Marcos Abalovich

Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline

OBJECTIVE The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Societys Journals Online web site at http://jcem.endojournals.org). EVIDENCE This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society, Asia and Oceania Thyroid Association, and the Latin American Thyroid Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes. CONCLUSIONS Practice guidelines are presented for diagnosis and treatment of patients with thyroid-related medical issues just before and during pregnancy and in the postpartum interval. These include evidence-based approaches to assessing the cause of the condition, treating it, and managing hypothyroidism, hyperthyroidism, gestational hyperthyroidism, thyroid autoimmunity, thyroid tumors, iodine nutrition, postpartum thyroiditis, and screening for thyroid disease. Indications and side effects of therapeutic agents used in treatment are also presented.

Unresolved questions in managing hypothyroidism during pregnancy

Diagnosing and managing hypothyroidism during pregnancy can be problematic. The scenario box on this page illustrates some typical problems encountered and raises pertinent questions concerning good medical practice. In this article, we define autoimmune thyroiditis as the presence of measurable circulating antithyroid autoantibodies (to thyroglobulin or thyroperoxidase), irrespective of abnormalities of thyroid function. Subclinical hypothyroidism is defined as an increase in serum thyroid stimulating hormone (TSH; usually 4-10 mU/l) associated with normal concentrations of serum thyroxine and triiodothyronine. Overt hypothyroidism is defined as an increase in serum TSH (usually >10 mU/l) associated with a decreased concentration of thyroxine, as a result of negative feedback; at that stage, most patients have symptoms and benefit from treatment. #### SCENARIO Mrs SC, aged 29 years, has a family history of goitre. Nine months after a first delivery in 1999, she had positive antithyroid peroxidase antibodies and a serum thyroid stimulating hormone (TSH) concentration of 3.1 mU/l. No treatment was given, but she was told that she should have her thyroid function monitored, advice that she did not follow. Two years later, when she was six weeks pregnant, she was diagnosed with hypothyroidism of autoimmune origin: serum TSH 150 mU/l, free thyroxine 2.6 pmol/l (normal 10-26), antithyroid peroxidase antibodies 990 U/ml (normal <60). She presented with severe hypothyroidism during the first weeks of pregnancy, although we cannot tell whether it was present before conception (though this is likely) or developed after the onset of pregnancy. Treatment with thyroxine was started immediately, and thyroid function returned to normal and remained so throughout the remainder of her pregnancy (table 1⇓). Delivery was full term and obstetrically uneventful. After parturition, the mothers thyroid function was equilibrated with 75 µg thyroxine/day. Six months postpartum, TSH rose transiently to 10.4 mU/l, as a result of postpartum thyroiditis, and thyroxine was …

Adequate Levothyroxine Doses for the Treatment of Hypothyroidism Newly Discovered During Pregnancy

BACKGROUND Recent guidelines recommend thyrotropin (TSH) target levels of ≤2.5 mIU/L for the first trimester and ≤3 mIU/L for the subsequent trimesters. Euthyroidism should be attained as soon as possible, but there are no precise indications about the initial levothyrorine (LT4) dose. The aim of our study was to determine the appropriate LT4 doses in order to normalize TSH levels in patients with newly discovered subclinical hypothyroidism (SCH) during pregnancy, and to correlate them with basal TSH levels. The adequate LT4 doses for women with SCH were also compared to those required in pregnant women with overt hypothyroidism (OH). METHODS Seventy-seven patients with newly diagnosed hypothyroidism during pregnancy were retrospectively analyzed. Patients were assigned to group 1 (n = 64) with SCH or group 2 (n = 13) with OH. SCH patients were subdivided into two groups: group 1a serum TSH >2.5 (1st trimester) or >3 (2nd or 3rd trimester) to 4.2 mIU/L; and group 1b TSH level > 4.21-10 mIU/L. All patients were treated with LT4 as soon as hypothyroidism was diagnosed. The dose that allowed a TSH of ≤2.5 mIU/L to be reached in the first trimester or one that allowed a TSH of ≤3 mIU/L to be reached during the second and third trimesters was considered the appropriate one. RESULTS A significant difference (p < 0.0001) in the appropriate LT4 dose (mean ± SD, μg/kg/day) was observed between group 1 and group 2: 1.31 ± 0.36 versus 2.33 ± 0.59. Patients in group 1a required a significantly lower LT4 dose (p < 0.014) than group1b: 1.20 ± 0.39 versus 1.42 ± 0.31 μg/kg/day. In 57 of the 64 (89.06%) women with SCH and in 10/13 (76.92%) women with OH, the appropriate LT4 dose coincided with the initial dose. Only 11% and 23% respectively required additional adjustments. Once the appropriate dose of LT4 was prescribed, the time at which euthyroidism (mean ± SD, weeks) was confirmed was similar in patients with SCH (6.06 ± 3.3) and OH (5.3 ± 1.8). There were no miscarriages or premature deliveries. CONCLUSIONS When hypothyroidism is newly discovered during pregnancy, we suggest initiating the treatment with the following LT4 doses: 1.20 μg/kg/day for SCH with TSH ≤ 4.2  mIU/L, 1.42 μg/kg/day with TSH > 4.2-10, and 2.33 μg/kg/day for OH. By taking this approach, patients will promptly attain the euthyroid state avoiding additional increments and, probably, obstetric risks.

An International Survey of Screening and Management of Hypothyroidism during Pregnancy in Latin America

OBJECTIVE To determine how endocrinologists in Latin America deal with clinical case scenarios related to hypothyroidism and pregnancy. MATERIALS AND METHODS In January 2013, we sent an electronic questionnaire on current practice relating to management of hypothyroidism in pregnancy to 856 members of the Latin American Thyroid Society (LATS) who manage pregnant patients with thyroid disease. Subsequently, we have analyzed responses from physician members. RESULTS Two hundred and ninety-three responders represent clinicians from 13 countries. All were directly involved in the management of maternal hypothyroidism and 90.7% were endocrinologists. The recommendation of a starting dose of L-thyoxine for a woman diagnosed with overt hypothyroidism in pregnancy, preconception management of euthyroid women with known thyroid autoimmunity and approach related to ovarian hyperstimulation in women with thyroid peroxidase antibodies were widely variable. For women with known hypothyroidism, 34.6% of responders would increase L-thyroxine dose by 30-50% as soon as pregnancy is confirmed. With regard to screening, 42.7% of responders perform universal evaluation and 70% recommend TSH < 2.5 mUI/L in the first trimester and TSH < 3 mUI/L in the second and third trimester as target results in known hypothyroid pregnant women. CONCLUSION Deficiencies in diagnosis and management of hypothyroidism during pregnancy were observed in our survey, highlighting the need for improvement of specialist education and quality of care offered to patients with thyroid disease during pregnancy in Latin America.

Pregnancy and Hypothyroidism: Autoimmune Thyroiditis and Iodine Deficiency Complicating Mother and Fetus

The prevalence of hypothyroidism during pregnancy is estimated to be 0.3–0.5% for overt hypothyroidism (OH) and 2–3% for subclinical hypothyroidism (SCH). The most important cause of maternal hypothyroidism is iodine deficiency, known to affect over 1.2 billion individuals in the world. If iodine nutrition status is adequate, chronic autoimmune thyroiditis is considered as the main cause of hypothyroidism. Several symptoms and signs may raise clinical suspicions, but only thyroid function tests can confirm the diagnosis. Serum TSH elevation suggests primary hypothyroidism and serum free T4 levels define whether one is dealing with SCH or OH, depending on whether free T4 is normal or below normal for gestational age. Patients should separate L-T4 ingestion and the ingestion of iron supplements vitamins containing iron, calcium supplements and soy-based food by at least 4 h. If OH is diagnosed during pregnancy, TFTs should be normalized as rapidly as possible. L-T4 dosage should be titrated rapidly to reach and thereafter maintain serum TSH concentrations lower than 2.5 mU/l (ideally lower than 2.0) or trimester-specific normal TSH ranges. TFTs should be readministered within 30–40 days. SCH has been shown to be associated with an adverse outcome for both the mother and the offspring. L-T4 treatment has been shown to improve obstetrical outcome, but has not been proved to modify long-term neurological development in the offspring. However, given that the potential benefits outweigh the potential risks, we recommend L-T4 replacement in women with SCH. After delivery, most hypothyroid women need the L-T4 dosage they received during pregnancy to be decreased to the preconception dosage. TSH level should be rechecked at 6 weeks postpartum, and it is important to continue monitoring TFTs for at least 6 months after delivery.

Pregnancy and Hypothyroidism

The prevalence of hypothyroidism during pregnancy is estimated to be 0.3–0.5% for overt hypothyroidism (OH) and 2–3% for subclinical hypothyroidism (SCH). The most important cause of maternal hypothyroidism is iodine deficiency, known to affect over 1.2 billion individuals in the world. If iodine nutrition status is adequate, chronic autoimmune thyroiditis is considered as the main cause of hypothyroidism. Several symptoms and signs may raise clinical suspicions, but only thyroid function tests can confirm the diagnosis. Serum TSH elevation suggests primary hypothyroidism and serum free T4 levels define whether one is dealing with SCH or OH, depending on whether free T4 is normal or below normal for gestational age. Patients should separate L-T4 ingestion and the ingestion of iron supplements vitamins containing iron, calcium supplements and soy-based food by at least 4 h. If OH is diagnosed during pregnancy, TFTs should be normalized as rapidly as possible. L-T4 dosage should be titrated rapidly to reach and thereafter maintain serum TSH concentrations lower than 2.5 mU/l (ideally lower than 2.0) or trimester-specific normal TSH ranges. TFTs should be readministered within 30–40 days. SCH has been shown to be associated with an adverse outcome for both the mother and the offspring. L-T4 treatment has been shown to improve obstetrical outcome, but has not been proved to modify long-term neurological development in the offspring. However, given that the potential benefits outweigh the potential risks, we recommend L-T4 replacement in women with SCH. After delivery, most hypothyroid women need the L-T4 dosage they received during pregnancy to be decreased to the preconception dosage. TSH level should be rechecked at 6 weeks postpartum, and it is important to continue monitoring TFTs for at least 6 months after delivery.