Hepatic metabolism of 11-oxygenated androgens in humans: an integrated in vivo and ex vivo approach.

Objective: Excess production of adrenal-derived 11-oxygenated androgens is observed in congenital adrenal hyperplasia, premature adrenarche, and polycystic ovary syndrome. 11-Ketotestosterone is equipotent to testosterone but does not decline with age. To date, the precise hepatic metabolism of 11-oxygenated androgens and subsequent urinary metabolite excretion have not been characterised.

Equity in initial health evaluation utilization among world trade center health program members enrolled during 2012-2022.

Background: The World Trade Center (WTC) Health Program, a limited federal healthcare program, provides medical monitoring and treatment for WTC-related conditions to eligible Responders and Survivors of the 9/11 terrorist attacks. Free initial health evaluations (IHE) represent the first step towards the Program's goal of providing equitable and timely member access to healthcare. This study aimed to evaluate equity in IHE utilization among Program members to inform the development of targeted interventions.

Pituitary disorders in pregnancy.

The management of pituitary disorders in pregnancy presents a unique challenge for maternal medicine specialists and endocrinologists. Advances in assisted reproductive technologies (ART) mean that women with hypopituitarism are increasingly able to conceive. The pituitary undergoes significant physiological changes during pregnancy.

POLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: Polycystic ovary syndrome: the impact of androgen excess on metabolic health.

In Brief: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterised by androgen excess, which drives not only reproductive dysfunction but also significant metabolic disturbances. This review outlines the mechanistic role of classical and 11-oxygenated androgens in tissue-specific metabolic dysfunction and their progression to the metabolic manifestations seen in women with PCOS.

Abstract: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterised by androgen excess, reproductive dysfunction and metabolic disturbances.

Fluid and electrolyte disorders following traumatic brain injury.

Abnormalities in salt and water balance are common following traumatic brain injury (TBI), manifesting clinically as either as hypo- or hypernatraemia. Dysnatraemia is associated with a greater risk of secondary brain injury from resultant changes in brain fluid levels, greater morbidity, longer length of hospital stay and in the case of hypernatraemia, greater mortality following TBI. Dysnatraemia occurs in the acute phase following TBI, is often transient and resolves in the majority of patients with recovery from the initial insult.

Ki-67 promotes inflammatory signaling governing neutrophil recruitment during respiratory infections.

Neutrophils defend against respiratory infections but cause acute lung injury (ALI) when excessively recruited to the lung. Early life environmental factors can shape lung development, but how they impact neutrophil recruitment is not known. We show that exposing newborn mice to hyperoxia increases the number of adult alveolar type 1 (AT1) epithelial cells expressing the proliferation marker Ki-67.

Society for Endocrinology Clinical Practice Guideline for the Evaluation of Androgen Excess in Women.

Context: Androgen excess is common in women and refers to clinical or biochemical evidence of elevated androgenic steroids such as testosterone. It is associated with underlying polycystic ovary syndrome in the majority of cases. However severe androgen excess is less common and may indicate the presence of underlying adrenal or ovarian neoplasms, genetic disorders or severe insulin resistance syndromes.

Outcomes and Toxicity following 3 or More Definitive Courses of Thoracic Radiation Therapy for Non-Small Cell Lung Cancer.

Purpose: Salvage re-irradiation is increasingly utilized to manage non-small cell lung cancer (NSCLC) locoregional recurrence or new lung primaries in previously treated areas. There is sparse information on efficacy and toxicity profile. We report a large experience of patients treated with multiple courses of definitive radiation for new and recurrent NSCLC.

A non-resolving cough in a 41-year-old woman: a case of familial pulmonary fibrosis.

https://bit.ly/42jJ3aO.

Patterns in prescribing and dispensing of influenza antivirals among adults with influenza presenting to urgent care and emergency department settings, VISION Network, 2023-2024.

Background: We describe prescribing and dispensing patterns of influenza antivirals among patients with laboratory-confirmed influenza within U.S. urgent care and emergency department settings.

Whole genome transcriptomics reveal distinct atrial versus ventricular responses to neonatal hyperoxia.

Preterm infants exposed to supplemental oxygen (hyperoxia) are at risk for developing heart failure later in life. Exposing rodents in early postnatal life to hyperoxia causes heart failure that resembles cardiac disease seen in adult humans who were born preterm. Neonatal hyperoxia exposure affects the left atrium and left ventricle differently, inhibiting the proliferation and survival of atrial cardiomyocytes while enhancing cardiomyocyte differentiation in the ventricle.

Systematic Review and Meta-Analysis on the Prevalence of Radiotherapy-Induced Hypopituitarism in Adults With Primary Non-Pituitary Brain Tumours.

Context: It is well recognised there is a high prevalence of pituitary dysfunction in childhood brain tumours survivors who are treated with radiotherapy. In contrast, the potential for survivors of brain tumours arising in adulthood to develop radiotherapy-induced hypopituitarism may be underestimated. The aim of this systematic review and meta-analysis is to determine the pooled prevalence of radiotherapy-induced hypopituitarism in survivors of primary non-pituitary brain tumours arising in adulthood.

Resistant hypertension post-transsphenoidal surgery for pituitary Cushing's disease, leading to a diagnosis of primary aldosteronism.

Summary: We describe a case of a 42-year-old gentleman, 5 years post-transsphenoidal surgery (TSS) for pituitary-dependent Cushing's disease, initially presenting with malignant hypertension. Despite an initial improvement in his blood pressure post-TSS, he was found to be persistently hypertensive on follow-up despite no clinical or biochemical evidence of recurrence of hypercortisolism. His blood pressure remained elevated despite five antihypertensive agents.

Definitive Radiotherapy for Oligometastatic and Oligoprogressive Thyroid Cancer: A Potential Strategy for Systemic Therapy Deferral.

Background: Definitive radiotherapy (dRT) has been shown to be an effective option for patients with oligometastatic and oligoprogressive cancers; however, this approach has not been well-studied in metastatic thyroid cancer.

Methods: This retrospective cohort included 119 patients with oligometastatic (34%) and oligoprogressive (66%) metastatic thyroid cancer treated from 2005 to 2024 with 207 dRT courses for 344 sites (50% thoracic, 37% bone, 7.5% brain, 4% abdominopelvic, and 1.

Extra-adrenal adrenocortical cancer associated with multiple endocrine neoplasia type 1.

Summary: Adrenocortical carcinoma (ACC) is a rare malignant tumour arising from the adrenal cortex, with an estimated annual incidence of one to two patients per million. Ectopic ACCs are extremely rare. The majority of ACCs are sporadic; however, ACC has been linked with genetic disease processes, including multiple endocrine neoplasia type-1 (MEN-1).

Salvage Reirradiation with Proton Beam Therapy for Locoregionally Recurrent Non-Small Cell Lung Cancer.

Background/objectives: This retrospective study evaluates outcomes of 66 patients who underwent reirradiation (re-RT) with proton beam therapy (PBT) for recurrent non-small cell lung cancer.

Methods: Toxicity was scored via the CTCAE v5.0, and outcomes estimated using the Kaplan-Meier method, with associations evaluated via Cox proportional hazards and logistic regression analyses.

Impaired 11β-Hydroxysteroid Dehydrogenase Type 2 Activity in Kidney Disease Disrupts 11-Oxygenated Androgen Biosynthesis.

Context: 11-Oxygenated androgens are a group of adrenal-derived steroids that require peripheral activation. In vitro data highlight a putative role for 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) in 11-oxygenated androgen biosynthesis, converting 11β-hydroxyandrostenedione to 11-ketoandrostenedione (11KA4), the direct precursor of the potent androgen 11-ketotestosterone (11KT). As the kidney is the major site of HSD11B2 expression, we hypothesized that patients with chronic kidney disease (CKD) would have reduced 11-oxygenated androgen biosynthesis due to impaired HSD11B2 activity.

Mechanisms in endocrinology: hypogonadism and metabolic health in men-novel insights into pathophysiology.

Hypogonadism in men is associated with an adverse metabolic phenotype and increased mortality. Reciprocally, obesity and insulin resistance can suppress the hypothalamic-pituitary-gonadal axis in the absence of structural organic disease, further perpetuating a cycle of metabolic dysfunction and low testosterone. The mechanisms underpinning this bidirectional association are complex as hypogonadism is a heterogenous syndrome, and obesity is associated with metabolic perturbations in glucose and lipid metabolism even in the presence of normal testicular function.

PPARγ drives mitochondrial stress signaling and the loss of atrial cardiomyocytes in newborn mice exposed to hyperoxia.

Diastolic dysfunction is increasingly common in preterm infants exposed to supplemental oxygen (hyperoxia). Previous studies in neonatal mice showed hyperoxia suppresses fatty acid synthesis genes required for proliferation and survival of atrial cardiomyocytes. The loss of atrial cardiomyocytes creates a hypoplastic left atrium that inappropriately fills the left ventricle during diastole.

Service evaluation suggests variation in clinical care provision in adults with congenital adrenal hyperplasia in the UK and Ireland.

Background: Congenital adrenal hyperplasia (CAH) encompasses a rare group of autosomal recessive disorders, characterised by enzymatic defects in steroidogenesis. Heterogeneity in management practices has been observed internationally. The International Congenital Adrenal Hyperplasia registry (I-CAH, https://sdmregistries.

Survival outcomes and toxicity of adjuvant immunotherapy after definitive concurrent chemotherapy with proton beam radiation therapy for patients with inoperable locally advanced non-small cell lung carcinoma.

Introduction: Adjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC.

Materials And Methods: We analyzed 354 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009 to 2021.

Iatrogenic adrenal insufficiency in adults.

Iatrogenic adrenal insufficiency (IAI) is the most common form of adrenal insufficiency in adult patients, although its overall exact prevalence remains unclear. IAI is associated with adverse clinical outcomes, including adrenal crisis, impaired quality of life and increased mortality; therefore, it is imperative that clinicians maintain a high index of suspicion in patients at risk of IAI to facilitate timely diagnosis and appropriate management. Herein, we review the major causes, clinical consequences, diagnosis and care of patients with IAI.