EndoBridge 2023: highlights and pearls.

EndoBridge 2023 took place on October 20-22, 2023, in Antalya, Turkey. Accredited by the European Council, the 3-day scientific program of the 11th Annual Meeting of EndoBridge included state-of-the-art lectures and interactive small group discussion sessions incorporating interesting and challenging clinical cases led by globally recognized leaders in the field and was well attended by a highly diverse audience. Following its established format over the years, the program provided a comprehensive update across all aspects of endocrinology and metabolism, including topics in pituitary, thyroid, bone, and adrenal disorders, neuroendocrine tumors, diabetes mellitus, obesity, nutrition, and lipid disorders. As usual, the meeting was held in English with simultaneous translation into Russian, Arabic, and Turkish. The abstracts of clinical cases presented by the delegates during oral and poster sessions have been published in JCEM Case Reports. Herein, we provide a paper on highlights and pearls of the meeting sessions covering a wide range of subjects, from thyroid nodule stratification to secondary osteoporosis and from glycemic challenges in post-bariatric surgery to male hypogonadism. This report emphasizes the latest developments in the field, along with clinical approaches to common endocrine issues. The 12th annual meeting of EndoBridge will be held on October 17-20, 2024 in Antalya, Turkey.

Machine Learning May Be An Alternative To BIPSS In The Differential Diagnosis Of ACTH-Dependent Cushing's Syndrome.

OBJECTIVE: This study aimed to develop machine learning (ML) algorithms for the differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) based on biochemical and radiological features. METHODS: Logistic regression algorithms were used for ML, and the area under the receiver operating characteristics curve (AUROC) was used to measure performance. We used Shapley Contributed Comments (SHAP) values, which help explain the results of the ML models to identify the meaning of each feature and facilitate interpretation. RESULTS: A total of 106 patients, 80 with Cushing's disease (CD) and 26 with ectopic ACTH syndrome (EAS), were enrolled in the study. The ML task was created to classify patients with ACTH-dependent CS into CD and EAS. The average AUROC value obtained in the cross-validation of the logistic regression model created for the classification task was 0.850. The diagnostic accuracy of the algorithm was 86%. The SHAP values indicated that the most important determinants for the model were the 2-day 2-mg dexamethasone suppression test, the > 50% suppression in the 8-mg high-dose dexamethasone test, late-night salivary cortisol, and the diameter of the pituitary adenoma. We have also made our algorithm available to all clinicians via a user-friendly interface. CONCLUSION: ML algorithms have the potential to serve as an alternative decision support tool to invasive procedures in the differential diagnosis of ACTH-dependent CS.

Depression, anxiety, body image scores, and sexual dysfunction in patients with polycystic ovary syndrome according to phenotypes.

Background: Polycystic ovary syndrome (PCOS) has been linked to both mental and metabolic disturbances. The purpose of this research was to investigate psychological features such as anxiety and depression, body image, sexual dysfunction, and associated factors among the PCOS phenotypes and to compare these with healthy controls. Methods: The study involved 167 reproductive-age women with PCOS and 73 healthy controls. Standardized scales assessing depression (the Beck Depression Inventory [BDI]), depression and anxiety (the Hospital Anxiety and Depression Scale [HADS] and the General Health Questionnaire [GHQ]), and body image scale (the Body Cathexis Scale [BCS]) were administered to all participants. Hirsutism scores, serum androgen levels, and metabolic parameters were recorded. Results: Significantly higher BDI, HADS depression, and GHQ scores, and a more negative body image in terms of BCS scores were observed in the women with PCOS than in the healthy controls. BDI scores were significantly higher in phenotypes A, B, and D compared with the healthy controls. No significant difference was observed in BDI and HADS depression scores among the phenotypes. Significant differences were observed only between phenotype A and the control group in terms of HADS depression and GHQ scores. BCS scores were significantly higher in phenotypes A, B, and C than in the healthy controls. No significant difference was determined in Female Sexual Function Index (FSFI) scores between the PCOS phenotypes and the healthy controls. When all participants were divided into three groups based on body mass index (BMI), a statistically significant difference was observed only between the phenotype A lean group (BMI: 18.5-24.9 kg/m2) and the control group in terms of BDI, HADS depression, and BCS scores. Conclusions: BDI, HADS depression scores, and GHQ scores were all higher in patients with PCOS compared with the healthy controls. These features were more pronounced in phenotypes A and B, including hyperandrogenism and oligo-anovulation. Physicians should be aware of the high risk of these disorders in women with PCOS.

Management of endocrine surgical disorders during COVID-19 pandemic: expert opinion for non-surgical options.

PURPOSE: The COVID-19 pandemic brought unprecedented conditions for overall health care systems by restricting resources for non-COVID-19 patients. As the burden of the disease escalates, routine elective surgeries are being cancelled. The aim of this paper was to provide a guideline for management of endocrine surgical disorders during a pandemic. METHODS: We used Delphi method with a nine-scale Likert scale on two rounds of voting involving 64 experienced eminent surgeons and endocrinologists who had the necessary experience to provide insight on endocrine disorder management. All voting was done by email using a standard questionnaire. RESULTS: Overall, 37 recommendations were voted on. In two rounds, all recommendations reached an agreement and were either endorsed or rejected. Endorsed statements include dietary change in primary hyperparathyroidism, Cinacalcet treatment in secondary hyperparathyroidism, alpha-blocker administration for pheochromocytoma, methimazole ± ß-blocker combination for Graves' disease, and follow-up for fine-needle aspiration results of thyroid nodules indicated as Bethesda 3-4 cytological results and papillary microcarcinoma. CONCLUSION: This survey summarizes expert opinion for the management of endocrine surgical conditions during unprecedented times when access to surgical treatment is severely disrupted. The statements are not applicable in circumstances in which surgical treatment is possible.

An overview of polycystic ovary syndrome in aging women

The manifestations of polycystic ovary syndrome (PCOS), a ubiquitous reproductive disorder, may vary significantly depending on the severity of a number of endocrine and metabolic changes. Although no diagnostic criteria are presently available for PCOS for perimenopausal and menopausal women, the condition can still be suspected in case of a previous diagnosis of the condition, a chronic history of irregular menstrual cycles and hyperandrogenism, and/or polycystic ovarian morphology during the reproductive period. PCOS is associated with long-term health risks, including obesity, diabetes, hypertension, dyslipidemia, metabolic syndrome and cardiovascular risk factors during reproductive age, especially in patients possessing classic phenotypes. The aim of this review was to outline the available data about the impact of PCOS on long-term health risks after reproductive age in patients with PCOS. Previously, it was assumed that women with PCOS would be more prone to develop cardiometabolic diseases after reproductive age but current data suggest that in accordance with the healing in the phenotypic characteristics of PCOS, no deterioration appears to occur in cardiometabolic health in these patients. While there is substantial evidence for a greater prevalence of abnormal subclinical atherosclerotic markers among younger patients with PCOS, data for older women are insufficient. However, there is also support for an increased risk of endometrial cancer in PCOS patients. Extensive prospective cohort studies in which healthy controls as well as patients with defining PCOS phenotypes are observed and monitored from the early reproductive period into the late postmenopausal period should now be performed in order to clarify morbidities and mortality in aging women with PCOS.

Long-term results of coronary surgery with endoscopic vein harvesting.

BACKGROUND: In this study, we aimed to evaluate early and longterm outcomes of both isolated or concomitant coronary artery bypass grafting with the endoscopic vein harvesting technique. METHODS: Between November 2012 and May 2017, a total of 324 patients (259 males, 65 females; mean age: 63.2±9.8 years; range, 36 to 91 years) who underwent coronary artery bypass grafting, with or without concomitant procedures, using the endoscopic vein harvesting technique were retrospectively analyzed. Early postoperative outcomes and long-term follow-up data of the patients, such as cardiovascular or cerebral events, cardiac reinterventions, and the images of coronary angiography were recorded. RESULTS: Median logistic EuroSCORE and in hospital mortality was 3.99 (0.8-81) vs. 0 .9% f or i solated c oronary surgery and 13.34 (1.5-76.4) vs. 1.5% for concomitant procedures. The long-term data could be obtained in 288 patients with a median of 59.6 (7-90) months of follow-up. During this period, 22 (7.6%) patients underwent coronary angiography for control or treatment, 12 (4.2%) patients needed revascularization, and none of the patients underwent redo coronary surgery. CONCLUSION: Our study results suggest that the endoscopic vein harvesting technique during coronary artery bypass grafting is safe in experienced hands.

Obesity and physical exercise.

Obesity represents a major health problem worldwide and is associated with increased prevalence of numerous health-related conditions, including diabetes, hypertension, cardiovascular disease, some forms of cancer and musculoskeletal disorders, among others. Studies that have examined the impact of physical exercise combined with energy restriction diets on weight have shown greater weight loss compared to interventions of exercise-only. Accordingly, the most effective approach to achieve significant weight loss includes a combination of diet, exercise and behavioral strategies. Current guidelines recommend participating in at least 150 minutes of moderate-intensity or 75 minutes of vigorous intensity aerobic exercise weekly, and resistance/muscle strengthening training, involving all major muscle groups at least twice a week. For patients seeking to maintain weight loss, high levels of exercise (225-420 min/week of moderate intensity exercise) have been associated with improved weight maintenance compared to lower levels (<150 min/week). Weight loss has been associated with improvements in prevalence and severity of several obesity associated comorbidities such as insulin resistance, inflammation, dyslipidemia, hypertension, metabolic syndrome, diabetes, pulmonary disease and cardiovascular disease. This review summarized the current knowledge regarding the role of exercise in prevention of weight gain, weight loss and maintenance of weight loss in obese individuals, also outlining the data on effects of exercise on complications of obesity and highlighting areas for future research.

Suprasellar germinoma with hypopituitarism in an 18-year old man: A case report and review of literature.

An 18 year old patient was presented to the ophtalmology outpatient clinic with blurrred vision, headache and fatigue for 6 months. Ophtalmological examination showed loss of visual acuity in the left eye and decreased in the right eye and bilateral optic atrophy. Further physical examination pointed out delayed sexual development. Hypopituitarism was observed in endocrinological examination. Brain magnetic resonance imaging (MRI) demonstrated contrast enhancing mass lesion at suprasellar region with involvement of posterior perimesencephalic cisternal region. The mass resected by craniotomy and pathology showed germinoma. Afterwards he received systemic chemotherapy with bleomisin, etoposide, cisplatin for 4 cycles followed by cranial radiotherapy with 30.6 Gy with a boost to the primary tumor at a dose of 19.8 Gy. On his follow-up MRI, there are no signs of residual tumor nor tumor recurrence. His final examination reveals slightly increased visual acuity in the right eye and he continued to take hydrocortisone and L-thyroxin. After one year follow-up, human chorionic gonadotropin (hCG) alpha treatment was started for sexual development. Here in, we present a case with suprasellar germinoma in the context of the review of the literature.

Primary pituitary abscess case series and a review of the literature.

OBJECTIVE: Pituitary abscess is a rare condition, with approximately 300 cases reported in the literature. Primary pituitary abscess, the most common type, occurs in previously healthy normal glands. Secondary pituitary abscess is secondary to pre-existing lesions in the pituitary region, such as pituitary adenoma, Rathke's cleft cysts, or craniopharyngioma and infections. MATERIAL AND METHODS: A total of 2281 patients underwent pituitary surgery via endoscopic transsphenoidal approach in Kocaeli University Pituitary Gland Research Center between 1997 and 2018. Among this cohort 9 patients (4 female and 5 male) were diagnosed with primary pituitary abscess based on both intraoperative findings and postoperative histopathological evidence. RESULTS: Primary pituitary abscess incidence was obtained 0.39% in our center. Mean age of the patients was 50 years old. There was no history of pituitary surgery, radiotherapy and infection diseases in our patients. Visual symptoms were prominent in two patients, hypopituitarism was found in 5 out of the 9 patients. All patients have typical pituitary lesion on pituitary magnetic resonance imaging. Staphylococcus species were the most commonly isolated organisms in the culture. A few weeks of antibiotic therapy were administered after surgery. CONCLUSION: Presentation of fever, headache, diabetes insipidus, hypopituitarism and a sellar cystic mass with an enhanced rim after gadolinium contrast on pituitary magnetic resonance imaging may be suggestive of a pituitary abscess. Transsphenoidal endoscopic surgery, proper antibiotics and appropriate hormone replacement therapy when necessary are the keys of pituitary abscess treatment.

Investigation of VEGF and IL-8 Gene Polymorphisms in Patients with Differentiated Thyroid Cancer.

BACKGROUND: Differentiated thyroid carcinomas (DTC) account for most of the thyroid cancers. The emergence of DTC may be affected by various predisposing genetic alterations and environmental factors The aim of this study was to investigate the role of VEGF C936T and IL-8 A251T gene polymorphisms in the pathogenesis and metastasis of differentiated thyroid cancer. METHODS: The study consisted of 101 patients DTC patients and 109 healthy controls. The parameters of the stage of cancer of the DTC patients at the time of diagnosis (TNM) were recorded. DNA was isolated from blood using a DNA isolation kit. VEGF C936T and IL-8 A251T gene polymorphisms were determined using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. Distributions of gene polymorphisms were evaluated according to the Hardy-Weinberg principle. RESULTS: The TT genotype from the VEGF C936T genotype distributions was higher in the control group than in the DTC group (p < 0.05). In contrast, the IL-8 A-251T genotype distributions were similar in both groups. No relationship was found between either cytokine gene polymorphism or the DTC stages. The frequency of IL-8 TT was higher in the DTC group with lymph gland metastasis (TT 92%) than in the group without lymph gland metastasis (TT 45.9%) (p < 0.05). CONCLUSIONS: We consider that the VEGF 936 TT genotype may play a protective role in the development of DTC and that the IL-8 A-251 TT genotype may contribute to the DTC lymph node metastasis. Therefore, these genotypes may hold a key to the evaluation of thyroid nodules and the metastasis of DTC.

Polymorphism of the NFKB1 affects the serum inflammatory levels of IL-6 in Hashimoto thyroiditis in a Turkish population.

Hashimoto thyroiditis (HT) is a chronic inflammatory autoimmune disease of thyroid gland affected by interaction of multiple genes and various cytokines. Variants in the genes coding for the NFKB and IKB proteins can be potentially involved in the development of the inflammatory diseases. NFKB, a key transcription factor of the regulation of immune responses, is interesting candidate for association studies about autoimmune disorder. The aim of the present study was to investigate the relationship between NFKB1 and NFKBIA (NFKB1 inhibitor gene) polymorphisms, and the risk of HT in a Turkish Population in the context of IL-6 serum levels which may contribute to susceptibility to the disease. We analyzed the distribution of NFKB1-94ins/del ATTG and NFKBIA 3'UTR A→G polymorphisms using PCR-RFLP method and IL-6 serum levels using ELISA method in 120 HT patients and 190 healthy controls in Turkish population. Although, there was no statistical significant difference in distribution of the genotypes and alleles of NFKB1-94ins/del ATTG or NFKBIA 3'UTR A→G polymorphisms in patients and control subjects as single, ins/ins/GG combined genotype had protective effect on the disease when compared to ins/ins/AG combined genotype as combined genotypes of both polymorphisms. In addition to this finding, IL-6 serum levels in HT patients with del/del genotype were significantly higher than in patients with del/ins genotype (p<0.001). According to the combined genotype analysis of NFKB1-94ins/del ATTG and NFKBIA 3'UTR A→G polymorphisms, IL-6 levels were also higher in patients with del/del genotype when at least one G allele existing (p=0.007). Therefore, our findings suggest that the functional promoter NFKB1-94ins/del ATTG polymorphism was significantly associated with population HT disease through acting by directly modulating IL-6 serum levels.

Investigation of insulin resistance gene polymorphisms in patients with differentiated thyroid cancer.

We aimed to investigate insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), insulin-like growth factor binding protein-3 (IGFBP-3) genotypes, which are thought to be involved in the pathogenesis of many solid tumors and have thus far not been studied in patients with differentiated thyroid cancer (DTC). The study consisted of 93 patients diagnosed with DTC (79 females, 14 males) and 111 healthy control subjects (63 females, 48 males). The anthropometric measurements, lipid profiles, thyroid function tests and homeostatic model assessment (HOMA) as an indicator of insulin resistance (IR) of all patients were recorded. In addition IRS-1, IRS-2 and IGFBP-3 gene polymorphisms were determined by using polymerase chain reaction and restriction fragment length polymorphism. Hardy-Weinberg equilibrium was tested for each gene polymorphisms, and genetic effects were evaluated by the Chi Square test and multiple logistic regression. Homeostasis model assessment of insulin resistance (HOMA-IR), body mass index, waist circumference and serum total cholesterol levels were significantly higher in patients with DTC than in the control group. There was no difference between the two groups with respect to IRS-1, IRS-2 and IGFBP-3 gene polymorphisms. In addition, these gene polymorphisms were found to have no effect on lymph node metastases or tumor staging. While, obesity and increased HOMA-IR may be risk factors in DTC development, we suggest that IRS-1, IRS-2 and IGFBP-3 gene polymorphisms do not play an important role in pathogenesis of DTC.

Pheochromocytoma presenting with rhabdomyolysis and acute renal failure: a case report.

Rhabdomyolysis ranges from an asymptomatic illness with elevated creatine kinase levels to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure, and disseminated intravascular coagulation. The most common causes are crush injury, overexertion, alcohol abuse, certain medicines, and toxic substances. A number of electrolyte abnormalities and endocrinopathies, including hypothyroidism, thyrotoxicosis, diabetic ketoacidosis, nonketotic hyperosmolar state, and hyperaldosteronism, cause rhabdomyolysis. Rhabdomyolysis and acute renal failure are unusual manifestations of pheochromocytoma. There are a few case reports with pheochromocytoma presenting rhabdomyolysis and acute renal failure. Herein, we report a case with pheochromocytoma crisis presenting with rhabdomyolysis and acute renal failure.

Acromegaly is not associated with irritable bowel syndrome: a pilot study.

BACKGROUND: In acromegaly, the gastrointestinal system is under the influence of excessive growth hormone (GH) and insulin like growth factor-1 (IGF-I). Increased bowel length and delayed transit time may cause functional disturbance of the bowel. The objective of the current study is to evaluate the frequency of irritable bowel syndrome (IBS) in cases with acromegaly. PATIENTS AND METHODS: Twenty-three active cases with acromegaly newly diagnosed between 2010-2011 were included in the study. The control group consisted of ninety gender and age-matched healthy controls (HC). All cases were questioned for presence of IBS using Rome III criteria. Abdominal ultrasonography and colonoscopy results of acromegalic patients were obtained. In addition, cases with acromegaly were evaluated for their quality of life and status of depression by using the Acromegaly Quality of Life Questionnaire (AcroQoL) and Beck Depression Inventory (BDI), respectively. RESULTS: The median GH and IGF-1 levels of cases with acromegaly were 5.72 [IQR: 2.2-34] ng/ml and 753 [IQR: 503-1050] ng/ml, respectively. The median AcroQoL score of patients with acromegaly was 56 [IQR: 43-71.5] and the median BDI score was 16 [IQR: 11-21]. Rome III diagnostic criteria were positive in 2 of 23 acromegaly patients and in 3 of 90 HC (p=0.26). IBS was present in 1 of 23 of the acromegaly patients compared to 3 of 90 HC (p=0.81). CONCLUSION: Although acromegaly and IBS may cause similar gastrointestinal symptoms, acromegaly is not associated with a greater incidence of true IBS.

Evaluation of depression, quality of life and body image in patients with Cushing's disease.

The aim of this study was to evaluate patients with Cushing's disease (CD) who had undergone transsphenoidal surgery in terms of depression, quality of life (QoL), and perception of body image in comparison to healthy controls. Forty patients with CD and 40 healthy controls matched for demographic characteristics were included in the study. The subjects were evaluated with the Beck depression inventory (BDI), the health survey-short form (SF-36) and the multidimensional body-self relations questionnaire (MBSRQ). Subgroups of the patients with CD were formed on the basis of remission status and BDI scores. In this study, QoL in the general health category and body image were lower in the patients with CD than in the healthy subjects. However, no differences in depression scores were found between the two groups. When the CD group was evaluated according to remission rate, the mean BDI score was significantly higher in the CD patients without remission than in both the CD patients with remission and the healthy subjects (p = 0.04). However, the physical functioning, bodily pain and general health scores of the CD patients without remission on the SF-36 questionnaire were lower than in the CD patients in remission and the healthy subjects (p = 0.002, p = 0.04, p = 0.002, respectively). Fitness evaluation, health evaluation and body areas satisfaction scores of the MBSRQ were significantly different in the three groups (p = 0.003, p = 0.009 and p = 0.001, respectively). In this study, patients with CD were found to have lower QoL, lower body image perception and higher levels of depression compared to healthy controls, particularly if the disease is persistant despite surgery.

Aromatase cytochrome P450 enzyme expression in prolactinomas and its relationship to tumor behavior.

The aim of the study was to evaluate the presence of aromatase cytochrome P450 enzyme (P450AROM) expression in normal pituitary tissues and tumor tissues of patients with prolactinoma and to examine the impact of the P450AROM expression on clinical outcome. Twenty-six consecutive human pituitary tissue samples were obtained from autopsies performed at the Institute of Forensic Medicine. Sixty-four patients who had an adenomectomy between 2000 and 2009 after prolactinoma diagnosis with histologically confirmed pituitary tumor tissues were retrospectively included in this study. The slices from the pituitary tissues were subjected to immunohistochemical staining for evaluation of P450AROM and estrogen receptor beta (ER beta) subunit. Immunohistochemistry results were compared according to age, gender, remission rate, resistance and invasion status of the patients. Higher than normal P450AROM expression was found in the pituitary tissues of the patients with prolactinoma (p < 0.001). P450AROM intensity had no relation to resistance or remission in patients with prolactinoma (p = 0.44, p = 0.45, respectively). The subgroup analysis showed that compared to males without invasive adenoma, males with invasive adenoma had higher P450AROM expression (p = 0.048). ER beta was found to have an impact on resistance (p = 0.049). This study shows that P450AROM expression is present in the pituitary tissues of patients with prolactinoma and that this presence could be important in development and tumor behavior of prolactinomas.

Gammaknife radiosurgery in patients with acromegaly.

We aimed to evaluate the efficacy and reliability of gamma-knife radiosurgery (GKR) in 22 patients with acromegaly at the Endocrinology-Metabolism Clinic of Cerrahpasa Medical School. We collected data retrospectively from hospital records on disease activity and other pituitary functions, pituitary MRI and visual fields, before GKR and 6, 12, 24, 36, 48 and 60 months after GKR. The median follow-up duration after GKR was 60 months (interquartile range [IQR]: 24-60 months). The remission rate was 54.5% after the 60 months of follow-up. The median growth hormone (GH) level at 60 months after GKR (0.99 ng/mL [IQR: 0.36-2.2]) was significantly lower than the median GH level before GKR (5.65 ng/mL [IQR: 3.85-7.2] (p=0.002). The median insulin-like growth factor-1 (IGF-1) level 60 months after GKR (221.5 ng/mL [IQR: 149-535]) was significantly lower than the median IGF-1 level before GKR (582.5 ng/mL [IQR: 515-655]) (p=0.008). Tumour growth was well controlled in 20 patients (95.2%). Six patients (28.6%) developed new-onset hypopituitarism. We concluded that GKR is an effective adjuvant treatment to control tumour growth, lower GH and IGF-1 levels, and to increase remission rates in patients with acromegaly who were refractory to surgical and medical treatment.

Ornithine transcarbamylase deficiency diagnosed in pregnancy.

Urea cycle enzymes deficiencies are rare metabolic disorders. Ornithine transcarbamylase (OTC) deficiency is the most common type. The syndrome results from a deficiency of the mitochondrial enzyme OTC which catalyses the conversion of ornithine and carbamoyl phosphate to citrulline. It shows X-linked inheritance and typically remains asymptomatic until late infancy or early childhood. The severity of the symptoms depends on the age of the patient and the duration of hyperammonemia. Female heterozygotes are more difficult to diagnose. They suffer from hyperammonemic periods which can be triggered by trauma, infections, surgery, childbirth, parenteral nutrition, and by the initiation of sodium valproate therapy. The prognosis of OTC deficiency is better for those with an onset after infancy, but morbidity from brain damage does not appear to be linked to the number of episodes of hyperammonemia that have occurred. However, early diagnosis and prompt initiation of ammonia-lowering treatment are essential for survival of these patients. This case presents a patient who was diagnosed with OTC deficiency following mental confusion during pregnancy.