Thyroid Function Abnormalities in Patients Receiving Anticancer Agents

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Endocrine Disrupting Chemicals: Effects on Endocrine Glands

In recent years, endocrine disrupting chemicals have gained interest in human physiopathology and more and more studies aimed to explain how these chemicals compounds affect endocrine system. In human populations, the majority of the studies point toward an association between exposure to endocrine disrupting chemicals and the disorders affecting endocrine axis. A great number of endocrine disrupting chemicals seem to be able to interfere with the physiology of hypothalamus-pituitary-gonadal axis; however, every endocrine axis may be a target for each EDCs and their action is not limited to a single axis or organ. Several compounds may also have a negative impact on energy metabolic homeostasis altering adipose tissue and promoting obesity, metabolic syndrome, and diabetes. Different mechanism have been proposed to explain these associations but their complexity together with the degree of occupational or environmental exposure, the low standardization of the studies, and the presence of confounding factors have prevented to establish causal relationship between the endocrine disorders and exposure to specific toxicants so far. This manuscript aims to review the state of art of scientific literature regarding the effects of endocrine-disrupting chemicals (EDCs) on endocrine system

Ultrasound-guided laser ablation for local control of neck recurrences of medullary thyroid cancer. A feasibility study.

Surgery is the standard treatment for cervical metastases of medullary thyroid cancer (MTC) diagnosed after initial surgical treatment. Repeated neck dissections, however, carry an elevated risk of complications, have an adverse impact on the quality of life, and sometimes do not achieve cure of the disease Clinical case: In a patient who had undergone two cervical neck dissections complicated by accessory nerve injury, an US-guided laser ablation (LA) of a lymph node metastasis of MTC was performed. LA was performed with two treatments during a five month period. The procedure was carried out with one optical fiber and an energy delivery of 3300 and 360 Joules. Treatments were well tolerated and resulted in complete structural and biochemical cure during a 12 month follow-up. No major complication was registered.LA is a promising tool for the management of relapsing cervical metastases that are localized in non- critical areas and are characterized by low progression rate. Advantages of LA are the outpatient setting, the absence of general anesthesia, the tolerability and the safety of the procedure. Thus, LA may be considered as an alternative approach to surgery or active surveillance for the management of local recurrences of MTC in selected patients

The prevalence of secondary neoplasms in acromegalic patients:possible preventive and/or protective role of metformin

Background Acromegaly is a rare disease due to chronic growth hormone (GH) excess and the consequent increase in insulin-like growth factor-1 (IGF-1) levels. Both GH and IGF-1 play a role in intermediate metabolism affecting glucose homeostasis. The association between hyperinsulinemia/impaired glucose tolerance and an increased risk of cancer has been clarified. Insulin has a mitogenic effect through its interaction with the IGF-1 receptor (IGF-1R) that also binds IGF-1. On the other hand, metformin, an anti-hyperglycemic drug that decreases serum levels of insulin and IGF-1, could have a protective role in the treatment of endocrine tumors. Methods A retrospective, observational, multicenter study in 197 acromegalic patients, receiving/not receiving metformin, was performed to assess whether the prevalence of neoplasms might be correlated with insulin resistance and could eventually be modified by metformin treatment. Results In general, the occurrence of secondary neoplasia among our patients was significantly (pV = 0.035) associated with a positive family history of malignancy and with disease duration; a trend towards significance was observed in patients aged > 50 years. Acromegalic subjects who had undergone surgery showed a lower probability of developing a malignant tumor, whereas a higher prevalence of malignancies was observed in obese patients. No significant statistical difference was found when comparing metformin-treated or -untreated subjects for the presence of a second tumor. More interestingly, a trend towards statistical significance (pV = 0.065) was demonstrated in the metformin-treated group for the onset of a benign neoplasm. Conclusion Metformin could act directly on tumor cell metabolism and may have an adjuvant role in benign lesion progression

Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis

Partial response to first generation SSA guides the choice and predict the outcome of second line therapy in acromegaly

Treatment of acromegaly resistant to first generation somatostatin analogues (first gen-SSA) is often difficult. We aimed to investigate the role of partial response and resistance to first gen-SSA in the choice of second line treatments and their outcomes

Patient Age Is an Independent Risk Factor of Relapse of Differentiated Thyroid Carcinoma and Improves the Performance of the American Thyroid Association Stratification System

Background: The 2015 American Thyroid Association (ATA) guidelines proposed a three-category system for estimating the risk of recurrence of differentiated thyroid carcinoma (DTC). This system includes several perioperative features, but not age at diagnosis. However, age has traditionally been recognized as a critical factor in the survival of DTC patients, and the eighth edition of TNM stated that patients older than 55 years were at higher risk of death. In this study, we raised the question of whether age at DTC diagnosis impacts on its risk of recurrence. Specifically, the present study aimed to (i) evaluate the association between age at diagnosis and structural recurrence and (ii) investigate whether age at diagnosis could improve the performance of the ATA system. Methods: During the study period, four institutions selected DTC patients treated with both thyroidectomy and radioiodine and who had follow-up for at least one year. Patients with proven structural evidence of disease during follow-up were identified, and disease-free survival (DFS) was calculated accordingly. Results: The study involved 1603 DTC patients with a median age of 49 years and DFS of 44 months. Disease recurred in 8%. The shortest DFS was found in the oldest patients. The Kaplan-Meier curves were calculated for each decade of age, and there was a significant association with DFS (p = 0.0014). Patients older than 55 years had significantly higher risk (hazard ratio [HR] 1.78, 95% confidence interval [CI 1.23-2.56]). The Kaplan-Meier curves of DFS in high-, intermediate-and low-risk groups showed a significant association only in the high-risk group (p = 0.0058). Patients older than 55 years had significantly higher risk of relapse over time only in the high-risk group (HR 2.15 [CI 2.01-4.53]). Cox's proportional analysis showed that the age cutoff of 55 years and the ATA system were significant predictors of relapse. Adding age at diagnosis above 55 years to the ATA system identified a subgroup of patients at highest risk for relapse. Conclusions: The age threshold adopted in the eighth edition of TNM staging system for DTC patients' prognosis also identifies cases at higher risk of relapse. Applying age at diagnosis, with a cutoff of 55 years, to the ATA risk stratification system identifies cases at highest risk of relapse

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database

: Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083)