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18 pages, 930 KB  
Article
Adding L-Carnitine and Selenium to Methimazole in Graves’ Disease: A Prospective Randomized Trial on Thyroid Markers and Quality of Life
by Mattia Rossi, Letizia Meomartino, Marco Zavattaro, Gloria Selvatico, Ruth Rossetto Giaccherino and Loredana Pagano
Nutrients 2025, 17(16), 2693; https://doi.org/10.3390/nu17162693 - 20 Aug 2025
Viewed by 2378
Abstract
Background: The therapeutic response in Graves’ Disease (GD) remains largely unpredictable. Patients often experience persistent symptoms that are poorly correlated with thyroid hormone levels, an undefined treatment duration, and the need for long-term or definitive therapies. Based on the nuclear antagonistic properties [...] Read more.
Background: The therapeutic response in Graves’ Disease (GD) remains largely unpredictable. Patients often experience persistent symptoms that are poorly correlated with thyroid hormone levels, an undefined treatment duration, and the need for long-term or definitive therapies. Based on the nuclear antagonistic properties of L-carnitine (LCT) on thyroid hormone action and the immunomodulatory role of selenium (Se), we aimed to assess the impact of adding a combined LCT and Se supplement to standard methimazole (MMI) therapy on the biochemical profile and quality of life (QoL) of patients with overt GD. Methods: This multicenter prospective randomized trial enrolled 60 consecutive patients with newly diagnosed overt GD. Participants were randomized to receive either standard treatment with MMI alone (Control Group) or MMI plus the combined LCT/Se supplement (Intervention Group). TSH, fT3, fT4, and TSH–receptor antibodies (TRAb) levels were evaluated every two months for up to 24 months or until spontaneous remission or definitive therapy. At each visit, patients completed a symptom questionnaire addressing the frequency of typical thyrotoxic symptoms. Results: No significant differences were observed between groups in the trend or time-to-normalization of TSH, fT3, and fT4 levels. However, the Intervention Group reached TRAb negativity significantly earlier (HR = 2.35 (1.14–4.81), p = 0.016), with a synergistic interaction with MMI therapy. MMI requirements were consistently lower in the Intervention Group, both in average dosage (p = 0.013) and cumulative dose (p = 0.020). The rate of spontaneous remission was significantly higher (OR = 11.22 (3.35–46.11), p < 0.001). Overall symptom burden did not differ significantly between groups; however, the supplement exerted an independent effect in reducing the severity of tremor, irritability, mood lability, heat intolerance, and exertional dyspnea. Conclusions: Our findings suggest the clinical benefits of adding combined LCT and Se supplementation to MMI in the treatment of overt GD, including shorter disease duration, lower cumulative MMI exposure and earlier TRAb normality, that could positively influence TRAb-related prognostic outcomes. Full article
(This article belongs to the Section Nutrition and Metabolism)
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18 pages, 6054 KB  
Article
Mitotic Activity, Cell Survival, and Neuronal Differentiation in the Hilus of the Dentate Gyrus Under Physiological and Hypothyroid Conditions in Adult Wistar Rats
by Karla Sánchez-Huerta, Ana Karen García-Juárez, Lía Diana Colmenero-Rodríguez, Yuliana García-Martínez and Jorge Pacheco-Rosado
Cells 2025, 14(14), 1112; https://doi.org/10.3390/cells14141112 - 19 Jul 2025
Viewed by 488
Abstract
The adult rodent hippocampus is capable of maintaining its capacity to generate new neurons in the subgranular zone (SGZ) of the dentate gyrus (DG). Interestingly, proliferative cells have also been described in the hilus. The involvement of the hilar neurogenesis process in hippocampal [...] Read more.
The adult rodent hippocampus is capable of maintaining its capacity to generate new neurons in the subgranular zone (SGZ) of the dentate gyrus (DG). Interestingly, proliferative cells have also been described in the hilus. The involvement of the hilar neurogenesis process in hippocampal physiology is unknown. Thyroid hormones (THs) are necessary for the survival of postmitotic progenitor cells, neuroblasts, and immature granule neurons in the SGZ. In contrast, evidence concerning the role of THs in the hilar neurogenesis process is limited. The present study characterized the mitotic activity, cell survival, and neuronal differentiation of hilar neurogenesis under physiological and hypothyroid conditions and compared them with those of the granular layer (GL) and the SGZ of the DG in adult Wistar rats. We found that, under physiological conditions, the hilus harbors fewer proliferative cells than the neurogenic zone (GL/SGZ) does, with a rate of cell survival of 18.9% and a rate of differentiation into granular neurons of 19%. Interestingly, hypothyroidism provokes decreased cell proliferation and an increased rate of cell survival without affecting neuronal differentiation. These effects induced by hypothyroidism in the hilus were different or inclusive, contrary to those observed in the neurogenic zone. Full article
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14 pages, 3810 KB  
Article
Methimazole-Induced Hypothyroidism Increases the Content of Glycogen and Changes the Expression of LDH, GLUT4, and Aromatase in the Pregnant Uterus of Rabbits
by Marlen Espindola-Lozano, Maribel Méndez-Tepepa, Marlenne Castillo-Romano, Rubicela Rojas-Juárez, Leticia Nicolás-Toledo, Jorge Rodríguez-Antolín, Francisco Castelán and Estela Cuevas-Romero
Metabolites 2025, 15(2), 82; https://doi.org/10.3390/metabo15020082 - 30 Jan 2025
Cited by 1 | Viewed by 1079
Abstract
Objective: To determine the impact of hypothyroidism on uterine glycogen accumulation during pregnancy. Methods: Non-pregnant and pregnant (days 5, 10, and 20) rabbits were grouped into control and methimazole (MMI) groups. In rabbits, serum concentrations of thyroxine (T4), triiodothyronine, glucose, insulin, [...] Read more.
Objective: To determine the impact of hypothyroidism on uterine glycogen accumulation during pregnancy. Methods: Non-pregnant and pregnant (days 5, 10, and 20) rabbits were grouped into control and methimazole (MMI) groups. In rabbits, serum concentrations of thyroxine (T4), triiodothyronine, glucose, insulin, progesterone, and estradiol were quantified. In uterine inter- and implantation sites, the glycogen content and expression of lactate dehydrogenase (LDH), GLUT4, and aromatase were quantified via Western blot. Fetuses’ characteristics at 20 days of pregnancy were analyzed. Two-way ANOVA was used to compare variables between groups. Results: Pregnancy reduced T4 concentrations but not T3. In virgin groups, MMI treatment significantly reduced the concentrations of T4 and T3 and increased the expression of GLUT4 and aromatase in the uterus compared to the control group. In pregnant groups, T4, T3, glucose, insulin, progesterone, and estradiol levels were similar between control and MMI-treated rabbits. Compared to controls, MMI treatment in pregnant rabbits (a) reduced GLUT4 expression on inter-implantation sites on day 5; (b) increased glycogen content on implantation sites but reduced GLUT4 expression on inter-and implantation sites on day 10; (c) increased glycogen content and LDH and aromatase expression but reduced GLUT4 on inter-implantation sites; and (d) increased glycogen content and the expression of LDH, GLUT4, and aromatase on day 20 on implantation sites. Moreover, the fetus characteristics were similar between groups. Conclusions: MMI-induced hypothyroidism is associated with changes in the uterine content of glycogen and the expression of LDH, GLUT4, and aromatase during pregnancy. Full article
(This article belongs to the Special Issue Glucose Metabolism in Pregnancy)
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14 pages, 2633 KB  
Article
Methimazole-Related Substances: Structural Characterization and In Silico Toxicity Assessment
by Leo Štefan, Ivica Đilović, Lara Saftić Martinović, Robert Vianello and Ana Čikoš
Crystals 2024, 14(12), 1073; https://doi.org/10.3390/cryst14121073 - 12 Dec 2024
Viewed by 1576
Abstract
The continuous tightening of pharmaceutical regulations forces drug manufacturers to unambiguously characterize the substances related to the active pharmaceutical ingredients (API). Here, we report the synthesis, complete spectroscopic, chromatographic, thermal and computational characterization, as well as in silico prediction of bacterial mutagenicity for [...] Read more.
The continuous tightening of pharmaceutical regulations forces drug manufacturers to unambiguously characterize the substances related to the active pharmaceutical ingredients (API). Here, we report the synthesis, complete spectroscopic, chromatographic, thermal and computational characterization, as well as in silico prediction of bacterial mutagenicity for two previously reported but never fully characterized impurities of methimazole. Additionally, their structures were analyzed by single-crystal X-ray diffraction. 1-Methyl-(2-methylthio)-1H-imidazole also known as methimazole impurity C, was obtained mainly in the form of the iodide salt (C5H9IN2S) crystallizing in monoclinic space group P21/c. The disulfide (2,2′-disulphanylbis(1-methyl-1H-imidazole)), C8H10N4S2) was obtained in yellow form crystallizing in the monoclinic C2/c space group. Full article
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8 pages, 581 KB  
Guidelines
Approach to Hyperthyroidism
by Raisa Chowdhury, Sena Turkdogan, Jennifer A. Silver, Jessica Hier, Stuart Bursey, Danah Quttaineh, Mark Khoury and Lamiae Himdi
J. Otorhinolaryngol. Hear. Balance Med. 2024, 5(2), 20; https://doi.org/10.3390/ohbm5020020 - 10 Dec 2024
Cited by 1 | Viewed by 6610
Abstract
Background: Hyperthyroidism, characterized by excessive thyroid hormone production, presents in diverse clinical forms, including overt and subclinical disease. Accurate and timely diagnosis is critical to prevent complications such as cardiac dysfunction, osteoporosis, and thyroid storm. Objective: To provide a comprehensive review of the [...] Read more.
Background: Hyperthyroidism, characterized by excessive thyroid hormone production, presents in diverse clinical forms, including overt and subclinical disease. Accurate and timely diagnosis is critical to prevent complications such as cardiac dysfunction, osteoporosis, and thyroid storm. Objective: To provide a comprehensive review of the clinical presentation, diagnostic methods, and management strategies for hyperthyroidism, focusing on current practices, advancements, and challenges in treatment. Methods: This review synthesizes findings from peer-reviewed literature on the diagnosis and management of hyperthyroidism. Results: Thyroid function tests (TFTs) are the cornerstone of hyperthyroidism diagnosis, with suppressed TSH levels and elevated T3 and/or T4 levels confirming overt disease. Thyroid receptor antibodies (TRAb) are critical for diagnosing autoimmune hyperthyroidism and predicting relapse risk. Iodine scintigraphy is utilized in specific cases, such as suspected toxic adenoma or multinodular goiter. Management strategies include beta-blockers for symptomatic relief, though side effects such as bradycardia and fatigue may occur. Antithyroid medications, including methimazole and propylthiouracil, inhibit hormone synthesis, with remission more likely in patients with low TRAb levels and small goiters. Definitive treatments include radioactive iodine therapy (RAI), which effectively reduces thyroid activity but often results in hypothyroidism, and thyroidectomy, a surgical option for large goiters or malignancy, with potential complications like hypocalcemia and recurrent laryngeal nerve injury. Conclusions: The management of hyperthyroidism necessitates a personalized approach integrating diagnostic precision, emerging innovations, and patient-centered care. Full article
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17 pages, 8563 KB  
Article
The Comparison of Catalytic Activity of Carbimazole and Methimazole on Electroreduction of Zinc (II) in Chlorates (VII): Experimental and Molecular Modelling Study
by Jolanta Nieszporek, Tomasz Pańczyk and Krzysztof Nieszporek
Molecules 2024, 29(15), 3455; https://doi.org/10.3390/molecules29153455 - 23 Jul 2024
Cited by 2 | Viewed by 1484
Abstract
With the help of electrochemical methods, including CV and EIS, the influence of methimazole, carbimazole, and the concentration of the supporting electrolyte on the kinetics and mechanism of zinc electroreduction on a mercury electrode was compared and analyzed. Moreover, molecular dynamics simulations of [...] Read more.
With the help of electrochemical methods, including CV and EIS, the influence of methimazole, carbimazole, and the concentration of the supporting electrolyte on the kinetics and mechanism of zinc electroreduction on a mercury electrode was compared and analyzed. Moreover, molecular dynamics simulations of zinc/carbimazole and zinc/methimazole solutions were carried out to determine the effect of drugs on the hydration sphere of Zn2+ ions. It was shown that the electroreduction of Zn2+ in the presence of methimazole and carbimazole occurs in two steps and the first one determines the kinetics of the entire process. The presence of both drugs in the solution and the increase in the concentration of the supporting electrolyte reduce the degree of hydration of the depolarizer ions and the hydration of the electrode surface, what is a factor favoring the rate of electroreduction. Based on theoretical studies, the formation of stable complexes between Zn2+ and the molecules of both drugs in a solution was considered unlikely. However, active complexes can be formed between depolarizer ions and molecules adsorbed at the electrode surface. They constitute a bridge facilitating charge exchange during the electrode reaction, revealing the catalytic abilities of methimazole and carbimazole. In the range of cdrug ≤ 1 × 10−3 mol dm−3, carbimazole is a better catalyst, whereas in the range of cdrug ≥ 5 × 10−3 mol dm−3, it is methimazole. The effectiveness of both compounds in catalyzing the first stage of the electrode reaction increases with the increase in the NaClO4 concentration. Full article
(This article belongs to the Special Issue Novel Studies of Organic Electrosynthesis)
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11 pages, 8345 KB  
Case Report
A Rare Encounter: Unstable Vasospastic Angina Induced by Thyrotoxicosis
by Artiomas Širvys, Arvydas Baranauskas and Povilas Budrys
J. Clin. Med. 2024, 13(11), 3130; https://doi.org/10.3390/jcm13113130 - 27 May 2024
Cited by 1 | Viewed by 1650
Abstract
Coronary artery vasospasm plays a crucial role in the prevalence of unstable angina. Despite common misdiagnosis, there is limited evidence on this topic. Here, we present a rare case of unstable vasospastic angina in a female with severe thyrotoxicosis. Case Report: A [...] Read more.
Coronary artery vasospasm plays a crucial role in the prevalence of unstable angina. Despite common misdiagnosis, there is limited evidence on this topic. Here, we present a rare case of unstable vasospastic angina in a female with severe thyrotoxicosis. Case Report: A 62-year-old female patient was admitted to the cardiac intensive care unit due to crushing chest pain at rest. The patient exhibited ischemic changes on the ECG with a normal troponin I level. Recurrent chest pain prompted urgent coronary angiography, revealing generalized vasospasm of all coronary artery branches including the left main coronary artery. Intracoronary nitroglycerin injection partially alleviated the vasospasm; however, there was a persistent stenosis in the left main artery. Subsequent intravascular ultrasound demonstrated an anatomically normal left main artery. Post-procedure, laboratory tests revealed undetectable levels of thyroid-stimulating hormone and thyroid hormones above the detectable level. The patient was initiated on methimazole and discharged symptom-free, expecting a good prognosis under conservative management. Conclusions: Clinically significant coronary vasospasm triggered by thyrotoxicosis remains a rarity in clinical practice, often posing diagnostic challenges. This case emphasizes the significance of intracoronary nitroglycerin and intravascular ultrasound in discerning the etiology of coronary lesions seen on angiography. We advocate for these techniques to optimize invasive coronary artery diagnostics, enabling the selection of the appropriate treatment strategies and improving long-term prognosis. Full article
(This article belongs to the Section Cardiology)
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17 pages, 367 KB  
Review
Human Leucocyte Antigen Genetics in Idiosyncratic Drug-Induced Liver Injury with Evidence Based on the Roussel Uclaf Causality Assessment Method
by Rolf Teschke and Gaby Danan
Medicines 2024, 11(4), 9; https://doi.org/10.3390/medicines11040009 - 11 Apr 2024
Cited by 5 | Viewed by 3086
Abstract
The human leucocyte antigen (HLA) allele variability was studied in cohorts of patients with idiosyncratic drug-induced liver injury (iDILI). Some reports showed an association between HLA genetics and iDILI, proposing HLA alleles as a potential risk factor for the liver injury. However, the [...] Read more.
The human leucocyte antigen (HLA) allele variability was studied in cohorts of patients with idiosyncratic drug-induced liver injury (iDILI). Some reports showed an association between HLA genetics and iDILI, proposing HLA alleles as a potential risk factor for the liver injury. However, the strength of such assumptions heavily depends on the quality of the iDILI diagnosis, calling for a thorough analysis. Using the PubMed database and Google Science, a total of 25 reports of case series or single cases were retrieved using the terms HLA genes and iDILI. It turned out that in 10/25 reports (40%), HLA genetics were determined in iDILI cases, for which no causality assessment method (CAM) was used or a non-validated tool was applied, meaning the findings were based on subjective opinion, providing disputable results and hence not scoring individual key elements. By contrast, in most iDILI reports (60%), the Roussel Uclaf Causality Assessment Method (RUCAM) was applied, which is the diagnostic algorithm preferred worldwide to assess causality in iDILI cases and represents a quantitative, objective tool that has been well validated by both internal and external DILI experts. The RUCAM provided evidence-based results concerning liver injury by 1 drug class (antituberculotics + antiretrovirals) and 19 different drugs, comprising 900 iDILI cases. Among the top-ranking drugs were amoxicillin–clavulanate (290 cases, HLA A*02:01 or HLA A*30:02), followed by flucloxacillin (255 cases, HLA B*57:01), trimethoprim–sulfamethoxazole (86 cases, HLA B*14:01 or HLA B*14:02), methimazole (40 cases, HLA C*03:02), carbamazepine (29 cases, HLA A*31:01), and nitrofurantoin (26 cases, HLA A*33:01). In conclusion, the HLA genetics in 900 idiosyncratic drug-induced liver injury cases with evidence based on the RUCAM are available for studying the mechanistic steps leading to the injury, including metabolic factors through cytochrome P450 isoforms and processes that activate the innate immune system to the adaptive immune system. Full article
(This article belongs to the Special Issue The 10th Anniversary of Medicines: Future Directions)
14 pages, 3648 KB  
Article
A Molecularly Imprinted Fluorescence Sensor Based on Upconversion-Nanoparticle-Grafted Covalent Organic Frameworks for Specific Detection of Methimazole
by Yan Liu, Tian Zhao, Shuzhen Li, Yichuan Cao and Guozhen Fang
Processes 2024, 12(3), 626; https://doi.org/10.3390/pr12030626 - 21 Mar 2024
Cited by 1 | Viewed by 1978
Abstract
Rapid detection and sensitive analysis of MMZ is of great importance for food safety. Herein, a fluorescent molecularly imprinted sensor based on upconversion nanoparticles (UCNPs) grafted onto covalent organic frameworks (COFs) was designed for the detection of MMZ. COFs with a high specific [...] Read more.
Rapid detection and sensitive analysis of MMZ is of great importance for food safety. Herein, a fluorescent molecularly imprinted sensor based on upconversion nanoparticles (UCNPs) grafted onto covalent organic frameworks (COFs) was designed for the detection of MMZ. COFs with a high specific surface area and excellent affinity serve as substrates for grafting of UCNPs, which can inhibit the aggregation burst of UCNPs and improve the mass transfer rate of the sensor. Through a series of characterizations, it was found that the proposed UCNP-grafted COFs@MIP-based sensor had good optical stability, high adsorption efficiency, strong anti-interference ability, and high sensitivity owing to the integration of the advantages of UCNPs, COFs and MIPs. Under the optimal conditions, a good linear relationship was presented between the fluorescence intensity of UCNP-grafted COFs@MIPs and the methimazole concentration in the range of 0.05–3 mg L−1, and the detection limit was 3 μg L−1. The as-prepared UCNP-grafted COFs@MIPs were successfully applied for the detection of MMZ in actual samples, and the results were relevant with those determined by high-performance liquid chromatography. The sensor has good sensitivity, reusability, and high selectivity, which are highly valuable in the rapid analysis and detection of food safety. Full article
(This article belongs to the Section Materials Processes)
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16 pages, 3890 KB  
Article
Morphological and Transcriptomic Analyses Reveal the Toxicological Mechanism and Risk of Nitrate Exposure in Bufo gargarizans Embryos
by Lei Xie, Ziyi Niu, Shimin Xiao, Hongyuan Wang and Yongpu Zhang
Animals 2024, 14(6), 961; https://doi.org/10.3390/ani14060961 - 20 Mar 2024
Cited by 2 | Viewed by 1697
Abstract
In recent years, nitrate (NO3-N) pollution in water bodies has been increasing due to the excessive use of nitrogen-based fertilizers. Exposure to NO3-N during the development of amphibian embryos may have lasting effects on the growth and development of [...] Read more.
In recent years, nitrate (NO3-N) pollution in water bodies has been increasing due to the excessive use of nitrogen-based fertilizers. Exposure to NO3-N during the development of amphibian embryos may have lasting effects on the growth and development of individuals and even threaten their survival, but the toxicity mechanism of NO3-N in amphibian embryos prior to thyroid morphogenesis remains unclear. In the present study, Bufo gargarizans was selected as the model organism to investigate the toxic effects of 10 mg/L and 100 mg/L NO3-N exposure (N10 and N100) on amphibian embryos using methimazole (MMI) and exogenous thyroxine (T4) as the reference groups. We found that T4, MMI, N10 and N100 inhibited B. gargarizans embryo growth and development, with MMI and N100 showing the earliest and strongest effects. Transcriptome analysis revealed that MMI and NO3-N (especially N100) significantly downregulated genes related to thyroid morphogenesis and cholesterol metabolism, while upregulating genes related to inflammation and apoptosis. Together, these results contribute to a deeper understanding of the complex mechanisms by which NO3-N disrupts B. gargarizans embryonic development, reveal the potential risks of NO3-N pollution to other aquatic organisms, and provide insights into the conservation of a broader ecosystem. Full article
(This article belongs to the Section Ecology and Conservation)
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9 pages, 270 KB  
Case Report
Autoimmune Implications in a Patient with Graves’ Hyperthyroidism, Pre-eclampsia with Severe Features, and Primary Aldosteronism
by Benjamin Lin, Lauren Robinson, Basem Soliman, Jill Gulizia and Stephen Usala
Medicina 2024, 60(1), 170; https://doi.org/10.3390/medicina60010170 - 17 Jan 2024
Viewed by 3263
Abstract
Background and Objectives: Graves’ disease (GD) and primary aldosteronism (PA) are two pathologies that can cause significant morbidity and mortality. GD is mediated by autoantibodies, and recent studies have shown autoantibody involvement in the pathophysiology behind both PA and pre-eclampsia. The coexistence [...] Read more.
Background and Objectives: Graves’ disease (GD) and primary aldosteronism (PA) are two pathologies that can cause significant morbidity and mortality. GD is mediated by autoantibodies, and recent studies have shown autoantibody involvement in the pathophysiology behind both PA and pre-eclampsia. The coexistence of GD and PA, however, is reportedly rare. This report describes a unique case of Graves’ hyperthyroidism and concomitant PA in a patient with a history of pre-eclampsia with severe features. Case Presentation: The patient presented at 17 weeks pregnancy with mild hyperthyroidism, negative TSH receptor antibodies, and a low level of thyroid-stimulating immunoglobulins (TSI). Her TSH became detectable with normal thyroid hormone levels, and therefore, no anti-thyroid medication was administered. At 34 weeks she developed pre-eclampsia with severe features, and a healthy child was delivered; her TSH returned to normal. Seven months after delivery, she presented emergently with severe hyperthyroidism, hypertensive crisis, and a serum potassium of 2.5 mmol/L. Her hypertension was uncontrolled on multiple anti-hypertensives. Both TSI and TSH receptor antibodies were negative. The aldosterone(ng/dL)/renin(ng/mL/h ratio was (13/0.06) = 216.7, and abdominal CT imaging demonstrated normal adrenal glands; thus, a diagnosis of PA was made. Her blood pressure was subsequently controlled with only spironolactone at 50 mg 2xday. Methimazole was started but discontinued because of an allergic reaction. Consequently, a thyroidectomy was performed, and pathology revealed Graves’ disease. The patient remained well on levothyroxine at 125 mcg/day and spironolactone at 50 mg 2xday three months after the thyroidectomy. Conclusions: This patient manifested severe GD with antibodies undetectable by conventional TSI and TSH receptor assays and accelerated hypertension from PA simultaneously. These conditions were successfully treated separately by spironolactone and thyroidectomy. Autoimmune PA was considered likely given the clinical picture. The diagnosis of PA should be considered in hypertension with GD. Full article
(This article belongs to the Section Endocrinology)
10 pages, 1089 KB  
Case Report
Fetal Hyperthyroidism with Maternal Hypothyroidism: Two Cases of Intrauterine Therapy
by Lu Hong, Mary Hoi Yin Tang, Ka Wang Cheung, Libing Luo, Cindy Ka Yee Cheung, Xiaoying Dai, Yanyan Li, Chuqin Xiong, Wei Liang, Wei Xiang, Liangbing Wang, Kelvin Yuen Kwong Chan and Shengmou Lin
Diagnostics 2024, 14(1), 102; https://doi.org/10.3390/diagnostics14010102 - 3 Jan 2024
Cited by 4 | Viewed by 5166
Abstract
Fetal hyperthyroidism can occur secondary to maternal autoimmune hyperthyroidism. The thyroid-stimulating hormone receptor antibody (TRAb) transferred from the mother to the fetus stimulates the fetal thyroid and causes fetal thyrotoxicosis. Fetuses with this condition are difficult to detect, especially after maternal Graves disease [...] Read more.
Fetal hyperthyroidism can occur secondary to maternal autoimmune hyperthyroidism. The thyroid-stimulating hormone receptor antibody (TRAb) transferred from the mother to the fetus stimulates the fetal thyroid and causes fetal thyrotoxicosis. Fetuses with this condition are difficult to detect, especially after maternal Graves disease therapy. Here, we present two cases of fetal hyperthyroidism with maternal hypothyroidism and review the assessment and intrauterine therapy for fetal hyperthyroidism. Both women were referred at 22+ and 23+ weeks of gestation with abnormal ultrasound findings, including fetal heart enlargement, pericardial effusion, and fetal tachycardia. Both women had a history of Graves disease while in a state of hypothyroidism with a high titer of TRAb. A sonographic examination showed a diffusely enlarged fetal thyroid with abundant blood flow. Invasive prenatal testing revealed no significant chromosomal aberration. Low fetal serum TSH and high TRAb levels were detected in the cord blood. Fetal hyperthyroidism was considered, and maternal oral methimazole (MMI) was administered as intrauterine therapy, with the slowing of fetal tachycardia, a reduction in fetal heart enlargement, and thyroid hyperemia. During therapy, maternal thyroid function was monitored, and the dosage of maternal levothyroxine was adjusted accordingly. Both women delivered spontaneously at 36+ weeks of gestation, and neonatal hyperthyroidism was confirmed in both newborns. After methimazole and propranolol drug treatment with levothyroxine for 8 and 12 months, both babies became euthyroid with normal growth and development. Full article
(This article belongs to the Special Issue Fetal Medicine: From Basic Science to Prenatal Diagnosis and Therapy)
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10 pages, 277 KB  
Article
Therapeutic Management and Long-Term Outcome of Hyperthyroidism in Patients with Antithyroid-Induced Agranulocytosis: A Retrospective, Multicenter Study
by Carlos García Gómez, Elena Navarro, Victoria Alcázar, Antonio López-Guzmán, Francisco Arrieta, Emma Anda, Betina Biagetti, Fernando Guerrero-Pérez, Carles Villabona, Andrés Ruiz de Assín Valverde, Cristina Lamas, Beatriz Lecumberri, José Antonio Rosado Sierra, Julia Sastre, Juan José Díez and Pedro Iglesias
J. Clin. Med. 2023, 12(20), 6556; https://doi.org/10.3390/jcm12206556 - 16 Oct 2023
Cited by 1 | Viewed by 5645
Abstract
Background: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism. Methodology: Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The [...] Read more.
Background: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism. Methodology: Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves’ disease (n = 21), amiodarone-induced thyrotoxicosis (n = 7), and hyperfunctioning multinodular goiter (n = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil. Results: The median (IQR) time to development of agranulocytosis was 6.0 (4.0–11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves’ disease), and two patients died of septic shock secondary to AIA. Conclusions: AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously. Full article
13 pages, 2307 KB  
Article
Preventive Effect of Molecular Iodine in Pancreatic Disorders from Hypothyroid Rabbits
by Julia Rodríguez-Castelán, Evangelina Delgado-González, Esteban Rodríguez-Benítez, Francisco Castelán, Estela Cuevas-Romero, Brenda Anguiano, Michael C. Jeziorski and Carmen Aceves
Int. J. Mol. Sci. 2023, 24(19), 14903; https://doi.org/10.3390/ijms241914903 - 5 Oct 2023
Cited by 2 | Viewed by 1974
Abstract
Pancreatic alterations such as inflammation and insulin resistance accompany hypothyroidism. Molecular iodine (I2) exerts antioxidant and differentiation actions in several tissues, and the pancreas is an iodine-uptake tissue. We analyzed the effect of two oral I2 doses on pancreatic disorders [...] Read more.
Pancreatic alterations such as inflammation and insulin resistance accompany hypothyroidism. Molecular iodine (I2) exerts antioxidant and differentiation actions in several tissues, and the pancreas is an iodine-uptake tissue. We analyzed the effect of two oral I2 doses on pancreatic disorders in a model of hypothyroidism for 30 days. Adult female rabbits were divided into the following groups: control, moderate oral dose of I2 (0.2 mg/kg, M-I2), high oral dose of I2 (2.0 mg/kg, H-I2), oral dose of methimazole (MMI; 10 mg/kg), MMI + M-I2,, and MMI + H-I2. Moderate or high I2 supplementation did not modify circulating metabolites or pancreatic morphology. The MMI group showed reductions of circulating thyroxine (T4) and triiodothyronine (T3), moderate glucose increments, and significant increases in cholesterol and low-density lipoproteins. Acinar fibrosis, high insulin content, lipoperoxidation, and overexpression of GLUT4 were observed in the pancreas of this group. M-I2 supplementation normalized the T4 and cholesterol, but T3 remained low. Pancreatic alterations were prevented, and nuclear factor erythroid-2-related factor-2 (Nrf2), antioxidant enzymes, and peroxisome proliferator-activated receptor gamma (PPARG) maintained their basal values. In MMI + H-I2, hypothyroidism was avoided, but pancreatic alterations and low PPARG expression remained. In conclusion, M-I2 supplementation reestablishes thyronine synthesis and diminishes pancreatic alterations, possibly related to Nrf2 and PPARG activation. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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14 pages, 5794 KB  
Article
Effect of Combined Levothyroxine (L-T4) and 3-Iodothyronamine (T1AM) Supplementation on Memory and Adult Hippocampal Neurogenesis in a Mouse Model of Hypothyroidism
by Grazia Rutigliano, Andrea Bertolini, Nicoletta Grittani, Sabina Frascarelli, Vittoria Carnicelli, Chiara Ippolito, Stefania Moscato, Letizia Mattii, Claudia Kusmic, Alessandro Saba, Nicola Origlia and Riccardo Zucchi
Int. J. Mol. Sci. 2023, 24(18), 13845; https://doi.org/10.3390/ijms241813845 - 8 Sep 2023
Cited by 4 | Viewed by 2292
Abstract
Mood alterations, anxiety, and cognitive impairments associated with adult-onset hypothyroidism often persist despite replacement treatment. In rodent models of hypothyroidism, replacement does not bring 3-iodothyronamine (T1AM) brain levels back to normal. T1AM is a thyroid hormone derivative with cognitive [...] Read more.
Mood alterations, anxiety, and cognitive impairments associated with adult-onset hypothyroidism often persist despite replacement treatment. In rodent models of hypothyroidism, replacement does not bring 3-iodothyronamine (T1AM) brain levels back to normal. T1AM is a thyroid hormone derivative with cognitive effects. Using a pharmacological hypothyroid mouse model, we investigated whether augmenting levothyroxine (L-T4) with T1AM improves behavioural correlates of depression, anxiety, and memory and has an effect on hippocampal neurogenesis. Hypothyroid mice showed impaired performance in the novel object recognition test as compared to euthyroid mice (discrimination index (DI): 0.02 ± 0.09 vs. 0.29 ± 0.06; t = 2.515, p = 0.02). L-T4 and L-T4+T1AM rescued memory (DI: 0.27 ± 0.08 and 0.34 ± 0.08, respectively), while T1AM had no effect (DI: −0.01 ± 0.10). Hypothyroidism reduced the number of neuroprogenitors in hippocampal neurogenic niches by 20%. L-T4 rescued the number of neuroprogenitors (mean diff = 106.9 ± 21.40, t = 4.99, pcorr = 0.003), while L-T4+T1AM produced a 30.61% rebound relative to euthyroid state (mean diff = 141.6 ± 31.91, t = 4.44, pcorr = 0.004). We performed qPCR analysis of 88 genes involved in neurotrophic signalling pathways and found an effect of treatment on the expression of Ngf, Kdr, Kit, L1cam, Ntf3, Mapk3, and Neurog2. Our data confirm that L-T4 is necessary and sufficient for recovering memory and hippocampal neurogenesis deficits associated with hypothyroidism, while we found no evidence to support the role of non-canonical TH signalling. Full article
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