Endocrine, metabolic & immune disorders drug targets最新文献

Objective: The aim of the study was to explore the optimal timing of gonadotropin initiation and the reasonable interval of luteinizing hormone (LH) levels in the gonadotropin-releasing hormone antagonist (GnRH-A) protocol.

Methods: A retrospective cohort study was conducted to analyze the data concerning the oocyte retrieval cycles from 1,361 cases with the GnRH-A protocol implemented. The ovarian responses (including AMH, AFC) in these patients were divided into the poor ovarian response group (an antral follicle count [AFC] ≤ 6, n = 394), the normal ovarian response group (an AFC > 6 and < 15, n = 570), and the high ovarian response group (an AFC ≥ 15, n = 397), according to the AFC. The patients were sub-grouped according to LH levels on the protocol initiation day, and the clinical outcomes (including dose of Gn initiation, Gn administration days, GnRH-ant administration days, P levels on the HCG day, E2 levels on the HCG day, LH levels on the HCG day, number of embryos transferred, total fertilization rate, embryo implantation rate(%), proportion of 2PN, proportion of good-quality embryos, endometrial thickness on the hCG injection day(mm), moderate to severe OHSS, AFC on the initiation day, proportion of type A endometrium on the hCG injection day, clinical pregnancy rate, biochemical pregnancy rate, early abortion rate, ectopic pregnancy rate) were compared.

Results: On the GnRH-A protocol initiation day, among all patients with different ovarian responses, the body mass index (BMI) in those with an LH ≥ 5 IU/L was lower. The differences in pregnancy outcomes between the LH < 5 IU/L group and the LH ≥ 5 IU/L group were not statistically significant across the different ovarian response groups, but the LH < 5 IU/L group had a higher proportion of good-quality embryos (80.3±24.9 vs. 74.8±26.9, P =0.035) than the LH≥5IU/Lgroup in those with poor ovarian response. The total fertilization rate (82.2±18.1 vs 85.4±15.1, P =0.021) and proportion of two pronuclei (2PN) (69.0±20.9 vs 72.7±19.9, P =0.035) were higher in the LH ≥ 5 IU/L group than the LH<5 IU/L group for those with normal ovarian responses. The embryo implantation rate (41.4±41.3 vs 52.6±43.4, P =0.012) was higher in the LH ≥ 5 IU/L group than in the LH<5 IU/L group in those with high ovarian response. The results of the multivariate logistic analysis showed that the age of the female partner, number of embryos transferred, proportion of good-quality embryos, endometrial thickness on the hCG injection day, and moderate- to-severe ovarian hyperstimulation syndrome (OHSS) were independent factors correlated with the outcome of live births (P < 0.05).

Conclusion: The LH levels on the gonadotropins (Gn) initiation day in the GnRH-A protocol will not affect pregnancy outcomes.

Background: The possibility of sustained disease remission in functioning pituitary adenomas after drug withdrawal is well-known for prolactinomas and it has also been described in a subset of acromegalic patients. On the contrary, medical treatment for Cushing’s Disease (CD) is generally considered a life-long measure except for previously radio-treated patients. Sparse evidence of spontaneous remissions in CD has been reported, mainly related to a possible pituitary tumor apoplexy. To the best of our knowledge, none of these cases has included the use of a pituitary targeting agent.

Case presentation: Herein, we have reported the case of a radiotherapy-naïve patient with persistent CD after pituitary surgery who participated in the CSOMG230 trials, presenting sustained remission after Long-acting Release (LAR) pasireotide withdrawal. Under monthly pasireotide LAR 40 mg, the patient achieved urinary hormone control and clinical signs of cortisol excess normalization. After 8 years of treatment, the patient completed the study protocol and had to withdraw the drug as it was no longer available for CD in Italy. Before starting new therapies, we reassessed hormone levels that were surprisingly within normal ranges. At 24 months after the last dose of pasireotide, the patient was still in clinical and biochemical full remission. We have also briefly reviewed previous cases of sustained remission after somatostatin analogues withdrawal in other functioning pituitary adenomas.

Conclusion: Far from the general rule, this case suggests that prolonged treatment with pasireotide LAR might induce a durable CD remission. A dose down-titration/suspension might be considered in patients well-controlled on long-term therapy and with negative pituitary imaging. However, close monitoring is recommended given the high rate of complications in untreated patients.

Background: The pseudo-Cushing's encompass several disorders that can occur in high-stress situations and that show biochemical features like those of Cushing's syndrome. We present a case with difficult differential diagnosis for overlapping laboratory findings.

Case report: A 74-year-old man was admitted to our hospital for worsening dyspnoea for a month, 15 kilograms of weight loss in the previous months, asthenia, hypotonia, and muscle hypotrophy. Moreover, due to the onset of acute hypoxic-hypercapnic respiratory failure, the patient was treated with non-invasive ventilation and then admitted to the intensive care unit, for pneumonia and respiratory failure due to Meticillin-sensitive Staphylococcus aureus and Klebsiella Aerogenes. Antibiotic therapy was started. During the treatment in the ICU, the patient underwent endotracheal intubation for the worsening of respiratory function, and inotropic drug therapy was introduced for the development of septic shock. Hormones were tested, showing an ACTH-dependent hypercortisolism. The results of Nugent, Liddle, and the dexamethasone- suppressed CRH stimulation tests suggested a not-neoplastic ACTH-dependent hypercortisolism. The pituitary contrasted magnetic resonance image showed gland hypertrophy, and the abdominal computed tomography ruled out adrenal lesions. Unfortunately, the patient developed a multi-organ failure and died. The autopsy finding confirmed the absence of pituitary and other neuroendocrine tumors and showed bilateral adrenal hypotrophy.

Conclusion: Our clinical case described a patient with pseudo-Cushing's syndrome during sepsis and pre-agonist phase, with a difficult differential diagnosis, in which the combination of the low-dose dexamethasone suppression test and the CRH test allowed a conclusive and correct diagnostic orientation.

Due to the lack of accurate registration of RSA and miscarriages, many early miscarriages are overlooked and not diagnosed or treated promptly in hospitals. This uncertainty in pathogenesis prevents clinicians from taking targeted therapeutic measures, leading to unsatisfactory treatment outcomes and placing a heavy burden on the patient's family and the healthcare system. Oxidative stress is present in embryonic development and affects the regulation of oxidative stress in pregnancy and the reproductive endocrine system. Oxidative stress injury is a significant pathogenesis of RSA, so improving the body's ability to resist oxidative stress injury is crucial in treating RSA. For patients with RSA, there is an urgent need for safe, efficient, and cost-effective anti-oxidative stress drugs, and there is growing evidence that treatment with Traditional Chinese medicine (TCM) can improve pregnancy success with fewer adverse effects. Many active ingredients for treating RSA are mainly derived from certain components of TCM, including flavonoids, phenols, and other compounds, which have been shown to treat RSA directly or indirectly by targeting anti-oxidative stress-related pathways. This article summarizes the experimental and clinical evidence of several common TCM compounds for treating RSA. It provides ideas and perspectives for further exploring the pathogenesis of RSA and TCM compounds for treating RSA.

Objective: The aim of this study was to reveal the biological functionalities associated with endoplasmic reticulum stress (ERS)-related genes (ERSGs) in the context of diabetic retinopathy (DR).

Methods: Differentially expressed genes (DEGs) within the DR group and the Control group were identified and then integrated with ERSGs. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) methodologies were used to investigate potential biological mechanisms. A diagnostic model for ERS and a nomogram were formulated based on biomarkers selected through the Least Absolute Shrinkage and Selection Operator method. The diagnostic efficacy of this model was thoroughly evaluated. ERS-associated subtypes were identified, and the Single-Sample GSEA (ssGSEA) and CIBERSORT algorithms were used to assess immune infiltration.

Results: We identified 10 ERS-related DEGs (ERSRDEGs) within the DR Group. Subsequently, a diagnostic model was constructed based on 5 ERS genes, namely CCND1, IGFBP2, TLR4, TXNIP, and VIM. The validation analysis demonstrated the commendable diagnostic performance of the model. Analysis of the ssGSEA immune characteristics revealed a positive correlation in the DR group between myeloid-derived suppressor cells (MDSC), regulatory T cells (Tregs), and CCND1 TXNIP. Furthermore, a significant negative correlation was observed between central memory CD4 T cells and CCND1. In the context of CIBERSORT, the results indicated a positive correlation between macrophages and IGFBP2, as well as Tregs and IGFBP2 in the DR group. Notably, a conspicuous negative correlation was identified between resting mast cells and IGFBP2.

Conclusion: The present study provides novel diagnostic biomarkers for DR from an ERS perspective.

Background: Postmenopausal androgen excess often occurs due to the imbalance between the rapid decline in ovarian estrogen and a relatively gradual decline in androgen secretion. The rapid onset of hirsutism, alopecia, and acne, on the other hand, is a rare occurrence and requires further investigation in order to rule out an underlying neoplasm.

Case report: A 54-year-old woman arrived at the endocrinology outpatient clinic for the appearance of hirsutism and defluvium capitis in the past 9 months. She had hypertrichosis of the face, trunk, and mammary areolae and reduced timbre of voice. Circulating androgens were higher than normal levels (testosterone: 7.7 ng/mL, DHEAS: 5437 mcg/L, 17-OH-progesterone: 3.1 nmol/L), gonadotropin and prolactin levels were normal, and Nugent test was negative. Abdominal CT scan was negative for adrenal lesions, while transvaginal ovarian ultrasonography revealed a left adnexal formation (19x18x24 mm) compatible with stromal neoplasm. A bilateral hysteroannessiectomy was performed. Histological examination was diagnostic for multiple ovarian Leydig cell tumors.

Conclusion: The most frequent cause of postmenopausal hyperandrogenism is polycystic ovary syndrome. It is necessary to exclude the presence of neoplastic causes (ovarian or adrenal androgen- secreting tumors). In case of marked virilization and severe hyperandrogenism, it is useful to perform transvaginal ultrasonography to search for the presence of ovarian hypertrichosis or androgen-secreting ovarian tumors and a CT/RM scan to study the adrenal glands. The best treatment for hyperandrogenism of neoplastic origin is surgery. Patients who are not candidates for this approach are candidates for therapy with GnRH agonists.

Introduction: Significant results have been achieved using ultrasound-guided and ultrasound-assisted ablative techniques,such as Laser Thermal Ablation (LTA), Radiofrequency Ablation (RFA), High-Intensity Focused Ultrasound (HIFU), and MicrowaveAblation (MWA). These techniques are ideally suited for the treatment of normally functioning benign thyroid nodes with localcompressive symptoms or aesthetic problems. These treatments have been applied to hyperfunctioning “hot” nodes. LTA and RFAare the most commonly used. From January 2021 to July 2023 at our Center, a total of 160 patients with benign thyroid nodules weretreated, of which 35 had autonomous nodules [1-4]. Our analysis focused on evaluating the locoregional treatment of the latter.Based on the volume and ultrasound-vascular characteristics, patients were selected for thermoablative treatment with either RFA orMWA (Amica Gen HS - Hospital Service) starting in July 2022.

Results: No complications were documented. However, one patient was referred for surgery and 1 patient was re-treated with MWA.

Conclusion: In the light of personal experience ultrasound-guided thermal ablation treatment with RFA in patients with a single pretoxicor toxic thyroid nodule with or without associated compressive or aesthetic symptoms has proven to be very effective andsatisfactory. The treatment must be preceded by adequate information regarding the advantages and disadvantages of the variousprocedures and the methods of the treatment session. MWA proved to be more effective than RFA with no functional recovery of thetreated nodules even if they were relatively larger in size. We obtained the suspension of thyrostatic therapy with normalization ofthe TSH level in the third month after treatment.

Introduction: The term empty sella refers to a shrunken or displaced (by a subarachnoid diverticulum) pituitary gland. It can be primary (genetically determined) or secondary (due to trauma/surgery/radiation). It has been reported that 50% of patients are asymptomatic, and others experience symptoms, such as headache, hypertension, or visual field defects. Few cases have an empty sella syndrome, i.e., lacking functional pituitary hormones. Diagnosis is made through NMR or CT. If asymptomatic, this condition requires no treatment; otherwise, empty sella syndrome needs hormonal replacement therapy. We examined the case of asymptomatic empty sella syndrome.

Case report: A 67-year-old female patient was admitted for dilatative cardiomyopathy. She had a past medical history of arterial hypertension and right ICA endovascular repair. Blood tests demonstrated hypothyroidism, hypoadrenalism, and GH deficiency, without any signs or symptoms. NRM confirmed an empty sella, hence replacement therapy with levothyroxine and cortisone acetate was started. During a follow-up evaluation, we discovered that this biochemical profile of the patient had been known for more than a decade and never treated. Despite being exposed to stress conditions, vascular surgery and angiography, she never developed an adrenal crisis, nor has she ever been symptomatic for severe hypothyroidism. Hormonal replacement therapy was performed.

Conclusion: The described clinical scenario is rare, as usually, empty sella syndrome presents with signs of hormone deficiency, even if asymptomatic cases have been described. Some authors suggest considering it as a hypothalamic dysfunction requiring treatment; others identify it as a paraphysiological variant. However, more cases are needed to establish a correct therapeutic strategy for these patients.

Ultrasound examination of the left adrenal gland is generally associated with relatively low sensitivity and specificity. It is stronglyinfluenced by the operator’s experience, patient characteristics, and the type of equipment available. In particular, the left adrenalgland remains a structure that is diffcult to investigate, even for experts. Therefore, we aimed to improve the ultrasound explorabilityof the left adrenal gland and, thus, contributing to enhancing the overall diagnostic sensitivity of the technique, allowing for a morewidespread application by the addition, alongside traditional structural landmarks, of vascular landmarks. The vascular landmarks arerepresented by 1) the abdominal aorta at the level of the emergence of the superior mesenteric artery, 2) the splenic vein, and 3) thevascular pedicle of the left kidney. The adrenal gland is located in the space between the aorta medially, the renal pedicle caudally,and the splenic vein anteriorly. Therefore, with a left paramedian axial section, the abdominal aorta is sought at the level of D12,where the superior mesenteric artery originates. Aligning with the splenic vein, which acts as the roof of the space under examination,the area of interest is explored by tilting the probe superiorly and medially towards the aorta, inferiorly and medially towardsthe left renal vein, and superiorly and laterally towards the renal border, trying to maintain the view of the splenic vein as the trueanterior-lateral margin of the area. In cases where the conditions allow for accurate visualization and measurement of the lesion, ultrasoundmay be preferred over CT for long-term surveillance, especially in young individuals, due to its lack of radiation exposure,simplicity, and lower cost.

Background: Thyroid thermoablative techniques have been developed as an alternative to surgery for the treatment of symptomatic benign nodes, with the advantage of being minimally invasive, repeatable, with a minimal complication rate, and avoiding the perioperative risks and irreversible consequences of surgery.

Methods: A series of patients undergoing laser thermoablation by the same team of endocrinologists operating in 2 centers from May 2016 to December 2022 is presented. The procedure was performed in patients with compressive symptomatology determined by a thyroid node typed TIR 2, or TIR 3A with rejection of the surgical option. We analyzed cases that required surgery because of persistent compressive symptoms, reduction failure, or increase in volume.

Results: From May 2016 to December 2022, 207 thermoablative procedures were performed (187 patients). Single ablative session was unresolved in 28 patients (15%). The proportion of nodes with TIR 3A cytology was significantly higher (21.4 vs 7.0%). In this group, the response in terms of volumetric reduction 6 months after the procedure was significantly lower (5.7% vs 50%). Ten patients (5.3%) underwent surgery, whose histological outcome demonstrated malignancy in 50% of cases.

Conclusions: Data show the importance of timely re-evaluation with referral to surgical treatment for patients presenting a less than 20% volume reduction 6 months after thermoablation, in order to ensure promptly effective treatment of misrecognized malignancies.