Endocrine Management of Transgender Adults: A Clinical Approach

The attention to transgender medicine has changed over the last decade and the interest is most likely going to increase in the future due to the fact that gender-affirming treatments are now being requested by an increasing number of transgender people. Even if gender-affirming hormone therapy (GAHT) is based on a multidisciplinary approach, this review is going to focus on the procedures adopted by the endocrinologist in an out-clinic setting once an adult patient is referred by another specialist for ‘gender affirming’ therapy. Before commencing this latter treatment, several background information on unmet needs regarding medical and surgical outcomes should be investigated. We summarized our endocrinological clinical and therapeutic approaches to adult transgender individuals before and during GAHT based on a non-systematic review. Moreover, the possible relationships between GAHT, gender-related pharmacology, and COVID-19 are also reported

Malignancy Analyses of Thyroid Nodules in Patients Subjected to Surgery with Cytological- and Ultrasound-Based Risk Stratification Systems

The fine needle aspiration (FNA) cytology is the gold standard for the preoperative diagnosis of thyroid cancer. However, up to 30% of FNA examinations yield nondiagnostic or indeterminate results and this complicates patient management. Clinical features and ultrasound (US) patterns, including US risk stratification systems, could be useful in the preoperative diagnostic workup and prediction of malignancy, but the evidences are not univocal. Methods: 400 consecutive patients subjected to thyroid surgery were retrospectively enrolled at our institution in Calabria, Southern Italy. Preoperative US and FNA cytological descriptions, formulated according to the “Italian consensus for reporting thyroid fine-needle aspiration cytology” (ICCRTC) classification and three US risk stratification systems (those developed by the American Association of Clinical Endocrinologists, American College of Endocrinology and Associazione Medici Endocrinologi (AACE/ACE/AME), American Thyroid Association (ATA), and American College of Radiology (ACR-TIRADS)), were collected, along with histological results. Results: 147 thyroid cancer cases, in large majority papillary carcinomas, were detected on final histological examination. Almost two-thirds of patients subjected to thyroid surgery for either benign or malignant lesions were female. Patient’s age ≤20 years and between 21–30 years were clinical features associated with increased risk of thyroid cancer in logistic regression analyses. US features associated with thyroid cancer included irregular margins, solid composition, microcalcifications, and marked hypoechogenicity. The AACE/ACE/AME, ATA, and ACR-TIRADS risk categories, corresponding to specific US patterns, were strong predictors of malignancy in both genders, but not in nodules with indeterminate cytology. A measured difference between the longitudinal (L) and the anteroposterior (AP) diameter >5 mm, a proxy for a parallel-oriented oval shape of a nodule, emerged as a robust protective factor against thyroid cancer (OR 0.288 (95%CI 0.817–0.443); p < 0.001), regardless of cytological risk. Conclusions: Some, but not all, well-established predictors of TC have been confirmed in this study. Controversy surrounds the diagnostic performance of US risk stratification systems for the detection of thyroid cancer in the subgroup of nodules with indeterminate cytology, suggesting their use only to set the thresholds for FNA. A measured difference between L and AP diameters >5 mm may represent an additional and practical tool for ruling out malignancy in thyroid nodules, with the potential to reduce unnecessary surgical procedures

Autoimmune Hypophysitis with Late Renal Involvement: A Case Report

We report a case of a 50-year-old male admitted to the Endocrinology Unit because of persistent headaches, nausea, feeling tired, sudden weight loss, cold intolerance, decreased appetite, and lack of sex interest. Diagnostic workup showed a 6-millimeter pituitary tumor without signs of compression, and a condition of progressive panhypopituitarism. After 12 months of hormone replacement therapy, the patient was hospitalized because of sudden weight gain, periorbital-peripheral edema, severe dyslipidemia, hypertension, and proteinuria. Corticosteroid therapy was shifted from oral to continuous intravenous infusion, and once the diagnosis of “immune complex-mediated glomerulonephritis with mesangial deposits suggestive for membranoproliferative glomerulonephritis type IIIIgG4-positive” was made, the immunosuppressant mycophenolate (1500 mg/day) was started. After a 6-month follow-up, the complete resolution of renal symptoms was accompanied by the disappearance of a pituitary lesion and the patient was back to prior hormone replacement therapy. Autoimmune hypophysitis (AH) is a rare autoimmune inflammatory disease of the pituitary gland that can impair hormone secretion and function. IgG4-hypophysitis is rare and is usually associated with other IgG4-related diseases. Herein, we describe a rare case of AH associated with late renal disease, and without any other organ involvement

Overexpression of p75NTR in Human Seminoma: A New Biomarker?

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr = 40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in seminoma tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker for seminoma and staging in TGCTs

Consultation between forensic and clinical pathologists for histopathology examination after forensic autopsy

The magnitude of the diagnostic benefit conferred by performing histopathological examinations after medico-legal/forensic autopsies remains debatable. We have tried to address this issue by reviewing a series of histopathology referrals concerning medico-legal autopsies in real-world routine practice. We present an audit of the consultations provided to forensics by clinical pathologists at our institute between 2015 and 2018. Over this period, 493 post-mortem examinations were performed by forensic pathologists. Of these cases, 52 (11%) were referred for histopathology. Gross assessment was requested in 22/52 (42%) cases. Histopathology examination was performed on single organs in 15/52 (29%) cases, primarily on the lung and heart, whereas parenchymatous multi-organ analysis was carried out in 14/52 (27%) cases. Bone-marrow sampling was studied in 4/52 (8%) cases. Immunohistochemistry was needed in 16/52 (31%) cases, special stains in 9/52 (21%) cases and molecular analysis in 4/52 (8%) cases. Focusing on technical processes, standard methodology on pre-analytical procedures was changed in 10/52 (19%) cases in order to answer specific diagnostic questions. We showed that although most of the time the diagnosis is clear by the end of dissection on the basis of the macroscopic findings, histopathology can provide, modify or confirm the cause of death in many medico-legal/forensic cases. Therefore, it is desirable that forensic pathologists and clinical pathologists establish robust working relationships in a cooperative environment. We conclude that it is important to implement guidelines based on real-world routine practice in order to identify cases where histopathology can provide useful contributions, which in our experience applied to 11% of forensic cases

Clinical Outcome of Discordant Empirical Therapy and Risk Factors Associated to Treatment Failure in Children Hospitalized for Urinary Tract Infections

With the spread of antibiotic resistance in pediatric urinary tract infections (UTIs), more patients are likely to be started empirically on antibiotics to which pathogens are later found to be resistant (discordant therapy). However, in-vivo effectiveness may be different from in-vitro susceptibility. Aims of this study were to describe clinical outcomes of discordant empirical treatments in pediatric UTIs and to investigate risk factors associated to treatment failure. This observational, retrospective study was conducted on children hospitalized for febrile UTIs with positive urine culture and started on discordant empirical therapy. Failure rates of discordant treatments and associated risk factors were investigated. A total of 142/1600 (8.9%) patients were treated with inadequate empirical antibiotics. Clinical failure was observed in 67/142 (47.2%) patients, with no fatal events. Higher failure rates were observed for combinations of penicillin and beta-lactamase inhibitors (57.1%). Significant risk factors for failure of discordant treatment were history of recurrent UTIs (95% CI: 1.13–9.98, OR: 3.23, p < 0.05), recent use of antibiotics (95% CI: 1.46–21.82, OR: 5.02, p < 0.01), infections caused by Pseudomonas aeruginosa (95% CI: 1.85–62.10, OR: 7.30, p < 0.05), and empirical treatment with combinations of penicillin and beta-lactamase inhibitors (95% CI: 0.94–4.03, OR: 1.94, p = 0.05). This study showed that discordant empirical treatments may still be effective in more than half of pediatric UTIs. Clinical effectiveness varies between different discordant antibiotics in pediatric UTIs, and patients presenting risk factors for treatment failure may need a differentiated empirical approach

Retrospective 8-Year Study on the Antibiotic Resistance of Uropathogens in Children Hospitalised for Urinary Tract Infection in the Emilia-Romagna Region, Italy

The development and spread of antibiotic resistance is an increasingly important global public health problem, even in paediatric urinary tract infection (UTI). In light of the variability in the data, it is necessary to conduct surveillance studies to determine the prevalence of antibiotic resistance in specific geographical areas to optimize therapeutic management. In this observational, retrospective, multicentre study, the medical records of 1801 paediatric patients who were hospitalised for UTI between 1 January 2012, and 30 June 2020, in Emilia-Romagna, Italy, were analysed. Escherichia coli was the most frequently detected pathogen (75.6%), followed by Klebsiella pneumoniae (6.9%) and Pseudomonas aeruginosa (2.5%). Overall, 840 cases (46.7%) were due to antimicrobial-resistant uropathogens: 83 (4.7%) extended spectrum beta-lactamase (ESBL)-producing, 119 (6.7%) multidrug resistant (MDR) and 4 (0.2%) extensively drug resistant (XDR) bacteria. Empirical antibiotic therapy failed in 172 cases (9.6%). Having ESBL or MDR/XDR uropathogens, a history of recurrent UTI, antibiotic therapy in the preceding 30 days, and empirical treatment with amoxicillin or amoxicillin/clavulanate were significantly associated with treatment failure, whereas first-line therapy with third-generation cephalosporins was associated with protection against negative outcomes. In conclusion, the increase in the resistance of uropathogens to commonly used antibiotics requires continuous monitoring, and recommendations for antibiotic choice need updating. In our epidemiological context, amoxicillin/clavulanate no longer seems to be the appropriate first-line therapy for children hospitalised for UTI, whereas third-generation cephalosporins continue to be useful. To further limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be implemented

Antibiotic Prophylaxis for the Prevention of Urinary Tract Infections in Children: Guideline and Recommendations from the Emilia-Romagna Pediatric Urinary Tract Infections (UTI-Ped-ER) Study Group

Background: Urinary tract infection (UTI) represents one of the most common infectious diseases and a major cause of antibiotic prescription in children. To prevent recurrent infections and long-term complications, low-dose continuous antibiotic prophylaxis (CAP) has been used. However, the efficacy of CAP is controversial. The aim of this document was to develop updated guidelines on the efficacy and safety of CAP to prevent pediatric UTIs. Methods: A panel of experts on pediatric infectious diseases, pediatric nephrology, pediatric urology, and primary care was asked clinical questions concerning the role of CAP in preventing UTIs in children. Overall, 15 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results: The use of CAP is not recommended in children with a previous UTI, with recurrent UTIs, with vesicoureteral reflux (VUR) of any grade, with isolated hydronephrosis, and with neurogenic bladder. CAP is suggested in children with significant obstructive uropathies until surgical correction. Close surveillance based on early diagnosis of UTI episodes and prompt antibiotic therapy is proposed for conditions in which CAP is not recommended. Conclusions: Our systematic review shows that CAP plays a limited role in preventing recurrences of UTI in children and has no effect on its complications. On the other hand, the emergence of new antimicrobial resistances is a proven risk