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Thyroid Disorders in Pregnancy

Prof. Md. Farid Uddin


Founder Chairman & Course Co-ordinator
Department of Endocrinology
BSMMU, Dhaka

Thyroid function during normal Pregnancy

TSH and hCG during Gestation

Thyroid hormone changes in different trimester


Hormone

1sttrimester 2ndtrimester 3rdtrimester

TSH

Normal or
decrease

Normal

Normal

Free T4

Normal

Normal

Normal

Free T3

Normal

Normal

Normal

Total T4

High

High

High

Total T3

High

High

High

Pregnancy and Thyroid Disease - Facts


Gestational

Postpartum

Hyperthyroidism
Hypothyroidism (TSH)
Thyr Antibodies [antiTPO]
PPTD
PP depression
PP Graves

0.24%
2-2.5%
10%

5-9%
30% [ vs 20%]
up to 40% of Graves

Fetal Mortality and Morbidity


in Pregnant Hyperthyroid Patients

Number of reports
Number of pregnancies
Total number of pregnancies
Fetal death and stillbirth
Fetal and neonatal abnormality

11(1954-1983)
3 - 41
249
14 (5.6%)
15 (5%)

NB:Incidence of Hyperthyroidism in pregnancy app 0.24%

Outcome of Poorly Treated Hyperthyroidism


in Pregnancy

MATERNAL

Miscarriage
Placenta abruptio
Preterm delivery
Congestive Ht failure
Thyroid Storm
Pre-eclampsia

FETAL
Hyperthyroidism
Neonatal
hyperthyroidism
Prematurity
IUGR
Fetal death /stillbirth
Fetal abnormalities

Causes of Thyrotoxicosis in Pregnancy


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

Pregnant & Suppressed TSH


TSH < 0.1

TSH 0.1 0.4


Recheck in 5 wks

FT4, FT3, T4, T3


Thyroid Abs
Examine

Still suppressed

Normalizes

Hyperemesis Gravidarum

Very High TFTs:


TSH undetectable
very high free/total T4/T3
hyperthyroid symptoms
no hyperemesis
TSH-R ab +
orbitopathy
goitre, nodule/TMNG
pretibial myxedema

Dont treat with PTU

Abnormal TFTs past 20 wk

Treat Hyperthyroidism (PTU)

Treatment of Hyperthyroidism in Pregnancy


Aim for high-normal to slightly elevated hormone levels
T4 150-230 nM, T3 3.8-4.6 nM, FT4 26-32 pM

Confirm diagnosis

No RAI ever (destroy fetal thyroid)

Start propylthiouracil or other ATD

Render patient euthyroid - continue with low dose


ATD up to and including labour
Monitor thyroid function regularly throughout
gestation (4-6wkly).Adjust ATD if necessary

Treatment of Hyperthyroidism in Pregnancy


continued.

Check TSAb at 36 wks. Gestation


Discuss treatment with patient
[effect on patient, effect on fetus, breast
feeding]
If allergy/Neutrogena on PTU: 2nd trimester
thyroidectomy
Review postpartum - check for exacerbation

Effect of Antithyroid Drugs


in Pregnancy on Offspring
Messer et al Acta Endoc. 1990, 123:311-316S

Studied 17 children of 13 hyperthyroid mothers


(ATD) and 25 children of 15 euthyroid mothers 711 years after birth
No differences between groups in clinical/mental
psychological development

Similar to data from


1) McCarrol et al. Arch Dis Child 1976, 51:532-536
2) Burrow et al. Yale J Biol Med 1978, 51: 151-156

Thyrotoxicosis & Lactation

ATD generally dont get into breast milk


unless at higher doses:
PTU > 450-600 mg/d
MTZ > 20 mg/d

Generally safe
Take ATD dose just after breast-feeding

Should provide 3-4h interval before lactates


again

Patterns of Thyroid Function Post Partum

From AMINO

Post Partum Graves Disease

Immune rebound phenomenon

TSHR Ab decrease during pregnancy - rebound in


postpartum (Gonzalez-Jimenez et al 1993)

37/92 patients of child bearing age had onset


postpartum i.e. 40% (Tada et al 1994)

But PP Graves often de novo presentation

Of 96 episodes postpartum hyperthyroidism - silent


thyroiditis was seen occasionally coincidental with
Graves (Momotani et al 1994).

Indications for Testing


Thyroid Function in Pregnancy

On T4 prior to gestation

History of autoimmune thyroid disease


+ve thyroid autoantibodies
Previous postpartum thyroiditis
Graves disease in remission

+ve FH autoimmune thyroid disease

Type 1 DM and/ other autoimmune disease

Previous neck irradiation/ partial


thyroidectomy [decreased thyroid reserve]

Epidemiology

Prevalence :
Overt Hypothyroid (OH) : 0.3 % 0.5 %
TSH >10 and Free T4: Low

Sub-Clinical Hypothyroid (SCH): 2 % - 3 %


TSH: High >5 but <10 mIu/liter, Free t4 : Normal

Thyroid Autoimmunity (TAI) & causes of hypothyroid in pregnancy

Thyroid autoantibodies : 5 % - 15 % in child bearing age ,


even with normal thyroid function. Associated with
increased rate of pregnancy loss.
Dr. A. Hasanat, Prof. M.N. Alam et al (1997).... 135/397
(34 % with different thyroid disease

in Bangladesh)

Chronic autoimmune thyroiditis is the leading cause of


hypothyroidism in pregnancy.
Iodine deficiency (UIE < 10 g/dl) by WHO
Lymphocytic hypophysitis

Thyroid function in the Fetus :


TSH appears at 10 12 weeks.
Little hormone synthesis until 18 20 th weeks.
At term TSH is much higher FT4 is lower.
Soon after birth TSH is ~ 50 80 mIU/liter
Comes down to 10 -15 mIU/liter within 48 hours.

Congenital hypothyroid is not related to maternal


thyroid dysfunction. Iodine deficiency may contribute.

Clinical features :
Usually not very prominent symptoms
May have wt gain, cold intolerance, lethargy,
constipation, edema etc.
Asymptomatic

Lab Investigations

Free T4
TSH
Antithyroid antibody : TPO (Thyroid peroxidase)
TG (Thyroglobulin)
Total T4 and T3 level is increased (~ 1.5 folds) due to
increased TBG. TBG is increased about 2 folds.
No change in Free T4 or FT3

Patients may present as


Diagnosed Hypothyroid on Replacement
became pregnant
Newly diagnosed Hypothyroid during pregnancy
(OH or SCH)

Diagnostic criteria : during pregnancy

Still controversial .
Trimester specific reference ranges1 of FT4 and TSH is
coming up.
TSH is Lowest in first trimester , highest in third trimester and
In between in the second trimester
Normal Ref. Range is 0.4 mIU/liter 4.0 mIU/liter

1. Deshe et al.J Clin Endocrinol Metab. August 2007, 92(8)(Suppl): S8

Some of the Authors if

TSH > 2.3 in first trimester and


TSH > 3.5 in the Second and Third Trimester
With normal Free T4

Should be considered as Subclinical Hypothyroidism

Obstet gynecol 2005;106:753-757

Evidence :
Repercussion of Hypothyroid: Maternal aspect
Infertility
Abortion
Anemia
Hypertension (Gestational)
Placental abruption
PPH

J Med Screen 7:127-130

Repercussion of Hypothyroid: Fetal aspect


Premature birth
LBW (30 %)
ARDS
Cognitive impairment of the baby
Abnormal brain development
Increased perinatal mortality (12 %)
Psychoneurological impairment, Low I.Q. etc
J Med Screen 7:127-130
Endocrine Clinics of North America 2006

The maternal and fetal repercussion depends on ..


Severity of hypothyroidism (in case of OH is more than SCH)
Time of onset ( First trimester is more important)
Adequacy of treatment (under treatment is associated with
Increased adverse outcome)

Therapeutic Aspects :
Levothyroxin
30 % - 50 % above preconception dose
Non Pregnant 1.7 2.0 g/kg/day, increased upto
2.0 -2.4 g/kg/day
New onset hypothyroid should be initiated with higher dose
100 150 g per day or titrate according to B.W.

Dose adjustment every 4-6 weeks.


Those who are already on thyroxin, may increase the dose
by 25 % as soon as pregnancy is confirmed.
10 % - 20 % may not need to increase the dose.

Hypothyroid due to other causes (Surgery, Post ablative,


Congenital agenesis ) requires greater increment than H.T.
Aim is to maintain normal FT4 and TSH
Dose increment may be difficult in hyperemesis

Target of TSH and FT4 :

Treatment to target TSH 0.3 2.5 in First Trimester


and 0.5 3.0 in the Second or Third trimester1
FT4 should be kept either at trimester specific target or
above the median of the Laboratory Reference Range.
eg. Normal Range 9 23 pmol/l , keep above 16 .

1. US Preventive Study Task Force

Whom to screen ?
Universal screening not yet recommended except by AACE.
High risk subjects should be screened :
- H/O thyroid disease
- F/H of thyroid disorders
- Known case of TAI ( Antibody +)
-Other autoimmune disease
- High degree of suspicion
- Bad obstetric history
- Obese or Rapidly gaining weight

Recommendations:
Both OH and SCH should be treated
Treatment is very safe and Effective. Drug interaction
with Calcium and Ferrous Sulfate ( absorption)
Usually life long
New onset SCH subjects may be re-evaluated after
stopping the drug for 6 wks.

Continue throughout pregnancy and Lactation (Do not


stop to see any reason )
Increase dose during pregnancy ( 30 50 %)
Normal delivery or as per obstetric indication
Target TSH and FT4 must be achieved

After delivery mostly need to decrease the dose


Close monitoring by Endocrinologist and Obstetrician &
Gynecologist for better outcome.
Dependable Laboratory support

Neonatal screening

CH is one of the major causes of mental and


physical retardation. (1:4000)
The condition is reversible if detected in first few
weeks of life and treatment starts
Unfortunately the clinical manifestation is often
late
Neonatal screening is now a well established
program throughout the world for detection of CH

Procedure of screening

Few drops of blood are collected in filter paper,


dried and sent to laboratory for analysis
The blood is collected from cord at birth or from
heel prick after 72 hrs of birth
For detection of CH TSH is estimated
The screening positive babies are recalled and
confirmed by serum T4 & TSH

SCH INMU Experience

Period of
screen-ing

No. of
babies
screen-ed

No. of
positive
babies

No. of
babies
detected

Incidence of
CH

19992008

98314

1094

38

1:2587

Thank You

20.19 Thyroid disease in pregnancy Normal pregnancy Trimester-specific normal


ranges: should be used to interpret thyroid function test results in pregnancy. In the first
trimester, TSH is lower and free free T4 and T3 higher, in part due to thyroid stimulation by
human chorionic gonadotrophin (hCG). In later pregnancy, free T4 and T3 are lower. Binding
globulin levels are induced by oestrogen, so total T4 and T3 levels are invariably high.
Iodine requirements: increased in pregnancy. The World Health Organization (WHO)
recommends minimum intake of 200 g/day.
Screening of thyroid function and autoantibodies: not recommended for every woman,
but should be performed in first trimester in those with a personal or family history of thyroid
disease, goitre, other autoimmune disease including type 1 diabetes, or when there is clinical
suspicion of thyroid dysfunction.
Thyrotoxicosis Hyperemesis gravidarum: associated with thyrotoxic biochemistry,
sometimes requiring antithyroid drugs.
Subclinical thyrotoxicosis: not usually treated, to avoid fetal hypothyroidism.
Anti-thyroid drugs: propylthiouracil is first choice.
Hypothyroidism Preterm labour and impaired cognitive development in the offspring:
may be associated with even subclinical hypothyroidism.
Thyroxine replacement therapy dose requirements: increase by 30-50% from early in
pregnancy. Monitoring to maintain TSH results within the trimester-specific reference range is
recommended in early pregnancy and at least once in each trimester.
Post-partum thyroiditis Screening: not recommended for every woman, but thyroid function
should be tested 4-6 weeks post-partum in those with a personal history of thyroid disease,
goitre or other autoimmune disease including type 1 diabetes, those known to have positive
anti-thyroid peroxidase antibodies, or when there is clinical suspicion of thyroid dysfunction.