Lack of association between autonomously functioning thyroid nodules and germline polymorphisms of the thyrotropin receptor and Gαs genes in a mild to moderate iodine-deficient Caucasian population

Vicchio, Teresa Manuela; Giovinazzo, Salvatore; Certo, Rosaria; Cucinotta, Mariapaola; Micali, Carmelo; Baldari, Sergio; Benvenga, Salvatore; Trimarchi, Francesco; Campennì, Alfredo; Ruggeri, Rosaria Maddalena

doi:10.1007/s40618-014-0081-x

Cited by 8 publications

(5 citation statements)

References 18 publications

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“…All the TSHR mutations are known mutations that were previously reported in AFTNs, and are somatic gain-of-function mutations (Figure 1 ) ( 36 – 39 ). In previous studies, somatic mutations of TSHR gene have been reported in toxic adenomas and toxic multinodular goiters, with a frequency ranging from 8 to 82% of cases ( 40 , 41 ). It is not surprising that the mutation rate described in our study was much lower when compared with existing data, because we were not doing the molecular testing in selected functioning nodular diseases.…”

Section: Discussionmentioning

confidence: 98%

Clinical Significance of Thyroid-Stimulating Hormone Receptor Gene Mutations and/or Sodium-Iodine Symporter Gene Overexpression in Indeterminate Thyroid Fine Needle Biopsies

et al. 2018

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Objectives: To examine the prevalence of genetic alterations of thyroid-stimulating hormone receptor (TSHR) gene and sodium-iodine symporter (NIS) in a series of thyroid fine needle biopsy (FNB) specimens with indeterminate cytology, and to assess the correlation of the type of genetic changes with clinical features and follow-up results in the target thyroid nodule.Methods: Between February 2015 and September 2017, 388 consecutive FNBs with indeterminate cytology were evaluated for TSHR mutations and NIS gene overexpression using ThyroSeqV.2 next-generation sequencing (NGS) panel. Medical records were reviewed for target nodules.Results: Among 388 indeterminate FNBs, TSHR mutations and/or NIS overexpression were detected in 25 (6.4%) nodules. Ten nodules (2.6%) harbored TSHR mutations only, 7 nodules (1.8%) over-expressed NIS gene only, and 8 nodules (2.1%) had both alterations. The TSHR mutations were located between codons 281 and 640, with codon 453 being the most frequently affected. The allelic frequency of the mutated TSHR ranged from 6 to 36%. One nodule with NIS overexpression was simultaneously detected EIF1AX mutation and GNAS mutation. Nodules with TSHR mutations and/or NIS overexpression presented hyperfunctioning (n = 4), hypofunctioning (n = 5), and isofunctioning (n = 3) on the available thyroid scintigraphies. Eight cases accompanied with hyperthyroidism in which only 1 was caused by the target nodule. Evidence of co-existing autoimmune thyroid disease (AITD) and multinodular goiter were found in 52% and 52% of cases, respectively. Seven nodules underwent surgeries and all were benign on final pathology. None of 9 nodules with follow-up by ultrasound (3~33 mon, median 12 mon) showed grow in size.Conclusions: TSHR mutations and/or NIS overexpression can be detected in pre-operative FNB specimens using the NGS approach. These genetic alterations occurred in 6.4% thyroid nodules in this consecutive series with indeterminate cytology. They present not only in hyperfunctioning nodules but also in hypo- or iso-functional nodules, indicating their prevalence may be higher than previously expected. Co-existing AITD was common in cases with these molecular alterations. None of our patients with TSHR mutations and/or NIS overexpression manifested malignant outcomes. How to use these two molecular markers in thyroid FNBs to guide our clinical practice warrants further investigation.

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Section: Discussionmentioning

confidence: 98%

Clinical Significance of Thyroid-Stimulating Hormone Receptor Gene Mutations and/or Sodium-Iodine Symporter Gene Overexpression in Indeterminate Thyroid Fine Needle Biopsies

et al. 2018

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“…A somatic activating mutation affecting the thyrotropin receptor (TSHR) gene and the gene encoding for the stimulatory GPT-binding protein (Gsα) have been reported as the main cause of TNG and have also been described in many TMNG patients [1,[103][104][105].…”

Section: Definition and Epidemiologymentioning

confidence: 99%

The EANM guideline on radioiodine therapy of benign thyroid disease

Campennì

Avram

Verburg

et al. 2023

Eur J Nucl Med Mol Imaging

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This document provides the new EANM guideline on radioiodine therapy of benign thyroid disease. Its aim is to guide nuclear medicine physicians, endocrinologists, and practitioners in the selection of patients for radioiodine therapy. Its recommendations on patients’ preparation, empiric and dosimetric therapeutic approaches, applied radioiodine activity, radiation protection requirements, and patients follow-up after administration of radioiodine therapy are extensively discussed.

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“…A group of 100 age-and sex-matched healthy subjects from the same geographic area, in which TV had been previously estimated (27), were used as controls. 3 , and 0.4-4.0 mU/l for TSH).…”

Section: Patientsmentioning

confidence: 99%

“…Any nodular lesions were recorded, and the nodule sizes were reported in terms of their largest diameter in millimetres. When US revealed nodule(s) of R10 mm in maximum diameter, a thyroid scintigraphy was performed in order to exclude autonomously functioning nodules, as commonly used in iodine deficient areas (27).…”

Section: Thyroid Imagingmentioning

confidence: 99%

Effects of GH replacement therapy on thyroid volume and nodule development in GH deficient adults: a retrospective cohort study

Curtò

Giovinazzo

Alibrandi

et al. 2015

European Journal of Endocrinology

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Objective: Despite the well-known effects of GH/IGF1 signaling on the thyroid, few data are available on the risk of developing nodular goiter in hypopituitary subjects during GH replacement therapy (GHRT). We aimed to define the effects of GH therapy on thyroid volume (TV) and nodular growth. Design: The records of 96 subjects (47 males and 49 females, median age 48 years) with GH deficit (GHD) were investigated. Seventy also had central hypothyroidism (CH). At the time of our retrospective evaluation, median treatment duration was 5 years. Results: Pre-treatment TV was smaller in GHD patients than in healthy subjects (PZ0.030). During GH treatment, TV significantly increased (PZ0.016 for the entire group and PZ0.014 in euthyroid GHD patients). Before starting GH therapy, 17 patients harbored thyroid nodules. During GH therapy, nodule size increased slightly in seven patients, and new thyroid nodules occurred in nine patients. Among the 79 patients without pre-existing thyroid nodules, 17 developed one or more nodules. There was no difference in the prevalence of CH in GHD patients with or without thyroid nodules (PZ0.915; PZ0.841, when patients with pre-therapy nodular goiter were excluded), the main predictor for nodule development being serum IGF1 (PZ0.038). Conclusions: GHRT is associated with TV's increase in GHD patients. Thyroid nodules developed in 27% of patients, mainly in relation to pre-therapy IGF1 levels, independently of normal or impaired TSH stimulation.

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Lack of association between autonomously functioning thyroid nodules and germline polymorphisms of the thyrotropin receptor and Gαs genes in a mild to moderate iodine-deficient Caucasian population

Abstract: These results suggest that these two SNPs do not confer susceptibility for the development of AFTN.

Cited by 8 publications

References 18 publications

Clinical Significance of Thyroid-Stimulating Hormone Receptor Gene Mutations and/or Sodium-Iodine Symporter Gene Overexpression in Indeterminate Thyroid Fine Needle Biopsies

Clinical Significance of Thyroid-Stimulating Hormone Receptor Gene Mutations and/or Sodium-Iodine Symporter Gene Overexpression in Indeterminate Thyroid Fine Needle Biopsies

The EANM guideline on radioiodine therapy of benign thyroid disease

Effects of GH replacement therapy on thyroid volume and nodule development in GH deficient adults: a retrospective cohort study

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