Thyroid dysfunction during pregnancy

Thyroid dysfunction during pregnancy Resident Survival Guide Microchapters
Overview
Causes
Diagnosis
Treatment
Do's
Don'ts

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Roghayeh Marandi, M.D.

Synonyms and keywords: Thyroxine(T4), Triiodothyronine(T3), Thyroid Peroxidase Antibody( TPOAb), Thyroglobulin Antibody( TgAb), Placenta human chorionic gonadotropin( hCG), Thyroxine-binding globulin (TBG), Total T4 (TT4), TSH( Thyroid Stimulating Hormone, Thyrotropin)

Overview

Normal pregnancy is associated with: an increase in renal iodine excretion, an increase in thyroxine-binding proteins, an increase in thyroid hormone production, and thyroid stimulatory effects of hCG. The healthy thyroid adapts to these alterations through changes in thyroid hormone metabolism, iodine uptake, and the regulation of the hypothalamic-pituitary-thyroid axis. circulating thyroxine-binding globulin (TBG) and total T4 (TT4) concentrations increase by week 7 of gestation and reach a peak by approximately week 16 of gestation. These concentrations then remain high until delivery. In the first trimester, maternal hCG directly stimulates the TSH receptor, increasing thyroid hormone production and resulting in a subsequent reduction in serum TSH concentration. Therefore, during pregnancy, women have lower serum TSH concentrations than before pregnancy, and a TSH below the nonpregnant lower limit of 0.4 mU/L is observed in as many as 15% of healthy women during the first trimester of pregnancy. In the first trimester, the lower reference range of TSH can be reduced by approximately 0.4 mU/L, while the upper reference range is reduced by approximately 0.5mU/L. For the typical patient in early pregnancy, this corresponds to a TSH upper reference limit of 4.0mU/L. Unbound T4 represents only about 0.03% of serum TT4 content. However, reference values should take the 50% increase in TBG witnessed during pregnancy into account by calculating the FT4 index using a serum thyroid hormone uptake test (such as the thyroid hormone binding ratio). Changes are predictable, with an increase in TT4 concentration from weeks 7–16 of gestation, ultimately reaching*50% above the pre-pregnancy level. If a T4 measurement is required before that time (i.e., weeks 7–16 of pregnancy), a calculation can be made for the upper reference range based on increasing the nonpregnant upper reference limit by 5% per week, beginning with week 7.Maternal dietary iodine deficiency results in impaired maternal and fetal thyroid hormone synthesis. All pregnant women should ingest approximately 250 µg iodine daily. During pregnancy, the thyroid gland increases in size by 10% in iodine replete countries but by 20% to 40% in areas of iodine deficiency. Production of the thyroid hormones, thyroxine (T4), and triiodothyronine (T3), increases by nearly 50%, in conjunction with a separate 50% increase in the daily iodine requirement. Placental human chorionic gonadotropin (hCG) stimulates thyroid hormone secretion, often decreasing maternal thyrotropin (TSH) concentrations, especially in early pregnancy. Up to 18% of all pregnant women are thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TgAb) positive. Increasingly, data suggest that TPOAb positivity adversely modulates the impact of maternal thyroid status (especially hypothyroidism) on the pregnancy and the developing fetus. Thyroid antibody positivity separately increases the risk of thyroid dysfunction following delivery and during the postpartum period. Women at high risk of thyroid dysfunction (• History of previous thyroid dysfunction• Current symptoms suggestive of hyperthyroidism or hypothyroidism• Known positive thyroid antibodies• Age 30 years or above• Any history of autoimmune disease• History of previous pregnancy loss, preterm delivery or infertility• Use of lithium, amiodarone or recent iodinated contrast use • History of head and neck radiation • Molar pregnancy• Goitre, Morbid Obesity) should undergo screening with measurement of thyroid stimulating hormone (TSH) levels in early pregnancy. If the TSH level is 2.5mIU/L or more on early pregnancy screening, levels of thyroid peroxidase antibodies should be measured to identify women who may benefit from treatment for subclinical hypothyroidism. Transient gestational hyperthyroidism is a common cause of mild hyperthyroidism in early pregnancy. Referral of the patient to an endocrinologist is recommended if TSH levels remain persistently undetectable and/or T3 or T4 levels are elevated and/or TSH receptor antibodies (TRAb) are positive.

Causes

Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

• Thyroid storm due to infection, surgery, preeclampsia, or delivery

Common Causes

• Subclinical hypothyroidism
• Thyroid nodules
• Human chorionic gonadotropin-mediated hyperthyroidism
• Subclinical hypothyroidism + anti-thyroid peroxidase antibodies negative
• Subclinical hypothyroidism + antithyroid peroxidase antibodies positive
• Overt hypothyroidism
• Post partum Thyroiditis

Diagnosis

Shown below is an algorithm summarizing the diagnosis of thyroid dysfunction during pregnancy according to the 2017 guidlines of American thyroid Association.

Known Thyroid disease?

Yes

No ❑ Check TSH in patients if any of these risk factors are identified: ❑ 1.Current symptoms/signs of thyroid dysfunction ❑ 2. Known thyroid antibody positivity or presence of goiter ❑ 3. History of the head or neck radiation or prior thyroid surgery ❑4. Age >30 years ❑5. Type 1 diabetes or other autoimmune disorders ❑6. History of pregnancy loss, preterm delivery, or infertility ❑7. Multiple prior pregnancies ❑8. Family history of autoimmune thyroid disease or thyroid dysfunction ❑9.Morbid obesity (BMI ‡40 kg/m2) ❑10. Use of amiodarone or lithium, or recent administration of iodinated radiologic contrast ❑11. Residing in an area of known moderate to severe iodine insufficiency

Hyperthyroidism ❑The most common cause of hyperthyroidism in women of childbearing age is Graves’ disease ❑ Women with a history of Graves’ disease treated with surgery or radioactive iodine ablative therapy should have TRAb levels measured in early pregnancy. ❑ If positive, TRAb measurement should be repeated at 18 to 22 weeks’ gestation. ❑ As TRAb can cross the placenta and cause fetal hyperthyroidism and neonatal Graves’ disease, women with active Graves’ disease or positive TRAb at 18 to 22 weeks’ gestation should have monitoring for fetal hyperthyroidism by a maternal-fetal medicine specialist. ❑If the TRAb level is elevated at 18 to 22 weeks’ gestation or in women with active Graves’ disease on treatment,measurement of TRAb levels at 30 to 34 weeks’ gestation can guide decisions about neonatal and postnatal monitoring

Hypothyroidism

❑ Thyroid nodules ❑Thyroid cancer

TSH < 0.1 mIU/L

TSH 0.1 - 2.5 mIU/L

TSH 2.5 -10 mIU/L, Check TPOAb

TSH > 10 mIU/L

Check TRAb, T3 and T4 levels for: ❑ Hyperthyroidism ❑Transient Hyperthyroidism ❑thyrotoxicosis

No further workup

Subclinical Hypothyroidism suspected, Check TPOAb, to identify women who may benefit from treatment for subclinical hypothyroidism and TPOAb positive have increased rates of miscarriage and preterm delivery

Overt Hypothyroidism, Check TPOAb to confirm the cause is Autoimmune Hypothyroidism

Treatment

Shown below is an algorithm summarizing the treatment of thyroid dysfunctions during pregnancy according the 2017 Guidelines of the American Thyroid Association.

Known Thyroid disease?

Yes

No ❑Check TSH in patients if any of these risk factors are identified: ❑1.Current symptoms/signs of thyroid dysfunction ❑2. Known thyroid antibody positivity or presence of goiter ❑3. History of the head or neck radiation or prior thyroid surgery ❑4. Age >30 years ❑5. Type 1 diabetes or other autoimmune disorders ❑6. History of pregnancy loss, preterm delivery, or infertility ❑7. Multiple prior pregnancies ❑8. Family history of autoimmune thyroid disease or thyroid dysfunction ❑9.Morbid obesity (BMI ‡40 kg/m2) ❑10. Use of amiodarone or lithium, or recent administration of iodinated radiologic contrast ❑11. Residing in an area of known moderate to severe iodine insufficiency

Hyperthyroidism ❑ medication, such as carbimazole or propylthiouracil, may be required in cases of overt hyperthyroidism. Both medications are associated with a small increase in rates of fetal malformations.

Hypothyroidism ❑All women with overt hypothyroidism should be treated with levothyroxine

Thyroid nodules, Thyroid cancer: ❑Monitoring ❑ Surgery

TSH < 0.1 mIU/L

TSH 0.1 - 2.5 mIU/L

TSH 2.5 -10 mIU/L

TSH > 10 mIU/L

Treat with anti thyroid medications for : ❑ Hyperthyroidism ❑thyrotoxicosis

No further workup

Subclinical Hypothyroidism suspected, Check TPOAb

Overt Hypothyroidism, Check TPOAb to confirm the cause is Autoimmune Hypothyroidism

TPOAb Positive

TPOAb Negative

TSH 2.5 mIU/L-4mIU/l

TSH 4-10mIUL

TSH 2.5mIU/L-4mIU/L

TSH 4-10mIU/L

Conider treatment with Levothyroxin

Treat with Levothyroxin

No Treatment

Consider treatment with Levothyroxin

Do's

• Thyroid nodules found during pregnancy can be further assessed by ultrasound. Referral to an endocrinologist should be considered for women with nodules detected during pregnancy.
• The 2015 ATA guidelines recommend that a nodule with cytology indicating papillary thyroid carcinoma discovered early in pregnancy should be monitored by ultrasound and, if either it grows substantially by 24 weeks gestation (50% in volume and 20% in diameter in two dimensions), or if metastatic cervical lymph nodes are present, surgery should be considered in the second trimester. If the disease remains stable by midgestation, or if it is diagnosed in the second half of pregnancy, surgery may be deferred until after delivery
• Postpartum thyroiditis is the occurrence of thyroid dysfunction, in the first postpartum year in women who were euthyroid prior to pregnancy.

Don'ts

• No need to initiate iodine supplementation in pregnant women who are being treated for hyperthyroidism.
• Selenium supplementation is not recommended for the treatment of TPOAb-positive women during pregnancy.