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Background: Recently, several devices exploiting the near-infrared autofluorescence (NIR-AF) of parathyroid glands (PGs) have been developed. Nevertheless, their impact on both preserving PGs from inadvertent surgical dissection and on post-surgical hypoparathyroidism (hypoPTH) is controversial., Methods: A retrospective study of 845 patients undergoing thyroid surgery in 2 academic tertiary centres was conducted. In 291 patients, a NIR-AF device was used during surgery to identify PGs. The characteristics of the cohort were examined. The number of PGs identified during surgery, missed PGs, auto-transplants, inadvertent parathyroidectomies, as well as the occurrence of transient and permanent hypoPTH, were analysed., Results: The use of NIR-AF device resulted in a higher identification of PGs (92% versus 88%, p = 0.0008), and a significant reduction in the number of PGs inadvertently removed and detected on histopathological examination (4.7% versus 6.5%, p = 0.045). An increase in PG auto-transplantations was observed in the NIR-AF + group (10.4% versus 3.5%, p < 0.0001). The use of NIRAF did not significantly impact the occurrence of either transient or permanent hypoPTH., Conclusion: Intraoperative NIR-AF detection is a promising technology to reduce incidental parathyroidectomies in thyroid surgery. The impact of this technology on the occurrence of post-surgical hypoPTH needs to be furtherly investigated., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Research involving human participants and/or animals: The ethics committee and review board in our Institute approved the study and treatment protocol. Informed consent: Informed consent was obtained from all patients who agreed to participate in the study., (© 2025. Italian Society of Surgery (SIC).)

Objectives: to describe prevalence of disability in the population of the Agency for Health Protection of Milan (ATS Milan), integrating current administrative healthcare, socio-healthcare, and social data; to classify disability with a diagnosis into a predominant structural and functional category according to the International Classification of Functioning, Disability and Health (ICF), supplementing it with additional levels of detail., Design: retrospective observational study., Setting and Participants: subjects residing in the territory of ATS Milan in the years from 2018 to 2022.  Main outcomes measures: prevalence of disability in the population of ATS Milan from 2018 to 2022; average annual costs since disability diagnosis of the entire population and stratified by the most common ICF classifications., Results: the prevalence of disability ranges from 5.8% in 2018 to 8.4% in 2022. In general, women have a higher prevalence than men. However, there are significant differences in the gender distribution depending on the considered age group. The main disabilities (32.2%) affect the structures of the nervous system and mental functions, followed by disabilities identified solely by major prosthetic devices (9.4%) and sensory disabilities with alterations in sensory functions with the presence of a major device (5.2%). Analysis of average total annual per capita costs shows an upward trend with increasing years since the diagnosis., Conclusions: the definition of standardized tools, such as the selection from several available healthcare data provided by service suppliers, can be helpful in obtaining reliable data on the prevalence of disability in the population. This evidence can be useful in planning public health interventions to address the needs of this population. The work developed by ATS Milan has been carried out in alignment with the activities outlined in Mission 5 of the National Recovery and Resilience Plan (PNRR), in particular for the reform of disability legislation, which foresees the definition of standardized tools for the in-depth study of the epidemiological aspects of the phenomenon.

Objective: The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort., Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4'-DDT and 4,4'-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants' levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods., Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10-3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41-0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants' mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180., Conclusion: Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants' mixture, likely due to a potential reverse causality.

Background: Fatigue is a frequent adverse event during systemic treatments for advanced thyroid cancer, often leading to reduction, interruption, or discontinuation. We were the first group to demonstrate a correlation between fatigue and primary adrenal insufficiency (PAI)., Aim: The objective was to assess the entire adrenal function in patients on systemic treatments., Methods: ACTH, cortisol and all the hormones produced by the adrenal gland were evaluated monthly in 36 patients (25 on lenvatinib, six on vandetanib, and five on selpercatinib). ACTH stimulation tests were performed in 26 cases., Results: After a median treatment period of 7 months, we observed an increase in ACTH values in 80-100% of patients and an impaired cortisol response to the ACTH test in 19% of cases. Additionally, dehydroepiandrosterone sulphate, ∆-4-androstenedione and 17-OH progesterone levels were below the median of normal values in the majority of patients regardless of the drug used. Testosterone in females and oestradiol in males were below the median of normal values in the majority of patients on lenvatinib and vandetanib. Finally, aldosterone was below the median of the normal values in most cases, whilst renin levels were normal. Metanephrines and normetanephrines were always within the normal range. Replacement therapy with cortisone acetate improved fatigue in 14/17 (82%) patients with PAI., Conclusion: Our data confirm that systemic treatments for advanced thyroid cancer can lead to impaired cortisol secretion. A reduction in the other hormones secreted by the adrenal cortex has been first reported and should be considered in the more appropriate management of these fragile patients.

Background: Hypertension (HTN) is the most frequent adverse event during treatment with lenvatinib (LEN), but data on its best management are limited., Aim: The objective of this study was to assess incidence, features and best management of LEN-related HTN in a consecutive single tertiary-care centre cohort., Methods: Twenty-nine patients were followed up for a mean time of 29.8 months (6-77 months)., Results: After a mean follow-up of 6.8 months, HTN was recorded in 76% of cases, as a de novo occurrence in half of them. HTN significantly correlated with LEN dose and was of grade 1, grade 2 and grade 3 in 5%, 50% and 45% of patients, respectively. The majority (77%) of patients with HTN developed proteinuria. There was no correlation between HTN and proteinuria or clinical features or best morphological response or any other adverse event (AE), with the exception of diarrhoea. Patients with or without pre-existing HTN or any other cardiovascular disease had a similar incidence of HTN during LEN, thus excluding the impact of this potential predisposing factor. After evaluation by a dedicated cardiologist, medical treatment was introduced in 21/22 patients (polytherapy in 20 of them). The most frequently used drugs were calcium channel blockers (CCBs) due to their effect on vasodilation. In case of poor control, CCBs were associated with one or more anti-hypertensive drug., Conclusion: HTN is a frequent and early AE in patients on LEN treatment. We suggest a diagnostic and therapeutic algorithm to be applied in clinical practice to allow efficient HTN control and improve patient compliance, reducing LEN discontinuation.

Tyrosine kinase inhibitors (TKIs) have improved outcome for many tumors. Although better tolerated than cytotoxic chemotherapy, they may cause several adverse events (AEs) and various endocrine-related toxicities have been reported under TKI treatment. The toxicity profile varies between the different TKI compounds. This review focuses on the main endocrinopathies caused by TKIs. Thyroid dysfunction and, in particular, hypothyroidism are the most frequent and best described. Several potential mechanisms have been hypothesized, including thyroid gland dysfunction, hormone metabolism impairment and hypothalamus-pituitary-thyroid axis imbalance. TKIs have been reported to influence almost all glands. In particular, they are associated with adrenal insufficiency, growth retardation due to growth hormone (GH) and/or insulin-like growth factor-1 (IGF1) deficiency, hypogonadism, and male and female fertility impairment. TKIs may affect bone metabolism, in particular decreasing osteoclastogenesis and bone turnover and, in turn, they may cause secondary hyperparathyroidism. Hypocalcemia has been reported under lenvatinib and vandetanib treatment and parathyroid hormone (PTH)-dependent and PTH-independent mechanisms have been hypothesized. Metabolic alterations during TKI treatment range from hypoglycemia with imatinib and dasatinib to hyperglycemia with nilotinib; dyslipidemia improved with imatinib and worsened with nilotinib, sunitinib, pazopanib, sorafenib, and famitinib. Endocrine-related AEs should be managed by dedicated endocrinologists. Hormone deficiencies are easily managed by replacement therapy, while endocrine hyperfunction may be improved by symptomatic treatment. Severe situations should be managed in coordination with the oncologist, trying to limit the need for TKI dose reduction or interruption., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Several toxicities are recorded during treatment of advanced thyroid cancer (TC) with antiangiogenic drugs, including lenvatinib (LEN). Hypocalcemia was reported in registration studies, but little data are available from real-life cohorts. The aim of our study was to describe the incidence, characteristics, and the management of hypocalcemia in patients on LEN treatment. Methods: This is a retrospective cohort study of consecutive patients with advanced TC, treated with LEN for at least six months at a single tertiary center in Italy. Phosphocalcic metabolism was evaluated during treatment. Results: We included 25 patients treated for a mean of 29 ± 19 months (range 6-68 months). Hypocalcemia occurred in 6 of the 25 patients (24% [95% confidence interval 9.36-45.13%]), being of grade ≥3 in 2 of the 25 patients (8%), and recurrent in 4 of 6 patients (67%). The median time to hypocalcemia onset was 3 months (range 0.5-13 months) from starting LEN. No differences were found between patients who developed or not hypocalcemia regarding either starting/mean dose of LEN or clinicopathological characteristics. During the hypocalcemic crisis, the 2 patients with grade ≥3 hypocalcemia had low magnesium and low or inappropriately normal parathormone (PTH) levels, while 2 of 3 patients with grade 2 hypocalcemia had a secondary hyperparathyroidism. Hypocalcemia was managed with calcium oral supplementation in most cases, although up to 10% of patients required intravenous calcium treatment and transient LEN withdrawal. Conclusions: In this relatively small cohort, we observed an incidence of hypocalcemia of 24%, which is higher than that reported in the registration trial (6.9%). Both PTH-dependent and PTH-independent mechanisms explained hypocalcemia in the present cohort. Monitoring of serum calcium levels is strongly advised during the first year of LEN treatment, as hypocalcemia may be severe. More research is needed to confirm our findings and inform possible risk factors for hypocalcemia in advanced TC patients treated with LEN.

Context: Radioiodine refractory differentiated thyroid cancer can be effectively treated with multi-tyrosine-kinase inhibitors (MKIs). Hypocalcaemia has been reported among the side effects of these drugs, but little is known about its pathophysiology and clinical relevance., Case Report: We report the case of a 78-years-old woman with an aggressive papillary thyroid cancer infiltrating perithyroidal structures. The extent of surgery was limited to hemithyroidectomy, RAI treatment could not be performed, and she started lenvatinib treatment. After 4 months of therapy, the patient accessed the Emergency Department for a grade III hypocalcaemia (corrected serum calcium: 6.6 mg/dL, n.v. 8.1-10.4 mg/dL), due to primary hypoparathyroidism (serum PTH: 12.6 ng/L, n.v. 13-64 ng/L). The patient was treated with intravenous calcium infusions and vitamin D supplementation. After discharge, the oral dose of carbonate calcium (CaCO 3 ) was of 6 g/day, and was titrated according to blood exams. Two weeks after discharge, while taking CaCO 3 at the dose of 3 g/day, the patient experienced symptomatic grade II hypercalcemia (corrected serum calcium: 11.6 mg/dL), associated to the spontaneous reprise of PTH secretion, and leading to oral calcium withdrawal. During the subsequent follow-up, the patient remained eucalcemic without calcium supplementation., Conclusions: Though hypocalcaemia has been described as potential side effect of MKI treatment, this is the first report of a lenvatinib-induced primary hypoparathyroidism, in a patient with a documented normal parathyroid function after surgery. The periodical assessment of calcium-phosphorus metabolism is thus warranted to prevent this potentially lethal side effect, in both post-surgical hypoparathyroid and euparathyroid patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Controversies remain about the ideal risk-based surgical approach for differentiated thyroid cancer (DTC)., Methods: At a single tertiary care institution, 370 consecutive patients with low- or intermediate-risk DTC were submitted to either lobectomy (LT) or total thyroidectomy (TT) and were followed up., Results: Event-free survival by Kaplan-Meier curves was significantly higher after TT than after LT for the patients with either low-risk (P = 0.004) or intermediate-risk (P = 0.032) tumors. At the last follow-up visit, the prevalence of event-free patients was higher in the TT group than in the LT low-risk group (95% and 87.5%, respectively; P = 0.067) or intermediate-risk group (89% and 50%; P = 0.008). No differences in persistence prevalence were found among microcarcinomas treated by LT or TT (low risk, P = 0.938 vs. intermediate-risk, P = 0.553). Nevertheless, 15% of the low-risk and 50% of the intermediate-risk microcarcinomas treated by LT were submitted to additional treatments. On the other hand, macrocarcinomas were significantly more persistent if treated with LT than with TT (low-risk, P = 0.036 vs. intermediate-risk, P = 0.004). Permanent hypoparathyroidism was more frequent after TT (P = 0.01). After LT, thyroglobulin (Tg)/thyroid-stimulating hormone (TSH) had shown decreasing trend in 68% of the event-free patients and an increasing trend in the persistent cases., Conclusions: Lobectomy can be proposed for low-risk microcarcinomas, although in a minority of cases, additional treatments are needed, and a longer follow-up period usually is required to confirm an event-free outcome compared with that for patients treated with TT. On the other hand, to achieve an excellent response, TT should be favored for intermediate-risk micro- and macro-DTCs despite the higher frequency of postsurgical complications.

Background: For the past century, ferroalloy industries in Brescia province, Italy produced particulate emissions enriched in manganese (Mn), lead (Pb), zinc (Zn), copper (Cu), cadmium (Cd), chromium (Cr), iron (Fe), and aluminum (Al). This study assessed metal concentrations in soil and vegetables of regions with varying ferroalloy industrial activity levels., Methods: Home gardens (n=63) were selected in three regions of varying ferroalloy plant activity durations in Brescia province. Total soil metal concentration and extractability were measured by X-Ray Fluorescence (XRF), aqua regia extraction, and modified Community Bureau of Reference (BCR) sequential extraction. Unwashed and washed spinach and turnips cultivated in the same gardens were analyzed for metal concentrations by flame atomic absorption spectrometry., Results: Median soil Al, Cd, Fe, Mn, Pb, and Zn concentrations were significantly higher in home gardens near ferroalloy plants compared to reference home gardens. The BCR method yielded the most mobile soil fraction (the sum of extractable metals in Fractions 1 and 2) and all metal concentrations were higher in ferroalloy plant areas. Unwashed spinach showed higher metal concentrations compared to washed spinach. However, some metals in washed spinach were higher in the reference area likely due to history of agricultural product use. Over 60% of spinach samples exceeded the 2- to 4-fold Commission of European Communities and Codex Alimentarius Commission maximum Pb concentrations, and 10% of the same spinach samples exceeded 2- to 3-fold maximum Cd concentrations set by both organizations. Turnip metal concentrations were below maximum standard reference values., Conclusions: Prolonged industrial emissions increase median metal concentrations and most soluble fractions (BCR F1+F2) in home garden soils near ferroalloy plants. Areas near ferroalloy plant sites had spinach Cd and Pb metal concentrations several-fold above maximum standard references. We recommend thorough washing of vegetables to minimize metal exposure., (Copyright © 2015 Elsevier B.V. All rights reserved.)