Macroprolactin: From laboratory to clinical practice.

Prolactin measurement is very common in standard clinical practice. It is indicated not only in the study of pituitary adenomas, but also when there are problems with fertility, decreased libido, or menstrual disorders, among other problems. Inadequate interpretation of prolactin levels without contextualizing the laboratory results with the clinical, pharmacological, and gynecological/urological history of patients leads to erroneous diagnoses and, thus, to poorly based studies and treatments. Macroprolactinemia, defined as hyperprolactinemia due to excess macroprolactin (an isoform of a greater molecular weight than prolactin but with less biological activity), is one of the main causes of such erroneous diagnoses, resulting in poor patient management when not recognized. There is no unanimous agreement as to when macroprolactin screening is required in patients with hyperprolactinemia. At some institutions, macroprolactin testing by polyethylene glycol (PEG) precipitation is routinely performed in all patients with hyperprolactinemia, while others use a clinically based approach. There is also no consensus on how to express the results of prolactin/macroprolactin levels after PEG, which in some cases may lead to an erroneous interpretation of the results. The objectives of this study were: 1. To establish the strategy for macroprolactin screening by serum precipitation with PEG in patients with hyperprolactinemia: universal screening versus a strategy guided by the alert generated by the clinician based on the absence or presence of clinical symptoms or by the laboratory when hyperprolactinemia is detected. 2. To create a consensus document that standardizes the reporting of prolactin results after precipitation with PEG to minimize errors in the interpretation of the results, in line with international standards.

The triglyceride/glucose index as an insulin resistance marker in the pediatric population and its relation to eating habits and physical activity.

INTRODUCTION: To examine the triglyceride/glucose index (TyG) as an insulin resistance marker in obese children and adolescents and its relation to clinical and biochemical parameters, body composition and lifestyle. PATIENTS AND METHOD: Sixty patients aged 7-16 years of age were enrolled. Anthropometric variables were recorded, together with pubertal stage, blood pressure and body composition assessed by bioimpedance. The TyG index was calculated as ln (fasting glucose (mg/dL) × triglycerides (mg/dL))/2 and the HOMA (homeostatic model assessment) index as fasting insulin (µU/mL) × fasting glucose (mmol/L)/22.5. Feeding habits were documented by adherence to the Mediterranean dietary pattern questionnaire, while physical activity was assessed using the International Sedentary Assessment Tool (ISAT), as well as accelerometry (Actigraph wGT3X+). RESULTS: The mean TyG index was 4.45 ±â€¯0.18, and proved higher in the pubertal group. We found a positive correlation with the HOMA index (r = 0.39; P = 0.03) and TG/HDL-c index (r = 0.53; P < 0.001). The best cut-off point of the TyG index for predicting insulin resistance was 4.21 in prepubertal children (sensitivity 84%, specificity 100%; AUC: 0.84) and 4.33 in pubertal children (sensitivity 89%, specificity 69%; AUC: 0.61). A positive correlation was found with screen time (r = 0.39; P = 0.01), as well as a negative correlation with caloric expenditure (Kcal/day) in the prepubertal group (r = -0.81; P = 0.005). CONCLUSIONS: The TyG index could be a useful insulin resistance marker in the pediatric population. Moderate to vigorous physical activity should be encouraged, as well as restricting screen time for leisure purposes, mainly in the prepubertal group.

Assessment of exposure-response relationship for bevacizumab in patients with metastatic colorectal cancer.

Limited literature is available for bevacizumab exposure-response relationship and there is not a concentration threshold associated with an optimal disease control. This prospective observational study in patients with metastatic colorectal cancer (mCRC) aims to evaluate, in a real-life setting, the relationship between bevacizumab through concentrations at steady state (Ctrough, SS) and disease control. Ctrough, SS were drawn, coinciding with the radiological evaluation of the response (progression or clinical benefit). Generalized estimating equations (GEE) analysis was performed. To test the association between Ctrough, SS in each patient with overall survival (OS) or progression-free survival (PFS), Cox proportional hazard models were developed. Data included 50 bevacizumab Ctrough, SS from 27 patients. The GEE model did not suggest any positive association between bevacizumab Ctrough, SS and clinical benefit (OR 0.99, 95% CI: 0.98-1.02, p = 0.863). The Cox regression showed association between higher median Ctrough, SS with better OS (HR 0.86, 95% CI: 0.73-1.01, p = 0.060), but not with PFS. We cannot confirm a relationship between bevacizumab Ctrough, SS and clinical benefit but this is the first real-world study trying to show a relationship between bevacizumab Ctrough, SS and disease control in mCRC. It was conducted in a small sample size which reduces the level of evidence. Further controlled randomized studies with a sufficient number of patients are required.

Macroprolactin: From laboratory to clinical practice. / Macroprolactina: del laboratorio a la práctica clínica. Recomendaciones del grupo de trabajo de laboratorio de la SEEN y de la comisión de hormonas de la SEQCML sobre la medición e informe del resultado de la macroprolactina.

Prolactin measurement is very common in standard clinical practice. It is indicated not only in the study of pituitary adenomas, but also when there are problems with fertility, decreased libido, or menstrual disorders, among other problems. Inadequate interpretation of prolactin levels without contextualizing the laboratory results with the clinical, pharmacological, and gynecological/urological history of patients leads to erroneous diagnoses and, thus, to poorly based studies and treatments. Macroprolactinemia, defined as hyperprolactinemia due to excess macroprolactin (an isoform of a greater molecular weight than prolactin but with less biological activity), is one of the main causes of such erroneous diagnoses, resulting in poor patient management when not recognized. There is no unanimous agreement as to when macroprolactin screening is required in patients with hyperprolactinemia. At some institutions, macroprolactin testing by polyethylene glycol (PEG) precipitation is routinely performed in all patients with hyperprolactinemia, while others use a clinically based approach. There is also no consensus on how to express the results of prolactin/macroprolactin levels after PEG, which in some cases may lead to an erroneous interpretation of the results. The objectives of this study were: 1. To establish the strategy for macroprolactin screening by serum precipitation with PEG in patients with hyperprolactinemia: universal screening versus a strategy guided by the alert generated by the clinician based on the absence or presence of clinical symptoms or by the laboratory when hyperprolactinemia is detected. 2. To create a consensus document that standardizes the reporting of prolactin results after precipitation with PEG to minimize errors in the interpretation of the results, in line with international standards.

The triglyceride / glucose index as an insulin resistance marker in the pediatric population and its relation to eating habits and physical activity. / El índice triglicéridos-glucosa como marcador de insulinorresistencia en población pediátrica y su relación con hábitos de alimentación y actividad física.

INTRODUCTION: To examine the triglyceride/glucose index (TyG) as an insulin resistance marker in obese children and adolescents and its relation to clinical and biochemical parameters, body composition and lifestyle. PATIENTS AND METHOD: Sixty patients aged 7-16 years of age were enrolled. Anthropometric variables were recorded, together with pubertal stage, blood pressure and body composition assessed by bioimpedance. The TyG index was calculated as ln (fasting glucose (mg/dL)×triglycerides (mg/dL))/2 and the HOMA (homeostatic model assessment) index as fasting insulin (µU/mL)×fasting glucose (mmol/L)/22.5. Feeding habits were documented by adherence to the Mediterranean dietary pattern questionnaire, while physical activity was assessed using the International Sedentary Assessment Tool (ISAT), as well as accelerometry (Actigraph wGT3X+). RESULTS: The mean TyG index was 4.45±0.18, and proved higher in the pubertal group. We found a positive correlation with the HOMA index (r=0.39; P=.03) and TG/HDL-c index (r=0.53; P<.001). The best cut-off point of the TyG index for predicting insulin resistance was 4.21 in prepubertal children (sensitivity 84%, specificity 100%; AUC: 0.84) and 4.33 in pubertal children (sensitivity 89%, specificity 69%; AUC: 0.61). A positive correlation was found with screen time (r=0.39; P=.01), as well as a negative correlation with caloric expenditure (Kcal/day) in the prepubertal group (r=-0.81; P=.005). CONCLUSIONS: The TyG index could be a useful insulin resistance marker in the pediatric population. Moderate to vigorous physical activity should be encouraged, as well as restricting screen time for leisure purposes, mainly in the prepubertal group.

Utilidad para médicos no radiólogos de la clasificación tirads y las características ecográficas de los nódulos tiroideos / Usefulness for non radiologist physicians of tirad classification and ecographic characteristics of thyroid nodules

Dada la mayor accesibilidad a la ecografía tiroidea, se diagnostican más nódulos de forma incidental aumentando su prevalencia al 65% en las tres últimas décadas. Todo ello ha supuesto un aumento de punciones innecesarias. El objetivo de nuestro estudio es identificar la utilidad de la clasificación TIRADS y de las características ecográficas de los nódulos tiroideos para establecer la probabilidad de malignidad de los mismos y seleccionar aquellos sospechosos para realizar la punción y aspiración con aguja fina (PAAF). Se encontró una relación estadísticamente significativa entre la malignidad y nódulo sólido, hipoecogenicidad, márgenes irregulares y microcalcificaciones. Sin embargo, no se encontró relación estadísticamente significativa entre malignidad y número de nódulos, tamaño nodular, diámetro craneocaudal y vascularización central. Asimismo, un 26.1% de los nódulos TIRADS-2 (todos ellos microcarcinomas), un 30% de los TIRADS-3 y un 54 % de los TIRADS-4 fueron malignos (p 0.027). Tanto el TIRADS como las características ecográficas aisladas son útiles para identificar nódulos sugerentes de malignidad.

Owed to the easier accessibility to thyroid ecography, more incidental nodules are discovered reaching their prevalence the 65 % of population in the last three decades. All of it has resulted in a growth of unnecessary fine needle aspirations (FNA). Our study objective is to identify the TIRADS classification utility and the nodules sonographic characteristics to establish their probability of malignancy and to select those suspicious susceptible of FNA. We found a statistically significant relationship between malignancy and solid nodule, hypoechogenicity, irregular margins and microcalcifications. However we didn´t find a relation between malignancy and number, size, shape (taller than wide) and central vascularity. With respect to TIRADS classification, 26,1% of TIRADS-2 (all of them microcarcinomas), 30% of TIRADS-3 and 54% of TIRADS-4 were malignant (p: 0,027). Both of them, TIRADS and individual sonographic characteristics are useful to identify nodules suspicious of malignancy.

Hypogonadism associated with muscle atrophy, physical inactivity and ESA hyporesponsiveness in men undergoing haemodialysis.

BACKGROUND: Testosterone deficiency (hypogonadism) is common among men undergoing haemodialysis, but its clinical implications are not well characterized. Testosterone is an anabolic hormone that induces erythrocytosis and muscle synthesis. We hypothesized that testosterone deficiency would be associated with low muscle mass, physical inactivity and higher dosages of erythropoietin-stimulating agents (ESA). METHODS: Single-center cross-sectional study of 57 male haemodialysis patients. None of the patients was undergoing testosterone replacement therapy. Total testosterone was measured in serum. Body composition (by bioelectrical impedance analysis) and physical activity (by the use of pedometers) were assessed. Patients with testosterone levels below the normal range were considered hypogonadal. RESULTS: Mean testosterone level was 321±146ng/dL; 20 patients (35%) were hypogonadal. Hypogonadal patients were older and had lower mean arterial blood pressure, higher interleukin-6 levels, lower lean body mass and higher fat body mass. A negative association between testosterone and normalized ESA dose was found in uni- and multivariate regression analyses. Testosterone levels directly correlated with lean body mass regardless of confounders. Hypogonadal patients had lower physical activity than their counterparts [2753±1784 vs. 4291±3225steps/day (p=0.04)]. The relationship between testosterone and physical activity was independent of age, comorbidities and inflammatory markers, but dependent on the proportion of muscle mass. CONCLUSION: Hypogonadism is common in our male haemodialysis population and is associated with higher ESA doses, reduced muscle mass and lower physical activity. The link between low testosterone levels and physical inactivity may conceivably relate to reduced muscle mass due to inadequate muscle protein synthesis.

Intragenic GNAS deletion involving exon A/B in pseudohypoparathyroidism type 1A resulting in an apparent loss of exon A/B methylation: potential for misdiagnosis of pseudohypoparathyroidism type 1B.

CONTEXT: Several endocrine diseases that share resistance to PTH are grouped under the term pseudohypoparathyroidism (PHP). Patients with PHP type Ia show additional hormone resistance, defective erythrocyte G(s)alpha activity, and dysmorphic features termed Albright's hereditary osteodystrophy (AHO). Patients with PHP-Ib show less diverse hormone resistance and normal G(s)alpha activity; AHO features are typically absent in PHP-Ib. Mutations affecting G(s)alpha coding exons of GNAS and epigenetic alterations in the same gene are associated with PHP-Ia and -Ib, respectively. The epigenetic GNAS changes in familial PHP-Ib are caused by microdeletions near or within GNAS but without involving G(s)alpha coding exons. OBJECTIVE: We sought to identify the molecular defect in a patient who was diagnosed with PHP-Ia based on clinical presentation (hormone resistance and AHO) but displayed the molecular features typically associated with PHP-Ib (loss of methylation at exon A/B) without previously described genetic mutations. METHODS: Microsatellite typing, comparative genome hybridization, and allelic dosage were performed for proband and her parents. RESULTS: Comparative genome hybridization revealed a deletion of 30,431 bp extending from the intronic region between exons XL and A/B to intron 5. The same mutation was also demonstrated, by PCR, in the patient's mother, but polymorphism and allele dosage analyses indicated that she had this mutation in a mosaic manner. CONCLUSION: We discovered a novel multiexonic GNAS deletion transmitted to our patient from her mother who is mosaic for this mutation. The deletion led to different phenotypic manifestations in the two generation and appeared, in the patient, as loss of GNAS imprinting.