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European Thyroid Journal Jun 2023Graves' disease (GD) among children has attracted wide attention. However, data on long-term follow-up are scarce, especially in China. This study aimed to investigate... (Review)
Review
BACKGROUND
Graves' disease (GD) among children has attracted wide attention. However, data on long-term follow-up are scarce, especially in China. This study aimed to investigate the prognosis after regular treatments of GD and to identify possible influencing factors.
METHODS
A total of 204 newly diagnosed GD children in the Children's Hospital of Nanjing Medical University between 2013 and 2019 were included in this study. The cases involved were divided into remission group, relapse group, and continuing treatment group according to therapy outcomes. Relationships between prognosis and possible influencing factors in remission and relapse groups were analyzed.
RESULTS
All 204 cases were treated with methimazole at presentation with GD. Due to severe complications, 4 (2.0%) cases changed medication to propylthiouracil. Of all the GD children included, 79 (38.7%) had remission, and 40 (50.6%) relapsed after remission. For each additional month before free thyroxine fell into the reference range with treatment, the risk of relapse increased 1.510 times (adjusted odds ratio (OR)=2.510, 95%CI: 1.561-4.034) compared to those in the remission group. On the contrary, the risk of relapse was reduced by 0.548 times for each additional hour of sleep duration per day (adjusted OR=0.452, 95%CI: 0.232-0.879).
CONCLUSION
GD children have a high relapse rate after remission, and most of them occur within 1 year. Thyroid function should be reexamined regularly after drug withdrawal. The response to medication and lifestyle of GD children may affect the prognosis.
Topics: Humans; Child; Antithyroid Agents; Retrospective Studies; East Asian People; Graves Disease; Recurrence
PubMed: 36944106
DOI: 10.1530/ETJ-23-0018 -
Journal of Cellular and Molecular... Apr 2023This study tested the hypothesis that Jagged2/Notches promoted the endothelial-mesenchymal transition (endMT)-mediated pulmonary arterial hypertension (PAH) (i.e....
This study tested the hypothesis that Jagged2/Notches promoted the endothelial-mesenchymal transition (endMT)-mediated pulmonary arterial hypertension (PAH) (i.e. induction by monocrotaline [MCT]/63 mg/kg/subcutaneous injection) through increasing the expression of GATA-binding factors which were inhibited by propylthiouracil (PTU) (i.e. 0.1% in water for daily drinking since Day 5 after PAH induction) in rodent. As compared with the control (i.e. HUVECs), the protein expressions of GATAs (3/4/6) and endMT markers (Snail/Zeb1/N-cadherin/vimentin/fibronectin/α-SMA/p-Smad2) were significantly reduced, whereas the endothelial-phenotype markers (CD31/E-cadherin) were significantly increased in silenced JAG2 gene or in silenced GATA3 gene of HUVECs (all p < 0.001). As compared with the control, the protein expressions of intercellular signallings (GATAs [3/4/6], Jagged1/2, notch1/2 and Snail/Zeb1/N-cadherin/vimentin/fibronectin/α-SMA/p-Smad2) were significantly upregulated in TGF-ß/monocrotaline-treated HUVECs that were significantly reversed by PTU treatment (all p < 0.001). By Day 42, the results of animal study demonstrated that the right-ventricular systolic-blood-pressure (RVSBP), RV weight (RVW) and lung injury/fibrotic scores were significantly increased in MCT group than sham-control (SC) that were reversed in MCT + PTU groups, whereas arterial oxygen saturation (%) and vasorelaxation/nitric oxide production of PA exhibited an opposite pattern of RVW among the groups (all p < 0.0001). The protein expressions of hypertrophic (ß-MHC)/pressure-overload (BNP)/oxidative-stress (NOX-1/NOX-2) biomarkers in RV and the protein expressions of intercellular signalling (GATAs3/4/6, Jagged1/2, notch1/2) and endMT markers (Snail/Zeb1/N-cadherin/vimentin/fibronectin/TGF-ß/α-SMA/p-Smad2) in lung parenchyma displayed an identical pattern of RVW among the groups (all p < 0.0001). Jagged-Notch-GATAs signalling, endMT markers and RVSBP that were increased in PAH were suppressed by PTU.
Topics: Animals; Pulmonary Arterial Hypertension; Fibronectins; Vimentin; Up-Regulation; Receptors, Notch; Serrate-Jagged Proteins; Monocrotaline; Familial Primary Pulmonary Hypertension
PubMed: 36942326
DOI: 10.1111/jcmm.17723 -
Endocrinology and Metabolism (Seoul,... Apr 2023
Topics: Humans; Propylthiouracil; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Vasculitis; Agranulocytosis
PubMed: 36914241
DOI: 10.3803/EnM.2022.1643 -
Veterinary Sciences Feb 2023Thyroid hormones play an important role in the modeling of neural networks in the brain. Besides its metabolic effects, thyroid dysfunction, and hypothyroidism in...
Thyroid hormones play an important role in the modeling of neural networks in the brain. Besides its metabolic effects, thyroid dysfunction, and hypothyroidism in particular, is frequently associated with cognitive decline and depressive-like behavior. The current study aimed to examine the changes in behavior, cognition, and memory in rats with propylthiouracil-induced overt hypothyroidism. The behavior and cognition were assessed using the open field test, T-maze, and novel object recognition test. We found significant differences in the behavioral patterns of the hypothyroid animals showing a reduction in locomotor activity, frequency of rearing, and impaired memory function compared to the euthyroid controls. As serotonin is an essential biomarker regulating cognition and mood, we tried to modulate the serotonin mediation in hypothyroid animals through tryptophan administration. Treatment with 5-hydroxy-tryptophan (5-OH-TRP) intraperitoneally for 10 days or directly into the hippocampus as a single injection led to attenuation of the hypothyroidism-induced cognitive and memory decline. A staggering amount of research is suggesting that the common denominators in the pathophysiology of depression and the behavior changes in hypothyroidism are the hippocampal complex and the distorted serotonin metabolism. In our study, it was observed a significant alleviation of cognitive impairment and an improvement of memory performance in hypothyroid rats after 5-OH-TRP administration. Current results are promising and may serve as groundwork for further investigation of functional and structural changes in the hippocampus during a hypothyroid state, and in particular, the effects of serotonin mediation in hypothyroid-associated depressive-like behavior.
PubMed: 36851426
DOI: 10.3390/vetsci10020122 -
Frontiers in Endocrinology 2023Thyroid hormone (TH) action controls brain development in a spatiotemporal manner. Previously, we demonstrated that perinatal hypothyroidism led to formation of a...
Thyroid hormone (TH) action controls brain development in a spatiotemporal manner. Previously, we demonstrated that perinatal hypothyroidism led to formation of a periventricular heterotopia in developing rats. This heterotopia occurs in the posterior telencephalon, and its formation was preceded by loss of radial glia cell polarity. As radial glia mediate cell migration and originate in a progenitor cell niche called the ventricular zone (VZ), we hypothesized that TH action may control cell signaling in this region. Here we addressed this hypothesis by employing laser capture microdissection and RNA-Seq to evaluate the VZ during a known period of TH sensitivity. Pregnant rats were exposed to a low dose of propylthiouracil (PTU, 0.0003%) through the drinking water during pregnancy and lactation. Dam and pup THs were quantified postnatally and RNA-Seq of the VZ performed in neonates. The PTU exposure resulted in a modest increase in maternal thyroid stimulating hormone and reduced thyroxine (T4). Exposed neonates exhibited hypothyroidism and T4 and triiodothyronine (T3) were also reduced in the telencephalon. RNA-Seq identified 358 differentially expressed genes in microdissected VZ cells of hypothyroid neonates as compared to controls (q-values ≤0.05). Pathway analyses showed processes like maintenance of the extracellular matrix and cytoskeleton, cell adhesion, and cell migration were significantly affected by hypothyroidism. Immunofluorescence also demonstrated that collagen IV, F-actin, radial glia, and adhesion proteins were reduced in the VZ. Immunohistochemistry of integrin αvβ3 and isoforms of both thyroid receptors (TRα/TRβ) showed highly overlapping expression patterns, including enrichment in the VZ. Taken together, our results show that TH action targets multiple components of cell junctions in the VZ, and this may be mediated by both genomic and nongenomic mechanisms. Surprisingly, this work also suggests that the blood-brain and blood-cerebrospinal fluid barriers may also be affected in hypothyroid newborns.
Topics: Pregnancy; Female; Rats; Animals; Animals, Newborn; Thyroxine; Antithyroid Agents; Thyroid Hormones; Hypothyroidism; Brain; Intercellular Junctions
PubMed: 36843608
DOI: 10.3389/fendo.2023.1090081 -
Internal Medicine (Tokyo, Japan) Oct 2023A 38-year-old woman with untreated Graves' disease was admitted to our hospital because of headache and diplopia for 3 months. A neuro-ophthalmic examination showed...
A 38-year-old woman with untreated Graves' disease was admitted to our hospital because of headache and diplopia for 3 months. A neuro-ophthalmic examination showed bilateral papilledema and abducens nerve paralysis. The cerebrospinal fluid pressure was extremely high. Brain magnetic resonance imaging showed cerebral venous thrombosis in the superior sagittal and right transverse and sigmoid sinuses. Laboratory investigations revealed elevated factor VIII and von Willebrand factor levels. The patient recovered after propylthiouracil and anticoagulation therapy. We herein report a rare case of cerebral venous thrombosis with hyperthyroidism presenting as chronic isolated intracranial hypertension. Hyperthyroidism can induce a hypercoagulable state and lead to venous thromboembolism.
Topics: Female; Humans; Adult; Hyperthyroidism; Intracranial Thrombosis; Intracranial Hypertension; Graves Disease; Venous Thrombosis; Sinus Thrombosis, Intracranial
PubMed: 36792193
DOI: 10.2169/internalmedicine.1113-22 -
Environment International Feb 2023Neural stem cells in the murine subventricular zone (SVZ) reactivate during postnatal development to generate neurons and glia throughout adulthood. We previously...
Neural stem cells in the murine subventricular zone (SVZ) reactivate during postnatal development to generate neurons and glia throughout adulthood. We previously demonstrated that a postnatal thyroid hormone (TH) peak orchestrates this remodelling, rendering this process vulnerable to endocrine disruption. We exposed mice to 2 or 200 µg/kg bw/day of the bisphenol A-replacement and suspected TH-disruptor bisphenol F (BPF) in the drinking water, from embryonic day 15 to postnatal day 21 (P21). In parallel, one group was exposed to the TH-synthesis blocker propylthiouracil (0.15 % PTU). In contrast to PTU, BPF exposure did not affect serum TH levels at P15, P21 or P60. RNA-seq on dissected SVZs at P15 revealed dysregulated neurodevelopmental genes in all treatments, although few overlapped amongst the conditions. We then investigated the phenotype at P60 to analyse long-term consequences of transient developmental exposure. As opposed to hypothyroid conditions, and despite dysregulated oligodendrogenesis-promoting genes in the P15 SVZ exposed to the highest dose of BPF, immunostainings for myelin and OLIG2/CC1 showed no impact on global myelin content nor oligodendrocyte maturation in the P60 corpus callosum, apart from a reduced thickness. The highest dose did reduce numbers of newly generated SVZ-neuroblasts with 22 %. Related to this were behavioural alterations. P60 mice previously exposed to the highest BPF dose memorized an odour less well than control animals did, although they performed better than PTU-exposed animals. All mice could discriminate new odours, but all exposed groups showed less interest in social odours. Our data indicate that perinatal exposure to low doses of BPF disrupts postnatal murine SVZ remodelling, and lowers the adult neuron/oligodendroglia output, even after exposure had been absent for 40 days. These anomalies warrant further investigation on the potential harm of alternative bisphenol compounds for human foetal brain development.
Topics: Pregnancy; Female; Animals; Mice; Adult; Humans; Neural Stem Cells; Neurons; Benzhydryl Compounds; Phenols; Thyroid Hormones
PubMed: 36706583
DOI: 10.1016/j.envint.2023.107770 -
BMC Endocrine Disorders Jan 2023Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as Drug-induced hypersensitivity syndrome (DiHS), is a severe adverse drug reaction....
BACKGROUND
Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as Drug-induced hypersensitivity syndrome (DiHS), is a severe adverse drug reaction. Propylthiouracil, a member of thiouracils group, is widely used in medical treatment of hyperthyroidism. Propylthiouracil is associated with multiple adverse effects such as rash, agranulocytosis hepatitis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, but rarely triggers DRESS/DiHS syndrome. Here, we describe a severe case of propylthiouracil-induced DRESS/DiHS syndrome.
CASE PRESENTATION
A 38-year-old female was treated with methimazole for hyperthyroidism at first. 4 weeks later, the patient developed elevated liver transaminase so methimazole was stopped. After liver function improved in 2 weeks, medication was switched to propylthiouracil therapy. The patient subsequently developed nausea and rash followed by a high fever, acute toxic hepatitis and multiple organ dysfunction (liver, lung and heart), which lasted for 1 month after propylthiouracil was started. According to the diagnostic criteria, the patient was diagnosed of DRESS/DiHS syndrome which was induced by propylthiouracil. As a result, propylthiouracil was immediately withdrawn. And patient was then treated with adalimumab, systematic corticosteroids and plasmapheresis in sequence. Symptoms were finally resolved 4 weeks later.
CONCLUSIONS
Propylthiouracil is a rare cause of the DRESS/DiHS syndrome, which typically consists of severe dermatitis and various degrees of internal organ involvement. We want to emphasize through this severe case that DRESS/DiHS syndrome should be promptly recognized to hasten recovery.
Topics: Female; Humans; Adult; Drug Hypersensitivity Syndrome; Propylthiouracil; Methimazole; Eosinophilia; Exanthema; Hyperthyroidism
PubMed: 36691013
DOI: 10.1186/s12902-023-01273-x -
Journal of the ASEAN Federation of... 2022Thyroid crisis is an emergency due to impaired thyroid function caused by various conditions, particularly infections such as severe acute respiratory syndrome...
Thyroid crisis is an emergency due to impaired thyroid function caused by various conditions, particularly infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that result in the dysfunction of various vital organs. We report a case of a 31-year-old Indonesian female with a 2-year history of hyperthyroidism with elevated thyroid-stimulating hormone (TSH) receptor antibodies. (TRAb) who developed thyroid crisis possibly in association with SARS-CoV-2 pneumonia, sepsis, and disseminated intravascular coagulation (DIC). Prior to admission, she was treated for her hyperthyroidism with propylthiouracil and had been in stable remission for a year. She was admitted to the Emergency Room with complaints of watery stools, icteric sclerae, jaundice, coughing, and shortness of breath. The physical examination showed a World Health Organization (WHO) performance score of 4, delirium, blood pressure within normal limits, tachycardia, tachypnea, axillary temperature of 36.7°C, icteric sclerae, jaundice, and exophthalmos. There was a 3 cm palpable nodule on the right side of the neck. Auscultation of the lungs revealed bilateral pulmonary rales. Abdominal examination noted a palpable liver and enlarged spleen. Laboratory tests showed thrombocytopenia, electrolyte imbalance, hypoalbuminemia and elevated transaminases. The thyroid function tests showed a suppressed TSH level with an elevated free thyroxine (FT4) level. The SARS-CoV-2 polymerase chain reaction (PCR) swab test was positive. Initial patient management was with supportive therapy that included favipiravir and anti-hyperthyroidism medication; however, despite these interventions, her condition continued to deteriorate and she died after a few hours. This case demonstrates no difference in therapy between patients with thyroid crises and COVID-19 or other infections. Proper and timely treatment is important for reducing mortality rates.
Topics: Humans; Female; Adult; Thyroid Crisis; COVID-19; SARS-CoV-2; Thyroid Hormones; Thyrotropin
PubMed: 36578885
DOI: 10.15605/jafes.037.02.19 -
Arthritis Research & Therapy Dec 2022
PubMed: 36517894
DOI: 10.1186/s13075-022-02973-w