SLCOG crestSLCOG Digital GuidelinesSri Lanka College of Obstetricians & Gynaecologists
Guidelines / Medical disorders in pregnancy
SLCOG Clinical Practice Guideline

Thyroid Disease in Pregnancy and the Postpartum Period

Guideline 15June 2022Medical disorders in pregnancy2 tables0 figures
Open source PDF

Background

Thyroid disease in pregnancy, Hypothyroidism and Hyperthyroidism (thyrotoxicosis) can lead to adverse pregnancy outcomes. It can also affect foetal development and contribute to negative outcomes in infancy and childhood1.

Worldwide, the most common cause of hypo- thyroidism is an inadequate dietary intake of iodine. Universal Salt Iodination (USI) was first introduced in Sri Lanka in 1995, which led to a remarkable decrease in the prevalence of iodine deficiency and goitre2. Updated data regarding the prevalence of thyroid disease in the Sri Lankan population is relatively sparse. According to population-based studies done in Sri Lanka, prevalence of goitre was found to be around 6.8% while that of subclinical hypothyroidism was found to be approximately 4-5% with females being the most commonly affected group3,4,5. It is also interesting to note that the prevalence of the presence of thyroid auto-antibodies has been observed to be rising following the introduction of USI4.

Physiological changes of thyroid function during pregnancy

During an average pregnancy, the volume of the thyroid gland increases by 10-30% and the iodine uptake rises by three-fold. Maternal Thyroid-Binding Globulin level increases due to the increased hepatic synthesis under oestrogen stimulation. TSH receptors in the thyroid gland are weakly stimulated by Human Chorionic Gonadotropin (hCG) hormone. Therefore, the total thyroxine (T4) and triiodothyronine (T3) levels increase, although free T4 levels are altered slightly and usually fall during the late course of pregnancy1.

During pregnancy, Thyroid Stimulating Hormone (TSH) levels initially rise with conception and then fall during the first trimester as the increased T4, T3 levels suppress the hypothalamic Thyroid Releasing Hormone (TRH) thus in turn suppressing the release of TSH from the pituitary gland6.

After the first trimester, TSH levels normalize to baseline levels and can increase gradually in the third trimester due to the presence of Placental Deiodinase. In Hyperemesis Gravidarum, increased hCG levels can result in a benign transient biochemical hyperthyroidism in around 60% of cases.

Foetal thyroid gland starts functioning at about 12 weeks after gestation. However, maternal T4 is transferred to the foetus throughout the pregnancy and is considered to be important factor for foetal neural development. This is of particular significance during the first 12 weeks. At birth, about 30% of umbilical cord-measured T4 is derived from the maternal thyroid. Therefore, a history of anti-thyroid drugs or presence of Thyroid Receptor Antibodies in the mother should be communicated to the neonatal physician.

Thyroid function tests during pregnancy

SLCOG recommends the following cut-off limits in Thyroid Function Tests during pregnancy in accor-dance with the reference ranges accepted by the American Thyroid Association7.

Table 1
Hormone1st trimester 2nd trimester3rd trimester
TSH0.1 - 2.5 mIU/L 0.2 - 3.0 mIU/L0.3 - 3.0 mIU/L
Total T 46.5 - 10.1 ug/dl 7.5 - 10.3 ug/dl6.3 - 9.7 ug/dl
Total T 397 - 149 ng/dl 117 - 169 ng/dl123 - 162 ng/dl
Free T 40.8 - 1.7 ng/dl 0.6 - 1.0 ng/dl0.5 - 0.8 ng/dl
Free T 34.1 - 4.4 pg/ml 4.0 - 4.4 pg/ml4.0 - 4.4 pg/ml

Early Gestational Hyperthyroidism (EGH)

EGH is a recognized new entity in the spectrum of thyroid disease in pregnancy, usually presenting with Hyperemesis Gravidarum and mildly symptomatic hyperthyroidism. It is more common in people of Asian descent. Management includes supportive care and hydration. We recommend not starting antithyroid medications for this condition. However, many with symptoms would require beta blockers to control symptoms which can generally be discontinued in the second trimester1.

With regard to thyroid functions, four clinical entities can be deduced apart from the normal euthyroid status. These are,

Table 1 demonstrates the associated changes in thyroid function tests for each condition.

Table 1. Pregnancy associated changes in thyroid function tests in thyroid disorders indicated above

Table 2
Maternal StatusThyroid Stimulating Hormone (TSH) StatusFree T4 Level
Overt HyperthyroidismDecreaseIncrease
Subclinical HyperthyroidismDecreaseUnchanged
Overt HypothyroidismIncreaseDecrease
Subclinical HypothyroidismIncreaseUnchanged

Table 1. Abbreviations: T4, thyroxine; TSH, thyroid-stimulating hormone. *The level of TSH decreases in early pregnancy because of weak TSH receptor stimulation due to substantial quantities of human chorionic gonadotropin during the first 12 weeks of gestation. After the first trimester, TSH levels return to baseline values.

Hyperthyroidism

Hyperthyroidism occurs in about 1 in 500 pregnancies and is most commonly due to Graves’ Disease. De novo cases can be due to solitary toxic adenomas, toxic multinodular goitre, subacute thyroiditis, acute thyroiditis (viral/de Quervain’s) or due to medications (Iodine/Lithium/Amiodarone). Increased thyroid activity in pregnancy can lead to the aggravation of Grave’s thyrotoxicosis in the first trimester and puerperium. Generally, auto-immune thyroid diseases are relatively quiescent during pregnancy due to the relatively immune-suppressive state of pregnancy.

Well controlled disease can achieve good maternal and foetal outcomes. If untreated however, can lead to miscarriage, fetal loss, fetal growth restriction, preterm labour and increased perinatal mortality. Thyroid antibodies can cross the placenta and result in foetal and neonatal thyrotoxicosis.

Hyperthyroidism will lead to maternal sinus tachycardia, supraventricular tachycardia, atrial fibrillation, thyroid storm and heart failure.

Clinical features

Resembles early normal pregnancy symptoms; heat intolerance, palpitations, tachycardia, palmar erythema, vomiting, emotional lability and goitre. De novo cases usually present in the early second trimester.

Discriminating features;

Management

Normal ranges for pregnancy trimesters should be used for assessment and the diagnosis is by raised levels of free T4 and T3 and suppressed TSH.

Antithyroid Drugs (ATD)

Eg: Carbimazole starting dose 15-40 mg, then reduced to 5-15mg,

PTU starting dose 150-400 mg, then reduced to 50-150 mg.

PTU can cause a rare complication i.e. liver failure of the mother (1 in 10,000).

Beta Blockers

Surgery

Radio-active Iodine

Thyroid Storm – Diagnosis and Management

A rare disorder with a mortality rate of 8-25% which presents with multi-organ dysfunction. Symptoms include; pyrexia, tachycardia, arrhythmia, heart failure, delirium, stupor or coma, liver failure, vomiting and diarrhoea.

Precipitants; sudden withdrawal of ATD, following radio-iodine treatment, stress due trauma (surgery) or acute febrile illness. Thus, ensuring euthyroid status of the mother at the elective caesarean section or at labour is of paramount importance.

Diagnosis should be made clinically in severe-level thyrotoxicosis patients with evidence of decom- pensation. Burch-Wartofsky point scale or Japanese Thyroid Association categories can be used to decide on the need for aggressive treatment.

Supportive care, starting PTU recommended for control of thyroxin production from both in gland and peripheral conversion (preferred over Carbimazole/ Methimazole), beta blockers, glucocorticoid therapy with strict ICU / HDU care is useful for control of effect or symptoms and to revive decompensated systems.

Poor respondents should be offered plasmapheresis and emergency surgery10.

Foetal/ Neonatal monitoring

Subclinical Hyperthyroidism

Subclinical Hyperthyroidism is reported in about 0.8-1.7 percent of pregnant women12,13. Diagnosis is done using low TSH levels with normal free T4, T3 levels. This diagnosis not shown to be associated with an effect on pregnancy. Therefore, treatment is not recommended.

Hypothyroidism

Hypothyroidism affects around 1% of pregnancies. Most women will have a positive family history of auto-immune hypothyroidism and will be diagnosed and placed on treatment prenatally. Most common types are Atrophic Thyroiditis and Hashimoto’s Thyroiditis (Auto-Immune Thyroiditis and goitre). Hashimoto’s Thyroiditis is the most common cause of hypothyroidism in developed countries. In contrast, worldwide, the most common cause of hypothyroidism is the inadequate dietary intake of iodine.

Hypothyroidism can also be iatrogenic; due to radio-iodine therapy, thyroidectomy, and due to medications (Antithyroid drugs, Iodine, Lithium, Amiodarone). It can also be associated with other auto-immune diseases.

Hashimoto Thyroiditis is an autoimmune disease that destroys thyroid cells by cell and antibody-mediated immune responses. The pathology of the disease involves the formation of antithyroid antibodies that target and destroy the thyroid tissue, causing progressive fibrosis. Most patients develop antibodies to a variety of thyroid antigens, the most common of which is anti-thyroid peroxidase (anti-TPO, previously named Anti-microsomal antibody). Many also form antithyroglobulin (anti-Tg) and TSH receptor-blocking antibodies (TBII).

Pregnancy has no effect on hypothyroidism. Twenty- five percent of women will require higher requirements of thyroxine dosing during the course of the pregnancy. If untreated, it can lead to miscarriage, fetal loss, foetal anaemia and low birthweight. Foetal thyroid functions begin around the 12th week of gestation. Thus, the foetus is dependent on maternal thyroxine during early gestation. Therefore, if untreated, hypothyroidism and severe maternal iodine deficiency will affect fetal neuro-development leading to cretinism (condition of severe physical and mental retardation specifically due to deficiency of thyroid hormones during early pregnancy, hypothyroidism, spastic motor disorder and deaf mutism-congenital deafness that results in inability to speak). Untreated maternal hypothyroidism has a higher chance of low birth- weight. In rare cases, maternal thyroid antibodies could cross the placenta and cause foetal hypothyroidism but this is extremely rare.

Mothers who are well controlled and euthyroid at conception can achieve good maternal and foetal outcomes.

Diagnosis of hypothyroidism is done when TSH level is over the reference range for the gestational age of pregnancy and the free T4/T3 levels are below the lower limit of normal.

Adverse perinatal outcomes could be reduced by appropriate therapy.

Clinical features

Symptoms may resemble normal pregnancy symptoms; lethargy, tiredness, weight gain, hair loss, dry skin, constipation, fluid retention and goitre.

Discriminating features;

Management

Subclinical Hypothyroidism

Include the group of women who do not have symptoms and signs suggestive of thyroid dysfunction and who present with high TSH and normal thyroxine levels. It is common in the presence of anti-thyroid antibodies. Evidence reports improved pregnancy outcome in women supplemented with thyroxine in the presence of anti-thyroid antibodies. However, TSH level between 2.5-4.0 mU/L in asymptomatic patients does not require treatment5.

Controlled Anti Thyroid Screening trial (CATS) and Maternal-Foetal Medicine Units Networks randomized trials published in 2017 demonstrated no difference in neuro cognitive functions of babies born to mothers with sub clinical hypothyroidism up to the age of 5 in both arms of treatment or no treatment. Recently CATs study in its publication of follow up at 9 years also confirmed no difference in the neurodevelopment of the offspring. However, reading through published trials some have shown higher incidences of preterm birth, abruption, admission to (PBU) premature baby unit, Preeclampsia and gestational diabetes14,15,16,17. But some studies have not shown the same results18,19,20. Therefore our conclusion is at present there is no clinical advantage in treatment of subclinical hypothyroidism unless there is the presence of anti-thyroid antibodies of the mother.

We recommend thyroxine replacement with 25-50 microgram/ day for prenatal women with positive antibodies and subclinical hypothyroidism and titration of TSH to normal levels.

Untreated severe hypothyroidism in the mother can lead to impaired brain development in the foetus. Given ambiguity in outcome of many studies in evaluating pros and cons of treating subclinical hypothyroidism, there is no world-wide consensus of opinion regarding screening all women for hypothyroidism during pregnancy.

General recommendation is to check a woman’s TSH as soon as pregnancy is confirmed in women at high risk for thyroid disease, such as those with prior treatment for hyper- or hypothyroidism, a family history of thyroid disease, a personal history of autoimmune disease, and those with a goiter.

Women with established hypothyroidism should have a TSH test as soon as pregnancy is confirmed. They also should immediately increase their levothyroxine dose, because thyroid hormone requirements increase during pregnancy. If new onset hypothyroidism has been detected, the woman should be treated with levothyroxine to normalize her TSH values.

Foetal / Neonatal Hypothyroidism

Occur due to transplacental passage of maternal anti- thyroid antibodies with incidence of 1 in 180,000 pregnancies.

We recommend screening of all neonates with TSH levels via Guthrie Heel Prick Neonatal Screening test.

Postpartum Thyroiditis

Incidence around 1-17% of pregnancies and is more common among women with anti-thyroid peroxidase (anti-TPO) antibodies. It is usually asymptomatic and present around 3-4 months postpartum. It can present as transient hyperthyroidism, transient hypothyroidism or as a biphasic disease (first hyperthyroidism followed by prolonged hypothyroidism). Small, painless goitre can be present in about 50% of women.

Treatment should be guided by symptom control while most recover spontaneously without treatment. 3-4% of women will have permanent hypothyroidism and about 10-25% of women will have recurrence in future pregnancies.

Most women with positive antibodies will develop postpartum depression despite thyroid status.

SLCOG is of the view, that uncomplicated thyroid disease could be managed by the Obstetrics and Gynaecology Consultant with clear knowledge of the disease process.

References

AA. The prevalence of autoimmune thyroiditis after universal salt iodisation in Sri Lanka. Ceylon Med J 2012; 57(3): 116-19.

84-7.

Cochrane Database of Systematic Reviews 2017, Issue 3. Art. No.: CD011761. DOI: 10.1002/ 14651858.CD011761.

DOI: 10.1089/thy.2016.0229.

Review and MetaAnalysis