Introduction: Histoplasmosis is a rare opportunistic, inhalation-acquired systemic mycosis caused by Histoplasma capsulatum, endemic to Southeast Asia, including Malaysia. Although classically seen in immunocompromised hosts, it is increasingly reported in immunocompetent individuals. Infection is associated with environmental exposures such as bat or bird droppings and soil disruption. Histoplasmosis is a progressive granulomatous disease that can closely mimic tuberculosis and malignancy, making diagnosis challenging. Case: An 87-year-old Malay male with a history of treated pulmonary tuberculosis presented with a 6-month history of intermittent fever, anorexia, weight loss, and hypotension. Initial computed tomography imaging demonstrated bilateral heterogeneous adrenal masses (right: 2.2 × 3.7 × 5.0 cm; left: 2.0 × 3.7 × 5.2 cm) with indeterminate washout characteristics. Biochemical adrenal evaluation, including a short Synacthen test, confirmed primary adrenal insufficiency. Extensive microbiological and malignancy workup, including bronchoscopy, cultures, and tumor markers, was non-diagnostic. In view of clinical deterioration and epidemiological risk, empirical antituberculous therapy was initiated; however, no clinical improvement was observed after 2 months. PET-FDG revealed intensely hypermetabolic bilateral adrenal masses (SUVmax right 16.7, left 13.2) with no other abnormal foci. Non-invasive fungal investigations were negative. Definitive diagnosis was established via computed tomography-guided adrenal biopsy, which demonstrated necrotizing granulomatous inflammation with intracellular yeasts, subsequently identified as H. capsulatum. The patient was treated with oral itraconazole and corticosteroid replacement, resulting in significant clinical improvement and planned interval radiological reassessment. Conclusion Disseminated histoplasmosis is a diagnostic challenge, particularly in frail elderly patients, where invasive procedures may be delayed. It can mimic tuberculosis and malignancy and may lack an identifiable exposure history. Non-invasive tests may be inconclusive, making tissue biopsy essential. Adrenal involvement may result in primary adrenal insufficiency, further complicating the clinical picture. Early consideration and timely confirmation are crucial for appropriate management.
Adrenal incidentaloma ; Lung Neoplasms

Introduction: Skeletal disease in transfusion-dependent thalassemia is commonly attributed to reduced bone mineral density and managed with anti-resorptive therapy. However, chronic iron overload can induce progressive endocrine siderosis, disrupting anabolic pathways essential for bone homeostasis. This mechanism remains under-recognized and may underlie treatment failure in severe cases. Case: We describe a 34-year-old female with transfusiondependent HbE β-thalassemia, post-splenectomy, receiving regular transfusions and iron chelation, who sustained multiple pathological fractures following a trivial fall, including bilateral supracondylar femur fractures and a distal radius fracture. She had severe systemic iron overload (ferritin 2,621 ng/mL) complicated by hepatic cirrhosis, insulin-dependent diabetes, and hypogonadotropic hypogonadism. Bone mineral density assessment demonstrated severe osteoporosis (hip T-score −5.4) despite prolonged bisphosphonate therapy, with prior vertebral compression fracture. Endocrine evaluation revealed multiaxis dysfunction, including gonadal failure and probable growth hormone deficiency, consistent with pituitary and peripheral endocrine siderosis. Conclusion This case demonstrates that skeletal fragility in transfusiondependent thalassemia reflects an endocrine-driven failure of bone formation rather than isolated loss of bone mineral density. Iron overload–induced endocrine siderosis impairs osteoblast function and suppresses anabolic signaling, leading to profound skeletal vulnerability. The progression of osteoporosis despite anti-resorptive therapy highlights the limitation of conventional approaches and supports reframing thalassemia-associated bone disease as an endocrine disorder. Severe osteoporosis should prompt systematic endocrine evaluation, with early hormonal replacement and consideration of anabolic therapy to prevent catastrophic fractures and long-term disability.
Siderosis ; Thalassemia

Introduction: Arginine vasopressin (AVP) deficiency is an uncommon but important presentation of infiltrative hypothalamic– pituitary disorders. In adults, isolated AVP deficiency with pituitary stalk thickening is diagnostically challenging, especially in the absence of systemic disease. Langerhans cell histiocytosis (LCH) is a rare cause and may precede systemic involvement by several years. Case: We report a 42-year-old male who presented in 2017 with polyuria and polydipsia, with urine output of up to 10 L/ day. AVP deficiency was confirmed by the water deprivation test, and desmopressin was initiated. Initial pituitary magnetic resonance imaging (MRI) was normal, baseline anterior pituitary hormonal evaluation was unremarkable, and contrast-enhanced computed tomography (CECT) of the thorax and abdomen showed no abnormalities. Repeat pituitary MRI 1 year later demonstrated loss of the posterior pituitary bright spot with pituitary stalk thickening. In the absence of systemic involvement, a presumptive diagnosis of lymphocytic hypophysitis was made, and pituitary biopsy was deferred due to the high procedural risk. Serial pituitary MRIs over the following years showed persistent infundibular thickening and continued absence of the posterior pituitary bright spot, without interval progression or development of additional hormonal deficiencies. The patient remained clinically stable until June 2024, when new-onset left hip pain prompted MRI, revealing a heterogeneous mass involving the femoral neck and intertrochanteric region with a pathological fracture. Histopathological examination following wide resection confirmed LCH, with negative BRAF V600 mutation. Postoperative PET scan revealed a multisystem disease involving the skeleton, lymph nodes, spine, and gastrointestinal tract, with no bone marrow involvement. He subsequently completed six cycles of intravenous methotrexate and cytarabine. Conclusion Adult-onset AVP deficiency may be the earliest manifestation of occult multisystem Langerhans cell histiocytosis. This case highlights the importance of longterm follow-up and reconsideration of the initial diagnosis when new systemic features emerge.
Histiocytosis, Langerhans-Cell

Introduction: Langerhans cell histiocytosis (LCH) is a clonal proliferative disorder of langerin-positive histiocytes. Endocrine involvement most frequently manifests as central diabetes insipidus or secondary hypothyroidism, caused by infiltration of the hypothalamic-pituitary axis. Conversely, direct infiltration of the thyroid gland leading to primary hypothyroidism is an exceptionally rare clinical entity, particularly when presenting concurrently with central disease. Case: A 21-year-old female with known right otic and multisystem LCH presented with septic shock secondary to a right ear abscess accompanied by polyuria and polydipsia. Physical examination revealed a palpable goiter. Clinical and biochemical evaluation confirmed central diabetes insipidus with associated anterior hypopituitarism (low adrenocorticotropic hormone, follicle-stimulating hormone, and luteinizing hormone). However, concurrent thyroid function tests demonstrated overt primary hypothyroidism, evidenced by an appropriately elevated thyroid-stimulating hormone (26.19 mIU/L) and low free T4 (5.47 pmol/L), rather than the anticipated secondary hypothyroidism. Neck ultrasound showed diffuse thyroid enlargement with heterogeneous echotexture. Crucially, anti-thyroid peroxidase and anti-thyroglobulin antibodies were both negative, rendering Hashimoto’s thyroiditis highly unlikely. Although the patient declined confirmatory fine-needle aspiration, the constellation of a palpable goiter, characteristic ultrasonographic findings, negative autoimmunity, and active multisystem disease strongly supported a diagnosis of direct histiocytic infiltration of the thyroid gland. She was initiated on appropriate glucocorticoid coverage and subsequent levothyroxine replacement, alongside systemic intravenous cytarabine. Conclusion This case highlights a rare, mixed endocrine profile in multisystem LCH, demonstrating that pituitary and direct end-organ infiltration can coexist. Hypothyroidism in LCH patients with established central diabetes insipidus should not be reflexively assumed to be central in origin. A comprehensive diagnostic workup, including autoantibody screening, ultrasound, and ideally histopathological confirmation, is essential to accurately identify primary endocrine failure and guide appropriate clinical management in these complex cases.
Histiocytosis, Langerhans-Cell ; Hypothyroidism ; Pituitary Gland

Introduction: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. Complications such as cystic fibrosis–related diabetes (CFRD) are well recognized. The association between CF and autoimmune thyroid disease, however, is rare and poorly understood. We report a case of CFRD complicated by Graves’ disease. Case: A 22-year-old male was diagnosed with CF at age 5, confirmed by a positive sweat chloride test. Following the diagnosis, lifelong pancreatic enzyme replacement therapy (Creon) was initiated to treat exocrine pancreatic insufficiency. In 2021, he developed type 3c diabetes, attributed to endocrine pancreatic insufficiency, and required regular basal insulin therapy. In early 2024, he developed hypokalemic periodic paralysis with proximal myopathy, despite potassium correction, and was admitted to the hospital. On admission, examination revealed a fine tremor and diffuse bilateral neck swelling. Biochemical evaluation showed thyrotoxicosis with Free T4 of 37 pmol/L and thyroid-stimulating hormone (TSH) <0.01 mIU/L. He started a tapering dose of carbimazole and propranolol. An urgent neck ultrasound showed a heterogeneous thyroid parenchyma with increased vascularity and no nodules. Elevated anti-thyroid peroxidase (anti-thyroid peroxidase, >600 IU/mL) and TSH receptor antibodies (thyrotropin receptor antibody, 2.57 IU/L) confirmed a diagnosis of Graves’ disease. During follow-ups, he had issues with compliance with the antithyroid therapy. However, the latest thyroid function test in February 2026 showed Free T4 of 20.5 pmol/L with suppressed TSH of <0.01 mIU/L. He remains clinically euthyroid throughout the follow-up. Conclusion This case highlights a rare but clinically relevant coexistence. Clinicians managing symptomatic CF patients should vigilantly screen for thyroid dysfunction to ensure early diagnosis and timely intervention. Early recognition and treatment may improve patient outcomes. Further research is needed to clarify the immunological link between CF and autoimmunity.
Cystic Fibrosis ; Graves Disease

OBJECTIVE: To investigate the effect of traditional Chinese Five-body balance exercise on patients with preserved ratio impaired spirometry (PRISm). METHODS: Fifteen patients with PRISm and 15 patients diagnosed with chronic obstructive pulmonary disease (COPD) were recruited from the Outpatient Department of Guang'anmen Hospital and Beijing Niujie Health Service Center from April to December, 2023. Participants in both groups attended supervised Five-body balance exercise training twice a week for 12 weeks. Patients with COPD continued their regular medication regimen during the intervention period. The endpoints were mean changes in the 6-min walk test (6MWT), St. George's Respiratory Questionnaire (SGRQ) score, cardiopulmonary exercise testing (CPET), pulmonary function, and scores of COPD assessment test (CAT), modified British Medical Research Council, Self-Rating Anxiety Scale, and Self-Rating Depression Scale from baseline to 12 weeks. Adverse events were monitored throughout the study. RESULTS: The PRISm group showed a significant improvement from baseline to week 12 in 6MWT, SGRQ symptom score, and forced vital capacity (FVC) compared to the COPD group (P<0.05). No significant between-group changes were observed in other outcome measurements (P>0.05). In addition, compared with baseline, both groups exhibited improvements in 6MWT, SGRQ score, and CPET at week 12 (P<0.05). The PRISm group also showed a significant increase in forced expiratory volume in 1 s and FVC, as well as a significant decrease in CAT score at week 12 (P<0.05). No adverse events were reported. CONCLUSION Patients with PRISm may benefit from Five-body balance exercise training, which can improve the exercise capacity, health-related quality of life, and lung function. (Registration No. ChiCTR2200059290).
Humans ; Spirometry ; Male ; Female ; Pulmonary Disease, Chronic Obstructive/therapy* ; Lung/physiopathology* ; Middle Aged ; Exercise Tolerance/physiology* ; Exercise Therapy ; Aged ; Medicine, Chinese Traditional ; Respiratory Function Tests ; East Asian People

OBJECTIVES: Non-small cell lung cancer (NSCLC) is associated with poor prognosis, with 30% of patients diagnosed at an advanced stage. Mutations in the EGFR and KRAS genes are important prognostic factors for NSCLC, and targeted therapies can significantly improve survival in these patients. Although tissue biopsy remains the gold standard for detecting gene mutations, it has limitations, including invasiveness, sampling errors due to tumor heterogeneity, and poor reproducibility. This study aims to develop machine learning models based on radiomic features to predict EGFR and KRAS gene mutation status in NSCLC patients, thereby providing a reference for precision oncology. METHODS: Imaging and mutation data from eligible NSCLC patients were obtained from the publicly available Lung-PET-CT-Dx dataset in The Cancer Imaging Archive (TCIA). A three-dimensional-convolutional neural network (3D-CNN) was used to extract imaging features from the regions of interest (ROI). The LightGBM algorithm was employed to build classification models for predicting EGFR and KRAS gene mutation status. Model performance was evaluated using 5-fold cross-validation, with receiver operator characteristic (ROC) curves, area under the curve (AUC), accuracy, sensitivity, and specificity used for validation. RESULTS: The models effectively predicted EGFR and KRAS mutations in NSCLC patients, achieving an AUC of 0.95 for EGFR mutations and 0.90 for KRAS. The models also demonstrated high accuracy (EGFR 89.66%; KRAS 87.10%), sensitivity (EGFR 93.33%; KRAS 87.50%), and specificity (EGFR 85.71%; KRAS 86.67%). CONCLUSIONS A radiogenomics-machine learning predictive model can serve as a non-invasive tool for anticipating EGFR and KRAS gene mutation status in NSCLC patients.
Humans ; Carcinoma, Non-Small-Cell Lung/diagnostic imaging* ; Lung Neoplasms/diagnostic imaging* ; Mutation ; Proto-Oncogene Proteins p21(ras)/genetics* ; ErbB Receptors/genetics* ; Machine Learning ; Positron Emission Tomography Computed Tomography ; Female ; Male ; Neural Networks, Computer ; Middle Aged ; Aged

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic pulmonary infection that commonly occurs in immunocompromised children. We report a case of infantile leukemia complicated by PJP and review the relevant literature. A summary and analysis of 10 infantile leukemia patients with PJP infection (9 cases reported in the literature and 1 case from our center) showed that PJP mostly occurred in the early stages of chemotherapy (80%, 8/10). The main clinical manifestations were dyspnea (100%, 10/10) and hypoxemia (50%, 5/10), while pulmonary imaging findings lacked specificity. In most cases (50%, 5/10), diagnosis was established by identifying pathogens in bronchoalveolar lavage fluid under microscopy. In our case, diagnosis was confirmed using targeted next-generation sequencing (tNGS) of bronchoalveolar lavage fluid. Treatment with intravenous sulfamethoxazole complex was administered in 8 patients, all of whom eventually recovered. PJP may occur in the early stages of chemotherapy for infantile leukemia, thus early prevention is necessary. tNGS facilitates early diagnosis of PJP, and sulfamethoxazole complex remains an effective therapeutic option.
Humans ; Infant ; Bronchoalveolar Lavage Fluid/microbiology* ; Immunocompromised Host ; Leukemia/complications* ; Pneumocystis carinii/isolation & purification* ; Pneumonia, Pneumocystis/diagnosis* ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use*

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major chronic respiratory condition with high morbidity and mortality, imposing a serious economic and public health burden. The World Health Organization ranks COPD among the top 4 chronic diseases worldwide. Zangsiwei Qingfei Mixture (ZSWQF), a novel Tibetan herbal formulation independently developed by our research team, has shown therapeutic potential for chronic respiratory diseases. This study aims to evaluate the effects of aerosolized ZSWQF on cigarette smoke-induced COPD in mice and explore its underlying mechanisms. METHODS: Thirty C57 mice were randomly divided into a Control group, a COPD group, and a ZSWQF group. The Control group received saline aerosol inhalation without cigarette smoke exposure; both the COPD group and the ZSWQF group were exposed to cigarette smoke, with the former receiving saline inhalation and the latter treated with ZSWQF aerosol. White blood cell (WBC) count was performed using a fully automatic blood cell analyzer. Serum, alanine transaminase (ALT), and serum creatinine (SCr), as well as interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). BALF cell classification was determined using a hematology analyzer. Lung function was assessed with a small animal pulmonary function system, including airway resistance (RI) and cyclic dynamic compliance (CyDN). Lung tissues were stained with hematoxylin and eosin (HE), and mean linear intercept (MLI) and destruction index (DI) were calculated to evaluate morphological changes. Network pharmacology was applied to identify disease-related and ZSWQF-related targets, followed by intersection and protein-protein interaction (PPI) network analysis, and enrichment analysis of biological functions and pathways. Primary type II alveolar epithelial cell (AEC II) from SD rats were isolated and divided into a Control group, a lipopolysaccharide (LPS) group, a normal serum group, a water extract of ZSWQF (W-ZSWQF) group, a ZSWQF containing serum group, and a MLN-4760 [angiotensin-converting enzyme (ACE) 2 inhibitor]. Western blotting was performed to assess protein expression of ACE, p38 [a mitogen-activated protein kinase (MAPK)], phospho (p)-p38, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p-ERK1/2, c-Jun N-terminal kinase (JNK), p-JNK, inhibitor of nuclear factor-kappa B alpha (IκBα), p-IκBα, and p-p65 subunit of nuclear factor-kappa B (NF-κBp65). RESULTS: WBC counts were significantly higher in the COPD group than in controls (P<0.01) and decreased following ZSWQF treatment (P<0.05). No significant intergroup differences were found in organ weights, ALT, or SCr (all P>0.05). Serum and BALF levels of IL-6, IL-8, and TNF-α, as well as total BALF cells, neutrophils, and macrophages, were elevated in the COPD group compared with controls and reduced by ZSWQF treatment (P<0.05). COPD mice exhibited increased RI, decreased CyDN, marked alveolar congestion, inflammatory infiltration, thickened septa, and higher MLI and DI values versus controls (P<0.05); ZSWQF treatment significantly reduced MLI and DI (P<0.05). Network pharmacology identified 151 potential therapeutic targets for ZSWQF against COPD, with key nodes including TNF, IL-6, protein kinase B (Akt) 1, albumin (ALB), tumor protein p53 (TP53), non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT) 3, matrix metalloproteinase (MMP)-9, and beta-catenin (CTNNB1). Enrichment analysis indicates involvement of cancer-related, phosphatidylinositol 3-kinase (PI3K)/Akt, hypoxia-inducible factor (HIF)-1, calcium, and MAPK signaling pathways. Western blotting results showed that compared with the LPS group, AEC II treated with ZSWQF-containing serum exhibited decreased expression of ACE, p-p38/p38, p-ERK1/2/ERK1/2, p-JNK/JNK, p-IκBα/IκBα, and p-NF-κBp65, while ACE2 expression was upregulated, consistent with the MAPK/nuclear factor-kappa B (NF-κB) pathway regulation predicted by network pharmacology. CONCLUSIONS Aerosolized ZSWQF provides protective effects in COPD mice by reducing airway inflammation and remodeling.
Animals ; Pulmonary Disease, Chronic Obstructive/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Mice, Inbred C57BL ; Male ; Network Pharmacology ; Smoke/adverse effects* ; Bronchoalveolar Lavage Fluid ; Administration, Inhalation ; Inflammation/drug therapy* ; Tumor Necrosis Factor-alpha ; Lung/drug effects* ; Interleukin-6/blood*

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare multi-system disease that presents significant diagnostic challenges due to its complexity and low incidence (White and Dubey, 2023). It affects males and females equally, though males may exhibit more active disease at diagnosis and often require more aggressive treatment (Liu et al., 2023). The hallmark features of EGPA include delayed-onset asthma, eosinophilia in tissues and blood, and vasculitis affecting small to medium-sized arteries (White and Dubey, 2023). EGPA falls under the category of antineutrophil cytoplasmic antibody (ANCA)‍-associated vasculitis (AAV), whereas only about half of EGPA patients test positive for ANCA (Khoury et al., 2023).
Humans ; Male ; Hemorrhage/etiology* ; Granulomatosis with Polyangiitis/complications* ; Heart Arrest/etiology* ; Early Diagnosis ; Eosinophilia/diagnosis* ; Kidney Diseases/etiology* ; Churg-Strauss Syndrome/complications* ; Middle Aged