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

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.

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

Nuklearmedizin ◽

10.1055/s-0038-1623919 ◽

2004 ◽

Vol 43 (06) ◽

pp. 217-220 ◽

Cited By ~ 8

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.

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APPROACH TO THE PATIENT Fetal and neonatal thyroid dysfunction

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab747 ◽

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.

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When thyroid labs do not add up, physicians should ask patients about biotin supplements

BMJ Case Reports ◽

10.1136/bcr-2019-231337 ◽

2020 ◽

Vol 13 (3) ◽

pp. e231337

Author(s):

Michael S Lundin ◽

Ahmad Alratroot ◽

Fawzi Abu Rous ◽

Saleh Aldasouqi

Keyword(s):

Thyroid Function ◽

Dose Adjustment ◽

Radioactive Iodine ◽

Graves Disease ◽

Thyroid Function Tests ◽

Medication List ◽

Function Tests ◽

Extensive Evaluation ◽

History Of ◽

Radioactive Iodine Ablation

A 69-year-old woman with a remote history of Graves’ disease treated with radioactive iodine ablation, who was maintained on a stable dose of levothyroxine for 15 years, presented with abnormal and fluctuating thyroid function tests which were confusing. After extensive evaluation, no diagnosis could be made, and it became difficult to optimise the levothyroxine dose, until we became aware of the recently recognised biotin-induced lab interference. It was then noticed that her medication list included biotin 10 mg two times per day. After holding the biotin and repeating the thyroid function tests, the labs made more sense, and the patient was easily made euthyroid with appropriate dose adjustment. We also investigated our own laboratory, and identified the thyroid labs that are performed with biotin-containing assays and developed strategies to increase the awareness about this lab artefact in our clinics.

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

Acta Endocrinologica ◽

10.1530/eje-14-0254 ◽

2014 ◽

Vol 171 (4) ◽

pp. 451-460 ◽

Cited By ~ 46

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.

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Neonatal Hyperthyroidism m Infants of Mothers Previously Thyroidectomized due to Graves’ Disease

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2001-0817 ◽

2001 ◽

Vol 14 (8) ◽

Cited By ~ 5

Author(s):

Maria Victoria Borras-Perez ◽

David Moreno-Pérez ◽

Amalia Zuasnabar-Cotro ◽

Juan P. López-Siguero

Keyword(s):

Total Thyroidectomy ◽

Radioiodine Therapy ◽

Graves Disease ◽

Transplacental Passage ◽

The Third ◽

Thyroid Stimulating Immunoglobulins ◽

Thyroid Ablation ◽

Neonatal Hyperthyroidism ◽

History Of

AbstractNeonatal hyperthyroidism generally arises as a result of active maternal Graves’ disease via transplacental passage of thyroid stimulating immunoglobulins (TSI). On occasions, production of these antibodies may continue after thyroid ablation, either surgically or with radioiodine therapy. We present data concerning three patients (two of them twins) whose mothers had previously undergone near-total thyroidectomy prior to conception. Two of the neonates had neonatal hyperthyroidism due to persistence of TSI in the mother, and the third due to relapse of the maternal Graves’ disease during pregnancy. We recommend monitoring TSI during pregnancy in mothers with a history of Graves’ disease, even if they are in a state of post-surgical hypothyroidism.

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

Acta Endocrinologica ◽

10.1530/eje-13-0994 ◽

2014 ◽

Vol 170 (6) ◽

pp. 855-862 ◽

Cited By ~ 55

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.

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A Case of Rare Autoimmune Pancytopenia Due to Graves’ Disease

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1855 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A908-A909

Author(s):

Ally Wen Wang ◽

Geeti Mahajan ◽

Aaron Etra ◽

Shira R Saul

Keyword(s):

Bone Marrow ◽

Rare Complication ◽

Hematopoietic Cells ◽

Graves Disease ◽

High Dose ◽

Thyroid Function Tests ◽

Molecular Abnormalities ◽

Radioiodine Ablation ◽

Patient Reported ◽

History Of

Abstract Introduction: Graves’ disease has been associated with cytopenias, most commonly anemia. Pancytopenia is a rare complication and is not often encountered. Case Presentation: A 54-year-old woman with history of multiple sclerosis on alemtuzumab was referred for abnormal thyroid function tests. At the initial visit, the patient reported a 20-pound unintentional weight loss, tremors, sweating and heat intolerance. She was 3 years post-menopausal and had no history of recent viral illness, contrast exposure or family history of thyroid disease. Physical exam revealed an anxious appearing woman with fine tremors in both hands, hyperreflexia but no lid lag or exophthalmos. Labs included TSH <0.005 uIU/mL (0.400-4.2), free T4 2.89 ng/dL (0.80-1.50), TSH receptor binding antibody 8.24 IU/L (< 2.00), TSI 7.27 IU/L (<0.56), WBC 2900/uL (4500-11000), ANC 1746/uL (1900 - 8000), hemoglobin 11.4 g/dL (11.7-15.0) and platelet 207,000/uL (150,000-450,000). Thyroid ultrasound noted sub-centimeter hypoechoic/cystic nodules and 24-hour thyroid uptake showed 56.4% symmetric uptake (upper limit of normal 30%). Due to leukopenia, the patient was started on propranolol and underwent radioiodine ablation with 14.8 mCI. Two weeks later, she reported easily bruising and gum bleeding and her blood work was significant for pancytopenia. The patient was referred to hematology and two bone marrow samples were obtained. Though MDS/MPN was initially suspected based on atypia in both specimens, there were no immunophenotypic, cytogenetic or molecular abnormalities suggesting a neoplastic process. Instead the patient was thought to have autoimmune pancytopenia secondary to Graves’ and the atypia was believed to be secondary to peripheral consumption. She was started on prednisone 1 mg/kg/day with resolution of her cytopenias. Discussion: Graves’ disease has been associated with hematological abnormalities including isolated anemia (the most common), thrombocytopenia or leukopenia. Pancytopenia is an uncommon complication and is rarely described in the literature. The exact mechanism remains unclear, but may be related to either reduced production of hematopoietic cells from the bone marrow or increased destruction of mature hematopoietic cells due to autoantibodies. Since thyroid hormones are known to increase erythropoietin, this leads to an exaggerated consumption of iron, folic acid and vitamin B12 and can cause various forms of anemias. Leukopenia may be secondary to immunologic destruction whereas thrombocytopenia may be due to antiplatelet antibodies or increased splenic sequestration. Pancytopenia is rare. Our patient was treated with high dose prednisone with resolution of her pancytopenia, which suggests an autoimmune process as the mechanism. Our case showcases a rare complication of Graves’ disease and highlights that high dose steroid therapy may improve cytopenias associated with this condition.

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PANCYTOPENIA SECONDARY TO AUTOIMMUNE VITAMIN B12 DEFICIENCY IN GRAVES DISEASE

AACE Clinical Case Reports ◽

10.4158/accr-2020-0055 ◽

2020 ◽

Vol 6 (6) ◽

pp. e282-e285

Author(s):

Vilmarie Rodriguez ◽

Kristen M. Gonzales ◽

Anoop Mohamed Iqbal ◽

Natasha Arbelo-Ramos ◽

Kirk D. Wyatt ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Biopsy ◽

White Blood Cells ◽

Vitamin B12 Deficiency ◽

Thyroid Stimulating Hormone ◽

Antithyroid Drugs ◽

Graves Disease ◽

Vitamin B ◽

Thyroid Function Tests ◽

Drug Induced

Objective: To describe a case of Graves disease (GD) and coexistent pancytopenia associated with autoimmune vitamin B12 deficiency. While thyrotoxicosis and antithyroid drugs can cause pancytopenia, other autoimmune conditions such as vitamin B12 deficiency can occur, leading to severe anemia and pancytopenia. Methods: A 19-year-old female with GD treated with methimazole presented with thyrotoxicosis and evidence of pancytopenia. Diagnostic studies included a complete blood cell count, peripheral blood smears, thyroid function tests, and a bone marrow biopsy. Results: White blood cells were 2.4 × 109 cells/L (reference range [RR] is 3.4 to 9.6 × 109 cells/L), hemoglobin was 7.9 g/dL (RR is 11.6 to 15.0 g/dL), neutrophil count was 1.2 × 109 cells/L, and platelets were 84 × 109 cells/L (RR is 157 to 371 × 109 cells/L). Thyroid-stimulating hormone was <0.01 mIU/L (RR is 0.50 to 4.30 mIU/L), free thyroxine was 3.7 ng/dL (RR is 1.0 to 1.6 ng/dL), and total triiodothyronine was 221 ng/dL (RR is 91 to 218 ng/dL). Due to suspicion for drug-induced pancytopenia, methimazole was discontinued. Three days later, she was hospitalized for a syncopal episode with a further decline in hemoglobin to 6.7 g/dL, neutrophils to 0.68 × 109 cells/L, and platelets to 69 × 109 cells/L. Bone marrow biopsy findings showing marrow hypercellularity and hypersegmented neutrophils suggested vitamin B12 deficiency. Vitamin B12 was <70 ng/L (RR is 180 to 914 ng/L). Intramuscular vitamin B12 injections were initiated, and pancytopenia resolved within 1 month. Conclusion: Although rarely described in the literature, autoimmune vitamin B12 deficiency can be missed as an underlying etiology for pancytopenia in patients with GD. The clinical picture can be further confounded when these patients are treated with antithyroid drugs known to cause bone marrow suppression.

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