Rathke's cleft cyst (RCC) is a benign pituitary lesion that is often asymptomatic but can cause hypopituitarism, including central adrenal insufficiency, which may become clinically apparent under physiological stress. However, RCC presenting with adrenal insufficiency unmasked by acute respiratory illness is rare, particularly in elderly patients. We report a case of RCC diagnosed after adrenal insufficiency became evident following pneumonia-associated asthma exacerbation. An 89-year-old woman presented with fever, productive cough, and generalized fatigue and was diagnosed with pneumonia-triggered asthma exacerbation. Initial laboratory evaluation revealed hyponatremia (serum sodium 126 mEq/L). She was treated with bronchodilators, systemic corticosteroids, and antibiotics, resulting in prompt improvement of respiratory symptoms and normalization of serum sodium levels. After discontinuation of corticosteroids and discharge, she developed persistent fatigue, anorexia, and right eyelid ptosis. Brain magnetic resonance imaging revealed a 22-mm cystic lesion in the pituitary gland consistent with RCC. Endocrine evaluation demonstrated markedly reduced adrenocorticotropic hormone and cortisol levels, along with central hypothyroidism, hypogonadism, and growth hormone deficiency, confirming panhypopituitarism with central adrenal insufficiency. Hydrocortisone replacement therapy was initiated, leading to clinical stabilization. Surgical intervention was deferred due to advanced age and absence of visual field defects, and the patient was managed conservatively with hormone replacement and follow-up imaging. This case highlights that acute respiratory illness may precipitate overt adrenal insufficiency in patients with previously unrecognized RCC. Transient improvement with corticosteroids during acute treatment may mask the underlying endocrine disorder, delaying diagnosis. Persistent fatigue, hyponatremia, or neurological findings after resolution of respiratory illness should prompt evaluation for central adrenal insufficiency and pituitary pathology, as early recognition and hormone replacement are essential to prevent life-threatening complications.

Background The diagnosis of adrenal insufficiency traditionally relies on peak cortisol values during stimulation testing, with a cut-off of 18 µg/dL established using polyclonal antibody assays. However, newer monoclonal antibody-based assays show reduced cross-reactivity with other glucocorticoids. In April 2022, our hospital changed the cortisol measurement method from Roche Elecsys Cortisol II to Tosoh AIA-CL2400, both using monoclonal antibodies but with potentially different measurement characteristics. In addition to stimulation test results, physicians initiate hydrocortisone replacement based on the patient's clinical condition. Methods We retrospectively reviewed 226 patients who underwent adrenocorticotropic hormone (ACTH) or corticotropin-releasing hormone (CRH) stimulation testing for suspected adrenal insufficiency between March 2016 and September 2023. Patients with baseline cortisol ≥18 µg/dL or receiving steroid medications other than hydrocortisone were excluded. Assessment variables included baseline cortisol, baseline ACTH, peak cortisol, and the change in cortisol during stimulation tests. Clinical diagnosis of adrenal insufficiency was defined by initiation of hydrocortisone replacement therapy. Receiver operating characteristic (ROC) curve analysis was performed to determine optimal cut-off values. Background factors included gender, age, presence of adrenal insufficiency symptoms, and structural or functional abnormalities of the hypothalamus-pituitary-adrenal (HPA) axis. Simple and multiple logistic regression analyses were conducted with the diagnosis of adrenal insufficiency as the dependent variable. Results The mean age was 54 years, and 75 (33.2%) of the participants were male. Adrenal insufficiency symptoms were present in 118 (52.2%), while 135 (59.7%) had either structural or functional abnormalities of the HPA axis. When comparing values between the two assay periods, peak cortisol was significantly different (mean: 14.6 vs. 16.8 µg/dL for Elecsys Cortisol II vs. AIA-CL2400). The proportion of patients with cortisol peaks <18 µg/dL differed (128 (68.1%) vs. 18 (47.4%)), but hydrocortisone initiation remained similar (82 (43.6%) vs. 14 (36.8%)). Multiple logistic regression analysis identified peak cortisol, presence of symptoms, and structural or functional abnormalities of the HPA axis as significant factors associated with the clinical diagnosis. ROC curve analysis revealed that the optimal cut-off value increased from 14.5 µg/dL before the assay change to 17.0 µg/dL after the change. When stratified by symptom presence, cut-off values were 14.5 µg/dL (with symptoms) and 13.1 µg/dL (without symptoms) before the change, and 17.0 µg/dL (with symptoms) and 15.1 µg/dL (without symptoms) after the change. When stratified by structural or functional abnormalities of the HPA axis, cut-off values were 13.7 µg/dL (with abnormalities) and 14.5 µg/dL (without abnormalities) before the change, and 17.5 µg/dL (with abnormalities) and 16.4 µg/dL (without abnormalities) after the change. Conclusion Our study provides two key messages: First, differences in assay methodology can significantly alter cortisol values and appropriate diagnostic cut-offs, even when transitioning between monoclonal antibody-based assays. Second, both peak cortisol and symptom presence were crucial for clinical diagnosis of adrenal insufficiency, with potentially lower cut-off values being appropriate for asymptomatic cases.

BACKGROUND Metaplastic breast carcinoma (MpBC), a rare subtype of breast malignancy characterized by low response rates to conventional chemotherapy, often presents as triple-negative breast cancer (TNBC). Recently, systemic therapy including immune checkpoint inhibitors (ICIs) has emerged as a promising treatment option for TNBCs in perioperative or metastatic settings. However, evidence regarding the efficacy of ICIs for MpBC remains limited. CASE REPORT A 52-year-old Japanese woman underwent radical surgery for primary MpBC of the breast, which confirmed the triple-negative subtype. Despite adjuvant chemotherapy with epirubicin and cyclophosphamide, metastases to the sternum and lungs developed during treatment. Because the initial surgical specimen was PD-L1-positive, the treatment was changed to chemoimmunotherapy consisting of pembrolizumab, gemcitabine, and carboplatin based on the KEYNOTE-355 trial. Although the precordial mass and multiple lung metastases temporarily increased in size soon after treatment initiation, the metastatic lesions subsequently showed marked shrinkage. The patient developed treatment-related adrenal insufficiency, rash, pruritus, and anemia, all categorized as Grade 2. Hydrocortisone replacement therapy was initiated for adrenal insufficiency, while pembrolizumab was continued without interruption. Ten months after treatment initiation, carboplatin plus gemcitabine was discontinued because of adverse events, including myelosuppression, and the patient was transitioned to pembrolizumab monotherapy. At 30 months after the initiation of chemoimmunotherapy, PET/CT showed only mild [18]F-fluorodeoxyglucose uptake in the sternal metastasis, with no evidence of disease progression. CONCLUSIONS This report describes the successful treatment of metastatic MpBC with pembrolizumab-containing chemoimmunotherapy. Pembrolizumab combination therapy may be a promising treatment option for metastatic MpBC.

Endometriosis affects approximately 10% of women of reproductive age and is characterized by the presence of endometrial tissue outside the uterine cavity. Diagnostic delays are common due to nonspecific symptoms and the absence of reliable biomarkers. Serum CA125, prolactin, and cortisol have been implicated in the pathophysiology of endometriosis through inflammatory, neuroendocrine, and stress-response mechanisms. However, their role as biomarkers in endometriosis remains poorly studied. This study aimed to investigate the relationships between serum CA125, prolactin, and cortisol levels with endometriosis staging and pain severity in endometriosis patients. A cross-sectional study was conducted at Dr. Zainoel Abidin General Hospital, Banda Aceh, Indonesia, involving women with laparoscopically confirmed endometriosis. Serum CA125, prolactin, and cortisol levels were measured using electrochemiluminescence immunoassay (ECLIA). Disease staging followed the American Society for Reproductive Medicine (ASRM) classification, and pain severity was assessed using the Numeric Rating Scale (NRS). Statistical analyses were performed using the Spearman correlation test. A total of 30 women with confirmed endometriosis were included in this study, with a mean age of 37.2 years. Endometriosis stages were distributed as stage II (20.0%), stage III (16.7%), and stage IV (63.3%), and the mean pain score was 5.60 ± 1.48. Elevated serum biomarker levels were observed with CA125 of 72.65 ± 55.39 U/mL, prolactin of 1456.77 ± 1799.79 μIU/mL, and cortisol of 341.92 ± 189.02 nmol/L. The serum CA125 level was positively correlated with endometriosis staging (r = 0.580, p = 0.001) but not with pain severity. Prolactin and cortisol had no significant correlations with disease stage or pain severity (all p > 0.05). This study shows that serum CA125 levels are significantly correlated with endometriosis staging, supporting its potential as a biomarker of disease progression. Although prolactin and cortisol levels were elevated, their lack of association with clinical parameters suggests broader neuroendocrine dysregulation rather than direct markers of disease severity.

We present a case of probable anaphylactic shock induced by intravenous hydrocortisone in a 72-year-old male patient with septic shock. The patient, admitted for management of infected pressure injuries, was initiated on hydrocortisone (200 mg/day) for vasopressor-resistant shock. Within 30 min of the first dose administration, he manifested clinical signs consistent with anaphylaxis, including refractory hypotension, tachycardia, and prolonged capillary refill time. Immediate hydrocortisone discontinuation, aggressive fluid resuscitation, norepinephrine uptitration, intravenous methylene blue administration, and amiodarone initiation for ventricular rate control resulted in hemodynamic stabilization and vital sign normalization. This event was categorized as severe (Hartwig scale level 5) and assessed as probably preventable (Modified Schoumock and Thornton scale). A Naranjo score of four supported a probable adverse drug reaction (ADR). A concurrent disulfiram-like reaction (DLR) secondary to cefoperazone-sulbactam was excluded based on clinical timeline and presentation. This case underscores that glucocorticoids, despite their anti-allergic properties, can precipitate anaphylaxis in critically ill patients, emphasizing the necessity for heightened clinical vigilance and strict adherence to administration guidelines within this vulnerable population.

Sleep disturbance has emerged as a major modifier of immune homeostasis in chronic inflammatory diseases, yet its immunological relevance to oral tissues remains incompletely integrated. Accumulating evidence indicates that sleep and oral inflammatory diseases are linked through coordinated neuroendocrine-immune pathways, with melatonin and cortisol constituting a central circadian hormonal axis that shapes immune balance. Melatonin, predominantly secreted during the nocturnal phase, exerts antioxidant, anti-inflammatory, and immunomodulatory effects that support periodontal immune homeostasis and salivary gland function. In contrast, sleep disruption and chronic activation of the hypothalamic-pituitary-adrenal axis led to dysregulated cortisol secretion, promoting immune suppression, microbial dysbiosis, and progressive periodontal tissue breakdown. Experimental, observational, and clinical studies consistently associate poor sleep quality with suppressed melatonin rhythms, elevated cortisol levels, and increased prevalence of periodontitis and xerostomia, while sleep disorders such as obstructive sleep apnea further exacerbate oral inflammatory vulnerability through both circadian and mechanical mechanisms. Despite these associations, the causal immune pathways linking circadian hormonal dysregulation to oral disease progression remain insufficiently defined. This review synthesizes current mechanistic and clinical evidence to conceptualize the melatonin-cortisol axis as an immunoregulatory bridge between disturbed sleep and oral inflammatory disease, and discusses its implications for biomarker development and immune-informed therapeutic strategies.

This study examines whether habitual emotional suppression-a response-focused emotion regulation strategy documented to be more prevalent among men adhering to traditional U.S. masculine norms-predicts chronic physiological dysregulation across the life course. Using a cross-sectional sample of 412 men aged 25-70 years recruited in a single U.S. metropolitan region, we measured habitual suppression with the four-item Suppression subscale of the Emotion Regulation Questionnaire (ERQ), diurnal salivary cortisol collected across three weekdays as an index of hypothalamic-pituitary-adrenal (HPA) axis regulation, and inflammatory burden as a z-standardized composite of serum high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). Masculine norm conformity was assessed using the Emotional Control subscale of the Conformity to Masculine Norms Inventory-46 (CMNI-46), and stressor exposure was indexed by a life events checklist. Structural equation models (SEMs) indicate that habitual suppression significantly predicts flatter diurnal cortisol slopes (β = 0.34) and elevated inflammatory burden (β = 0.28) after controlling for demographics, health behaviors, and medical factors. Suppression also acts as a stress amplifier, magnifying the physiological effects of stressor exposure beyond additive contributions. Age-stratified analyses demonstrate that suppression effects strengthen across the life course, consistent with cumulative biological loading. Mediation analyses indicate that suppression explains 38%-43% of the association between masculine norm conformity and physiological dysregulation. These findings position emotional suppression as a biologically consequential risk pathway through which masculine gender socialization is physiologically embodied among men in the United States.

Sensitive, non-invasive detection of the steroid hormone cortisol aids in preventing chronic diseases such as depression and anxiety caused by stress. This study presents the development of a novel sweat cortisol sensor, integrating core-shell structured molecularly imprinted polymer (MIP) nanoparticles with a three-dimensional conductive aerogel to enable efficient, non-invasive monitoring of stress-related cortisol levels. This sensor leverages the large specific surface area and conductive network of aerogel to enhance electron transport efficiency and sensor sensitivity. The MIP nanoparticles are engineered with a gold nanoparticle-modified Prussian blue analogue core, providing stable redox activity and optimizing electrochemical performance. The sensor exhibits an extensive detection range from 10 pM to 100 µM and a remarkably low detection limit of 4.36 × 10[- 12] M, alongside selectivity against other interfering substances. Screen printing technology was employed to fabricate the sensor into a wearable form, validating its stable detection performance and paving the way for mass production and practical applications. This research effectively addresses the limitations of conventional cortisol detection methods, offering a novel approach for real-time dynamic monitoring of stress-related physiological indicators, with significant implications for mental health surveillance and disease prevention.

Panic attacks are characterized by intense feelings of uncontrollable threat and induce experiences of intense stress. As one of the major physiological stress systems of the body, the hypothalamic-pituitary-adrenocortical axis (HPA) may be a key to our understanding of a biological basis of this anxiety disorder. While recent studies have found evidence for short-term HPA changes in panic disorder with flattened cortisol responses to stimulation, no data have been available on tonic, i.e., long-term HPA activity in these patients. The current study therefore investigated the cumulative cortisol incorporation in hair over the period of three months in patients with panic disorder (n = 45) and healthy individuals (n = 45). Results showed higher hair cortisol concentration in patients with panic disorder compared to healthy controls. The duration and the severity of the disorder was unrelated to hair cortisol concentrations. In subsample analyses, patients with panic disorder and comorbid depression showed no significant differences in hair cortisol concentration compared to patients with pure panic disorder. The present findings do not support to the notion that a hypoactive HPA axis may be an important biological feature of patients suffering from panic disorder. Future studies will have to show in a large sample whether a changed HPA axis reactivity is present and causally related to the development and course of the disorder.

The 2026 Conference on Retroviruses and Opportunistic Infections (CROI) featured important new and impactful findings relevant to the neurologic HIV (neuro-HIV) field. Reports included new evidence linking herpesvirus coinfections to cognitive heterogeneity; studies on neuroinflammation, neuronal injury, and amyloid-related processes in treated HIV; and studies using advanced technologies to address the HIV-infected cells that persist in the central nervous system during antiretroviral therapy and the mechanisms that may maintain those populations. New therapeutic findings were presented on low-dose hydrocortisone and pregnenolone as potential strategies to improve cognition and reduce inflammatory signaling. Additional studies linked brain health in people with HIV to antiretroviral-associated neuropsychiatric effects and to aging-related comorbidities, including cerebrovascular disease, diabetes, metabolic syndrome, insulin resistance, and metabolic dysfunction-associated steatohepatitis. This review summarizes these findings and highlights new mechanistic and therapeutic directions for the neuro-HIV field.

The Rice's whale (Balaenoptera ricei) is a recently described species of baleen whale found in the Gulf of Mexico. With fewer than 50 adults remaining, the Rice's whale is the most endangered baleen whale species. Analyses of reproductive and adrenal hormones promote the understanding of reproductive cycles and stress physiology in this rare and poorly understood species. Baleen plates contain steroid hormones stored throughout the period of baleen growth and have been used for continuous, multi-year retrospective assessment of the reproductive and glucocorticoid history of individual whales. We measured progesterone, testosterone, cortisol, and corticosterone in baleen plates of seven individual Rice's whales (four males - one of which was the holotype - and three females), including two individuals believed to have died from starvation and one known to have been killed by ship strike. Baleen powder was obtained by drilling every 1 cm (~15-30 day intervals) from the base of the plates to the distal end. Hormones were quantified with enzyme immunoassay kits, and presence of the specific hormones was further confirmed with analytical chemistry. All assays passed validation assays for Rice's whale baleen extract. In the two individuals that likely died of starvation, all four steroid hormones show increases in the most recently grown baleen, a pattern observed in other baleen whales in cases of prolonged illness or injury before death. A female with a known recent pregnancy had a sustained elevation of progesterone spanning the majority of her plate, indicating that baleen analysis in this species can detect recent pregnancies. No evidence of annual testosterone cycles was noted in three adult males, suggesting that this subtropical species might not have strong seasonal reproduction, which is atypical for baleen whales. Thus, we conclude that baleen hormone analysis can be used to clarify life history patterns in this critically endangered species.