Quality of Life but not Cognition is Impacted by Radiotherapy in Patients with Non-Functioning Pituitary Adenoma.

Non-functioning pituitary adenomas (NFPA) are benign neoplasms that are first treated by surgery and secondary radiation therapy in case of residual tumor or regrowth. The consequences of surgery and radiotherapy are still debated. The objective of the work was to assess the impact of surgery, radiotherapy (RT) and pituitary deficiencies on long term health-related quality of life (QoL) and cognitive function among NFPA patients. Forty-six NFPA patients were studied after 9.6±7.5 years follow-up using: i) the MoCA questionnaire to detect mild cognitive disabilities, ii) the McNair and Kahn scale to assess perceived cognitive impairment, iii) the HADS questionnaire to score anxiety and depression, and iv) the SF-36 and QLS-H questionnaires to assess QoL. All NFPA patients had surgery and 54% patients had radiation therapy (RT+). The MoCA score was abnormal in 41% NFPA patients. Neither the type of surgery nor radiotherapy influenced the prevalence of cognitive disabilities. The depression score was higher in RT+than RT- patients. Overall, no alteration in SF-36 and QLS-H QoL scales were observed in NFPA patients when compared with the French reference population. Among NFPA patients, mental composite score, general health and vitality scores were altered in RT+compared to RT- patients. The presence of multiple pituitary axis deficiencies worsened general health and vitality scale scoring. Consistent follow-up had a beneficial impact on psycho-emotional dimensions of health. Surgery and radiotherapy had no adverse effects on cognitive functions, however, QoL was altered in RT+patients. These latter alterations may be partly related to pituitary hormone deficiencies.

Local aromatase excess with recruitment of unusual promoters of CYP19A1 gene in prepubertal patients with gynecomastia.

OBJECTIVES: Gynecomastia may be due to aromatase excess in several diseases such as obesity and cancer. Aromatase excess syndrome (AEXS) is an autosomal dominant disorder caused by overexpression of CYP19A1. Germinal mutations occurring in AEXS include various genomic rearrangements including duplication, deletion, and inversion identified in the upstream region of CYP19A1. Aromatase overexpression caused by a CYP19A1 somatic mutation has been rarely described. METHODS: Breast adipose tissue biopsies or surgical specimens were obtained from 19 subjects with gynecomastia. Aromatase quantification was performed by digital PCR and CYP19A1 sequencing by RACE PCR products. RESULTS: We observed localized aromatase overexpression (>10 fold greater than normal) in breast adipose tissue from three prepubertal males with gynecomastia out of the 19 cases. One carried a chromosomal rearrangement between CYP19A1 and DMXL2, consistent with AEXS. In the 2 others, the first exon of CYP19A1 contained 11 different tissue-specific promoter subtypes, specifically I.4 or I.3 normally expressed by adipose tissue, but also the placental I.2 promoter and the more ubiquitous I.7 which is usually expressed in breast cancer, uterine, and endothelial tissues. No differences in clinical or biochemical characteristics were observed between these 3 subjects and 16 others without aromatase overexpression. CONCLUSIONS: We describe two cases of aromatase overexpression in breast adipose tissue associated with nonspecific promoter recruitment. Further investigations are necessary to understand the mechanisms involved in aberrant promoter selection.

MANAGEMENT OF ENDOCRINE DISEASE: The role of confirmatory tests in the diagnosis of primary aldosteronism.

The strategy for diagnosis of primary aldosteronism (PA) in the hypertensive population includes firstly a screening step, based on the measurement of plasma aldosterone-to-renin ratio (ARR), a test which must have high sensitivity, and secondly a confirmatory step based on the demonstration of excessive aldosterone production independent of the renin-angiotensin-aldosterone system (RAAS) activity. The high proportion of false-positive ARR results and conversely of actual PA without a persistent elevation in baseline plasma aldosterone concentration necessitates the addition of a confirmatory step in the work-up of PA diagnosis. The present review focuses on the description of the different dynamic tests available for demonstrating autonomy of aldosterone secretion, on the performance and limitations of confirmatory tests and on possible strategies for PA diagnosis which may either include or avoid the confirmatory step for PA diagnosis. Large prospective studies comparing different strategies with and without dynamic testing are mandatory to delineate clearly the role and limits of confirmatory tests in the work-up of PA.

Impact of a Serious Videogame Designed for Flexible Insulin Therapy on the Knowledge and Behaviors of Children with Type 1 Diabetes: The LUDIDIAB Pilot Study.

BACKGROUND: Flexible (or functional) insulin therapy method is a self-management education approach for intensive insulin therapy in patients with type 1 diabetes. The serious game (or applied game) "L'Affaire Birman" ("Mr. Birman's File") (available at www.gluciweb.com ) was specifically designed as an educational tool for the flexible insulin therapy method. Its educational impact was evaluated in children with type 1 diabetes. MATERIALS AND METHODS: This prospective multicenter pilot study evaluated the effect of this videogame on the therapeutic knowledge and behavior of children with type 1 diabetes. PedCarbQuiz (PCQ) and Diabetes Self-Management Profile (DSMP) questionnaires were used before (T0), immediately after (T1), and 6 months after (T2) the unstructured use of the videogame. RESULTS: The 38 children enrolled in the study were 42% boys and 58% girls; they had a mean age of 13.7 ± 2.1 years old, a diabetes duration of 6.0 ± 3.8 years, and hemoglobin A1c (HbA1c) levels of 8.5 ± 1.4% (69.4 ± 9.4 mmol/mol). The children connected to the game 3.3 ± 2.8 times during this 6-month study. Their PCQ score increased from 31.6 ± 4.9 at T0 to 36.0 ± 4.0 at T2 (P < 0.05). Two PCQ subscores also increased significantly: the insulin titration score at T1 and T2 and the carbohydrate quantification score at T2. Conversely, the DSMP score was not different at T0, T1, and T2 (59.1 ± 9.9, 60.2 ± 9.8, and 60.0 ± 10.0, respectively), and HbA1c levels also remained stable throughout the study (8.4 ± 1.3%, 8.4 ± 1.2%, and 8.5 ± 1.5% at T0, T1, and T2, respectively). Subgroup analysis found a greater impact of the game in children with poor glycemic control and low knowledge at baseline. Adherence to the game was rather low (half of the children played less than 2.5 bouts), but no criterion was found to be predictive of this low attractiveness. CONCLUSIONS: Nonsupervised usage of the serious game "L'Affaire Birman" was able to improve insulin titration and carbohydrate quantification in children with type 1 diabetes.

Potential Insulin Underdelivery from Prefilled and Reusable Insulin Pens in Cases of Premature Needle Withdrawal: A Laboratory Evaluation.

BACKGROUND: Devices for the treatment of diabetes are not always used as recommended in good practice. Our aim was to evaluate potential insulin underdelivery in cases of premature needle withdrawal after injection with insulin pens, which is a commonly observed misuse, especially in young type 1 diabetes patients. MATERIALS AND METHODS: Potential insulin underdelivery was evaluated using five prefilled insulin pens (lispro Kwikpen(®) [Eli Lilly, Indianapolis, IN], aspart Flexpen(®) [Novo Nordisk, Bagsvaerd, Denmark], glulisine Solostar(®) [Sanofi, Paris, France], detemir Flexpen(®) [Novo Nordisk], and glargine Solostar(®) [Sanofi]) and three reusable insulin pens (Humapen(®) Luxura HD with lispro cartridge [Eli Lilly], Novopen(®) Echo with aspart and detemir cartridge [Novo Nordisk], and JuniorSTAR(®) with glulisine and glargine cartridge [Sanofi]) in a laboratory. For each pen and insulin, we simulated premature needle withdrawal 2 and 3 s after an insulin injection of 5 and 10 units, respectively. RESULTS: With prefilled pens, mean potential insulin underdelivery was 0.43±0.30 and 0.44±0.32 units after injection of 5 and 10 units, respectively. With reusable pens, mean potential insulin underdelivery was lower (0.29±0.13 and 0.29±0.12 units after injection of 5 and 10 units, respectively; P<0.001). The results were heterogeneous across pens, ranging from 2.6%/1.6% to 20.2%/8.6% of the selected insulin dose for prefilled/reusable pens, respectively (P<0.001). CONCLUSIONS: Potential insulin underdelivery varies across prefilled and reusable insulin pens but may represent up to one-fifth of the total injected dose. Clinicians should be aware of the potential consequences of premature needle withdrawal and should reinforce insulin injection education.

Neuromuscular electrostimulation and insulin sensitivity in patients with type 2 diabetes: the ELECTRODIAB pilot study.

AIM: Physical activity (PA) improves insulin sensitivity and is particularly important for type 2 diabetes (T2D) management; however, patient adherence is poor. Neuromuscular electrostimulation (NMES) is widely used for rehabilitation issues, but the metabolic impact of provoked involuntary muscular contractions has never been investigated. MATERIALS AND METHODS: ELECTRODIAB is a prospective, bi-centric, and 4-week-long pilot study that enrolled 18 patients with T2D who did not require insulin treatment. Insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp before and after (1) a single NMES session and (2) a week of daily NMES training. Energy expenditure (EE) at baseline and during NMES was evaluated by indirect calorimetry. Dietary and background PA were monitored to avoid bias. RESULTS: After a single session (T1) or a week (T2) of NMES training, insulin sensitivity (M value) increased by 9.3 ± 38.2 % (ns) and 24.9 ± 35.8 % (p = 0.009), respectively, compared with the baseline (T0). Insulin sensitivity increased up to 46.2 ± 33.8 % (p = 0.002) at T2 in the more insulin-resistant subjects (baseline M value ≤4 mg/Kg/min, n = 10). The NMES session-generated EE was 1.42 ± 9.27 kcal/h, which was not significantly increased from the baseline. CONCLUSIONS: Insulin sensitivity was significantly improved in patients with T2D after 1 week of daily NMES training, with very low EE. NMES could be an alternative to conventional PA, but the putative mechanisms of action must still be investigated.

Autonomy of patients with type 2 diabetes with an insulin pump device: is it predictable?

BACKGROUND: Insulin pump therapy may be offered to patients with type 2 diabetes that is not controlled by multiple daily injections. Patients with type 2 diabetes may suffer from unrecognized cognitive disabilities, which may compromise the use of a pump device. METHODS: To predict patient autonomy, we evaluated 39 patients with type 2 diabetes from our database (n = 143) after continuous subcutaneous insulin infusion (CSII) initiation using (1) an autonomy questionnaire evaluating the patient's cognitive and operative capacities for CSII utilization, (2) the Montreal Cognitive Assessment (MOCA) for the detection of mild cognitive disabilities, (3) the Hospital Anxiety and Depression Scale (HADS) for the detection of anxiety and depression, and (4) the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Patients were selected to constitute 3 groups matched for age, with different degrees of autonomy at discharge after the initial training program: complete (n = 13), partial (n = 13), or no autonomy (n = 13). RESULTS: The satisfaction level with the pump device was high. At the last follow-up visit, only 23% of patients did not reach complete autonomy. The autonomy score correlated fairly with the MOCA score (R = 0.771, P < .001). A receiver operating characteristic (ROC) analysis showed that at a cut-off score of 24, the MOCA identified autonomous versus dependent patients at long-term follow-up (area under the ROC curve [AUC], 0.893; sensitivity, 81%; specificity, 81%). The HADS correlated negatively with the autonomy score, and the sociocultural level also influenced autonomy with pump utilization. CONCLUSION: Patients with type 2 diabetes with partial autonomy at discharge may progress to complete autonomy. The MOCA and HADS may help predict a patient's ability to manage with a pump device.

Cross-sectional survey and retrospective analysis of a large cohort of adults with type 1 diabetes with long-term continuous subcutaneous insulin infusion treatment.

Background. Continuous subcutaneous insulin infusion (CSII) is an established modality for intensive insulin treatment of type 1 diabetes (T1D), but long-term data concerning satisfaction, CSII function use, safety, and efficacy in real-life conditions are scarce. Methods. We analyzed a cohort of adult patients with T1D treated with CSII for more than 1 year in a single diabetes center. We performed a cross-sectional survey in 2010 (tolerance/satisfaction and behavior forms) and a retrospective analysis of medical records (including HbA1c level, hospitalization, and catheter infections). The primary objective was to assess long-term tolerance/satisfaction, and secondary objectives were safety and efficacy. Results. There were 295 patients analyzed. After a median duration of CSII use of 5 years, overall satisfaction was high for about 90% of patients. Mean CSII-related discomfort scores were low for work, recreation, and sleep and moderate for sport and sexual activity (2.5 ± 1.9, 2.6 ± 1.8, 2.6 ± 2.1, 3.4 ± 2.3, and 4.0 ± 2.9 of 10, respectively). Despite a high level of diabetes education, only one third of patients were using advanced CSII functions. During long-term follow-up, the safety of CSII treatment was good; the hospitalization rate was 0.18 patients/year, and catheter infections were scarce. The HbA1c level dropped about -0.5% independently from CSII duration (P < .05). Conclusions. In this adult cohort, satisfaction and tolerance, together with safety, of CSII were maintained at long-term follow up. The sole basic functions of CSII were currently used by patients. A 0.5% decrease in the HbA1c level was maintained during the study period.

BMP system expression in GCs from polycystic ovary syndrome women and the in vitro effects of BMP4, BMP6, and BMP7 on GC steroidogenesis.

BACKGROUND: The bone morphogenetic proteins (BMPs) are growth factors involved in the folliculogenesis. Alteration in their expression may compromise the reproductive process in disease such as the polycystic ovary syndrome (PCOS). This study investigated the expression and role of granulosa cell (GC) BMP from normal cycling and PCOS women. METHODS AND RESULTS: This prospective study was performed in GCs obtained from 14 patients undergoing IVF: i) six women with normal ovulatory cycles and tubal or male infertility and ii) eight women with PCOS. BMP2, BMP4, BMP5, BMP6, BMP7, and BMP8A and their receptors BMPR1A, BMPR1B, and BMPR2 were identified by RT-PCR in GCs from normally cycling and PCOS women. BMP4, BMP6, and BMP7 expressions were confirmed by immunohistochemistry. Quantitative transcript analysis showed the predominant expression of BMP6. In GCs from PCOS women, an overexpression of BMP6 (P<0.01) and BMPR1A mRNA (P<0.05) was observed. GC culture experiments demonstrated that basal estradiol (E2) production was threefold higher but FSH-induced E2 increment was twofold lower in PCOS compared with controls. In PCOS, BMP6 and BMP7 exerted a stimulatory effect on basal E2 production while BMP4 and BMP6 inhibited FSH-induced E2 production. FSH receptor and aromatase expression were not different between both groups. CONCLUSION: The BMP system is expressed in human GCs from normal cycling and PCOS women. The BMP may be involved in reproductive abnormalities found in PCOS.

Dual-phase 99mTc sestamibi scintigraphy with neck and thorax SPECT/CT in primary hyperparathyroidism: a single-institution experience.

PURPOSE: To assess the diagnostic value of dual-phase (99m)Tc sestamibi scintigraphy with neck and thorax single-photon emission computed tomography/computed tomography (SPECT/CT) in patients with primary hyperparathyroidism, and to analyze the relationships between SPECT/CT data and serum calcium or parathyroid hormone (PTH) concentrations. MATERIALS AND METHODS: (99m)Tc sestamibi scintigraphy was performed in 94 consecutive patients. Images included early and delayed planar neck images and delayed neck and thorax SPECT/CT. Scintigraphy was scored positive or negative. RESULTS: Fifty-nine sestamibi studies (63%) were positive. SPECT/CT demonstrated a single focus in 56 patients, in usual parathyroid sites in 80% of cases and in unusual sites in the remaining 20% (retrotracheal area, 7%; intrathyroidal, 9%; mediastinum, 4%), and double foci in 3. Serum calcium values were higher in patients with a positive scintigraphy than in those with a negative scintigraphy (2.80 vs. 2.66 mmol/L, P = 0.001) with similar figures for serum PTH values (129 vs. 107 pg/mL, P = 0.0649). In patients with a measurable parathyroid adenoma on integrated CT scan (n = 43), the greatest axial diameter of the adenoma was correlated to serum calcium (r = 0.405, P < 0.0071) or PTH concentrations (r = 0.589, P < 0.0001). Fifty-four patients underwent surgery, 45 with a positive, and 9 with a negative preoperative scintigraphy, resulting in a sensitivity of 92% (95% CI: 80-98) and a specificity of 83% (95% CI: 36-100). CONCLUSIONS: Dual-phase (99m)Tc sestamibi scintigraphy with SPECT/CT enables to identify a parathyroid adenoma in about two-thirds of patients with primary hyperparathyroidism and allows the surgeon to plan appropriate surgery. The likelihood of scintigraphy to be positive is affected by calcium or PTH concentrations.

Efficacy of continuous subcutaneous insulin infusion in type 2 diabetes mellitus: a survey on a cohort of 102 patients with prolonged follow-up.

OBJECTIVES: We evaluated the long-term efficacy of continuous subcutaneous insulin infusion (CSII) for treating type 2 diabetes patients uncontrolled by multiple daily injections. RESEARCH DESIGN AND METHODS: All 102 type 2 diabetes patients who began insulin pump therapy at Caen University Hospital (Caen, France) between January 1998 and August 2008 were included in a retrospective observational study. Ninety-three percent of the patients were previously treated by insulin with a mean duration of 5.6 years. RESULTS: The median duration of follow-up with CSII was 24 months. A1c glycated hemoglobin (HbA1c) improved from baseline (9.3 ± 1.8%) to the 1-year evaluation (7.8 ± 1.4%) (P < 0.001). The magnitude of HbA1c improvement was highly dependent on (1) pretreatment HbA1c level, (2) degree of patient's autonomy, and (3) previous antidiabetes treatment. HbA1c decreased by 0.9 ± 1.6% (P = 0.002) in the group previously treated by a basal-bolus regimen. HbA1c decrease was maintained at follow-up until 6 years (P < 0.05). Mean body weight gain was 3.9 ± 8.6 kg at 1 year (P < 0.001) and remained stable at follow-up. No significant change in insulin requirement was observed. CONCLUSIONS: The use of CSII in patients with type 2 diabetes is safe and effective for improving glycemic control, particularly in those patients with baseline HbA1c above 8%. Such beneficial effect of CSII may persist until 6-year follow-up, suggesting the durability of CSII efficacy in our study population.