Endocrine immune-related adverse events by immune checkpoint inhibitors and potential predictive markers: a prospective study from a single tertiary center.

Immune checkpoint inhibitors (ICIs) can trigger immune-related adverse events (irAEs). The appearance pattern of irAEs, who is prone to them, and their mechanisms are still uncertain. In this study, we aimed to monitor patients initiated on ICIs for endocrinological aspects and to investigate the potential predictive markers in the development of endocrine-irAE. The study prospectively included forty-three patients with metastatic disease scheduled for anti-PD-1/L1 therapy. Endocrinological follow-up was conducted at specified intervals as well as in response to any additional reported complaints. Serum concentrations of CXCL10, IL-1beta and IL-17A were measured prior to ICI and during the endocrine-irAE. A total of 39.5% of the patients experienced endocrine-irAEs, with a median onset time of 3 months. Among patients, 34.9% developed thyroid-related adverse events, and 4.6% experienced hypophysitis. Thyroid autoantibodies were associated with a higher incidence of thyroid-related irAE (p=0.004). In irAE group, median pre-ICI CXCL10 and baseline TSH levels were significantly higher, baseline total testosterone level in men was lower than non-irAE group (p<0.05), whereas IL-1beta and IL-17A levels did not differ (p<0.05). Serum CXCL10, IL-1beta, and IL-17A concentrations did not differ significantly pre-ICI and during adverse events (p<0.05). Pre-ICI CXCL10 concentration was correlated positively with anti-TPO levels in patients with at least one thyroid autoantibody positivity (r=0.706,p=0.01) and negatively with baseline total testosterone level of men (r=0.509,p=0.002). Our results suggest that higher pre-ICI serum CXCL10 and TSH levels might have a predictive role in the development of endocrinopathies. Besides, baseline thyroid antibody measurements could be beneficial in predicting thyroid dysfunction.

Beyond symptomatology: A comparative analysis of unilateral and bilateral macronodular mild autonomous cortisol secretion.

OBJECTIVE: To investigate the clinical, laboratory findings and signal intensity index (SII) on magnetic resonance imaging (MRI) of patients with bilateral and unilateral macronodular mild autonomous cortisol secretion (MACS). PATIENTS AND MEASUREMENTS: Clinical and laboratory findings of 81 patients with MACS were examined from retrospective records. SII of adenomas and internodular areas were evaluated by MRI. The unilateral group included patients with an adrenal macronodule (≥1 cm) in a single adrenal gland, while the bilateral group included patients with at least one macronodule in both adrenal glands. RESULTS: In total, 46 patients were in the unilateral (57%), while 35 (43%) patients were in the bilateral groups. The dehydroepiandrosterone sulphate (DHEA-S) level was lower in the unilateral than in the bilateral group (p < .001). The presence of type 2 diabetes mellitus (T2DM), glycosylated haemoglobin (HbA1c) and low-density lipoprotein (LDL) concentrations were higher in the bilateral group (p < .05). However, no significant difference was detected in terms of adrenocorticotropic hormone (ACTH) and overnight 1 mg dexamethasone suppression test (DST) between the two groups (p > .05). There was no difference in SII between adenomas within the same patient, as well as between the unilateral and bilateral groups (p > .05). Logistic regression analysis based on the differentiation between unilateral and bilateral macronodular MACS demonstrated that DHEA-S, HbA1c and LDL concentrations were associated factors. CONCLUSION: DHEA-S levels may not be as suppressed in patients with bilateral macronodular MACS as compared to those with unilateral adenoma. T2DM and hypercholesterolaemia have a higher frequency in bilateral patients. However, ACTH, overnight 1 mg DST and SII may not provide additional information for differentiation of bilaterality and unilaterality.

Cognitive functions and the brain-derived neurotrophic factor in patients with mild autonomous cortisol secretion.

CONTEXT: The impact of abnormal cortisol secretion on cognitive functions in patients with mild autonomous cortisol secretion (MACS) remains uncertain. OBJECTIVE: To assess cognitive functions, determine serum brain-derived neurotrophic factor (BDNF) concentration in patients with MACS, and investigate the association between cognitive subdomains and BDNF. METHODS: We prospectively recruited 84 participants-28 patients with MACS, 28 patients with nonfunctional adrenal adenoma (NFAA), and 28 control subjects matched for age, gender, body mass index (BMI), visceral adiposity, and educational level. The serum BDNF concentration of participants was measured. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-focused interviews and Montreal Cognitive Assessments (MoCA) were carried out by an experienced psychiatrist. RESULTS: Patients with MACS had a higher serum BDNF concentration than the NFAA (P = .001), while that of patients with NFAA was lower than the controls (P = .044). Linear regression analysis revealed BMI and morning cortisol after overnight 1 mg dexamethasone (DST) were mostly associated with BDNF (P < .05). No significant difference was found in MoCA scores between MACS and NFAA groups (P = .967), whereas those were lower than the control group (P = .004). When the cognitive subdomains were examined separately, MACS group performed higher memory score than NFAA (P = .045), but lower language scores than both the NFAA (P = .024) and control groups (P < .001). In the whole group, BDNF concentration was positively correlated with memory score (r = 0.337, P = .002), whereas DST was negatively correlated with language score (r = -0.355, P = .008). CONCLUSION: Low-grade hypercortisolism is associated with elevated BDNF concentrations, which may be a protective factor for memory function in patients with MACS relative to those with NFAA.

Relationship between gut microbiome and bone deficits in primary hyperparathyroidism: A proof-of-concept pilot study.

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age-sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of Subdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium, and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy.

Clinical prediction model for primary aldosteronism subtyping and special focus on adrenal volumetric assessment.

PURPOSE: Our aim was to develop a prediction model based on a simple score with clinical, laboratory, and imaging findings for the subtype diagnosis of primary aldosteronism (PA). The contribution of adrenal volumetric assessment to PA subtyping was also investigated. METHODS: Thirty-five patients with adequate cannulation in adrenal venous sampling (AVS) were included. Laboratory data, the saline infusion test (SIT), and the AVS results of patients with PA were retrospectively evaluated. Volumetric assessment was performed using magnetic resonance imaging (MRI) and the ratio of adrenal volumes was calculated after adjusting for gender- and side-specific mean reference values of both adrenal glands. RESULTS: The AVS was consistent with unilateral PA in 49% and bilateral in 51% of the patients. Hypertension as a reason for work-up, the highest aldosterone/lowest potassium value higher than 12, the percentage of plasma aldosterone concentration (PAC) reduction after SIT by equal or less than 43.5%, the use of oral potassium replacement, unilateral disease at pre-AVS imaging, and a ratio of adjusted adrenal volumes equal to or below 1.7 were indicative of unilateral disease in univariate logistic regression analysis concerning the distinction of PA subtyping (p < 0.05). Multivariate logistic regression analysis also revealed that adrenal volumetric assessment has an impact on PA subtyping (p < 0.05). In the prediction model, when each of the six parameters that were significant in the univariate logistic regression analysis was assigned one point, < 4 predicted bilateral PA, whereas ≥ 4 predicted unilateral PA (AUC:0.92, p < 0.001). CONCLUSION: This prediction model before AVS may serve as a convenient and practical approach, while an adjusted adrenal volumetric assessment can make a positive contribution to PA subtyping.

Credibility of ChatGPT in the assessment of obesity in type 2 diabetes according to the guidelines.

BACKGROUND: The Chat Generative Pre-trained Transformer (ChatGPT) allows students, researchers, and patients in the medical field to access information easily and has gained attention nowadays. We aimed to evaluate the credibility of ChatGPT according to the guidelines for the assessment of obesity in type 2 diabetes (T2D), which is one of the major concerns of this century. MATERIALS AND METHOD: In this cross-sectional non-human subject study, experienced endocrinologists posed 20 questions to ChatGPT in subsections, which were assessments and different treatment options for obesity according to the American Diabetes Association and American Association of Clinical Endocrinology guidelines. The responses of ChatGPT were classified into four categories: compatible, compatible but insufficient, partially incompatible and incompatible with the guidelines. RESULTS: ChatGPT demonstrated a systematic approach to answering questions and recommended consulting a healthcare provider to receive personalized advice based on the specific health needs and circumstances of patients. The compatibility of ChatGPT with the guidelines was 100% in the assessment of obesity in type 2 diabetes; however, it was lower in the therapy sections, which included nutritional, medical, and surgical approaches to weight loss. Furthermore, ChatGPT required additional prompts for responses that were evaluated as "compatible but insufficient" to provide all the information in the guidelines. CONCLUSION: The assessment and management of obesity in T2D are highly individualized. Despite ChatGPT's comprehensive and understandable responses, it should not be used as a substitute for healthcare professionals' patient-centered approach.

Detecting the interferences in adrenocorticotropic hormone measurement - three cases reinforcing the efficiency of the complementary clinical and laboratory audit.

Accurate measurement of adrenocorticotropic hormone (ACTH) is crucial in the evaluation of pituitary and adrenal disorders. Although great progress has been achieved in ACTH measurement with immunometric assays, interference may occur and adversely affect the clinical management. The report contributes to compiling the evidence on the clinical challenges with the management of the interferences in the ACTH measurement by presenting three cases: two with clinically overt hypercortisolism and discrepant ACTH concentrations within the reference interval; the third case describes the falsely elevated ACTH in a patient with secondary adrenal insufficiency. In all patients, the results obtained with the two immunometric platforms, chemiluminescence (CLIA) immunoassay (Siemens, Immulite) and electrochemiluminescence (ECLIA) immunoassay (Roche, Cobas), were discordant. Serial dilution of plasma samples revealed nonlinearity. After polyethylene glycol (PEG) precipitation recoveries were less than 22%, 26%, and 3%, respectively, supporting interference. Moreover, a decrease in ACTH concentration after incubation in a heterophile antibody-blocking tube was observed in the second case. In the first case, misinterpretation of ACTH led to inferior petrosal sinus sampling (IPSS), whereas timely detection of assay interference prevented further investigations in other cases. Increasing awareness regarding ACTH interference and comprehensive approach in evaluation could allow timely detection, helping to prevent unnecessary testing and perplexing clinical outcomes.

The impact of classical music on anxiety and pain perception during a thyroid fine needle aspiration biopsy.

AIM: To determine the impact of classical music on the anxiety and pain perception of patients who underwent thyroid fine-needle aspiration biopsy (TFNAB) for the first time. METHODS: In a prospective randomized controlled design, TFNAB patients were randomized into the intervention and control groups. The State Anxiety Inventory (SAI) before and after the procedure and the visual analog scale (VAS) after procedure were used for measuring anxiety and pain. RESULTS: A total of 82 patients were included. There was no significant difference between the music intervention group (n = 41) and control group (n = 41) in terms of age, gender, work status, highest education level, SAI score before TFNAB, and duration of the procedure (p > 0.05). It was observed that the anxiety level before TFNAB was higher in women in all patient groups (p = 0.009). While the SAI score decreased significantly in the music intervention group (Z = - 3.62, p < 0.001), there was no significant difference in the control group (Z = - 1.41, p = 0.157) after TFNAB. However, no significant difference was found in terms of VAS between two groups (p = 0.075). The duration of the TFNAB procedure was correlated with the change in the SAI score (r = 0.382, p < 0.001). CONCLUSION: This is the first study to examine the impact of music on patients' anxiety and pain perception during the TFNAB procedure. Despite the fact that classical music intervention did not decrease pain perception, it significantly reduced patient anxiety. Music is an easy-to-implement intervention that can be considered as an effective method for reducing patient anxiety during TFNAB.

Sleep quality in patients with non-functioning pituitary adenoma: impact of replacement therapies with an emphasis on the time of hydrocortisone.

PURPOSE: Sleep disturbances are widespread and associated with pituitary diseases, even those under long-term therapeutic management. The aim of this study was to investigate sleep quality in patients with non-functioning pituitary adenoma (NFPA) and determine the factors that might influence sleep quality, including the detailed features of replacement therapy. METHODS: Eighty-two patients with NFPA and 82 age- and gender-matched control subjects were included. Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS) and International Physical Activity Questionnaire (IPAQ) were used. RESULTS: In the NFPA group, 57.3% of patients had decreased sleep quality, compared to 35.4% in the control group (p=0.005). Although there was no relationship between the presence of hydrocortisone replacement and sleep quality (p>0.05), a strong positive correlation was observed between PSQI and morning hydrocortisone replacement time in patients with secondary adrenal insufficiency (r=0.834, p<0.001). Diabetes insipidus was found to be significantly higher in the group with decreased sleep quality (p=0.01). Moreover, there was a negative correlation between PSQI and IGF-1 in patients with NFPA (r=-0.259, p=0.01). A multivariate logistic regression model revealed that depression score and free T4 level in the upper half of the normal limit influence the sleep quality of patients with NFPA. CONCLUSION: Our study indicated the presence of depression, and a free T4 level in the upper half of the normal range have an impact on the sleep quality of patients with NFPA. The time of hydrocortisone replacement might be important factor for improved sleep quality in patients with secondary adrenal insufficiency.

Evaluation of Lipohypertrophy in Patients With Type 1 Diabetes Mellitus on Multiple Daily Insulin Injections or Continuous Subcutaneous Insulin Infusion.

OBJECTIVE: To determine lipohypertrophy (LH) in patients with type 1 diabetes mellitus (T1DM) on multiple daily insulin injections (MDII) or continuous subcutaneous insulin infusion (CSII) and to reveal the factors associated with the development and severity of LH. METHODS: Sixty-six patients with T1DM treated with MDII (n = 35, 53%) or CSII (n = 31, 47%) for at least 1 year were included. LH localizations were detected with palpation and ultrasonography (USG). RESULTS: The LH detection rate with USG was significantly higher than that by palpation in the whole group (P < .001). The LH was detected with USG in 30 (85.7%) patients in the MDII group and 22 (71.0%) patients in the CSII group (P = .144). Advanced LH was detected in 13 (37.1%) of the patients treated with MDII and in 3 (9.7%) of the patients treated with CSII. LH was more severe in the MDII group than in the CSII group (P = .013). Diabetes duration and length of infusion set use were significantly longer and body mass index, hypoglycemia, and complication rates were higher in patients with LH than those in patients without LH (P < .05). A positive correlation was found between LH severity and HbA1C and insulin dose (P < .05, for both). MDII as insulin administration method, incorrect rotation, and a history of ketosis were found to be the most related factors with LH severity in a multiple linear regression analysis (P < .05). CONCLUSION: USG might be an effective approach for detecting and evaluating the severity of LH. MDII might cause more severe LH than CSII in patients with T1DM. In this study, LH was found to be associated mostly with incorrect rotation technique and a history of ketosis.

Overlooked complication of Cushing's syndrome: Reactivation of hepatitis B.

OBJECTIVE: Individuals infected with hepatitis B virus (HBV) are at increased risk of reactivation when they receive immunosuppressive therapies. Although exogenous corticosteroid use as immunosuppressive therapy is elaborated in current guidelines on HBV reactivation, Cushing's syndrome (CS) with endogenous hypercortisolemia is not addressed. We aimed to investigate the prevalence of HBV infection and discuss the necessity of antiviral prophylaxis in patients with CS as in other immunosuppressed patients. DESIGN AND PATIENTS: We included 72 patients with CS (Adrenocorticotropic hormone (ACTH) dependent or independent) who were screened for HBV between 2016 and 2021. Patients were categorized into three groups: overt, mild autonomous cortisol secretion (MACS), and remission according to the cortisol burden. Changes in patients' HBV serology and clinical findings over time were analyzed retrospectively. RESULTS: Twenty-six patients had overt hypercortisolism, 18 had mild autonomous cortisol secretion and 28 patients were in remission. Nineteen (26.3%) patients were anti-HBc IgG positive, 4 of them were chronic HBV and 15 were isolated anti-HBc IgG positive. HBsAg was positive in four (5.5%) of the patients, who were all compatible with inactive chronic HBV. While two patients developed HBV reactivation, HBV flare was observed in one patient. CONCLUSION: Since it is not always possible to achieve rapid remission in CS and these patients have long-term hypercortisolemia, we suggest that consensus should be reached on HBV serological assessment, standardization of follow-up, and planning of HBV prophylaxis in required instances in patients with CS especially in regions with a high prevalence of HBV infection.

The quality and reliability analysis of YouTube videos about insulin resistance.

AIM: There is an increasing trend in the use of internet as a search tool for health-related informations. Insulin resistance is one of the most searched subjects online and some of the videos about insulin resistance have been watched by millions of YouTube users. This study aims to determine the quality and reliability of the most popular videos about insulin resistance on YouTube. METHODS: On March 1, 2022, the term "insulin resistance" was searched on YouTube. The videos' popularity was assessed with Video Power Index (VPI). The quality and reliability were assessed with DISCERN score, modified DISCERN score and global quality score (GQS). RESULTS: A total of 100 most popular videos were evaluated after applying the exclusion criteria. Fifty-four percent of the videos were very poor-poor, 35 % moderate, and 11 % good-excellent quality. Although few in number, the videos with relatively higher quality and more reliable had higher numbers of views, likes and comments (p < 0.01). There was a positive correlation between DISCERN score and VPI, duration, view, like, dislike, comment numbers of the videos (p < 0.01). Healthcare providers uploaded 58 % of the videos, while independent users uploaded 42 %. Video like ratio (VLR) at healthcare providers' videos was significantly higher than independent users' videos (p = 0.001). CONCLUSIONS: Despite the high viewing rates of YouTube videos about insulin resistance, the overall quality and reliability were found to be very low. However, when high quality content regarding popular medical topics is produced, more people can be informed correctly.

Infections in hematopoietic stem cell transplant patients admitted to Hematology intensive care unit: a single-center study.

OBJECTIVE: The aim of this study was to investigate the data of HSCT patients who were admitted to our Hematology ICU due to infections or infectious complications. MATERIALS AND METHODS: HSCT patients who were admitted to our Hematology ICU between 01 January 2014 and 01 September 2017 were analyzed retrospectively. RESULTS: 62 HSCT patients were included in this study. The median age was 55.5 years and 58% of the patients were allogeneic HSCT patients. Major underlying hematologic disorders were multiple myeloma (29%) and lymphoma (27.4%). The most common reasons for ICU admission were sepsis/septic shock (61.3%) and acute respiratory failure (54.8%). Overall ICU mortality rate was 45.2%. However, a lot of factors were related with ICU mortality of HSCT patients in univariate analysis, only APACHE II score was found to be an independent risk factor for ICU mortality. While there was infection in 58 patients at ICU admission, new infections developed in 38 patients during ICU stay. The most common new infection was pneumonia/VAP, while the most frequently isolated bacteria were Acinetobacter baumannii. Length of ICU stay, sepsis/septic shock as a reason for ICU admission and the presence of urinary catheter at ICU admission were determined factors for ICU-acquired infections. There was no difference between autologous and allogeneic stem cell transplant patients in terms of ICU morbidities and mortality. However, pneumonia/VAP developed in the ICU was higher in autologous HSCT patients, while bloodstream/catheter-related bloodstream infection was higher in allogeneic HSCT patients. CONCLUSION: It was concluded that early or late post-HSCT infections and related complications (sepsis, organ failure, etc.) constituted a major part of the reasons for ICU admission, ICU mortality and ICU morbidities.