Neonatal Hyperthyroidism Research Articles

Abstract 105: A case of transient neonatal thyrotoxicosis

A 2 months old male infant born at 37 weeks of gestation to a mother with Grave's disease on therapy who had a failed radioactive iodine ablation in the past, presented to us with history of failure to gain weight, excessive cry and increased feeding frequency since 1st week of life. On examination he was irritable, weighed 3.5 kg (<5th centile, CDC charts) and had no goiter. The thyroid profile showed TSH <0.0025 IU/l, free T3 5.43 pg/ml, free T4 1.57 ng/dl and elevated TRAb levels (3.66 IU/l). The mother had high TRAb levels (40 IU/l) and the child was diagnosed with neonatal thyrotoxicosis, both the mother and the child were treated with carbimazole. The child received tapering dose of carbimazole during follow-up and achieved TRAb negative status by 8 months. The child is healthy currently and is off treatment.

Neonatal Screening for Hyperthyroidism Proof of Concept.

Early treatment is essential to avoid the cardiac complication of neonatal hyperthyroidism (NH). Our results have direct implications for clinical care. NH can cause potentially fatal neonatal thyrotoxicosis. Here, we have evaluated the feasibility of neonatal hyperthyroidism screening using the thyroid-stimulating hormone value in dried blood collected routinely on filter paper on the third postnatal day of life for congenital hypothyroidism screening. Retrospective case-control study. Cases were identified using data from our previously published study of 280 000 infants born in 10 maternity units in France in 2007-2014. Controls were identified among the 1 362 564 infants born in the Ile-de-France region during the same period. A screening thyroid-stimulating hormone level below 0.18 mIU/L on the third postnatal day had 71% (95% CI 44-90%) sensitivity, 99% (95% CI 99-100%) specificity, 81% (95% CI 74-86%) positive predictive value, and 98% (95% CI 97-99%) negative predictive value for detecting severe NH. By univariate regression analysis, the screening thyroid-stimulating hormone value was the strongest predictor of NH (P < .00001), with an area under the receiver-operating characteristics curve of 0.98 (95% CI 0.95-1.0). Expected frequencies were not significantly different from observed frequencies (Hosmer-Lemeshow test, P = .99). The screening thyroid-stimulating hormone test can be used to detect severe NH, the optimal cut-off being 0.18 mIU/L. The additional cost compared with screening for congenital hypothyroidism would be small. Infants with neonatal hyperthyroidism would benefit from an earlier diagnosis with treatment initiation at the presymptomatic stage in many cases, ensuring optimal outcomes.

A Case of Neonatal Thyrotoxicosis with Cardiac Insufficiency

Neonatal thyrotoxicosis is rare and most of the cases are secondary to maternal Graves’ disease. It is usually transient, but can be associated with significant morbidity and mortality if not recognized promptly and treated adequately. Neonates born to mothers treated with antithyroid drugs or those who receive maternal thyroid blocking antibodies may exhibit normal thyroid function or even hypothyroidism at birth. Since there may not be any obvious symptoms of hyperthyroidism at birth, it may be overlooked. Therefore, such neonates should be evaluated properly and monitored regularly to prevent serious complications of hyperthyroidism. We report a case of a 21-day-old male infant who developed thyrotoxicosis with dyspnea, irritability, tachycardia, and cardiac insufficiency. He was born to a mother who was treated for Graves’ disease with antithyroid drugs during pregnancy. We have also discussed the importance of careful examination and monitoring to prevent the development of clinical hyperthyroidism.

Abstract 13044: Hemodynamic Changes In Neonates Born To Mothers With Graves’ Disease

Purpose: Cardiac insufficiency is a major morbidity in neonatal hyperthyroidism. It is therefore important to assess the hemodynamics in neonates born to mothers with Graves’ disease (GD). This study prospectively evaluated the hemodynamic changes in neonates born to mothers with GD. Methods: The subjects of this study were neonates born to mothers with GD who became pregnant between April 2006 and May 2018 and visited Hamamatsu University Hospital. This study included two groups: neonates born to mothers consistently negative for thyroid-stimulating hormone (TSH) receptor antibody (TRAb) in the third trimester of pregnancy, and neonates born to mothers with at least one positive TRAb assay in the third trimester of pregnancy. The serum levels of TSH, free triiodothyronine (FT3), free thyroxine (FT4), and N-terminal-pro-B-type natriuretic peptide (NT-proBNP), the cardiac output, and cardiac index (CI) evaluated by echocardiography were compared between the two groups at several postnatal points (day of delivery and 5, 10, and 30 days of life). Results: Overall, 80 newborns were enrolled. Thirty-six neonates were born to mothers with GD who were positive for TRAb, and 44 were born to mother negative for TRAb. During the study period, four newborns (11.1%) in the TRAb-positive group required treatment with ATD for overt neonatal hyperthyroidism. Eight newborns (22.2%) in the TRAb-positive group were diagnosed with subclinical hyperthyroidism based on findings of laboratory tests in the absence of any clinical symptoms. One neonate in the TRAb-positive group had subclinical hypothyroidism at birth, but there were no symptoms, so no treatment was required. The TRAb-positive newborns had higher FT4 levels and CI on Day 5 (both p &lt; 0.05) and higher FT3 (p &lt; 0.05) and FT4 levels (p &lt; 0.01) and CI (p &lt; 0.01) but lower TSH levels (p &lt; 0.05) on Day 10 than the TRAb-negative newborns. The TRAb-positive newborns had significantly higher NT-proBNP levels on Days 5 (median 752 vs. 563 pg/mL, p = 0.034) and 10 (median 789 vs. 552 pg/mL, p = 0.002) than the TRAb-negative newborns. Conclusions: Hemodynamic changes in neonates born to TRAb-positive mothers with GD resulted in a higher CI and NT-proBNP levels than in those with TRAb-negative mothers from postnatal days 5 to 10.

Thyroid Disorders.

Thyroid Disorders.

A case of Transient Neonatal Thyrotoxicosis born to mother with Graves’ Disease

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Hyperthyroidism in Pregnancy: The Delicate Balance between Too Much or Too Little Antithyroid Drug.

Overt hyperthyroidism (HT) during pregnancy is associated with a risk of maternal–fetal complications. Antithyroid drugs (ATD) have a potential risk for teratogenic effects and fetal–neonatal hypothyroidism. This study evaluated ATD treatment and thyroid function control during pregnancy, and pregnancy outcome in women with HT. Patients and methods: A retrospective analysis of 36 single fetus pregnancies in 29 consecutive women (median age 30.3 ± 4.7 years) with HT diagnosed before or during pregnancy; a control group of 39 healthy euthyroid pregnant women was used. Results: Twenty-six women had Graves’ disease (GD, 33 pregnancies), 1 had a hyperfunctioning autonomous nodule, and 2 had gestational transient thyrotoxicosis (GTT). Methimazole (MMI) was administered in 22 pregnancies (78.5%), Propylthiouracil (PTU) in 2 (7.1%), switch from MMI to PTU in 4 (14.2%), no treatment in 8 pregnancies (3 with subclinical HT, 5 euthyroid with previous GD remission before conception). In the 8 pregnancies of GD patients diagnosed during gestation or shortly before (<6 weeks), i.e., with fetal exposure to uncontrolled HT, there was 1 spontaneous abortion at 5 weeks (3.4% of all ATD-treated pregnancies), and 1 premature delivery at 32 weeks with neonatal death in 24 h (3.4%); 1 child had neonatal hyperthyroidism (3.3% of live children in GD women) and a small atrial sept defect (4% of live children in ATD treated women). In women treated more than 6 months until conception (20 pregnancies): (a) median ATD doses were lower than those in women diagnosed shortly before or during pregnancy; (b) ATD was withdrawn in 40% of pregnancies in trimester (T)1, all on MMI < 10 mg/day (relapse in 14.2%), and in up to 55% in T3; (c) TSH level was below normal in 37%, 35% and 22% of pregnancies in T1, T2 and T3 respectively; FT4 was increased in 5.8% (T1) and subnormal in 11.75% in T2 and T3; (d) no fetal birth defects were recorded; one fetal death due to a true umbilical cord knot was registered. Mean birth weight was similar in both ATD-treated and control groups. Hyperthyroidism relapsed postpartum in 83% of GD patients (at median 3 ± 2.6 months). Conclusion: In hyperthyroid women with long-term ATD treatment before conception, drugs could be withdrawn in T1 in 40% of them, the thyroid function control was better, and pregnancy and fetal complications were rarer, compared to women diagnosed during pregnancy. Frequent serum TSH and FT4 monitoring is needed to maintain optimal thyroid function during pregnancy.

Follow-up of infants born to mothers with Graves’ disease

IntroductionThe prevalence of neonatal hyperthyroidism (HN) due to maternal Graves Disease (GD) ranges from 0.1 to 2.7%. It may occur in pregnant women with the following: active DG, after treatment with radioactive iodine, anti-thyroid or thyroidectomy or with a previous child with hyperthyroidism. The aim of our observational study was to evaluate the follow-up of infants born to mothers with GD at a Tertiary Hospital prior to the implementation of a follow-up protocol. MethodsThis was a retrospective observational study using data from the medical records of mothers with a diagnosis of GD and their newborns from January 2013 until May 2018. Newborns were divided into two groups: high and low risk for NH according to maternal TRAb, third trimester treatment and signs of fetal hyperthyroidism. ResultsWe identified 31 newborns, 58% female; 87% high risk. In none of the newborns was umbilical cord blood collected. In the high risk group, 22% had thyroid function evaluation at day-1, one patient presented with hyperthyroidism and 82% were asymptomatic. Considering the cases with an insufficient blood sample for analysis, 9 consultations would have been spared. We found a significant delay in obtaining the high-risk group results which would have spared 10 appointments. A positive correlation was found between age at outpatient clinic discharge and the number of appointments and the maternal TRAb titer. ConclusionThe correct surveillance of pregnancy and newborns with identification of those at high risk is essential to avoid unnecessary consultations and blood analyses that increase parental anxiety and hospital costs. Consequently, a multidisciplinary protocol was created to standardize the approach.

50 Years Ago in TheJournalofPediatrics: Advances in Neonatal Thyrotoxicosis

50 Years Ago in TheJournalofPediatrics: Advances in Neonatal Thyrotoxicosis

Prevalence and course of thyroid dysfunction in neonates at high risk of Graves' disease or with non-autoimmune hyperthyroidism.

Neonatal hyperthyroidism may be caused by a permanent non-autoimmune genetic disorder or, more frequently, by maternally transmitted high serum TRAb levels. Variable thyroid dysfunction may be observed in this second context. We aimed to evaluate the prevalence of neonatal non-autoimmune hyperthyroidism and of the different types of thyroid function in neonates with a high risk of hyperthyroidism due to maternal Graves' disease (GD). This observational cohort study included all neonates identified in the database of a single academic pediatric care center, over a period of 13 years, as having non-autoimmune hyperthyroidism or an autoimmune disorder with high TRAb levels (above 6 IU/L) transmitted by their mothers. Patients were classified as having neonatal hyperthyroidism, hypothyroidism, or euthyroidism with a permanent or transient disorder. Two of the 34 consecutive neonates selected (6%) had permanent non-autoimmune hyperthyroidism due to germline (n = 1) or somatic (n = 1) mutations of the TSH receptor gene. The patients with high serum TRAb levels at birth had transient hyperthyroidism (n = 23), hypothyroidism (primary n = 2, central n = 3) or persistent euthyroidism (n = 4). These original findings highlight the need for careful and appropriate monitoring of thyroid function in the long term, not only for the rare patients with non-autoimmune neonatal hyperthyroidism, but also for repeat monitoring during the first month of life in neonates with maternally transmitted high TRAb levels, to ensure the early identification of thyrotoxicosis in more than two thirds of cases and to detect primary or central hypothyroidism, thereby potentially decreasing associated morbidity.

Neonatal Thyrotoxicosis Co-existing With Early Onset Sepsis

Neonatal Thyrotoxicosis Co-existing With Early Onset Sepsis

Follow-up of infants born to mothers with Graves’ disease

IntroductionThe prevalence of neonatal hyperthyroidism (HN) due to maternal Graves Disease (GD) ranges from 0.1 to 2.7%. It may occur in pregnant women with the following: active DG, after treatment with radioactive iodine, anti-thyroid or thyroidectomy or with a previous child with hyperthyroidism. The aim of our observational study was to evaluate the follow-up of infants born to mothers with GD at a Tertiary Hospital prior to the implementation of a follow-up protocol. MethodsThis was a retrospective observational study using data from the medical records of mothers with a diagnosis of GD and their newborns from January 2013 until May 2018. Newborns were divided into two groups: high and low risk for NH according to maternal TRAb, third trimester treatment and signs of fetal hyperthyroidism. ResultsWe identified 31 newborns, 58% female; 87% high risk. In none of the newborns was umbilical cord blood collected. In the high risk group, 22% had thyroid function evaluation at day-1, one patient presented with hyperthyroidism and 82% were asymptomatic. Considering the cases with an insufficient blood sample for analysis, 9 consultations would have been spared. We found a significant delay in obtaining the high-risk group results which would have spared 10 appointments. A positive correlation was found between age at outpatient clinic discharge and the number of appointments and the maternal TRAb titer. ConclusionThe correct surveillance of pregnancy and newborns with identification of those at high risk is essential to avoid unnecessary consultations and blood analyses that increase parental anxiety and hospital costs. Consequently, a multidisciplinary protocol was created to standardize the approach.

Hemodynamic changes in neonates born to mothers with Graves' disease.

Cardiac insufficiency is a major morbidity in neonatal hyperthyroidism. It is important to assess the hemodynamics in neonates born to mothers with Graves' disease (GD). This study prospectively evaluated the hemodynamic changes in neonates born to mothers with GD. Overall, 80 newborns were enrolled. Thirty-six neonates were born to mothers with GD who were positive for thyroid-stimulating hormone (TSH) receptor antibody (TRAb), and 44 were born to mother negative for TRAb. The serum levels of TSH, free triiodothyronine (FT3), free thyroxine (FT4), and N-terminal-pro-B-type natriuretic peptide (NT-proBNP), the cardiac output, and cardiac index (CI) evaluated by echocardiography were compared between the two groups at several postnatal points (day of delivery and 5, 10, and 30 days of life). The TRAb-positive newborns had higher FT4 levels and CI on Day 5 (both p < 0.05) and higher FT3 (p < 0.05) and FT4 levels (p < 0.01) and CI (p < 0.01) but lower TSH levels (p < 0.05) on Day 10 than the TRAb-negative newborns. The TRAb-positive newborns had significantly higher NT-proBNP levels on Days 5 (median 752 vs. 563 pg/mL, p = 0.034) and 10 (median 789 vs. 552 pg/mL, p = 0.002) than the TRAb-negative newborns. Hemodynamic changes in neonates born to TRAb-positive mothers with GD resulted in a higher CI and NT-proBNP levels than in those with TRAb-negative mothers from postnatal days 5 to 10.

SAT-075 Pulmonary Hypertension in a Patient with Neonatal Graves Disease

INTRODUCTIONNeonatal hyperthyroidism is a transient disorder seen in neonates born to mothers with current or past history of Graves’ disease. We present a rare case of a Neonatal Graves’ disease with pulmonary hypertension (PH) which completely resolved with treatment of hyperthyroidism.CLINICAL CASEBaby B was a 3200 g term male born to a 40-year-old hypothyroid mother. He was prenatally diagnosed with Trisomy 21 and coarctation of the aorta (CoA). He developed respiratory distress soon after birth and was admitted to the NICU. His echocardiogram (echo) showed a large patent ductus arteriosus (PDA) and increased tortuosity of juxtaductal aorta with no significant gradient. Near-systemic pulmonary artery pressure was noted in the absence of any evidence of left heart failure. Cardiology determined his CoA to be hemodynamically insignificant and not the cause of his PH. Successive trials of 100% FiO2, Nitric Oxide (NO), and Sildenafil resulted in only minimal improvement of his PH.Thyroid function tests (TFT) obtained on day of life (DOL) 8 showed serum TSH of 0.01 uIU/ml [0.87 - 6.43] and FT4 of 3.5 ng/dl [0.9 - 1.5]. Further interaction with the mother revealed that she had a history of Graves’ disease treated with radioactive iodine (RAI) and resultant hypothyroidism. Baby B’s TSH receptor antibody (TRAb) and thyroid stimulating immunoglobulin levels were elevated at 7.38 IU/l [0-1.75] and 3.38 IU/l [0-0.55], respectively.He was thus diagnosed with Neonatal Graves’ disease and was started on Methimazole (MTZ) 1 mg/kg/day on DOL 8. Subsequently, potassium iodide was added. FT4 showed gradual normalization by DOL 15. Beta blockers were not added due to absence of hypertension or significant tachycardia. Serial echo showed improvement of PH, consistent with the decline in FT4 levels. Sildenafil and FiO2 were slowly weaned and discontinued by DOL 30. MTZ was then tapered and discontinued. A final echo showed complete resolution of PH, unobstructed aortic arch and persistent PDA.DISCUSSIONNeonatal hyperthyroidism occurs due to transplacental transfer of TRAb from mother to fetus, stimulating the fetal thyroid to make excessive thyroid hormones. Risk correlates with TRAb titers in the mother. Our patient had pulmonary hypertension which did not resolve with FiO2, NO and Sildenafil. However, it showed complete resolution with normalization of FT4 levels by antithyroid drugs. Hyperthyroidism commonly presents with systemic HTN, but we found 3 neonatal cases in the literature presenting with PH that resolved with treatment of hyperthyroidism. The mechanism is unclear, but hypotheses include increased clearance of pulmonary vasodilators and decreased clearance of pulmonary vasoconstrictor and decreased surfactant production/function(1).REFERENCES1) Oden J, Cheifetz IM. Neonatal thyrotoxicosis and persistent PH necessitating extracorporeal life support. Pediatrics 2005-115: e105-8.

SUN-525 Successful Surgical Management of Graves’ Disease in Pregnancy

Background: Total thyroidectomy in pregnancy is not a widely used approach for management of Graves’ disease (GD) but is indicated when thyrotoxicosis persists in spite of efforts to optimise thyroid status. Clinical case: A 27-year-old lady with history of GD, presented at the 9th week of her second pregnancy. She had been counselled about anti-thyroid medications but was on carbimazole (CBZ) 30 mg tds and propranolol LA 80 mg od at presentation. She complained of palpitations, heat intolerance, irritability, weight loss and difficulty swallowing. On clinical examination, she had a heart rate of > 100/min and diffusely enlarged goiter with a bruit. Thyroid Ultrasound showed a right lobe of 6.5 x 2.8 x 2.7 cm and left lobe 5.3 x 2.6 x 2.4 cm. Free thyroxine (FT4) was 42.3 pmol/L (12–22), free triiodothyronine (FT3) 9.09 nmol/L (1.3–3.1), and TSH < 0.01 mIU/L (0.27–4.2). TRAB titer was >40 IU/L (0.0–1.75). She was advised to switch to propylthiouracil (PTU) and labetalol to minimize fetal adverse outcomes. She reported that she was unable to afford PTU and requested a switch back to CBZ.During her course of therapy, she had recurrent admissions with thyrotoxicosis, tachycardia, panic attacks and difficulty in swallowing. A decision was made to manage her with total thyroidectomy in the second trimester. She was treated with Lugol’s iodine, beta blockers and CBZ 2 weeks prior to her surgery and there were no immediate post-operative adverse events. Histology was consistent with GD. Her post-op TRAB titer remained >40 IU/L until present.She delivered at 28 weeks of gestation due to threatened premature labor a baby boy who had neonatal thyrotoxicosis, required admission to the neonatal ICU and therapy with flecanide and CBZ. His TSH was 0.09 mIU/L, (FT4) 68.7 pmol/L and TRAB 19.4 IU/L. He is currently 18 months old, well and not on any medications. Conclusion: Poor control of thyrotoxicosis is associated with pregnancy loss, prematurity, stillbirth, thyroid storm, and maternal congestive heart failure. Therefore, pre-pregnancy counseling is crucial to establish Euthyroid state for the safety of mother and fetus. Reference: (1) Davis LE, Lucas MJ, Hankins GD, Roark ML, Cunningham FG. Thyrotoxicosis complicating pregnancy. Am J Obstet Gynecol. 1989;160:63–70. doi: 10.1016/0002-9378(89)90088-4. (2) Vini L, Hyer S, Pratt B, et al. Management of differentiated thyroid cancer diagnosed during pregnancy. Eur J Endocrinol. 1999;140:404–406.

SUN-517 Methimazole-Induced Neutropenia in Premature Twins with Graves’ Disease

Introduction: Neonatal Graves’ disease (NGD) occurs in approximately 1-5% of infants born to women with Graves’ disease. It is caused by trans-placental crossing of thyroid stimulating immunoglobulin (TSI) antibodies during third trimester. Hyperthyroidism during pregnancy can lead to craniosynostosis, goiter, premature bone maturation, developmental delay or even heart failure in the neonate. Neonatal Hyperthyroidism is usually transient and resolves in few weeks. Treatment consists of beta blockers and Methimazole. Studies in adults recommend discontinuing of Methimazole if patients develop neutropenia. However due to lack of alternatives, we present a case of continued use of Methimazole with neutropenia in newborn twins.Case Report:33 weeks gestational age mono-chorionic/di-amniotic twins born to a 34-year-old woman with poorly controlled hyperthyroidism. Mother diagnosed with Graves’ disease during 2nd trimester with poor control throughout pregnancy. At the time of delivery, maternal TSH was <0.005uIU/mL(0.358-3.74uIU/mL) and FT4 2.18ng/dL(0.76-1.46ng/dL). Antenatal ultrasound at 32 weeks showed homogeneous enlargement of fetal thyroid glands with increased vascularity in both twins. Babies found to have diffuse goiter and exophthalmos at birth. Thyroid tests remained normal for first 3 days of life. By day 3, babies labs showed TSH <0.005uIU/mL, FT4 -8 ug/dL and TSI >700%. Baseline CBC showed ANC of 4.95K/mm3. Babies were started on Methimazole 0.5mg/kg/day and Propranolol 2mg/kg/day. TFTs fluctuated throughout their stay in NICU and they developed neutropenia with ANC 1.23K/mm3 on day 20 of life. Methimazole was initially discontinued then restarted at 0.25 mg/kg/day 3 days later. There is no recommended protocol for restarting Methimazole. Further follow up showed persistent neutropenia despite multiple dose adjustments in Methimazole, including dosing every other day. ANC was maintained around 800-1100K/mm3. At age 2 months, Methimazole was discontinued completely after TSI antibodies decreased to 400%. ANC remained low until 6 months of life, even after discontinuing Methimazole. Both babies ultimately developed central hypothyroidism and were started on l-thyroxine.Discussion:NGD can range anywhere from transient hyperthyroidism to persistent central hypothyroidism. Early diagnosis and treatment is crucial to prevent significant morbidity and mortality. Methimazole is the only approved treatment at this age, and management of Methimazole-induced neutropenia has not been established. Adult studies recommend discontinuing Methimazole in context of neutropenia; we took an approach of decreasing dose gradually. Further studies are needed to establish step-wise approach in managing Methimazole-induced neutropenia.

TSH-Receptor testing in pregnancy allows stratification of risk of neonatal thyrotoxicosis and promotes earlier discharge

TSH-Receptor testing in pregnancy allows stratification of risk of neonatal thyrotoxicosis and promotes earlier discharge

Functional condition of the thyroid gland of newborns from methers with a diffuse toxic goiter

Objective: to study the functional state of the thyroid gland in newborns from mothers with diffuse toxic goiter, depending on the level of antibodies to thyroid stimulating hormone receptors (AB-rTSH).Materials and methods: 68 newborns from 67 mothers with diffuse toxic goiter were examined. The control group included 49 newborns from 49 mothers without thyroid pathology. To assess the functional state of the thyroid gland of newborns, we determined the levels of thyroid stimulating hormone, free thyroxine (fT4), and AB-rTSH in cord blood and calculated the TSH/fT4 coefficient, which allows us to differentiate congenital hypothyroidism from neonatal thyrotoxicosis. On the 4-7th day of life, all newborns underwent ultrasound examination (ultrasound) of the thyroid gland.Results: newborns from mothers with diffuse toxic goiter had lower growth-weight indices in comparison with the same indices of the control group and they often showed thyroid hyperplasia. It was shown that the increased content of AB-rTSH in the blood serum of pregnant women with diffuse toxic goiter and in the umbilical cord blood of newborns can contribute to the development of neonatal thyrotoxicosis, detected in 16.2 % of newborns.Conclusions: increased levels of AB-rTSH in the blood serum of mothers with DTG, especially in the second half of pregnancy, and in the umbilical cord blood of newborns affect the formation of thyroid hyperplasia in newborns and contribute to the development of neonatal thyrotoxicosis.

Role of Maternal Thyroid-Stimulating Immunoglobulin in Graves' Disease for Predicting Perinatal Thyroid Dysfunction.

Objective To assess maternal thyroid-stimulating immunoglobulin (TSI) as a predictor of neonatal thyroid hyperthyroidism in pregnancies complicated by Graves' disease. Methods This is a 10-year retrospective study of patients with a history of Graves' disease and elevated TSI activity level defined as 1.3 times the normal. All subjects underwent cordocentesis for ultrasound findings of suspected fetal thyrotoxicosis (fetal tachycardia, oligohydramnios, hydrops, and thyromegaly). Neonatal diagnosis was made based on neonatal thyroid function testing or symptoms. Results Fourteen patients were included in the study, seven with active Graves' disease requiring antithyroid drug (“ATD group”) and seven with iatrogenic hypothyroidism on levothyroxine (“levothyroxine group”). Four cases (57%) of neonatal thyrotoxicosis were diagnosed in the levothyroxine group compared with two cases (28%) in the ATD group. The lowest maternal TSI level at which a neonate did not develop hyperthyroidism was 2.6 for the levothyroxine group and 2.5 for the ATD group. The odds ratio of a neonate from the levothyroxine group developing hyperthyroidism compared with one from the ATD group is 3.3 (95% confidence interval: 0.4–30.7). Conclusion For patients with Graves' disease, those with iatrogenic hypothyroidism and TSI > 2.5 times the basal level are at the highest risk for neonatal thyrotoxicosis.

Fetal Heart Rate as an Indirect Indicator of Treatment Response in Fetal Hyperthyroidism Secondary to Transplacental Passage of Maternal Thyrotropin Receptor Antibodies

Maternal hyperthyroidism is prevalent in 0.2-0.4% of pregnancies. Graves’ disease accounts for 85% of these cases. Approximately 1-5% of neonates born to these mothers develop hyperthyroidism. Transplacental passage of thyrotropin receptor antibodies (TRAbs) are considered to be the likely cause of transient fetal and neonatal hyperthyroidism. An 18-year-old G1P0 with a history of Graves’ disease treated by radioactive ablation presented with persistent fetal tachycardia at 23 weeks gestational age. TRAb was elevated and fetal hyperthyroidism secondary to transplacental crossing of maternal TRAb was suspected. There was no evidence of overt fetal hyperthyroidism or goiter on ultrasound examination. Oral methimazole was initiated and the fetal tachycardia resolved. Upon decrease of the methimazole dosage, the fetal tachycardia returned. Methimazole dosing was again increased and stabilized at a higher dose and the fetal tachycardia remained resolved. At birth at 40 weeks gestation, the neonate was tachycardic with elevated TRAb. She was initiated on methimazole. At 1 month of life, the methimazole dose was halved. At 2 months of life, all medication was held. On further testing, the thyroid function test remained normal. In our patient who did not display evidence of fetal hyperthyroidism on ultrasound examination, as there were no abnormal fetal markers on ultrasound to evaluate treatment response, fetal heart rate on non-stress testing was successfully used as an indirect indicator of fetal thyroid status and guided appropriate titration of methimazole. J Clin Gynecol Obstet. 2019;8(3):91-96 doi: https://doi.org/10.14740/jcgo564