A mutation in the estrogen receptor alpha gene (ESR1m) following first-line treatment with endocrine therapy in hormone receptor-positive metastatic breast cancer occurs in nearly half of patients. Detection of this mutation prior to radiologic progression using circulating tumor DNA (ctDNA)-based monitoring is an emerging practice that may allow an early switch to a more effective therapy. To discuss approaches to managing ESR1m advanced breast cancer (aBC) including ctDNA-based monitoring, AMCP Market Insights virtually convened an expert panel of managed care stakeholders in February 2026. This article provides a qualitative summary of the panel discussion along with key insights and suggested payer practices meant to support informed coverage decisions and guide future work. Key insights include that community oncologists and patients may benefit from support, for example, with treatment pathways and patient navigators. Additionally, patients care about survival outcomes when combined with sustained quality of life and want monitoring practices that take patient-specific considerations into account. A primary consideration of payers related to aBC is that the optimal biomarker testing parameters, including ctDNA-based monitoring for ESR1m aBC, are uncertain, which leads to inconsistent testing practices and the need for management that promotes consistency while mitigating delays in care. Payers acknowledge that the role of next-generation selective estrogen receptor degraders is evolving based on current data and ongoing clinical trials. Suggested payer practices involve care delivery, coverage, and system advancements including engaging in multistakeholder conversations and advocating for or participating in evidence generation.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with heterogeneous outcomes after resection. We conducted a retrospective single-institution cohort study of 65 resected primary ACCs from 2010 to 2025. Clinicopathologic features, tumor-type-specific histologic scoring, immunohistochemistry for p53, β-catenin, and Ki-67, clinical molecular testing results, and outcomes were analyzed. Survival was evaluated using Kaplan-Meier methods and Cox models adjusted for pT category. Increased mitotic activity (> 5 mitoses per 50 high-power fields) was present in 41/55 tumors (74.5%). Clinical molecular testing was performed in 32 tumors; 12 (37.5%) had at least one pathogenic or likely pathogenic (P/LP) alteration, most commonly involving TP53 (6/12) and CTNNB1 (3/12). P/LP alteration positivity was associated with worse overall survival (OS) after pT adjustment (HR, 4.67; 95% CI, 1.26-17.26; p = 0.021). Nuclear β-catenin expression was also associated with worse OS after pT adjustment (HR, 3.23; 95% CI, 1.19-8.79; p = 0.022). Increased mitotic activity remained associated with worse OS after pT adjustment (HR, 4.62; 95% CI, 1.07-19.91; p = 0.040), whereas its association with disease-specific survival did not reach statistical significance after pT adjustment (HR, 7.44; 95% CI, 0.98-56.21; p = 0.052). Ki-67 ≥ 10%, aberrant p53 staining, tumor necrosis, and angioinvasion were not significantly associated with survival after pT adjustment. Oncocytic ACCs had less frequent increased mitotic activity than conventional ACCs (44.4% vs. 79.1%; p = 0.048). Mitotic activity, nuclear β-catenin expression, and clinically reported P/LP alterations may provide complementary prognostic information in resected primary ACC. Larger cohorts with standardized pathology review and uniform molecular profiling are needed.

Klinefelter syndrome (KS) is a common, yet underdiagnosed sex chromosome aneuploidy characterized by considerable phenotypic variability and multisystem involvement beginning in early life. The increasing use of noninvasive prenatal testing has led to earlier diagnosis, highlighting the need to redefine clinical management across the pediatric age. In this narrative review, pediatric endocrinologists, neuropsychiatrists, psychologists, and genetic experts critically examine current evidence on genetic mechanisms, growth, pubertal development, cardiometabolic risk, and neuropsychological features of KS, and includes a dedicated patient advocacy perspective highlighting family priorities and unmet needs. Emerging evidence indicates that altered body composition, insulin resistance, and neurodevelopmental vulnerabilities may arise in childhood, often preceding overt hypogonadism. Language impairment, executive dysfunction, and social cognitive difficulties represent key determinants of functional outcomes and require early recognition. Early childhood represents a window of opportunity for targeted interventions. A proactive, multidisciplinary, and preventive approach is essential to optimize long-term clinical, cognitive, and social outcomes in individuals with KS.

West Nile virus (WNV) is an uncommon but serious case of encephalitis and meningitis, often presenting with nonspecific symptoms that can mimic a wide range of infectious, metabolic, and endocrine disorders. We present the case of a 61-year-old male with multiple comorbidities who arrived with 5 days of fever, chills, profuse diarrhea, black stools, and worsening confusion. Initial evaluation in the emergency department revealed hyponatremia, transaminitis, and concern for tick-borne illness, prompting empiric doxycycline. However, the patient denied any tick bites. Given his known thyroid nodule and Burch-Wartofsky screening score of 70, he was empirically treated for thyroid storm despite laboratory evidence of subacute hypothyroidism. During hospitalization, our patient developed acute hypoxic respiratory failure requiring emergent intubation, as well as second-degree heart block and supraventricular tachycardia following propranolol administration. Neurologic workup revealed moderate encephalopathy on EEG and an opening pressure of 36 cm H2O on lumbar puncture. CSF examination revealed pleocytosis with mixed neutrophilic and lymphocytic predominance. Despite broad-spectrum antibiotic coverage, initial testing, which included a tick panel, Monospot, respiratory studies, and viral PCR assays, was insignificant. On hospital day eight, CSF serologies were positive for WNV IgM with negative IgG, confirming acute WNV neuroinvasive disease presenting as meningitis. This case highlights the diagnostic complexity of WNV infection, which may initially resemble tick-borne illness, endocrine crisis, or bacterial meningitis. Early consideration of WNV in patients with unexplained encephalopathy, GI symptoms, hyponatremia, and CSF lymphocytic pleocytosis, especially during mosquito season, may reduce delays in diagnosis and prevent unnecessary interventions.

Postnatal mammary gland development is a hormone-dependent process involving extensive epithelial expansion and stromal remodeling. Although endocrine regulation of mammary morphogenesis is well established, the role of the immune system during normal mammary gland development remains incompletely understood. Here, we characterized immune remodeling across pre-puberty, peri-puberty, and adulthood in the rat mammary gland by integrating bulk transcriptomics, immune-stromal deconvolution, pathway enrichment analysis, cytokine and chemokine profiling, and immunolocalization. Our analyses identified peri-puberty as a distinct phase of immune-stromal remodeling. Pre-puberty was enriched in innate immune populations and immune establishment programs associated with tissue organization. In contrast, peri-puberty displayed increased adaptive immune signatures and activation of chemokine pathways involved in leukocyte recruitment and spatial organization. Notably, this transition occurred alongside lower tissue concentrations of several inflammatory cytokines, suggesting that immune recruitment during peri-puberty reflects a developmentally programmed signaling state rather than classical inflammation. By adulthood, immune composition and signaling profiles stabilized, consistent with immune homeostasis and surveillance. Transcript-protein integration revealed limited concordance between developmental changes in cytokine and chemokine transcripts and their corresponding proteins. No paired RNA-protein associated remained significant after multiple-testing correction, suggesting that regulation beyond transcription may contribute to soluble mediator profiles. Together, these findings demonstrate that postnatal mammary gland development is accompanied by stage-specific immune programming and establish a systems-level framework for understanding developmental immunology in the mammary gland.

Epidemiological studies undertaken following the first and second decade after the introduction of Universal salt iodisation (USI) in 1986 had pointed towards mild persistence in goitre, iodine excess as measured by spot urinary iodine concentration (UIC) and increase in thyroid autoimmunity. We aim to look at the status of iodine nutrition, goitre prevalence, thyroid dysfunction, and autoimmunity in Indian school-children in the fourth decade of implementation of USI.