scholarly journals Value of Apoptotic, Antiapoptotic, and Cell Proliferation Markers in the Treatment of Graves’ Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jessica Castro de Vasconcelos ◽  
Icléia Siqueira Barreto ◽  
Patrícia Sabino Matos ◽  
Frederico Fernandes Ribeiro Maia ◽  
Marcos Antônio Tambascia ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Beta Blockers ◽  
Expression Level ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Thyroid Cells ◽  
Antiapoptotic Effect ◽  
Hyperthyroid State ◽  
Diagnostic Time ◽  
Lower Expression

To better understand the genesis of autoimmunity in Graves’ disease (GD), it is essential to study the mechanism of apoptosis and cell proliferation in thyroid cells and intrathyroidal lymphocytic infiltrate of GD patients. Methods. A cross sectional, observational study performed by evaluating histopathological samples of thyroidectomy products from GD patients using immunohistochemistry. New histological sections were prepared for immunohistochemical analysis with markers of cell proliferation, antiproliferation, apoptosis, and antiapoptosis. Results. Patients with GD who underwent radioiodine therapy (RIT) had a lower lymphocytic expression level of p27Kip1, and those who took beta-blockers had higher expression levels of BID (BH3-interacting domain) and a lower Ki-67 expression level in thyrocytes than those who did not. The association of a shorter diagnostic time with a lower expression level of MCL-1 in thyroid cells suggests that the hyperthyroid state was related to a lower antiapoptotic effect on thyrocytes. In comparison to patients with GD not using antithyroid drugs (ATD), we found a lower expression level of BID in lymphocytes for those who used ATD. Conclusion. In GD, the hyperthyroid state was associated with a lower antiapoptotic effect on thyroid cells. RIT, beta-blockers, and thionamide act by stimulating apoptosis of thyrocytes by intrathyroidal lymphocytes.

scholarly journals See-Saw Relationship and its Reversal after Immunotherapy in a Case of Graves’ Disease with Coexisting Myasthenia Gravis

2019 ◽  
Vol 10 (01) ◽  
pp. 136-138 ◽  
Author(s):  
Sathish Kumar Mallikarjuna ◽  
S. Sakthi Velayutham ◽  
P. R. Sowmini ◽  
Malcolm K. Jeyaraj ◽  
S. Arunan
Keyword(s):  
Clinical Practice ◽  
Myasthenia Gravis ◽  
Beta Blockers ◽  
Reciprocal Relationship ◽  
The Other ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Immunomodulatory Effects ◽  
The Relationship ◽  
Unique Association

ABSTRACTThe unique association of myasthenia gravis (MG) with Graves' disease in clinical practice emphasizes that one autoimmune disease can coexist with another or many. The relationship between these two entities has remained controversial till date. Some authors have reported a see-saw relationship between these two entities, MG waning with hyperthyroidism and waxing with treatment of hyperthyroidism. Treatment of both these disorders concurrently may be challenging at times as treatment for one entity may worsen the other. The use of beta-blockers and steroids for Graves' disease may worsen myasthenic weakness. Antithyroid drugs can worsen myasthenia probably by immunomodulatory effects. We report a case of Graves' disease coexisting with MG in a reciprocal relationship which was subsequently reversed after immunotherapy.

scholarly journals CRABP2 involvement in a mechanism of Golgi stress and tumor dry matter in non-small cell lung cancer cells via ER dependent Hippo pathway

2021 ◽  
Author(s):  
Jian-Feng Meng ◽  
Ming-Jie Luo
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Hippo Pathway ◽  
Small Cell ◽  
Expression Level ◽  
Control Group ◽  
Nsclc Cell Line ◽  
Small Cell Lung ◽  
Lower Expression ◽  
Er Expression

Objective: The paper aimed to explore the mechanism of cellular retinoic acid binding protein 2 (CRABP2) involvement in Golgi stress and tumor dryness in non-small cell lung cancer (NSCLC) cells through the estrogen receptor (ER) dependent Hippo pathway. Methods: Human NSCLC cell line A549 was purchased from ATCC andcultured in RPMI-1640 with 10% FBS. Attractene reagent was used for plasmid transfection. ER (sh) RNA was designed using RNAi Designer. Seventy-six hours after infection, stable cells were obtained after treated with puromycin for 3 weeks. ER silencing cells (with inhibited ER expression) were compared to the control cells (normal cultured NSCLC cell line A549, CRABP2 normal expression). CRABP2 and ER expression levels were detected by RT-PCR. MTT assay was used to detect cell proliferation, and the cell localization of ER and Golgi was observed by confocal microscopy. The invasion and metastasis of cells were analyzed by Boden chamber invasion and migration assays. Western blotting assays was used for detecting the protein expression of E-cadherin, vimentin, ZO-1 protein and epithelial-mesenchymal transition (EMT) related factors. Results: The lower expression level of mRNA was detected in the ER-silencing group compared to the control group (P<0.05). We also found a higher proliferation level of cells, the number of invading and metastatic cells, the expression of vimentin, p-Lats1T1079, Lats1 and p-YAPS127 mRNA in the control group compared to the ER silencing group (P<0.05). And the expression level of protein kinase RNA-like endoplasmic reticulum kinase (PERK), phosphorylate eukaryotic initiation factor 2 (p-eIF2 alpha), activating transcription factor 4 (ATF4) and C/EBP-homologous protein (CHOP) in the control group was higher than that in the ER silencing group (P<0.05). Adversely, a lower expression level of E-cadherin and ZO-1 protein was found in the control group compared to the ER silencing group (P<0.05). Conclusion: The expression of CRABP2 in NSCLC cells was regulated by ER, and cell proliferation and invasion were regulated by the Hippo pathway. At the same time, it was found that decreased expression of CRABP2 enhanced endoplasmic reticulum/Golgi stress response.

scholarly journals Propylthiouracil-induced agranulocytosis as a rare complication of antithyroid drugs in a patient with Graves’ disease

2019 ◽  
Vol 65 (6) ◽  
pp. 755-760 ◽  
Author(s):  
Patrícia Novais Rabelo ◽  
Paula Novais Rabelo ◽  
Allyne Fernanda de Paula ◽  
Samuel Amanso da Conceição ◽  
Daniela Pultrini Pereira de Oliveira Viggiano ◽  
...  
Keyword(s):  
Total Thyroidectomy ◽  
Beta Blockers ◽  
Rare Complication ◽  
Young Male ◽  
Autoimmune Disorder ◽  
Lithium Carbonate ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Lugol Solution ◽  
Therapeutic Alternatives

SUMMARY INTRODUCTION: Graves’ disease (GD) is an autoimmune disorder characterized by hyperthyroidism. Antithyroid drugs (ATDs) are available as therapy. Agranulocytosis is a rare but potentially fatal complication of this therapy. In this study, we report agranulocytosis induced by propylthiouracil (PTU) in a patient with GD and the difficulties of clinical management. CASE: RNBA, male, 30 years old, with GD, treated with propylthiouracil (PTU). He progressed with pharyngotonsillitis. Then, PTU was suspended and antibiotic, filgrastim, propranolol, and prednisone were initiated. Due to the decompensation of hyperthyroidism, lithium carbonate, dexamethasone, and Lugol's solution were introduced. Total thyroidectomy (TT) was performed with satisfactory postoperative progression. DISCUSSION: We describe here the case of a young male patient with GD. For the treatment of hyperthyroidism, thioamides are effective options. Agranulocytosis induced by ATDs is a rare complication defined as the occurrence of a granulocyte count <500/mm3 after the use of ATDs. PTU was suspended, and filgrastim and antibiotics were prescribed. Radioiodine (RAI) or surgery are therapeutic alternatives. Due to problems with ATD use, a total thyroidectomy was proposed. The preoperative preparation was performed with beta-blocker, glucocorticoid, lithium carbonate, and Lugol solution. Cholestyramine is also an option for controlling hyperthyroidism. TT was performed without postoperative complications. CONCLUSION: Thionamide-induced agranulocytosis is a rare complication. With a contraindication to ATDs, RAI and surgery are definitive therapeutic options in GD. Beta-blockers, glucocorticoids, lithium carbonate, iodine, and cholestyramine may be an adjunctive therapy for hyperthyroidism.

scholarly journals SUN-520 Graves Disease and T3 Thyrotoxicosis: A Case Report

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nishanth thalambedu ◽  
Iqra iqbal ◽  
Shristi khanal ◽  
Muhammad Atique Alam Khan
Keyword(s):  
African American Woman ◽  
Beta Blockers ◽  
American Woman ◽  
Care Physician ◽  
Definitive Treatment ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Free T4 ◽  
Duration Of Action ◽  
Definitive Therapy

Abstract Introduction: Hyperthyroidism is one of the common problems in the world of endocrinology. Identifying the type of thyrotoxicosis is crucial before starting treatment. We present a case of a 37-year-old woman presented with hyperthyroidism and was started on methimazole. Her symptoms persisted and further workup showed T3 thyrotoxicosis. Her symptoms improved after switching her to PTU. She eventually underwent thyroidectomy. Case description: Thirty-seven-year old African American woman presented to her primary care physician(PCP) with symptoms suggestive of hyperthyroidism for three months. Her past medical history is significant for recent delivery one year ago. Her Physical exam is pertinent for hypertension of 160/80 with a heart rate of 120. Her neck is diffusely enlarged with bilateral bruits. Bilateral lid retraction with lid lag was noted along with left lid proptosis. There were no tremors or leg swelling noted. Her Initial workup showed sinus tachycardia in the electrocardiogram. Her TSH level was &lt;0.010 and a free T4 level of 3.48. Ultrasound showed diffuse enlargement of the thyroid gland with no focal nodule. She was started on methimazole 10mg twice daily and metoprolol 25mg twice daily. Three months later, she presented to the emergency room(ER) with tachycardia of 130 and hypertension of 170/85. Work up showed a TSH level of &lt;0.010 and a free T4 level of 3.94. She was compliant with medications. When free T3 levels were checked it turned out to be &gt;30. She was diagnosed with T3 Thyrotoxicosis and was started on propylthiouracil 150mg every 8 hours. Her metoprolol was increased to 50mg every 12 hours. Her symptoms improved and she finally underwent surgery for thyroidectomy. Discussion: Hyperthyroidism is seen in about 1 in 5000 with a strong female predominance. Graves disease, the most common cause of hyperthyroidism is due to excess production of TSH receptor stimulating antibodies. Hyperthyroid patients with graves disease sometimes have a disproportionate increase in serum T3 levels when compared to serum T4. This is thought to be due to increased T3 production or extrathyroidal conversion of T4 to T3. It is very crucial to identify the free hormone levels in a new patient with hyperthyroidism because of the difference in management. Antithyroid drugs are traditionally the first-line treatment option along with beta-blockers prior to definitive therapy like radioactive iodine or thyroidectomy. The main drugs used are methimazole and propylthiouracil(PTU). Methimazole is more commonly used than PTU because of its rapid efficacy, longer duration of action and less adverse effects. For patients with T3 thyrotoxicosis, PTU is preferred as it is known to reduce the peripheral conversion of T4 to T3. Our patient medication was changed from methimazole to PTU, after which she started to notice improvement. She eventually underwent definitive treatment with thyroidectomy.

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

2004 ◽  
Vol 43 (06) ◽  
pp. 217-220 ◽  
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.

Early change of thyroid hormone concentration after 131I treatment in patients with solitary toxic adenoma

2002 ◽  
Vol 41 (04) ◽  
pp. 178-183 ◽  
Author(s):  
V. Fidler ◽  
K. Zaletel ◽  
S. Gaberšček ◽  
S. Hojker ◽  
E. Pirnat
Keyword(s):  
Thyroid Hormone ◽  
Antithyroid Drugs ◽  
Prospective Clinical Study ◽  
Hormone Concentration ◽  
Toxic Adenoma ◽  
Free Triiodothyronine ◽  
Thyroid Cells ◽  
131I Treatment ◽  
Before And After ◽  
Thyroid Hormone Concentration

Summary Aim: In spite of extensive use of 131I for treatment of hyperthyroidism, the results of early outcome are variable. In our prospective clinical study we tested whether 131I induced necrosis causing clinical aggravation of hyperthyroidism and increasing the free thyroid hormone concentration in the serum of patients with solitary toxic adenoma not pretreated with antithyroid drugs. Patients and methods: 30 consecutive patients were treated with 925 MBq 131I. Serum concentration of thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), thyroglobulin (Tg), and interleukin-6 (IL-6) were measured before and after application of 131I. Results: After application of 131I no clinical worsening was observed. FT4 and fT3 concentration did not change significantly within the first five days, whereas both of them significantly decreased after 12 days (p <0.0001). Slight and clinically irrelevant increase in the level of the two thyroid hormones was observed in 9 patients. Furthermore, we observed a prolonged increase in Tg concentration and a transient increase in IL-6 concentration. Conclusion: Neither evidence of any clinical aggravation of hyperthyroidism nor any significant increase in thyroid hormone concentration by 131I induced necrosis of thyroid cells was found. Therefore, the application of 131I may be considered as a safe and effective treatment for patients with hyperthyroidism due to toxic adenoma.

Graves' disease and radioiodine therapy

2008 ◽  
Vol 47 (04) ◽  
pp. 153-166 ◽  
Author(s):  
I. Weber ◽  
W. Eschner ◽  
F. Sudbrock ◽  
M. Schmidt ◽  
M. Dietlein ◽  
...  
Keyword(s):  
Success Rate ◽  
Thyroid Function ◽  
Therapeutic Dose ◽  
Radioiodine Therapy ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Inclusion Criteria ◽  
End Point ◽  
Point Measure ◽  
The Impact

SummaryAim: This study was performed to analyse the impact of the choice of antithyroid drugs (ATD) on the outcome of ablative radioiodine therapy (RIT) in patients with Graves' disease. Patients, material, methods: A total of 571 consecutive patients were observed for 12 months after RIT between July 2001 and June 2004. Inclusion criteria were the confirmed diagnosis of Graves' disease, compensation of hyperthyroidism and withdrawal of ATD two days before preliminary radioiodine-testing and RIT. The intended dose of 250 Gy was calculated from the results of the radioiodine test and the therapeutically achieved dose was measured by serial uptake measurements. The end-point measure was thyroid function 12 months after RIT; success was defined as elimination of hyperthyroidism. The pretreatment ATD was retrospectively correlated with the results achieved. Results: Relief from hyperthyroidism was achieved in 96 % of patients. 472 patients were treated with carbimazole or methimazole (CMI) and 61 with propylthiouracil (PTU). 38 patients had no thyrostatic drugs (ND) prior to RIT. The success rate was equal in all groups (CMI 451/472; PTU 61/61; ND 37/38; p=0.22). Conclusion: Thyrostatic treatment with PTU achieves excellent results in ablative RIT, using an accurate dosimetric approach with an achieved post-therapeutic dose of more than 200 Gy.

Lentiviral-Mediated Overexpression of MicroRNA-141 Promotes Cell Proliferation and Inhibits Apoptosis in Human Esophageal Squamous Cell Carcinoma

2019 ◽  
Vol 14 (2) ◽  
pp. 170-176 ◽  
Author(s):  
Jun-He Zhang ◽  
Hai-Bin Xia
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumour Growth ◽  
Direct Interaction ◽  
Vital Role ◽  
Expression Level ◽  
Luciferase Reporter

Background:Esophageal Carcinoma (EC) is the eighth most common cancer worldwide. Numerous studies have highlighted a vital role of microRNAs (miRNAs) in the development of EC. However, the mechanism of microRNA (miRNA)-141 in Esophageal Squamous Cell Carcinoma (ESCC) remains unknown.Objective:In this study, we explored the effects of miRNA-141 on EC cell proliferation, apoptosis, xenograft tumour growth and their possible mechanisms.Methods :A lentivirus-vector-expressing miRNA-141 was constructed, and a TE-1 cell line of ESCC with a stable expression of miRNA-141 was transfected and screened. The miRNA-141 expression level was detected using qRT-PCR. Effects of miRNA-141 overexpression on cell proliferation and apoptosis were detected using MTT and flow cytometry, respectively. Using a dual-luciferase reporter assay, a direct interaction between miRNA-141 and the 3'-Untranslated Region (UTR) of YAP1 and SOX17 was confirmed. Tumour xenograft experiment in nude mice was used to detect the tumour growth, and the effects of miRNA-141 overexpression on YAP1 and SOX17 were analysed using Western blot.Results:We found that miRNA-141 was highly expressed in TE-1 cells, and miRNA-141 overexpression promoted cell proliferation and inhibited apoptosis. Moreover, the miRNA-141 group showed significantly increased tumour growth ability, luciferase activities and expression levels of YAP1 and SOX17 in the miRNA-141group were significantly down-regulated.Conclusion:miRNA-141 promotes cell proliferation and inhibits apoptosis in ESCC by downregulating the expression level of YAP1 and SOX17, indicating that miRNA-141 may be a potential molecular target for the treatment of ESCC.

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