Prolactinoma is the most common subtype of pituitary adenoma, and dopamine agonists are the gold standard for treatment, primarily cabergoline. Current guidelines suggest that transsphenoidal surgery could be offered, especially to young women with noninvasive microprolactinomas, due to its cost-effectiveness. Additionally, concerns regarding the long-term use of dopamine agonists and their lower remission rates have been raised. The SPARAGMOS trial (NCT07463235) will be an interventional, randomized, open-label, multicenter study utilizing a high dose of cabergoline for approximately 6 months to suppress prolactin levels, with the hypothetical goal of achieving greater tumor apoptosis and remission rates. Under this protocol, a remission rate of approximately 70% is hypothesized, similar to that achieved through neurosurgery in specialized pituitary centers or when cabergoline is carefully considered for withdrawal (i.e. treatment duration exceeding 2 years, low dosing, tumor shrinkage, and normoprolactinemia). The control group will receive cabergoline for 2 years at the lowest dose necessary to achieve normoprolactinemia, as per current guidelines. Under these conditions, the remission rate is expected to be low, around 30%. The findings from this trial have the potential to influence and redefine future therapeutic strategies for microprolactinoma.
BACKGROUND:Diabetic kidney disease (DKD) is a major complication of type 2 diabetes (T2D). Fibroblast growth factor 19 (FGF19) is a key metabolic regulator, but its relationship with DKD, as defined by estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR), remains unclear. METHODS:This cross-sectional study included 330 T2D inpatients and 60 normal controls (NC group). Serum FGF19 levels were measured by ELISA. Renal function was evaluated according to eGFR (CKD-EPI equation) and UACR. Associations between FGF19 levels and renal parameters were analyzed according to Spearman's correlation, partial correlation, and multiple linear regression analyses adjusted for confounders. RESULTS:Serum FGF19 levels were lower in the T2D group than in the NC group (110.25 [68.40-169.32] vs. 242.06 [143.74-319.51] pg/mL, p < 0.001). Among those with T2D, patients with DKD had higher FGF19 levels than those without DKD (122.61 [83.38-189.02] vs. 106.97 [66.54-164.22] pg/mL, p = 0.023). In T2D patients, FGF19 was positively correlated with UACR (r = 0.185; p = 0.005) and inversely correlated with eGFR (r = -0.210; p = 0.001), and these correlations persisted after adjustment for confounders. In fully adjusted linear regression models, FGF19 remained independently associated with a higher UACR (β = 0.203, t = 2.286, p = 0.024) and a lower eGFR (β = -0.170, t = -2.542, p = 0.012). Restricted cubic spline analyses confirmed linear relationships between lnFGF19 and both lnUACR (p = 0.480) and eGFR (p = 0.162). CONCLUSION:Serum FGF19 levels are independently associated with DKD status in T2D patients; the serum FGF19 level is decreased in T2D patients but relatively elevated in those with DKD. FGF19 levels are independently associated with a higher UACR and a lower eGFR. Restricted cubic spline analyses confirmed linear, rather than nonlinear, associations. These cross-sectional findings suggest an association between FGF19 and diabetic kidney pathology, though the modest effect sizes and study design limit causal interpretation.
BACKGROUND:PCOS is a hormonal disorder with no medication, hence treatment is symptomatic. Letrozole plus chromium, L-arginine, or myoinositol was tested in PCOS-infertile women. METHODS:This prospective trial randomly assigned 240 PCOS patients (n = 60) to one of four groups: letrozole + chromium, L-arginine, myoinositol, or the control. Insulin resistance, testosterone, HOMA-IR, hirsutism, DHEA, and ovulatory function were examined before and after treatment. RESULTS:At each follow-up, all groups showed substantially different ovulation rates (p = 0.026, 0.039, and 0.008 at 1, 2, and 3 months, respectively). Weight, HOMA-IR, and hirsutism were decreased with chromium and myoinositol (p = 0.001). Chromium, myoinositol, and L-arginine significantly reduced testosterone. Myoinositol had the highest pregnancy rates at one and two months (36.7% and 41.9%, respectively). Conclusion: letrozole combined with chromium or myoinositol improves PCOS ovulation, HOMA-IR, and hirsutism.
INTRODUCTION:Thyroid cancer (TC) represents the most frequently diagnosed malignancy of the endocrine system, with its incidence continuing to increase worldwide. Multimerin 1 (MMRN1), a glycoprotein implicated in various cancers, exhibits context-dependent roles, but its function in TC remains unexplored. The Hippo pathway, a key regulator of cell proliferation and apoptosis, is frequently dysregulated in TC. We hypothesized that MMRN1 inhibits TC progression by activating the Hippo signaling pathway. METHODS:Bioinformatics analysis of GSE33630 identified differentially expressed genes (DEGs) in TC. MMRN1 expression was validated in TC cell lines (BCPAP, TPC-1, IHH-4, HTH83) and normal thyroid cells (NTHY-ORI3.1) via RT-qPCR and Western blot. Functional assays assessed proliferation, migration, and invasion. Hippo pathway activity was evaluated after MMRN1 modulation. Oxidative stress and ferroptosis markers (ROS, SOD, CAT, GSH, MDA, GPX4, TF, TFR1) were analyzed. RESULTS:MMRN1 was downregulated in TC tissues and cell lines. Overexpression of MMRN1 suppressed TC cell proliferation, migration, and invasion while promoting apoptosis. Mechanistically, MMRN1 activated Hippo signaling, increasing p-MST1/2, p-LATS1/2, and p-YAP levels. Verteporfin reversed these effects. Additionally, MMRN1 modulated oxidative stress markers (including ROS and the indirect lipid peroxidation marker MDA) and altered GPX4 activity and iron metabolism, suggesting enhanced ferroptosis sensitivity. CONCLUSION:MMRN1 acts as a tumor suppressor in TC by activating the Hippo pathway and modulating oxidative stress and ferroptosis. These findings highlight MMRN1 as a potential therapeutic target for TC treatment.
