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

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Estefania Rodriguez Ballestas ◽  
Sehar Ejaz
Keyword(s):  
Beta Blockers ◽  
Graves Disease ◽  
Third Trimester ◽  
Bone Maturation ◽  
Central Hypothyroidism ◽  
Thyroid Glands ◽  
Diffuse Goiter ◽  
Neonatal Hyperthyroidism ◽  
Fetal Thyroid

Abstract 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.

scholarly journals Predictive value of maternal second-generation thyroid-binding inhibitory immunoglobulin assay for neonatal autoimmune hyperthyroidism

2014 ◽  
Vol 171 (4) ◽  
pp. 451-460 ◽  
Author(s):  
Juliette Abeillon-du Payrat ◽  
Karim Chikh ◽  
Nadine Bossard ◽  
Patricia Bretones ◽  
Pascal Gaucherand ◽  
...  
Keyword(s):  
First Generation ◽  
Second Generation ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Thyroid Ultrasound ◽  
Second Trimester ◽  
Neonatal Hyperthyroidism ◽  
Fetal Thyroid ◽  
Current Guidelines

ContextHyperthyroidism occurs in 1% of neonates born to mothers with active or past Graves' disease (GD). Current guidelines for the management of GD during pregnancy were based on studies conducted with first-generation thyroid-binding inhibitory immunoglobulin (TBII) assays.ObjectiveThis retrospective study was conducted in order to specify the second-generation TBII threshold predictive of fetal and neonatal hyperthyroidism, and to identify other factors that may be helpful in predicting neonatal hyperthyroidism.MethodsWe included 47 neonates born in the Lyon area to 42 mothers harboring measurable levels of TBII during pregnancy. TBII measurements were carried out in all mothers; bioassays were carried out in 20 cases.ResultsNine neonates were born with hyperthyroidism, including five with severe hyperthyroidism requiring treatment. Three neonates were born with hypothyroidism. All hyperthyroid neonates were born to mothers with TBII levels >5 IU/l in the second trimester (sensitivity, 100% and specificity, 43%). No mother with TSH receptor-stimulating antibodies (TSAb measured by bioassay) below 400% gave birth to a hyperthyroid neonate. Among mothers of hyperthyroid neonates, who required antithyroid drugs during pregnancy, none could stop treatment before delivery. Analysis of TBII evolution showed six unexpected cases of increasing TBII values during pregnancy.ConclusionMaternal TBII value over 5 IU/l indicates a risk of neonatal hyperthyroidism. Among these mothers, a TSAb measurement contributes to identify more specifically those who require a close fetal thyroid ultrasound follow-up. These results should be confirmed in a larger series.

scholarly journals Management of neonates born to women with Graves' disease: a cohort study

2014 ◽  
Vol 170 (6) ◽  
pp. 855-862 ◽  
Author(s):  
Alix Besançon ◽  
Jacques Beltrand ◽  
Isabelle Le Gac ◽  
Dominique Luton ◽  
Michel Polak
Keyword(s):  
Cord Blood ◽  
Thyroid Function ◽  
Prospective Observational Study ◽  
Graves Disease ◽  
Thyroid Function Tests ◽  
Third Trimester ◽  
Free Triiodothyronine ◽  
Bone Maturation ◽  
Thyrotropin Receptor Antibody ◽  
Neonatal Hyperthyroidism

ObjectiveHyperthyroidism in neonates born to mothers with Graves' disease (GD) can be associated with significant morbidity and mortality, but is still overlooked by clinicians. Management of neonatal hyperthyroidism would be improved by a better understanding of the predictive factors involved. The aim of this study was to evaluate the course of thyroid function and clinical outcomes during the first postnatal month in babies born to mothers with GD.DesignProspective observational study.MethodsSixty-eight neonates born to mothers with GD were managed from birth and divided into three groups based on thyrotropin receptor antibody (TRAb) and anti-thyroid drug (ATD) status in the mother: TRAb−ve/ATD−ve,n=27; TRAb−ve/ATD+ve,n=8; and TRAb+ve/ATD+ve,n=33. The main outcome measures were clinical examination, thyroid function tests (TSH, free thyroxine (FT4), free triiodothyronine, and TRAb), echocardiography, thyroid ultrasonography, and bone maturation assessment.ResultsNone of the infants born to TRAb−vemothers with GD developed neonatal hyperthyroidism. Of the 33 TRAb+ve/ATD+veneonates, 24 (72.7%) had positive TRAb on cord blood assays, and seven of these developed neonatal hyperthyroidism. FT4elevation between days 3 and 7 but not at birth was predictive of the development of hyperthyroidism.ConclusionsTRAb status should be checked in the third trimester in mothers with GD and on cord blood in their neonates; if positive, it indicates a high risk of neonatal hyperthyroidism. FT4measurement at birth should be repeated between days 3 and 5 (and by day 7 at the latest); rapid FT4elevation during the first postnatal week is predictive of hyperthyroidism and warrants ATD therapy.

scholarly journals Management of Graves’ Disease during Pregnancy: The Key Role of Fetal Thyroid Gland Monitoring

2005 ◽  
Vol 90 (11) ◽  
pp. 6093-6098 ◽  
Author(s):  
Dominique Luton ◽  
Isabelle Le Gac ◽  
Edith Vuillard ◽  
Mireille Castanet ◽  
Jean Guibourdenche ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Tsh Receptor ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Test Results ◽  
Bone Maturation ◽  
Normal Test ◽  
Fetal Thyroid

Abstract Background: Fetuses from mothers with Graves’ disease may experience hypothyroidism or hyperthyroidism due to transplacental transfer of antithyroid drugs (ATD) or anti-TSH receptor antibodies, respectively. Little is known about the fetal consequences. Early diagnosis is essential to successful management. We investigated a new approach to the fetal diagnosis of thyroid dysfunction and validated the usefulness of fetal thyroid ultrasonograms. Methods: Seventy-two mothers with past or present Graves’ disease and their fetuses were monitored monthly from 22 wk gestation. Fetal thyroid size and Doppler signals, and fetal bone maturation were determined on ultrasonograms, and thyroid function was evaluated at birth. Thyroid function and ATD dosage were monitored in the mothers. Results: The 31 fetuses whose mothers were anti-TSH receptor antibody negative and took no ATDs during late pregnancy had normal test results. Of the 41 other fetuses, 30 had normal test results at 32 wk, 29 were euthyroid at birth, and one had moderate hypothyroidism on cord blood tests. In the remaining 11 fetuses, goiter was visualized by ultrasonography at 32 wk, and fetal thyroid dysfunction was diagnosed and treated; there was one death, in a late referral, and 10 good outcomes with normal or slightly altered thyroid function at birth. The sensitivity and specificity of fetal thyroid ultrasound at 32 wk for the diagnosis of clinically relevant fetal thyroid dysfunction were 92 and 100%, respectively. Conclusion: In pregnant women with past or current Graves’ disease, ultrasonography of the fetal thyroid gland by an experienced ultrasonographer is an excellent diagnostic tool. This tool in conjunction with close teamwork among internists, endocrinologists, obstetricians, echographists, and pediatricians can ensure normal fetal thyroid function.

Diagnostic re-evaluation and predictors of congenital hypothyroidism with eutopic thyroid gland in Jiangxi, China

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shao-Hong Chen ◽  
Bi-Cheng Yang ◽  
Jiang-Ying Li ◽  
Ping Xu ◽  
Feng Wang
Keyword(s):  
Congenital Hypothyroidism ◽  
Operating Characteristics ◽  
Dose Requirement ◽  
Bone Maturation ◽  
Screening Programs ◽  
Receiver Operating Characteristics Curve ◽  
Thyroid Glands ◽  
History Of ◽  
Predictive Role

Abstract Objectives An increase in the incidence of congenital hypothyroidism (CH) with eutopic gland has been reported worldwide due to neonatal screening programs. In this study, we aimed to determine the prevalence of transient CH (TCH) and to investigate predictive factors that could distinguish between permanent and transient CH in patients with eutopic thyroid glands. Methods We retrospectively reviewed 508 children treated for CH with eutopic thyroid glands between June 1998 and June 2020 in Jiangxi Newborn Screening Center. All patients were treated with levothyroxine and underwent Diagnostic re-evaluation after 2–3 years of age. Patients were classified as having TCH or permanent CH (PCH) during follow-up. Results Of the 508 patients initially treated for CH with a normally located gland, 335 patients (65.9%) were classified in the TCH group and 173 (34.1%) in the PCH group based on the defined criteria. Multivariate analysis revealed that TCH was associated with a lower levothyroxine dose at 24 months of age (p<0.001) and a lower likelihood of having a first-degree family history of CH (p=0.026) than PCH. Gender, prematurity, low birth weight, initial CH severity such as serum TSH and FT4 levels, or bone maturation delay at diagnosis had no effect. Receiver operating characteristics curve analysis showed that a cutoff of 2.3 μg/kg/day for levothyroxine dose requirement at 24 months of age had a sensitivity of 71% and a specificity of 70% for predicting transient CH, with values below this threshold considered predictive of transient CH. Conclusions TCH presents a significant portion of patients with CH. The levothyroxine dose requirement at 24 months of age has a predictive role in differentiating TCH from PCH in CH patients with eutopic thyroid glands.

Heart failure from thyrotoxicosis due to Graves’ disease

2021 ◽  
Vol 20 (1) ◽  
pp. 68-73
Author(s):  
Avinash Aujayeb ◽  
◽  
James Dundas ◽  
Keyword(s):  
Heart Failure ◽  
Beta Blockers ◽  
Pernicious Anaemia ◽  
Graves Disease ◽  
Thyroid Function Tests ◽  
Past Medical History ◽  
Pleuritic Chest Pain ◽  
History Of

A 30-year-old female patient with a past medical history of pernicious anaemia presented with pleuritic chest pain, palpitations, fatigue, coryzal symptoms and a high temperature. She was hypoxic and tachycardic and was extensively investigated as well as aggressively treated. A type 1 ‘gut feeling’ assessment by the admitting medical registrar made the diagnosis possible as thyroid function tests were grossly deranged and pointed to Graves’ disease causing heart failure, complicated by pneumonia. The patient was discharged on carbimazole, antibiotics and beta blockers. Due to a resultant thrombocytopaenia, she has now been swapped onto propylthiouracil and is under active follow up.

scholarly journals Immunization with thyroglobulin induces Graves'-like disease in mice

2009 ◽  
Vol 202 (2) ◽  
pp. 217-222 ◽  
Author(s):  
Toyoshi Endo ◽  
Tetsuro Kobayashi
Keyword(s):  
High Titer ◽  
High Serum ◽  
Graves Disease ◽  
Antibody Activity ◽  
Iodide Uptake ◽  
Serum Free ◽  
Thyroid Stimulating Antibody ◽  
Thyroid Glands ◽  
Diffuse Goiter ◽  
Uptake Activity

We immunized AKR/N mice with bovine thyroglobulin (Tg) once every 2 weeks and monitored their time-dependent changes in 125I uptake activity in the thyroid glands. After 3 months, anti-Tg antibody was positive in all sera from the immunized mice. Serum free tri-iodothyronine (T3) and free thyroxine (T4) levels in the immunized mice (n=6) were significantly higher than those in the saline injected (control) mice (n=6). Neck counts as well as scintigraphy of the thyroid glands revealed that iodide uptake activity of the immunized mice was not suppressed, but was instead higher than that of the control mice. Two of the six immunized mice showed extremely high iodide uptake activity. The thyroid glands of these two mice were diffusely enlarged and the height of the epithelial cells was also increased. In addition, two mice with high iodide uptake activity produced a high titer of thyroid-stimulating antibody. Additional experiments showed that 4 out of 11 AKR/N mice and 3 out of 10 C57BL6 mice immunized with Tg had high serum free T3/free T4 levels, high 125I uptake activity of the thyroid, and positive thyroid-stimulating antibody activity. Diffuse goiter, thyrotoxicosis, high iodide uptake activity, and positive thyroid-stimulating antibody are the characteristics of Graves' disease. Thus, these mice exhibit the symptoms of Graves' disease. These results suggest that immunization with Tg induces Graves'-like disease in mice and that our methods will provide a new animal model of Graves' disease.

scholarly journals Pregnancy and Graves’ Disease

2021 ◽  
Author(s):  
Anca Maria Panaitescu
Keyword(s):  
Thyroid Gland ◽  
Radioiodine Therapy ◽  
Reproductive Age ◽  
Antithyroid Drugs ◽  
Surgical Removal ◽  
Graves Disease ◽  
Neonatal Hypothyroidism ◽  
Autoimmune Conditions ◽  
Neonatal Hyperthyroidism ◽  
Fetal Thyroid

Graves’ disease (GD) is one of the most common autoimmune conditions in women of reproductive age. The disorder is characterized by the presence of pathogenic immunoglobulins that bind the TSH receptors (TRAbs) and stimulate the production of thyroid hormones leading to hyperthyroidism (the occurrence of inhibiting or neutral antibodies being rare). Affected individuals can be treated by radioiodine therapy, surgical removal of the gland or by antithyroid drugs (ATDs). Thyroid stimulating immunoglobulins may persist for years after medical treatment, radioiodine therapy or surgical removal of the gland in those affected by GD and during pregnancy can cross the placenta and can act on the fetal thyroid gland resulting in the development of fetal and neonatal hyperthyroidism and sometimes to goiter. Antithyroid drugs used during pregnancy can also cross the placenta and may be teratogenic and act on the fetal thyroid gland, leading to fetal and neonatal hypothyroidism and goiter. This chapter will discuss specific aspects of GD during pregnancy and postpartum focusing on fetal and neonatal consequences related to this disorder.

Short- and Long-Term Results of Total vs Subtotal Thyroid- ectomies in the Surgical Treatment of Graves' Disease

Swiss Surgery ◽  
2001 ◽  
Vol 7 (1) ◽  
pp. 20-24 ◽  
Author(s):  
Robert ◽  
Mariéthoz ◽  
Pache ◽  
Bertin ◽  
Caulfield ◽  
...  
Keyword(s):  
Recurrent Laryngeal Nerve ◽  
Nerve Palsy ◽  
Recurrent Laryngeal Nerve Palsy ◽  
Laryngeal Nerve ◽  
Long Term Results ◽  
Graves Disease ◽  
Laryngeal Nerve Palsy ◽  
Short And Long Term

Objective: Approximately one out of five patients with Graves' disease (GD) undergoes a thyroidectomy after a mean period of 18 months of medical treatment. This retrospective and non-randomized study from a teaching hospital compares short- and long-term results of total (TT) and subtotal thyroidectomies (ST) for this disease. Methods: From 1987 to 1997, 94 patients were operated for GD. Thirty-three patients underwent a TT (mostly since 1993) and 61 a ST (keeping 4 to 8 grams of thyroid tissue - mean 6 g). All patients had received propylthiouracil and/or neo-mercazole and were in a euthyroid state at the time of surgery; they also took potassium iodide (lugol) for ten days before surgery. Results: There were no deaths. Transient hypocalcemia (< 3 months) occurred in 32 patients (15 TT and 17 ST) and persistent hypocalcemia in 8 having had TT. Two patients developed transient recurrent laryngeal nerve palsy after ST (< 3 months). After a median follow-up period of seven years (1-15) with five patients lost to follow-up, 41 patients having had a ST are in a hypothyroid state (73%), thirteen are euthyroid (23%), and two suffered recurrent hyperthyroidism, requiring completion of thyroidectomy. All 33 patients having had TT - with follow-ups averaging two years (0.5-8) - are receiving thyroxin substitution. Conclusions: There were no instances of persistent recurrent laryngeal nerve palsy in either group, but persistent hypoparathyroidism occurred more frequently after TT. Long after ST, hypothyroidism developed in nearly three of four cases, whereas euthyroidy was maintained in only one-fourth; recurrent hyperthyroidy was rare.

Impact of the serum thyroglobulin concentration on the diagnostics of benign and malignant thyroid diseases

2000 ◽  
Vol 39 (05) ◽  
pp. 133-138 ◽  
Author(s):  
W. Dembowski ◽  
H.-J. Schroth ◽  
K. Klinger ◽  
Th. Rink
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Thyroid Volume ◽  
Nodular Goiter ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Normal Range ◽  
Serum Thyroglobulin ◽  
Diffuse Goiter ◽  
Hyperthyroid Patients

Summary Aim of this study is to evaluate new and controversially discussed indications for determining the thyroglobulin (Tg) level in different thyroid diseases to support routine diagnostics. Methods: The following groups were included: 250 healthy subjects without goiter, 50 persons with diffuse goiter, 161 patients with multinodular goiter devoid of functional disorder (108 of them underwent surgery, in 17 cases carcinomas were detected), 60 hyperthyroid patients with autonomously functioning nodular goiter, 150 patients with Hashimoto’s thyroiditis and 30 hyperthyroid patients with Graves’ disease. Results: The upper limit of the normal range of the Tg level was calculated as 30 ng Tg/ml. The evaluation of the collective with diffuse goiter showed that the figure of the Tg level can be expected in a similar magnitude as the thyroid volume in milliliters. Nodular tissue led to far higher Tg values then presumed when considering the respective thyroid volume, with a rather high variance. A formula for a rough prediction of the Tg levels in nodular goiters is described. In ten out of 17 cases with thyroid carcinoma, the Tg was lower than estimated with thyroid and nodular volumes, but two patients showed a Tg exceeding 1000 ng/ml. The collective with functional autonomy had a significantly higher average Tg level than a matched euthyroid group being under suppressive levothyroxine substitution. However, due to the high variance of the Tg values, the autonomy could not consistently be predicted with the Tg level in individual cases. The patients with Hashimoto’s thyroiditis showed slightly decreased Tg levels. In Graves’ disease, a significantly higher average Tg level was observed compared with a matched group with diffuse goiter, but 47% of all Tg values were still in the normal range (< 30 ng/ml). Conclusion: Elevated Tg levels indicate a high probability of thyroid diseases, such as malignancy, autonomy or Graves’ disease. However, as low Tg concentrations cannot exclude the respective disorder, a routine Tg determination seems not to be justified in benign thyroid diseases.

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