Triiodothyronine-predominant Graves' disease in childhood: detection and therapeutic implications (original) (raw)
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Frontiers in Endocrinology, 2021
Background/purposeGraves’ disease (GD) is the most common cause of thyrotoxicosis in children and adolescents. There is some debate regarding the optimal treatment and predicting factors of remission or relapse in children and adolescents with GD. In this study, we report a retrospective study of 195 children and adolescents with GD treated at a single tertiary institution in Korea.MethodsThis study included children and adolescents with GD diagnosed before 19 years of age from January of 2000 to October of 2020. The diagnosis of GD was based on clinical features, high thyroxine (FT4), suppressed thyroid-stimulating hormone, and a positive titer of thyrotropin receptor antibodies. Remission was defined as maintenance of euthyroid status for more than six months after discontinuing antithyroid drug (ATD).ResultsA total of 195 patients with GD were included in this study. The mean age at diagnosis was 12.9 ± 3.2 years, and 162 patients (83.1%) were female. Among all 195 patients, five...
2020
Background: As the treatment approaches of Graves’ disease (GD) and thyroiditis are different, the differential diagnosis is essential. Aim: To assess the diagnostic value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio for differentiation between GD and destructive thyroiditis. Subjects and Methods: The present study was conducted on 100 newly diagnosed thyrotoxicosis patients; 61 with thyroiditis (group 1) and 39 with GD (group 2) and 20 healthy, age-matched subjects representing a control group (Group 3). All participants underwent medical history taking and clinical examination, serum levels of thyroid-stimulating hormone (TSH), FT3, and FT4 were measured, Technetium 99m thyroid Scan was done to all recruited patients. Results: The present results recorded significant increases in FT3, FT4, and decreases in TSH levels in Graves’ disease group than in the thyroiditis group. There was a statistically significant difference between the study groups regarding FT3/FT4 ra...
Curēus, 2024
Background: Graves' disease (GD) and subacute thyroiditis (SAT) are important causes of thyrotoxicosis. The differentiation between these diseases is of great value because it will affect the management plan of either of them. The study aimed to assess the triiodothyronine/free thyroxine (T3/fT4) ratio as a criterion for the differentiation of hyperthyroidism due to GD and SAT. Method: A retrospective study with database retrieval was conducted at Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC), Basrah, southern Iraq. Patients attending the center who presented with thyrotoxicosis due to GD and SAT from January 2010 to January 2024 were included in the analysis that was conducted from October 2023 to February 2024. For comparison between GD and SAT, the baseline thyroid-stimulating hormone (TSH), fT4 and T3 were used to calculate the fT4 ratio (fT4 level (ng/dL)/1.7 ng/dL), T3 ratio (T3 level (ng/dL)/200 ng/dL), and T3/fT4 ratio (T3 level (ng/dL)/fT4 (ng/dL)). Results: As compared to SAT, patients with GD had a significantly lower TSH and higher T3, T3 ratio, and T3/fT4 ratio. A T3/fT4 ratio with a cutoff equal to or more than 25 had 95% sensitivity and 18.1% specificity for GD with 94.4% positive predictive value. Raising the cutoff to equal or more than 100 results in the reduction of sensitivity to 32.7% but with 100% specificity and positive predictive value. Conclusion: The T3/fT4 ratio presents as a valuable diagnostic tool in differentiating GD from SAT, with potential applications in refining the diagnostic approach to hyperthyroidism.
Thyroid, 2014
Background: The management of Graves' disease (GD) in children is associated with a dilemma. Although the established initial treatment for GD in children is antithyroid drug (ATD) treatment, the remission rate in children is said to be lower than in adults, and severe propylthiouracil-induced adverse events (AEs) are an issue. Definitive treatments are effective, but they often result in permanent hypothyroidism and the need for lifelong T4 supplementation. Objective: The objective of this study was to investigate the outcome of ATD treatment, identify significant predictors of a remission, and evaluate the AEs of ATDs in a large pediatric population of GD patients. Methods: We retrospectively assessed the reports of 1138 children up to 18 years of age who had been newly diagnosed with GD at our institution between 1982 and 2006. Their median age at diagnosis was 16 years (range: 3-18 years), and there were 995 females and 143 males. All patients were initially treated with an ATD. Remission was defined as maintenance of euthyroidism for more than 12 months after discontinuing ATD treatment and the absence of any relapses during the follow-up period. Results: Of the 1138 patients, 723 continued on ATD treatment, 271 underwent surgery or radioactive iodine therapy, and 144 dropped out. Of the 723 patients who continued on ATD treatment, ATD treatment was subsequently ongoing in 84 and was discontinued in 639 (median duration of treatment: 3.8 years; range: 0.3-24.8 years). Of the 639 patients who discontinued ATD treatment, 334 (46.2%) achieved a remission, 247 (34.2%) experienced a relapse, and 58 (8.0%) dropped out. The cumulative remission rate increased with the duration of ATD treatment up until five years. No significant predictors of a remission were identified. The overall incidences of AEs associated with methimazole and propylthiouracil were 21.4% and 18.8% respectively. There were no fatal AEs in our population. While most AEs (91.6%) occurred within the first three months of ATD treatment, 2.7% developed more than two years after the start of ATD treatment. Seven of the eight late-onset AEs were induced by propylthiouracil. Conclusion: Long-term ATD treatment is a useful treatment option for GD in children.
Graves Disease in Children: Thyroid-Stimulating Hormone Receptor Antibodies as Remission Markers
The Journal of Pediatrics, 2014
Objective To evaluate clinical and biochemical features of 115 children (98 female, mean age 11.3 AE 3.5 years) with Graves disease to identify possible determinants of remission. Study design We defined as positive outcome the improvement of clinical features and restoration of euthyroidism or induction of hypothyroidism after antithyroid drug (ATD) therapy and as negative outcome hyperthyroidism persistent over 2 years of ATD therapy or relapsed after ATD withdrawal. Results Thirty-eight children (33%) had remission after 2 years of ATD therapy. The absence of goiter at diagnosis was correlated with a better outcome. Median thyroid-stimulating hormone receptor antibody (TRAb) values at diagnosis were significantly lower in patients with a positive outcome (P = .031). We found a significant relationship between the time required for TRAb normalization and the patient outcome; TRAb normalization within 1 year from time of Graves disease diagnosis was significantly more common among patients with a positive outcome (P < .0001), and the mean time for TRAb normalization was significantly shorter in patients with a positive outcome (1.3 AE 0.8 years) compared with that observed in patients with a negative outcome (2.5 AE 2.7 years, P = .026). Conclusions Although no clinical variable investigated is constantly associated with a definite outcome, the absence of goiter at the diagnosis may be associated with a better outcome. The most relevant predictor of Graves disease outcome was serum level; TRAb at time of Graves disease diagnosis less than 2.5 times the upper reference limit, TRAb normalization during ATD, and TRAb normalization timing each may predict positive outcomes. These results may have a role in the empiric clinical management of pediatric patients with Graves disease.
Managing paediatric Graves' disease
International Journal of Research in Medical Sciences, 2014
INTRODUCTION Graves' disease is the most common cause of hyperthyroidism in children, adolescents and adults. 1 Graves 'disease accounts for 10-15% of all childhood thyroid diseases. As in adults, Graves' disease occurs more frequently in female subjects. It may occur at any age during childhood, but it increases in frequency with age .3. The incidence is 0.1 per 100,000 person per year in young children to 3 per 100,000 person per year in adolescents. 3 Graves' disease occur more frequently in children who are suffering from other autoimmune diseases like rheumatoid arthritis, SLE, Pernicious anaemia and type 1 diabetes. 4 CAUSES OF HYPERTHYROIDISM IN CHILDREN Primary hyperthyroidism Graves` disease Toxic adenoma Autoimmune neonatal hyperthyroidism(passage of maternal TRAbs from placenta) Iodine induced hyperthyroidism (iodine, radio contrast agents) Activating mutations of TSH receptor gene. Somatic activating mutation of Gsα (McCune Albright syndrome) Secondary hyperthyroidism TSH secreting pituitary adenoma Thyroid hormone resistance syndrome Thyrotoxicosis without hyperthyroidism Sub-acute thyroiditis Silent thyroiditis Thyrotoxicosis facticia (ingestion of excess thyroid hormone or tissue) PATHOPHYSIOLOGY OF GRAVES' DISEASE A complex interaction of genetic, environmental and immune factors play an important role in the ABSTRACT Graves' disease is the most common cause of hyperthyroidism in children. Anti-thyroid drug treatment with carbimazole or its active metabolite methimazole is offered as first line initial treatment but it induces remission in only 30%of children. Propylthiouracil is not recommended in children because of its association with severe hepatic toxicity. For those who relapse after ATD, radioactive iodine can be offered as definitive therapy except in cases with severe Graves' ophthalmopathy or patients with large goitre who are the candidates for surgery. Total (or near total) thyroidectomy is the surgical procedure of choice for treating paediatric patients with Graves' disease as it reduces the risk of recurrent hyperthyroidism which was seen in patients undergoing subtotal or partial thyroidectomy.
Clinical Pediatric Endocrinology, 2017
Graves' disease (GD) accounts for a large proportion of pediatric hyperthyroidism, and the first-line treatment is antithyroid drug (ATD) therapy. Methimazole (MMI) is effective in most patients but is associated with significant adverse events (AEs). We reviewed the medical records of GD patients (n = 56) with onset age of <15 yr and investigated the relationship between MMI dose and AEs. The study population comprised 11 male and 45 female patients and the median age at diagnosis was 11 yr. All patients were initially treated with ATDs. Among the 52 patients initially treated with MMI, 20 received a low dose, and 32 received a high dose of MMI (< 0.7 vs ≥ 0.7 mg/kg/ day, respectively). AEs occurred in 20% of the patients in the low-dose MMI group, and in 50% patients in the high-dose MMI group (p = 0.031). A greater variety of AEs was observed in the high-dose group. Neutropenia and rash were observed in both groups. With treatment transition to low-dose MMI according to the Japanese Society for Pediatric Endocrinology guidelines, we expect a decrease in the incidence of AEs in future. However, we should be careful as neutropenia and rash can occur independently of the MMI dose.
Treatment outcome of Graves' disease in Thai children
Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2007
Graves' disease is the most common cause of thyrotoxicosis in children. Treatment of Graves' disease consists of anti-thyroid drugs, radioactive iodide and thyroidectomy but the optimal treatment of GD in children is still controversial. To review treatment outcome of Graves' disease in Thai children. Retrospective review of 32 children with Graves' disease, diagnosed between Jan. 1994 and Dec. 2004, at the Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand was performed. All patients (median age 10.5 yrs, range 2.85-15 yrs) presented with goiter and increased serum T4 (median 18.4 mcg/dL, range 8.8-30 mcg/dL), serum T3 (median 443 ng/dL, range 206-800 ng/dL) and suppressed TSH levels (median 0.009 mU/L, range 0-0.18 mU/L). Anti-thyroglobulin and Anti-microsomal antibodies were positive in 70% and 82% respectively. All patients except two were initially treated with propylthiouracil (PTU)....