Osteoporosis and Fragility Fractures in Patients with Liver Cirrhosis: Usefulness of FRAX® as a Screening Tool.

PURPOSE: The purpose of this study is to assess the prevalence of osteoporosis and fragility fractures in patients with liver cirrhosis (LC) and determine the associated risk factors, evaluating the usefulness of FRAX® as a screening method to identify patients at a higher risk of fracture. METHODS: This was a cross-sectional study. Demographic, clinical, and analytical data were collected in a randomized sample of LC patients attending the Hepatology Department of a university hospital. We assessed the absolute risk of fracture at 10 years (FRAX®) and based on the bone mineral density (BMD), the presence of morphometric vertebral fracture with a vertebral fracture assessment (VFA), or a thoracic and lumbar X-ray and bone microarchitecture with a trabecular bone score (TBS). RESULTS: Ninety-two patients were included (71% male); the mean age was 63 ± 11.3 years. The main etiology of LC was alcoholism (52.2%), and most patients were Child-Pugh A (80.4%), with a mean model for end-stage liver disease (MELD) score of 10.1 ± 3.6. Sixteen patients (17.4%) had osteoporosis, and fifty-four (58.7%) had osteopenia. Eight patients (8.7%) had suffered at least one fragility fracture. The absolute risk of a major fracture according to FRAX without the BMD was 5.7 ± 4.5%. Risk factors associated with osteoporosis were age and the female sex. BMI > 30 was a protective factor. A FRAX cut-off point for a major fracture > 6.6% had a sensitivity of 69% and a specificity of 85% for a diagnosis of osteoporosis. CONCLUSIONS: The prevalence of osteoporosis and fractures in patients with LC is high, particularly in older women. FRAX® may be a useful method to identify candidates for bone densitometry. A FRAX value below 6.6% without the BMD can avoid unnecessary testing.

Measurement of Serum N-Glycans in the Assessment of Early Vascular Aging (Arterial Stiffness) in Adults With Type 1 Diabetes.

OBJECTIVE: Vascular aging (arterial stiffness [AS]) is an inflammation-linked process that predicts macro- and microvascular complications in adults with type 1 diabetes (T1D). We evaluated the utility of measuring the inflammation-linked N-glycans GlycA and GlycB to assess vascular aging in adults with T1D. RESEARCH DESIGN AND METHODS: Eighty-four adults with T1D (>10-year duration without cardiovascular events) and 68 healthy control subjects were evaluated for clinical characteristics (including microvascular complications in patients with T1D), aortic pulse wave velocity (aPWV) (surrogate measure of AS), and serum GlycA and GlycB (peak area [concentration] and height/width [H/W] ratio) using 1H-nuclear magnetic resonance spectroscopy. RESULTS: Patients with T1D had higher median (interquartile range) values than healthy control subjects for (P < 0.001 for all comparisons) aPWV 7.9 (6.9-9.1) vs. 6.1 (5.5-6.7) m/s, GlycA 850.4 (781.3-916.1) vs. 652.4 (581.5-727.1) µmoL; GlycB 386.1 (353.2-426.3) vs. 310.0 (280.5-331.9) µmol/L), H/W ratio of GlycA 16.5 (14.9-18.1) vs. 15.0 (13.7-16.7), and H/W ratio of GlycB 5.0 (4.6-5.5) vs. 4.0 (3.4-4.3). Moreover, aPWV correlated (P < 0.001 for all correlations) with GlycA (r = 0.550) and GlycB (r = 0.423) concentrations and with H/W ratios of GlycA (r = 0.453) and GlycB (r = 0.510). Adjusting for potential confounders, GlycA concentration (ß = 0.212, P < 0.001) and the H/W ratios of GlycA (ß = 0.150, P = 0.009) and GlycB (ß = 0.155, P = 0.011) remained independently associated with aPWV. C-statistics for detecting individuals with aPWV >10 m/s were 0.866 (95% CI 0.794-0.937) for GlycA levels and 0.862 (0.780-0.943) for H/W ratio of GlycB. CONCLUSIONS: Measurement of serum GlycA and GlycB may have utility in assessing vascular aging in adults with T1D of >10-year duration and no previous cardiovascular events.

Arterial Stiffness in Type 1 Diabetes: The Case for the Arterial Wall Itself as a Target Organ.

Arterial stiffness (AS) integrates the cumulative burden of known and unknown cardiovascular risk factors on the elastic wall of large arteries along the lifespan of an individual. As a marker of vascular aging, AS is an independent predictor of cardiovascular events and improves cardiovascular risk prediction when added to the Framingham Risk Score. In addition, AS may affect the microvasculature and promote the development of microvascular complications. Its impact on both the macro- and microvasculature has led to the concept that the arterial wall itself should be considered as a target organ. Here, we review the biological and clinical consequences of AS on the macro- and microvasculature and the measurement of AS in routine clinical practice. We also discuss the pathophysiological mechanisms underpinning AS development using diabetes and, in particular, type 1 diabetes, as a disease model with a high risk of cardiovascular events and microvascular complications that are accelerated by AS.

Papel central del laboratorio en el diagnóstico de un caso de infiltración de sistema nervioso central por mieloma múltiple refractario / Central role of the laboratory in the diagnosis of a case of central nervous system infiltration by refractory multiple myeloma

La infiltración leptomeníngea en el mieloma múltiple es una complicación poco frecuente y grave que se presenta generalmente tras recaídas de la enfermedad. Para establecer un correcto diagnóstico es necesario demostrar por citología la presencia de células plasmáticas clonales en el líquido cefalorraquídeo. Desde el laboratorio clínico detectamos esta complicación en una paciente diagnosticada de mieloma múltiple refractario, tras analizar una muestra de líquido cefalorraquídeo. La paciente presentaba diversos síntomas neurológicos como incontinencia fecal y disminución de la movilidad en ambas extremidades inferiores. Inicialmente observamos en el líquido pleocitosis, proteinorraquia y niveles elevados de células de alta fluorescencia, asociadas en ocasiones a células malignas. El proteinograma e inmunofijación del líquido confirmó la presencia del componente monoclonal ya detectado en sangre, y tras procesar la muestra por citometría de flujo pudimos confirmar la infiltración de células plasmáticas malignas en el sistema nervioso central. Nuestro laboratorio desempeñó un papel central y esencial en el diagnóstico de esta infrecuente complicación, mediante el uso combinado del proteinograma, la inmunofijación, la citometría de flujo y el autoanalizador hematológico, incluyendo en este último las células de alta fluorescencia, prometedor biomarcador en el cribado de la presencia de células tumorales en líquidos biológicos

Leptomeningeal involvement in multiple myeloma is a rare and serious complication that usually occurs after relapses of the disease. To establish a correct diagnosis, it is necessary to demonstrate, by cytology, the presence of clonal plasma cells in the cerebrospinal fluid. The clinical laboratory detected this complication in a patient diagnosed with refractory multiple myeloma after analysing a cerebrospinal fluid sample. The patient suffered from several neurological symptoms, such as faecal incontinence and lower limb mobility limitation. Pleocytosis and proteinorachia was initially observed, along with high levels of high-fluorescence cells, which are sometimes associated with malignant cells. The protein electrophoresis and immunofixation of the cerebrospinal fluid confirmed the presence of the monoclonal component, already detected in blood. After processing the sample by flow cytometry it was confirmed that there was infiltration of malignant plasma cells in the central nervous system. This laboratory played a central and essential role in the diagnosis of this uncommon complication, by the combined use of protein electrophoresis, immunofixation, flow cytometry, and the haematology autoanalyser. This latter included the high fluorescence cells as a promising biomarker in the screening for the presence of tumour cells in biological fluids

Salivary Cortisol Determination in ACTH Stimulation Test to Diagnose Adrenal Insufficiency in Patients with Liver Cirrhosis.

PURPOSE: The prevalence of adrenal insufficiency (AI) in patients with decompensated liver cirrhosis is unknown. Because these patients have lower levels of cortisol-binding carrier proteins, their total serum cortisol (TSC) correlates poorly with free serum cortisol (FC). Salivary cortisol (SaC) correlates better with FC. We aimed to establish SaC thresholds for AI for the 250 µg intravenous ACTH test and to estimate the prevalence of AI in noncritically ill cirrhotic patients. METHODS: We included 39 patients with decompensated cirrhosis, 39 patients with known AI, and 45 healthy volunteers. After subjects fasted ≥8 hours, serum and saliva samples were collected for determinations of TSC and SaC at baseline 0'(T0) and at 30-minute intervals after intravenous administration of 250 µg ACTH [30'(T30), 60'(T60), and 90'(T90)]. RESULTS: Based on the findings in healthy subjects and patients with known AI, we defined AI in cirrhotic patients as SaC-T0< 0.08 µg/dL (2.2 nmol/L), SaC-T60 < 1.43 µg/dl (39.5 nmol/L), or ΔSaC<1 µg/dl (27.6 nmol/L). We compared AI determination in cirrhotic patients with the ACTH test using these SaC thresholds versus established TSC thresholds (TSC-T0< 9 µg/dl [248 nmol/L], TSC-T60 < 18 µg/dl [497 nmol/L], or ΔTSC<9 µg/dl [248 nmol/L]). SaC correlated well with TSC. The prevalence of AI in cirrhotic patients was higher when determined by TSC (48.7%) than by SaC (30.8%); however, this difference did not reach statistical significance. AI was associated with sex, cirrhosis etiology, and Child-Pugh classification. CONCLUSIONS: Measuring SaC was more accurate than TSC in the ACTH stimulation test. Measuring TSC overestimated the prevalence of AI in noncritically ill cirrhotic patients.

Gamma heavy-chain disease accompanied with follicular lymphoma: a case report.

Heavy chain diseases (HCD) are B-cell lymphoprolipherative disorders characterized by the production of monoclonal heavy chains without associated light chains. Some cases of gamma-HCD (γ-HCD) are concurrent with other lymphoid neoplasm. The monoclonal component is not always detectable by serum electrophoresis, and often an immunofixation procedure is necessary to detect this component. Prognosis is variable, and no established guidelines for follow-up are available. We describe a case of a challenging diagnosis of γ-HCD due to the absence of clinical signs frequently reported in the disease (anaemia and palatal oedema among others). Haematological malignancy was the first suspicion but bone marrow examination was negative. In addition, the presence of an autoimmune bicytopenia and a Klinefelter syndrome complicated the clinical context of the patient. A thoracoabdominal computed tomography reported many small adenopathies whose pathological and immunohystochemical study revealed a follicular lymphoma. Shortly after, serum inmunofixation secondary to an abnormal electrophoretic pattern revealed a gamma paraprotein without light chains. Eventually, γ-HCD in association with follicular lymphoma was the final diagnosis. This is the first case reporting this association.

Evaluation of biological fluid analysis using the sysmex XN automatic hematology analyzer.

BACKGROUND: Hematological cytometers with a biological fluid module could potentially correct the limitations of the manual chamber method. This study evaluates the agreement between the manual technique and the Sysmex XN-1000 analyzer for white blood cell (WBC) and red blood cell (RBC) counts, as well as for leukocyte differentiation in different types of fluids. This study also evaluates the advantages of incorporating the technique in routine laboratory work. METHODS: One hundred and three fluid samples examined were 45 ascite (AF), 21 synovial (SF), 33 pleural (PF), and 31 cerebrospinal (CSF) fluid samples. All cell counting was performed with a Sysmex XN-1000 and a Fuchs-Rosenthal counting chamber. May Gründwald-Giemsa stain was used for manual WBC differentiation. The manual analysis data were obtained in duplicate by the same two observers. Passing-Bablok regression and the Kappa index were used to evaluate the interchangeability and concordance. RESULTS: Good agreement was observed for WBC differentiation in all fluids and for WBC counts in SF and PF. An optimal Kappa index was obtained, which indicated agreement and clinical significance for WBC and RBC counts in CSF and for RBC counts in PF. There was disagreement for WBC and RBC analysis in AF, with significantly higher results from the Sysmex XN-1000 than from the manual method. A reduction in laboratory response time was observed when using the automatic method. CONCLUSIONS: Except for AF, the Sysmex XN-1000 results agree with those of the manual method, although to different degrees depending on the fluid type. © 2017 International Clinical Cytometry Society.

Biomarkers kinetics in the assessment of ventilator-associated pneumonia response to antibiotics - results from the BioVAP study.

PURPOSE: Our aim was to evaluate the role of biomarker kinetics in the assessment of ventilator-associated pneumonia (VAP) response to antibiotics. MATERIALS AND METHODS: We performed a prospective, multicenter, observational study to evaluate in 37 microbiologically documented VAP, the kinetics of C-reactive protein (CRP), procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM). The kinetics of each variable, from day 1 to 6 of therapy, was assessed with a time dependent analysis comparing survivors and non-survivors. RESULTS: During the study period kinetics of CRP as well as its relative changes, CRP-ratio, was significantly different between survivors and non-survivors (p=0.026 and p=0.005, respectively). On day 4 of antibiotic therapy, CRP of survivors was 47% of the initial value while it was 96% in non-survivors. The kinetics of other studied variables did not distinguish between survivors and non-survivors. In survivors the bacterial load also decreased markedly. Adequate initial antibiotic therapy was associated with lower mortality (p=0.025) and faster CRP decrease (p=0.029). CONCLUSIONS: C-reactive protein kinetics can be used to identify VAP patients with poor outcome as soon as four days after the initiation of treatment. (Trial registration - NCT02078999; registered 3 August 2012).

Type 1 diabetes: Developing the first risk-estimation model for predicting silent myocardial ischemia. The potential role of insulin resistance.

OBJECTIVES: The aim of the study was to develop a novel risk estimation model for predicting silent myocardial ischemia (SMI) in patients with type 1 diabetes (T1DM) and no clinical cardiovascular disease, evaluating the potential role of insulin resistance in such a model. Additionally, the accuracy of this model was compared with currently available models for predicting clinical coronary artery disease (CAD) in general and diabetic populations. RESEARCH, DESIGN AND METHODS: Patients with T1DM (35-65years, >10-year duration) and no clinical cardiovascular disease were consecutively evaluated for: 1) clinical and anthropometric data (including classical cardiovascular risk factors), 2) insulin sensitivity (estimate of glucose disposal rate (eGDR)), and 3) SMI diagnosed by stress myocardial perfusion gated SPECTs. RESULTS: Eighty-four T1DM patients were evaluated [50.1±9.3 years, 50% men, 36.9% active smokers, T1DM duration: 19.0(15.9-27.5) years and eGDR 7.8(5.5-9.4)mg·kg-1·min-1]. Of these, ten were diagnosed with SMI (11.9%). Multivariate logistic regression models showed that only eGDR (OR = -0.593, p = 0.005) and active smoking (OR = 7.964, p = 0.018) were independently associated with SMI. The AUC of the ROC curve of this risk estimation model for predicting SMI was 0.833 (95%CI:0.692-0.974), higher than those obtained with the use of currently available models for predicting clinical CAD (Framingham Risk Equation: 0.833 vs. 0.688, p = 0.122; UKPDS Risk Engine (0.833 vs. 0.559; p = 0.001) and EDC equation: 0.833 vs. 0.558, p = 0.027). CONCLUSION: This study provides the first ever reported risk-estimation model for predicting SMI in T1DM. The model only includes insulin resistance and active smoking as main predictors of SMI.

Biomarker kinetics in the prediction of VAP diagnosis: results from the BioVAP study.

BACKGROUND: Prediction of diagnosis of ventilator-associated pneumonia (VAP) remains difficult. Our aim was to assess the value of biomarker kinetics in VAP prediction. METHODS: We performed a prospective, multicenter, observational study to evaluate predictive accuracy of biomarker kinetics, namely C-reactive protein (CRP), procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM), for VAP management in 211 patients receiving mechanical ventilation for >72 h. For the present analysis, we assessed all (N = 138) mechanically ventilated patients without an infection at admission. The kinetics of each variable, from day 1 to day 6 of mechanical ventilation, was assessed with each variable's slopes (rate of biomarker change per day), highest level and maximum amplitude of variation (Δ (max)). RESULTS: A total of 35 patients (25.4 %) developed a VAP and were compared with 70 non-infected controls (50.7 %). We excluded 33 patients (23.9 %) who developed a non-VAP nosocomial infection. Among the studied biomarkers, CRP and CRP ratio showed the best performance in VAP prediction. The slope of CRP change over time (adjusted odds ratio [aOR] 1.624, confidence interval [CI]95% [1.206, 2.189], p = 0.001), the highest CRP ratio concentration (aOR 1.202, CI95% [1.061, 1.363], p = 0.004) and Δ (max) CRP (aOR 1.139, CI95% [1.039, 1.248], p = 0.006), during the first 6 days of mechanical ventilation, were all significantly associated with VAP development. Both PCT and MR-proADM showed a poor predictive performance as well as temperature and white cell count. CONCLUSIONS: Our results suggest that in patients under mechanical ventilation, daily CRP monitoring was useful in VAP prediction. Trial registration NCT02078999.

FGF-23/Vitamin D Axis in Type 1 Diabetes: The Potential Role of Mineral Metabolism in Arterial Stiffness.

OBJECTIVE: To investigate the usefulness of Fibroblast Growth Factor 23 (FGF-23) and vitamin D as possible biomarkers of pre-clinical atherosclerosis, assessed as arterial stiffness (AS), in a group of subjects with type 1 diabetes (T1DM) and no previous cardiovascular events. RESEARCH DESIGN AND METHODS: 68 T1DM patients and 68 age- and sex-matched controls were evaluated for 1) age, sex, diabetes duration, physical activity, smoking, alcohol intake, BMI, blood pressure, fasting plasma glucose, HbA1c, estimated glomerular filtration rate (eGFR) and lipid profile; 2) microvascular complications; 3) blood concentrations of FGF-23 and mineral metabolism parameters (calcium, phosphate, parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25(OH)D)); 4) AS, assessed as aortic pulse wave velocity (aPWV); and 5) low-grade inflammation (hsCRP, IL-6, sTNFαR1, sTNFαR2) and endothelial dysfunction (ED) markers (ICAM-1, VCAM-1, E-Selectin). RESULTS: Patients with T1DM had higher aPWV compared with controls (p<0.001), but they did not present differences in 25(OH)D (70.3(50.4-86.2)nmol/L vs. 70.7(59.7-83.0)nmol/L; p = 0.462) and in FGF-23 plasma concentrations (70.1(38.4-151.9)RU/mL vs. 77.6(51.8-113.9)RU/mL; p = 0.329). In T1DM patients, higher concentrations of FGF-23 were positively associated with aPWV after adjusting for eGFR and classical cardiovascular risk factors (model 1: ß = 0.202, p = 0.026), other mineral metabolism parameters (model 2: ß = 0.214, p = 0.015), microvascular complications, low-grade inflammation and ED markers (model 3: ß = 0.170, p = 0.045). Lower 25(OH)D concentrations were also associated with higher aPWV after adjusting for all the above-mentioned factors (model 3: ß = -0.241, p = 0.015). CONCLUSIONS: We conclude that both FGF-23 plasma concentrations (positively) and 25(OH)D serum concentrations (negatively) are associated with AS in patients with T1DM and no previous cardiovascular events.

Lack of confirmation of thyroid endophenotype in Bipolar Disorder Type I and their first-degree relatives.

BACKGROUND: Among the biological factors associated with the development and outcomes in Bipolar Disorder Type I (BD-I), previous studies have highlighted the involvement of both thyroid function and/or auto-immunity, proposing a thyroid endophenotype. The objective of this study was to determine the presence of thyroid alterations in BD-I and their first-degree relatives (FDR). METHODOLOGY: Unselected, cross-sectional case-control study with parallel analysis of individuals affected by BD-I (239), their FD-R (131), and 108 healthy controls. Thyroidal functional abnormalities (TSH and free T4) and thyroidal antibodies (thyroglobulin and thyroperoxidase antibodies) were studied. Assessments were carried out in parallel. The sample was described using arithmetic means, standard deviations, percentages and ranges. Chi-square, Student-t tests, ANOVA and Pearson correlation coefficients were used when indicated. RESULTS: BD-I on actual and/or ever treated with lithium showed significant thyroidal functional abnormalities as compared to their FD-R and healthy controls. This BD-I subgroup showed a significant greater proportion of subjects suffering from subclinical hypothyroidism (22%). The role of gender/lithium interactions was relevant. The groups did not show differences in terms of positivization of thyroidal antibodies. LIMITATIONS: The crosssectional design and the lack of determination of dietary iodine deficiencies and/or thyroidal ecographical controls may be a drawback. CONCLUSIONS: The present study supports previous findings on the effect of lithium treatment on thyroidal functional, but did not support previous findings related to a familial association or endophenotype. In addition, the present study did not support a familial aggregation of thyroidal antibodies positivization in pedegrees of BD-I.

Can augmentation index substitute aortic pulse wave velocity in the assessment of central arterial stiffness in type 1 diabetes?

The aim of this study was to test whether the augmentation index adjusted for heart rate (AIx@HR75) can be used as a substitute for aortic pulse wave velocity (aPWV) in the measurement of arterial stiffness (AS) in type 1 diabetes. Sixty-eight patients with type 1 diabetes and 68 age- and sex-matched controls were evaluated. AS was assessed by aPWV and AIx@HR75 using applanation tonometry. Subjects with type 1 diabetes had higher aPWV compared to controls, but no differences were found between groups regarding AIx@HR75 [men: 10.75 % (2.63-20.75) vs. 8.25 % (4.00-11.38); p = 0.462. Women: 20.75 % (5.00-30.16) vs. 14.50 % (11.38-22.16); p = 0.418]. In univariate analyses, aPWV correlated positively with AIx@HR75 in both groups (type 1: r = 0.340, p = 0.005; healthy subjects: r = 0.451, p < 0.001). However, AIx@HR75 was not associated with aPWV after adjustment for cardiovascular risk factors in multivariate models (type 1: p = 0.342; healthy subjects: p = 0.976). Our findings suggest that AIx@HR75 should not be used as a substitute for aPWV for measuring AS in type 1 diabetes.

Men with hyperferritinemia and diabetes in the Mediterranean area do not have a higher iron overload than those without diabetes.

AIM: To assess the role of iron overload in type 2 diabetic men with hyperferritinemia. METHODS: 150 men were recruited from a genetic screening programme for hereditary hemocromatosis (HH) and were tested for type 2 diabetes, other components of the metabolic syndrome, beta cell function (BCF), insulin sensitivity, high-sensitivity C-reactive protein and iron overload. RESULTS: Fifty-one men had type 2 diabetes. They were older (p=0.017) and 99 had lower BCF (p<0.001) than non-diabetic men. None of the iron overload indexes was associated with diabetes. CONCLUSIONS: Our findings dispute a role of iron overload in the pathogenesis of type 2 diabetes.

Serum soluble transferrin receptor concentrations are increased in central obesity. Results from a screening programme for hereditary hemochromatosis in men with hyperferritinemia.

BACKGROUND: A decrease in the serum concentrations of the soluble transferrin receptor (sTfR) is considered a good index of tissue iron. Because obesity is associated with hyperferritinemia and this is considered a sign of iron overload, a decrease in sTfR would be expected for the obese. We evaluated whether obese men with hyperferritinemia, detected in a genetic screening programme for hereditary hemochromatosis (HH), have lower serum concentrations of sTfR than their non-obese counterparts. METHODS: 75 men (age: 55.4+/-12.4 years) with hyperferritinemia (serum ferritin--SF > 200 microg/L) and no known conditions of iron overload were evaluated for body mass index (BMI), waist circumference (WC), blood pressure, traditional indices of iron status, sTfR, fasting plasma glucose, lipid profile, insulin resistance (HOMA-IR), highly-sensitive C-reactive protein, hepatic enzymes and HFE gene mutations of HH. RESULTS: sTfR correlated with BMI (r=0.289; p=0.014) and with WC (r=0.420; p<0.001). Thirty-two subjects were obese (BM > or = 30 kg/m(2)) and had a significantly higher sTfR (2.95 (2.22-3.28) vs 2.28 (1.88-2.91) mg/L; p=0.013), hemoglobin (157+/-12 vs 152+/-11 gr/L; p=0.049) and HOMA-IR (1.38 (1.04-2.69) vs 1.02 (0.60-1.55) mg/L; p=0.009) than the non-obese. WC explained separately more variability of the sTfR than BMI (r(2)=0.177; p=0.002 and r=0.077; p=0.042, respectively), after adjusting for potential confounders. CONCLUSION: An increase in serum concentrations of sTfR is associated with central obesity in men with hyperferritinemia.

[Vitamin D deficiency and related factors in patients with osteoporotic hip fracture]. / Déficit de vitamina D en la fractura osteoporótica de cadera y factores asociados.

BACKGROUND AND OBJECTIVE: Hypovitaminosis D is frequent in the elderly, and it is especially prevalent among patients with hip fracture. The prevalence of vitamin D deficiency and its related factors are not well known in our population. The objective of this study was to determine the prevalence of hypovitaminosis D in patients with osteoporotic hip fracture and to analyze which factors are associated with this deficit. PATIENTS AND METHOD: Transversal study. Inclusion of all consecutive patients older than 65 years, admitted in our hospital with osteoporotic hip fracture during the period of March 2002-February 2003. The prevalence of hypovitaminosis D and secondary hyperparathyroidism were analysed. Sunlight exposure, functional and nutritional status, and presence of comorbidity were investigated. RESULTS: 324 patients were included. Mean (standard deviation) age was 83 (7) years, and 80% were female. Vitamin D deficiency was observed in 217 cases (67%; 95% confidence interval [CI], 62-72%); and 57% of these patients had secondary hyperparathyroidism. A low nutritional status -albumin < 4 g/l (odds ratio [OR] = 4.5; 95% CI, 1.3-16; p = 0.019)- and a low functional status (Barthel index < 60; OR = 3; 95% CI, 1.3-6.7; p = 0.008) - were factors independently associated with hypovitaminosis D. However, an active sunlight exposure was a protective factor (OR = 0.09; 95% CI, 0.02-0.5; p = 0.004). CONCLUSIONS: The prevalence of hypovitaminosis D is high in patients with osteoporotic hip fracture, and in more than a half of the cases a secondary hyperparathyroidism is observed. The vitamin D deficiency is especially prevalent among patients with low sunlight exposure and low nutritional and functional status.

A lesser postprandial suppression of plasma ghrelin in Prader-Willi syndrome is associated with low fasting and a blunted postprandial PYY response.

OBJECTIVE: Ghrelin and polipeptide YY (PYY) are involved in the regulation of food intake. We evaluated these two peptides and their possible relationship in adult patients with Prader-Willi syndrome (PWS). PATIENTS: Seven patients with PWS, 16 age-sex-BMI matched obese and 42 age-sex matched lean subjects. DESIGN AND MEASUREMENTS: Fasting plasma PYY and ghrelin levels were measured in all subjects and, postprandially until 6 h, in seven matched subjects of each group. RESULTS: Fasting ghrelin levels were higher in PWS than in the other two groups. Fasting PYY levels were lower in patients with PWS than in lean subjects but similar to those in obese subjects. The postprandial decrease in ghrelin concentrations was lower in PWS as compared to the other two groups and therefore the 6-h-postprandial area under the curve (AUC) for ghrelin was higher in PWS than in obese subjects. PYY response after the meal was blunted in patients with PWS, but not in the other two groups that showed a peak at 60 min The AUC for PYY was lower in PWS as compared to the other two groups. Fasting PYY levels correlated negatively with fasting ghrelin levels and with ghrelin AUC and they were the only predictor for ghrelin AUC (beta = -0.464, P = 0.034). The increase in PYY correlated negatively with the decrease in ghrelin at times 60 min and 120 min in PWS. CONCLUSIONS: In PWS, the low decrease in postprandial ghrelin levels could be related to the low fasting PYY concentrations and their blunted postprandial response.

Diagnóstico bioquímico del exceso de secreción de prolactina / Biochemical diagnosis of prolactin secretion excess

La prolactina actúa principalmente en la glándula mamaria iniciando y manteniendo la lactación. El exceso de secreción de prolactina se presenta tanto en varones como en mujeres y se manifiesta clínicamente por disfunciones sexuales o reproductivas o galactorrea. En los casos en que se detecta hiperprolactinemia, el principal objetivo es demostrar o descartar la presencia de un adenoma hipofisario secretor de prolactina. Para valorar la normalidad de la secreción de la hormona son suficientes, en general, las determinaciones basales de prolactina y no se requiere de pruebas de estimulación o frenación para establecer o confirmar el diagnóstico bioquímico. Es preciso controlar estrictamente las condiciones de extracción de la muestra para poder valorar correctamente los resultados. En individuos sanos, la prolactina circula en la sangre en tres formas moleculares; una de ellas es un complejo antígeno-anticuerpo formado por la prolactina y una inmunoglobulina de la clase IgG, denominado macroprolactina, que, aunque tiene una actividad biológica limitada y menor biodisponibilidad que la forma monomérica, es inmunorreactiva y produce resultados de prolactina por encima del intervalo de referencia en el 10-15% de los casos de hiperprolactinemia. Para detectar la macroprolactina se utiliza, generalmente, un método basado en la precipitación de las proteínas con polietilenglicol

Prolactin (PRL) acts mainly on the mammary gland, initiating and maintaining lactation. Excess PRL secretion occurs in both men and women and manifests clinically with sexual or reproductive dysfunction or galactorrhea. When hyperprolactinemia is detected, the main aim is to establish or rule out the presence of a PRL-secreting pituitary adenoma. In general, hormone secretion levels can be evaluated using baseline PRL determinations without the need for stimulation or suppression tests to establish or confirm the biochemical diagnosis. The conditions under which the blood sample is extracted must be strictly controlled for correct interpretation of the results. In healthy individuals, PRL circulates in blood in three molecular forms, one of which is an antigen-antibody complex composed of PRL and an IgG immunoglobulin called macroprolactin. Although the biological activity and bioavailablity of macroprolactin is more limited than those of the monomeric form, this complex is immunoreactive and produces PRL levels that are above the reference range in 10-15% of individuals with hyperprolactinemia. To detect macroprolactin, a method based on polyethylene glycol precipitation is generally used

Diagnóstico bioquímico del exceso de secreción de somatotropina (I) / Biochemical diagnosis of excess growth hormone secretion (I)

El exceso de secreción de somatotropina produce los cuadros clínicos de la acromegalia cuando se presenta en adultos o del gigantismo cuando afecta a niños antes del cierre de las epífisis óseas. El diagnóstico bioquímico se establece mediante las determinaciones basales de somatotropina y de factor de crecimiento insulinoide de tipo 1 y, en casos de dudosa interpretación, la prueba de sobrecarga oral de glucosa. Para valorar correctamente los resultados emitidos por el laboratorio hay que tener en cuenta variables como el sexo, la edad, el índice de masa corporal o la presencia de patología asociada, así como la propia variabilidad analítica, debida a la heterogeneidad de la molécula, el tipo de anticuerpos utilizados en el inmunoanálisis, la estandarización del método o la interferencia de la proteína enlazante de somatotropina. Los valores discriminantes que se utilizan para excluir la presencia de acromegalia o como criterios de control y tratamiento de la enfermedad, se establecieron por consenso en el año 2000, aunque han sido puestos en entredicho debido a la sensibilidad y especificidad analíticas de los modernos inmunoanálisis

Excess growth hormone (GH) secretion produces acromegaly when it occurs in adults or gigantism when it occurs in children before closure of the epiphyses. Biochemical diagnosis is established through baseline determinations of GH and insulin-like growth factor type-1, and, when the results are unclear, through oral glucose load. To correctly evaluate the results of laboratory tests, variables such as sex, age, body mass index, and the presence of associated diseases should be taken into account. Also of relevance are variability in laboratory results, due to the heterogeneity of the molecule, the type of antibodies used in the immunoassay, the standardization of the method, and the interference of the GH binding protein. The cut-off values used to rule out the presence of acromegaly or as criteria for monitoring and treatment of the disease were established by consensus in 2000. However, these values have been questioned due to the sensitivity and specificity of modern immunoassays