Objective: Multiple endocrine neoplasia type 2 (MEN 2) is a genetic disease characterized by medullary thyroid carcinoma (MTC) associated (MEN 2A and 2B) or not familial MTC (FMTC) with other endocrine neoplasia due to germline RET gene mutations. The prevalence of these rare genetic diseases and their corresponding RET mutations are unknown due to the small size of the study population. Methods: We collected data on germline RET mutations of 250 families with hereditary MTC followed in 20 different Italian centres. Results and conclusions: The most frequent RET amino acid substitution was Val804Met (19.6%) followed by Cys634Arg (13.6%). A total of 40 different germline RET mutations were present. Six families (2.4%) were negative for germline RET mutations. The comparison of the prevalence of RET germline mutations in the present study with those published by other European studies showed a higher prevalence of Val804Met and Ser891Ala mutations and a lower prevalence of Leu790Phe and Tyr791Phe (P!0.0001). A statistically significant higher prevalence of mutations affecting non-cysteine codons was also found (P!0.0001). Furthermore, the phenotype data collection showed an unexpected higher prevalence of FMTC (57.6%) with respect to other MEN 2 syndromes (34% MEN 2A and 6.8% of MEN 2B). In conclusion, we observed a statistically significant different pattern of RET mutations in Italian MEN 2 families with respect to other European studies and a higher prevalence of FMTC phenotype. The different ethnic origins of the patients and the particular attention given to analysing apparently sporadic MTC for RET germline mutations may explain these findings.

Incidentally discovered adrenal masses, or adrenal incidentalomas, have become a common clinical problem owing to wide application of radiologic imaging techniques. This definition encompasses a heterogeneous spectrum of pathologic entities, including primary adrenocortical and medullary tumors, benign or malignant lesions, hormonally active or inactive lesions, metastases, and infections. Once an adrenal mass is detected, the clinician needs to address two crucial questions: is the mass malignant, and is it hormonally active? This article provides an overview of the diagnostic clinical approach and management of the adrenal incidentaloma. Mass size is the most reliable variable to distinguish benign and malignant adrenal masses. Adrenalectomy should be recommended for masses greater than 4.0 cm because of the increased risk of malignancy. Adrenal scintigraphy has proved useful in discriminating between benign and malignant lesions. Finally, fine-needle aspiration biopsy is an important tool in the evaluation of oncological patients and it may be useful in establishing the presence of metastatic disease. The majority of adrenal incidentalomas are non-hypersecretory cortical adenomas but an endocrine evaluation can lead to the identification of a significant number of cases with subclinical Cushings syndrome (5-15%), pheochromocytoma (1.5-13%) and aldosteronoma (0-7%). The first step of hormonal screening should include an overnight low dose dexamethasone suppression test, the measure of urinary catecholamines or metanephrines, serum potassium and, in hypertensive patients, upright plasma aldosterone/plasma renin activity ratio. Dehydroepiandrosterone sulfate measurement may show evidence of adrenal androgen excess. Correspondence

Thyroid cancers represent about 1% of all human cancers. Differentiate thyroid carcinomas (DTCs), papillary and follicular cancers, are the most frequent forms, instead Anaplastic Thyroid Carcinoma (ATC) is estimated to comprise 1–2% of thyroid malignancies and it accounts for 14–39% of thyroid cancer deaths. The annual incidence of ATC is about one to two cases/million, with the overall incidence being higher in Europe (and area of endemic goiter) than in USA. ATC has a more complex genotype than DTCs, with chromosomal aberrations present in 85–100% of cases. A small number of gene mutations have been identified, and there appears to be a progression in mutations acquired during dedifferentiation. The mean survival time is around 6 months from diagnosis an outcome that is frequently not altered by treatment. ATC presents with a rapidly growing fixed and hard neck mass, often metastatic local lymph nodes appreciable on examination and/or vocal paralysis. Symptoms may reflect rapid growth of tumor with local invasion and/or compression. The majority of patients with ATC die from aggressive local regional disease, primarily from upper airway respiratory failure. For this reason, aggressive local therapy is indicated in all patients who can tolerate it. Although rarely possible, complete surgical resection gives the best chance of long-term control and improved survival. Therapy options include surgery, external beam radiation therapy, tracheostomy, chemotherapy, and investigational clinical trials. Multimodal or combination therapy should be useful. In fact, surgical debulking of local tumor, combined with external beam radiation therapy and chemotherapy as neoadjuvant (before surgery) or adjuvant (after surgery) therapy, may prevent death from local airway obstruction and as best may slight prolong survival. Investigational clinical trials in phase I or in phase II are actually in running and they include anti-angiogenetic drugs, multi-kinase inhibitor drugs.

BackgroundHyponatraemia has been reported with targeted therapies in cancer patients. Aim of the study was to perform an up-to-date meta-analysis in order to determine the incidence and relative risk (RR) in cancer patients treated with these agents.Materials and MethodsThe scientific literature regarding hyponatraemia was extensively reviewed using MEDLINE, PubMed, Embase and Cochrane databases. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% Confidence Intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies.Results4803 potentially relevant trials were identified: of them, 13 randomized phase III studies were included in this meta-analysis. 6670 patients treated with 8 targeted agents were included: 2574 patients had hepatocellular carcinoma, whilst 4096 had other malignancies. The highest incidences of all-grade hyponatraemia were observed with the combination of brivanib and cetuximab (63.4) and pazopanib (31.7), while the lowest incidence was reported by afatinib (1.7). The highest incidence of high-grade hyponatraemia was reported by cetuximab (34.8), while the lowest incidences were reported by gefitinib (1.0). Summary RR of developing all-grade and high-grade hyponatraemia with targeted agents was 1.36 and 1.52, respectively. The highest RRs of all-grade and high-grade hyponatraemia were associated with brivanib (6.5 and 5.2, respectively). Grouping by drug category, the RR of high-grade hyponatraemia with angiogenesis inhibitors was 2.69 compared to anti-Epidermal Growth Factor Receptors agents (1.12).ConclusionTreatment with biological therapy in cancer patients is associated with a significant increased risk of hyponatraemia, therefore frequent clinical monitoring should be emphasized when managing targeted agents.