Skeletal muscle deterioration is a relevant complication of obesity associated with poor physical function, impairment of metabolic homeostasis, and worse lifelong outcomes. The phenomenon can be accentuated by weight loss, especially in patients with poor skeletal muscle health at baseline (e.g., sarcopenic obesity) and those experiencing rapid and significant slimming. Preserving and even strengthening skeletal muscle mass during weight loss would be a novel therapeutic target, as disproportionate fat to skeletal muscle mass loss reduces metabolic rate, physical performance, and long-term health benefits. Anti-obesity pharmacotherapies, especially glucagon-like peptide 1 receptor agonists and tirzepatide, preferentially reduce fat mass while partially sparing skeletal muscle, though significant lean mass loss has been described in individuals with pronounced weight reduction. The review aims to elucidate innovatively the mechanistic role of the activin/myostatin receptor pathways in obesity-associated skeletal muscle atrophy and explore therapeutic strategies targeting this axis to preserve muscle mass, quality, and function. Targeted inhibition of the activin/myostatin pathway is a novel strategy to enhance muscle trophism. Activin receptor (IIA/IIB) blockade prevents the small mothers against decapentaplegic homolog 2/3-mediated muscle catabolism, promoting myofibrillar synthesis, myoblast differentiation, and hypertrophy. Bimagrumab - a human anti-activin receptor antibody - consistently increases skeletal muscle mass and improves body composition across populations, including sarcopenic adults, patients with disuse atrophy, and individuals with obesity. While gains in strength are variable, this approach represents a promising adjunct to lifestyle and pharmacologic interventions. Integrating skeletal muscle preservation into obesity management may optimize functional, metabolic, and clinical outcomes, representing a paradigm shift in comprehensive care.

Background Thyroid nodules are highly prevalent in the general population, yet their diagnostic assessment may require accurate differential diagnosis in patients with hematologic malignancies. In this context, immune dysregulation, prior cytotoxic therapies, and the potential for atypical extramedullary involvement may confound conventional risk stratification algorithms. Although ultrasonography remains the first-line imaging modality, fine-needle aspiration with ancillary studies is often required for definitive characterization. Case report A 47-year-old woman with relapsed multiple myeloma, previously treated with multiagent chemotherapy, radiotherapy, and autologous stem cell transplantation, was evaluated for biochemical and clinical disease progression. Bone marrow biopsy demonstrated no evidence of plasma cell infiltration. However, 18F-fluorodeoxyglucose positron emission tomography/computed tomography identified focal hypermetabolic uptake in the right thyroid lobe. Dedicated neck ultrasonography revealed a 26-mm solid, markedly hypoechoic nodule with peri-nodular vascularity and without definitive sonographic features of papillary thyroid cancer. Given the discordance between imaging findings and marrow status, ultrasound-guided fine-needle aspiration was performed. Cytologic evaluation demonstrated numerous atypical plasma cells, and immunocytochemistry confirmed lambda light chain restriction, consistent with clonal plasma cell proliferation. These findings established intrathyroidal involvement by multiple myeloma, representing an isolated extramedullary relapse in the absence of bone marrow disease. Discussion Intrathyroidal manifestation of multiple myeloma is rare but clinically significant. In patients with systemic malignancies, fluorodeoxyglucose-avid thyroid nodules should prompt consideration of secondary involvement, even when bone marrow evaluation is negative. Conventional ultrasound-based risk stratification systems are primarily designed to detect epithelial thyroid malignancies and may fail to identify nonepithelial neoplasms. Cytologic assessment supplemented by immunophenotypic analysis remains essential for accurate diagnosis. Conclusion This case highlights the importance of integrating clinical history, functional imaging, cytopathology, and immunocytochemistry to avoid diagnostic pitfalls and to guide appropriate oncologic management.

Background. It is unclear if dietary education may increase adherence to the Mediterranean diet (MD). Study aim. We estimated the effect of dietary counseling on nutritional knowledge and adherence to MD in T2D adult patients. Methods. T2D patients who attended the Diabetology Center of the Grande Ospedale Metropolitano Niguarda were recruited (April to September 2019) and categorized into two groups: the intervention group (IG), receiving a 2.5-h education, and the control group (CG). The Moynihan questionnaire and the Mediterranean Diet Adherence Assessment Questionnaire (MDAAQ) were administered to estimate the overall knowledge and adherence to MD at baseline (T0), 1 week (T1), and 1 month (T2) later. Results. Seventy-two individuals (69.5 ± 8.6 years old) were included in the IG, and 52 (67.7 ± 9.2 years old) were included in the CG. All patients had sufficient dietary knowledge and intermediate adherence to MD at baseline. Those assigned to the IG showed a significant reduction in the Moynihan score from T0 (24.9 ± 2.6) to T1 (20.3 ± 1.8; p < 0.001) and T2 (20.4 ± 2.2; p < 0.001). CG had the same Moynihan score as IG individuals at T0 (24.8 ± 1.8), but their dietary knowledge was unchanged at T1 and T2 (24.9 ± 1.8). MD adherence was similar at each time in the IG, with a MDAAQ score of 4.4 ± 1.7 (T0), 5.1 ± 1.7 (T1), and 5.3 ± 1.8 (T2), and in the CG (T0: 5.1 ± 1.7; T1: 5 ± 1.5; T2: 5.1 ± 1.5). Discussion and Conclusions. The 2.5-h dietary counseling session improves dietary knowledge, but it is not enough to improve adherence to MD.

The impact of work engagement and burnout on medical activities, physicians’ performance, and quality of care has gained interest over the last decades. However, the effect of demographics, job-related, and organizational variables on burnout and work engagement in young endocrinologists has not been fully investigated. To assess the impact of demographics, job-related, and organizational variables on burnout and work engagement in young endocrinologists who joined the Italian Association of Clinical Endocrinologists. The levels of burnout and work engagement were assessed by the Maslach Burnout Inventory and the Utrecht Work Engagement Scale, respectively, as a part of an online survey of the “Associazione Medici Endocrinologi” addressed to young members (31–40 years). Eighteen MANOVAs were applied to analyze differences in burnout and work engagement based on demographic, job-related, and organizational factors. We collected responses from 160 young endocrinologists, mainly women (80.6%), aged 31–35 years (33.8%) and 36–40 years (66.2%). Most were in a stable relationship with (40%) or without (45%) children. Most of them worked in hospitals or local healthcare districts (35.6%), as independent contractors (31.9%), or as Ph.D. students or residents (25.6%). Multivariate analyses found no statistically significant differences in burnout and work engagement due to demographics (gender, age, and partnership) and job-related variables (type of job and contract). On the other hand, organizational variables (levels of conflict amongst colleagues, more than expected time spent working, and no involvement in team-building activities) were associated with higher emotional exhaustion, lower dedication, and less vigor. The novelty of the study is that both burnout and work engagement can be affected by organizational variables in early-career Italian endocrinologists, highlighting the need for supporting the healthcare system to overcome this gap.

Overweight and obesity represent common chronic metabolic disorders in the general population, and observed trends describe a substantial growth in the prevalence of weight excess also among individuals with type 1 diabetes (T1D), the so-called 'lean phenotype' of diabetes. The sharp rise of weight excess and obesity-related cardio-nephron-metabolic burdens observed in T2D is expected to produce similar consequences in T1D, leading to the urgent need to endorse therapeutic protocols as in most parts of the World no adjunctive treatments are approved for T1D, making weight excess management challenging in these individuals. The notable results shown by newer glucagon-like peptide 1 receptor agonists (GLP-1RAs) and emerging dual agonists, especially while managing cardio-metabolic burdens, in T2D have encouraged fervent anecdotal and non-anecdotal research also in T1D, indicating that non-insulin injective agents can be effective and safe. With this expert opinion paper, the members of four of the most representative Committees of the Italian Association of Clinical Endocrinologists provide the scientific community with a state-of-the-art report on the use of GLP-1RAs and other incretin-based injective therapy to treat body weight excess in T1D individuals and new insights on the topic with reliable methodology and clinical expertise.

Benign thyroid nodules are common in adults, with incidental detection rates reaching 50–60

Entheses are specialized tissues that connect ligaments and tendons to the bone surface and are frequently involved in seronegative spondyloarthritis. Enthesitis can also be detected in patients with metabolic disorders (MD), regardless of baseline autoimmune rheumatic disease, posing real diagnostic challenges. The present review discusses the pathophysiology of enthesitis and metabolic-associated enthesitis, the clinical relevance of metabolic disorders on enthesitis-related outcomes, diagnostic challenges for adequate differential diagnosis, and possible therapeutic strategies to improve clinical outcomes. PubMed/MEDLINE and the Cochrane Library were searched for original articles, systematic reviews, and meta-analyses. References were screened according to a hierarchical analysis of studies by title, abstract, and full text, collected, presented, and discussed. Metabolic-associated enthesitis is attributable to mechanical stress/overload due to weight excess typically observed in metabolic disorders (MD), such as overweight/obese comorbid patients, metabolic syndrome (MS), and type 2 diabetes (T2D). Interleukin 1β, 6, 17, 18, and 23 and tumor necrosis factor-α play a crucial role in initiating and maintaining entheseal inflammation. Chronic hyperglycemia and insulin resistance lead to a vicious circle as they stimulate, upon activated, specialized T cells to produce these specific cytokines, thus maintaining entheseal inflammation chronically. MD is associated with more severe clinical presentation, worse response to pharmacological treatments, and poor entheseal outcomes also in patients with existing seronegative spondyloarthritis. Non-immune-mediated metabolic-associated enthesitis poses a real diagnostic challenge, possibly underestimating cases and potential misdiagnoses. From a therapeutic viewpoint, glucose control improvement and weight loss are associated with relevant amelioration of entheseal-related outcomes. Pharmacological and non-pharmacological interventions aiming to reduce body weight, improve glucose control and insulin sensitivity, and attenuate inflammation are desirable to achieve the therapeutic target. Glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter type 2 inhibitors, in add-on to non-steroidal anti-inflammatory drugs and immunomodulators when necessary, may have a therapeutic rationale in patients with metabolic-associated enthesitis. Awareness of metabolic-associated enthesitis is essential to improve the accuracy of differential diagnosis in patients with MD and prescribe appropriate therapeutic strategies. However, basic and clinical research is needed to understand the role of “antihyperglycemic” agents in better managing metabolic-associated enthesitis.

The present guideline (GL) is aimed to improve and standardize the treatment of primary hypothyroidism in non-pregnant adults and to offer all the patients the best possible care across the Italian country. Non-pregnant adults with hypothyroidism. This GL does not cover the treatment of hypothyroidism in children and adolescents under 18 years of age, in women who are pregnant or breastfeeding, nor in subjects with central hypothyroidism. Also patients who require suppressive therapy with levothyroxine after thyroidectomy for thyroid cancer and those with transient iatrogenic hypothyroidism were not considered in this GL. The direct costs and the utilization of resources over time were evaluated for the implementation of the appropriate management within the National Health Service. Recommendations were based on the analysis, according to the GRADE methodology, of the evidence from literature. Patients preferences were collected and verified by means of specific bibliographic research and the active participation of two patients’ representatives in the GL development group. The present GL provides 4 formal graded recommendations and 16 ungraded indications for good clinical practice. An elevated agreement was consistently obtained among the panel members. The present GL provides operative recommendations—based on the best available evidence and cost-effectiveness analysis—for the treatment of adult patients with primary hypothyroidism. The expected benefits from the dissemination, application and implementation of this GL are the improvement of the quality of care, its homogenization across the national territory and the rationalization of health expenditure in the respect of patient preferences.

Background: The selection of thyroid nodules ≤ 10 mm requiring characterization and treatment should be improved, as extensive detection, cytological assessment, and surgery of small and well-differentiated thyroid carcinoma are not cost-effective. Aim: To assess the accuracy of algorithms and ultrasonographic characteristics in selecting actual high-risk thyroid nodules ≤ 10 mm. Methods: A cross-sectional study was conducted on 38 of 112 outpatients who attended the University of Bari and underwent echo-assisted FNA for cytological characterization of thyroid nodules ≤ 10 mm (65 out of 118) and thyroid surgery from January 01 to December 31, 2016. Results: The median age of patients was 49.5 years [16; 69]. Thyroid cytology (SIAPeC-IAP 2014) was classified as TIR1 (one nodule), TIR2 (15), TIR3A (7), TIR3B (10), TIR4 (8), and TIR5 (24). Thirty-nine thyroid nodules were diagnosed as well-differentiated thyroid microcarcinoma. The clinical performance of 4 algorithms widely employed in clinical practice was low (AACE/ACE/AME, 38%; ACR-TIRADS, 45%; K-TIRADS, 60%; EU-TIRADS, 66%). Ultrasonographic features indicating high-risk nodules were hypoechogenicity (p=0.0047), irregular margins (p=0.004), and microcalcifications (p=0.0019). Multivariable analyses indicated that hypoechogenicity was the main ultrasonographic characteristic associated with high-risk nodules (OR = 5.48, p=0.0484). Discussion: Validated algorithms fail to select thyroid nodules ≤ 10 mm for which cytological characterization is needed. Our results are expected to improve the reliability of current algorithms by improving the weight of variables associated with a more consistent risk of thyroid malignancy in nodules ≤ 10 mm.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Background: Chronic stress is a condition of pressure on the brain and whole body, which in the long term may lead to a frank disease status, even including type 2 diabetes (T2D). Stress activates the hypothalamus-pituitary-adrenal axis with release of glucocorticoids (GCs) and catecholamines, as well as activation of the inflammatory pathway of the immune system, which alters glucose and lipid metabolism, ultimately leading to beta-cell destruction, insulin resistance and T2D onset. Alteration of the glucose and lipid metabolism accounts for insulin resistance and T2D outcome. Furthermore, stress-related subversion of the intestinal microbiota leads to an imbalance of the gut-brain-immune axis, as evidenced by the stress-related depression often associated with T2D. Inflammatory mechanisms: A condition of generalized inflammation and subversion of the intestinal microbiota represents another facet of stress-induced disease. In fact, chronic stress acts on the gut-brain axis with multi-organ consequences, as evidenced by the association between depression and T2D. Novel Therapeutic Options: Oxidative stress with the production of reactive oxygen species and cytokine-mediated inflammation represents the main hallmarks of chronic stress. ROS production and pro-inflammatory cytokines represent the main hallmarks of stress-related disorders, and therefore, the use of natural antioxidant and anti-inflammatory substances (nutraceuticals) may offer an alternative therapeutic approach to combat stress-related T2D. Single or combined administration of nutraceuticals would be very beneficial in targeting the neuro-endocrine-immune axis, thus, regulating major pathways involved in T2D onset. However, more clinical trials are needed to establish the effectiveness of nutraceutical treatment, dosage, time of administration and the most favorable combinations of compounds. Therefore, in view of their antioxidant and anti-inflammatory properties, the use of natural products or nutraceuticals for the treatment of stress-related diseases, even including T2D, will be discussed. Several evidences suggest that chronic stress represents one of the main factors responsible for the outcome of T2D.

Obesity and metabolic syndrome are linked to steatotic liver disease (SLD), the most common form of chronic liver disease. Lifestyle modifications and dieting are strategies that can prevent metabolic dysfunction-associated steatotic liver disease (MASLD). The very low-calorie ketogenic diet (VLCKD) is a helpful treatment for MASLD and has been recommended for people affected by obesity; we evaluated the effect of gender on steatosis and fibrosis in a cohort of 112 overweight or obese patients undergoing an eight-week treatment with a VLCKD. Differences between the genders in terms of anthropometric measures, body composition, and metabolic indicators were examined before, during, and after the nutritional intervention. At baseline, there were significant differences between men and women in terms of anthropometric parameters, blood pressure, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting insulin, hepatic markers, and lipid profile. Men had considerably higher levels of liver steatosis (measured by CAP) and liver stiffness (measured by E) under basal conditions than women. After the VLCKD, there were reductions in both genders of controlled attenuation parameter (CAP), body weight, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, insulin resistance, fat mass (FM), free fat mass (FFM), and fasting blood glucose, insulin, glycated hemoglobin (HbA1c), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, alanine transaminase (ALT), gamma-glutamyl transferase (γGT), and uric acid levels. Only in men, liver stiffness, aspartate aminotransferase (AST), creatinine, and C-reactive protein (CRP) levels significantly decreased. Moreover, men had significantly greater levels of liver steatosis: the male gender featured an increase of 23.96 points of the Fibroscan CAP. Men exhibited higher levels of steatosis and fibrosis than women, and these differences persist despite VLCKD. These gender-specific variations in steatosis and fibrosis levels could be caused by hormonal and metabolic factors, suggesting that different therapeutic strategies might be required depending on the gender.

Introduction Perchlorates are ionic inhibitors antagonizing iodine transport into thyrocytes, hampering thyroid hormone synthesis. Nevertheless, perchlorates are not considered as first-line treatment in hyperthyroidism and thyrotoxicosis as compared to other pharmacological and non-pharmacological interventions. Aim Reassessing the therapeutic role of perchlorates in hyperthyroidism and thyrotoxicosis throughout a systematic review of the Literature. Methods Guidelines were searched and examined to summarize current recommendations on the use of perchlorates in the management of hyperthyroidism. Randomized and non-randomized clinical trials were also searched and reviewed to summarize the efficacy/effectiveness and safety of perchlorates in hyperthyroidisms and thyrotoxicosis. Results The management of specific forms of hyperthyroidism was considered, including Graves’ disease (GD) in non-pregnant adults, hyperthyroidisms in pregnancy, iodine media contrast-induced hyperthyroidism, amiodarone-induced hyperthyroidisms, and thyroid storm. Most of the reported studies had remarkable limitations in terms of study design (non-controlled trials, lack of blinding), low number of participants, and the lack of clinically relevant endpoints, such as cardiovascular events, cardiovascular mortality, and teratogenicity. Overall, perchlorates could be considered a second-line treatment after thionamides, radioiodine, and total thyroidectomy in both GD and hyperthyroidisms in pregnancy. The therapeutic potential of perchlorates alone or in combination with other agents could be considered a second-line treatment of iodine-related hyperthyroidisms and thyroid storm. Conclusion Despite the low level of evidence, perchlorates could be considered in such specific forms of thyroid disorders, including iodine-induced hyperthyroidism and thyroid storm.

BACKGROUND:Evidence indicates a wide range of andrological alterations in patients with the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection and Coronavirus Disease 2019 (COVID-19). AIM:To provide an update on the andrological effects of SARS-CoV-2 infection and COVID-19. METHODS:PubMed/MEDLINE and Institutional websites were searched for randomized clinical trials, non-systematic reviews, systematic reviews, and meta-analyses. RESULTS:Fifty-four records were included from 2020 to 2024. The most representative paper categories were non-systematic reviews (n = 26) and systematic reviews/meta-analyses (n = 27). One randomized, prospective, phase 2 trial was also included. Eight topics were identified and discussed as follows: short- and long-term seminal changes attributable to SARS-CoV-2 infection or COVID-19; andrological effects of anti-SARS-CoV-2 vaccines; the potential impact of SARS-CoV-2 infection and COVID-19 on male fertility; the relationship between serum testosterone levels and COVID-19 prognosis in men; fertility care during the pandemic; urinary/genital male system tract impairment in SARS-CoV-2 infection and COVID-19; the effect of SARS-CoV-2 infection and COVID-19 on circulating levels of sex steroid hormones; the impact of SARS-CoV-2 and COVID-19 on sexual function and activity. DISCUSSION:SARS-CoV-2 can affect the whole testicular function through direct and indirect mechanisms, with a positive relation between the severity of SARS-CoV-2 infection and the level of deterioration of testicular function. Testicular function recovers along with the recovery from the disease. In vitro fertilization techniques ensure similar results in patients with or without previous SARS-CoV-2 infection or COVID-19. Immunization with anti-SARS-CoV-2 vaccines prevents andrological complaints due to naturally occurring infection. Erectile dysfunction and sexual dysfunction are frequently diagnosed in COVID-19 patients due to several contributing factors, including hormonal imbalance and psychosocial complaints related to the pandemic.

Background: The initial phases of the COVID-19 pandemic posed a real need for clinicians to identify patients at risk of poor prognosis as soon as possible after hospital admission. Aims: The study aimed to assess the role of baseline anamnestic information, clinical parameters, instrumental examination, and serum biomarkers in predicting adverse outcomes of COVID-19 in a hospital setting of Internal Medicine. Methods: Fifty-two inpatients consecutively admitted to the Unit of Internal Medicine "Baccelli," Azienda Ospedaliero - Universitaria Policlinico of Bari (February 1 - May 31, 2021) due to confirmed COVID-19 were grouped into two categories based on the specific outcome: good prognosis (n=44), patients discharged at home after the acute phase of the infection; poor prognosis, a composite outcome of deaths and intensive care requirements (n=8). Data were extracted from medical records of patients who provided written informed consent to participate. Results: The two study groups had similar demographic, anthropometric, clinical, and radiological characteristics. Higher interleukin 6 (IL-6) levels and leucocyte count, and lower free triiodothyronine (fT(3)) levels were found in patients with poor than those with good prognosis. Higher IL-6 levels and leucocyte count, lower fT(3) concentration, and pre-existing hypercholesterolemia were independent risk factors of poor outcomes in our study population. A predicting risk score, built by assigning one point if fT(3) < 2 pg/mL, IL-6 >25 pg/mL, and leucocyte count >7,000 n/mm(3), revealed that patients totalizing at least 2 points by applying the predicting score had a considerably higher risk of poor prognosis than those scoring <2 points (OR 24.35 (1.32; 448), p = 0.03). The weight of pre-existing hypercholesterolemia did not change the risk estimation. Conclusion: Four specific baseline variables, one anamnestic (pre-existing hypercholesterolemia) and three laboratory parameters (leucocyte count, IL-6, and fT3), were significantly associated with poor prognosis as independent risk factors. To prevent adverse outcomes, the updated 4-point score could be useful in identifying at-risk patients, highlighting the need for specific trials to estimate the safety and efficacy of targeted treatments.

BACKGROUND:The neuropeptide oxytocin (OT) is crucial in several conditions, such as lactation, parturition, mother-infant interaction, and psychosocial function. Moreover, OT may be involved in the regulation of eating behaviors.METHODS:This review briefly summarizes data concerning the role of OT in eating behaviors. Appropriate keywords and medical subject headings were identified and searched for in PubMed/MEDLINE. References of original articles and reviews were screened, examined, and selected.RESULTS:Hypothalamic OT-secreting neurons project to different cerebral areas controlling eating behaviors, such as the amygdala, area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus nerve. Intracerebral/ventricular OT administration decreases food intake and body weight in wild and genetically obese rats. OT may alter food intake and the quality of meals, especially carbohydrates and sweets, in humans.DISCUSSION:OT may play a role in the pathophysiology of eating disorders with potential therapeutic perspectives. In obese patients and those with certain eating disorders, such as bulimia nervosa or binge/compulsive eating, OT may reduce appetite and caloric consumption. Conversely, OT administered to patients with anorexia nervosa may paradoxically stimulate appetite, possibly by lowering anxiety which usually complicates the management of these patients. Nevertheless, OT administration (e.g., intranasal route) is not always associated with clinical benefit, probably because intranasally administered OT fails to achieve therapeutic intracerebral levels of the hormone.CONCLUSION:OT administration could play a therapeutic role in managing eating disorders and disordered eating. However, specific studies are needed to clarify this issue with regard to dose-finding and route and administration time.

Background: Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. Aims: The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. Results: The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA1c levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). Conclusions: Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits.

Introduction: The prevalence of hypothyroidism increases along with aging, resulting in one of the most common comorbidities among patients over 75 years. The leading causes of hypothyroidism in older adults are iatrogenic, Hashimoto's thyroiditis, and medications. The narrative review aimed to discuss the clinical characteristics of hypothyroidism in older adults and the impact of hormonal replacement therapy on survival rates. Thyroid function declines over time due to physiological changes in the thyroid stimulating hormone signaling, iodine absorption and metabolism, thyroid hormone metabolism, and activity at peripheral sites. A serum TSH value over the upper limit of the normal reference range is not necessarily attributable to hypothyroidism. However, an appropriate diagnostic work-up is required to rule out true hypothyroidism and discriminate the etiology (i.e., thyroid autoimmune diseases, iodine deficiency, drug-induced hypothyroidism). Levothyroxine treatment should be considered in cases of overt hypothyroidism. A complete risk-to-benefit assessment, particularly considering the overall health status, life expectancy, cognitive function, mood, and cardiovascular and neurological background, should be considered before treating subclinical hypothyroidism with more potential benefits in patients under 75 years old. Levothyroxine formulations facilitating hormone absorption and increasing compliance to long-term treatment should be preferred. TSH target should usually be set over 3 mIU/ml. Defining optimal diagnostic approaches and targeted therapeutic strategies should be considered in the personalized management of aged patients with hypothyroidism. Results: Thyroid function declines over time due to physiological changes in the thyroid stimulating hormone signaling, iodine absorption and metabolism, thyroid hormone metabolism, and activity at peripheral sites. A serum TSH value over the upper limit of the normal reference range is not necessarily attributable to hypothyroidism. However, an appropriate diagnostic work-up is required to rule out true hypothyroidism and discriminate the etiology (i.e., thyroid autoimmune diseases, iodine deficiency, drug-induced hypothyroidism). Levothyroxine treatment should be considered in cases of overt hypothyroidism. A complete risk-to-benefit assessment, particularly considering the overall health status, life expectancy, cognitive function, mood, and cardiovascular and neurological background, should be considered before treating subclinical hypothyroidism with more potential benefits in patients under 75 years old. Levothyroxine formulations facilitating hormone absorption and increasing compliance to long-term treatment should be preferred. TSH target should usually be set over 3 mIU/ml.