Thickened pituitary stalks (TPSs) on magnetic resonance imaging (MRI) result from diverse pathologies; therefore, it is essential to make specific diagnoses for clinical decision-making. The diagnoses and indications for surgical biopsies in patients with central diabetes insipidus (CDI) and TPSs are thoroughly discussed in this paper. Thirty-seven patients with CDI and TPSs were retrospectively reviewed. The mean age at the diagnosis of CDI was 29.0 ± 15.9 years (range 8.0-63.3), and the median duration of follow-up was 5.5 ± 2.8 years (range 0.7-13.0). Anterior pituitary hormone deficiencies were documented in 26 (70.3 %) patients. All patients had a TPS on MRI at the diagnosis of CDI, and 21 (56.8 %) patients exhibited radiological changes during the follow-up. Of these 21 patients, 11 exhibited increases in the thickness of the stalk, and two patients exhibited reversals of the TPSs. Involvements of the hypothalamus, pituitary gland, basal ganglia or supersellar, and pineal gland were found in four, three, one, and 1 patient, respectively. Ultimately, clear diagnoses were established in 17 patients who underwent biopsies, nine of whom had germinomas, six of whom had Langerhans cell histiocytosis, one of whom had a granular cell tumor, and one of whom had Erdheim-Chester disease. Patients with CDI and TPSs should submit to periodic clinic follow-ups with serial MRI assessments to establish anterior pituitary deficiencies and to detect radiological progressions that are appropriate for surgical biopsies. Endoscopic-assisted microsurgery via the supraorbital keyhole approach is a good choice for the biopsy of pituitary stalk lesions.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women. Women with PCOS have a 2.7-fold increased risk for developing endometrial cancer (EC). This study was performed to investigate the potential stimulatory effects of serum exosomes isolated from patients with PCOS on EC cell lines and to explore the underlying mechanism. EC cell lines exposed to exosomes derived from PCOS patients serum exhibited an enhanced migration and invasion phenotype. Next, sequence-based analysis of exosomal miRNA was conducted to screen the differentially expressed miRNAs in serum exosomes from PCOS patients and normal controls. The levels of 55 mature miRNAs significantly differed in serum exosomes from PCOS patients compared with those from normal controls. Real-time PCR was used to verify the expression of eight of these miRNAs, among which miR-27a-5p was the most significantly elevated in PCOS patients serum exosomes. The role of miR-27a-5p in EC migration and invasion was further investigated via miR-27a-5p mimics or inhibitor transfection in Ishikawa and HEC-1A EC cell lines. In addition, the SMAD4 gene was identified as the target of miR-27a-5p by several target prediction databases and was validated by a luciferase assay. SMAD4 mRNA and protein levels were downregulated in EC cells transfected with the miR-27a-5p mimics, but upregulated in cells transfected with the miR-27a-5p inhibitor. Furthermore, in vitro experiments results confirmed that miR-27a-5p prohibited migration and invasion via SMAD4 downregulation. Thus, serum exosomal miR-27a-5p may play a role in EC development in PCOS patients.

Sirtuin 1 (SIRT1), a nicotinamide adenosine dinucleotide-dependent histone deacetylase, is an important regulator of energy homeostasis in response to nutrient availability. In pancreatic β-cells, SIRT1 has been shown to up-regulate insulin secretion in response to glucose stimulation. However, the potential roles of SIRT1 in islet β-cells against lipotoxicity remain poorly understood. Here, we demonstrated that SIRT1 mRNA and protein expressions were markedly reduced in the islets isolated from rats infused with 20% Intralipid for 24h. Long-term exposure to 0.4mmol/L palmitate also decreased SIRT1 expression in cultured INS-1 cells and isolated rat islets, which was prevented by 10μmol/L resveratrol, a SIRT1 agonist. In addition, resveratrol improved glucose-stimulated insulin secretion decreased by palmitate, which was abrogated by EX527, a specific SIRT1 inhibitor. Furthermore, inhibition of SIRT1 activity by EX527 or a knockdown of SIRT1 suppressed insulin promoter activity, along with decreased insulin, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), and NK6 homeodomain 1 (NKX6.1) mRNA expressions. Activation of SIRT1 by resveratrol or overexpression of SIRT1 antagonized palmitate-inhibited insulin transcriptional activity. SIRT1 overexpression exerted an additive effect on pancreatic and duodenal homeobox 1 (PDX1)-stimulated insulin promoter activity and abolished forkhead box O1 protein (FOXO1)-decreased insulin transcriptional activity. Resveratrol reversed FOXO1 nuclear translocation induced by palmitate. Our findings indicate that SIRT1 protects against palmitate-induced β-cell dysfunction.

Cushing's disease is primarily caused by pituitary adrenocorticotropin-secreting adenoma. However, its pathogenesis has remained obscure. In the present study, whole transcriptome analysis was performed by RNA sequencing (RNA-Seq) and expression of secreted frizzled-related protein 2 (SFRP2) was decreased in corticotroph tumors compared with normal pituitary glands. Furthermore, the RNA-Seq results were validated and the expression of SFRP2 in tumor tissues was analyzed by comparing another cohort of 23 patients with Cushing's disease and 3 normal human pituitary samples using reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemistry staining. Clinically, there was an association between lower SFRP2 expression and aggressive adenoma characteristics, including larger size and invasiveness. Conversely, SFRP2 overexpression reduced the ability of AtT20 cells to proliferate and migrate, and reduced production of the adrenocorticotrophic hormone in vitro. Mechanistically, overexpressed SFRP2 reduced the level of β-catenin in the cytoplasm and nucleus, and decreased Wnt signaling activity in AtT20 cells. Therefore, SFRP2 appears to act as a tumor suppressor in Cushing's disease by regulating the activity of the Wnt signaling pathway.