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Aulinas A.,Autonomous University of Barcelona | Webb S.M.,Autonomous University of Barcelona | Webb S.M.,Center for Biomedical Network Research on Rare Diseases Unit 747
Expert Review of Pharmacoeconomics and Outcomes Research | Year: 2014

Adrenal insufficiency (AI) is characterized by a deficient production of glucocorticoids with or without associated mineralcorticoid and/or adrenal androgen deficiencies. Despite the low prevalence of AI, its impact on the affected patient is very high, and can be life-threatening disease if not adequately treated. Several glucocorticoid treatment regimens are available, but none is capable of perfectly imitating the cortisol circadian rhythm. Cortisol rhythmicity and treatment of other possible concomitant conditions often associated (e.g., autoimmune disorders and panhypopituitarism) are essential to improve outcome of AI. Morbidity often present in treated AI include an unhealthy metabolic profile, bad quality of sleep, infertility, sexual dysfunction and worse health-related quality of life. This review focuses on psychological morbidity and impaired quality of life in patients with primary or secondary AI of any origin, including a special section devoted to congenital adrenal hyperplasia. © 2014 Informa UK Ltd. Source


Caron P.J.,Center Hospitalier University Larrey | Bevan J.S.,Royal Infirmary | Petersenn S.,Center for Endocrine Tumors | Houchard A.,Ipsen | And 3 more authors.
Pituitary | Year: 2015

Purpose: To evaluate the effects of lanreotide Autogel on patient-reported outcomes and association with biochemical control, using PRIMARYS data. Methods: PRIMARYS was a 1-year, open-label study of lanreotide Autogel (Depot in USA) 120 mg every 4 weeks in 90 treatment-naïve patients with acromegaly. Symptoms were assessed using Patient-assessed Acromegaly Symptom Questionnaire (PASQ) and health-related quality of life (HRQoL) using the AcroQoL questionnaire. Correlations between PASQ and AcroQoL scores, and between PASQ/AcroQoL and growth hormone (GH)/insulin-like growth factor-1 (IGF-1) levels were also evaluated (post hoc). Results: Acromegaly symptoms and HRQoL significantly improved from week 12 to week 48, with modest correlations at week 48 between PASQ total score (R = –0.55, p < 0.0001) and AcroQoL global and physical scores (R = –0.67, p < 0.0001). Approximately 60 % of patients achieved a minimal important difference (MID; improvement >50 % of baseline standard deviation) in PASQ total score and >40 % achieved a MID in AcroQoL global score (post hoc). Changes in PASQ scores were similar in biochemically controlled (GH levels ≤2.5 μg/L and normal IGF-1 levels) and uncontrolled groups, while changes in global and psychological AcroQoL scores were greater in the controlled group. There was no correlation between changes in PASQ or AcroQoL scores and changes in GH or IGF-1 levels. Conclusions: Primary treatment with lanreotide Autogel over 1 year was associated with rapid and sustained improvements in clinical signs and symptoms and HRQoL in patients with acromegaly. Improvements in HRQoL, but not symptoms, were greater in those achieving biochemical control (ClinicalTrials.gov: NCT00690898; EudraCT: 2007–000155–34). © 2015 The Author(s) Source


Aulinas A.,Biomedical Research Institute Sant Pau | Ramirez M.-J.,Autonomous University of Barcelona | Barahona M.-J.,Hospital Universitari Mutua Terrassa | Barahona M.-J.,Center for Biomedical Network Research on Rare Diseases Unit 747 | And 15 more authors.
European Journal of Endocrinology | Year: 2014

Introduction: Hypercortisolism in Cushing's syndrome (CS) is associated with increased morbidity and mortality. Hypercortisolism also occurs in chronic depressive disorders and stress, where telomere length (TL) is shorter than in controls. We hypothesized that shortening of telomere might occur in CS and contribute to premature aging and morbidity. Aim: To investigate TL in CS patients compared with controls. Methods: Seventy-seven CS patients (14 males, 59 pituitary, 17 adrenal, and one ectopic; 21 with active disease) were compared with 77 gender-, age-, and smoking-matched controls. Fifteen CS were evaluated longitudinally, during active disease and after remission of hypercortisolism. Leukocyte TL was measured by telomere restriction fragment-Southern technique. Clinical markers were included in a multiple linear regression analysis to investigate potential predictors of TL. Results: Mean TL in CS patients and controls was similar (7667 vs 7483 bp, NS). After adjustment for age, in the longitudinal evaluation, TL was shorter in active disease than after remission (7273 vs 7870, P<0.05). Age and dyslipidemia were negative predictors (P<0.05), and total leukocyte count was a positive predictor for TL (P<0.05). As expected, a negative correlation was found between TL and age (CS, R=-0.400 and controls, R=-0.292; P!0.05). No correlation was found between circulating cortisol, duration of exposure to hypercortisolism or biochemical cure and TL. Conclusion: Even though in the cross-sectional comparison of CS and controls no difference in TL was found, in the longitudinal evaluation, patients with active CS had shorter TL than after biochemical cure of hypercortisolism. These preliminary results suggest that hypercortisolism might negatively impact telomere maintenance. Larger studies are needed to confirm these findings. © 2014 European Society of Endocrinology. Source


Aulinas A.,Autonomous University of Barcelona | Aulinas A.,Center for Biomedical Network Research on Rare Diseases Unit 747 | Ramirez M.-J.,Autonomous University of Barcelona | Barahona M.-J.,Center for Biomedical Network Research on Rare Diseases Unit 747 | And 16 more authors.
PLoS ONE | Year: 2015

Introduction: Cushing's syndrome (CS) increases cardiovascular risk (CVR) and adipocytokine imbalance, associated with an increased inflammatory state. Telomere length (TL) shortening is a novel CVR marker, associated with inflammation biomarkers. We hypothesized that inflammatory state and higher CVR in CS might be related to TL shortening, as observed in premature aging. Aim : To evaluate relationships between TL, CVR and inflammation markers in CS. Methods: In a cross-sectional study, 77 patients with CS (14 males, 59 pituitary-, 17 adrenal- and 1 ectopic-origin; 21 active disease) and 77 age-, gender-, smoking-matched controls were included. Total white blood cell TL was measured by TRF-Southern technique. Clinical data and blood samples were collected (lipids, adrenal function, glucose). Adiponectin, interleu-kin- 6 (IL6) and C-reactive protein (CRP) were available in a subgroup of patients (n=32).Correlations between TL and clinical features were examined and multiple linear regression analysis was performed to investigate potential predictors of TL. Results: Dyslipidemic CS had shorter TL than non-dyslipidemic subjects (7328±1274 vs 7957±1137 bp, p<0.05). After adjustment for age and body mass index, cured and active CS dyslipidemic patients had shorter TL than non-dyslipidemic CS (cured: 7187±1309 vs 7868 ±1104;active: 7203±1262 vs 8615±1056, respectively, p<0.05). Total cholesterol and triglycerides negatively correlated with TL (r-0.279 and -0.259, respectively, p<0.05), as well as CRP and IL6 (r-0.412 and -0.441, respectively, p<0.05). No difference in TL according the presence of other individual CVR factors (hypertension, diabetes mellitus, obesity) were observed in CS or in the control group. Additional TL shortening was observed in dyslipidemic obese patients who were also hypertensive, compared to those with two or less CVR factors (6956±1280 vs 7860±1180, respectively, p<0.001). Age and dyslipidemia were independent negative predictors of TL. Conclusion: TL is shortened in dyslipidemic CS patients, further worse if hypertension and/or obesity coexist and is negatively correlated with increased inflammation markers. Increased lipids and a "low" grade inflammation may contribute to TL shortening and consequently to premature ageing and increased morbidity in CS © 2015 Aulinas et al. Source

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