3U) is decreased
begins early in the first trimester, plateaus during midgestation, and persists until shortly after delivery
decrease in its hepatic clearance,estrogen-induced sialylation
free T4 and T3 increase slightly during the first trimester in response to elevated hCG. decline to nadir in third trimester

50. human chorionic gonadotropin (hCG)
intrinsic thyrotropic activity
begins shortly after conception, peaks around gestational week 10,declines to a nadir by about week 20
directly activate the TSH receptor
partial inhibition of the pituitary gland (by cross-reactivity of the α subunit)
transient decrease in TSH between Weeks 8 and 14
mirrors the peak in hCG concentrations
20% of normal women, TSH levels decrease to less than the lower limit of normal

51. Graves' hyperthyroidism occurs in approximately 0
Graves' hyperthyroidism occurs in approximately 0.2 percent of women, and it occurs in approximately one to five percent of infants born to these mothers [2-4].

52. Hyperthyroidism & Pregnancy
Causes
Graves disease (85–90% of all cases)
Sub-acute thyroiditis
Toxic MNG
Toxic adenoma
TSH-dependent thyrotoxicosis
Iodine-induced hyperthyroidism
Exogenous T3 or T4

53. Management TSH >2.5  monitor Target TSH  0.5—2.5 Always check FT4
TPO antibodies if TSH is 3-10
TSH to be checked every 8 weeks
LT4  1-2 mcg/kg/day
Dose adjustments by mcg

54. Neonatal Grave’s
Rare, 1 - 5% infants born to Graves’ moms
2 types:
Transplacental trnsfr of TSH-R ab (IgG)
Present at birth, self-limited
Rx PTU, Lugol’s, propanolol, prednisone
Prevention: TSI in mom 2nd trimester, if 5X normal then Rx mom with PTU (crosses placenta to protect fetus) even if mom is euthyroid (can give mom LT4 which won’t cross placenta)
Child develops own TSH-R ab
Strong family hx of Grave’s
3-6 mos
20% mortality, persistent brain dysfunction
Screen for fetal goiter even in mothers treated previously with RAI or ATD before consumption.

55. Pregnancy: screen for thyroid dysfn ?
Universal screening not currently recommended:
ACOG, AACE, Endo Society, ATA
Controversial !
Definitely screen:
Goitre, Family H/o thyroid dysfn., prior postpartum thyroiditis, T1DM
Ideally, check TSH preconception:
mU/L: recheck TSH during 1st trimester
mU/L: do not need to recheck during preg
If TSH not done preconception do at earliest prenatal visit:
mU/L: hCG effect (9% preg), recheck in 5wk
< 0.1 mU/L: recheck immediately with FT4, FT3, T4, T3

56. 8. SCREENING FOR THYROID DYSFUNCTION DURING PREGNANCY
1. Women with a history of hyperthyroid or hypothyroid disease, PPT, or thyroid lobectomy.
2. Women with a family history of thyroid disease.
3. Women with a goiter.
4. Women with thyroid antibodies (when known).
5. Women with symptoms or clinical signs suggestive of thyroid underfunction or overfunction, including anemia,elevated cholesterol, and hyponatremia.

57. Hyperthyroidism & Pregnancy
TPO antibodies are increased in (80–90%) of patients with Graves disease
+ Other autoimmune disorders
(TRAbs) are increased in >80% of patients with Graves disease