5α-Reductase type 2 deficiency in families from an isolated Andean population in Venezuela.

5α-Reductase type 2 deficiency causes a 46,XY disorder of sex development (DSD) characterized by ambiguous external genitalia, rudimentary prostate, and normal internal genitalia. The disease prevalence worldwide is low, but in a small and isolated village of the Venezuelan Andes, a higher incidence has been found. DNA analysis of the SRD5A2 gene was performed in three inbred affected individuals clinically diagnosed with DSD. The entire coding regions, the p.L89V polymorphism (rs523349) and five intragenic SNPs (rs2300702, rs2268797, rs2268796, rs4952220, rs12470196) used to construct haplotypes were analyzed by Sanger sequencing. To assess the probable ethnic origin of the mutation in this geographic isolate, a population structure analysis was performed. Homozygosis for the p.N193S mutation was found in all patients, with a mutation carrier frequency of 1:80 chromosomes (0.0125) in the geographic focus, suggesting a founder phenomenon. The results of the population structure analysis suggested a mutation origin closer to the Spanish populations, according to the clusters grouping. The genotype-phenotype correlation in the patients was not absolute, being hypospadias and cryptorchidism the main traits that differentiate affected individuals.

Triglycerides/High density lipoprotein cholesterol ratio as a cardiometabolic risk marker in children and adolescents from Mérida city, Venezuela. / Relación triglicéridos/colesterol de la lipoproteína de alta densidad como indicador de riesgo cardiometabólico en niños y adolescentes de la ciudad de Mérida, Venezuela.

OBJECTIVE: To determine the behavior of the triglycerides/HDL-cholesterol ratio (TG/HDL) as a cardiometabolic risk marker in children and adolescents from Mérida, Venezuela. METHODS: A total of 1292 children and adolescents aged 7-18 years who attended educational institutions in the Libertador Municipality were enrolled into this study. Anthropometric measurements and blood pressure values were recorded. Fasting blood glucose, insulin and lipid levels were measured. The TG/HDL ratio, HOMA-IR, and QUICKI indexes were calculated. Subjects were categorized as with and without cardiometabolic risk based on the presence or absence of 2or more risk factors. Cut-off points for the TG/HDL ratio were determined by constructing ROC curves. RESULTS: Significantly higher mean TG/HDL ratios were found in pubertal (2.2 ± 1.7) as compared to prepubertal subjects (1.8 ± 1.5; P=.001), with no sex differences. Two or more risk factors were found in 14.7% (n=192) of the participants, in whom TG/HDL ratios were significantly higher as compared to those with no risk (3.5±2.9 versus 1.6±0.8 in prepubertal and 4.1 ± 3.5 versus 1.8 ± 0.9 in pubertal subjects; P=.0001). According to cardiometabolic risk, cut-off points for the TG/HDL ratio of 1.8 and 2.5 were found for prepubertal and pubertal children respectively. These cut-off points showed risks (odds ratio) higher than 2.5 for conditions such as metabolic syndrome, elevated non-HDL-C, abdominal obesity, and elevated HOMA-IR. CONCLUSION: In this sample of children and adolescents, an elevated TG/HDLc ratio was found to be a good marker for predicting cardiometabolic risk.

Ginecomastia de Origen Multifactorial en el Adulto Mayor: Revisión fisiopatológica de un caso / Multifactorial Gynecomastia in the Elderly: Pathophysiological review of a case

Objetivo: Describir los aspectos fisiopatológicos en un paciente adulto mayor quien consultó por ginecomastia bilateral de origen multifactorial. Caso clínico: Paciente masculino de 66 años de edad, quien inició enfermedad actual desde hace 5 años caracterizado por aumento de volumen en ambas mamas, de predominio derecho acompañado de mastalgia. Presenta diagnóstico previo de Diabetes Mellitus tipo 2 desde hace aproximadamente 10 años, mal controlado, recibiendo glimepiride 4 mg vía oral diarios. Hepatopatía crónica de probable etiología alcohólica diagnosticada hace 10 años, complicada con várices esofágicas en tratamiento con propranolol 40 mg vía oral diario hasta la actualidad; refiere haber recibido espironolactona 100 mg vía oral diario durante aproximadamente 5 años, el cual fue omitido debido a la aparición de aumento de volumen mamario y mastalgia. Hemorragia digestiva superior hace 10 años por várices esofágicas. Hábito alcohólico frecuente hasta la embriaguez, desde la juventud hasta hace 10 años. Al examen físico reporta peso: 85 kg, talla: 164 cms, índice de masa corporal: 31,7 kg/m², tensión arterial: 137/72 mmHg, frecuencia cardiaca: 57 Lpm en buenas condiciones. Mamas asimétricas ginecomastia grado 3 bilateral, no galactorrea. Abdomen con hepatometría 9-10-15 cms, manos con eritema palmar. Conclusión: La ginecomastia en los adultos mayores fisiopatológicamente puede ser de origen multifactorial, siendo el decremento de las concentraciones séricas de testosterona el denominador común. El tratamiento oportuno puede mejorar la sintomatología y progresión de la misma.

Objective: To describe the pathophysiology in an elderly patient who consulted for bilateral gynecomastia of multifactorial origin. Case report: Male patient, 66 years old, who started current disease for 5 years ago characterized by increased volume in both breasts, predominantly right, accompanied by mastalgia. He presented previous diagnosis of diabetes mellitus type 2 about 10 years ago, poorly controlled, receiving glimepiride 4 mg per day orally. Chronic liver disease of probable alcoholic etiology diagnosed 10 years ago, complicated with esophageal varices treated with propranolol 40 mg orally daily until today; he received spironolactone 100 mg orally daily for about five years, which was omitted due to the appearance of breast volume increase and pain. Upper gastrointestinal bleeding 10 years ago from esophageal varices. Frequent drinking habits until drunkenness since youth, for 10 years.. Physical examination reports weight: 85 kg, height: 164 cm, body mass index: 31.7 kg/m², blood pressure: 137/72 mmHg, heart rate: 57 lpm, in good condition. Asymmetrical breasts with grade 3 bilateral gynecomastia, not galactorrhea; liver measures by palpation 10-09-15 cms, hands with palmar erythema. Conclusion: Gynecomastia in older adults may have pathophysiologically a multifactorial origin, being the decrease in serum testosterone the common denominator. Early treatment can improve symptoms and progression of it.

[Effects of occupational exposure to pesticides on semen quality of workers in an agricultural community of Merida state, Venezuela]. / Efectos de la exposición ocupacional a plaguicidas sobre la calidad del semen en trabajadores de una comunidad agrícola del estado Merida, Venezuela.

Numerous studies report adverse effects of pesticides on male reproductive health. The objectives of this study were to investigate whether there is a relationship between occupational exposure to pesticides and semen quality, and to determine whether chronic exposure to pesticides differentially affects semen quality in men of different ages. A comparative study of 64 farmers and 64 control men was performed. The farmers were interviewed to determine their occupational history and particularly, activities that may involve exposure to pesticides. Semen parameters were evaluated and a comparative analysis of semen variables between exposed and control groups, as well as between age groups: 18-29, 30-37 and 38-60 years was done. Significant alterations of some semen parameters in the exposed group were found, such as: decreases in sperm concentration, slow progressive motility and sperm membrane integrity; at the same time, increases in eosin Y positive and sperm DNA fragmentation index. The results obtained by age groups showed significant differences between exposed and control groups for the parameters of membrane integrity, eosin Y positive and sperm DNA fragmentation index, being the exposed group between 18-29 years that showed the highest altered cases of these parameters. Our results prove that occupational pesticide exposure is associated with alterations in sperm quality, creating a risk to farm workers in their reproductive capacity.

Prevalence of the metabolic syndrome, insulin resistance index, leptin and thyroid hormone levels in the general population of Merida (Venezuela).

The metabolic syndrome (MetSyn) is a significant risk factor for cardiovascular events, but scarce information exists about its frequency in Venezuela. In this cross-sectional study, we quantified the prevalence of the MetSyn in a probabilistic, stratified sample of 274 subjects aged > or =18 years from the Libertador district in Merida, Venezuela. Secondary outcomes were the measurement of thyroid hormones (free T4 and TSH), leptin levels, and insulin resistance index (HOMA2-IR). The frequency of MetSyn (percentage +/- 95% confidence interval) according to several diagnostic criteria was as follows: National Cholesterol Education Panel (NCEP, original): 27.4% (22.1-32.7); modified NCEP: 31.8% (26.3-37.3); International Diabetes Federation: 40.9% (35.1-46.7); Latin American Diabetes Association: 27% (21.7-32.3), and Venezuelan criteria: 31.8% (26.3-37.3). The MetSyn was more frequent in males than in females with most diagnostic criteria. The estimated prevalence of type 2 diabetes mellitus was 2.9% either according to the patients' self reports or to fasting glucose level found to be above 126 mg/dL. Abnormal HOMA2-IR index, free T4 and TSH (above the 95th percentile) were detected in 4.5%, 4.4% and 5.1% of the sample, respectively. Free T4 and TSH levels below the 5th percentile were detected in 4.4% and 4.7% of subjects respectively. These values are presented for comparisons with forthcoming studies in specific clinical populations. While studies are being conducted about the different definitions of the MetSyn in Venezuela, we recommend analyzing and publishing local research data with all the available criteria so as to allow comparisons with the results already reported in the literature.

Diagnóstico y manejo del hipogonadismo masculino / Male hypogonadism management

El hipogonadismo masculino se caracteriza por disfunción testicular y/o del eje hipotálamo-hipofisario produciendo una reducción de las concentraciones de testosterona. Se clasifica en hipogonadismo hipogonadotrópico (Hh) e hipogonadismo hipergonadotrópico (HH), y a su vez en causas adquiridas y congénitas. Las gonadotropinas pueden estar elevadas (HH) o disminuidas (Hh) y en general cursan con niveles disminuidos de testosterona. Dentro de las pruebas que apoyan al diagnóstico y manejo se incluyen el ecosonograma testicular, evaluación genética, densitometría ósea, biopsia testicular, estudios imagenológicos, espermograma, anticuerpos antiespermáticos y las pruebas dinámicas. Por último, la terapia de reemplazo con testosterona es el principal tratamiento, y la meta es obtener valores de testosterona total entre 400 y 700 ng/dL. A continuación, se presenta el protocolo para el diagnóstico y manejo del hipogonadismo masculino, con la evidencia científica y la experiencia clínica de la Unidad de Endocrinología del IAHULA.

Male hypogonadism is characterized by testicular dysfunction secondary to testicular damage and/or hypothalamus-pituitary axis dysfunction resulting in a reduction in testosterone levels. It is classified as hypogonadotropic hypogonadism (Hh) or hypergonadotropic hypogonadism (HH), and these are also divided in acquired and congenital causes. Gonadotropins may be high (HH) or decreased (Hh) and generally occur with decreased testosterone levels. Among the tests supporting the diagnosis and management are included testicular ultrasonography, genetic screening, bone densitometry, testicular biopsy, imaging studies, spermogram, sperm antibodies and hormonal dynamic tests. Finally, testosterone replacement therapy is the main treatment, and the goal is to obtain total testosterone values between 400 and 700 ng/dL. Below, is presented the IAHULA Endocrinology Unit guidelines for male hypogonadism management, based on scientific evidence and clinical experience.

Efectos de la exposición ocupacional a plaguicidas sobre la calidad del semen en trabajadores de una comunidad agrícola del estado Mérida, Venezuela. / Effects of occupational exposure to pesticides on semen quality of workers in an agricultural community of Merida state, Venezuela.

Numerosos estudios informan de los efectos adversos de plaguicidas sobre la salud reproductiva masculina. Los objetivos de este estudio fueron investigar si existe una relación entre exposición ocupacional a plaguicidas y la calidad del semen, y determinar si la exposición crónica a plaguicidas afecta diferencialmente la calidad del semen de trabajadores de diferentes edades. Se realizó un estudio comparativo entre 64 agricultores y 64 hombres control. Los trabajadores agrícolas fueron entrevistados para determinar su historia ocupacional, particularmente las actividades que pueden involucrar exposición a plaguicidas. Se evaluaron los parámetros seminales y se hizo un análisis comparativo entre el grupo expuesto y control, así como entre los grupos de edad 18-29, 30-37 y 38-60 años. Se encontraron alteraciones significativas de algunos parámetros del semen en el grupo expuesto, tales como: disminuciones en la concentración, motilidad lenta progresiva e integridad de membrana espermática; a su vez, incrementos en eosina Y positiva e índice de fragmentación del DNA espermático. Los resultados obtenidos por grupo de edad mostraron diferencias significativas entre los grupos expuesto y control, para los parámetros de integridad de membrana, eosina Y positiva e índice de fragmentación del DNA espermático, siendo el grupo expuesto entre 18-29 años el que mostró mayores casos alterados de estos parámetros. Los resultados de este estudio comprueban que la exposición ocupacional a plaguicidas está asociada con alteraciones en la calidad espermática, creando riesgo para la capacidad reproductiva de los trabajadores del campo.

Numerous studies report adverse effects of pesticides on male reproductive health. The objectives of this study were to investigate whether there is a relationship between occupational exposure to pesticides and semen quality, and to determine whether chronic exposure to pesticides differentially affects semen quality in men of different ages. A comparative study of 64 farmers and 64 control men was performed. The farmers were interviewed to determine their occupational history and particularly, activities that may involve exposure to pesticides. Semen parameters were evaluated and a comparative analysis of semen variables between exposed and control groups, as well as between age groups: 18-29, 30-37 and 38-60 years was done. Significant alterations of some semen parameters in the exposed group were found, such as: decreases in sperm concentration, slow progressive motility and sperm membrane integrity; at the same time, increases in eosin Y positive and sperm DNA fragmentation index. The results obtained by age groups showed significant differences between exposed and control groups for the parameters of membrane integrity, eosin Y positive and sperm DNA fragmentation index, being the exposed group between 18-29 years that showed the highest altered cases of these parameters. Our results prove that occupational pesticide exposure is associated with alterations in sperm quality, creating a risk to farm workers in their reproductive capacity.

Metabolic syndrome in children and adolescents from Mérida city, Venezuela: Comparison of results using local and international reference values (CREDEFAR study).

OBJECTIVE: To obtain local reference values for blood lipids and blood pressure (BP), and to determine the prevalence of metabolic syndrome (MS) in children and adolescents from Mérida, Venezuela, and to compare results using local and international cut-off values. MATERIALS AND METHODS: The study enrolled 916 participants of both sexes aged 9-18 years of age from educational institutions. Demographic, anthropometric, and BP data were collected. Fasting blood glucose and lipid profile were measured. Percentile distribution of lipid and BP values was done by age group and sex. Prevalence of MS was estimated based on the NCEP-ATPIII classification (as modified by Cook et al.) and the classification of the International Diabetes Federation, using percentiles of Mérida and the USA as cut-off points. Agreement between both classifications was estimated using the kappa test (κ). RESULTS: Prevalence of MS was 2.2% by Cook-Merida percentiles, as compared to 1.8% by Cook-USA percentiles, a moderate agreement (κ=0.54). Agreement between Cook et al. and IDF using Merida percentiles was weak (κ=0.28). There was a higher frequency of abdominal obesity, hypertriglyceridemia and hypertension, and a lower frequency of low HDL-C using Mérida percentiles. The risk (odds ratio) of having MS is greater if abdominal obesity exists (OR: 98.63, CI: 22.45-433.35, p=0.0001). MS was significantly more common in obese subjects (18.3%, p=0.0001). CONCLUSIONS: Prevalence of MS in this sample of children and adolescents was 2.2%. Lipid and BP values were lower in Venezuelan as compared to US, European, and Asian children and adolescents, and similar to those in Latin-American references. Own reference values are required for accurate diagnosis of MS, as well as a worldwide consensus on its diagnostic criteria.

Diagnóstico y Manejo de la Insuficiencia Adrenal

La Insuficiencia Adrenal (IA) es una patología ocasionada por la disminución en la secreción de hormonas esteroideas por parte de la corteza adrenal, caracterizada por el déficit predominante de glucocorticoides. Esta puede ser clasificada en primaria cuando el defecto subyace en la glándula adrenal, siendo la causa más frecuente la adrenalitis autoinmune; o secundaria, por alteración en la secreción de la corticotropina (ACTH) o de la hormona liberadora de ACTH (CRH), cuya causa más común es la suspensión brusca de los glucocorticoides posterior a su administración por un período prolongado. Tanto las formas primarias como secundarias de IA pueden presentarse de manera aguda o crónica. La mayoría de los síntomas de la deficiencia de cortisol son inespecíficos incluyendo debilidad, anorexia, náuseas, entre otros; los signos principales son pérdida de peso, hiperpigmentación, hipotensión, siendo más característicos de la IA primaria. Una vez que se sospecha la IA, se determinarán las concentraciones de cortisol, con un valor basal menor de 3 mg/dL y post-estímulo menor de 18 mg/dL como diagnósticos de esta entidad. La determinación de ACTH permite la distinción entre una IA primaria y secundaria. El tratamiento de la IA en la mayoría de los casos es simplemente sustitutivo del déficit de glucocorticoides, siendo la hidrocortisona el fármaco de elección. Debido a que ésta patología puede estar asociada con una significativa morbilidad y mortalidad en los sujetos que la padecen, surgió la iniciativa por parte de nuestro servicio de Endocrinología de sintetizar en este protocolo la información hasta ahora disponible, así como nuestra experiencia, con respecto al diagnóstico y manejo de esta enfermedad.

Adrenal Insufficiency (AI) is a pathology caused by a decreased secretion of steroid hormones by the adrenal cortex, characterized by a predominant deficiency of glucocorticoids. AI can be classified as primary, when the underlying defect is in the adrenal gland, being the adrenalitis autoimmune the most common cause, or secondary, due to alterations in the secretion of corticotropin-releasing hormone (CRH) or corticotropin (ACTH), which most common cause is the abrupt discontinuation of glucocorticoids after its administration for an extended period. Both primary and secondary forms of IA may occur in an acute or chronic manner. Most symptoms of cortisol deficiency are nonspecific, including weakness, anorexia, nausea, among others; the main signs are weight loss, hyperpigmentation and hypotension, being more characteristics of the primary AI. A concentration less than 3 µg/ dL of basal cortisol or less than 18 µg/dL of cortisol post-stimulus confirm the diagnosis of this entity. The ACTH determination allows the distinction between primary and secondary AI. The treatment in most cases is simply to replace the deficit of glucocorticoid, being hydrocortisone the drug of choice. Because this condition can be associated with significant morbidity and mortality, an initiative was taken by our Endocrinology Service to synthesize in this protocol the information so far available, as well as our experience, with respect to the diagnosis and management of this disease.

Reference values of waist circumference and waist/hip ratio in children and adolescents of Mérida, Venezuela: comparison with international references.

OBJECTIVE: To collect regional reference values of waist circumference (WC), and waist/hip ratio (WHR) in children and adolescents from Merida, Venezuela, and to compare them to international references. SUBJECTS AND METHODS: A total of 919 students aged 9-17 years from public and private educational establishments were assessed. Weight, height, WC, and WHR were measured. Outliers (± 3 SD Z-Score) were excluded from the data collected. Percentile distribution of the tested variables was done by age and sex. RESULTS: Fifty-one percent of subjects were female, and 52.7% were from public institutions. WC (p=0.001) and WHR (p=0.0001) were statistically higher in boys. With advancing age, WC increased in both sexes, while WHR showed the opposite behavior (p=0.0001 for both). The 90th percentile (pc) for WC ranged from 69.7 and 83.6 cm in girls and from 69.2 and 86.7 cm in boys. The 90th pc values of WHR ranged from 0.79 and 0.91 in girls and from 0.86 and 0.93 in boys. Overall, our WC and WHR values were lower than North American values and similar to those of some Latin American references. CONCLUSION: Percentile reference charts for WC and WHR specific for age and sex, obtained from a representative sample of children and adolescents from Mérida, Venezuela, are provided. They may be used regionally, both for individual assessment and to implement prevention policies.

Occupational exposure to organophosphate and carbamate pesticides affects sperm chromatin integrity and reproductive hormone levels among Venezuelan farm workers.

OBJECTIVES: Several reports suggest that chronic pesticide exposure may affect semen quality and male fertility in humans. The objective of this study was to evaluate the association between occupational exposure to organophosphate (OP) and carbamate (CB) pesticides and semen quality, as well as levels of reproductive and thyroid hormones of Venezuelan farm workers. METHODS: Thirty-five healthy men (unexposed group) and 64 male agricultural workers (exposed group) were recruited for clinical evaluation of fertility status. Fresh semen samples were evaluated for sperm quality and analyzed for DNA fragmentation index (DFI) by flow cytometry. Pesticide exposure was assessed by measuring erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE) with a Test-mate ChE field kit. Serum levels of total testosterone (Tt), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH) and free thyroxine (FT4) were analyzed using enzyme immunoassay kits. RESULTS: Evidence of pesticide exposure was found in 87.5% of farmers based on AChE and BuChE inhibition. Significant increments were observed in sperm DFI with significant decreases in some semen parameters. DFI was negatively correlated with BuChE, sperm concentration, morphology and vitality in these workers. The levels of Tt, PRL, FT4 and TSH appeared to be normal; however, there was a tendency for increased LH and FSH levels in exposed workers. CONCLUSIONS: Our results confirm the potential impact of chronic occupational exposure to OP/CB pesticides on male reproductive function, which may cause damage to sperm chromatin, decrease semen quality and produce alterations in reproductive hormones, leading to adverse reproductive health outcomes.

Terapéutica en bocio multinodular (bmn): Protocolo del servicio de endocrinología del Instituto Autónomo Hospital Universitario de los Andes

La enfermedad tiroidea nodular benigna constituye un desorden tiroideo heterogéneo, el cual tiene una alta prevalencia en áreas con déficit de yodo. En países con estas características, la prevalencia de esta entidad alcanza el 30% de la población entre los 18 y 65 años, siendo más frecuente en el sexo femenino. Las características clínicas en un paciente con bocio multinodular (BMN) dependen del aumento del tamaño de la tiroides y la presencia de tirotoxicosis en el caso de BMN tóxico (BMNT). La evaluación clínica del tamaño, morfología y función de la glándula tiroides tiene baja sensibilidad, por lo que esto debe ser complementado con los parámetros de laboratorio como perfil tiroideo, estudio ecográfico que aporta información sobre tamaño, número de nódulos, características ecográficas de los mismos, así como, la posibilidad de realizar punción aspiración de los nódulos tiroideos sospechosos de malignidad. En ausencia de hallazgos clínicos, ecográficos y citológicos de malignidad, la selección de la mejor opción terapéutica dependerá de diversos factores incluyendo tamaño y localización del bocio, la presencia y severidad de síntomas compresivos y la función tiroidea; por tanto el tratamiento del BMN sigue siendo controvertido en la actualidad. En pacientes asintomáticos, con bocio de pequeño tamaño y citología negativa se recomienda observación y seguimiento. Así mismo, existen otras alternativas de tratamiento tales como el yodo radiactivo y la resección quirúrgica de la glándula con distintas modalidades. En la presente revisión se hace un resumen de las generalidades sobre BMN, su abordaje diagnóstico así como las distintas opciones terapéuticas.

Benign nodular thyroid disease constitutes a heterogeneous thyroid disorder, which is highly prevalent in iodine-deficient areas. In countries with these characteristics, the prevalence of this entity is 30% of the population between 18 and 65, being more common in females. Clinical features in a patient with multinodular goiter (MNG) can be attributed to thyroid enlargement and the presence of thyrotoxicosis in the case of toxic MNG (TMNG). Clinical evaluation of the size, morphology and function of the thyroid gland has a low sensitivity, so this should be supplemented with laboratory parameters such as thyroid profile, ultrasound examination that provides information on size, number of nodules, and other characteristics to decide the possibility of aspiration of thyroid nodules suspicious of malignancy. In the absence of clinical, ultrasound and cytological malignancy, selecting the best treatment option depends on several factors including size and location of the goiter, the presence and severity of compressive symptoms and thyroid function; therefore MNG treatment remains controversial today. In asymptomatic patients with a small goiter and negative cytology, a follow-up observation is recommended. Likewise, there are other treatment options such as radioactive iodine and surgical resection of the gland, with different modalities. The present review summarize the generalities on MNG, its diagnostic approach and the various treatment options.

Manejo de pacientes con acromegalia: Guías Clínicas del Servicio de Endocrinología del Instituto Autónomo Hospital Universitario De Los Andes

La acromegalia es una enfermedad caracterizada por un exceso de secreción de hormona de crecimiento (GH) y concentraciones circulantes elevadas del factor de crecimiento semejante a la insulina tipo 1 (IGF-1). Esta enfermedad presenta una elevada morbilidad y mortalidad asociada a complicaciones cardiovasculares, respiratorias y metabólicas. El aspecto facial es característico e incluye ensanchamiento y engrosamiento de la nariz, pómulos prominentes, abultamiento frontal y prognatismo. El diagnóstico clínico es confirmado por un incremento en los niveles séricos de GH e IGF-1. El objetivo terapéutico es disminuir dichos niveles y aminorar los síntomas del paciente. Las opciones terapéuticas incluyen cirugía, tratamiento médico y radioterapia. En el presente artículo, basados en niveles de evidencia científica y en la experiencia clínica de la Unidad de Endocrinología del IAHULA, se presenta el protocolo para el manejo de la acromegalia, el cual consta de los criterios diagnósticos, el manejo clínico, el tratamiento y seguimiento de esta condición.

Acromegaly is a disease characterized by excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) concentrations. This disease has an increased morbidity and mortality associated with cardiovascular, respiratory, and metabolic complications. The facial aspect is characteristic and includes a widened and thickened nose, prominent cheekbones, forehead bulges, and prognathism. The clinical diagnosis is confirmed by an increased serum GH and IGF-1 concentration. Therapy for acromegaly is targeted at decreasing GH and IGF-1 levels and ameliorating patient’s symptoms. The therapeutic options include surgery, medical therapies, and radiotherapy. In this paper, based on levels of scientific evidence and clinical experience in the Unit of Endocrinology, IAHULA, we present the protocol for the management of acromegaly, which includes: diagnostic criteria, clinical management, treatment and surveillance of this condition.

Efectos de exposición ocupacional a plaguicidas sobre la integridad de la cromatina espermática

Objetivo: Evaluar los efectos de la exposición a plaguicidas organofosforados y carbamatos sobre la integridad de cromatina espermática en trabajadores agrícolas. Métodos: Se evaluaron 64 trabajadores del campo, con edades entre 18 y 55 años, de la comunidad rural de Bailadores, Municipio Rivas Dávila, Estado Mérida, Venezuela, expuestos directamente a plaguicidas. Para el diagnóstico de exposición a plaguicidas, fueron determinados los niveles de las colinesterasas eritrocitaria (AChE) y plasmática (PChE). Para evaluar la fertilidad masculina, a cada trabajador se le realizó seminograma y se les evaluó la integridad de la estructura de cromatina espermática mediante la técnica "Sperm Chromatin Structure Assay" (SCSA). Resultados: El 25% de los trabajadores agrícolas presentó niveles deprimidos de AChE y el 83% con niveles anormales de PChE, con una reducción <75% del nivel normal. El grupo con edades entre 18 y 28 años fue el más afectado. Diferencias significativas fueron obtenidas en los promedios de los niveles de colinesterasas entre los casos normales y alterados, tanto para AChE (3,95±0,42 vs. 2,72±0,16, ρ<0,0001) así como para PChE (2,08±0,25 vs. 1,43±0,32, ρ<0,0001). El 69,7% de los trabajadores con niveles anormales de PChE presentó alteración en el ADN espermático. Se encontró una correlación negativa significativa entre el Índice de Fragmentación de ADN (IDF) espermático y los niveles de PChE (ρ=0,02). Conclusiones: En trabajadores agrícolas expuestos directamente a plaguicidas organofosforados y carbamatos, un alto porcentaje presentó niveles anormalmente deprimidos de PChE, junto con alteración en el ADN espermático. Estos resultados demuestran que los trabajadores se encuentran con alto riesgo de exposición a los efectos tóxicos de plaguicidas, lo cual efectivamente se comprueba con los resultados de análisis de las enzimas colinesterasas y la aplicación de la técnica SCSA para determinar la integridad de la cromatina espermática.

Objective: To evaluate the effects of exposure to organophosphate and carbamate pesticides on the integrity of sperm chromatin in farm workers. Methods: In this study, we evaluated 64 farm workers, aged between 18 and 55 years, from the rural community of Bailadores, Municipality of Rivas Dávila, Mérida State, Venezuela, directly exposed to pesticides. For the diagnosis of pesticide exposure, levels of erythrocyte (AChE) and plasma (PchE) cholinesterases. were determined. To evaluate male fertility, each worker underwent semen analysis and the integrity of sperm chromatin structure was assessed using the "Sperm Chromatin Structure Assay (SCSA) technique. Results: The results of this study showed that 25% of agricultural workers had depressed levels of AChE and a majority, 83%, was found with abnormal levels of PChE. The group with corresponding ages between 18 and 28 years was the most affected. Significant differences were obtained in the average cholinesterase levels between normal and altered cases for both AChE (3.95 ± 0.42 vs. 2.72 ± 0.16, p < 0.0001) and PChE (2.08 ± 0.25 vs. 1.43 ± 0.32, ρ < 0.0001). Among workers with abnormal PChE levels, 69.7% presented alterations of sperm chromatin structure. There was a significant negative correlation between sperm DNA Fragmentation Index (DFI) and the levels of PChE (ρ = 0.02). Conclusions: In agricultural workers directly exposed to organophosphate and carbamate pesticides, a high percentage showed abnormally depressed PChE, along with altered sperm chromatin structure. These results show that farm workers are at high risk of exposure to the toxic effects of pesticides, which were effectively demonstrated with the results of analysis of cholinesterase enzymes and the implementation of the SCSA technique for determining the status of the sperm chromatin structure.

[Evaluation of the quality of the human spermatozoon: comparison between spermatic DNA integrity and semen variables]. / Evaluación de la calidad del espermatozoide humano: comparación entre la integridad del ADN espermático y variables del semen.

Semen analysis does not have an absolute predictive value on fertility, however it is a reflection of male fertility potential, which is related to its spermatozoa quality and other semen variables. Great variability in human semen parameters has been demonstrated within a single individual, an observation that could explain why a male with low semen quality can successfully fertilize an egg. Although conventional semen analysis, such as sperm concentration, motility and morphology, provide important information about the clinical status of male fertility, new procedures to predict the sperm functional capability have been developed in the last decade, such as analysis of nuclear DNA integrity, which have improved considerably the clinical diagnosis of male infertility, and increased the knowledge about spermatozoa function. DNA fragmentation consist in interruptions, both in single and double DNA strains, that frequently occur in sperm samples from infertile patients. We have conducted a clinical study in semen samples from patients who have attended the Andrology laboratory of the University of Los Andes, between March 2007 and March 2009. The aim of this study was to compare sperm DNA integrity, analyzed by flow cytometry, with traditional semen parameters. Our results show remarkable correlations between conventional human semen variables and sperm chromatin integrity, contributing to asses an integral evaluation of sperm quality allowing the analysis of its fertilizing potential in clinical studies.