American Academy of Pediatrics statement

Dr. Thomas Hale's specialty is medicines and breast milk

METHIMAZOLE


Trade Names: Tapazole

Uses: Antithyroid agent

LRC: L3

AAP: Maternal Medication Usually Compatible with Breastfeeding

Methimazole, carbimazole, and propylthiouracil are used to inhibit the secretion of thyroxine. Carbimazole is a prodrug of methimazole and is rapidly converted to methimazole. Milk levels of methimazole depend on maternal dose but appear too low to produce clinical effect. In one study of a patient receiving 2.5 mg methimazole every 12 hours, the milk/serum ratio was 1.16, and the dose per day was calculated at 16-39 µg methimazole. This was equivalent to 7-16% of the maternal dose. In a study of 35 lactating women receiving 5 to 20 mg/day of methimazole, no changes in the infant thyroid function were noted in any infant, even those at higher doses. Further, studies by Lamberg in 11 women, who were treated with the methimazole derivative carbimazole (5-15 mg daily, equal to 3.3 -10 mg methimazole), found all 11 infants had normal thyroid function following maternal treatments. Thus, in small maternal doses, methimazole may also be safe for the nursing mother. In a study of a woman with twins who was receiving up to 30 mg carbimazole daily, the average methimazole concentration in milk was 43 µg/L. The average plasma concentrations in the twin infants were 45 and 52 ng/mL, which is below therapeutic range. Methimazole milk concentrations peaked at 2-4 hours after a carbimazole dose. No changes in thyroid function in these infants were noted. In a large study of over 134 thyrotoxic lactating mothers and their infants. Methimazole therapy was initiated at 10-30 mg/day for one month, and reduced to 5-10 mg/day subsequently. Even at methimazole doses of 20 mg/day, no changes in infant TSH, T4 or T3 were noted in over 12 months of study. The authors conclude that both PTU and methimazole can safely be administered during lactation. However, during the first few months of therapy, monitoring of infant thyroid functioning is recommended..

Methimazole use while Breastfeeding

http://www.drugs.com/breastfeeding/methimazole.html

Fetal free thyroxine concentrations in pregnant women with autoimmune thyroid disease.

http://www.thyroidmanager.org/2012/12/30/fetal-free-thyroxine-concentrations-in-pregnant-women-with-autoimmune-thyroid-disease/

Clinical Practice Guidelines for Hypothyroidism in Adults:
Cosponsored by the American Association of Clinical
Endocrinologists and the American Thyroid Association

Contains some useful information regarding pregnancy also.

This is a PDF file

http://www.thyroidguidelines.net/sites/thyroidguidelines.net/files/file/thy.2012.0205.pdf

This one is not extensive, but it does show how normal newly pregnant moms TSH changes naturally. So once again, do not dose by TSH.

This is another PDF file

http://www.thyroidresearchjournal.com/content/pdf/1756-6614-6-2.pdf

American Thyroid Associations guidelines for all types of thyroid problems during pregnancy.


http://thyroidguidelines.net/sites/thyroidguidelines.net/files/file/thy.2011.0087.pdf

Excellent reference.

Fetal free thyroxine concentrations in pregnant women with autoimmune thyroid disease.

http://www.thyroidmanager.org/2012/12/30/fetal-free-thyroxine-concentrations-in-pregnant-women-with-autoimmune-thyroid-disease/

Plus three Q&A's this week on Elaine Moore's site:

http://elaine-moore.com/QA/tabid/57/forumid/6/threadid/8966/scope/posts/Default.aspx

http://elaine-moore.com/QA/tabid/57/forumid/6/threadid/8968/scope/posts/Default.aspx

http://elaine-moore.com/QA/tabid/57/forumid/6/threadid/8980/scope/posts/Default.aspx

IVF pregnancy outcomes in women with treated hypothyroidism and women without thyroid disease

http://www.thyroid.org/patient-thyroid-information/ct-for-patients/vol-6-issue-8/vol-6-issue-8-p-4-5/

This study is NOT about Graves' patients and our unique antibodies, thus for these women they can consider TSH. I'm saving this here for possible Hashimotos patients that are looking for info.

Immune benefits of breastfeeding = Antibodies.

If you have TRab (Graves disease) antibodies in your blood, they are in your milk too --- and can attack the baby's thyroid next.

This is still the case even if you have had thyroid RA ablation or thyroidectomy.
In fact, in many cases, the RAI itself actually causes these antibodies to elevate to very high levels.

J Pediatr Endocrinol Metab. 2006 Jun;19(6):787-94.
Acquired neonatal thyroid disease due to TSH receptor antibodies in breast milk.

Abstract
INTRODUCTION:
We investigated whether thyroid receptor antibodies (TRAb) could result in transient neonatal thyroid disease by transfer through milk from mothers treated for thyrotoxicosis.

To analyse whether breast milk content of TRAb in euthyroid mothers with treated thyrotoxicosis resulted in neonatal thyroid disease and whether extended breastfeeding prolonged the neonatal disease.
PATIENTS:
We tested three TRAb-positive mothers and the course, treatment and outcome for their offspring with neonatal thyrotoxicosis, and six healthy and two TRAb-negative euthyroid mothers with treated thyrotoxicosis during breastfeeding.
RESULTS:
TRAb in serum was detectable in all treated mothers, in one mother during her four pregnancies, resulting in all neonates requiring treatment for thyrotoxicosis. Serum TRAb concentration decreased continuously with time after birth. Breast milk TRAb was detectable in all cases but not in the controls or in TRAb-negative mothers treated for thyrotoxicosis.
CONCLUSION:
Euthyroid TRAb-positive mothers may cause transient neonatal thyroid disease which seems to be worse and more prolonged during breastfeeding as a consequence of TRAb in breast milk.

Severe fetal and neonatal hyperthyroidism following radioiodine therapy in a woman with Graves’ disease

http://www.endocrine-abstracts.org/ea/0029/ea0029p464.htm

Therapy Insight: Management of Graves' Disease During Pregnancy: Thyroid Function in the Offspring

http://www.medscape.org/viewarticle/556279_4

In case this is not accessible, here is a copy of page 4.

Thyroid Function in the Offspring
Fetal Thyroid Function

By 10-12 weeks gestation, with the increased expression of the sodium iodide symporter gene, the fetal thyroid is capable of concentrating iodide, accumulating colloid, and producing thyroglobulin.[47,48] At around 20 weeks of gestation, the TSH receptor is capable of responding to TSH (as well as thyroid-stimulating antibodies).[47,49] The placenta is not permeable to TSH but is so to iodide.[47] Active iodide transport across the placenta can occur as well, as suggested by the expression of the sodium iodide symporter gene in trophoblasts, although the mechanism has not been fully elucidated.[50-52] Particularly in the second half of pregnancy when the fetal thyroid produces T4, adequate maternal intake of iodine is crucial as a substrate for fetal thyroid hormone synthesis. The placenta also contains the Type 3 deiodinase, which in activates much of the T4 and T3 from the maternal circulation and provides a secondary source of iodine for the fetus.[47] Maternal T4 crosses the placenta throughout gestation. This amount is biologically significant, particularly in the first trimester before fetal thyroid hormone production.[2,53,54]
Fetal Thyroid Dysfunction

Diagnosis of fetal thyroid dysfunction is challenging. Although transplacental passage of maternal antibodies (IgG class) to the fetus does occur early in gestation, the fetal concentration is quite low until the end of the second trimester. Placental permeability to these immunoglobulins then increases such that in the last trimester, fetal levels are equivalent to maternal.[55] This change in permeability, coupled with the ability of the fetal thyroid to respond to TSH and TRAbs, explains why fetal hyperthyroidism occurs in the second half of pregnancy. In women with Graves' disease receiving ATD therapy, fetal thyroid hormone synthesis therefore represents the balance between the transplacental passage of the inhibitory maternal ATD and concentrations of maternal thyroid-stimulating TRAbs.

Fetal thyroid ultrasound at 32 weeks to screen for clinically relevant fetal thyroid dysfunction has a reported sensitivity of 92% and a specificity of 100%;[22] however, if a fetal goiter is detected, fetal hyperthyroidism and hypothyroidism must be differentiated (Figure 3). Signs suggestive of fetal hyperthyroidism include intrauterine growth retardation, arrhythmias, congestive heart failure, advanced bone age, craniosynostosis, and hydrops.[49,56] Another suspicious feature is a diffuse Doppler ultrasound signal throughout the thyroid gland.[57] Tachycardia (>160 beats per minute) can indicate, but is not always present in, fetal thyrotoxicosis.[22,58,59] Fetal hypothyroidism can be difficult to diagnose. Studies have suggested criteria including a Doppler ultrasound signal in the periphery of the fetal thyroid gland and retarded bone maturation.[22,57,59]

As the maternal thyroid is influenced by the same factors (the inhibitory ATD and stimulating TRAbs) as the fetal thyroid, maternal thyroid hormone levels might be indicative of fetal thyroid function.[30,32] Extremely high TRAb concentrations associated with poor control of maternal hyperthyroidism usually, therefore, indicate fetal hyperthyroidism, but high maternal ATD doses coupled with low TRAb levels have been associated with fetal hypothyroidism.[22] If a fetal goiter indicating hypothyroidism is caused by maternal ATD ingestion, a dosage reduction or discontinuation leads to improvement in, and sometimes resolution of, the goiter that can be documented by serial ultrasounds.[57,60-62] There have also been case reports of weekly intra-amniotic levothyroxine therapy resulting in improved thyroid function on cordocentesis and prevention of goiter at delivery, but this treatment has been accompanied by simultaneous reduction in maternal ATD therapy.[61]

In addition, fetuses of levothyroxine-replaced women with a history of 131I-mediated thyroid ablation or surgery for Graves' disease are also at risk for hyperthyroidism. Unknown to clinician and patient, the continued maternal production of high levels of TRAbs could stimulate the fetal thyroid without the presence of the tempering effect of ATDs. These women should therefore have TRAb levels measured at 26-28 weeks gestation and, if levels are elevated, a fetal thyroid ultrasound should be performed.[63] There have been multiple reports of pregnancies in which fetal hyperthyroidism was treated with ATDs.[64-66] Maternal daily ATD doses have ranged between 50 and 300 mg for propylthiouracil, and 15 and 40 mg for methimazole or carbimazole. For levothyroxine-replaced hypothyroid women, the maternal levothyroxine dose might need to be increased as well. Although the optimal timing for ATD administration is uncertain, the cases reported initiation of ATDs between 20 and 34 weeks. Doses can be modulated clinically and decreased when the fetal heart rate normalizes.[65,66]

Umbilical cord blood sampling, also called cordocentesis or funipuncture, can be reserved for cases in which definitive diagnosis of fetal thyroid dysfunction is still in doubt after ultrasound. The procedure should, however, only be performed in centers with experience. It has been associated with a 0.5-2.0% risk of fetal bleeding, bradycardia, infection, and death.[67,68]
Neonatal Thyroid Dysfunction

Neonatal thyrotoxicosis due to persistence of maternal TRAbs occurs in about 1% of babies born to mothers with either active or previously treated Graves' disease and lasts for up to 3 months.[69] Multiple studies have attempted to predict neonatal thyroid status using maternal antibody levels. Strong correlation has been found between maternal and fetal TSI and TBII levels.[24,70] Maternal TSIs >350-500% (normal <125%) before delivery have predicted neonatal hyperthyroidism in several studies.[24,70,71] Maternal TBII levels >40-70% (normal <10-15%) before delivery have also predicted neonatal thyrotoxicosis.[9,70] Although there is no definitive threshold at which fetal TRAb levels predict neonatal hyperthyroidism, one study found that if TRAb levels on days 1-7 of life were three times the upper limit of normal, infants developed neonatal hyperthyroidism.[22,69]

When mothers have active Graves' disease or are TRAb-positive after 131I-mediated thyroid ablation or thyroidectomy, cord blood should be reserved at delivery for measurement of neonatal serum TSH and either total T4 or FT4 levels.[63] In addition, infants should be closely observed for signs of thyrotoxicosis in the first few days of life after maternal ATD has been cleared from their system.

It has also been suggested that a hyperthyroid fetal environment might cause central congenital hypothyroidism. If a fetus is constantly exposed to high levels of maternal thyroid hormone, the development of the fetal hypothalamic-pituitary-thyroid axis might be impaired.[72] The incidence of central congenital hypothyroidism in these cases has been found to be about 0.9%.[9]

continuing on from the previous link ( I remembered my username and logged in)

Conclusions

Graves' disease during pregnancy should be treated with an ATD (propylthiouracil, if available) in the lowest possible dose to maintain maternal serum FT4 levels at or just above the upper limit of the normal nonpregnant reference range, or serum total T4 levels at 1.5-times the normal nonpregnant reference range.

Maternal serum FT4 or total T4 should be measured every 2-4 weeks for close titration of the ATD. Second-trimester thyroidectomy after preoperative preparation with β-adrenergic blockade and iodide can be considered in selected cases. TRAb levels should be measured between 26 and 28 weeks of gestation, including in those women with a prior history of 131I-mediated thyroid ablation or thyroidectomy, to assess the risk of hyperthyroidism to the fetus. If antibody levels are elevated, or if the mother is taking an ATD, fetal ultrasound from 28-32 weeks should be performed to evaluate for fetal goiter. At delivery in women with active Graves' disease or who have elevated TRAb levels after 131Imediated thyroid ablation or thyroidectomy, cord blood should be checked for serum TSH, and T4 or FT4; if neonatal hyperthyroidism is suspected, cord TRAb levels should be measured as well.

Three areas of future research that would be beneficial include: determination of assay-specific and trimester-specific normative FT4 ranges to aid in the diagnosis of thyroid dysfunction, confirmation of maternal serum FT4 targets for optimal titration of ATD, and exploration of noninvasive detection methods for fetal thyroid dysfunction.

THYROID AND PREGNANCY
IVF pregnancy outcomes in women with treated hypothyroidism and women without thyroid disease, from Clinical Thyroidology

http://www.thyroid.org/patient-thyroid-information/ct-for-patients/vol-6-issue-8/vol-6-issue-8-p-4-5/

BACKGROUND
Hypothyroidism is common among women of child-bearing age. The most common cause of hypothyroidism in the United States is the autoimmune disease Hashimoto’s thyroiditis. This is caused by the body developing antibodies that attack and destroy the thyroid. Hypothyroidism that is either undiagnosed or under-treated can contribute to infertility and can result in miscarriage. Several, but not all studies have suggested that treating women with hypothyroidism with levothyroxine improves pregnancy rates and reduces the risk of miscarriage. This study was designed to compare the success of in vitro fertilization (IVF) carried out in hypothyroid women treated with adequate doses of levothyroxine compared to women undergoing the same procedure with normal thyroid function. The goal was to see if appropriate treatment of the hypothyroidism normalized the success and live birth rates following IVF.

THE FULL ARTICLE TITLE:
Busnelli A et al. In vitro fertilization outcomes in treated hypothyroidism. Thyroid. April 2, 2013 [Epub ahead of print].

SUMMARY OF THE STUDY
At an infertility clinic in Italy, 137 women with hypothyroidism were treated with levothyroxine to normalize their TSH and compared to 274 age-matched control women with normal thyroid function. Both groups underwent IVF. The main outcome measurement was live birth rate per IVF cycle. The two groups were similar in regards to baseline TSH, smoking history, menstrual regularity and cycle length, number of prior deliveries and indications for the IVF procedure. The treated hypothyroid women had more cancelled IVF cycles due to poor response, the need for longer hormone stimulation to get their ovaries to respond and a greater proportion who did not undergo embryo transfer than did the control women. However, once the embryos were transferred there was no difference between the groups in regards to pregnancy rate (36% vs. 34%), proportion of women who had a miscarriage (16% vs. 22%) and live birth rates (30% of treated hypothyroid vs. 27% of the controls). There were no differences in outcomes in the hypothyroid patients between those women who had antibody positive autoimmune thyroid disease and those who were hypothyroid without any antibodies.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
In this study, women with adequately treated hypothyroidism had no difference in pregnancy rates and live births compared to women with normal thyroid function, although the hypothyroid women did have less response to hormonal ovarian stimulation and a lower rate of embryo transfer. This adds to the data that shows the importance of identifying and treating women with hypothyroidism before attempting either natural conception or undergoing IVF.