Graves’ disease in a five-month-old boy with an unusual treatment course

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Svetlana Azova ◽  
Farrah Rajabi ◽  
Biren P. Modi ◽  
Laura Mansfield ◽  
Maureen M. Jonas ◽  
...  
Keyword(s):  
De Novo ◽  
Thyroid Autoimmunity ◽  
Mitochondrial Disorder ◽  
Male Infant ◽  
Left Ventricular ◽  
Definitive Treatment ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
First Line Therapy ◽  
Hpt Axis

AbstractObjectivesGraves’ disease (GD) is rare in children under age five years. Antithyroid drugs are typically first-line therapy but carry the risks of agranulocytosis and liver dysfunction.Case presentationA male infant with multiple congenital anomalies, left ventricular hypertrophy, and neurologic dysfunction developed GD at five months of life. The presence of chronic hepatitis complicated medical management. Potassium iodide was effective temporarily, but urgent thyroidectomy was required at nine months of age. Postoperatively, the patient developed a thyroid function pattern consistent with impaired pituitary sensitivity to thyroid hormone (TH) that responded to the addition of liothyronine. Exome sequencing revealed a heterozygous de novo duplication of the ATAD3 gene cluster, suggesting a possible mitochondrial disorder.ConclusionsThis case describes the youngest child to date to be diagnosed with endogenous GD and to successfully undergo definitive treatment with thyroidectomy. An underlying defect in mitochondrial function is suspected, suggesting a potential novel pathophysiologic link to early-onset thyroid autoimmunity. Additionally, this case illustrated the development of impaired pituitary sensitivity to TH following thyrotoxicosis of postnatal onset, which may contribute to our understanding of hypothalamic-pituitary-thyroid (HPT) axis development.

Aeromedical Decision Making for Military Aircrew with Graves’ Disease

2021 ◽  
Vol 92 (12) ◽  
pp. 980-986
Author(s):  
Edwin Hong-Teck Loh ◽  
Feng Wei Soh ◽  
Brian See ◽  
Benjamin Boon Chuan Tan
Keyword(s):  
Decision Making ◽  
Air Force ◽  
Case Series ◽  
Definitive Treatment ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
First Line Therapy ◽  
The Mean ◽  
Stable Maintenance ◽  
The Impact

BACKGROUND: Graves’ Disease (GD) is a common cause of hyperthyroidism. Although definitive treatment with radioactive iodine (RAI) is preferred for military aircrew, there are cultural and individual differences in receptivity toward RAI, and clinical guidelines that recommend antithyroid drugs (ATD) as the first line therapy. We examined a case series of Republic of Singapore Air Force (RSAF) aviators with GD treated with ATD and the impact of their condition on aeromedical disposition.CASE SERIES: All RSAF aircrew diagnosed with GD and treated with ATD over a 15-yr period were retrospectively identified and analyzed to determine the impact on their fitness for flying duties. The mean age of the 13 aircrew was 33 ± 7.1 yr (range, 25–47 yr), with 11 (84.6%) being males. There were 10 (76.9%) who had ATD as the only treatment while 3 (23.1%) were initially treated with ATD but subsequently underwent RAI or surgery. Of the 10 treated with only ATD, 3 (30.0%) were returned to restricted flying, 6 (60.0%) were returned to unrestricted flying, and 1 (10.0%) is still undergoing ATD titration. There were 10 (76.9%) aircrew who were returned to some form of flying duties while on low doses of ATD.DISCUSSION: This case series suggests that ATD is a viable treatment modality in the aeromedical management of military aviators with GD and it is possible to return military aircrew on a stable maintenance dose of ATD to flying duties. A framework is proposed to support the aeromedical decision-making process for military aircrew in the treatment of GD.Loh EH-T, Soh FW, See B, Tan BBC. Aeromedical decision making for military aircrew with Graves’ disease. Aerosp Med Hum Perform. 2021; 92(12):980–986.

Abstract 14541: Incidence, Risk Factors, and Outcomes of Heart Failure in Patients With Graves’ Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jwan A Naser ◽  
Sorin Pislaru ◽  
Marius N Stan ◽  
Grace Lin
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Cardiovascular Events ◽  
De Novo ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Graves Disease ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Overt Hyperthyroidism

Background: Graves’ disease (GD) can both aggravate pre-existing cardiac disease and cause de novo heart failure (HF). Due to the rarity of thyrotoxic HF, population-based studies are lacking, and data from smaller studies are widely variable. Methods: We reviewed the medical records of 1371 consecutive patients with GD evaluated at our clinic between 2009 and 2019. HF was defined according to Framingham criteria. GD-related HFrEF was defined by left ventricular ejection fraction of <50%, while HFpEF was defined according to the Heart Failure Association of the European Society of Cardiology. Outcomes of major cardiovascular events, all-cause mortality, and cardiac hospitalizations were analyzed with adjustments for age, gender, and history of coronary artery disease (CAD). 1:1 matching with controls (age, gender, and CAD) was additionally done. Results: HF occurred in 74 patients (31 HFrEF; 43 HFpEF). Incidence of GD-related HF, HFrEF, and HFpEF was 5.4%, 2.3%, and 3.1%, respectively. In HFrEF, atrial fibrillation (AF) (RR 10.05, p <0.001) and thyrotropin receptor antibodies (TRAb) level (RR 1.05 per unit, p=0.005) were independent predisposing factors. In HFpEF, independent risk factors were COPD (RR 5.78, p < 0.001), older age (RR 1.48 per 10 years, p = 0.003), overt hyperthyroidism (RR 5.37, p = 0.021), higher BMI (1.06 per unit, p = 0.003), and HTN (RR 3.03, p = 0.011). Rates of cardiac hospitalizations were higher in HFrEF (41.9% vs 3.2%, p <0.001) and HFpEF (44.2% vs 4.7%, p < 0.001) compared to controls. Furthermore, while both increased risk of strokes (HFrEF: RR 4.12, p = 0.027; HFpEF: RR 4.64, p = 0.009), only HFrEF increased risk of all-cause mortality (RR 3.78, p = 0.045). Conclusion: De novo HF occurs in 5.4% of patients with GD and increases the rate of cardiovascular events. HF occurs more frequently in GD patients with AF, higher TRAb, higher BMI, and overt hyperthyroidism, suggesting that these may be targets for treatment to prevent cardiovascular complications, especially in older multimorbid patients.

New Thoughts about the Cause and Treatment of the Severe Ocular Manifestations of Graves' Disease

1974 ◽  
Vol 19 (4) ◽  
pp. 165-169 ◽  
Author(s):  
I. R. McDougall ◽  
J. P. Kriss
Keyword(s):  
Corticosteroid Treatment ◽  
Immunosuppressive Drugs ◽  
Definitive Treatment ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
High Dose ◽  
Ocular Manifestations ◽  
Dose Corticosteroid

The ocular manifestations of Graves' disease are probably due to autoimmunity. Thyroglobulin and complexes of thyroglobulin and antithyroglobulin have a predilection to attach to extraocular muscle membranes in vitro. It is suggested that in vivo these molecules are directed, probably via lymphatics, to the orbit where they attach to the muscle cell membranes. B lymphocytes, which have been shown to be capable of combining with both thyroglobulin and complexes, attach on to these molecules. The tissue damage is probably caused by the complexes, the lymphocytes, or both. Treatment of hyperthyroidism in a patient with ophthalmopathy should be cautious and with antithyroid drugs. This will reduce, though not completely eliminate, the possibility of a post-treatment exacerbation. If for some reason definitive treatment of the hyperthyroidism is essential, worsening of the ophthalmopathy may be prevented by prescribing steroids or immunosuppressive drugs at the time of surgical or radioiodine treatment. When progressive eye disease has arisen, orbital radiotherapy is a safe effective alternative to high dose corticosteroid treatment or surgical decompression.

scholarly journals 2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease

2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Christiaan F Mooij ◽  
Timothy D Cheetham ◽  
Frederik A Verburg ◽  
Anja Eckstein ◽  
Simon H Pearce ◽  
...  
Keyword(s):  
Treatment Options ◽  
Behavioral Changes ◽  
Definitive Treatment ◽  
Dose Titration ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Large Goiter ◽  
Management Recommendations ◽  
Receptor Antibodies ◽  
Serum Tsh

Hyperthyroidism caused by Graves’ disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults – antithyroid drugs (ATD), radioactive iodine (RAI) or thyroid surgery, but the risks and benefits of each modality are different. The European Thyroid Association guideline provides new recommendations for the management of pediatric GD with and without orbitopathy. Clinicians should be alert that GD may present with behavioral changes or declining academic performance in children. Measurement of serum TSH receptor antibodies is recommended for all pediatric patients with hyperthyroidism. Management recommendations include the first-line use of a prolonged course of methimazole/carbimazole ATD treatment (3 years or more), a preference for dose titration instead of block and replace ATD, and to avoid propylthiouracil use. Where definitive treatment is required either total thyroidectomy or RAI is recommended, aiming for complete thyroid ablation with a personalized RAI activity. We recommend avoiding RAI in children under 10 years of age but favor surgery in patients with large goiter. Pediatric endocrinologists should be involved in all cases.

scholarly journals Thyroidectomy in Pediatric Patients with Graves’ Disease: A Systematic Review of Postoperative Morbidity

2020 ◽  
pp. 1-13
Author(s):  
Annabel S. Zaat ◽  
Joep P.M. Derikx ◽  
Nitash Zwaveling-Soonawala ◽  
A.S. Paul van Trotsenburg ◽  
Christiaan F. Mooij
Keyword(s):  
Systematic Review ◽  
Postoperative Complications ◽  
Postoperative Morbidity ◽  
Recurrent Laryngeal Nerve Injury ◽  
Definitive Treatment ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Permanent Hypocalcemia ◽  
Short And Long Term

<b><i>Background:</i></b> Graves’ disease (GD) is the most common cause of hyperthyroidism. In children, the overall relapse frequency after treatment with antithyroid drugs is high. Therefore, many pediatric GD patients eventually require thyroidectomy as definitive treatment. However, the postoperative complications of thyroidectomy in pediatric GD patients are poorly reported. <b><i>Objective:</i></b> To identify the frequency of short- and long-term postoperative morbidities after thyroidectomy in pediatric GD patients. <b><i>Methods:</i></b> A systematic review of the literature (PubMed and Embase) was performed to identify studies reporting short- and long-term postoperative morbidities after thyroidectomy in pediatric GD patients according to the PRISMA guidelines. <b><i>Results:</i></b> Twenty-two mainly retrospective cohort studies were included in this review evaluating short- and long-term morbidities in 1,424 children and adolescents. The frequency of transient hypocalcemia was 22.2% (269/1,210), with a range of 5.0–50.0%. The frequency of permanent hypocalcemia was 2.5% (36/1,424), with a range of 0–20.0%. Two studies reported high frequencies of permanent hypocalcemia, 20.0 (6/30) and 17.4% (9/52), respectively. The 20% frequency could be explained by low-volume surgeons in poorly controlled GD patients. Only 21 cases of permanent hypocalcemia were reported in the 1,342 patients included in the other 20 studies (1.6%). Transient and permanent recurrent laryngeal nerve injury were reported less frequently, with frequencies between 0–20.0 and 0–7.1%, respectively. Infection, hemorrhage/hematoma, and keloid development were only rarely reported as postoperative complications. <b><i>Conclusion:</i></b> The results of this systematic review suggest that thyroidectomy is a safe treatment option for pediatric GD patients. The minority of patients will experience transient and benign morbidities, with hypocalcemia being the most common transient postoperative morbidity. Permanent postoperative morbidities are relatively rare.

scholarly journals A Case of Neonatal Thyrotoxicosis with Cardiac Insufficiency

2021 ◽  
Vol 28 (4) ◽  
pp. 161-166
Author(s):  
Ji Eun Jeong ◽  
So Hee Lee ◽  
Young Hyun Kim ◽  
Yoon Young Jang ◽  
Jin-Kyung Kim
Keyword(s):  
Male Infant ◽  
Cardiac Insufficiency ◽  
Careful Examination ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Normal Thyroid ◽  
Normal Thyroid Function ◽  
Maternal Thyroid ◽  
Blocking Antibodies ◽  
Neonatal Thyrotoxicosis

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.

Results of Randomized Study on Dexrazoxane Administration in Children with De Novo Acute Leukaemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4584-4584
Author(s):  
Eva de Berranger ◽  
Estelle Thebaud-Leculee ◽  
Isabelle Wickaert ◽  
Guy Vaksman ◽  
Francoise Mazingue ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cardiac Function ◽  
De Novo ◽  
Randomized Study ◽  
Wall Stress ◽  
Initial Therapy ◽  
Left Ventricular ◽  
Dose Equivalent ◽  
First Line Therapy

Abstract Anthracyclins and anthracenediones represent major drugs for both myeloid and lymphoblastic acute leukemia. Among their efficient mechanisms, these drugs induce free radical production responsible of cardiac toxicity. Even though toxicity is mainly dose related, there is an inter-individual sensitivity, and then it appeared very important to develop drugs able to protect cardiomyocytes. Dexrazoxane was developed in this goal in adult patients where its efficiency was demonstrated both to protect heart and to respect anticancer therapy results. We conducted a prospective single bind randomized study using dexrazoxane associated with first-line therapy in pediatric acute leukemia. Patients and Methods: From Dec’00 to Sept’03, 16 patients (pts) were enrolled and randomized for receiving or not dexrazoxane (1000mg for 50mg of anthracyclines or anthracenedione doxorubicin dose equivalent) with chemotherapy. Cardiac function was evaluated by echocardiogram before induction and after each chemotherapy course of either CLG-EORTC 58951 trial arm VHR or French acute myeloid leukemia trial LAME01 and each year after treatment completion. The cardiologist operator did not know if child received dexrazoxane or not. The cumulative equivalent doxorubicin dose was 310mg/m2 for EORTC 58951 VHR group and 460mg/m2 for LAME01. The primary end-point was cardiac function evolution. The secondary end points were OS, EFS and the respect of initial therapy schedule. Results: 16 pts (9M/7F), median age 8.5y (range: 2.4 – 16.1) were enrolled. Initial diagnoses were AML: 11 and ALL: 5. Five AML pts and 3 ALL pts received dexrazoxane. Median follow-up was 28.5 months (10–47). 12 pts were alive, 6 in each arm of study. One pt relapsed in arm with dexrazoxane and 3 in the other arm. Two pts died of disease and 2 from infection equally dispatched in the 2 study arms. Mean left ventricular shortening fraction was 39.4+/−1.9% and 35.6+/−1.2% in pts without dexrazoxane and 40.2+/− 2.2% and 38.7+/− 2% in pts with dexrazoxane before chemotherapy and 1 year after diagnosis. All these values were comparable. Mean duration between day1 of each chemotherapy course was the same in different arms of study. Discussion and conclusion: Dexrazoxane may be used safely in children receiving anthracycline. No difference in OS and DFS appear in our study. Median follow-up was probably too short for distinguishing any cardiac alteration and patient number was low. In addition, shortening fraction may be not the better cardiac indicator and wall stress could be more efficient. Further investigations are on-going.

scholarly journals Hyperthyroidism in pregnancy: evidence and hypothesis in fetal programming and development

2021 ◽  
Author(s):  
Stine Linding Andersen ◽  
Stig Andersen
Keyword(s):  
Fetal Programming ◽  
Thyroid Autoimmunity ◽  
Experimental Studies ◽  
Fetal Brain ◽  
Potential Interaction ◽  
Human Studies ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Clinical Awareness ◽  
In Pregnancy

The management of hyperthyroidism in pregnant patients has been a topic of raised clinical awareness for decades. It is a strong recommendation that overt hyperthyroidism of Graves’ disease in pregnant women should be treated to prevent complications. The consequences of hyperthyroidism in pregnancy are less studied than hypothyroidism, and a literature review illustrates that the main burden of evidence to support current clinical guidance emerges from early observations of severe complications in Graves’ disease patients suffering from untreated hyperthyroidism in the pregnancy. On the other hand, the more long-term consequences in children born to mothers with hyperthyroidism are less clear. A hypothesis of fetal programming by maternal hyperthyroidism implies that excessive levels of maternal thyroid hormones impair fetal growth and development. Evidence from experimental studies provides clues on such mechanisms and report adverse developmental abnormalities in the fetal brain and other organs. Only few human studies addressed developmental outcomes in children born to mothers with hyperthyroidism and did not consistently support an association. In contrast, large observational human studies performed within the last decade substantiate a risk of teratogenic side effects to the use of antithyroid drugs in early pregnancy. Thus, scientific and clinical practice are challenged by the distinct role of the various exposures associated with Graves’ disease including the hyperthyroidism per se, the treatment, and thyroid autoimmunity. More basic and clinical studies are needed to extend knowledge on the effects of each exposure, on the potential interaction between exposures and with other determinants, and on the underlying mechanisms.

Graves’ disease and toxic nodular goiter – radioiodine therapy

2002 ◽  
Vol 41 (02) ◽  
pp. 63-70 ◽  
Author(s):  
M. Dietlein ◽  
H. Schicha
Keyword(s):  
Conservative Treatment ◽  
Radioiodine Therapy ◽  
Nodular Goiter ◽  
Human Thyroid ◽  
Definitive Treatment ◽  
Graves Disease ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Benign Thyroid

SummaryAt the 15th conference on the human thyroid in Heidelberg in 2001 the following aspects of the radioiodine therapy of benign thyroid disorders were presented: General strategies for therapy of benign thyroid diseases, criterions for conservative or definitive treatment of hyperthyroidism as first line therapy and finally preparation, procedural details, results, side effects, costs and follow-up care of radioiodine therapy as well as legal guidelines for hospitalization in Germany.The diagnosis Graves’ hyperthyroidism needs the decision, if rather a conservative treatment or if primary radioiodine therapy is the best therapeutic approach. In the USA 70–90% of these patients are treated with radioiodine as first line therapy, whereas in Germany the conservative therapy for 1–1.5 years is recommended for 90%.This review describes subgroups of patients with Graves’ disease showing a higher probability to relapse after conservative treatment. Comparing benefits, adverse effects, costs, and conveniences of both treatment strategies the authors conclude that radioiodine therapy should be preferred as first line therapy in 60–70% of the patients with Graves’ hyperthyroidism.

scholarly journals Graves’ disease with spontaneous resolution following ocrelizumab in primary progressive multiple sclerosis

2021 ◽  
Vol 55 (3) ◽  
pp. 169-173
Author(s):  
Diana Borges Duarte ◽  
Ana Martins da Silva ◽  
Claudia Freitas ◽  
Helena Cardoso
Keyword(s):  
Multiple Sclerosis ◽  
Immune Reconstitution ◽  
Thyroid Autoimmunity ◽  
Progressive Multiple Sclerosis ◽  
Spontaneous Resolution ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Primary Progressive Multiple Sclerosis ◽  
Thyroid Function Tests ◽  
Primary Progressive

Abstract Objectives. Immune reconstitution therapies (IRT), which include antibody-based cell-depleting therapies targeting CD52+ (alemtuzumab) or CD20+ (rituximab, ocrelizumab) leukocytes, are approved for the treatment of multiple sclerosis. Thyroid autoimmunity is a common adverse effect of alemtuzumab treatment, Graves’ disease (GD) being the most prevalent manifestation. To date, thyroid autoimmunity events have not been reported with CD20-targeting monoclonal antibodies. Case Report. A 59-year-old woman with primary progressive multiple sclerosis with no prior personal history of thyroid disease or autoimmunity, was diagnosed with GD 6 months following the first ocrelizumab infusion. She was asymptomatic and had no signs of ophthalmopathy. Due to the temporal association of GD diagnosis with ocrelizumab infusion, absence of symptoms and our experience with alemtuzumab-induced GD, we decided for an active surveillance strategy and antithyroid drugs were not started. She underwent spontaneous resolution of hyperthyroidism with thyroid-stimulating hormone (TSH) receptor antibodies (TRAb) negativity and a mild and transitory period of subclinical hypothyroidism, while she continued the biannually ocrelizumab administration schedule. To present date, she has maintained close clinical and biochemical surveillance with normal TSH, free thyroxine (fT4) and free triiodothyronine (fT3) levels and undetectable TRAb. Conclusions. This is the first case of GD reported after ocrelizumab administration. The timing, onset and course of this case is similar to alemtuzumab-induced GD, usually interpreted as an “immune reconstitution syndrome”; however, ocrelizumab cell count depletion is inferior in severity, cell population affected and duration of depletion. This case highlights the importance of pre-screening and follow-up with thyroid function tests in patients treated with ocrelizumab. As a novel therapeutic antibody, further investigation is required to unravel the causes of thyroid autoimmunity.

Sign in / Sign up

Export Citation Format

Share Document