Purpose Overt hypothyroidism during pregnancy is linked to various obstetric complications, such as premature birth and fetal death. While some studies have shown that maternal hypothyroidism can impact a child's Intelligence Quotient (IQ) and language development, findings are controversial. The aim of this study was to explore the connection between treated maternal hypothyroidism during pregnancy and offspring neurodevelopment, focusing on learning and language and examining related maternal obstetric complications. Methods Group 1 included 31 hypothyroid women with elevated thyroid stimulating hormone (TSH) (> 10 mU/L, > 10 µIU/mL) during pregnancy, and Group 2 had 21 euthyroid women with normal TSH levels (0.5–2.5 mU/L, 0.5–2.5 µIU/mL). Children underwent neuropsycological assessments using the Griffiths-II scale. Results Pregnancy outcome showed an average gestational age at delivery of 38.2 weeks for hypothyroid women, compared to 40 weeks for controls, and average birth weight of 2855.6 g versus 3285 g for controls, with hypothyroid women having children with higher intrauterine growth restriction (IUGR) prevalence and more caesarean sections. The 1-min APGAR score was lower for the hypothyroid group's children, at 8.85 versus 9.52. Neuropsychological outcomes showed children of hypothyroid mothers scored lower in neurocognitive development, particularly in the learning and language subscale (subscale C), with a notable correlation between higher maternal TSH levels and lower subscale scores. Conclusion Fetuses born to hypothyroid mothers appeared to be at higher risk of IUGR and reduced APGAR score at birth. Neurocognitive development seemed to affect language performance more than the developmental quotient. This alteration appeared to correlate with the severity of hypothyroidism and its duration.

Background Current management options for PTMC include lobo-isthmectomy and active surveillance (AS). Recently, ultrasound-guided minimally invasive procedures (MITs) are offered as a nonsurgical therapy for PTMC because they do not require hospitalization and general anaesthesia, and do not result in loss of thyroid function or cosmetic damage. MITs are reported to consistently provide, mostly in large retrospective series of patients, a rapid, safe, and cost-effective way to eradicate low-risk thyroid malignancies. However, conclusive data from well-conducted prospective studies on the histologically-proven completeness of tumor ablation and the long-term clinical advantages versus AS are still lacking.Objectives This study aimed to evaluate the efficacy and safety of ultrasound-guided minimally invasive treatments (MITs) for PTMC in comparison to traditional surgical methods and active surveillance, and to assess their role in current clinical practice.Methods A structured literature review was conducted using keywords related to PTMC, MIT, and comparative techniques. Studies were evaluated based on treatment modality, patient selection, follow-up duration, complication rates, and clinical outcomes.Results MITs have shown promising results in the management of PTMC. These treatments offer several advantages over surgery, such as reduced use of surgical resources, lower costs, minimal work disruption, and fewer major complications. However, there are still limitations, including the need for long-term surveillance and the potential risk of incomplete tumor ablation.Conclusions MITs represent a promising non-surgical option for managing low-risk PTMC, especially for patients ineligible for or refusing surgery. Despite favorable outcomes, more robust prospective data are needed to confirm their long-term benefits and completeness of tumor ablation. Interdisciplinary discussions and thorough patient education on the advantages and limitations of MITs are crucial for informed decision-making.

Purpose Nearly, 40% of the causes of male infertility remain idiopathic. The only suggested treatment in idiopathic oligo- and/or asthenozoospermia in normogonadotropic patients is the FSH. In the current clinical practice, efficacy is exclusively assessable through semen analysis after 3 months of treatment. No molecular markers of treatment efficacy are appliable in clinical practice. The aim of the present work is to evaluate the combination of extracellular signal regulated kinase (ERK) 1 and 2 and prolactin inducible peptide (PIP) as potential markers of idiopathic infertility and FSH treatment efficacy. Methods Western blot and confocal microscopy were performed to analyze the modulation of PIP and ERK1/2 in idiopathic infertile patients (IIP) sperm cells. Taking advantage of mass spectrometry analysis, we identified these proteins unequivocally in sperm cells. Results We demonstrated a significant decrease of both PIP protein and of ERK1/2 levels in spermatozoa obtained from IIP in comparison to healthy fertile patients (HFP). Conversely, we reported a significant increase of these markers comparing infertile patients before and after 3 months of FSH treatment. Importantly, this correlated with an increase in total number of sperm and sperm motility after FSH treatment. Finally, we identified of PIP and ERK2 proteins in sperm samples by proteomic analysis. Conclusions The combined evaluation of ERK1/2 and PIP proteins might represent a useful molecular marker to tailor FSH treatment in the management of male normogonadotropic idiopathic infertility.

AIMS/HYPOTHESIS:Type 2 diabetes (T2D) is characterized by a progressive loss of beta-cell function, and the "disappearance" of beta-cells in T2D may also be caused by the process of beta -cell dedifferentiation. Since noradrenergic innervation inhibits insulin secretion and density of noradrenergic fibers is increased in type 2 diabetes mouse models, we aimed to study the relation between islet innervation, dedifferentiation and beta-cell function in humans. METHODS:Using immunohistochemistry and electron microscopy, we analyzed pancreata from organ donors and from patients undergoing pancreatic surgery. In the latter, a pre-surgical detailed metabolic characterization by oral glucose tolerance test (OGTT) and hyperglycemic clamp was performed before surgery, thus obtaining in vivo functional parameters of beta-cell function and insulin secretion. RESULTS:The islets of diabetic subjects were 3 times more innervated than controls (0.91 ± 0.21 vs 0.32 ± 0.10, n.fibers/islet; p = 0.01), and directly correlated with the dedifferentiation score (r = 0.39; p = 0.03). In vivo functional parameters of insulin secretion, assessed by hyperglycemic clamp, negatively correlated with the increase in fibers [beta-cell Glucose Sensitivity (r = -0.84; p = 0.01), incremental second-phase insulin secretion (r = -0.84, p = 0.03) and arginine-stimulated insulin secretion (r = -0.76, p = 0.04)]. Moreover, we observed a progressive increase in fibers, paralleling worsening glucose tolerance (from NGT through IGT to T2D). CONCLUSIONS/INTERPRETATION:Noradrenergic fibers are significantly increased in the islets of diabetic subjects and this positively correlates with beta-cell dedifferentiation score. The correlation between in vivo insulin secretion parameters and the density of pancreatic noradrenergic fibers suggests a significant involvement of these fibers in the pathogenesis of the disease, and indirectly, in the islet dedifferentiation process.

In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID-19.

OBJECTIVE: This review inspects the relations between the microbiota and the intestinal immune system in the advancement of metabolic illnesses, such as obesity and diabetes mellitus. The role of the microbiota in intestinal immune defense and the control of metabolism are subject to examination. MATERIALS AND METHODS: In type 1 diabetes, the adhesion proteins prompt inside the intestinal epithelium prompt a more significant immune response that may result in the destruction of pancreatic beta cells by CD8+ T-lymphocytes, as well as increased articulation of interleukin-17, which is associated with autoimmunity. Studies suggest that the beginning of metabolic ailments and certain co-morbidities can be viewed in light of the protection between the gut microbiota and the intestinal immune system. The gut microbiota is analyzed as a key regulator of metabolic ailments. Research demonstrates that obese patients with type 2 diabetes have a certain gut microbiota and that the microbiota is translocated from the gut to the tissues in conjunction with the illness, which instigates inflammation. RESULTS: Research in animals and people suggests that a probiotic supplement may regulate the gut microbiota. thereby improving the prognosis for diabetes. CONCLUSIONS: The mechanism underlying this phenomenon relates to a decrease in the inflammatory reaction and oxidative stress, as well as a decrease in leaky gut. Such reactions increase insulin sensitivity and reduce autoimmune responses.

INTRODUCTION:Hypercortisolism requires a prompt therapeutic management to reduce the risk of development of a potential fatal emergency. A synchronous bilateral adrenalectomy (SBA) is effective in recovering hypercortisolism. However, specific indications for an SBA are not available. We aimed to evaluate the outcome of patients who underwent an SBA and to identify biomarkers able to predict the requirements of an SBA.PATIENTS AND METHODS:A mono-centric and longitudinal study was conducted on 19 consecutive patients who underwent SBA for ACTH-dependent hypercortisolism between December 2003 and December 2017. This study population was compared to two control groups composed of patients cured after the resection of the ACTH secreting pituitary adenoma (Group A: 44 patients) and of the ACTH-secreting neuroendocrine tumours (Group B: 8 patients).RESULTS:Short- or long-term SBA complications or the recurrence of hypercortisolism did not occur. A single patient experienced Nelson syndrome. Clinical features after SBA showed improvement in the glico-metabolic assessment, hypertension, bone metabolism and the occurrence of hypokalaemia and infections. The younger the age at the time of Cushing's disease diagnosis, the longer the duration of active hypercortisolism, higher values of plasmatic ACTH and Cortisol (1 month after pituitary neurosurgery) and higher values of Ki67 in pituitary adenomas were detected in this study population as compared to Group A.CONCLUSIONS:SBA is an effective and safe treatment for patients with unmanageable ACTH-dependent hypercortisolism. A multidisciplinary team in a referral centre with a high volume of patients is strongly recommended for the management of these patients and the identification of patients, for better surgical timing.

Diabetic foot ulcers (DFUs), a micro-vascular complication, are associated with a substantial increase in morbidity and mortality. DFUs are a complicated mixture of neuropathy, peripheral arterial diseases, foot deformities, and infections. Foot infections are frequent and potentially devastating complications. Infection prospers in more than half of all foot ulcers and is the factor that most often leads to lower extremity amputation. The complications of microbial flora span the spectrum from superficial cellulitis to chronic osteomyelitis and gangrenous extremity lower limb amputations. Wounds without confirmed soft tissue or bone infections do not require antibiotic therapy. Mild and moderate infections need empiric therapy covering Gram-positive cocci, while severe infections caused by drug-resistant organisms require broad-spectrum anti-microbials targeting aggressive Gram-negative aerobes and obligate anaerobes.

Several authors have underlined the limits of morphological analysis mostly in the diagnosis of follicular neoplasms (FN). The application of ancillary techniques, including immunocytochemistry (ICC) and molecular testing, contributes to a better definition of the risk of malignancy (ROM) and management of FN. According to literature, the application of models, including the evaluation of ICC, somatic mutations (ie, BRAFV600E ), micro RNA analysis is proposed for FNs. This study discusses the validation of a diagnostic algorithm in FN with a special focus on the role of morphology then followed by ancillary techniques.From June 2014 to January 2016, we enrolled 37 FNs with histological follow-up. In the same reference period, 20 benign nodules and 20 positive for malignancy were selected as control. ICC, BRAFV600E mutation and miR-375 were carried out on LBC.The 37 FNs included 14 atypia of undetermined significance/follicular lesion of undetermined significance and 23 FN. Specifically, atypia of undetermined significance/follicular lesion of undetermined significance resulted in three goitres, 10 follicular adenomas and one NIFTP whereas FN/suspicious for FN by seven follicular adenomas and 16 malignancies (nine non-invasive follicular thyroid neoplasms with papillary-like nuclear features, two invasive follicular variant of papillary thyroid carcinoma [PTC] and five PTC). The 20 positive for malignancy samples included two invasive follicular variant of PTC, 16 PTCs and two medullary carcinomas. The morphological features of BRAFV600E mutation (nuclear features of PTC and moderate/abundant eosinophilic cytoplasms) were associated with 100% ROM. In the wild type cases, ROM was 83.3% in presence of a concordant positive ICC panel whilst significantly lower (10.5%) in a negative concordant ICC. High expression values of MirR-375 provided 100% ROM.The adoption of an algorithm might represent the best choice for the correct diagnosis of FNs. The morphological detection of BRAFV600E represents the first step for the identification of malignant FNs. A significant reduction of unnecessary thyroidectomies is the goal of this application.

Skeletal fragility with high risk of vertebral fractures is an emerging complication of acromegaly in close relationship with duration of active disease. The aim of this cross-sectional study was to evaluate the prevalence and determinants of vertebral fractures in males and females with a history of long-standing active acromegaly undergoing treatment with Pegvisomant.

Multiple endocrine neoplasia type 1 (MEN1) is an inherited endocrine neoplastic syndrome associated with a greater risk of endocrine tumor development like pancreatic neuroendocrine tumors (p-NET), with different clinical characteristics from sporadic ones. This paper aims to compare clinical, hystological and morphological aspects of p-NET in patients affected from MEN1 (MEN1+) and not-affected ones (MEN1−).

Background Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Methods Six scientific Italian societies entitled to cure thyroid cancer patients (the Italian Thyroid Association, the Medical Endocrinology Association, the Italian Society of Endocrinology, the Italian Association of Nuclear Medicine and Molecular Imaging, the Italian Society of Unified Endocrine Surgery and the Italian Society of Anatomic Pathology and Diagnostic Cytology) felt the need to develop a consensus report based on significant scientific advances occurred in the field. Objective The document includes recommendations regarding initial evaluation of thyroid nodules, clinical and ultrasound criteria for fine-needle aspiration biopsy, initial management of thyroid cancer including staging and risk assessment, surgical management, radioiodine remnant ablation, and levothyroxine therapy, short-term and long-term follow-up strategies, and management of recurrent and metastatic disease. The objective of this consensus is to inform clinicians, patients, researchers, and health policy makers about the best strategies (and their limitations) relating to the diagnosis and treatment of differentiated thyroid cancer.

Thyroid ultrasonography (US) is the gold standard for thyroid imaging and its widespread use is due to an optimal spatial resolution for superficial anatomic structures, a low cost and the lack of health risks. Thyroid US is a pivotal tool for the diagnosis and follow-up of autoimmune thyroid diseases, for assessing nodule size and echostructure and defining the risk of malignancy in thyroid nodules. The main limitation of US is the poor reproducibility, due to the variable experience of the operators and the different performance and settings of the equipments. Aim of this consensus statement is to standardize the report of thyroid US through the definition of common minimum requirements and a correct terminology. US patterns of autoimmune thyroid diseases are defined. US signs of malignancy in thyroid nodules are classified and scored in each nodule. We also propose a simplified nodule risk stratification, based on the predictive value of each US sign, classified and scored according to the strength of association with malignancy, but also to the estimated reproducibility among different operators.

Neck pain is a common complain, being in most cases due to non-thyroidal causes. However, a minority of patients suffer from painful thyroid diseases. Among them, sub-acute thyroiditis (SAT) is the most frequent one. Rare thyroid-related causes of neck pain include hemorrhage within a thyroid nodule as well as Riedel’s thyroiditis and suppurative thyroiditis. In the last 30 years, a few cases of a painful variant of Hashimoto’s thyroiditis (HT) have been described. Biochemical, ultrasound, and histologic features were clearly suggestive for HT in all of the published cases and definitely ruled out the diagnosis of SAT. While sound descriptions of painful HT are present in the literature, it is important to emphasize that only 20 cases were reported from the year 2000 until now. The condition, however, is clinically relevant because neck pain was reported to be refractory both to steroids and to other analgesic drugs, being thyroidectomy the only effective treatment for pain relief in these patients. This short review analyzes currently available data supporting a role for HT as a rare cause of neck pain.

ABSTRACT Increasing evidence suggests that vitamin D exerts multiple effects beyond bone and calcium metabolism. Vitamin D seems to play a role in pancreatic disease, including type 1 and type 2 diabetes mellitus as well as pancreatic cancer. Vitamin D's immune-modulatory action suggests that it could help prevent type 1 diabetes. In type 2 diabetes, vitamin D may influence β-cell function, insulin sensitivity, and systematic inflammation—all characteristic pathways of that disease. Data from observational studies correlated vitamin D deficiency with risk of type 1 and type 2 diabetes. Prospective and ecological studies of pancreatic cancer incidence generally support a beneficial effect of higher 25-hydroxyvitamin D concentration as well as inverse correlations between UVB dose or exposure and incidence and/or mortality rate of pancreatic cancer. This review discusses the literature regarding vitamin D's role in risk of diabetes and pancreatic cancer. The results to date generally satisfy Hill's criteria for causality regarding vitamin D and incidence of these pancreatic diseases. However, large randomized, blinded, prospective studies are required to more fully evaluate the potential therapeutic role of vitamin D in preventing pancreatic diseases.

OBJECTIVE:FNA biopsy is considered as the most accurate method for the selection of patients with thyroid nodules that need for surgery or for the wait and see management. The aim of the present study is to clarify the risk of malignancy for the cytological data classified according to the 2014 Italian reporting system.METHODS:We report a retrospective analysis of 4043 patients in our institution's experience during the period April 2014 through December 2016 with the Italian reporting system for thyroid cytology.RESULTS:The diagnostic incidences of the 4043 cases were as follows: 9.8% TIR1; 1.3% TIR1C; 70% TIR2; 6.6% TIR3A; 4.5% TIR3B; 2.4% TIR4; 5.2% TIR5. A repeated aspiration was carried out in 68 out of 269 cases (25%) classified as TIR3A. A total of 407 cases with cytology underwent surgical resection. A malignant neoplasm was detected in 261 out of 407 (64%) cases. Regarding TIR3B, surgical excision was undertaken in 109 cases, which included 42 high-risk lesions and 67 Hürthle cell neoplasms. The risk of malignancy was significantly higher in the former compared to the latter (50% vs 9%; P<.05).CONCLUSIONS:This investigation emphasises the reliability of the 2014 Italian Reporting System concerning the mutual frequency of the diagnostic categories. The risk of malignancy is perfectly within the range of the estimated values.