Anna Aulinas

Maternal Body Mass Index Is a Predictor of Neonatal Hypoglycemia in Gestational Diabetes Mellitus

CONTEXT In diabetic pregnancy, neonatal hypoglycemia (NH) is usually attributed to insufficient regulation of maternal glycemic control. Recent data suggest that maternal body mass index (BMI) could have an influence. OBJECTIVE Our objective was to determine whether an association exists between maternal prepregnancy BMI category and occurrence of NH among infants born to women with gestational diabetes mellitus (GDM). DESIGN AND SETTING This was a retrospective study including all GDM pregnancies delivered between 1986 and 2006 at a tertiary care center (Hospital de la Santa Creu i Sant Pau, Barcelona). PATIENTS AND OUTCOMES: GDM was diagnosed using universal screening and National Diabetes Data Group criteria. Two thousand ninety-two newborns (1925 singletons, 85% of total GDM offspring) were studied. NH was defined according to Cornblath criteria. In addition to maternal BMI, we considered other variables such as glucose values at diagnosis or third-trimester glycated hemoglobin as potential predictors of NH. We explored whether the association between maternal BMI and NH could be due to intermediate steps such as cesarean section or abnormal birth weight. RESULTS The rate of NH was 3%. In the bivariate analysis, prepregnancy BMI was higher in the NH group (24.45 vs. 23.19 kg/m(2), P < 0.02). In the logistic regression analysis, prepregnancy BMI of at least 25 kg/m(2) was independently associated with NH whether the analysis included intermediate variables (odds ratio = 2.11; 95% confidence interval = 1.10-4.03) or not (odds ratio = 2.66; 95% confidence interval = 1.44-4.92). CONCLUSIONS Pregestational BMI should be considered among the predictors of NH in offspring of women with GDM.

Quality of life in Cushing’s syndrome

IntroductionCushing syndrome (CS) of any etiology (adrenal, pituitary or ectopic) impacts negatively on health-related quality of life (QoL), especially in active hypercortisolism but also after endocrine cure. Both generic questionnaires like the short-form 36 health survey -SF-36- and the derived SF-12, or the Hospital Anxiety and Depression Scale (HADS), and disease-specific measures like the CushingQoL and the Tuebingen CD-25 questionnaires have provided information on the impact of CS on patients perceived health.Materials and methodsStudies published since January 2013 until November 2014 on QoL in patients with CS were identified, reviewed and summarized.ConclusionsTreatment of CS improves patients perceived QoL, but it often takes many months and often never normalizes. In parallel to persistent QoL impairment in cured CS, brain and cerebellar volume are reduced. Depression, anxiety and cognitive dysfunction are common. Pediatric patients with CS also present worse QoL than normal children, as well as additional issues like delayed growth and pubertal development, next to abnormal body composition, psychological and cognitive maturation. Fluoxetine has been suggested as a neuroprotectant and antidepressant for patients with CS, although no prospective studies are yet available. The CushingQoL questionnaire has been mapped to well-validated instruments like SF-36 or EQ-5D, and therefore may be used in cost-utility and other health economy studies.

Poorer perinatal outcome in male newborns of women with pregestational diabetes mellitus

Diabet. Med. 28, 436–439 (2011)

Health-related quality of life in primary and secondary adrenal insufficiency.

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.

Telomere length analysis in Cushing's syndrome

INTRODUCTION Hypercortisolism in Cushings 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.

Telomeres and endocrine dysfunction of the adrenal and GH/IGF-1 axes

Telomeres, located at the end of linear chromosomes, are essential to maintain genomic stability. Telomere biology has recently emerged as an important player in the fields of ageing and disease. To maintain telomere length (TL) and reduce its degradation after mitosis, the telomerase enzyme complex is produced. Genetic, epigenetic, hormonal and environmental factors can regulate telomerase function. These include stress hormones such as cortisol and growth factors. The hypothalamic–pituitary–adrenal (HPA) axis has been evaluated in psychiatric diseases where hypercortisolism and oxidative stress are often present. Some researches have linked TL shortening to increases in stress‐related cortisol, but others have not. The effects of cortisol on the telomere system are complex and may depend on the intensity and duration of exposure. On the other hand, low levels of IGF‐1 are associated with inflammation and ageing‐related diseases (ischaemic heart disease, congestive heart failure). Both IGF‐1 and TL diminish with age and are positively and strongly correlated with each other. It is not clear whether this positive correlation reflects a single association or a cause–effect relationship. Further research will ideally investigate longitudinal changes in telomeres and both these hormonal axes. To our knowledge, TL dysfunction has not been described in either endogenous hypercortisolism (Cushings syndrome) or acromegaly where excessive amounts of GH and consequently IGF‐1 are produced. This review focuses on the possible relationships between telomere dysfunction and the hypothalamic–pituitary–adrenal (HPA) axis and GH‐IGF‐1 system.

Reduced DNA methylation of FKBP5 in Cushing’s syndrome

FKBP5 encodes a co-chaperone of HSP90 protein that regulates intracellular glucocorticoid receptor sensitivity. When it is bound to the glucocorticoid receptor complex, cortisol binds with lower affinity to glucocorticoid receptor. Cushing’s syndrome is associated with memory deficits, smaller hippocampal volumes, and wide range of cognitive impairments. We aimed at evaluating blood DNA methylation of FKBP5 and its relationship with memory and hippocampal volumes in Cushing’s syndrome patients. Polymorphism rs1360780 in FKBP5 has also been assessed to determine whether genetic variations can also govern CpG methylation. Thirty-two Cushing’s syndrome patients and 32 matched controls underwent memory tests, 3-Tesla MRI of the brain, and DNA extraction from total leukocytes. DNA samples were bisulfite treated, PCR amplified, and pyrosequenced to assess a total of 41CpG-dinucleotides in the introns 1, 2, 5, and 7 of FKBP5. Significantly lower intronic FKBP5 DNA methylation in CS patients compared to controls was observed in ten CpG-dinucleotides. DNA methylation at these CpGs correlated with left and right HV (Intron-2-Region-2-CpG-3: LHV, r = 0.73, p = 0.02; RHV, r = 0.58, p = 0.03). Cured and active CS patients showed both lower methylation of intron 2 (92.37, 91.8, and 93.34 %, respectively, p = 0.03 for both) and of intron 7 (77.08, 73.74, and 79.71 %, respectively, p = 0.02 and p < 0.01) than controls. Twenty-two subjects had the CC genotype, 34 had the TC genotype, and eight had the TT genotype. Lower average DNA methylation in intron 7 was observed in the TT subjects compared to CC (72.5vs. 79.5 %, p = 0.02) and to TC (72.5 vs. 79.0 %, p = 0.03). Our data demonstrate, for the first time, a reduction of intronic DNA methylation of FKBP5 in CS patients.

Thyroglobulin as early prognostic marker to predict remission at 18–24 months in differentiated thyroid carcinoma

Thyroglobulin (Tg), the most common marker to determine remission of differentiated thyroid carcinoma (DTC), can take 18 months or longer to be undetectable. We hypothesized that Tg stimulated after surgery and immediately before radioiodine treatment (baseline‐stimulated Tg) could be a good predictor of remission at 18–24 months. The aim of this study was to evaluate the role of baseline‐stimulated Tg as early prognostic marker of DTC.

Dyslipidemia and Chronic Inflammation Markers Are Correlated with Telomere Length Shortening in Cushing’s Syndrome

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, interleukin-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.

Reduction of trabecular and cortical volumetric bone mineral density at the proximal femur in patients with acromegaly

OBJECTIVE Data on dual energy absorptiometry (DXA)-measured bone mineral density (BMD) at the level of the total hip (TH) and femoral neck (FN) in patients with acromegaly (ACRO) are conflicting. Increase in bone size associated with ACRO may limit the reliability of DXA. Our objective is to evaluate trabecular and cortical volumetric BMD (vBMD) across the proximal femur in ACRO patients. DESIGN Cross sectional study in a clinical research center. PATIENTS Thirty-five ACRO patients (19 males; mean age, 48±7 years; BMI, 27.5±4.4 kg/m(2); 17 with active disease) and 35 age, gender, and BMI-matched controls. RESULTS vBMD was assessed by quantitative computed tomography at the level of the TH, FN, trochanter (TR), and intertrochanteric (IT). Trabecular vBMD was lower in both total and active ACRO as compared with controls (P<0.01). Cortical vBMD was lower in ACRO patients (active and controlled) vs controls at both TH and TR sites (P<0.05). These findings were confirmed when only eugonadal patients were analyzed. Both total cross sectional area (CSA) and average cortical thickness (ACT) were greater in ACRO patients vs controls (P<0.05). An inverse association between disease duration and trabecular vBMD at TH (r=-0.42, P=0.023) and IT (r=-0.41, P=0.026) was also found. CONCLUSION Both cortical and trabecular vBMD are reduced at the proximal femur in ACRO patients, regardless of gender, gonadal status, and disease activity. Disease duration is negatively associated with trabecular vBMD at the TH and IT.