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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-irAEs. The study prospectively included 43 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-irAEs. 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 irAEs (P = 0.004). In the irAE group, median pre-ICI CXCL10 and baseline thyroid stimulating hormone (TSH) levels were significantly higher, baseline total testosterone level in men was lower than in the 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. [ABSTRACT FROM AUTHOR]

Objective Primary hypophysitis might be challenging to diagnose, and there is a lack of evidence regarding optimal treatment strategies due to rarity of the disease. We aim to investigate the clinical features and compare the outcomes of different management strategies of primary hypophysitis in a large group of patients recruited on a nationwide basis. Design A retrospective observational study. Methods The demographic, clinical, and radiologic features and follow-up data were collected in study protocol templates and analyzed. Results One hundred and thirteen patients (78.8% female, median age: 36 years) were included. Lymphocytic (46.7%) and granulomatous hypophysitis (35.6%) were the prevailing subtypes out of 45 patients diagnosed after pathologic investigations. Headache (75.8%) was the most common symptom, and central hypogonadism (49.5%) was the most common hormone insufficiency. Of the patients, 52.2% were clinically observed without interventions, 18.6% were started on glucocorticoid therapy, and 29.2% underwent surgery at presentation. Headache, suprasellar extension, and chiasmal compression were more common among glucocorticoid-treated patients than who were observed. Cox regression analysis revealed higher hormonal and radiologic improvement rates in the glucocorticoid-treated group than observation group (hazard ratio, 4.60; 95% CI, 1.62-12.84 and HR, 3.1; 95% CI, 1.40-6.68, respectively). The main indication for surgery was the inability to exclude a pituitary adenoma in the presence of compression symptoms, with a recurrence rate of 9%. Conclusion The rate of spontaneous improvement might justify observation in mild cases. Glucocorticoids proved superior to observation in terms of hormonal and radiologic improvements. Surgery may not be curative and might be considered in indeterminate, treatment-resistant, or severe cases. [ABSTRACT FROM AUTHOR]

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 S ubdoligranulum 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: One of the effects of the COVID-19 pandemic on the healthcare system has been the postponement of elective procedures. We aimed to investigate how the COVID-19 pandemic has affected our thyroid fine-needle aspiration biopsy (FNAB) results. Materials and Methods: The distribution of cytology results during the 16.5 months of the pandemic was compared with the pre-pandemic period by The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) diagnostic categories. Results: The number of FNABs performed during the pandemic period decreased by 27.3% compared to the pre-pandemic period in our center, in line with the recommendations (1,197 to 327 diagnostic FNABs). Benign biopsy results decreased during the pandemic period compared to the pre-pandemic period (77.3% to 49.5%, p<0.001), and indeterminate biopsy results (AUS/FLUS, FN/SFN, and SUS) increased from 19.5% to 45.9 %, p<0.001. Malign biopsy rates did not differ between pre-pandemic and pandemic periods (3.3% to 4.6%, p=0.25). Conclusion: Although the number of FNAB decreased due to pandemic measures, we found a decrease in benign cytology and an increase in indeterminate for malignancy. The pandemic period allowed us to be more selective when deciding on a biopsy for FNABs. We recommend that the risk assessment of nodules be done carefully when making the biopsy decision in the next period. Although it is recommended not to delay FNAB for nodules at risk for malignancy, it should not be forgotten that the surgical decision should not be hasty in indeterminate results, and follow-up can be continued, or biopsy can be performed again under appropriate conditions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim To investigate the alterations in the plantar fascia (PF), intrinsic muscles, and tendons in the feet of patients at high risk for developing diabetic foot. Methods The healthy feet of 22 patients with type 2 diabetes, who had developed diabetic foot ulcers on a single foot without any pathology on the contralateral extremity, and those of 22 healthy volunteers were evaluated by magnetic resonance imaging. The volume of the Achilles tendon (AT), the surface area of the PF, the thickness of AT, flexor hallucis longus, flexor digitorum longus, tibialis posterior, and peroneus longus tendons, irregularity in the PF, and edema of intrinsic foot muscles were examined. Results Nineteen patients (86%) had irregularity in the PF, whereas none of the healthy controls had any (p<0.001). Intrinsic muscle edema was more common in the group with diabetes (p=0.006). The volume of AT and the surface area of PF were decreased in patients with peripheral arterial disease (PAD) (p<0.05). Patients with diabetes mellitus but without PAD had a larger surface area of PF than that of controls (p<0.05). There were no differences in the volume of AT, the surface area of the PF, and other tendon thickness between the groups. Conclusion Irregularity in the PF and muscle edema may indicate a high risk for the diabetic foot. The presence of PAD may lead to regression in the structure of AT and PF. [ABSTRACT FROM AUTHOR]