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Context: Liver function abnormalities (LFAs) have been described in patients with Turner syndrome (TS). Although a high risk of cirrhosis has been reported, there is a need to assess the severity of liver damage in a large cohort of adult patients with TS. Objective: Evaluate the types of LFAs and their respective prevalence, search for their risk factors, and evaluate the severity of liver impairment by using a noninvasive fibrosis marker. Methods: This was a monocentric retrospective cross-sectional study. Data were collected during a day hospital visit. The main outcome measures were liver enzymes (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase), FIB-4 score, liver ultrasound imaging, elastography, and liver biopsies, when available. Results: 264 patients with TS were evaluated at a mean age of 31.15 ± 11.48 years. The overall prevalence of LFAs was 42.8%. The risk factors were age, body mass index, insulin resistance, and an X isochromosome (Xq). The mean FIB-4 sore of the entire cohort was 0.67 ± 0.41. Less than 10% of patients were at risk of developing fibrosis. Cirrhosis was observed in 2/19 liver biopsies. There was no significant difference in the prevalence of LFAs between premenopausal patients with natural cycles and those receiving hormone replacement therapy (P = .063). A multivariate analysis adjusted for age showed no statistically significant correlation between hormone replacement therapy and abnormal gamma-glutamyl transferase levels (P = .12). Conclusion: Patients with TS have a high prevalence of LFA. However, 10% are at high risk of developing fibrosis. The FIB-4 score is useful and should be part of the routine screening strategy. Longitudinal studies and better interactions with hepatologists should improve our knowledge of liver disease in patients with TS. [ABSTRACT FROM AUTHOR]

Glyburide is mainly metabolized by the cytochrome P450 2C9 (CYP2C9) enzyme and enters the liver via the transporter OATP1B3. The variants OATP1B3*4 (699 G>A; rs7311358) and CYP2C9*2 and *3 are known to have a significant influence on the hepatic uptake and metabolism of glyburide, with lower clearance than in the wild type. In an ancillary study of the INDAO trial, we selected 117 pregnant women with gestational diabetes treated by glyburide and assessed the role of the combined CYP2C9 and OATP1B3 genetic polymorphisms in hypoglycemia and glycemic control. Three groups were constituted: (1) the wild‐type genotype group (wild‐type allele genotype for both CYP2C9*1 and OATP1B3*1 (699G)), (2) the intermediate group (carriers of CYP2C9*2 allele or OATP1B3*4 (699G>A) heterozygous), and (3) the variant group (carriers of CYP2C9*3 allele and/or OATP1B3*4 (699G>A) homozygous variant). We found that the risk of hypoglycemia was significantly higher in the variant genotype at the second week of treatment: 20.0% (4/20) vs. 8.1% (3/37) in the intermediate group and 4.1% (2/49) in the wild‐type genotype group (P = 0.03). The last daily dose of glyburide during pregnancy was lower for patients in the variant genotype group: 4.7 mg (SD 3.5) vs. 8.7 mg (SD 5.7) in the wild‐type group and 5.7 mg (SD 3.7) in the intermediate group (P < 0.01). In conclusion, the no‐function variants CYP2C9*3 and OATP1B3*4 are associated with a higher risk of hypoglycemia and a lower dose of glyburide in women with gestational diabetes treated with glyburide, which is consistent with the pharmacokinetic roles of both CYP2C9 and OATP1B3. [ABSTRACT FROM AUTHOR]

Objectives: Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival. Design: Multicenter retrospective study by members of the French Society of Endocrinology. Methods: Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included. Most tumors were corticotroph (n = 23) or lactotroph (n = 13), and 14 were carcinomas. Clinical/pathological characteristics of PT, as well as data from treatment evaluation and from the last follow-up were recorded. A partial response was considered as a decrease in the maximal tumor diameter by more than 30% and/or in the hormonal rate by more than 50% at the end of treatment. Results: The median treatment duration was 6.5 cycles (range 2-24), using a standard regimen for most and combined radiotherapy for six. Twenty-two patients (51.2%) were considered as responders. Silent tumor at diagnosis was associated with a poor response. The median follow-up after the end of treatment was 16 months (0-72). Overall survival was significantly higher among responders (P = 0.002); however, ten patients relapsed 5 months (0-57) after the end of TMZ treatment, five in whom TMZ was reinitiated without success. Discussion: Patients in our series showed a 51.2% response rate to TMZ, with an improved survival among responders despite frequent relapses. Our study highlights the high variability and lack of standardization of treatment protocols. [ABSTRACT FROM AUTHOR]

Objective: Congenital cardiovascular malformations and aortic dilatation are frequent in patients with Turner syndrome (TS). The objective of this study was to investigate the cardiovascular findings and management in a large cohort of patients, including children and adults. Design/methods: We recruited 336 patients with TS from a network of tertiary centers. We reviewed their files, checking for cardiovascular events, cardiac valve abnormalities, and aortic diameters indexed to body surface area (BSA) from magnetic resonance imaging (nZ110) or echocardiography (nZ300). Results: Informative cardiovascular data were available for only 233 patients. Vascular surgery was reported in 7.4% of the cohort. The first cause of surgery was aortic coarctation, detected in 6.9% at a median age of 9.5 (range: 0-60) years. Bicuspid aortic valve (BAV) was detected in 21% at a median age of 20 years (25th-75th percentiles: 15-30). At least one aortic diameter exceeded 32 mm in 12% of the cohort. This was detected at a median age of 19 (7-30) years.When indexed to BSA, at least one aortic diameter exceeded 20 mm/m2 in 39% of the cohort. Conclusion: Our study shows that cardiovascular monitoring for TS patients is currently insufficient in France. BAV is present at birth, but often remains undiagnosed until later in life. Therefore, improved management in cardiovascular monitoring is required and a more systematic approach should be taken. [ABSTRACT FROM AUTHOR]

Abstract: Background:: Non-islet cell tumor hypoglycemia(NICTH) is a rare cause of recurrent hypoglycemia. It has been associated with the tumoral overproduction of high-molecular-weight insulin-like growth factor (IGF)-2 (“big IGF-2”). Big IGF-2 suppresses growth hormone (GH) biosynthesis and impairs the storage of IGFs by suppressing the formation of the GH-dependent ternary complexes containing IGF, IGF binding protein 3 (IGFBP-3), and acid-labile subunit (ALS). Thus, big IGF-2 exerts hypoglycemic activity. The only effective treatment of NICTH is surgery. However, in inoperable patients with NICTH, treatment of hypoglycemia may require high doses of glucocorticoid (30–60 mg/d [0.5–1.0 mg/kg·d]) or recombinant human GH (rhGH) (2.6–12.0 mg/d [0.043–0.20 mg/kg·d]). Objective:: We hypothesized that the association of low doses of glucocorticoid and rhGH could be an effective therapy for hypoglycemia in inoperable patients with NICTH. Methods:: A 3-phase treatment regimen was conducted in an inoperable 67-year-old woman with NICTH. Decreasing dosages of prednisone (from 30 to 10 mg/d [from 0.50 to 0.15 mg/kg·d]), followed by decreasing doses of rhGH (from 2.6 to 1.3 mg/d [from 0.043 to 0.016 mg/kg·d]), and then a combination of the lowest doses of each, were tested. Glucose, insulin, and IGF monitoring were performed at each of the 3 treatment phases. Results:: Fasting plasma glucose (FPG) level was normalized and the IGF-1 concentration was increased with high-dose prednisone monotherapy (30 mg/d [0.50 mg/kg·d]) or rhGH (2.6 mg/d [0.043 mg/kg·d]). Prednisone monotherapy partially suppressed big IGF-2 secretion, and rhGH monotherapy acted on IGFBP-3 and ALS concentrations. FPG level was normalized with combined low-dose prednisone and rhGH, and this combination was more effective than high-dose monotherapy with either drug in reestablishing the IGF system. No adverse effects (AEs) were found. Conclusions:: In this patient with inoperable NICTH, the combination of low doses of prednisone and rhGH was a successful long-term therapy for hypoglycemia, with no AEs. This therapy could be proposed for use in patients with inoperable NICTH. [Copyright &y& Elsevier]