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We present a case of a Sertoli-Leydig cell tumour manifested with progressive hirsutism, frontal alopecia and secondary amenorrhea in a 46-years-old female, evolving for 6 years until presentation. Serum testosterone level was 8.01 ng/ml and gonadotropic hormones were LH 8.57 mIU/ml and FSH 9.52 mIU/ml. Computed tomography revealed a dense, solid, heterogeneous mass of 3.5/2.8 cm in the right ovary. Bilateral ovariectomy and hysterectomy were performed. The histopathological report mentioned a Sertoli-Leydig cell tumor with intermediate grade of differentiation. Immunohistochemical stains showed positive reaction for alpha-inhibin, calretin and for progesterone receptor. The testosterone levels dramatically decreased after surgery (0.31 ng/ml) while levels of gonadotropes increased: LH 40.98 mIU/ml and FSH 50.41 mIU/ml. At 6 months follow-up the diagnosis of a left lobe thyroid nodule leaded to fine needle aspiration biopsy with suspicion of papillary carcinoma. Total thyroidectomy established the diagnosis of thyroid papillary carcinoma (2.17/2.18 cm) T2N0M0, stage II, followed by radioiodine administration. This is to our knowledge the first presented case of ovarian Sertoli-Leydig cell tumour associated with papillary thyroid carcinoma. This could suggest a common genetic background.

Context. Hyperparathyroidism-jaw tumour (HPT-JT) syndrome is a rare autosomal dominant cause of familial hyperparathyroidism associated with ossifying fibromas (OF) of the maxillofacial bones and increased risk of parathyroid carcinoma, caused by inactivating germline mutation of the cell division cycle 73 (CDC73) gene.Objective. To report the first Romanian family with HPT-JT and genetic screening of CDC73 gene.Subjects and Methods. Mutational analysis of the CDC73 gene and genetic screening of the family of a proband with HPT-JT. Histological diagnosis of parathyroid tumors (WHO criteria) and immunohistochemistry (parafibromin) were performed.Results. Three of the six screened family members had evidence of PHPT and surgically proven parathyroid tumours. Two of the three affected members had parathyroid carcinomas and one had two parathyroid adenomas. Genetic screening of CDC73 gene revealed that 4 of 6 patients showed a heterozygous germline deletion of one nucleotide: c.128-IVS1+1 delG. All the three affected patients, resulted to be carriers of the CDC73 mutation, but each one bearing a different CDC73 polymorphism.Conclusions. We identified a new CDC73 germline mutation in a Romanian family of HPT-JT. Analysis of clinical phenotypes in the four mutated individuals confirmed the incomplete penetrance and the variable clinical expression of the disease.

Background/Aim: Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms are involved in a variety of biological processes including cell proliferation, apoptosis, and adhesion in malignant tumors. This study investigated whether vitamin D levels and genetic variations of VDR are risk factors for thyroid cancer. Patients and Methods: Patients who underwent surgery for differentiated thyroid carcinoma (n=113) and those with benign thyroid pathology (n=150) were genotyped for VDR gene polymorphisms (ApaI, TaqI, FokI, and BsmI) and their 25(OH)D levels were simultaneously measured. Demographic data and histopathologic reports were also acquired for all patients. Results: Vitamin D levels were significantly lower in the thyroid cancer group (p=0.03). FokI and TaqI polymorphisms were more frequent in the thyroid cancer patients (p<0.001). Compared to control, the proportion of the FokI Ff genotype was increased (p<0.0006) and the proportion of the TaqI Tt genotype was also higher among patients with thyroid cancer (p<0.0001). The Ff genotype of FokI was also associated with multifocality, invasive pattern, and risk for local metastasis. Conclusion: The VDR gene polymorphism FokI may be associated with the risk of thyroid cancer and its more aggressive forms.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an important mediator of invasion and metastasis in neoplasia. In thyroid cancer expression levels correlate with aggressiveness but data on peripheral MMP-9 levels are less definitive. OBJECTIVE: Prospective study evaluating serum MMP-9 in the diagnosis and prognosis of papillary thyroid cancer. METHODS: Serum samples of MMP-9 were drawn before surgery in 185 consecutively enrolled patients with nodular thyroid disease, stratified on pathology as benign disease (N= 88) and papillary thyroid cancer (N= 97). Serum MMP-9 was measured by an immunometric assay. RESULTS: MMP-9 levels were not different between benign vs malignant pathology (p= 0.3). In papillary thyroid cancer there was no significant difference in MMP-9 levels between histologies, TNM stage and invasive/non-invasive cancers. High-risk patients with multiple features of aggressiveness had significantly higher MMP-9 levels compared to low-intermediate risk patients (767.5 ± 269.2 ng/ml vs 563.7 ± 228.4 ng/ml, p= 0.019). A cut-off of 806 ng/ml distinguished high from low-intermediate risk patients with a sensitivity of 60% and a specificity of 87.36%, p= 0.018. In patients with available follow-up data (N= 78), MMP-9 was higher in patients who required ⩾ 2 doses of 131I therapy (p= 0.009) and in those with biochemical evidence of persistent disease/who required additional therapy to achieve disease-free status (p= 0.017). CONCLUSION: Serum MMP-9 is not useful in the diagnosis of PTC, but preliminary data shows that high pre-surgical serum MMP-9 levels may identify patients at higher risk of persistent disease who require intensive treatment. Large volume prospective studies are required to confirm this observation.