Hyperfunctioning Thyroid Nodules in Toxic Multinodular Goiter Share Activating Thyrotropin Receptor Mutations with Solitary Toxic Adenoma

Abstract INTRODUCTION The diagnosis of Graves′disease (GD) is likely when patient presents hyperthyroidism, symmetrical goiter and orbitopathy and further evaluation is unnecessary. Nevertheless patient with nodular thyroid or in the absence of clinical orbitopathy, measurement of TSH receptor antibodies (TRAb) is recommended to distinguish GD from toxic multinodular goiter, toxic adenoma and other etiologies. Radioiodine uptake (RAIU) also helps to diagnosis when TRAb is unavailable. Third generation TRAb assays measure all types of TSH receptor antibodies: stimulating, blocking and neutral with an excellent sensitivity and specificity for GD diagnosis. Recently, an automated bioassay for the thyroid stimulating immunoglobulin (TSI) was introduced to improve GD diagnosis. OBJECTIVE To analyze clinical performance of TSI and compare with TRAb assay for GD diagnosis. MATERIAL AND METHODS Serum samples of 117 patients with thyrotoxicosis due to GD, toxic multinodular goiter and toxic adenoma were runned simultaneously in two analytical system commercially available. TRAb was analyzed by Elecsys Anti-TSHR assay (Roche Diagnostics, Germany) in a Cobase411 analyzer (Roche Diagnostics, Germany) and results, according to the manufacturer interval reference, were negative if < 1.75 IU/L (analytical range: 0.3 to 40 IU/L). TSI was measured by Immulite TSI assay (Siemens Healthcare, UK) in Immulite XPi 2000 and results, according to the manufacturer interval reference, were negative if < 0.55 IU/L (analytical range: 0.1 to 40 IU/L). Clinical diagnoses of thyrotoxicosis were determined according to ATA guideline (2016). Statistical analyses were performed using SPSS and MedCalc softwares. Comparison were evaluated by regression equations and were considered significant when p values were < .05. RESULTS From 2017 to 2019 a total of 312 serum samples from 117 patients (96 females) were evaluated with mean age 49.5 ±15.8 years-old (18 to 90 yrs). We excluded 26 results above the analytical measurement range of both assays. A high degree correlation was observed with a slope of 0.647 and an intercept -.094 IU/L. Spearman correlation coefficient was 0.858 (p < 0.0001, 95% CI 0.825 to 0.886). TSI assay had higher sensibility and negative predictive value compared to TRAb (95.6% vs 88.5% and 83.6% vs 54.8%, respectively) but lower specificity and positive predictive value (90.3% vs 100% and 97.5% vs 100%, respectively). The results of TSI assay showed good agreement with those of the TRAb assay (k=0.74). A total of 31 samples were discordant, favoring to TSI assay in all but one case of GD according to clinical diagnosis (TRAb positive and TSI negative). CONCLUSION TSI assay showed an excellent performance for GD diagnosis with a better sensibility than TRAb assay.

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Minimally Invasive Radiofrequency Ablation for Large Thyroid Toxic Adenoma

Acta Medica Bulgarica ◽

10.2478/amb-2019-0031 ◽

2019 ◽

Vol 46 (3) ◽

pp. 50-52

Author(s):

M. Belitova ◽

S. Ivanov ◽

Ts. Marinov ◽

T. Popov ◽

R. Pandev

Keyword(s):

Radiofrequency Ablation ◽

Treatment Option ◽

Multinodular Goiter ◽

Thyroid Nodules ◽

Percutaneous Treatment ◽

Thyroid Stimulating Hormone ◽

Treatment Modalities ◽

Toxic Adenoma ◽

Effective Treatment Option ◽

Thyroid Lobectomy

Abstract Background: Most thyroid nodules are benign and do not need intervention. Toxic adenoma and toxic multinodular goiter (MNG) are common causes of hyperthyroidism, second in prevalence only to Graves’ disease. Toxic adenoma and MNG are the result of focal or diffuse hyperplasia of thyroid follicular cells whose functional capacity is independent from regulation by the thyroid stimulating hormone (TSH). When conservative treatment modalities fail to ensure an euthyroid state, surgical intervention is required, typically surgical left or right thyroid lobectomy. Radiofrequency ablation (RFA) is a new percutaneous treatment option that results in thermal tissue necrosis and fibrosis. As a result of this process, the thyroid nodules shrink. Case presentation: We describe a case of a young woman with a large toxic thyroid adenoma who refused surgery. She was admitted to a one-day surgery unit and underwent radiofrequency ablation under total intravenous anesthesia. Using “moving shot technique” the procedure went uneventfully and the toxic adenoma displayed a significant volume reduction with resolution of the hyperthyroid symptoms. The patient also reported a significant improvement of her neck symptoms (from 7/10 to 1/10 on a Visual Analogue Scale). Conclusions: Radiofrequency ablation is a new, well tolerated, safe and effective treatment option in selected patients with benign thyroid nodules, toxic adenomas of the thyroid gland and multinodular goiter. To the best of our knowledge, this is the first time such treatment modality is used in Bulgaria.

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Thyroid Cancer in Patients with Hyperthyroidism

World Journal of Endocrine Surgery ◽

10.5005/jp-journals-10002-1162 ◽

2015 ◽

Vol 7 (2) ◽

pp. 29-32 ◽

Cited By ~ 1

Author(s):

Baki Tastan ◽

Alper Dogu ◽

Yusuf Sevim

Keyword(s):

Differential Diagnosis ◽

Thyroid Cancer ◽

Multinodular Goiter ◽

Malignant Tumors ◽

Graves Disease ◽

Thyroid Malignancy ◽

Toxic Adenoma ◽

Endocrine Organs ◽

Toxic Multinodular Goiter ◽

Hyperthyroid Patients

ABSTRACT Background and objective Malignant tumors of the thyroid gland are the most common of the endocrine malignancies. Although, patients with thyroid cancer have high 5 years survival rate, thyroid cancer is the most seen cause of mortality among cancers of the endocrine organs. The incidence of thyroid cancer in hyperthyroid patients varies from 0.1 to 21% in the literature. We aimed in this study to analyze the frequency of coexisting thyroid cancer and hyperthyroidism in our experience. Results Total 230 patients, who were operated for hyperthyroidism without the suspicion of thyroid malignancy between January 2005 and September 2010 were included in our study. Toxic multinodular goiter, toxic adenoma and Graves’ disease were diagnosed preoperatively in 187, 16 and 27 patients respectively. Histopathological thyroid malignancy was detected in 13 patients (5.7%). Conclusion Thyroid cancer with variable incidence up to 21% should be remembered in differential diagnosis of hyperthyroid patients. How to cite this article Tastan B, Dogu A, Sevim Y. Thyroid Cancer in Patients with Hyperthyroidism. World J Endoc Surg 2015;7(2):29-32.

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Thyroglobulin as a possible predictor of doses radioiodine therapy in hyperthyroidism

Acta Medica Saliniana ◽

10.5457/ams.v48i1-2.445 ◽

2018 ◽

Vol 48 (1-2) ◽

Author(s):

Salih Azabagić

Keyword(s):

Multinodular Goiter ◽

Radioiodine Therapy ◽

Cost Effective ◽

Antithyroid Drugs ◽

Toxic Adenoma ◽

Effective Treatment Option ◽

Average Value ◽

Cost Effective Treatment ◽

Toxic Multinodular Goiter

Introduction According to guidelines for the management of hyperthyroidism, patients with hyperthyroidism should be treated with radioactive iodine, antithyroid drugs, or thyroidectomy. Oral administration of radioiodine is a safe and cost effective treatment option for patients with toxic multinodular goiter (TMG)/toxic adenoma (TA) or Grave’s disease (GD). The aim of the study was to evaluate the use of thyroglobulin values as a possible predictor of a dose of radioiodine therapy (RAI) in hyperthyroidism in patients GD, TA and TMG. Results The study included 105 patients (14.4 % males and 85.6% females). The average duration of the disease was 9 years. Graves’s disease is registered among 50.68%, toxic multinodular goiter among 30.83% and toxic adenoma among 18.49% of patients. Patients were divided into four groups, and they received four doses of radioiodine therapy: 10mCi, 15mCi, 20mCi and 25mCi. The values of thyroglubulin were measured before RAI, and in period of one, three and six months after the therapy. Conclusion It can be concluded that the higher average value of thyroglobulin before therapy suggests the need for administering a higher doses of RAI, so determination of thyroglobulin levels in serum, may serve as a good predictor to assist in monitoring the administered dose of RAI in patients with hyperthyroidism.

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A Patient With Graves’ Disease And Thyroid-Associated Orbitopathy Undergoing Radioactive Iodine in Dr. Soetomo General Academic Hospital, Surabaya

Biomolecular and Health Science Journal ◽

10.20473/bhsj.v4i1.26914 ◽

2021 ◽

Vol 4 (1) ◽

pp. 48

Author(s):

Rizki Adrian Hakim ◽

Stepanus Massora ◽

Delfitri Lutfi ◽

Hermina Novida

Keyword(s):

Multinodular Goiter ◽

Radioactive Iodine ◽

Graves Disease ◽

Academic Hospital ◽

Toxic Adenoma ◽

Relative Contraindication ◽

Graves Ophthalmopathy ◽

Common Etiology ◽

Toxic Multinodular Goiter

Graves’ Disease (GD) is the most common etiology of thyrotoxicosis, followed by toxic multinodular goiter and toxic adenoma. GD can be managed with anti-thyroid drugs (ATDs), surgery, or radioactive iodine (RAI). Thyroid-associated orbitopathy (TAO) or Graves’ Ophthalmopathy (GO) affects 25%-50% patients with GD, and its presence usually dissuade clinicians to use RAI in treating hyperthyroidism. The presence of GO is a relative contraindication use of RAI in patients with GD, as RAI can worsen existing GO. Corticosteroid prophylaxis can be given to such patients to reduce likelihood of worsening of GO. However, patient with moderate to severe active GO is currently advised against undergoing RAI. Established guidelines recommend the use of corticosteroid prophylaxis in these patients. We reported a patients with GD and orbitopathy who was treated with RAI and was given steroid prophylaxis to prevent worsening of GO.

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Frequency of Pathological Types of Hyperthyroidism in Thyroid Scan Patients

Current Medical Imaging Formerly Current Medical Imaging Reviews ◽

10.2174/1573405616666201118142752 ◽

2020 ◽

Vol 16 ◽

Author(s):

Ali Pooria ◽

Afsoun Pourya ◽

Alireza Gheini

Keyword(s):

Multinodular Goiter ◽

Clinical Information ◽

Thyroid Stimulating Hormone ◽

Graves Disease ◽

Toxic Adenoma ◽

Aged Patients ◽

Cross Sectional ◽

Radioiodine Uptake ◽

Systemic Disorder ◽

Toxic Multinodular Goiter

Background: Hyperthyroidism is a common systemic disorder where Graves’ disease is known as the leading cause of the disease. Thyroid stimulating hormone, T4 and T3 antibody assay are usually performed for the diagnosis of the pathology. However, with uncertainty in the results and in order to estimate the magnitude and the exact cause of the disease, radioactive iodine uptake (RAIU) test is recommended. The aim of this study is to evaluate underlying pathology in the patients presenting hyperthyroidism using RAIU test results. Methods: This is a cross-sectional retrospective study conducted on the patients with hyperthyroidism referred to Shahid Madani Hospital in Khorramabad. Data regarding the biochemical analysis and RAIU test was collected from the records and a questionnaire based on demographic and clinical information was completed for each patient. Results: Of 137 patients presenting hyperthyroidism, 62.04% were presented with Graves’ disease, 24.08% with toxic multinodular goiter and 13.86% with toxic adenoma. 24-hour RAIU test showed that the percent of radioiodine uptake was most in toxic adenoma 67.7%, Graves’ disease 53.5% and multinodular goiter 39%, respectively. From the age-based analysis, we found that Graves’ was most common in 20-30 years old individuals 34%, multinodular goiter in 50+ aged individuals 36.3% and toxic adenoma was most prevalent in 30-40 and 50+ aged patients, 26.3% each. In our population of interest, 81.8% toxic multinodular goiter patients were females. Conclusions: Our study presents the outcome of RAIU tests in hyperthyroidism based on the underlying pathologies. We also conclude, in light of other findings, Graves’ disease is the most common cause of hyperthyroidism in our population.

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Identification of Constitutively Activating Somatic Thyrotropin Receptor Mutations in a Subset of Toxic Multinodular Goiters1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.82.12.4441 ◽

1997 ◽

Vol 82 (12) ◽

pp. 4229-4233 ◽

Cited By ~ 1

Author(s):

Hans-Peter Holzapfel ◽

Dagmar Führer ◽

Peter Wonerow ◽

Gerhard Weinland ◽

Werner A. Scherbaum ◽

...

Keyword(s):

Multinodular Goiter ◽

The Other ◽

Tsh Receptor ◽

Surrounding Tissue ◽

Additional Patient ◽

Thyrotropin Receptor ◽

Activating Mutations ◽

Gsα Gene ◽

Toxic Multinodular Goiter ◽

Tshr Gene

Constitutively activating mutations in the TSH receptor (TSHR) gene and in the Gsα gene are frequent molecular causes for solitary toxic nodules of the thyroid. However, the etiology of toxic multinodular goiter is still largely unknown. Therefore, DNA from nodular and quiescent surrounding tissue of six patients with toxic multinodular goiters was screened for mutations in exons 9 and 10 of the TSHR gene and exons 7–10 of the Gsα gene by direct automated sequencing. In one patient, two different somatic TSHR mutations were identified in two different toxic nodules (L632I and F631L). In another patient, two different toxic nodules harbored the same TSHR mutation (I630L), whereas only one TSHR mutation (F631L) was identified in one of the two toxic nodules of an additional patient. In the other three patients, no mutations could be found in exons 9 and 10 of the TSHR gene or in exons 7–10 of the Gsα gene. Our results demonstrate that not only solitary toxic adenomas but also toxic multinodular goiters can be caused by constitutively activating mutations of the TSHR. In addition to mutations in the TSHR and possibly in Gsα, there are probably other still unknown mechanisms that cause hot nodules in toxic multinodular goiters.

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