Insufficiency In Patients Research Articles

Single-cell RNA sequencing reveals common interactions between follicle immune cells and granulosa cells in premature ovarian insufficiency patients

Abstract Objective To investigate the follicle microenvironment of individuals with premature ovarian insufficiency (POI), normal ovarian reserve (normal) and advanced maternal age (AMA), and identify potential therapeutic targets. Methods A total of 9 women, including 3 POI, 3 normal and 3 AMA women, underwent in vitro fertilization or intracytoplasmic sperm injection were included in this study. For each participant, the first punctured follicle not containing cumulus cells were submitted to single-cell RNA sequencing to explore the characteristics of the follicle microenvironment of POI, normal and AMA individuals. Result(s) A total of 87,323 cells were isolated and grouped into six clusters: T cells, B cells, neutrophils, basophils, mononuclear phagocytes, and granulosa cells. Further analysis demonstrated that the population of granulosa cells in cluster 6 was increased in AMA and POI patients, whereas the population of gamma delta T (GDT)-cells was decreased. We also found that the genes that were differentially expressed between GDT cells and monocytes were enriched in ribosome- and endoplasmic reticulum (ER)-related pathways. In addition, it showed that VEGFA-FLT1 interaction between the monocytes and granulosa cells may be lost in the AMA and POI patients as compared with the normal group. Conclusion(s) Loss of the VEGFA-FLT1 interaction in monocytes and granulosa cells, along with enriched ER- and ribosome-related pathways, may drive excess inflammation, accelerating granulosa cell senility and contributing to infertility. This study provides new insights into the pathogenesis of POI and aging and highlights the VEGFA/FLT1 interaction may be a potential therapeutic target for reducing inflammation and treating POI.

Diagnosis and approach to glucocorticoid-induced adrenal insufficiency and glucocorticoid withdrawal syndrome

Introduction and purpose: Primary adrenal insufficiency can result from diseases affecting the adrenal glands, while secondary adrenal insufficiency is caused by suppression of the hypothalamic-pituitary-adrenal axis. The most common cause of adrenal suppression is exogenous steroids, a condition recently termed glucocorticoid-induced adrenal insufficiency (GIAI). Glucocorticoid-induced adrenal suppression is a common adverse effect of glucocorticoid therapy, which can have severe consequences. This review provides a comprehensive overview of the diagnosis and management of glucocorticoid-induced adrenal insufficiency and glucocorticoid withdrawal syndrome. Material and methods: An extensive examination of articles published in scientific journals was carried out through online research platforms PubMed and Google Scholar. We searched articles by entering keywords in appropriate configuration: “glucocorticoid-induced adrenal insufficiency”, “glucocorticoids”, “steroids”, “adrenal crisis”, “substitution therapy”, “glucocorticoid withdrawal”. Description of the state of knowledge: Glucocorticoids are widely used in the treatment of various inflammatory and autoimmune disorders due to their potent anti-inflammatory and immunosuppressive effects. However, chronic glucocorticoid therapy can lead to a number of adverse effects, including adrenal suppression, which can result in adrenal insufficiency. Summary: Primary care clinicians should recognize the high prevalence of glucocorticoid-induced adrenal insufficiency in patients receiving non-oral glucocorticoid formulations. The glucocorticoid withdrawal syndrome exhibits symptoms analogous to glucocorticoid-induced adrenal insufficiency. Additional data on the morbidity and mortality linked to glucocorticoid-induced adrenal insufficiency is needed to comprehend the associated health risks, which will ultimately guide the approach to care for patients tapering long-term glucocorticoid therapy.

Clinical and Genetic Mechanisms in Patients with MC2R Deficiency Presenting with Early Puberty.

Melanocortin receptor 2 (MC2R) in the adrenal cortex controls the hypothalamic-pituitary-adrenal axis. The melanocortin system, influenced by leptin, regulates GnRH neurons, crucial for puberty onset and fertility. This study evaluates early puberty in primary adrenal insufficiency (PAI) patients due to MC2R gene alterations. Seven patients with PAI (P1-P7) from five unrelated families, all presenting with early or precocious puberty, were included. MC2R deficiency diagnosis ranged from 1 day to 11 months. MKRN3, DLK1, KISS1, and KISS1R genes were analyzed using Sanger sequencing in four cases (P2,P4,P6 and P7). All clinical data were obtained retrospectively. Puberty onset mean age was 8.6 years (7.4-9.5) in boys (P1, P2, P3, P7) and 8.5 years (7.4-9.5) in girls (P4, P5, P6). Tumor markers were negative; no adrenal rest or tumors were found. GnRH analogs were used for rapid puberty in P2, P3, P6. Final height in P1 and P2 was below target (-2.6 SDS, -0.7 SDS). Menarche occurred at 11 and 11.3 years in P4 and P5. No pathogenic variants were found. Genetic causes of early puberty were not identified. Elevated ACTH may stimulate kisspeptin neurons, triggering puberty. Close monitoring of these patients for pubertal development is recommended.

Impact of asprosin, interleukin-6, and adiponectin on exocrine pancreatic insufficiency in patients with type 2 diabetes mellitus and chronic pancreatitis

Exocrine pancreatic insufficiency (EPI) is a clinical condition often associated with chronic pancreatitis (CP) and type 2 diabetes mellitus (T2DM) leads to malabsorption and nutritional deficiencies, severely impacting patients’ quality of life. It has been identified that asprosin, a glucogenic protein, is a key player in carbohydrate metabolism and chronic inflammation. Elevated levels of asprosin, along with changes in interleukin‑6 (IL‑6) and adiponectin, may contribute to the pathophysiology of EPI in patients with T2DM and CP. Objective — to investigate the levels of asprosin, IL‑6, and adiponectin and their correlation with exocrine pancreatic function in patients with T2DM and CP. Materials and methods. The study included 100 patients treated at Kharkiv Regional Clinical Hospital from 2020 to 2022. Patients were divided into two groups: Group 1 (n=70) with comorbid T2DM and CP, and Group 2 (n=30) with T2DM alone. The control group included 20 healthy individuals. Blood levels of asprosin, IL‑6, and adiponectin were measured using immunoassays. Fecal elastase‑1 (FE‑1) levels were used to assess exocrine pancreatic function. Pearson’s correlation coefficient was calculated to determine the relationships between these markers. Results. Asprosin levels were significantly higher in Group 1 compared to Group 2 and the control group, with the highest levels observed in patients with comorbid T2DM and CP (10.06±3.56 ng/ml). IL‑6 levels were also elevated in Group 1 (64.44±4.35 pg/ ml), indicating heightened inflammation. Adiponectin levels were lower in Group 1 (2.80±0.38 ng/ml), correlating with worse metabolic profiles. FE‑1 levels were markedly reduced in Group 1 (142.2±6.3 mg/ g), confirming severe EPI. Significant correlations were found between asprosin levels and IL‑6 (positive correlation, r=0.49, p<0.01), as well as between asprosin levels and FE‑1 (negative correlation, r=–0.52, p<0.01). In the group of patients with isolated T2DM, significant moderate negative correlations were found between asprosin levels and adiponectin (r=–0.47, p<0.05) and FE‑1 (r=–0.44, p<0.05). The study also demonstrated a strong negative correlation between adiponectin and IL‑6 (r=–0.61, p<0.01) in patients with comorbid T2DM and CP. Conclusions. Elevated asprosin levels in patients with T2DM and CP are associated with increased inflammation and reduced exocrine pancreatic function. The significant correlations between asprosin, IL‑6, and FE‑1 suggest that asprosin could serve as a clinically valuable biomarker for assessing metabolic and inflammatory status in these patients. The findings highlight the complex interaction between metabolic and inflammatory pathways in the development of EPI.

7839 Assess Management of Adrenal Insufficiency in Melanoma Patients Treated with Cancer Immunotherapy

Abstract Disclosure: W. Lin: None. L. Min: None. Despite high prevalent of adrenal insufficiency in melanoma patients treated with cancer immunotherapy, no study has examined the management of adrenal insufficiency in these patients. We performed this retrospective, longitudinal cohort study at Mass General Brigham, Boston, aims to characterize the management of adrenal insufficiency in melanoma patients. Patients were identified through our RPDR search tool, and medical record reviews were conducted. Three patient groups were analyzed: Melanoma with secondary adrenal insufficiency group (Mel_SAI, n=74), Melanoma matched control group (Mel_Con, n=69), and Pituitary macroadenoma-related adrenal insufficiency matched control group (Pit_Con, n=37). We compared self-perceived quality of life, glucocorticoid replacement dose, and clinic visit. Mel_SAI patients exhibited significantly higher incidences of anxiety (43.1%, 95%CI: 32.3-54.6), fatigue (73.6%, 95%CI: 62.4-82.4), pain (58.3%, 95%CI: 46.8-69.0), and insomnia (36.1%, 95%CI: 26.0-47.6), as compared to Pit_Con group (21.6%, 11.4-37.2; 24.3, 13.4-40.1; 29.7%, 17.5-45.8; 5.4%, 1.5-17.7, respectively). The initial hydrocortisone dose was higher for Mel_SAI (30mg qd, 95%CI: 20.5-25.1) compared to Pit_Con (15mg qd, 95%CI: 12.8-18.3). Additionally, the Mel_SAI group had fewer endocrinology clinic visits (3, 95%CI: 3.40-5.04) than the Pit_Con group (9, 95%CI: 7.35-10.9). Subgroup analysis indicated a higher mortality risk (HR 2.61, 95% CI 1.11-6.13) in Mel_SAI patients with fewer than three endocrinology visits over five years. Compared to the Mel_Con group, Mel_SAI patients also showed higher incidences of fatigue (71.6%, 95%CI: 60.5-80.6; Mel_Con: 55.1%, 95%CI: 43.4%-66.2%), but lower rates of depression (25.7%, 95%CI: 17.1-36.7; Mel_Con: 43.5%, 95%CI: 32.4-55.2) and appetite loss (24.3%, 95%CI: 16.0-35.2; Mel_Con: 47.8%, 95%CI: 36.4-59.4). No significant difference in other self-perspective symptoms. Furthermore, Mel-SAI patients had more oncological clinic visits (71, 95%CI: 74.0-109.2) than those in the Mel_Con group (41, 95%CI: 42.1-64.1). Our study suggests that most self-perceived quality of life in the Mel_SAI group is related to melanoma rather than adrenal insufficiency. Therefore, a higher initiating dose of hydrocortisone in melanoma patients with adrenal insufficiency may not be necessary. However, increasing endocrine clinic visits in cancer patients with cancer immunotherapy-related adrenal insufficiency may improve their survival outcomes. Presentation: 6/3/2024

7243 COVID-19 Associated Primary Autoimmune Adrenal Insufficiency: A New Clinical Entity

Abstract Disclosure: J. Naredo Rojas: None. B. Udegbe: None. I. Remba-Shapiro: None. S.L. Stockman: None. L.B. Nachtigall: None. Background: The adrenal glands express angiotensin converting enzyme and transmembrane serine protease 2 receptors for SARS-CoV-2 protein S, facilitating viral entry. Cortisol levels are decreased in COVID-19 infection in correlation with disease severity. A number of potential mechanisms could relate autoimmune adrenal insufficiency (AI) to COVID-19, but whether or not SARS-CoV-2 infection plays a direct role in the autoimmune pathogenesis of primary AI is unknown. Furthermore, while single cases have been reported, autoimmune-mediated primary adrenal insufficiency following COVID-19 illness has not been formally studied. Purpose: To determine the association and clinical presentation of primary autoimmune adrenal insufficiency in patients with COVID-19 disease. Methods: A retrospective chart review was performed on patients presenting to Massachusetts General Hospital (MGH) with primary AI in the setting of recent COVID-19 illness. Review of the literature was performed to identify additional cases. Clinical, biochemical and radiographic characteristics, and interval between the diagnosis of COVID-19 and primary AI diagnosis were evaluated. Criteria for inclusion were biochemical confirmation of AI, clinical signs and/or symptoms of adrenal insufficiency within 6 months of COVID-19 illness, and evidence of autoimmune etiology of AI. Results: Five novel cases of COVID-19 associated primary autoimmune-mediated adrenal insufficiency from our Center were identified. Review of the literature yielded five additional cases. This series combines our Center’s experience, and the cases reported to date, including a total of 10 patients, 6 men and 4 women. All men (6/6) and 2 women (2/4) were < 30 years old. Patients demonstrated clinical evidence of adrenal insufficiency in a median time frame of 14 days (IQR 8.5-23.3) after SARS-CoV-2 infection. Vomiting, hypotension, and hyponatremia were present in all (N=10). Other common symptoms were nausea (90%), fatigue (70%), hyperpigmentation (70%) and hyperkalemia (50%). Nine (90%) had a positive past medical and/or family history of autoimmune disease. Nine (90%) had positive 21-hydroxylase antibodies. The median serum morning cortisol level was 1.1μg/dL with an IQR of 0.7-3.0 μg/dL. The mean ACTH level was 1235.2 pg/mL with a SD of 580.1 pg/mL. The mean ACTH was 19.3 x ULN with a SD of 10.0. Adrenal imaging did not show hemorrhage or necrosis but showed atrophy in 50%. Conclusions: This series reveals that autoimmune-mediated primary adrenal insufficiency may be diagnosed in the aftermath of COVID-19 illness. Age under 30, family history and/or past medical history of autoimmune disease may be associated. Future prospective studies are needed to determine causality. Presentation: 6/1/2024

6768 A Rare Presentation of Primary Adrenal Insufficiency with Hypertension & Hypokalemia

Abstract Disclosure: A.M. San Hernandez: None. R. Alshantti: None. G. Espinoza Mercado: None. J.L. San Hernandez: None. Introduction: Adrenal Insufficiency is caused by the failure of the adrenal cortex to produce glucocorticoids +/- mineralocorticoids. This can be due to a defect in the adrenal cortex, or in the hypothalamic pituitary axis. The clinical manifestations are usually non-specific, ranging from mild vague symptoms to life threatening crisis. Therefore, diagnosis requires a high level of suspicion by providers. Unusual presentations of primary adrenal insufficiency (PAI) with hypertension and hypokalemia have been rarely described in the literature. We present a rare case of PAI with hypertension and hypokalemia. Case Presentation: A 68 years old female with a medical history of rheumatoid arthritis, hypothyroidism on Levothyroxine, chronic transaminitis, and bicytopenia presented to the hospital with a 6 weeks history of generalized weakness, loss of appetite, weight loss, and dizziness. Patient denied any diuretic or steroid use within the last 2 years. On arrival, she was afebrile, hypertensive (168/84mmHg), with normal oxygenation and pulse. Physical examination was unremarkable with normal volume status. Initial laboratory results showed low sodium 116 mEq/L, low serum osmolality 247 MEQ/kg, normal potassium 3.6 mEq/L, Creatinine 0.3 mg/dL & BUN 9 mg/dL. She was initially started on IVF normal saline. Further workup revealed normal TSH & FT4 levels. Urine study showed urine osmolality (477 MOSM/KG), & urine sodium (127 mEq/L). Given these findings, SIADH was suspected and fluid restriction was started. Sodium level continued to be low with minimal improvement to 120 mEq/L, potassium levels also dropped (3.3-3.2 mEq/L), requiring daily replacement. BP remained elevated ranging from 150s to 160s systolic and 80s to 90s diastolic. Hypertension was controlled with her home medication Amlodipine. Although atypical presentation with hypertension & hypokalemia, the diagnosis of adrenal insufficiency was considered. Laboratory evaluation showed low morning cortisol 5.2 ug/dL, with album level 3.5 g/dL. Cosyntropin stimulation test showed 1.3 ug/dL (at baseline), 9.9 (30 min post administration), and 14.4 (1 hour post administration); results confirming PAI. ACTH, Renin, Aldosterone, & DHEAS levels were normal. CT adrenal was normal. Patient was started on hydrocortisone; some of her symptoms & Na level improved. Further investigation of the etiology of PAI and possible hyperaldosteronism is pending outpatient follow up. Conclusion: Adrenal insufficiency is a life threatening condition with serious consequences if diagnosis is missed. It manifests by a wide spectrum of symptoms and signs, some can be masked by the presence of other comorbid conditions leading to atypical presentations. Our case highlights the importance of maintaining a high level of suspicion of adrenal insufficiency in patients with atypical presentation, including those with hypertension & hypokalemia. Presentation: 6/3/2024

8145 Type 2 Diabetes In A Patient With IMAGe Syndrome

Abstract Disclosure: N. Mulpuri: None. S. Mirfakhraee: None. J. Abramowitz: None. Background: Individuals with mutations that lead to deficiency of POLE1 (a catalytic subunit of polymerase epsilon) may have clinical features of IMAGe syndrome (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenital, and genitourinary anomalies) in addition to distinctive facial features and variable immunodeficiency. Of 15 reported cases in the literature, none were previously characterized with type 2 diabetes mellitus (T2DM). Clinical case: This is a 25-year-old woman with a history of IMAGe syndrome (confirmed mutation in the POLE gene). With regards to IMAGe syndrome history, during the prenatal period, she had growth restriction in the third trimester with delivery at 38 weeks. At 4 years-old, she presented with adrenal crisis and was started on glucocorticoid and mineralocorticoid therapy, now taking hydrocortisone 2.5mg three times daily (8.6 mg/m2/day) and fludrocortisone 0.05mg daily. Initial labs in the adult endocrine clinic were notable for serum glucose 339 mg/dL (65-99 mg/dL), undetectable estradiol (< 15 pg/ml) with FSH 6.8 mIU[JA1] /mL and LH 2.0 mIU/mL, TSH 1.25 mIU/L (0.40-4.50 mIU/dL), FT4 0.7 ng/dL (0.8-1.8 ng/dL). The patient denied any history of T2DM. She also denied polyuria, polydipsia, or weight loss. There was no stigmata of peripheral insulin resistance on exam. Subsequent labs included HbA1c 8.9%, fructosamine 417 mcmol/L (200-285 mcmol/L), insulin 18.4 mcIU/mL (2.6-24.9 mcIU/mL), and C-peptide 3.9 ng/dL (1.1-4.4 ng/dL) with serum glucose 164 mg/dL. Islet cell, insulin, and GAD-65 antibodies were undetectable. CT abdomen/pelvis did not show any pancreatic mass or anomalies. Initially, prandial insulin (lispro 3 units prior to each meal) was initiated given post-prandial hyperglycemia noted on continuous glucose monitoring. Low-dose levothyroxine, 25 mcg daily, was initiated given concern for secondary hypothyroidism, with subsequent normalization of serum thyroxine. HbA1c improved to 7.4% six months later. Ultimately, she transitioned to sitagliptin 25 mg daily and her latest HbA1c was 6.2% three years after initial diagnosis of T2DM. Conclusion: Of the 15 cases of IMAGe syndrome with mutations in POLE described in Logan et al, none were noted to have diabetes. The patient described above was diagnosed with new-onset diabetes at age 21, presumably T2DM in the context of undetectable antibodies and high-normal C-peptide. Interestingly, she did not have any typical stigmata of peripheral insulin resistance. Glucocorticoids used for the treatment of adrenal insufficiency in patients with IMAGe syndrome can contribute to development of T2DM. Patients with IMAGe syndrome on chronic glucocorticoids should be monitored for hyperglycemia and diabetes. Additionally, glucocorticoid doses should be optimized to balance mitigating side effects such as hyperglycemia and osteoporosis while preventing adrenal crisis. Presentation: 6/3/2024

7695 Impact Of Day Of Admission On Outcomes Of Adrenal Insufficiency- A National Inpatient Sample Study

Abstract Disclosure: S. Karki: None. B. Neupane: None. S. Neupane: None. A. Bhandari: None. U. Farooq: None. K. Rajamani: None. Introduction: Admission day (weekend vs. weekday) significantly influences hospital outcomes and mortality in various diseases, with evidence suggesting higher mortality rates associated with weekend admissions. However, the “weekend effect” on adrenal insufficiency remains underexplored in national inpatient samples. Objective of the study:To assess the impact of admission day on mortality rates, hospital stays, costs, and overall outcomes in adrenal insufficiency patients. Methods: A retrospective cohort study encompassing adult patients (age>18 years) was conducted using the National Inpatient Sample (NIS) data spanning from 2017 to 2020. The International Classification of Disease (ICD-10) was used to select codes for diseases and outcomes. STATA was employed for statistical analysis, using multivariate regression analysis to calculate adjusted odds ratios and account for potential confounding variables. Continuous variables were compared using the student t-test, while proportions were compared using the Fisher exact test. The primary outcome was mortality, with secondary outcomes encompassing length of stay (LOS), total hospitalization charges, acute coronary syndrome (ACS), septic shock, pulmonary edema, acute respiratory failure (ARF), mechanical ventilation, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and cerebrovascular accidents (CVA). Results: A total of 150,005 patients diagnosed with adrenal insufficiency were included in the analysis. Patients with adrenal insufficiency were categorized into two groups based on the day of admission: weekend and weekday. Weekend admissions constituted 23.5% of the total cases of adrenal insufficiency, with 35,330 patients. Significant differences in outcomes were observed in septic shock (aOR=1.16, 7.24 % vs. 6.30 %, p=0.007), ARF (aOR=1.23, 11.82% vs. 9.87%, p<0.001), mechanical ventilation (aOR=1.35, 6.29% vs. 4.76%, p<0.001), ARDS (aOR=1.83, 0.57% vs. 0.33%, p=0.003), and AKI (aOR=1.15, 24.74% vs. 22.58%, p<0.001) in weekend vs weekday admissions. However, no significant differences were observed in mortality rates, mean length of hospital stay, total hospital costs, ACS, pulmonary edema, and CVA. Conclusion: Weekend admissions for adrenal insufficiency showed poorer outcomes which prompts further investigation into underlying factors. Insights gained might be helpful for strategic planning at state and national levels, aiding in outcome improvement. Presentation: 6/1/2024

9296 A Novel LC-MS/MS Salivary Fludrocortisone Method With Potential for Monitoring in Adrenal Insufficiency Patients

Abstract Disclosure: M. Dolan: None. D. Marshall: None. J. Hawley: None. N. Reisch: None. B.G. Keevil: None. Fludrocortisone (FC) is a fluorinated exogenous mineralocorticoid used to treat conditions associated with adrenal insufficiency including Addison’s disease and classic congenital adrenal hyperplasia (CAH). The mineralocorticoid action of FC allows the drug to compensate for aldosterone deficiency, thus helping to maintain blood pressure and other homeostatic mechanisms. Optimising FC replacement is vital as under-replacement can cause dizziness and hypotension, whereas over-replacement can lead to cardiometabolic disturbances. Treatment in classic CAH patients, who are typically diagnosed as new-borns, is even more complex as the requirement for mineralocorticoid replacement decreases with age. Endocrine Society guidelines recommend that FC monitoring should involve the clinical assessment of symptoms, which can be non-specific, and regular blood pressure measurements. Plasma renin activity (PRA) should be measured if clinical changes occur, aiming towards the upper end of the reference range. The utility of PRA is debated due to methodological issues and the inherent variability of the analyte itself, which may not always represent FC replacement status. Therefore, investigation into alternative biochemical markers of FC replacement is required. Here we aimed to facilitate this by developing an LC-MS/MS method for the measurement of salivary FC. Method: A salivary FC LC-MS/MS assay has been developed and validated for use according to FDA and EMA guidelines. Passive drool samples from 10 clinical trial patients with classic CAH were collected on two separate occasions at select time points throughout the day (0800, 1200, 1600, 2000 and 2300h). In most patients the 0800h sample was taken pre-FC dose. Once in the laboratory the patient samples were extracted and analysed using the FC method to produce a FC concentration day curve. Results: The method analysis time was 2.1 minutes, with a mean recovery of 102% and limit of quantification of 5 pmol/L (2.1 pg/mL). No analytical interference was identified. Analysis of patient samples using the method showed the presence of FC allowing the production of day curves. In most patients, the pre-dose sample contained no FC, with the subsequent samples showing a peak FC concentration corresponding to the Cmax. After this the FC concentration gradually tapered off throughout the remainder of the day. Conclusions: We have developed a novel assay for the measurement of salivary FC, which may allow the calculation of the area under the curve. As an optimal FC dose has yet to be determined this method may facilitate more in-depth pharmacokinetic studies into FC metabolism and blood pressure control. Thereby identifying patients that are fast metabolisers or poor absorbers of the medication, enabling a non-invasive strategy to optimise patient care. Presentation: 6/1/2024

Predictive Factors of Renal Insufficiency Among Patients with Diabetes and Hypertension in Northeastern Communities of Thailand

The purpose of this study was to study the predictive factors of chronic renal insufficiency in patients with diabetes, hypertension, and diabetes and hypertension in Tajong Subdistrict, Lahan Sai District, Buriram Province. This study, a retrospective case-control study, analyzed data from a 2023 database of patients with chronic diseases in Northeastern Thailand. A study of 4 3 5 community diabetes and hypertension patients analyzed predictive factors of renal insufficiency using SPSS, utilizing descriptive statistics, chi-square, and binary logistic regression analysis. The results showed that the subjects had an average glomerular filtration rate of 73.90 ml/min/1.73m2 (S.D. = 24.02), which was classified as the most abnormal filtration rate of 67.80%. CKD stage 2 (eGFR 60-89 ml/min/1.73m2) is the most. Among patients with diabetics, the predictive equation for renal insufficiency is -2.82+2.808 Age + 4.675BUN. In patients with hypertension, there is a prediction equation for the occurrence of renal insufficiency: -3.391 + 2.246Sex + 2.246Age + 2.637BUN, and in patients with hypertension and diabetics is an equation for predicting the occurrence of renal insufficiency: -4.021 + 1.554sex + 2.023Age + 3.332BUN. It is proposed that gender, age, and BUN all influence the occurrence of renal damage in patients with diabetes, hypertension, and diabetes plus hypertension. As a result, the healthcare team should have standards for assessing risk and preventing renal insufficiency in diabetic and hypertensive patients. Additional research should be conducted to examine the factors associated with kidney deterioration in patients who are unable to control their blood sugar levels.

Effects of herbal medicine on ovulation in premature ovarian insufficiency patients during in vitro fertilization

Introduction: Premature ovarian insufficiency (POI) is a condition in which menopause occurs before the age of 40 and is known to be a relatively common disease that occurs in 1% of all women. The only way for patients diagnosed with POI to become pregnant is through oocyte donation, in which fertilized ovums are transplanted by receiving oocytes from donors.4 Can POI patients increase their chances of normal ovulation? POI patients were more likely to observe and collect follicles larger than the average 15 mm diameter when herbal medicine was administered. Methods: This study is a retrospective cohort study conducted on POI patients undergoing in vitro fertilization (IVF) who visited our hospital from 2020 to 2022. We would like to report the response rate to gonadotropin-releasing hormone (GnRH) during IVF in the hyperovulation induction low response group after herbal medicine treatment. Statistical analysis was performed using IBM’s SPSS Statistics to verify significance with a P-value<0.05. Results: In recovering ovarian POI patient's ovarian function, herbal medicine treatment increased the response rate to GnRH (the number of oocytes collected) during IVF, follicle-stimulating hormone (FSH) and cortisol levels decreased, and estradiol (E2) and luteinizing hormone (LH) levels increased. Conclusions: It was confirmed that herbal medicine treatment can increase the probability of normal ovulation in patients with idiopathic POI with high cortisol levels. Until now, it has been known that ovarian function cannot be recovered once irreversibly decreased, but by increasing the probability of ovulation through herbal medicine treatment, it is significant that it may be possible to suppress ovarian aging or preserve fertility.

8555 Hourly Assessment Of Symptoms In 16 Adrenal Insufficiency Patients Correlates With AddiQoL

8555 Hourly Assessment Of Symptoms In 16 Adrenal Insufficiency Patients Correlates With AddiQoL

Features of the functional state of the endothelium and the hemocoagulation system in the formation of placental insufficiency in patients with gestational diabetes mellitus without insulin requirement

Background. There is a lot of data in the literature showing the state of the hemostatic system and endothelium separately in patients with gestational diabetes mellitus (GDM) and placental insufficiency (PI). However, with the combination of the above complications of pregnancy, there is very little research, therefore, the problem requires detailed study.Objective. To determine the contribution of the functional state of the endothelium and the hemocoagulation system to the formation of placental insufficiency in patients with gestational diabetes mellitus without insulin requirement.Materials and methods. A longitudinal cohort comparative study was conducted. The study included 120 patients in the II-III trimester of pregnancy with GDM without insulin requirement. The main group consisted of 70 women whose pregnancy was complicated by sub- and decompensated forms of PN. The comparison group included 50 pregnant women without pathology of the fetoplacental complex. The hemostasis system was studied using clotting tests and thromboelastometry. The concentrations of VEGF-A, total nitrite (NO2 total), endogenous nitrite (NO2 endogenous), nitric oxide (NO) in peripheral blood were determined by ELISA. Comparison of continuous quantitative data was carried out using the Mann-Whitney test, which was calculated using the MedCalc 15.8 application program. The null hypothesis was rejected at p<0.05.Result. The value of the integral index of coagulation, onset time and initial speed of clot formation in the main group was statistically significantly higher than in patients in the comparison group, p<0.05. The level of VEGF-A in pregnant women of the main group was statistically significantly lower than that in the comparison group, p<0.05. The indicator of total NO2 and NO in the main group was statistically significantly lower than in the comparison group, p<0.05. The endogenous NO2 indicator did not differ statistically significantly between groups.Conclusion. In patients with GDM on diet therapy and PN, endothelial dysfunction and, as a consequence, hypercoagulation occur.

Management of velopharyngeal insufficiency by a new modification of sphincter pharyngoplasty technique in cleft palate patients, clinical and radiographical prospective study

Background: This study was designed to investigate the effectiveness and outcome of a new modification of sphincter pharyngoplasty technique in the treatment of Velopharyngeal Insufficiency patients, with determination a specific dimension of Velopharyngeal port and velum length of no hypernasality, snoring and nasal regurgitation potential. Materials and methods: The study included 10 patients, who were suffering from consistent hypernasal speech after failure of conservative speech therapy. Clinical and Radiographic measurements of velopharyngeal port and velum length before and after surgery were done, with clinical patient follow-up to assess snoring and nasal regurgitation after surgery for 1,6,12 months. Results: Before surgery, the mean Clinical Anteroposterior distance/velopharyngeal depth was 16.40±1.7 mm, and the Mediolateral distance was 20.20±3.4 mm. After surgery, the mean Anteroposterior distance decreased to 8±0.9 mm, and the mean Mediolateral distance decreased to 12.60±2.06 mm. Both measurements showed statistically significant (P=0.0001). After 12 months post-operatively, the radiographic CT Axial Anteroposterior distance was 12.09±1.4 mm, and the mean Mediolateral distance was 19.82±5.6 mm, compared to the mean CT Anterioposterior before surgery 15.60±2 mm and Mediolaterally 21.28±2.7 mm. The Anteroposterior measurement showed a statistically significant (P=0.002), while the Mediolateral measurement did not (P=0.3). The mean velum length before surgery was 25.80±1.5 mm and 27.03±0.6 mm after 12 months post-operatively. Snoring and nasal regurgitation occurrence were assessed at 1, 6, and 12 months post-operatively, with all reports being negative. Conclusion: Sphincter pharyngoplasty using posterior tonsillar pillars for treating VPI patients results in improved speech outcomes without snoring or nasal regurgitation.

The evaluation of postoperative exocrine pancreatic insufficiency in patients with benign and low-malignant pancreatic tumor: A multicenter, prospective, observational study

Objectives: We assess the incidence of exocrine pancreatic insufficiency (EPI) at different time points after pancreatic surgery and explore pancreatic enzyme replacement therapy's (PERT) efficacy. Background: EPI is characterized by inadequate pancreatic enzymes, resulting in maldigestion and abdominal symptoms. EPI is a common postoperative complication of pancreatic surgery, yet often overlooked by surgeons. There is no clear answer to when EPI occurs after pancreatic surgery nor the duration of PERT after partial pancreatectomy. Methods: Benign or borderline pancreatic tumor patients undergoing surgeries were recruited between December 2020 and November 2021 from 10 medical centers in China. The EPI Questionnaire (EPI-Q) was performed at discharge, and 3-, 6-, 9-, and 12-month follow-ups to evaluate the occurrence of EPI. Statistical analyses were performed to identify the occurrence of EPI and explore PERT's efficacy. Results: Of the 146 patients, 105 (71.9%) were female, and the median age was 49 (range 16-78 yrs). Symptoms of EPI patients were most pronounced within 3 months post-surgery (15.7%), while most patients recovered after 1 year (96.9%). There was a negative correlation between symptom score and time since surgery. Lack of PERT in the 3-month post-surgery was associated with higher symptom scores in pancreatoduodenectomy (PD) patients, while not in distal pancreatectomy (DP) patients. Conclusions: Generally, the high-occurrence period for postoperative EPI is within 3 months after resection in patients with benign or borderline pancreatic tumors, and most will gradually recuperate with time. PERT can improve symptoms in PD patients, while reduced PERT duration may be considered for DP patients.

Assessment of left ventricular myocardial systolic dysfunction in premature ovarian insufficiency patients using echocardiographic layer-specific myocardial strain imaging

BackgroundDue to the lack of oestrogen, premature ovarian insufficiency (POI) is an independent risk factor for ischaemic heart disease and overall cardiovascular disease. This study aimed to apply layer-specific myocardial strain for early quantitative evaluation of subclinical left ventricular myocardial systolic function changes in patients with POI.MethodsForty-eight newly diagnosed, untreated patients with POI (POI group) and fifty healthy female subjects matched for age, height and weight (control group) were enrolled. Standard transthoracic echocardiography was used to measure conventional parameters and layer-specific strain parameters.The layer-specific strain parameters included subendomyocardial global longitudinal strain (GLSendo), mid-layer myocardial global longitudinal strain (GLSmid), subepimyocardial global longitudinal strain (GLSepi), subendomyocardial global circumferential strain (GCSendo), mid-layer myocardial global circumferential strain (GCSmid), and subepimyocardial global circumferential strain (GCSepi). ResultsThere were no significant differences in age, body mass index (BMI), blood pressure, or left ventricular ejection fraction (LVEF) between the two groups. The end-diastolic interventricular septal thickness (IVST) was greater in the POI group (8.29 ± 1.32 vs. 7.66 ± 0.82, P = 0.008), and the POI group had lower E, E/A, and lateral e′ (all P < 0.05). As for systolic functions,the POI group had lower GLSendo, GLSmid, GLSepi, GCSendo, GCSmid, and GCSepi (all P < 0.05).The intraobserver and interobserver coefficients of GLSendo, GLSmid, GLSepi, GCSendo, GCSmid, and GCSepi were greater than 0.900. ConclusionsPOI patients with normal LVEF may suffer from subclinical left ventricular myocardial systolic dysfunction. Echocardiography of layer-specific myocardial strain could more sensitively detect subclinical impairment of left ventricular systolic function in POI patients.Graphical abstract

54711 Nonconscious Proprioception Irregularities Observed in Chronic Venous Insufficiency (CVI) Patients with Healed Ulceration: An Age and Gender Matched Cross-Sectional Quantitative Comparative Study

54711 Nonconscious Proprioception Irregularities Observed in Chronic Venous Insufficiency (CVI) Patients with Healed Ulceration: An Age and Gender Matched Cross-Sectional Quantitative Comparative Study

Adaptation of the CIVIQ-20 Questionnaire as a measurement instrument on quality of life in chronic venous insufficiency patients in Jakarta, Indonesia

Adaptation of the CIVIQ-20 Questionnaire as a measurement instrument on quality of life in chronic venous insufficiency patients in Jakarta, Indonesia

Free cortisol and free 21-deoxycortisol in the clinical evaluation of congenital adrenal hyperplasia.

Some patients with classic congenital adrenal hyperplasia (CAH) survive without glucocorticoid treatment. Increased precursor concentrations in these patients might lead to higher free (biological active) cortisol concentrations by influencing the cortisol-protein binding. In 21-hydroxylase deficiency (21OHD), the most common CAH form, accumulated 21-deoxycortisol (21DF) may further increase glucocorticoid activity. Both mechanisms could explain the low occurrence of symptoms in some untreated classic CAH patients. Develop and validate an LC-MS/MS method for free cortisol and free 21DF to quantify these steroids in untreated patients with classic CAH (n=29), non-classic CAH (NCCAH, n=5), other forms of adrenal insufficiency (AI, n=3), and controls (n=11) before and 60 minutes after Synacthen® administration. Unstimulated total cortisol concentrations of untreated classic CAH patients (median 109 nmol/L) were lower than in untreated NCCAH patients (249 nmol/L, p=0.010) and controls (202 nmol/L, p=0.016), but free cortisol concentrations were similar. Basal free 21DF concentrations were high in 21OHD patients (median 5.32 nmol/L) and undetectable in AI patients and controls (<0.19 nmol/L). After Synacthen® administration, free 21DF concentrations increased in 21OHD patients, while free cortisol concentrations did not change. Free cortisol concentrations in classic CAH patients were similar to those in controls and NCCAH patients, indicating comparable cortisol availability. Additionally, 21OHD patients produce high concentrations of 21DF, possibly explaining the low occurrence of symptoms in some classic 21OHD patients. Free cortisol and 21DF levels should be considered in evaluating adrenal insufficiency in patients with CAH.