Diabetes-induced male infertility: potential mechanisms and treatment options.

Male infertility is a physiological phenomenon in which a man is unable to impregnate a fertile woman during a 12-month period of continuous, unprotected sexual intercourse. A growing body of clinical and epidemiological evidence indicates that the increasing incidence of male reproductive problems, especially infertility, shows a very similar trend to the incidence of diabetes within the same age range. In addition, a large number of previous in vivo and in vitro experiments have also suggested that the complex pathophysiological changes caused by diabetes may induce male infertility in multiple aspects, including hypothalamic-pituitary-gonadal axis dysfunction, spermatogenesis and maturation disorders, testicular interstitial cell damage erectile dysfunction. Based on the above related mechanisms, a large number of studies have focused on the potential therapeutic association between diabetes progression and infertility in patients with diabetes and infertility, providing important clues for the treatment of this population. In this paper, we summarized the research results of the effects of diabetes on male reproductive function in recent 5 years, elaborated the potential pathophysiological mechanisms of male infertility induced by diabetes, and reviewed and prospected the therapeutic measures.

Oncological and endocrinological outcomes for children and adolescents with testicular and ovarian sex cord-stromal tumors. Results of the TGM13 National Registry.

RATIONALE: Sex cord-stromal tumors (SCST) are hormonally active and rare. The aim was to describe their endocrinological presentation and outcomes. METHOD: Patients (< 19 years) registered in the TGM13 registry between 2014 and 2021 for SCST were selected. RESULTS: Sixty-three ovarian SCST (juvenile granulosa tumor (JGT) n = 34, Sertoli-Leydig cell tumor (SLCT) n = 17, other SCST n = 12) were included. Median age was 13.1 years (0.4-17.4). Germline DICER1 pathogenic variant was present in 9/17 SLCT. Sixty-one were FIGO stage I (IC n = 14). Adjuvant chemotherapy was administered for 15. Seven had recurrence (FIGO IA n = 3, IX n = 2, III n = 2), leading to one death. With a median follow-up of 42 months (2.5-92), the 3-year progression-free survival (PFS) was 89% (95% CI 76%-95%). Median age was 6.4 years (0.1-12.9) among the 15 testicular SCST (Leydig cell tumor n = 6, JGT n = 5, Sertoli cell tumor n = 3, mixed SCST n = 1). Tumor-nodes-metastases (TNM) stage was pSI in 14. Eight underwent a tumorectomy, 7 an orchiectomy. None experienced recurrence. Endocrinological data were reviewed for 41 patients (18 prepubescent). Endocrine symptoms were present at diagnosis in 29/34 females and 2/7 males (gynecomastia). After a median follow-up of 11 months, 15 patients had persistent endocrine abnormalities: gynecomastia/breast growth (2 males, 1 prepubescent female), precocious/advanced puberty (4 prepubescent females), and hirsutism/menstruation disorders/voice hoarseness/hot flashes (8 pubescent females). The mean height at the last follow-up was within normal ranges (+0.3 standard deviation). CONCLUSIONS: SCSTs have a favorable prognosis. Tumorectomy appears safe with testicular primary. Endocrinological disorders, common at diagnosis, may persist warranting endocrinological follow-up.

Pollution and endometriosis: A deep dive into the environmental impacts on women's health.

BACKGROUND: The interaction between pollution and endometriosis is a pressing issue that demands immediate attention. The impact of pollution, particularly air and water pollution, or occupational hazards, on hormonal disruption and the initiation of endometriosis remains a major issue. OBJECTIVES: This narrative review aims to delve into the intricate connection between pollution and endometriosis, shedding light on how environmental factors contribute to the onset and severity of this disease and, thus, the possible public health policy implications. DISCUSSION: Endocrine-disrupting chemicals (EDCs) in pollutants dysregulate the hormonal balance, contributing to the progression of this major gynaecological disorder. Air pollution, specifically PM2.5 and PAHs, has been associated with an increased risk of endometriosis by enhancing chronic inflammation, oxidative stress, and hormonal imbalances. Chemical contaminants in water and work exposures, including heavy metals, dioxins, and PCBs, disrupt the hormonal regulation and potentially contribute to endometriosis. Mitigating the environmental impact of pollution is required to safeguard women's reproductive health. This requires a comprehensive approach involving stringent environmental regulations, sustainable practices, responsible waste management, research and innovation, public awareness, and collaboration among stakeholders. CONCLUSION: Public health policies have a major role in addressing the interaction between pollution and endometriosis in a long-term commitment.

Role of Mediterranean diet in endocrine diseases: a joint overview by the endocrinologist and the nutritionist.

PURPOSE: The purpose of this review is to examine the current evidence on the potential role of Mediterranean diet (MD) in the prevention and management of endocrine disorders and to highlight the importance of interdisciplinary collaboration between endocrinologists and nutritionists. METHODS: A literature search was conducted using PubMed and Google Scholar databases to identify relevant studies published in English. Studies were selected based on their relevance to the role of MD in the prevention and management of endocrine disorders. The search terms included "Mediterranean diet," "endocrine disorders," "thyroid disorders," "gonadal disorders," and "neuroendocrine tumors". RESULTS: The studies reviewed suggest that MD may have a beneficial effect in the prevention and management of various endocrine disorders, including thyroid disorders, gonadal disorders, and neuroendocrine tumors. MD has been associated with decreased risk of nodular thyroid disease and thyroid cancer, improved male and female reproductive health, and a potential role in the management of neuroendocrine tumors. MD's anti-inflammatory and antioxidant properties, as well as its high levels of phytochemicals, may play a role in its beneficial effects. CONCLUSION: Interdisciplinary collaboration between endocrinologists and nutritionists is essential for the optimal management of endocrine disorders, including the potential role of MD in their prevention and management. While further research is needed, the current evidence suggests that MD may have a protective effect against endocrine disorders, and its incorporation into dietary recommendations may be beneficial.

Multi-omics Investigations in Endocrine Systems and Their Clinical Implications.

Innovative techniques such as the "omics" can be a powerful tool for the understanding of intracellular pathways involved in homeostasis maintenance and identification of new potential therapeutic targets against endocrine-metabolic disorders. Over the last decades, proteomics has been extensively applied in the study of a wide variety of human diseases, including those involving the endocrine system. Among the most endocrine-related disorders investigated by proteomics in humans are diabetes mellitus and thyroid, pituitary, and reproductive system disorders. In diabetes, proteins implicated in insulin signaling, glucose metabolism, and ß-cell activity have been investigated. In thyroid diseases, protein expression alterations were described in thyroid malignancies and autoimmune thyroid illnesses. Additionally, proteomics has been used to investigate the variations in protein expression in adrenal cancers and conditions, including Cushing's syndrome and Addison's disease. Pituitary tumors and disorders including acromegaly and hypopituitarism have been studied using proteomics to examine changes in protein expression. Reproductive problems such as polycystic ovarian syndrome and endometriosis are two examples of conditions where alterations in protein expression have been studied using proteomics. Proteomics has, in general, shed light on the molecular underpinnings of many endocrine-related illnesses and revealed promising biomarkers for both their detection and treatment. The capacity of proteomics to thoroughly and objectively examine complex protein mixtures is one of its main benefits. Mass spectrometry (MS) is a widely used method that identifies and measures proteins based on their mass-to-charge ratio and their fragmentation pattern. MS can perform the separation of proteins according to their physicochemical characteristics, such as hydrophobicity, charge, and size, in combination with liquid chromatography. Other proteomics techniques include protein arrays, which enable the simultaneous identification of several proteins in a single assay, and two-dimensional gel electrophoresis (2D-DIGE), which divides proteins depending on their isoelectric point and molecular weight. This chapter aims to summarize the most relevant proteomics data from targeted tissues, as well as the daily rhythmic variation of relevant biomarkers in both physiological and pathophysiological conditions within the involved endocrine system, especially because the actual modern lifestyle constantly imposes a chronic unentrained condition, which virtually affects all the circadian clock systems within human's body, being also correlated with innumerous endocrine-metabolic diseases.

PCOS and vitamin D: a clinical appraisal.

PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrine-reproductive disease linked not just to infertility but also to serious comorbidities. There is a reported association between low vitamin D levels and multiple health conditions including PCOS. This narrative review aims to analyze the role of vitamin D in PCOS development, use of the vitamin D in the treatment of PCOS, and the molecular basis of these observations. METHODS: A Medline and PubMed research was performed, during the years 1990-2023, using a combination of keywords on such topic. According to the author's evaluation and target, papers were identified and included for a narrative review. RESULTS: There are associations between lower levels of vitamin D and PCOS, as well as with insulin resistance, metabolic syndrome, hyperandrogenemia, metabolic and endocrine disorders as well as the onset of oxidative stress and pro-inflammatory milieu, in PCOS women. CONCLUSION: Vitamin D has a role in pathologic changes linked to PCOS. Molecular and clinical investigations which give new information about the role of vitamin D in the development of PCOS and related endocrine and metabolic disturbance are further needed.

Metabolic/endocrine disorders in survivors of childhood-onset and cranial radiotherapy- treated ALL/NHL: a meta-analysis.

BACKGROUND: Cranial radiotherapy (CRT) is recommended to high-risk pediatric patients with acute lymphoblastic leukemia or aggressive non-Hodgkin's lymphoma (ALL/NHL). However, effects of CRT treatment on the development of metabolic/endocrine disorders remain unclear. This meta-analysis aimed to identify metabolic and endocrine disturbances in survivors of childhood-onset and CRT-treated ALL/NHL. METHODS: Different online databases were searched using restricted search fields. Follow-up data and outcome measurements, including the prevalence of growth hormone (GH) deficiency, hypothyroidism, vitamin D deficiency, overweight/obesity, and hypogonadism were recorded. The height data was indicated by height-standard deviation score (height-SDS). Statistical estimates such as odds ratio (OR) and weighted standard mean difference (SMD) were compared between additional CRT treatment group and non-CRT treatment group. Study-to-study heterogeneity was calculated by calculating I-squared statistic, and fixed/random effect was applied to synthesize and analyze extracted data. RESULTS: Fifteen studies were included (4269 patients in total). Adult height SDS was lower in CRT-treated patients (pooled SMD = -0.581, 95% CI: -0.649--0.512), and CRT-treated patients were likely to develop short stature (pooled OR = 2.289, 95% CI:1.674-3.130). Regardless of the study year, which potentially reflects the state-of-the-art CRT technique, the prevalence of short stature and GH deficiency was time-independent. Additionally, previous CRT can increase the risk of precocious puberty (pooled OR = 2.937, 95% CI: 1.281-6.736), hypothyroidism (pooled OR = 2.057, 95% CI:1.510-2.801), and hypogonadism (pooled OR = 3.098, 95% CI:2.521-3.807). However, the risk of being overweight/obese was similar between the patients with and without CRT (pooled OR = 1.278, 95% CI: 0.675-2.421). CONCLUSION: Childhood-onset and CRT-treated ALL/NHL survivors are likely to have shorter height, precocious puberty, hypothyroidism, and hypogonadism.

Knowledge of osteoporosis prevention among people with endocrine disorders: A cross-sectional study.

People with endocrine disorders are at an increased risk of osteoporosis, yet their knowledge of osteoporosis prevention is rarely studied. This study aimed to assess the knowledge related to osteoporosis prevention and its associated factors among people with endocrine disorders in China. A cross-sectional study was conducted in a Chinese hospital's Department of Metabolism and Endocrinology. A total of 562 people with endocrine disorders completed the Chinese version of the Osteoporosis Prevention and Awareness Tool to assess their knowledge of osteoporosis prevention. Results showed that participants had a mean knowledge of 59.36 ± 23.90 out of 100, with only 52.1% scoring above 60 points. Being female, having higher education, with comorbidities, with a recent osteoporosis diagnosis, and having received health education related to osteoporosis prevention were associated with higher knowledge of osteoporosis prevention. Our study indicates that more efforts are needed to improve the knowledge related to osteoporosis prevention among people with endocrine disorders. This may be realized by strengthening and expanding diverse education, focusing on males and those with lower education and without comorbidities.

Endocrine disorders in Beta-Thalassemia major patients at a Tertiary Care Hospital.

Objectives: To determine the frequency of endocrine disorders in Beta-Thalassemia Major (BTM) patients presenting for Endocrine Evaluation to the Department of Diabetes, Endocrinology and Metabolic Diseases, Hayatabad Medical Complex, Peshawar, Pakistan, a tertiary care hospital. Method: This descriptive study was conducted in the Department of Diabetes, Endocrinology and Metabolic Diseases, Hayatabad Medical Complex, Peshawar from October 2019 to August 2021. All patients with BTM presenting for endocrine evaluation were included in the study. Height and weight were assessed and plotted on the standard charts. For secondary sexual characteristics tanner staging was used. Blood samples for hormonal profile were taken according to standard protocol and sent for endocrine assessment. Results: A Total of 135 patients BTM were enrolled in the study comprising of 70 (51.9%) males and 65 (48.1%) females. Their mean age was 14.8±3.9 years, mean height 138.5±13.01 cm, mean weight 35.9±8.4 kg, mean BMI 18.6±2.8 kg/m2, mean age of transfusion started was 6.7±3.99 months, mean duration of transfusion 13.6±4.03 years and mean duration of chelation therapy received 6.1±4.5 years. Regarding endocrine complications, out of 135 patients assessed, one hundred (74.1%) had height less than 5th centile and fifteen (11.1%) had diabetes mellitus. For thyroid and parathyroid function, 58 and 13 were tested respectively, out of which 16 (27.6%) and 6 (46.2%) had thyroid dysfunction and hypoparathyroidism. Out of 91 patients assessed for pubertal delay, 61 (67.03%) had delayed puberty. Conclusions: High percentage of endocrine complications were found in patients with BTM. Severity and multiplicity of endocrine organs involvement was dependent on duration of the disease and lack of compliance with chelation therapy.

Passing on the exercise baton: What can endocrine patients learn from elite athletes?

As elite athletes demonstrate through the Olympic motto 'Citius, Altius, Fortius- Communiter', new performance records are driven forward by favourable skeletal muscle bioenergetics, cardiorespiratory, and endocrine system adaptations. At a recreational level, regular physical activity is an effective nonpharmacological therapy in the treatment of many endocrine conditions. However, the impact of physical exercise on endocrine function and how best to incorporate exercise therapy into clinical care are not well understood. Beyond the pursuit of an Olympic medal, elite athletes may therefore serve as role models for showcasing how exercise can help in the management of endocrine disorders and improve metabolic dysfunction. This review summarizes research evidence for clinicians who wish to understand endocrine changes in athletes who already perform high levels of activity as well as to encourage patients to exercise more safely. Herein, we detail the upper limits of athleticism to showcase the adaptability of human endocrine-metabolic-physiological systems. Then, we describe the growing research base that advocates the importance of understanding maladaptation to physical training and nutrition in males and females; especially the young. Finally, we explore the impact of physical activity in improving some endocrine disorders with guidance on how lessons can be taken from athletes training and incorporated into strategies to move more people more often.

Moyamoya associated with Turner syndrome in a patient with type 2 spinocerebellar ataxia-Occam's razor or Hickam's dictum: a case report.

BACKGROUND: Turner syndrome (TS) is a rare condition associated with a completely or partially missing X chromosome that affects 1 in 2500 girls. TS increases the risk of autoimmune diseases, including Graves' disease (GD). Moyamoya disease is a rare cerebral arteriopathy of unknown etiology characterized by progressive bilateral stenosis of the internal carotid artery and its branches. Both TS and GD have been associated with Moyamoya. Type 2 spinocerebellar ataxia (SCA2) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in ATXN2. We present the first case of Moyamoya syndrome in a patient with a previous diagnosis of TS and GD who tested positive for SCA2 and had imaging findings compatible with an overlap of SCA2 and Moyamoya. CASE PRESENTATION: A 43-year-old woman presented with mild gait imbalance for 2 years. Her family history was positive for type 2 spinocerebellar ataxia (SCA2). She had been diagnosed with Turner Syndrome (45,X) and Graves disease three years before. Brain MRI revealed bilateral frontal and parietal cystic encephalomalacia in watershed zones, atrophy of pons, middle cerebellar peduncles and cerebellum. MR angiography showed progressive stenosis of both internal carotid arteries with lenticulostriate collaterals, suggestive of Moya-Moya disease. Molecular analysis confirmed the diagnosis of SCA2. CONCLUSIONS: With increased availability of tools for genetic diagnosis, physicians need to be aware of the possibility of a single patient presenting two or more rare diseases. This report underscores the modern dilemmas created by increasingly accurate imaging techniques and available and extensive genetic testing.

Endocrine disorders after primary gamma knife radiosurgery for pituitary adenomas: A systematic review and meta-analysis.

PURPOSE: Gamma Knife radiosurgery (GKRS) is feasible for pituitary adenomas, but post-surgery GKRS may cause severe hormone deficits. We reviewed the literature on primary GKRS for pituitary adenoma focusing on radiation-induced hormone deficiencies. METHODS: PubMed, Web-of-Science, Scopus, and Cochrane were searched upon the PRISMA guidelines to include studies describing primary GKRS for pituitary adenomas. Pooled-rates of GKRS-induced hormone deficiencies and clinical-radiological responses were analyzed with a random-effect model meta-analysis. RESULTS: We included 24 studies comprising 1381 patients. Prolactinomas were the most common (34.2%), and 289 patients had non-functioning adenomas (20.9%). Median tumor volume was 1.6cm3 (range, 0.01-31.3), with suprasellar extension and cavernous sinus invasion detected in 26% and 31.1% cases. GKRS was delivered with median marginal dose 22.6 Gy (range, 6-49), maximum dose 50 Gy (range, 25-90), and isodose line 50% (range, 9-100%). Median maximum point doses were 9 Gy (range, 0.5-25) to the pituitary stalk, 7 Gy (range, 1-38) to the optic apparatus, and 5 Gy (range, 0.4-12.3) to the optic chiasm. Pooled 5 year rates of endocrine normalization and local tumor control were 48% (95%CI 45-51%) and 97% (95%CI 95-98%). 158 patients (11.4%) experienced endocrinopathies at a median of 45 months (range, 4-187.3) after GKRS, with pooled 5-year rates of 8% (95%CI 6-9%). GKRS-induced hormone deficiencies comprised secondary hypothyroidism (42.4%) and hypogonadotropic hypogonadism (33.5%), with panhypopituitarism reported in 31 cases (19.6%). CONCLUSION: Primary GKRS for pituitary adenoma may correlate with lower rates of radiation-induced hypopituitarism (11.4%) than post-surgery GKRS (18-32%). Minimal doses to normal pituitary structures and long-term endocrine follow-up are of primary importance.

The Prevalence of Metabolic and Endocrine Disturbances on Fracture Nonunion.

OBJECTIVE: This study aims to determine the prevalence of metabolic disturbance in all fracture nonunion cases and identify the most common endocrine abnormalities seen using a simple screening algorithm. METHODS: A retrospective review study was performed evaluating patients who underwent operative intervention for nonunion from January 2010 to December 2018 at 2 level-1 trauma centers. Preoperative laboratory values were recorded for a 9-test "nonunion panel." A metabolic or endocrine abnormality, specifically an abnormality in the thyroid or parathyroid axis, was evaluated. RESULTS: 42% of patients had an undiagnosed metabolic laboratory abnormality. When multiple tests were used, the rate of metabolic dysfunction was between 60% and 75%, depending on the definition of vitamin D insufficiency vs deficiency used. CONCLUSION: Results indicate a relatively high prevalence of metabolic disturbance in patients with nonunion and suggest metabolic screening for all nonunion patients not only those without a mechanical or infectious cause. LEVEL OF EVIDENCE: IV, retrospective case series.

Craniopharyngiomas: Surgery and Radiotherapy.

Taking into account the benign nature of craniopharyngiomas, the main method of treatment is the resection of the tumor. However, the tendency of these tumors to invade critical structures (such as optic pathways, the hypothalamic-pituitary system, the Willis circle vessels) often limits the possibility of a radical surgery.Craniopharyngiomas of the third ventricle represent the greatest challenge for surgery. After radical surgery, hypothalamic disorders often occur, including not only obesity but also cognitive, emotional, mental, and metabolic disturbances. Metabolic disorders associated with damage to the hypothalamus progress after surgery and lead to impaired functions of the internal organs. This process is irreversible and, in many cases, becomes the direct cause of mortality. The life expectancy of patients with the surgically affected hypothalamus is significantly shorter than in patients with preserved diencephalic function. The incidence of hypothalamic disorders after surgery can reach 40%.Even with macroscopically total resection, craniopharyngiomas can recur in 10-30% of cases, and in the presence of tumor remnants and with no further radiation treatment, the risk of recurrence significantly increases to up to 50-85% according to various studies. For this reason, the observation of patients with residual tumors after surgery is an incorrect strategy.Radiation therapy significantly improves progression-free survival (PFS), and the use of stereotactic irradiation techniques ensures conformity of irradiation of tumor remnants with a complicated shape and location (Iwata H et al., J Neurooncol 106(3):571-577, 2012; Aggarwal et al., Pituitary 16(1):26-33, 2013; Savateev et al., Zh Vopr Neirokhir Im N N Burdenko 81(3):94-106; 2017), which potentially reduces the risk of undesirable postradiation effects. Therefore, the quality of life in patients with craniopharyngiomas infiltrating the hypothalamus is significantly higher after non-radical operations with subsequent stereotactic radiation than after a total or subtotal removal.

Impact of endocrine disorders on stillbirth: a prospective cohort study.

OBJECTIVE: Among risk factors for SB, maternal endocrine diseases (ED), such as thyroids dysfunction and gestational diabetes mellitus (GDM), are the most frequent. This study aimed to investigate the rate of ED in a population of SB cases collected prospectively, and the relationship between these and causes of death. METHODS: This is an area-based, prospective cohort study conducted in Emilia-Romagna, Italy between January 2014 and December 2020. Data included all cases of SB (>22 weeks). RESULTS: From 2014 to 2020, 766 SB occurred out of a total of 232.506 births (SB rate:0.3/1000). The ED were present in 197/766 cases of SB (25.7%), respectively, 104 thyroid disease (52.8%), 74 GDM (37.5%), and 19 cases of concomitant GDM and thyroid disease (9.6%). Women who had SB associated with ED presented significantly higher mean maternal age (p < 0.001), BMI (p < 0.001), obesity (p < 0.001) and lower smoking habit (p = 0.02) respect with control group. Neonatal and placental weight of stillborn women with ED was significantly higher (p < 0.001) in respect to stillborn of the control group. Women with ED as associated condition (ReCODE classification), present significantly higher cases of SB caused by placenta pathologies (p = 0.009) namely abruptio placentae (p = 0.001) respect than control group. CONCLUSIONS: ED was more frequent in older and obese women experiencing SB. The main cause of death was abruptio placentae. This information can be helpful when counseling mothers with ED and planning antenatal management to prevent SB.

Iatrogenic Cushing syndrome due to topical corticosteroids after skin graft surgery for giant nevus: A case report.

Iatrogenic Cushing syndrome (ICS) may be caused by exposure to corticosteroid therapy. We report a case of ICS caused by topical corticosteroids applied to the skin after skin graft surgery. We presume that the development of ICS, in this case, was attributed to a combination of skin barrier disruption, usage of high-potency corticosteroids, broad application area/ large quantity of the corticosteroid, and the extended treatment period. Patients may be at risk for ICS after extensive skin graft surgery if large amounts of very potent topical corticosteroids are applied for an extended period to prevent scar formation or relieve itching.

The effect of online and in-person team-based learning (TBL) on undergraduate endocrinology teaching during COVID-19 pandemic.

BACKGROUND: Team-based learning (TBL) combines active and collaborative learning, while incorporating aspects of the flipped classroom approach and problem-based learning. The COVID-19 pandemic presented certain challenges in the delivery of TBL in class. In this study, we investigated the impact of TBL on the academic performance of final year Biomedical Sciences' undergraduate students in the context of an "Endocrine Disorders" study block. We did so by comparing the classical in-person approach and online delivery due to the COVID-19 pandemic. METHODS: A non-compulsory TBL session was introduced to the curriculum of this block, which followed the traditional 2-h lecture delivery. Comparative analysis was performed for the exam and coursework performance of students who attended the TBL sessions (online and in-person) and those that did not. RESULTS: Both cohorts of students who attended either in-person (n = 66) or online TBL sessions (n = 109) performed significantly better in their exams (p < 0.05) and a related coursework (p < 0.001 and p < 0.05, respectively) when compared to those that did not attend. For both these cohorts the exam mark distribution was much narrower compared to those that did not attend the TBL sessions where the majority of fails and "no shows" were recorded. CONCLUSIONS: Online and in-person TBL, can successfully supplement traditional lecture-based teaching and enhance the learning/performance, for complex medical subjects/topics. Our findings demonstrate that it is possible to deliver these sessions online with demonstrable benefit for students suggesting that there is greater flexibility in the use of TBL in higher education.

The Role of Placental Growth Factor in the Prediction of Carbohydrate and Thyroid Disorders during Pregnancy.

Background and objectives: To assess whether placental growth factor (PlGF) levels may have a predictive value for the onset of gestational diabetes mellitus (GDM) and thyroid dysfunction during pregnancy. Materials and Methods: This single-center retrospective analysis was conducted at the Specialized Hospital for Active Treatment in Obstetrics and Gynecology "Dr. Shterev", Sofia, Bulgaria, from December 2017 to December 2019. Using pregnant women's electronic records, we analyzed and compared the data of 412 women diagnosed with GDM and 250 women without evidence for carbohydrate disorders. Thyroid function was tested in all patients at the time of performing GDM screening. The following measurements were compared and assessed: body mass index (BMI), fasting blood glucose levels, thyroid-stimulating hormone levels (TSH), free thyroxine, and triiodothyronine (FT4 and FT3) levels, and serum placental growth factor (PlGF). The sensitivity and specificity of PlGF as a predictive marker for GDM and thyroid dysfunction were analyzed using receiver operating characteristic (ROC) curves. Results: There were no significant differences between GDM and control groups in terms of age and BMI (p > 0.05). In patients with established GDM, the PlGF corrected multiple of the median (MoM) was significantly higher compared to the control group (0.9 vs. 0.7, p < 0.001). The ROC-AUC for the prediction of GDM and thyroid dysfunction during pregnancy was 0.68 (95% CI 0.64-0.72) and 0.61 (95% CI 0.57-0.65), respectively. Conclusions: Our results underscore the potential role of PlGF as a biomarker in the prediction and diagnosis of GDM and thyroid dysfunction during pregnancy.

A case of Melkersson-Rosenthal syndrome with endocrine disorders: Extraordinary efficiency of hydroxychloroquine and mechanism hypothesis.

BACKGROUND AND PURPOSE: Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disease. In addition to the traditional clinical triad, there is also a diversity of clinical signs, and it may be related to other systemic diseases. METHODS: In the present study, we report a case of MRS with endocrine disorders that exhibits extraordinary therapeutic efficiency by using hydroxychloroquine (HCQ), explore whether there is an internal connection between MRS and endocrine disorders, and discuss the mechanism of the therapeutic efficiency of using HCQ. The hypothesis proposed for the first time is that MRS may essentially be a systemic granulomatous disease. RESULTS: The physical examination revealed orofacial swelling and fissured tongue. The histopathologic examination showed epithelioid granulomas. Combined with the other examination, this case was diagnosed as incomplete MRS. HCQ and local drugs were introduced. The patient achieved clinical recovery and psychological cure by the 18-week follow-up, and the 1-year follow-up found no reactivation of MRS. Moreover, the levels of cortisol and adrenocorticotropic were within normal ranges. CONCLUSIONS: After the drug therapy was targeted at granuloma, not only did all of the symptoms related to MRS disappear, but the endocrine system also returned to normal. It is speculated that the endocrine disorder in this patient may be related to MRS. We further propose the first-time hypothesis that MRS may essentially be a systemic granulomatous disease. It provides a new medication method with high-level efficiency.

Detection of parathyroid adenomas with multiphase 4DCT: towards a true four-dimensional technique.

BACKGROUND: Four-dimensional computed tomography (4DCT) is a commonly performed examination in the management of primary hyperparathyroidism, combining three-dimensional imaging with enhancement over time as the fourth dimension. We propose a novel technique consisting of 16 different contrast phases instead of three or four different phases. The main aim of this study was to ascertain whether this protocol allows the detection of parathyroid adenomas within dose limits. Our secondary aim was to examine the enhancement of parathyroid lesions over time. METHODS: For this prospective study, we included 15 patients with primary hyperparathyroidism and a positive ultrasound prior to surgery. We performed 4DCT with 16 different phases: an unenhanced phase followed by 11 consecutive arterial phases and 4 venous phases. Continuous axial scanning centered on the thyroid was performed over a fixed 8 cm or 16 cm coverage volume after the start of contrast administration. RESULTS: In all patients, an enlarged parathyroid lesion was demonstrated, and the mean lesion size was 13.6 mm. The mean peak arterial enhancement for parathyroid lesions was 384 Hounsfield units (HU) compared to 333 HU for the normal thyroid. No significant difference could be found. The time to peak (TTP) was significantly earlier for parathyroid adenomas than for normal thyroid tissue: 30.8 s versus 32.3 s (p value 0.008). The mean slope of increase (MSI) of the enhancement curve was significantly steeper than that of normal thyroid tissue: 29.8% versus 22.2% (p value 0.012). The mean dose length product was 890.7 mGy cm with a calculated effective dose of 6.7 mSv. CONCLUSION: Our 4DCT protocol may allow better visualization of the pattern of enhancement of parathyroid lesions, as enhancement over time curves can be drawn. In this way, wash-in and wash-out of contrast in suspected lesions can be readily demonstrated. Motion artifacts are less problematic as multiple phases are available. Exposure to our proposed 4DCT technique is comparable to that for classic helical 4DCT. Careful selection of parameters (lowering kV and SNR) can help to further reduce the dose.