H. Bihan

Ketoconazole in Cushing's Disease: Is It Worth a Try?

BACKGROUND The use of ketoconazole has been recently questioned after warnings from the European Medicine Agencies and the Food and Drug Administration due to potential hepatotoxicity. However, ketoconazole is frequently used as a drug to lower circulating cortisol levels. Several pharmacological agents have recently been approved for the treatment of Cushings disease (CD) despite limited efficacy or significant side effects. Ketoconazole has been used worldwide for more than 30 years in CD, but in the absence of a large-scale study, its efficacy and tolerance are still under debate. PATIENTS AND METHODS We conducted a French retrospective multicenter study reviewing data from patients treated by ketoconazole as a single agent for CD, with the aim of clarifying efficacy and tolerance to better determine the benefit/risk balance. RESULTS Data from 200 patients were included in this study. At the last follow-up, 49.3% of patients had normal urinary free cortisol (UFC) levels, 25.6% had at least a 50% decrease, and 25.4% had unchanged UFC levels. The median final dose of ketoconazole was 600 mg/d. Forty patients (20%) received ketoconazole as a presurgical treatment; 40% to 50% of these patients showed improvement of hypertension, hypokalemia, and diabetes, and 48.7% had normal UFC before surgery. Overall, 41 patients (20.5%) stopped the treatment due to poor tolerance. Mild (<5N, inferior to 5-fold normal values) and major (>5N, superior to 5-fold normal values) increases in liver enzymes were observed in 13.5% and 2.5% of patients, respectively. No fatal hepatitis was observed. CONCLUSIONS Ketoconazole is an effective drug with acceptable side effects. It should be used under close liver enzyme monitoring. Hepatotoxicity is usually mild and resolves after drug withdrawal.

Sarcoidosis: Clinical, Hormonal, and Magnetic Resonance Imaging (mri) Manifestations of Hypothalamic-pituitary Disease in 9 Patients and Review of the Literature

Hypothalamic-pituitary (HP) sarcoidosis has 2 main endocrine manifestations: diabetes insipidus and hyperprolactinemia. We conducted the current study to investigate pituitary dysfunction and perform imaging of the HP area in patients both immediately following diagnosis and after treatment. The study included 6 men and 3 women, with a mean age of 30 years at the onset of sarcoidosis. All patients had both hormonal and magnetic resonance imaging (MRI) HP disorders. All patients had anterior pituitary dysfunction, 7 of them with associated diabetes insipidus. Nine patients had gonadotropin deficiency and 3 had hyperprolactinemia. MRI revealed infundibulum involvement in 5 patients, pituitary stalk thickness abnormality in 5, and involvement of the pituitary gland in 2, associated with other parenchymal brain or spinal cord lesions in 6 patients. All patients had multiple localizations of sarcoidosis, and 5 had histologically confirmed sinonasal localizations. Mean follow-up of the HP disorder was 7.5 years. All patients received prednisone. There was no correlation between the number of hormonal dysfunctions and the area of the HP axis involved as assessed by MRI. Although corticoid treatment was associated with a reduction of radiologic lesions, only 2 patients had partial recovery of hormonal deficiency. In conclusion, hormonal deficiencies associated with HP sarcoidosis frequently include hypogonadism (all patients) and to a lesser degree diabetes insipidus (7 of 9 patients). MRI abnormalities improved or disappeared in 7 cases under corticosteroid treatment, but most endocrine defects were irreversible despite regression of the granulomatous process. Most cases presented with multivisceral localizations and an abnormally high proportion of sinonasal localizations. Abbreviations: ACTH = adrenocorticotropic hormone, BHL = bilateral hilar lymphadenopathy, FSH = follicle-stimulating hormone, FT3 = free triiodothyronine, FT4 = free thyroxine, GH = growth hormone, GHD = growth hormone deficiency, GnRH = gonadotropin-releasing hormone, HP = hypothalamic-pituitary, IGF = insulinlike growth factor, LH = luteinizing hormone, MRI = magnetic resonance imaging, PRL = prolactin, TRH = thyrotropin-releasing hormone, TSH = thyroid-stimulating hormone.

Traitement de la super super obésité morbide par gastrectomie longitudinale

Resume Interet du travail La gastrectomie longitudinale, ou “sleeve gastrectomy”, est une technique restrictive avec reduction de la capacite gastrique de 75%. Nous rapportons notre experience chez 4 patientes super super obeses (indice de masse corporelle “IMC”; > 60 kg/m2. Methodes Quatre patientes avec une super super obesite ont eu une gastrectomie longitudinale. Leur poids preoperatoire moyen etait de 173 kg (extremes de 147 a 190 kg), et l’IMC moyen de 65 kg/m2 (extremes de 61 a 67 kg/m2. Resultats Le suivi postoperatoire moyen a ete de 6 mois (extremes de 2 a 12 mois). La perte de poids moyenne a 6 mois a ete de 40 kg (extremes de 20 a 60 kg). La chute moyenne de l’IMC a 6 mois a ete de 16,3 kg/m2 (extremes de 6 a 23 kg/m2. Nous avons constate une complication postoperatoire chez une seule patiente (abces sous-phrenique traite par drainage). Perspectives La gastrectomie longitudinale est associee a peu de complications perioperatoires, et est rapidement efficace sur la super super obesite morbide. Les resultats a long terme doivent etre evalues. Voir aussi dans ce numero l’editorial de Boyan Christoforov, Patients obeses : quelle place pour la chirurgie bariatrique ? p. 371-2.

Laparoscopic Sleeve Gastrectomy for a Super-Super-Obese Patient with Situs Inversus Totalis

Situs inversus totalis is a rare defect which can present difficulties in the management in laparoscopic surgery due to the mirror-image anatomy. Herein, we report a patient with situs inversus totalis and super-super-obesity (BMI 76 kg/m2). We performed successful laparoscopic sleeve gastrectomy. Technical details of this operation, with situs inversus totalis, are presented. There were no major difficulties compared to patients with usual anatomy. There are potential diseases associated with situs inversus and obesity; therefore, a careful investigation, including a chest x-ray and cardiac and abdominal ultrasounds should be performed before surgery. Sleeve gastrectomy is an adequate procedure in super-super-obese patients with situs inversus totalis.

Impact of fruit and vegetable vouchers and dietary advice on fruit and vegetable intake in a low-income population

Background/Objectives:Lower-income subgroups consume fewer servings of fruit and vegetables (FVs) compared with their more advantaged counterparts. To overcome financial barriers, FV voucher delivery has been proposed.Subjects/Methods:In a 12-month trial, 302 low-income adults 18–60 years old (defined by evaluation of deprivation and inequalities in health examination centers, a specific deprivation score) were randomized into two groups: dietary advice alone (‘advice’), or dietary advice plus FV vouchers (‘FV vouchers’) (10–40 euros/month) exchangeable for fresh fruits and vegetables. Self-reported data were collected on FV consumption and socioeconomic status at baseline, 3, 9 and 12 months. Anthropometric and blood pressure measurements were conducted at these periods, as well as blood samples obtained for determination of vitamins. Descriptive analyses, multiple linear regression and logistic regression were performed to evaluate the impact of FV.Results:Between baseline and 3-month follow-up, mean FV consumption increased significantly in both the ‘advice’ (0.62±1.29 times/day, P=0.0004) and ‘FV vouchers’ groups (0.74±1.90, P=0.002), with no difference between groups. Subjects in the FV vouchers group had significantly decreased risk of low FV consumption (<1 time/day) compared with those in the advice group (P=0.008). No change was noted in vitamin levels (vitamin C and β-carotene). The high number of lost-to-follow-up cases did not permit analysis at 9 or 12 months.Conclusion:In the low-income population, FV voucher delivery decreased the proportion of low FV consumers at 3 months. Longer-term studies are needed to assess their impact on nutritional status.

French consensus on the management of acromegaly

. Chanson a,∗, J. Bertherat b, A. Beckers c, H. Bihan d, T. Brue e, P. Caron f, O. Chabre g, M. Cogne h, C. Cortet-Rudelli i, B. Delemer j, H. Dufour k, R. Gaillard l, M. Gueydan e, I. Morange e, J.-C. Souberbielle m, A. Tabarin n, on behalf of the Club français de l’hypophyse (French Pituitary Club) and of the Société française d’endocrinologie (French Endocrinology Society) a Service d’endocrinologie et des maladies de la reproduction, hôpital de Bicêtre, université Paris-Sud-11, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France b Service des maladies endocriniennes et métaboliques, hôpital Cochin, université Paris Descartes, 27, rue du Faubourg-St-Jacques, 75014 Paris, France c Service d’endocrinologie, CHU de Liège, domaine universitaire du Sart-Tilman, 4000 Liège, Belgique d Service d’endocrinologie, diabétologie et maladies métaboliques, hôpital Avicenne, université Paris-13, 125, route de Stalingrad, 93009 Bobigny, France e Service d’endocrinologie, diabète et maladies métaboliques, hôpital de la Timone, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France f Service d’endocrinologie, maladies métaboliques et nutrition, pôle cardiovasculaire et maladies métaboliques, hôpital Larrey, 24, chemin de Pouvourville, TSA 30030, 31059 Toulouse cedex 9, France g Service d’endocrinologie, Pavillon des Écrins, hôpital Nord, CHU, BP 217 X, 38043 Grenoble cedex 09, France h Service d’endocrinologie, CHR de la Réunion, site de Saint-Pierre, BP 350, 97448 Saint-Pierre, Réunion i Service de diabétologie et pathologies hypothalamohypophysaire, clinique Marc-Linquette, CHRU de Lille, 6, rue du Professeur-Laguesse, 59037 Lille cedex, France j Service d’endocrinologie, CHU de Reims, 51092 Reims cedex, France k Service de neurochirurgie, université de la Méditerranée, CHU de la Timone Adultes, 264, rue St-Pierre, 13385 Marseille cedex 5, France l Service d’endocrinologie, diabétologie et métabolisme, CHU Vaudois (CHUV), 1011 Lausanne, Suisse m Service d’explorations fonctionnelles, hôpital Necker–Enfants malades, 149, rue de Sèvres, 75015 Paris, France n Service d’endocrinologie-diabétologie et maladies métaboliques, hôpital Haut-Lévêque, CHU de Bordeaux, avenue de Magellan, 33600 Pessac, France

A Novel Method for Assessing Insulin Dose Adjustments by Patients with Diabetes

Background: Insulin treated diabetic patients often do not adjust their insulin doses. We developed a method to provide a quantitative and qualitative assessment of this behavior. Methods: Fourteen patients provided logbook pages of their self-monitoring of blood glucose (SMBG) data and insulin doses. We compared the actual decisions of patients in real-life to what they would decide on the same SMBG, as an a posteriori exercise. We also compared these decisions and those proposed by 6 diabetologists on the same sets of data to the recommendations made by HumaLink, an automated insulin dosage system. Results: 1) Patients in real-life modified their insulin doses least often. However, given a chance to make these decisions a posteriori, they modified their insulin doses more often. HumaLink proposed changes even more often, and diabetologists were the most aggressive in changing insulin doses. 2) The decisions proposed by the patients in real-life or a posteriori and by the diabetologists were compared to the recommendations made by HumaLink, using a decisions analysis grid (DAG). For these three groups, full disagreement with HumaLink (patient or physician increases while HumaLink decreases and the opposite) was observed for less than 5% of the cases. 3) By comparison to HumaLink, patient decisions seemed guided by the desire to avoid hypoglycemia. By contrast, decisions by diabetologists seemed often to be guided by the desire to avoid hyperglycemia. Conclusion: These methods provide an objective evaluation of insulin dose adjustments by patients with diabetes and may be useful to assess the effectiveness of educational programs.

Weight Loss after Sleeve Gastrectomy in Super Superobesity

Objective. This prospective study evaluated laparoscopic sleeve gastrectomy for its safety and efficiency in excess weight loss (%EWL) in super superobese patients (BMI >60 Kg/m2). Results. Thirty patients (33 women and 7 men) were included, with mean age of 35 years (range 18 to 59). Mean preoperative BMI was 66 Kg/m2 (range 60 to 85). The study included one patient with complete situs inversus and 4 (14%) with previous restrictive gastric banding. The mean operative time was 120 minutes (range 80 to 220 min) and the mean hospital stay was 7.5 days (4 to 28 days). There was no postoperative mortality or need for a laparotomy conversion. Two subphrenic hematomas, one gastric fistula, and one pulmonary embolism, were the major complications. After 18 months 17 (77%) had sufficient weight loss and six had insufficient results, leading to either re-sleeve gastrectomy (3), or gastric bypass (2). Three years after the initial laparoscopic sleeve gastrectomy, the mean EWL was 51% (range 21 to 82). Conclusion. The laparoscopic sleeve gastrectomy is a safe and efficient operating procedure for treating super superobesity. In the case of insufficient weight loss, a second-stage operation like resleeve gastrectomy or gastric bypass can be proposed.

Improving postpartum glucose screening after gestational diabetes mellitus: a cohort study to evaluate the multicentre IMPACT initiative

To evaluate a mobilization campaign, the IMPACT initiative, which included multidisciplinary meetings, provision of information and a systematic prescription of an oral glucose tolerance test to improve the rate of glucose screening in women with gestational diabetes mellitus in the four largest maternity units in our area, starting in March 2011.

Factors associated with screening for glucose abnormalities after gestational diabetes mellitus: Baseline cohort of the interventional IMPACT study

INTRODUCTION Although it is important to screen women who have had gestational diabetes mellitus (GDM) for abnormal post-partum glucose levels, such testing is rarely performed. The aim of this study was to use data from the first observational phase of the IMPACT study to determine rates of screening within 6 months of delivery in a multiethnic cohort, focusing in particular on the effects of social deprivation and the risk of future diabetes. PATIENTS AND METHODS To investigate the frequency of post-partum screening, charts were analyzed, and all women attending four centres located in a deprived area who had had GDM between January 2009 and December 2010 were contacted by phone. The Evaluation of Precarity and Inequalities in Health Examination Centres (EPICES) deprivation index and Finnish Diabetes Risk Score (FINDRISK) questionnaire were also evaluated. RESULTS Data were evaluable for 589 of the 719 women contacted (mean age: 33.4 ± 5.2 years; mean body mass index: 27.6 ± 5.4 kg/m(2)), and 196 (33.3%) reported having been screened. On multivariate analysis, factors associated with a lack of screening were smoking [odds ratio (OR): 0.42 (0.20-0.90), P<0.05], low consumption of fruit and vegetables [OR: 0.58 (0.39-0.82), P<0.01] and heavier offspring birth weight (P<0.05), although there were no differences in FINDRISK and EPICES scores between screened and unscreened women. CONCLUSION One-third of women who had had GDM reported having been screened for dysglycaemia at 6 months post-partum. However, it is expected that the interventional phase of the IMPACT study will increase screening rates, especially in women with the risk factors associated with lower screening rates during this observational phase.