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

Lung cancer is the malignancy with the highest incidence and mortality burden globally, ranking first in both morbidity and mortality among all types of malignant tumors. Pathologically, lung cancer is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer, with NSCLC accounting for approximately 85% of cases. Due to the often subtle or nonspecific clinical manifestations in early-stage disease, many patients are diagnosed at a locally advanced or metastatic stage, where treatment options are limited and prognosis remains poor. Therefore, molecular targeted therapy focusing on driver genes has become a key strategy to improve the survival outcomes of patients with advanced NSCLC. The epidermal growth factor receptor (EGFR) is one of the most common driver genes in NSCLC. While EGFR mutations occur in approximately 12% of advanced NSCLC patients globally, the incidence rises to 55.9% in Chinese patients. Among EGFR mutations, P-loop and αC-helix compressing (PACC) mutations account for about 12.5%. Currently, EGFR tyrosine kinase inhibitors (TKIs) have become the first-line standard treatment for advanced NSCLC patients with classical EGFR mutations, with efficacy well-established through clinical studies and real-world evidence. However, with rapid advancements in NSCLC precision medicine and deeper exploration of the EGFR mutation spectrum, EGFR PACC mutations have emerged as a key clinical focus. The structural characteristics of these mutations lead to significant variability in responses to EGFR TKIs, leaving therapeutic options still limited, while detection challenges persist due to the sensitivity constraints of current testing technologies, driving increasing demand for improved diagnostic and treatment approaches. The current clinical evidence primarily stems from retrospective analyses and small-scale exploratory studies, while prospective, large-scale, high-level evidence-based medical research specifically targeting this mutation subtype remains notably insufficient. This evidence gap has consequently led to the absence of standardized guidelines or expert consensus regarding optimal treatment strategies for advanced NSCLC with EGFR PACC mutations. As a clinical consensus specifically addressing EGFR PACC-mutant NSCLC, this document provides a comprehensive framework encompassing the clinical rationale for EGFR PACC mutation testing, therapeutic strategies for advanced-stage disease, management of treatment-related adverse events, and follow-up protocols. The consensus underscores the pivotal role of EGFR PACC mutation detection in precision medicine implementation while offering evidence-based recommendations to guide personalized therapeutic decision-making. By establishing clear clinical pathways encompassing molecular testing, therapeutic intervention, and long-term monitoring for EGFR PACC-mutant NSCLC, this consensus aims to meaningfully improve patient survival outcomes while serving as a robust, evidence-based foundation for developing personalized clinical management approaches.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; ErbB Receptors/antagonists & inhibitors* ; Mutation ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/therapeutic use* ; Molecular Targeted Therapy ; Consensus

Mutations in the human epidermal growth factor receptor 2 (HER-2) gene are recognized as significant but relatively rare driver alterations in non-small cell lung cancer (NSCLC). These mutations predominantly manifest as gene mutation, amplification, and protein overexpression, with an estimated prevalence from 2.8% to 15.4% among NSCLC patients in China. Research indicates that HER-2 mutations, particularly exon 20 insertions (ex20ins), are strongly correlated with aggressive tumor biology, poor prognosis, and limited responsiveness to immunotherapy, thereby exhibiting characteristics of "cold tumors". Overexpression and amplification of HER-2 are also indicative of a heightened risk of chemotherapy resistance and unfavorable survival outcomes, suggesting a distinct molecular subtype with unique biological behaviors. In recent years, novel antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan (T-DXd), have demonstrated groundbreaking efficacy in HER-2-mutant advanced NSCLC patients. These ADCs have shown significant clinical benefits, including high objective response rates and progression-free survival advantages, making T-DXd the first targeted therapy approved for this patient population globally. Additionally, ADCs have exhibited therapeutic potential in patients with HER-2 overexpression, thus broadening the scope of their indications. To standardize the clinical diagnosis and treatment of HER-2 variant NSCLC, the Chinese Anti-cancer Association convened multidisciplinary experts from oncology, pulmonology, thoracic surgery, pathology, and molecular diagnostics to develop this consensus based on the latest evidences from both domestic and international studies, coupled with China's clinical practice experience. This consensus focuses on the molecular characteristics, clinical significance, diagnostic strategies, treatment options, and safety management of HER-2 alterations, addressing ten critical clinical questions in a systematic manner. It is recommended that HER-2 status be routinely tested at initial diagnosis, disease progression, or recurrence in NSCLC. Mutation detection should prioritize next-generation sequencing (NGS), while protein overexpression may be assessed using immunohistochemistry (IHC) standards for gastric cancer. Fluorescence in situ hybridization (FISH) is recommended for detecting HER-2 amplification. Regarding treatment, for HER-2-mutant patients, first-line therapy may involve chemotherapy with or without immune checkpoint inhibitors (ICIs), similar to treatment approaches for driver-gene negative populations. Upon failure of first-line treatment, trastuzumab deruxtecan, may be considered as alternative therapeutic options. For patients with HER-2 overexpression, ADCs should be considered after failure of standard systemic therapy. However, the management of HER-2 amplification remains insufficiently supported by evidence, necessitating a cautious, individualized approach. The consensus also includes detailed recommendations for screening and managing adverse effects associated with ADCs, such as interstitial lung disease (ILD), emphasizing the crucial role of safety management in ensuring treatment efficacy. The publication of this consensus aims to drive the standardization of molecular diagnosis and treatment pathways for HER-2 variant NSCLC, improve clinical outcomes and quality of life for patients, and facilitate the implementation of personalized precision treatment strategies.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Receptor, ErbB-2/metabolism* ; Mutation ; Immunoconjugates/therapeutic use* ; Consensus ; Trastuzumab/therapeutic use* ; Camptothecin/analogs & derivatives*

OBJECTIVE: To observe the skin surface temperature at the related back-shu points in the patients with the different levels of pulmonary ventilation function in chronic persistent asthma, and to explore the correlation between the skin temperature at the back-shu points and pulmonary ventilation function indexes based on "lung governing the skin and hair". METHODS: Sixty-one patients with chronic persistent asthma, based on the level of pulmonary ventilation function, were assigned into a reduced pulmonary ventilation function group (reduced function group, 32 cases) and a normal pulmonary ventilation function group (normal function group, 29 cases). In the two groups, the skin surface temperature was measured in the sites of bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23); and the pulmonary ventilation function indexes (the percentage of predicted value of forced vital capacity [FVC%pred], the percentage of predicted value of forced expiratory volume in the first second [FEV1%pred], the percentage of predicted value of FEV1/FVC [FEV1/FVC%pred] and the percentage of predicted value of the peak expiratory flow [PEF%pred]) were recorded. The correlation between the skin surface temperature of acupoints and pulmonary ventilation function was analyzed. RESULTS: Compared with the normal function group, the surface skin temperature at the bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23) was higher in the reduced function group (P<0.05, P<0.01). Compared with the normal function group, FEV1%pred, FEV1/FVC%pred and PEF%pred were decreased in the reduced function group (P<0.001). There was no significant difference in FVC%pred between the two groups (P>0.05). The skin surface temperature at the bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23) was negatively correlated with FVC%pred, FEV1%pred, FEV1/FVC%pred and PEF%pred in 61 patients with chronic persistent asthma (P<0.001, P<0.01, P<0.05). CONCLUSION The skin surface temperature at back-shu points is elevated in line with the the decline of pulmonary ventilation function in the patients with chronic persistent asthma, presenting a negative correlation with pulmonary ventilation function indexes. It is preliminarily verified that back-shu point is characterized by reflecting the visceral disorders.
Humans ; Female ; Male ; Asthma/therapy* ; Middle Aged ; Adult ; Skin Temperature ; Lung/physiopathology* ; Acupuncture Points ; Pulmonary Ventilation ; Aged ; Chronic Disease/therapy* ; Young Adult ; Hair

OBJECTIVE: To analyze the research progress, hotspots, frontier trends and existing limitations of acupuncture and moxibustion treatment for respiratory diseases in the past decade using bibliometric and scientific knowledge mapping methods. METHODS: Literature on acupuncture and moxibustion treatment for respiratory diseases published from January 1st, 2014 to June 30th, 2024, from CNKI, VIP, Wanfang, PubMed and Web of Science was retrieved. CiteSpace 6.1.R6 and VOSviewer V1.6.20 were used to perform visual analysis, including keyword co-occurrence and clustering, and to construct knowledge maps of acupuncture and moxibustion treatment for respiratory diseases. RESULTS: A total of 1,106 Chinese articles and 185 English articles were included. High-frequency keywords focused on clinical diseases, treatment methods, efficacy observation, mechanisms etc. The main respiratory diseases treated with acupuncture and moxibustion included chronic obstructive pulmonary disease (COPD), asthma and cough. Commonly used acupoints included Feishu (BL13), Zusanli (ST36), Dazhui (GV14) and Shenshu (BL23), primarily involving the bladder meridian of foot-taiyang, conception vessel and lung meridian of hand-taiyin. Among the treatment methods dominated by acupuncture and moxibustion, the primary treatment method was electroacupuncture combined with moxibustion, and acupoint application was supplemented, with increasing emphasis on integrative Chinese and Western medicine and acupuncture combined with medication. The therapeutic mechanisms involved anti-inflammatory effects and inhibition of airway remodeling, with targets mainly associated with the NF-κB signaling pathway. CONCLUSION Acupuncture and moxibustion demonstrates certain advantages in treating respiratory diseases such as COPD, asthma and cough, with mechanisms related to anti-inflammatory effects and inhibition of airway remodeling. Future research should focus on multi-center, large-sample, high-quality clinical and experimental studies to explore the optimal clinical treatment protocols and underlying mechanisms.
Moxibustion/trends* ; Humans ; Acupuncture Therapy/trends* ; Acupuncture Points ; Asthma/therapy* ; Pulmonary Disease, Chronic Obstructive/therapy*

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the intestinal flora in rats with chronic obstructive pulmonary disease (COPD) and explore its possible mechanism based on the gut-lung axis theory. METHODS: A total of 30 male SD rats of SPF grade were randomly divided into a normal control (NC) group, a model group and an EA group, 10 rats in each one. In the model group and the EA group, COPD model was established by intratracheal instillation of lipopolysaccharide combined with cigarette fumigation. In the EA group, EA was applied at bilateral "Feishu" (BL13) and "Zusanli" (ST36), with disperse-dense waves, in frequency of 4 Hz/20 Hz, current of 1-3 mA, 20 min a time, once a day for 14 days continuously. Before and after modeling, as well as after intervention, body weight was observed; after intervention, the lung function indexes (forced expiratory volume in 0.1 second [FEV_0.1], FEV_0.1/forced vital capacity [FVC]%, forced expiratory volume in 0.3 second [FEV_0.3] and FEV_0.3/FVC%) were measured, serum levels of inflammatory factors (tumor necrosis factor-α[TNF-α], interleukin-6[IL-6], interleukin-1β[IL-1β] and interleukin-10[IL-10]) were detected by ELISA, histopathology of lung and colon tissues was observed by HE staining, the intestinal flora were analyzed by 16S rRNA, and the correlations between lung function and intestinal flora were analyzed. RESULTS: Compared with the NC group, in the COPD group, the body weight and lung function indexes were reduced (P<0.01); the lung and colon tissues were damaged, the mean linear intercept (MLI) of alveolus and inflammatory cell numbers of 100 μm² in lung tissue were increased (P<0.01); the serum levels of TNF-α, IL-6 and IL-1β were increased (P<0.01, P<0.05), and the serum level of IL-10 was decreased (P<0.01); α-diversity indexes of intestinal flora were increased (P<0.01); the relative abundance of Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus was increased (P<0.01), the relative abundance of Firmicutes, Actinobacteria, Tenericutes, TM7 and Lactobacillus, Allobaculum, Bifidobacterium, YRC22 was decreased (P<0.01, P<0.05); 31 different expressed metabolic pathways were identified between the two groups. Compared with the COPD group, in the EA group, the body weight and lung function indexes were increased (P<0.01); the damage of lung and colon tissues was improved, the MLI of alveolus was decreased (P<0.05); the serum levels of TNF-α, IL-6 and IL-1β were decreased (P<0.05), and the serum level of IL-10 was increased (P<0.05); α-diversity indexes of intestinal flora were decreased (P<0.01); the relative abundance of Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus was decreased (P<0.01, P<0.05), the relative abundance of Firmicutes, Actinobacteria, Tenericutes, TM7 and Lactobacillus, Allobaculum, Bifidobacterium, YRC22 was increased (P<0.01); 35 different expressed metabolic pathways were identified between the two groups. The lung function was positive related with Actinobacteria, Tenericutes, TM7 and YRC22, and was negative related with Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus. CONCLUSION EA may ameliorate lung function and tissue injury of COPD by regulating intestinal flora dysbiosis and inflammatory response, suggesting an anti-inflammatory effect mediated via "gut-lung" axis.
Animals ; Pulmonary Disease, Chronic Obstructive/genetics* ; Male ; Electroacupuncture ; Rats ; Rats, Sprague-Dawley ; Lung/metabolism* ; Gastrointestinal Microbiome ; Humans ; Interleukin-6/immunology* ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/microbiology* ; Interleukin-10/immunology*