Abnormal thyroid Function in pregnancy

Miza Hiryanti zakaria

Introduction
 Abnormal thyroid functions test are prevalent in pregnancy
 They may be caused by physiological changes in pregnancy or due to
underlying pathology such as thyroid autoimmunity.
 They can be symptomatic or asymptomatic.
 At times there will be disparities between symptoms and thyroid function
test results.
 Assays problems
 Autoimmune condition
 Trimester specific cut off points
 Differences in laboratory units n reference levels.
Physiology
Normal physiology Mother
 The hypothalamic pituitary axis
 Thyrotropin-releasing hormone (TRH)
 Produced in a tonic fashion in the paraventricular nucleus of the
hypothalamus.
 TSH has an α and β subunit;β subunit confers specificity.
 TSH secretion regulated by negative feedback from circulating
thyroid hormone, dopamine, and somatostatin.
 TSH then stimulates the thyroid gland to produce, as well as
secrete, thyroxine(T4) and triiodothyronine (T3).
Thyroid changes during pregnancy
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
 hCG
TSH
 Every 10,000 IU/L increment in hCG = A decrease in basal TSH of
0.1 mU/L
 reduction in plasma iodide
 fetal :monodeiodinase types II and III in the placenta
 increased maternal glomerular filtration rate-- increased renal clearance
of iodide throughout pregnancy
 transplacental passage of T4 and iodide and placental
metabolism of iodothyronines
 stimulate the maternal thyroid ; depleting the maternal circulation of
thyroid hormone and its precursors
TSH changes
 A downward shift of the TSH reference range occurs during
pregnancy, with
 a reduction in both the lower (decreased by about 0.1–0.2 mU/L)
and the upper limit of maternal TSH (decreased by about 0.5–1.0
mU/L), relative to the typical nonpregnant TSH reference range.
TSH recommended
 1. H/O hypothyroidism  7. Multiple prior pregnancies (‡2)
/hyperthyroidism or current
symptoms/signs of thyroid  8. Family history of autoimmune
dysfunction thyroid disease or thyroid
dysfunction
 2. Known thyroid antibody positivity
or presence of goiter  9. Morbid obesity (BMI ‡40 kg/m2)

 3. H/O head or neck radiation or prior  10. Use of amiodarone or lithium, or

thyroid surgery recent administration of iodinated
radiologic contrast
 4. Age >30 years
 11. Residing in an area of known
 5. Type 1 diabetes or other moderate to severe iodine
autoimmune disorders insufficiency
 6. History of pregnancy loss,
pretermdelivery, or infertility
Trimester Specific TFT
TSH miu/L T4 pmol/L
Non Pregnant 0.38 – 5.35 Non Pregnant 7.86– 14.40
1st Trimester 0.05 – 3.70 1st Trimester 6.67 – 14.12
2nd Trimester 0.31 – 4.35 2nd Trimester 5.79 – 12.70
3rd Trimester 0.41 – 5.18 3rd Trimester 6.11 – 12.2
 Case 1

 32 year old lady G2P1 at 16 weeks with family history of hypothyroid (hashimoto) was
referred to you for interpretation of thyroid function test.
 She is otherwise asymptomatic
 Examination : small diffuse goitre non tender
 Clinically euthyroid
 TSH 2.63------------------- 3.8 miu/L ( 0.31 -4.35)
 T4 7.44 --------------------- 5.45 pmol/L ( 5.79 – 12.7)
 TPO positive
 Treat or not to treat
Hypothyroidism SCH IHT
TSH T4

HypoThyroidism high low

Subclinical Hypothyroidism high normal

Isolated hyperthyroxinemia normal low

RECOMMENDATION 28 &29
 TSH >2.5 mU/L should be evaluated for TPOAb status.
 Subclinical Hypothyroid - LT4 therapy is recommended for
 TPOAb-positive women with a TSH greater than the pregnancy-
specific reference range
 TPOAb-negative women with a TSH greater than 10.0 mU/L.
.
LT4 therapy may be considered for
 -TPOAb-positive with TSH >2.5 mU/L and T4below the
upper limit of the pregnancy-specific reference range
 TPOAb-negative with TSH greater than the pregnancy
specific reference range and below 10.0 mU/L.
LT4 therapy is not recommended for

TPOAb-negative women with a normal TSH (TSH within the

pregnancy-specific reference range or <4.0 mU/L if unavailable).
 Strong recommendation, high-quality evidence
Case 2
 34 year old Chinese lady
At 18 weeks pregnancy was referred to your clinic for abnormal
thyroid function test.
She was other wise asymptomatic and she was well through out the
first pregnancy
Clinically small diffuse goitre. no hypothyroid features
TSH 0.38miu/L ( 0.31 – 4.35)
T4 4.81 pmol/L (5.79 -12.7)
What is your opinion?
Repeat TFT in 1 month
 TSH 0.38 miu/L ( 0.31 – 4.35)
 T4 5.62 pmol/L (5.79 -12.7)
 T3 normal
 Anti TPO Anti TG - negatives
Isolated hypothyroxinemia
the prevalence of IMH in the literature has ranged from 1.3 to 23.9%.
ATA 2017
 RECOMMENDATION 30
 Isolated hypothyroxinemia should not be routinely treated in
pregnancy.
 Weak recommendation, low-quality evidence.
Case 3
 24 year old G1P0 at 20 weeks POA with background history of Hashimoto Disease
on Euthyrox 125mcg OD) ( prepregnancy 75mcg OD)
 Came for follow up
 TSH 6.33 mIU/L (0.31 – 4.35)
 T4 5.2 pmol/L (5.79 – 12.7)
 How do you manage her thyroxine dose?
RECOMMENDATION 36
 Hypothyroid patients receiving LT4 treatment with a suspected or confirmed
pregnancy (e.g., positive home pregnancy test) should independently increase
their dose of LT4 by*20%–30% and urgently notify their caregiver for prompt
testing and further evaluation.
 One means of accomplishing this is to administer two additional tablets weekly of
the patient’s current daily LT4 dosage
Strong recommendation, high-quality evidence.

DONE actually exceeded 50% increment – 112.5mcg

RECOMMENDATION 32
 In parallel to the treatment of hypothyroidism in a general
population, it is reasonable to target a TSH in the lower half of the
trimester-specific reference range.
 When this is not available, it is reasonable to target maternal TSH
below 2.5 mU/L.
 Weak recommendation, moderate-quality evidence.
 Should we increase thyroxine dose - target a TSH in the lower half of the
trimester-specific reference range.

 TSH 6.33 mIU/L (0.31 – 4.35)

 T4 5.2 pmol/L (5.79 – 12.7)
Further interview
 Patient was also prescribed calcium carbonate for cramping and mild anemia
since early pregnancy.
 She was taking those medications with thyroxine
Case 4
 27 year old G1P0 with twin gestation presented at 10 weeks gestation
complaining of vomiting which began at week 5 of pregnancy.
 She lost 4kg (~8% weight loss).
 Her sister has Graves’ disease.
 TSH 0.01miu/L (0.05-3.70)
 T4 17.04 pmol/l (6.67 – 14.12)
Transient nonimmune
hyperthyroidism of early pregnancy
In 1992, Goodwin -“transient thyrotoxicosis of hyperemesis gravidarum”
In 1993“gestational thyrotoxicosis” was proposed in 1993 as a new clinical entity by
Kimura et al.
Other nomenclatures were and are still employed when describing the syndrome,
such as gestational hyperthyroidism (GH) and gestational transient thyrotoxicosis
(GTT).
In most of these reports, the common findings are vomiting of different intensity
and thyroid tests in the hyperthyroid range without evidence of thyroid
autoimmunity.
Definition
 Hyperthyroidism diagnosed for the first time in early pregnancy, transient,
without evidence of thyroid autoimmunity, lack of physical findings consisting
with Graves’ disease, resolving spontaneously by the end of the first or early
second trimester of pregnancy.
Transient nonimmune
hyperthyroidism of early pregnancy
Hyperemesis gravidarum
 Hyperemesis gravidarum (HG) is reported to occur in 0.3% to 1.0% of pregnancies;
 it is defined as persistent nausea and vomiting resulting in greater than 5% weight
loss, ketonuria, dehydration, and electrolytes (hypokalemia, metabolic alkalosis,
hyponatremia, and hypochloremia), and liver abnormalities in severe cases.
 Decreased risk of miscarriage has been reported in women with nausea and
vomiting .
 The cause of nausea and vomiting is unclear although high levels of estrogen
and/or Vitamin B deficiency have been implicated.
emesis
GTT versus Graves
GTT
progress
 Her symptoms resolved in second trimester 22 weeks without any ATD
 Her TSH 0.4miu/L
 T4 11.7 pmol/L
 Thyroid antibodies negative.
Management
 Treat symptomatically
 Rehydrate
 Correct electrolyte imbalance
 Several case reports – small percentage of patients needs ATD initially
 Symptoms resolved usually by 18 weeks (by second trimester ATD was not
needed)
ATA 2017
 Antithyroid drugs (ATDs) are not indicated because the serum T4 returns to
normal by 14–18 weeks gestation and ATD use in early pregnancy increases risk of
birth defects.
 Importantly, obstetrical outcome was not improved in isolated cases in which
gestational transient thyrotoxicosis was treated with ATDs.
 However, there are no studies reported in the literature comparing ATD therapy
versus supportive therapy.
 In situations in which symptomatic therapy is indicated, small amounts of β-
blockers given over a limited time period may be useful, and close follow-up with
repeat investigation for the cause of disease should be performed.
 RECOMMENDATION 42
 The appropriate management of abnormal maternal thyroid tests attributable
to gestational transient thyrotoxicosis and/or hyperemesis gravidarum includes
supportive therapy, management of dehydration, and hospitalization if needed.
ATDs are not recommended, though β-blockers may be considered.
 Strong recommendation, moderate-quality evidence.
Case 5
 27 year old Indian lady G2P1 at 24 week POA with Background history og Graves
disease on Carbimazole 15mg OD
 Came for follow up
 Good weight gain
 Clinically euthyroid
 T4 6.77 pmol/L ( 5.79 – 12.7 )
 TSH 2.45 miU/L (0.31 – 4.35)
ATA 2017
 RECOMMENDATION 48
 (a) In women being treated with ATDs in pregnancy, FT4/TT4 and TSH should be
monitored approximately every 4 weeks.
 Strong recommendation, moderate-quality evidence.
 (b) Antithyroid medication during pregnancy should be administered at the
lowest effective dose of MMI or PTU, targeting maternal serum FT4/TT4 at the
upper limit or moderately above the reference range.
 Strong recommendation, high-quality evidence.
Progress
 Carbimazole was reduced to 5mg OD
 Repeated TFT after 4 weeks
 T4 13.22 pmol ( 5.79 – 12.7 )
 TSH 1. 89 miU/L (0.31 – 4.35)
 Because the fetal thyroid responds more strongly to ATD therapy than the
maternal thyroid, mothers on an ATD in the second half of pregnancy, who by
nonpregnancy standards would be considered euthyroid, should have the ATD
dose reduced to protect the fetus.
 Discontinuation of all ATD therapy is feasible in 20%–30% of patients in the last
trimester of gestation.
 Maternal serum TSH well within the reference range is a sign that the ATD dose
has to be reduced to avoid fetal overtreatment. If this is not done, fetal
hypothyroidism and goiter may develop from overtreatment with ATDs.
 Disappearance of maternal TRAb in late pregnancy indicates a high likelihood of
successful ATD withdrawal.
Summary
 Management of thyroid Disease in Pregnancy requires understanding of
physiology of pregnancy itself, pathophysiology of the disease and side effects of
the medication involved.
 Trimester specific TSh range is important in management of thyroid disease
especially hypothyroidism.
 Hypothyroid - target a TSH in the lower half of the trimester-specific reference
range. When this is not available, it is reasonable to target maternal TSH
concentrations below 2.5 mU/L.
 Hyperthyroid - Antithyroid medication during pregnancy should be administered
at the lowest effective dose of MMI or PTU, targeting maternal serum FT4/TT4 at
the upper limit or moderately above the reference range.
Thank you