Tehran University Medical Journal

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Differentiated carcinoma of the thyroid occruing within the gland is generally not regarded as an aggressive tumor however, when the tumor extends beyond the gland's capsule and onto adjacent structures, its prognosis worsens. During the past three decades such locally invasive thyroid cancer has been studied, specifically concerning invasion into the airway. Progress in tracheal operations in the past 20 years has changed remarkably in terms of the operative methods and indications for thyroid carcinoma invading the trachea. Resection and primary reconstruction of the trachea invaded by carcinoma of the thyroid should be done in the absence of extensive metastases when technically, feasible. It offers prolonged palliation, avoidance of suffocation and an opportunity for cure. In carefully selected patient with massive regional involvement, radical excision laryngopharyngoesophagectomy and mediastinal tracheostomy is also appropriate. In this article, management of one patient with intraluminal involvement of trachea by thyroid carcinoma is presented and management of upper aerodigestive tract invasion by thyroid cancer reviewed.

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Background: The purpose of this study was to evaluate the effect of treatment with radioactive iodine on the function of gonads in males and females with follicular and papillary thyroid carcinoma.

Materials and Methods: Consenting patients in the reproductive age were grouped according to the cumulative dose of received radioiodine and followed for at least 12 months. For all men, serum levels of FSH, LH, and testosterone were measured some (53 cases) were also studied by semen analysis. For women, tests for serum levels of LH, FSH, estrogen, and progesterone were performed.

Results: Overall, 246 patients (159 females, 87 males) were studied. In 87.4% of men, there was an increase in serum FSH level after radioiodine therapy, in 20.7% of whom the level remained high during follow-up period. The average serum level of FSH after each course of treatment was significantly higher than the level before treatment (p<0.01), and there was a meaningful correlation with the cumulative dose of received iodine (p<0.001). Reduced number of sperms was shown in 35.8% of male patients, among whom 73.7% also showed reduced motility. In 36.8% of the patients with reduced sperm number (13.2% of the total), this finding was persistent during the follow-up period. Increased level of FSH was correlated with reduced sperm counts in all doses (p 

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Background: Thyroid carcinoma is the most frequent malignant tumor of the endocrine system in human body and accounts for nearly 1% of all cancers. Medullary thyroid carcinoma is the third frequent of thyroid cancer and accounts about 5-8% of thyroid cancer. Osteocalcin, known as a Bone Gamma-carboxyglutamic Acid-containing Protein (BGLAP), is the most non collagenous protein. Retinol binding proteins are the family of proteins that have diverse actions but mainly transport retinol in human body. In this study to evaluate effect of existence medullary thyroid carcinoma on metabolism of bone and adipose tissue, plasma level of two mentioned proteins had analyzed. Methods: Population in this study consists of 46 individuals with medullary thyroid carcinoma and 44 healthy subjects referred individuals to Research Institute for Endo-crine Sciences, Shahid Beheshti University of Medical Sciences. People with the disease after diagnosis of medullary thyroid carcinoma and pathologically confirmed by biopsy in the initial stages of the study were called. After informed consent, 10 ml of blood from the antecubital vein of left hand in sitting position obtained and after cen-trifugation, plasma was isolated from all samples until analyzed kept in the freezer. Plasma levels of hormones were measured by sandwich type ELISA method. Obtained results were analyzed by SPSS version 16 with independent t-test method. Results: Mean plasma level of osteocalcin in patients was 33.1±3.5 and in healthy sub-jects was 12.5±1.2 ng/ml (Mean±SD) and Odds Ratio (OR) value was 1.04. In patients, mean plasma level of retinol binding protein was 82.5±2.7 and in healthy subjects was 22.8±1.6 μg/ml and OR value was 2.1. The confidence level considered at 95%. These differences of plasma levels were statistically significant (P= 0.001). Conclusion: According to difference between plasma levels of osteocalcin and retinol binding protein-4 in patients suffered of medullary thyroid carcinoma comparison with normal subjects, it can be said that, probably medullary thyroid carcinoma has effect on bone and adipose tissue metabolism, so osteocalcin and retinol binding protein-4 hormones have potential to be used for confirmation of diagnosis or following treatment of medullary thyroid carcinoma.

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Background: Thyroid carcinoma is the most common endocrine malignancy. Medullary thyroid carcinoma (MTC) approximately accounts for 5-10% of all thyroid carcinoma. Nowadays, it is obviously, the mutations in REarranged during transfection (RET) proto-oncogene, especially, mutations in exons 10, 11 and 16 are associated with MTC pathogenesis and occurrence. Thus, early diagnosis of MTC by mutation detection in RET proto-oncogene allows to identify patients who do not have any developed symptoms. The aim of this study was to screening of germline mutations in RET proto-oncogene exons 17 and 18 in MTC patients and their first degree relatives in Iranian population.

Methods: In this cross-sectional study, three hundred eleven participates (190 patients, 121 their relatives) were referred to endocrine research center, Shahid Beheshti University of Medical Science during September 2013 until September 2015. The inclusion criteria were pathological and clinical diagnosis. After whole blood sampling, genomic DNA was extracted from peripheral blood leucocytes using the standard Salting Out/Proteinase K method. Nucleotide change detection in exons 17 and 18 was performed using PCR and direct DNA sequencing methods.

Results: In this study, twenty missense mutations [CGC>TGC, c.2944C>T, p.Arg982Cys (rs17158558)] which included 16 heterozygote and 4 homozygote mutations were found in codon 982 (exon 18). In the present study, 154 G>A (rs2742236) and 4 C>T (rs370072408) nucleotide changes were detected in exons 18 and intron 17 respectively. There was no mutation in exon 17. Conclusion: It seems that because of arginine to cysteine substitutions in RET tyrosine kinase protein structure and its polyphen score (0.955) and SIFT score (0.01) the mutation in codon 982 (exon 18) could be have pathogenic effects. On the other hands, the mentioned mutation frequency was 6.4% among MTC patients, so this mutation of exon 18 could be checked in genetic screening tests of RET proto-oncogene. Although this needs more study.

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Medullary thyroid cancer accounts for 5-10% of thyroid carcinomas. RET proto-oncogene mutations occur in all of the hereditary MTCs and about 66% of the sporadic MTCs. So, the detection of the RET mutations is necessary for rapid and proper diagnosis and treatment. This systematic review seeks to find a comprehensive list of RET gene mutations in the diagnosis of medullary thyroid cancer.
The previous studies on RET proto-oncogene mutations in the diagnosis of medullary thyroid cancer were searched in the major databases including PubMed, Scopus, Medline, Embase and NCBI between 2010 and 2021.
Missense mutations in exons 10, 11, 13, 14, 15, and 16 of the RET proto-oncogene have the highest frequency in MTCs. The most common mutations in FMTC, are in codons 609, 611, 618, and 620 in exon 10, codon 768 in exon 13, codon 804 in exon 14, and codon 634 in exon 11. In the case of MEN2A, RET gene mutations have been observed in exons 5, 8, 10, 11, with the highest mutations in exons 10 (codons 609, 611, 618, and 620) and exon 11 (codons 630 and 634). Moreover, M918T mutation in exon 16 and A883F mutation in exon 15 have been detected in 95% and 5% of the patients with MEN2B respectively. In the case of MTC, the M918T mutation in exon 16 is the most common mutation, which is associated with a poor prognosis. RET genetic screening is crucial for an exact approach to the diagnosis and treatment of MTC. Anyone with MTC, even without a family history of MEN2, should be genetically tested for the RET mutations to confirm or rule out the inherited disease and, if necessary, preventive thyroidectomy. This systematic review provided a comprehensive list of the reported mutations in the RET gene for the diagnosis of medullary thyroid cancer.