3. Functions of Thyroid hormone
Target Tissue Effect of
hormone
Mechanism
Heart Chronotropic
and inotropic
Increased number of β-adrenergic receptors
Enhanced responses to circulating
catecholamines
Increased proportion of α-myosin heavy chain
(with higher ATPase activity)
Adipose tissue Catabolic Stimulate lipolysis
Muscle Catabolic Increase protein breakdown
Bone Developmental Promote normal growth and skeletal
development
CNS Developmental Promote normal brain development
Gut Metabolic Increased rate of carbohydrate absorption
Lipoprotein Metabolic Formation of LDL receptors
Others Calorigenic Stimulated oxygen consumption by
metabolically active tissues (exceptions: testes,
uterus, lymph nodes, spleen, anterior pituitary)
Increased metabolic rate
4. Functions of Thyroid hormone
• Hepatic conversion of carotene to vitamin A
• The accumulation of carotene in the
bloodstream (carotenemia) in hypothyroidism is
responsible for the yellowish tint of the skin
• Milk secretion is decreased in hypothyroidism
and stimulated by thyroid hormones
• Essential for normal menstrual cycles and
fertility
• Thyroid hormones also exert effects on reflexes
• The reaction time of stretch reflexes is
shortened in hyperthyroidism and prolonged in
hypothyroidism
5. How to interpret thyroid function results?
TSH Free T4 Free T3 Interpretation
Undetectable Raised Raised Primary thyrotoxicosis
Undetectable Normal Raised Primary T3 - toxicosis
Undetectable Normal Normal Subclinical thyrotoxicosis
Elevated High High Secondary thyrotoxicosis
Undetectable or
low
Raised Low or
normal
Non-thyroidal illness
Amiodarone therapy
Undetectable or
low
Raised Normal Over-treatment of hypothyroidism
with levothyroxine
Factitious thyrotoxicosis
6. How to interpret thyroid function results?
TSH Free T4 Free T3 interpretation
Mildly elevated
5-20 mU/l
Low Low Primary hypothyroidism
Secondary hypothyroidism
Elevated
> 20 mU/l
Low Low Primary hypothyroidism
Mildly elevated
5-20 mU/l
Normal Normal Subclinical hypothyroidism
Normal Low Low Secondary hypothyroidism
Undetectable Low Low Secondary hypothyroidism
Elevated
20-500 mIU/L
Normal Normal Artefact
Heterophilic antibodies
7. THYROID PHYSIOLOGY DURING NORMAL
PREGNANCY
• Major changes in thyroid function during pregnancy:
• An increase in serum thyroxine-binding globulin
(TBG)
• Estrogen increases TBG production and TBG sialylation,
which results in decreased clearance of TBG
• TBG excess leads to an increase in both serum total, but
not free, T4 and T3 concentrations
• Stimulation of the thyrotropin (TSH) receptor by
human chorionic gonadotropin (hCG)
• There is considerable homology between the beta
subunits of hCG and TSH
• As a result, hCG has weak thyroid-stimulating activity
8. Causes of Hyperthyroidism
Hyperthyroidism with a normal
or high radioiodine uptake
• Autoimmune thyroid disease
• Graves' disease
• Hashitoxicosis
• Autonomous thyroid tissue
• Toxic adenoma
• Toxic multinodular goiter
• TSH-mediated
hyperthyroidism
• TSH-producing pituitary
adenoma
• Non-neoplastic TSH-mediated
• Human chorionic
gonadotropin-mediated
hyperthyroidism
• Hyperemesis gravidarum
• Trophoblastic disease
Hyperthyroidism with a near
absent radioiodine uptake
• Thyroiditis
• Subacute granulomatous
• Painless thyroiditis
• Amiodarone
• Checkpoint inhibitor-induced
• Radiation thyroiditis
• Palpation thyroiditis
• Exogenous thyroid hormone
intake
• Excessive replacement therapy
• Intentional suppressive therapy
• Factitious hyperthyroidism
• Ectopic hyperthyroidism
• Struma ovarii
• Metastatic follicular thyroid
cancer
11. Common causes in pregnancy
• Human chorionic gonadotropin (hCG)-mediated
hyperthyroidism due to gestational transient
thyrotoxicosis (1 to 3 percent of pregnancies)
• Graves’ disease (occurring in 0.1 to 1 percent of
all pregnancies)
12. Graves’disease
• Hyperthyroidism, goiter, thyroid eye disease
(orbitopathy) , and occasionally a dermopathy referred to
as pretibial or localized myxedema
• Autoimmune disorder
• The presence of TRAbs in serum and thyroid eye
disease on clinical examination distinguishes the
disorder from other causes of hyperthyroidism
• The thyroid gland is usually, but not always, diffusely
enlarged
13. hCG-mediated Hyperthyroidism
• During normal pregnancy, serum human chorionic
gonadotropin (hCG) concentrations rise soon after
fertilization and peak at 10 to 12 weeks gestation, after
which time the levels decline
• There is considerable homology between the beta-
subunits of hCG and TSH
• As a result, hCG has weak thyroid-stimulating activity
and may cause hyperthyroidism during the period of
highest serum hCG concentrations
• Include gestational transient thyrotoxicosis (GTT),
hyperemesis gravidarum, and trophoblastic
hyperthyroidism
14. Gestational transient thyrotoxicosis
• During the time of peak hCG concentrations (10 to 12
weeks), total serum T4 and T3 concentrations increase
• Serum free T4 and T3 concentrations increase slightly,
usually within the normal range, and serum TSH
concentrations are appropriately reduced
• Thus, in some women, the high serum concentration of
hCG during early pregnancy can lead to subclinical or
mild overt hyperthyroidism
• This phenomenon is called GTT
• It occurs near the end of the first trimester, and
symptoms (if present) and thyroid hyperfunction subside
as hCG production falls (typically 14 to 18 weeks
gestation)
15. Hyperemesis gravidarum
• Women who develop hyperemesis gravidarum have
higher serum hCG and estradiol concentrations than
normal pregnant women,in addition, their hCG has more
thyroid-stimulating activity
• Therefore, their serum TSH concentrations are often
lower than those in normal pregnant women and have
high serum free T4 concentrations
16. Features that distinguish the transient hyperthyroidism
of hyperemesis gravidarum from hyperthyroidism of
other causes (Graves)
• Vomiting, absence of goiter and ophthalmopathy, and
absence of the common symptoms and signs of
hyperthyroidism (tachycardia greater than 100
beats/minute, hyperdefecation, muscle weakness,
tremor)
• Hyperemesis gravidarum
• Serum free T4 minimally elevated and serum T3 may not
be elevated
• Usually does not require treatment, subsides as hCG
production falls
• Graves disease
• Serum free T4 and T3 are unequivocally elevated
17. Trophoblastic hyperthyroidism
• A hydatidiform mole (molar pregnancy) is benign but
may give rise to choriocarcinoma
• Both are associated with high serum hCG concentrations
and abnormal hCG isoforms
• Many patients with hyperthyroidism caused by
trophoblastic disease have a normal thyroid gland and
few symptoms of thyroid hormone excess
• Some patients have more typical clinical findings of
hyperthyroidism and a diffuse goiter, but ophthalmopathy
is not present
• Nausea and vomiting may predominate, as in
hyperemesis gravidarum
• Treatment is needed
18. Familial gestational hyperthyroidism
• Recurrent gestational hyperthyroidism has been
described in one family due to a mutant
thyrotropin receptor that is hypersensitive to
physiologic concentrations of hCG
22. Treatment
• Goal
• Maintain persistent but mild hyperthyroidism in the
mother to prevent fetal hypothyroidism since the fetal
thyroid is more sensitive to the action of antithyroid drugs
• Overtreatment of maternal hyperthyroidism with
thioamide antithyroid drugs can cause fetal goiter and
primary hypothyroidism
• On the other hand, transient central hypothyroidism may
be seen in infants whose mothers had poorly controlled
hyperthyroidism during pregnancy, presumably due to
suppression of the fetal pituitary-thyroid axis
23. Indications for treatment
• Women with symptomatic, moderate to severe,
overt hyperthyroidism due to Graves' disease,
toxic adenoma, toxic multinodular goiter, or
gestational trophoblastic disease require
treatment of hyperthyroidism
24. Treatment of hyperthyroidism is not required in
the following settings
• Transient, subclinical hyperthyroidism
• hCG-mediated, overt hyperthyroidism
• Hyperemesis gravidarum associated
hyperthyroidism
• Subclinical and mild asymptomatic,overt
hyperthyroidism due to Graves' disease, toxic
adenoma, or toxic multinodular goiter
25. Therapeutic options
• Most women are treated with thioamides
• Thyroidectomy in the second trimester is an option for
women who are unable to take thioamides
• Thioamides
• They are actively transported into the thyroid gland,
where they inhibit both the organification of iodine to
tyrosine residues in thyroglobulin and the coupling of
iodotyrosines
• Beta blockers
• Metoprolol or propranolol (but not atenolol), can be used
to treat tachycardia and tremor
• They are the primary treatment for patients with
hydatidiform mole or gestational trophoblastic neoplasia
who generally cannot wait for three to six week for
thioamides to control hyperthyroidism prior to surgery
26. Therapeutic options
• Thyroidectomy
• Thyroidectomy during pregnancy is rarely
necessary but is an option for women who cannot
tolerate thioamides because of allergy or
agranulocytosis
• Plasmapheresis has also been used to rapidly
control hyperthyroidism in women with
trophoblastic disease and severe hyperthyroidism
27. MEDICAL MANAGEMENT
• Control of symptoms
• Metoprolol 25 to 50 mg daily or
• Propranolol, 20 mg every six to eight hours
• The dose can be increased as needed to control
symptoms
• Beta blockers should be weaned as soon as the
hyperthyroidism is controlled by thionamides
because occasional cases of neonatal growth
restriction, hypoglycemia, respiratory
depression, and bradycardia have been reported
after maternal administration
28. • Decrease thyroid hormone synthesis
• Pretreatment evaluation
• Prior to initiating thionamides,obtain baseline
blood tests, including a complete blood count
and a liver profile
• Do not use thionamides in patients with a
baseline absolute neutrophil count <1000
cells/microL or elevated liver transaminases
(more than fivefold the upper limit of normal)
except in selected patients after careful
assessment of alternatives and risks
29. • Choice of thioamide
• The choice of thionamide depends upon which
trimester the drug is being initiated
• Methimazole is preferred to PTU except during
the first trimester of pregnancy
30. Mechanism of action of antithyroid drugs
TSH activates steps 1, 2, 3, 4, and 5,Ionic inhibitors blockstep 1
Excess iodide interferes with steps 1, 2, 3 and 5 with primary action on step 3 and 5
Propylthiouracil inhibits steps 2 and 6,Carbimazole inhibits step 2 only
31. Diagnosed prior to pregnancy
• Women diagnosed with Graves' disease prior to
pregnancy who are taking methimazole : Definitive
therapy with surgery or radioiodine prior to pregnancy
• Women should then postpone pregnancy until they have
become euthyroid following definitive treatment and on
replacement therapy
• Switch to PTU before trying to conceive in younger
women with normal periods who are expected to
conceive within one to three months
• Switch to PTU as soon as the pregnancy test is
confirmed for older individuals having difficulty conceiving
32. • Diagnosed during the first trimester
• Symptomatic, moderate to severe
hyperthyroidism : Propylthiouracil (PTU)
• May continue PTU for the remainder of
pregnancy or switch back to Methimazole or
Carbimazole at 16 weeks
• Diagnosed after the first trimester
• Symptomatic, moderate to severe
hyperthyroidism : Methimazole or Carbimazole
33. Teratogenic effects of antithyroid drugs
• Teratogenic effects are more severe
with methimazole and carbimazole compared with
PTU
• Aplasia cutis, a scalp defect, in newborns exposed
to methimazole in utero
• Tracheoesophageal fistulas, patent vitellointestinal
duct, choanal atresia, omphalocele, and
omphalomesenteric duct anomaly with maternal use
of methimazole and carbimazole but not PTU
• Mild congenital anomalies, including preauricular
sinuses and cysts and urinary tract abnormalities,
have been observed after PTU
34. • Initial dosing
• PTU 50 mg two to three times daily
• Methimazole 5 to 10 mg daily
• Carbimazole 5 to 15 mg daily
• In patients with severe hyperthyroidism, full
initial doses of PTU (100 mg three times per
day) or methimazole (10 to 30 mg daily) may be
required to control hyperthyroidism
• For patients switching between PTU
and methimazole, the closest dose
approximation should be made
• 300 mg of PTU would be roughly equivalent to
10 or 15 mg of methimazole
35. Monitoring and dose adjustments
• Graves' disease frequently ameliorates in the
third trimester
• Whenever possible, based on thyroid function
tests and assessment of TRAb measurements,
thioamides should be tapered and potentially
discontinued during the third trimester
• Toxic adenoma and toxic multinodular goiter are
unlikely to remit during pregnancy, and therefore
maintained on thioamides throughout pregnancy
36. Monitoring and dose adjustments
• Thyroid function tests : every four weeks
throughout pregnancy
• Maintain serum free T4 concentrations at or just
above the upper limit of normal, using a
trimester-specific reference range, or the total T4
and T3 should be maintained at approximately
1.5 times the upper limit of normal for
nonpregnant adults
• Recommended therapeutic target
• Total T4: 12-18 μg/dL (or freeT4 : 2-2.5 ng/dL)
• The recommended range for TSH in patients on
ATDs 0.1-0.4 mIU/L
37. • TRAb
• For women diagnosed with hyperthyroidism
during pregnancy who will be taking
thionamides, serum TRAb should be measured
at diagnosis and, if elevated, again at 18 to 22
weeks and at 30 to 34 weeks of gestation
• Disappearance of TRAb indicates potential
remission of Graves' disease, and the dose of
thioamides can be reduced and potentially
discontinued
• High TRAb levels in late pregnancy are
associated with an increased risk of fetal and
neonatal hyperthyroidism
38. • Adverse effects of thioamides
• Liver failure (PTU)
• Symptoms weakness, malaise, nausea and vomiting,
jaundice, dark urine, or light-colored stools
• Agranulocytosis
• Loss or graying of hair
• Loss of taste
• Fever
• G.i. intolerance
• Skin rashes
• Joint pain
39. • Thioamide intolerance
• Who cannot tolerate thioamides because of allergy or
agranulocytosis, thyroidectomy during pregnancy may
be necessary
• Increased risk of spontaneous abortion or premature
delivery and significantly higher rates of surgical
complications than nonpregnant women
• Risks are minimized by operating during the second
trimester
• Prior to thyroidectomy, pregnant women with intolerance
to thionamides should be pretreated with beta blockers
(metoprololor propranolol) and a short course (ie, 7 to 10
days) of potassium iodine solution (35 to 50 mg iodine
per drop, 1 to 3 drops daily)
• Iodine lowers serum thyroid hormone concentrations
acutely and, in addition, decreases thyroid gland
vascularity
40. • History of treated hyperthyroidism
• Euthyroid women with a history of remission after prior
treatment of Graves' disease with thionamides have a
small risk of recurrence when they become pregnant
or postpartum
• In such women, thyroid function tests should be
measured in early pregnancy, again if hyperthyroid
symptoms appear, and postpartum
• Euthyroid women taking thyroid hormone after
definitive therapy with radioiodine or surgery have a
small risk of fetal hyperthyroidism from transplacental
transfer of TRAb
• TRAb should be measured during the first trimester
and, if elevated, at 18 to 22 weeks of gestation
• If TRAb levels are elevated, the fetus should be
monitored for hyperthyroidism
41. POSTPARTUM ISSUES
• BREAST FEEDING
• Methimazole or Carbimazole is preferred rather
than PTU for nursing mothers given the concerns
about propylthiouracil (PTU) associated
hepatotoxicity
• Methimazole should be administered following a
feeding in divided doses
• When the maternal dose of methimazole is >20
mg daily, infants should have thyroid function
tests assessed after one and three months
42. • Relapse
• Postpartum hyperthyroidism may be due to a relapse of
Graves' disease or to postpartum thyroiditis
• Differentiated from one another based upon the clinical
presentation, the number of months postpartum (earlier
onset favors thyroiditis), thyrotropin receptor antibody
(TRAb) measurement, and evaluation of serum T3-to-T4
ratio
• Women with Graves' disease who have been treated
during pregnancy need careful monitoring during the
postpartum period as they may experience an
exacerbation
• One approach is to measure thyroid function tests (TSH,
free T4) six weeks postpartum, then every six weeks if
an adjustment in thionamide dose is needed or every
four months if thyroid tests remain normal
43. Hypothyroidism in pregnancy
• Overt hypothyroidism (elevated TSH,
reduced free T4)
• Subclinical hypothyroidism (elevated TSH,
normal free T4)
44. Screening for hypothyroidism
• It is recommended that all pregnant women
should be screened at 1st antenatal visit by
measuring TSH levels
• TSH cut off should be lower rather than keeping
it on 4.0 mIU/L
• However, the trimester specific TSH cut off
recommended are:
• 1st trimester 2.5 mIU/L
• 2nd trimester 3.0 mIU/L
• 3rd trimester 3.0 mIU/L
47. Pregnancy complications
• Overt hypothyroidism
• Overt hypothyroidism complicating pregnancy is unusual
• Two factors contribute to this finding; some hypothyroid
women are anovulatory , and hypothyroidism complicating
pregnancy is associated with an increased rate of first
trimester spontaneous abortion
• In continuing pregnancies,associated with an increased
risk of several complications, including :
• Preeclampsia and gestational hypertension
• Placental abruption
• Nonreassuring fetal heart rate tracing
• Preterm delivery
• Low birth weight
• Increased rate of cesarean section
• Postpartum hemorrhage
• Perinatal morbidity and mortality
• Neuropsychological and cognitive impairment in the child
48. Pregnancy complications
• Subclinical hypothyroidism
• The risk of complications during pregnancy is lower in
women with subclinical, rather than overt,
hypothyroidism
• Increased risk for severe preeclampsia, preterm
delivery, placental abruption, neonatal respiratory
distress syndrome, and/or pregnancy loss compared
with euthyroid women
• Assessment of antibody status is important
• Women with subclinical hypothyroidism and positive
anti-thyroid peroxidase (TPO) antibodies tend to have
the highest risk of adverse pregnancy outcomes, and
adverse outcomes occur at a lower TSH than in
women without TPO antibodies
49. Patients not currently taking thyroid
hormone
• Indications for treatment
• TSH >4 mU/L
• Free T4 below the reference range, TPO
antibodies positive or negative – should be
treated with thyroid hormone
• Free T4 within the reference range, TPO
antibodies positive or negative – Because
maternal euthyroidism is potentially important for
normal fetal cognitive development, suggest
treatment
50. • TSH 2.6 to 4 mU/L TPO antibodies positive and a
history of recurrent miscarriage, many experts offer
treatment with T4 (50 mcg daily)
• In the absence of a history of recurrent miscarriage,
some experts also offer T4 (50 mcg daily)
• If a decision is made not to treat, TSH should be
reassessed every four weeks during the first trimester
and once each in the second and third trimester
• If TSH rises above the population and trimester-specific
upper limit of normal (approximately 4 mU/L), begin
treatment with T4
• TSH 2.6 to 4 mU/L TPO antibodies negative – do not
treat with T4
• TSH between the trimester-specific lower limit of
normal and 2.5 mU/L – do not require T4 treatment
• Low free T4, normal TSH (maternal
hypothyroxinemia) do not treat with T4
51. Levothyroxine initial dosing
• The goal of T4 replacement in pregnancy is to
restore euthyroidism as soon as possible
• General dosing guidance is as follows:
• TSH >4 mU/L with low free T4 – Close to full
replacement dose (approximately 1.6-2mcg/kg body
weight per day)
• TSH >4 mU/L, with normal free T4 – Intermediate
dose (approximately 1 mcg/kg per day)
• TSH 2.6 to 4 mU/L – If a decision has been made to
treat euthyroid women with TPO antibodies, low
dose (typically 50 mcg daily)
• T4 should be taken on an empty stomach, ideally an
hour before breakfast
52. Monitoring and dose adjustments
• The goal is to maintain TSH in the lower half of the
trimester-specific reference range
• If not available, a goal TSH of <2.5 mU/L is reasonable
• If the TSH remains above the normal trimester-specific
reference range, the dose of T4 can be increased by 12
to 25 mcg/day
• TSH should be measured every four weeks during the
first half of pregnancy because dose adjustments are
often required
• TSH can be monitored less often (at least once each
trimester) in the latter half of pregnancy, as long as the
dose is unchanged
• Overtreatment should be avoided
53. • Postpregnancy adjustments
• Since the criteria for treating pregnant women
differ from the criteria from treating nonpregnant
women, it is not always necessary to
continue levothyroxine after delivery
• Unless another pregnancy is imminent, however,
the majority of women who were started on
levothyroxine for TSH between 2.5 and 4.0 mU/L
do not need to continue levothyroxine treatment
55. Preexisting treated hypothyroidism
• Goal preconception TSH
• Women with preexisting hypothyroidism who are
planning to become pregnant should optimize
their thyroid hormone dose preconception
• The goal preconception serum TSH level is
between the lower reference limit and 2.5 mU/L
• Approximately 50 to 85 percent of women with
preexisting hypothyroidism need more T4 during
pregnancy
56. • Early dose adjustments
• Hypothyroid women who are newly pregnant
should preemptively increase their levothyroxine dose by
approximately 30 percent
• Further dose changes are made based upon serum TSH
concentrations measured every four weeks until the TSH
becomes normal
• Another approach is to measure serum TSH as soon as
pregnancy is confirmed, then again four weeks later, four
weeks after any change in the dose of T4, and at least
once each trimester
• The dose should be adjusted as needed every four
weeks to achieve a normal TSH level
57. • Monitoring
• The T4 dose should be reduced to prepregnancy
levels after delivery, but serum TSH should be
measured four to six weeks later to confirm that
the reduction was appropriate
58. CASE SCENARIO 1
• ANC with 8 weeks of gestation came to OPD
• Her TSH <0.05 micro IU/ml
• Free T4 1.30 ng/dl (0.93-1.70)
• What is the diagnosis?
• What is the management?
59. CASE SCENARIO 2
• ANC with 8 weeks of gestation came with
complaints of excessive vomiting
• Her TSH <0.05 micro IU/ml
• Free T4 1.80 ng/dl
• What is the diagnosis?
• What is the management plan?
60. CASE SCENARIO 3
• ANC with 10 weeks of gestation came to OPD
for normal check up
• No vomiting
• No twin gestation
• O/E thyroid enlarged ,PR 140/min,tremors
present
• Her TSH <0.05 micro IU/ml
• Free T4 2.90 ng/dl
• What is the diagnosis?
• What is the management plan?
61. CASE SCENARIO 4
• ANC with 6 weeks of gestation k/c/o Graves
disease on carbimazole came to OPD
• Her TSH 2.5 micro IU/ml
• Free T4 1.30 ng/dl
• What is the management plan?
62. CASE SCENARIO 5
• ANC with 9 weeks of gestation came to OPD
• Her TSH 7.0 micro IU/ml
• Free T4 1.40 ng/dl
• What is the diagnosis?
• What is the management plan?
63. CASE SCENARIO 6
• ANC with 6 weeks of gestation came to OPD
• Her TSH >100 micro IU/ml
• Free T4 0.20 ng/dl
• What is the diagnosis?
• What is the management plan?
64. CASE SCENARIO 7
• ANC with 8 weeks of gestation came to OPD
• Her TSH 3.8 micro IU/ml
• Free T4 1.40 ng/dl
• TPO antibodies positive
• What is the diagnosis?
• What is the management plan?
65. CASE SCENARIO 8
• ANC with 6 weeks of gestation k/c/o
hypothyroidism came to OPD
• Her TSH 2.5 micro IU/ml
• Free T4 1.40 ng/dl
• What is the management plan?
66. • References
• UPTODATE
• RECOMMENDATIONS FOR THE
MANAGEMENT OF THYROID DYSFUNCTION
IN PREGNANCY BY ITS & FOGSI
