The RET polymorphic allele S836S is associated with early metastatic disease in patients with hereditary or sporadic medullary thyroid carcinoma

The possible role of RET variants in modifying the natural course of medullary thyroid carcinoma (MTC) is still a matter of debate. Here, we investigate whether the RET variants L769L, S836S, and G691S/S904S influence disease presentation in hereditary or sporadic MTC patients. One hundred and two patients with hereditary MTC and 81 patients with sporadic MTC attending our institution were evaluated. The frequencies of RET polymorphisms in hereditary MTC were as follows: L769L, 17.3%; S836S, 7.95%; and S904S/G691S, 18.2%. No associations were observed between these polymorphisms and pheochromocytoma, hyperparathyroidism, lymph node, or distant metastasis. However, patients harboring the S836S variant were younger than those without this allele (17±8.2 vs 28.6±14.4 years, P=0.01), suggesting that these patients had metastases at a young age. Accordingly, the cumulative frequency of local and/or distant metastases as estimated by Kaplan–Meier curves showed that lymph node and distant metastases occurred earlier in patients harboring the S836S variant (P=0.003 and P=0.026 respectively). The S836S allele frequency was higher in sporadic MTC patients than in controls (10.5 vs 3.1%, P=0.01). Individuals harboring the S836S variant were younger (38.6±13.3 vs 48.5±16.7 years, P=0.02) and showed a higher percentage of lymph node and distant metastases (P=0.02 and P=0.04 respectively). Kaplan–Meier estimates of lymph node and distant metastases yielded distinct curves for patients with or without the S836S allele (P=0.002 and P=0.001 respectively). Additional analyses using a COX regression model showed that the S836S variant was independently associated with metastatic disease (hazard ratio 2.82 (95% confidence interval 1.51–5.26), P=0.001). In conclusion, the RET S836S variant is associated with early onset and increased risk for metastatic disease in patients with hereditary or sporadic MTC.

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Atypical Presentation of a Medullary Thyroid Carcinoma Producing Acth and Serotonin

Case Reports in Oncology ◽

10.1159/000502856 ◽

2019 ◽

Vol 12 (3) ◽

pp. 742-748 ◽

Cited By ~ 1

Author(s):

Mariana Ferreira ◽

Christianne Toledo de Souza Leal ◽

Lize Vargas Ferreira ◽

Danielle Guedes Andrade Ezequiel ◽

Mônica Barros Costa

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Distant Metastases ◽

Medullary Carcinoma ◽

Needle Aspiration ◽

Disease Stage ◽

Medical Attention ◽

Medullary Thyroid ◽

Superior Mediastinum ◽

Increased Risk

Medullary carcinoma accounts for about 5% of all thyroid malignancies. The tumor may produce other hormones in addition to calcitonin that typically occurs in the presence of distant metastases. The aim of this report is to present a case of invasive medullary thyroid carcinoma producing ACTH and serotonin. A male patient sought medical attention due to facial plethora and distal paresthesia. On thyroid ultrasound, he presented a hypoechoic nodule measuring 6.7 × 3.2 × 3.5 cm, with punctate calcifications and central vascular pattern. The chest computed tomography showed an extensive solid lesion with epicenter in the superior mediastinum and absence of a cleavage plane with the left thyroid lobe. The lesion extended from the glottic area to the lower portion of the trachea and invaded esophagus, posterior tracheal wall, and left jugular. The patient presented hyperglycemia, hypokalemia, increased free urinary cortisol, calcitonin, ACTH and 5-hydroxyindoleacetic acid levels. The nodule cytological examination obtained by fine-needle aspiration was inconclusive, and the open biopsy confirmed the diagnosis of medullary thyroid carcinoma. Due to the advanced disease stage and increased risk of large caliber vessels injury in case of surgery, local chemotherapy and radiotherapy were recommended. With this report, we want to draw attention to an unusual association between advanced medullary thyroid carcinoma with an aggressive course and ectopic production of ACTH and serotonin.

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131I-MIBG as a treatment in medullary thyroid carcinoma with distant metastases.

Endocrine Abstracts ◽

10.1530/endoabs.56.p1176 ◽

2018 ◽

Author(s):

Nerea Utrilla Uriarte ◽

Pedro Gonzalez Fernandez ◽

Alba Esteban Figueruelo ◽

Marina Nevares Herrero ◽

Javier Santamaria Sandi

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Distant Metastases ◽

Medullary Thyroid ◽

131I Mibg

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A Review of the Significance in Measuring Preoperative and Postoperative Carcinoembryonic Antigen (CEA) Values in Patients with Medullary Thyroid Carcinoma (MTC)

Medicina ◽

10.3390/medicina57060609 ◽

2021 ◽

Vol 57 (6) ◽

pp. 609

Author(s):

Ioannis Passos ◽

Elisavet Stefanidou ◽

Soultana Meditskou-Eythymiadou ◽

Maria Mironidou-Tzouveleki ◽

Vasiliki Manaki ◽

...

Keyword(s):

Thyroid Carcinoma ◽

Carcinoembryonic Antigen ◽

Medullary Thyroid Carcinoma ◽

Clinical Significance ◽

Relevant Literature ◽

Distant Metastases ◽

Lymph Node Involvement ◽

C Cells ◽

Gastrointestinal Malignancies ◽

Medullary Thyroid

Background and Objectives: Medullary thyroid carcinoma (MTC) accounts for 1–2% of all thyroid malignancies, and it originates from parafollicular “C” cells. Carcinoembryonic antigen (CEA) is a tumor marker, mainly for gastrointestinal malignancies. There are references in literature where elevated CEA levels may be the first finding in MTC. The aim of this study is to determine the importance of measuring preoperative and postoperative CEA values in patients with MTC and to define the clinical significance of the correlation between CEA and the origin of C cells. Materials and Methods: The existing and relevant literature was reviewed by searching for articles and specific keywords in the scientific databases of PubMedCentraland Google Scholar (till December 2020). Results: CEA has found its place, especially at the preoperative level, in the diagnostic approach of MTC. Preoperative CEA values >30 ng/mL indicate extra-thyroid disease, while CEA values >100 ng/mL are associated with lymph node involvement and distant metastases. The increase in CEA values preoperatively is associated with larger size of primary tumor, presence of lymph nodes, distant metastases and a poorer prognosis. The clinical significance of CEA values for the surgeon is the optimal planning of surgical treatment. In the recent literature, C cells seem to originate from the endoderm of the primitive anterior gut at the ultimobranchial bodies’ level. Conclusions: Although CEA is not a specific biomarker of the disease in MTC, itsmeasurement is useful in assessing the progression of the disease. The embryonic origin of C cells could explain the increased CEA values in MTC.

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Percutaneous Ethanol Injection for Treatment of Cervical Lymph Node Metastases in Patients with Papillary and Medullary Thyroid Carcinoma

10.1210/endo-meetings.2011.part2.p18.p1-720 ◽

2011 ◽

pp. P1-720-P1-720

Author(s):

Ejigayehu Gigi Abate ◽

Robert Smallridge ◽

Tammy Bozik ◽

Ricardo Paz-Fumagalli

Keyword(s):

Lymph Node ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Lymph Node Metastases ◽

Cervical Lymph Node ◽

Percutaneous Ethanol Injection ◽

Ethanol Injection ◽

Medullary Thyroid ◽

Cervical Lymph Node Metastases ◽

Node Metastases

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Medullary thyroid carcinoma: recent advances in identification, treatment, and prognosis

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/20420188211049611 ◽

2021 ◽

Vol 12 ◽

pp. 204201882110496

Author(s):

Marisa A. Bartz-Kurycki ◽

Omowunmi E. Oluwo ◽

Lilah F. Morris-Wiseman

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Distant Metastases ◽

Hereditary Disease ◽

Patient Specific ◽

Medullary Thyroid ◽

Recent Advances ◽

Initial Surgery ◽

Biochemical Testing ◽

Thyroid Malignancies

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that represents <5% of all thyroid malignancies and is generally more aggressive than differentiated thyroid cancer. The aim of this study is to provide an update, through review of clinical studies of patients with MTC published between January 1, 2016, and June 1, 2021, on recent advances in the diagnosis and treatment of MTC. This review focuses on updates in biochemical testing, imaging, hereditary disease, surgical management, adjuvant therapies, and prognosis. Recent advances reviewed herein have sought to diagnose MTC at earlier stages of disease, predict when patients with a hereditary syndrome may develop MTC, use functional imaging to assess for distant metastases, perform optimal initial surgery with appropriate lymphadenectomy, employ targeted systemic therapies for patients with progressive metastatic disease, and better predict patient-specific outcomes.

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