APPROACH TO THE PATIENT Fetal and neonatal thyroid dysfunction

2021 ◽  
Author(s):  
Juliane Léger ◽  
Clemence Delcour ◽  
Jean-Claude Carel
Keyword(s):  
Developed Countries ◽  
Antithyroid Drugs ◽  
Pituitary Hormone ◽  
Rare Disorders ◽  
Neonatal Hypothyroidism ◽  
Thyrotropin Receptor Antibodies ◽  
Neonatal Hyperthyroidism ◽  
History Of ◽  
Receptor Antibodies

Abstract Fetal and neonatal dysfunctions include rare serious disorders involving abnormal thyroid function during the second half of gestation, which may persist throughout life, as for most congenital thyroid disorders, or be transient, resolving in the first few weeks of life, as in autoimmune hyperthyroidism or hypothyroidism and some cases of congenital hypothyroidism (CH) with the thyroid gland in situ. Primary CH is diagnosed by neonatal screening, which has been implemented for 40 years in developed countries and should be introduced worldwide, as early treatment prevents irreversible neurodevelopmental delay.Central CH is a rarer entity occurring mostly in association with multiple pituitary hormone deficiencies. Other rare disorders impair the action of thyroid hormones. Neonatal Grave’s disease (GD) results from the passage of thyrotropin receptor antibodies (TRAb) across the placenta, from mother to fetus. It may affect the fetuses and neonates of mothers with a history of current or past GD, but hyperthyroidism develops only in those with high levels of stimulatory TRAb activity. The presence of antibodies predominantly blocking TSH receptors may result in transient hypothyroidism, possibly followed by neonatal hyperthyroidism, depending on the balance between the antibodies present. Antithyroid drugs taken by the mother cross the placenta, treating potential fetal hyperthyroidism,but they may also cause transient fetal and neonatal hypothyroidism. Early diagnosis and treatment are key to optimizing the child’s prognosis. This review focuses on the diagnosis and management of these patients during the fetal and neonatal periods. It includes the description of a case of fetal and neonatal autoimmune hyperthyroidism.

scholarly journals Remission Rate of Graves' Disease and the Trend of Changes in Serum TSH Receptor Antibodies in Prolonged Antithyroid Drug Treatment

2020 ◽  
Vol 18 (Suppl) ◽  
Author(s):  
Danilo Villagelin ◽  
Roberto Bernardo Santos ◽  
João Hamilton Romaldini
Keyword(s):  
Drug Treatment ◽  
Remission Rate ◽  
Antithyroid Drug ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Remission Rates ◽  
Thyrotropin Receptor Antibodies ◽  
Antithyroid Drug Treatment ◽  
The Impact ◽  
Receptor Antibodies

Context: Graves’ disease is an autoimmune disease caused by thyrotropin receptor antibodies (TRAb). These antibodies can be measured and used for the diagnosis, prediction of remission, and risk of Graves’ orbitopathy development. There are three treatments for Graves’ disease that have remained unchanged for the last 75 years: Antithyroid drugs, radioiodine, and surgery. Antithyroid drugs are the first treatment option worldwide and are usually used for 12 - 18 months. Recent reports suggest the use of antithyroid drugs for more than 18 months with better outcomes. This review focuses on two aspects of treatment with antithyroid drugs: The impact of using antithyroid drugs for more than 12 - 18 months on remission rates and the trend of TRAb during prolonged antithyroid drug treatment. Evidence Acquisition: A review was performed in Medline on the published work regarding the duration of ATD treatment and remission of Graves' disease and also ATD treatment and TRAb status during the 1990 - 2019 period. Results: Remission rates are variable (30% - 80%), and many clinical and genetic factors serve as predictors. The long-term use of antithyroid drugs appears to increase remission rates. TRAb values usually decline during ATD treatment, but the trend could occur in two ways: Becoming negative or showing a fluctuating pattern. However, approximately 10% of the patients will remain TRAb-positive after five years of treatment with antithyroid drugs. Conclusions: Antithyroid drugs can be used for long periods with an increase in remission rates, and a gradual decrease in TRAb levels, with the disappearance of TRAb in 90% of the patients after 60 months.

scholarly journals Neonatal Thyrotoxicosis with Tricuspid Valve Regurgitation and Hydrops in a Preterm Infant Born to a Mother with Graves' Disease

2018 ◽  
Vol 08 (02) ◽  
pp. e85-e88
Author(s):  
Stefani Doucette ◽  
Anne Tierney ◽  
Anne Roggensack ◽  
Kamran Yusuf
Keyword(s):  
Tricuspid Regurgitation ◽  
Tricuspid Valve Regurgitation ◽  
Grave’S Disease ◽  
First Case ◽  
Neonatal Hyperthyroidism ◽  
History Of ◽  
Grave's Disease ◽  
Thyroid Receptor ◽  
Neonatal Thyrotoxicosis ◽  
Receptor Antibodies

AbstractNeonatal hyperthyroidism is rare disorder due to the passage of thyroid receptor antibodies (TRBs) from the mother to the fetus. Neonatal thyrotoxicosis can present in several ways and if unrecognized, can be fatal. We present a preterm neonate who developed fetal hydrops and tricuspid regurgitation in utero. The mother had a history of treated Grave's disease. The infant responded to maternal treatment antenatally and postnatal anti-thyroid treatment, with resolution of both the tricuspid regurgitation and hydrops. To our knowledge, this is the first case report of tricuspid regurgitation associated with fetal and neonatal thyrotoxicosis. Our case also highlights the importance of obtaining a detailed and accurate history in a mother with previous Grave's disease, even if treated.

Hyperthyroidism in an infant of a mother with autoimmune hypothyroidism with positive TSH receptor antibodies

2018 ◽  
Vol 31 (5) ◽  
pp. 577-580 ◽  
Author(s):  
Kriti Joshi ◽  
Margaret Zacharin
Keyword(s):  
Thyroid Function ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Disorder ◽  
Free Triiodothyronine ◽  
Autoimmune Hypothyroidism ◽  
Normal Thyroid Function ◽  
Neonatal Hyperthyroidism ◽  
History Of ◽  
Blocking Antibodies ◽  
Receptor Antibodies

Abstract Background: Neonatal hyperthyroidism is rare, seen in infants of mothers with Graves’ disease (GD), with transplacental transfer of thyroid-stimulating hormone receptor (TSHR) antibodies (TRAbs). We describe a neonate with severe hyperthyroidism due to TRAbs, born to a mother with autoimmune hypothyroidism. Case presentation: A baby boy born preterm at 35 weeks had irritability, tachycardia and proptosis after birth. The mother had autoimmune hypothyroidism, from age 10, with thyroxine replacement and normal thyroid function throughout her pregnancy. She had never been thyrotoxic. There was a family history of Hashimoto’s thyroiditis (HT) and GD. The baby’s thyroid function on day 3 demonstrated gross thyrotoxicosis, TSH<0.01 mIU/L (normal range [NR]<10 mIU/L), free thyroxine (FT4)>77 pmol/L (20–35), free triiodothyronine (FT3) 15.4 pmol/L (4.2–8.3) and TRAb 18.4 IU/L (<1.8). The mother’s TRAb was 24.7 IU/L. Thyrotoxicosis required propranolol and carbimazole (CBZ). Thyroid function normalized within 10 days. The baby was weaned off medication by 7 weeks. He remains euthyroid. Conclusions: We postulate that this mother had co-existing destructive thyroiditis and thyroid-stimulating antibodies (TSAbs) and TSHR blocking antibodies (TBAb), rendering her unable to raise a thyrotoxic response to the TSAbs but with predominant TSAb transmission to her infant. Maternal history of any thyroid disorder may increase the risk of transmission to an infant, requiring a careful clinical assessment of the neonate, with important implications for future pregnancies.

scholarly journals DIAGNOSIS OF ENDOCRINE DISEASE: Congenital hypothyroidism: update and perspectives

2018 ◽  
Vol 179 (6) ◽  
pp. R297-R317 ◽  
Author(s):  
C Peters ◽  
A S P van Trotsenburg ◽  
N Schoenmakers
Keyword(s):  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Epidemiological Data ◽  
Developed Countries ◽  
Thyroid Stimulating Hormone ◽  
Pituitary Hormone ◽  
Hormone Production ◽  
Neonatal Hypothyroidism ◽  
Developmental Abnormalities ◽  
Delayed Treatment

Congenital hypothyroidism (CH) may be primary, due to a defect affecting the thyroid gland itself, or central, due to impaired thyroid-stimulating hormone (TSH)-mediated stimulation of the thyroid gland as a result of hypothalamic or pituitary pathology. Primary CH is the most common neonatal endocrine disorder, traditionally subdivided into thyroid dysgenesis (TD), referring to a spectrum of thyroid developmental abnormalities, and dyshormonogenesis, where a defective molecular pathway for thyroid hormonogenesis results in failure of hormone production by a structurally intact gland. Delayed treatment of neonatal hypothyroidism may result in profound neurodevelopmental delay; therefore, CH is screened for in developed countries to facilitate prompt diagnosis. Central congenital hypothyroidism (CCH) is a rarer entity which may occur in isolation, or (more frequently) in association with additional pituitary hormone deficits. CCH is most commonly defined biochemically by failure of appropriate TSH elevation despite subnormal thyroid hormone levels and will therefore evade diagnosis in primary, TSH-based CH-screening programmes. This review will discuss recent genetic aetiological advances in CH and summarize epidemiological data and clinical diagnostic challenges, focussing on primary CH and isolated CCH.

scholarly journals Hyperthyroidism in Pregnancy: The Delicate Balance between too Much or too Little Antithyroid Drug

2021 ◽  
Vol 10 (16) ◽  
pp. 3742
Author(s):  
Monica Livia Gheorghiu ◽  
Roxana Georgiana Bors ◽  
Ancuta-Augustina Gheorghisan-Galateanu ◽  
Anca Lucia Pop ◽  
Dragos Cretoiu ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Antithyroid Drug ◽  
Antithyroid Drugs ◽  
Premature Delivery ◽  
Control Group ◽  
Neonatal Hypothyroidism ◽  
Fetal Complications ◽  
Neonatal Hyperthyroidism ◽  
And Control

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.

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.

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

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Erica Wee ◽  
Ramya Ramachandra ◽  
Ana Maria Paez ◽  
John Brownlee ◽  
Rajan Senguttuvan
Keyword(s):  
Pulmonary Hypertension ◽  
Complete Resolution ◽  
Life Support ◽  
Ductus Arteriosus ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Thyroid Function Tests ◽  
Left Heart Failure ◽  
Neonatal Hyperthyroidism ◽  
History Of

Abstract INTRODUCTION Neonatal 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 CASE Baby 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. DISCUSSION Neonatal 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). REFERENCES 1) Oden J, Cheifetz IM. Neonatal thyrotoxicosis and persistent PH necessitating extracorporeal life support. Pediatrics 2005-115: e105-8.

Guideline for radioiodine therapy for benign thyroid diseases (version 3)

2004 ◽  
Vol 43 (06) ◽  
pp. 217-220 ◽  
Author(s):  
J. Dressler ◽  
F. Grünwald ◽  
B. Leisner ◽  
E. Moser ◽  
Chr. Reiners ◽  
...  
Keyword(s):  
Radioiodine Therapy ◽  
Thyroid Volume ◽  
Thyroid Diseases ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Co Morbidity ◽  
History Of ◽  
Individual Decisions ◽  
Prophylactic Use ◽  
Benign Thyroid

SummaryThe version 3 of the guideline for radioiodine therapy for benign thyroid diseases presents first of all a revision of the version 2. The chapter indication for radioiodine therapy, surgical treatment or antithyroid drugs bases on an interdisciplinary consensus. The manifold criteria for decision making consider the entity of thyroid disease (autonomy, Graves’ disease, goitre, goitre recurrence), the thyroid volume, suspicion of malignancy, cystic nodules, risk of surgery and co-morbidity, history of subtotal thyroidectomy, persistent or recurrent thyrotoxicosis caused by Graves’ disease including known risk factors for relapse, compression of the trachea caused by goitre, requirement of direct therapeutic effect as well as the patient’s preference. Because often some of these criteria are relevant, the guideline offers the necessary flexibility for individual decisions. Further topics are patients’ preparation, counseling, dosage concepts, procedural details, results, side effects and follow-up care. The prophylactic use of glucocorticoids during radioiodine therapy in patients without preexisting ophthalmopathy as well as dosage and duration of glucocorticoid medication in patients with preexisting ophthalmopathy need to be clarified in further studies. The pragmatic recommendations for the combined use of radioiodine and glucocorticoids remained unchanged in the 3rd version.

CONSTITUTIONAL AND LEGAL IDEA OF THE “SOCIAL STATE” IN THE HISTORY OF LEGAL AND POLITICAL THOUGHT

2020 ◽  
Author(s):  
Roman Fedorov
Keyword(s):  
Political Thought ◽  
Historical Development ◽  
Significant Contribution ◽  
Developed Countries ◽  
State Structure ◽  
Thomas More ◽  
Social State ◽  
Classical Liberal ◽  
The Social ◽  
History Of

The article is devoted to the problem of the social state as one of the fundamental constitutional principles of the state structure of modern developed countries. The course of historical development of philosophical and legal thought on this problem is considered. The idea of a close connection between the concept of the social state and the ideas of utopian socialism of Thomas More and Henri Saint-Simon is put forward. Liberals also made a significant contribution to the development of the idea of the social state, they argued that the ratio of equality and freedom is a key problem for the classical liberal doctrine. It is concluded that the emergence of the theory of the social state for objective reasons was inevitable, since it is due to the historical development of society.

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