The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT).

BACKGROUND: Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient. METHODS: Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT. DISCUSSION: The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663828 . The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis.

Morphological and molecular characterization of the parasite Dipylidium caninum infecting an infant in Colombia: a case report.

BACKGROUND: Dipylidium caninum is the causal agent of dipylidiasis affecting mainly cats and dogs worldwide. Human cases of dipylidiasis are rare, and the diagnosis is prevalently based on morphological features of the parasite. Here we report the diagnosis of dipylidiasis through morphological and molecular characterization of D. caninum infecting an 11-month-old boy in Cajicá, Colombia. METHODS: Fresh faecal samples were obtained from the infant, and morphological identification of the parasite was performed through faecal smears. DNA was extracted from proglottids and used in PCR analyses for amplification of a 653-bp fragment of the nuclear ribosomal RNA (rRNA) encoding the 28S rRNA gene. A phylogeny study to better characterize the obtained DNA sequence was inferred using the maximum likelihood method and the Tamura-Nei model. RESULTS: After morphological and molecular analyses, D. caninum was identified as the etiological agent causing the infection in the infant. Results of phylogenetical analyses showed that the obtained sequence clusters within the feline genotype clade. After the diagnosis of the parasite, effective treatment with praziquantel was administered to the infant. CONCLUSIONS: This is the third human case of dipylidiasis reported in Colombia, and the first study in South America to provide a molecular identification of D. caninum.

Using coding and non-coding rare variants to target candidate genes in patients with severe tinnitus.

Tinnitus is the phantom percept of an internal non-verbal set of noises and tones. It is reported by 15% of the population and it is usually associated with hearing and/or brain disorders. The role of structural variants (SVs) in coding and non-coding regions has not been investigated in patients with severe tinnitus. In this study, we performed whole-genome sequencing in 97 unrelated Swedish individuals with chronic tinnitus (TIGER cohort). Rare single nucleotide variants (SNV), large structural variants (LSV), and copy number variations (CNV) were retrieved to perform a gene enrichment analysis in TIGER and in a subgroup of patients with severe tinnitus (SEVTIN, n = 34), according to the tinnitus handicap inventory (THI) scores. An independent exome sequencing dataset of 147 Swedish tinnitus patients was used as a replication cohort (JAGUAR cohort) and population-specific datasets from Sweden (SweGen) and Non-Finish Europeans (NFE) from gnomAD were used as control groups. SEVTIN patients showed a higher prevalence of hyperacusis, hearing loss, and anxiety when they were compared to individuals in the TIGER cohort. We found an enrichment of rare missense variants in 6 and 8 high-constraint genes in SEVTIN and TIGER cohorts, respectively. Of note, an enrichment of missense variants was found in the CACNA1E gene in both SEVTIN and TIGER. We replicated the burden of missense variants in 9 high-constrained genes in the JAGUAR cohort, including the gene NAV2, when data were compared with NFE. Moreover, LSVs in constrained regions overlapping CACNA1E, NAV2, and TMEM132D genes were observed in TIGER and SEVTIN.

A novel nonsense variant in the CENPP gene segregates in a Swiss family with autosomal dominant low-frequency sensorineural hearing loss.

Low-frequency sensorineural hearing loss (SNHL) is a rare hearing impairment affecting frequencies below 1000 Hz, previously associated with DIAPH1, WSF1, MYO7A, TNC, SLC26A4 or CCDC50 genes. By exome sequencing, we report a novel nonsense variant in CENPP gene, segregating low-frequency SNHL in five affected members in a Swiss family with autosomal dominant inheritance pattern. Audiological evaluation showed up-sloping audiometric configuration with mild-to-moderate losses below 1000 Hz, that progresses to high-frequencies over time. Protein modeling shows that the variant truncates five amino acids at the end, losing electrostatic interactions that alter protein stability. CENPP gene is expressed in the supporting cells of the organ of Corti and takes part as a subunit of the Constitutive Centromere Associated Network in the kinetochore, that fixes the centromere to the spindle microtubules. We report CENPP as a new candidate gene for low-frequency SNHL. Further functional characterization might enable us to elucidate its molecular role in SNHL.

Multicenter international assessment of a SARS-CoV-2 RT-LAMP test for point of care clinical application.

Continued waves, new variants, and limited vaccine deployment mean that SARS-CoV-2 tests remain vital to constrain the coronavirus disease 2019 (COVID-19) pandemic. Affordable, point-of-care (PoC) tests allow rapid screening in non-medical settings. Reverse-transcription loop-mediated isothermal amplification (RT-LAMP) is an appealing approach. A crucial step is to optimize testing in low/medium resource settings. Here, we optimized RT-LAMP for SARS-CoV-2 and human ß-actin, and tested clinical samples in multiple countries. "TTTT" linker primers did not improve performance, and while guanidine hydrochloride, betaine and/or Igepal-CA-630 enhanced detection of synthetic RNA, only the latter two improved direct assays on nasopharygeal samples. With extracted clinical RNA, a 20 min RT-LAMP assay was essentially as sensitive as RT-PCR. With raw Canadian nasopharygeal samples, sensitivity was 100% (95% CI: 67.6% - 100%) for those with RT-qPCR Ct values ≤ 25, and 80% (95% CI: 58.4% - 91.9%) for those with 25 < Ct ≤ 27.2. Highly infectious, high titer cases were also detected in Colombian and Ecuadorian labs. We further demonstrate the utility of replacing thermocyclers with a portable PoC device (FluoroPLUM). These combined PoC molecular and hardware tools may help to limit community transmission of SARS-CoV-2.

Unification of Treatments and Interventions for Tinnitus Patients (UNITI): a study protocol for a multi-center randomized clinical trial.

BACKGROUND: Tinnitus represents a relatively common condition in the global population accompanied by various comorbidities and severe burden in many cases. Nevertheless, there is currently no general treatment or cure, presumable due to the heterogeneity of tinnitus with its wide variety of etiologies and tinnitus phenotypes. Hence, most treatment studies merely demonstrated improvement in a subgroup of tinnitus patients. The majority of studies are characterized by small sample sizes, unstandardized treatments and assessments, or applications of interventions targeting only a single organ level. Combinatory treatment approaches, potentially targeting multiple systems as well as treatment personalization, might provide remedy and enhance treatment responses. The aim of the present study is to systematically examine established tinnitus therapies both alone and in combination in a large sample of tinnitus patients. Further, it wants to provide the basis for personalized treatment approaches by evaluating a specific decision support system developed as part of an EU-funded collaborative project (Unification of treatments and interventions for tinnitus patients; UNITI project). METHODS/STUDY DESIGN: This is a multi-center parallel-arm randomized clinical trial conducted at five different clinical sites over the EU. The effect of four different tinnitus therapy approaches (sound therapy, structured counseling, hearing aids, cognitive behavioral therapy) applied over a time period of 12 weeks as a single or rather a combinatory treatment in a total number of 500 chronic tinnitus patients will be investigated. Assessments and interventions are harmonized over the involved clinical sites. The primary outcome measure focuses on the domain tinnitus distress assessed via the Tinnitus Handicap Inventory. DISCUSSION: Results and conclusions from the current study might not only provide an essential contribution to combinatory and personalized treatment approaches in tinnitus but could also provide more profound insights in the heterogeneity of tinnitus, representing an important step towards a cure for tinnitus. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663828 . Registered on 11 December 2020.

Antiparasitic Effects of Potentially Toxic Beetles (Tenebrionidae and Meloidae) from Steppe Zones.

Arthropods and specifically beetles can synthesize and/or sequester metabolites from dietary sources. In beetle families such as Tenebrionidae and Meloidae, a few studies have reported species with toxic defensive substances and antiparasitic properties that are consumed by birds. Here we have studied the antiparasitic activity of extracts from beetle species present in the habitat of the Great Bustard (Otis tarda) against four pathogen models (Aspergillus niger, Meloidogyne javanica, Hyalomma lusitanicum, and Trichomonas gallinae). The insect species extracted were Tentyria peiroleri, Scaurus uncinus, Blaps lethifera (Tenebrionidae), and Mylabris quadripunctata (Meloidae). M. quadripunctata exhibited potent activity against M. javanica and T. gallinae, while T. peiroleri exhibited moderate antiprotozoal activity. The chemical composition of the insect extracts was studied by gas chromatography coupled with mass spectrometry (GC-MS) analysis. The most abundant compounds in the four beetle extracts were hydrocarbons and fatty acids such as palmitic acid, myristic acid and methyl linoleate, which are characteristic of insect cuticles. The presence of cantharidin (CTD) in the M. quadripunctata meloid and ethyl oleate (EO) in T. peiroleri accounted for the bioactivity of their extracts.

Bifidobacterium breve CNCM I-4035, Lactobacillus paracasei CNCM I-4034 and Lactobacillus rhamnosus CNCM I-4036 Modulate Macrophage Gene Expression and Ameliorate Damage Markers in the Liver of Zucker-Lepr fa/fa Rats.

Non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions worldwide. We have previously reported that the probiotic strains Bifidobacterium breve CNCM I-4035, Lactobacillus paracasei CNCM I-4034 and Lactobacillus rhamnosus CNCM I-4036 exert anti-inflammatory effects in the intestine of Zucker-Lepr fa/fa rats. In this work, we focused on their hepatic effects. M1 macrophages are related to inflammation and NAFLD pathogenesis, whereas M2 macrophages release anti-inflammatory mediators. We evaluated the effects of these 3 strains on macrophage polarization, inflammation and liver damage of Zucker-Lepr fa/fa rats. The animals received either a placebo or 1010 CFU of probiotics orally for 30 days. Nos2 and Cd86 mRNA levels were determined as markers of M1 macrophages, and Cd163 and Arg1 as M2 markers, respectively, by qRT-PCR. Liver damage was determined by lipid peroxidation, leukocyte infiltration and myeloperoxidase activity. We evaluated a panoply of circulating chemokines, the hepatic ratio P-Akt/Akt, NF-kB and P-NF-kB protein levels. All 3 probiotic strains modulated macrophage polarization in liver and circulating levels of inflammation-related mediators. L. paracasei CNCM I-4034 increased the ratio P-Akt/Akt and NF-kB protein levels. B. breve CNCM I-4035, L. paracasei CNCM I-4034 and L. rhamnosus CNCM I-4036 decreased both pro-inflammatory macrophage gene expression and leukocyte infiltration in the liver.

Genome-Wide Identification and Functional Classification of Tomato (Solanum lycopersicum) Aldehyde Dehydrogenase (ALDH) Gene Superfamily.

Aldehyde dehydrogenases (ALDHs) is a protein superfamily that catalyzes the oxidation of aldehyde molecules into their corresponding non-toxic carboxylic acids, and responding to different environmental stresses, offering promising genetic approaches for improving plant adaptation. The aim of the current study is the functional analysis for systematic identification of S. lycopersicum ALDH gene superfamily. We performed genome-based ALDH genes identification and functional classification, phylogenetic relationship, structure and catalytic domains analysis, and microarray based gene expression. Twenty nine unique tomato ALDH sequences encoding 11 ALDH families were identified, including a unique member of the family 19 ALDH. Phylogenetic analysis revealed 13 groups, with a conserved relationship among ALDH families. Functional structure analysis of ALDH2 showed a catalytic mechanism involving Cys-Glu couple. However, the analysis of ALDH3 showed no functional gene duplication or potential neo-functionalities. Gene expression analysis reveals that particular ALDH genes might respond to wounding stress increasing the expression as ALDH2B7. Overall, this study reveals the complexity of S. lycopersicum ALDH gene superfamily and offers new insights into the structure-functional features and evolution of ALDH gene families in vascular plants. The functional characterization of ALDHs is valuable and promoting molecular breeding in tomato for the improvement of stress tolerance and signaling.

Assessing the Risk of Secondary Transfer Via Fingerprint Brush Contamination Using Enhanced Sensitivity DNA Analysis Methods.

Experiments were performed to determine the extent of cross-contamination of DNA resulting from secondary transfer due to fingerprint brushes used on multiple items of evidence. Analysis of both standard and low copy number (LCN) STR was performed. Two different procedures were used to enhance sensitivity, post-PCR cleanup and increased cycle number. Under standard STR typing procedures, some additional alleles were produced that were not present in the controls or blanks; however, there was insufficient data to include the contaminant donor as a contributor. Inclusion of the contaminant donor did occur for one sample using post-PCR cleanup. Detection of the contaminant donor occurred for every replicate of the 31 cycle amplifications; however, using LCN interpretation recommendations for consensus profiles, only one sample would include the contaminant donor. Our results indicate that detection of secondary transfer of DNA can occur through fingerprint brush contamination and is enhanced using LCN-DNA methods.

Análisis de costos de esquemas de transferencia de embriones bovinos utilizados en Colombia / Custo análise de esquemas de transferência de embriões de bovinos utilizado na Colômbia / Cost analysis of protocols for transfer of bovine embryos used in Colombia

En el presente trabajo se presenta el análisis de los costos de tres esquemas de transferencia de embriones aplicados en Colombia, realizado con base en la cotización de los productos en las casa comerciales a precios actualizados del año 2008. Las fuentes de variación consideradas en el análisis fueron las siguientes:1) superovulación (SOV) de donadoras, 2) sincronización de las receptoras, y 3) mano de obra. Los esquemas comparados fueron:esquema 1 (E1), sincronización con implantes de progesterona, dosis constante de FSH y sincronización de la ovulación con GnRH, seguidas de la IA; esquema 2 (E2), sincronización con prostaglandinas, dosis constante de FSH, LH e inseminación; y esquema 3 (E3), sincronización con progesterona, dosis constante de FSH, prostaglandina, GnRH (36h), LH e IA. El costo por embrión transferible producido se calculó con base en 6.3, 6.6, y 10.3 embriones transferibles/lavado, para los esquemas 1, 2, y 3, respectivamente; cuatro lavados/donadora/año, y 50 o 100% de embriones implantados, para los tres esquemas. Los costos estimados por embrión transferible, asumiendo un 100% de tasas de gestación fueron:US 239.8 ($ 479.585.7), US 156 ($ 312.879.0), y US 115.1 ($ 230.186.5), para los esquemas E1, E2 y E3, respectivamente, sin diferencias estadísticas significativas (p>0.05) en los componentes de costos entre esquemas. Los costos aumentaron a US 359.7 ($719.378.6), US 234.7 ($ 469.318.4), y US 172.6 ($ 345.279.7), respectivamente, cuando se incluyeron las pérdidas por embriones transferidos no implantados (50%). En el trabajo se discuten otros costos fijos del proceso de TE que fueron invariables para los tres esquemas. Hasta donde se pudo consultar la literatura, este es el primer reporte que hace un análisis de costos de programa de TE en Colombia. Este trabajo aporta elementos del sistema de costos que se proponen para el cálculo de costos en programas de transferencia de embriones.

In this work an estimated calculation of the cost of three of the most common protocols for superovulation and embryo trasnsfer in Colombia is presented. Estimate costs were defined according to commercial avalilable products at december 2005, taking into account the following sources of costs: 1) Superovulation of donor cows, 2) sinchronization of receptor cows, and 3) personnel. Hormonal schedules that were analyzed included: schedule 1 (S1), sinchronization with progesterone implants, FSH (continuous dose) GnRH (synchronization of ovulation), and AI; schedule 2 (S2), sinchronization with two dose prostaglandins, FSH (continuous dose), LH source and insemination; and schedule 3 (S3), sinchronization with progesterone implants, FSH (continuous dose), prostaglandin, GnRH (36h) after, and AI. Costs were calculated on the basis of 6.3, 6.6, and 10.3 transferable embryos/flush, for schedule 1, 2 and 3, respectively; flushes/donor/year (n = 4), and global pregnancy rate (50 or 100%). The estimated costs for transferable embryo were US 239.8 ($ 479.585.7), US 156 ($ 312.879.0), y US 115.1 ($ 230.186.5) for S1, S2, and S3, respectively. No statistically significant differences (p>0.05) between schedules were found for cost components. Average costs/transferable embryo were increased to US 359.7 ($719.378.6), US 234.7 ($ 469.318.4), y US 172.6 ($ 345.279.7), respectively, when 50% of transferred embryo losses were included in the analysis. To our knowledge, this is the first report on estimated costs for embryo transfer in Colombia. In this work several cost components for calculating the cost of ET according to each hormonal schedule are provided.

Neste trabalho apresenta a análise dos custos de transferência embrionária três esquemas utilizados na Colômbia, feita com base no preço de produtos comerciais na casa dos preços em 2005. Os regimes avaliados hormônio-cio referência ao: esquema 1 (E1), sincronização com progesterona implantes, estável dose de FSH e de calendário da ovulação com GnRH, seguido pelo IA; esquema 2 (E2), sincronização com prostaglandinas, estável dose de FSH, LH e de inseminação; e esquema 3 (E3), sincronização com progesterona, estável dose de FSH, prostaglandina, GnRH (36h), LH e AI. As fontes de variação consideradas na análise foram as seguintes: 1) superovulação (SOV) da doadora, 2) sincronização do destinatário, ET 3) personel. Como fontes de variação na análise foram consideradas as seguintes: 6.3, 6.6 et 10.3 embriões transferibles produzidos/lavagem, lavados/doadora/ano (n = 4), e 50 o 100% taxa de gestação. Os custos estimados para a implantação do embrião para E1, E2 e E3, foram E.U. $ 239.8 ($ 479.585.7), E.U. 156 ($ 312.879.0), e E.U. 115.1 ($ 230.186.5), respectivamente, que passou a assumir as perdas embriões não implantados (50% aprox.) e receber o valor de E.U. $ 359.7 ($719.378.6), E.U. $ 234.7 ($ 469.318.4), e E.U. $ 172.6 ($ 345.279.7). No que diz respeito poderia consultar a literatura, este é o primeiro relatório que uma análise de custos TE programa na Colômbia. Este trabalho traz elementos do sistema de custos que são propostos para o cálculo dos custos de programas de transferência embrionária.

Racionalidad de los esquemas de superovulación y sincronización en la transferencia de embriones en bovinos: ¿terapéutica basada en la evidencia o ausencia de ética / Racionalidade dos esquemas de superovulação e sincronização na transferência de embriões em bovinos: terapêutica baseada em provas ou falta de ética / Rational of superovulation and synchronization protocols for bovine embryo transfer ¿Evidence-based therapeutics or lack of ethics

Desde el inicio del uso intensivo de la transferencia de embriones (TE) en Colombia, los esquemas hormonales para la inducción de la superovulación (SOV) en las donadoras y la sincronización de las receptoras (SR), se han aplicado de conformidad con los estudios realizados en otras partes del mundo. Una gran cantidad de variaciones en los esquemas está disponible en la literatura, cuya aplicación no ha obedecido al diseño de estudios clínicos completos, sino que se basan en el principio de la utilización de productos hormonales por su presumida farmacología, sin hacer seguimiento ni de su farmacocinética ni de los potenciales efectos colaterales adversos en la fertilidad. Los esquemas utilizados podrían tener efectos colaterales asociados de manera directa o indirecta con el uso incontrolado de hormonas exógenas, o con el tiempo durante el cual las donadoras o receptoras son sometidas a los tratamientos, olvidando aspectos fundamentales de la ética en la experimentación animal. La proliferación de esquemas de SOV y de SR busca mejorar las tasas de respuesta en la producción de embriones de calidad I y II (transferibles o congelables), y aumentar las tasas de gestación de los embriones transferidos, pero los resultados no han mejorado significativamente a lo largo de los últimos 20, situación común en todos los países del mundo. En el presente trabajo se hace una revisión sobre el uso de hormonas en los esquemas de SOV y sincronización de receptoras, con énfasis en la racionalidad del uso de las hormonas y los resultados obtenidos. Finalmente, se proponen varios elementos de juicio para plantear una discusión sobre la racionalidad y la bioética de los esquemas utilizados en la TE.

Since the beginning of the use of bovine embryo transfer (ET) in Colombia, hormonal protocols for superovulation (SOV) of donors and for synchronization of recipients (RS) have been used in accordance with protocols reported elsewhere. Several variations of ET protocols have been reported most of they not based in controlled clinical studies but in the supposed pharmacological mechanisms of action of the used hormones, neither with pharmacokinetic studies nor considering the potential collateral effects on cow’s fertility. Such collateral effects could be directly or indirectly related with the uncontrolled use of exogenous hormones, or with the time-related additional open days of donor and recipients, without considering the bioethics for animal experimentation. The huge proliferation of protocols for SOV and RS aims for improving both grade I and II (transferable or freezable embryos) embryo yield per transfer, and pregnancy rates for transferred embryos, without having achieved significant improvements during the last 20 years all around the world. In the present review we critic the use of exogenous hormones in bovine ET with emphasis in the rationality of indiscriminating use of exogenous hormones and embryo yield. Finally, we suggest several arguments on the bioethics of the protocols for SOV and RS in bovine ET.

Desde o início da transferência de embriãos (TE) na Colômbia, nos esquemas hormonais para a indução da superovulação (SOV) no dadora e sincronização do receptor (SR), foram executadas de acordo com estudos realizados noutras partes do mundo. Um lote de variações nos esquemas está disponível na literatura, cuja execução não tenha obedecido a concepção dos estudos clínicos completos, sem controlo ou a sua farmacocinética ou potenciais efeitos colaterais adversos sobre a fertilidade. Os esquemas utilizados poderiam ter efeitos secundários associados direta ou indiretamente com o uso descontrolado de hormônios exógenos, ou o tempo durante o qual o doador ou receptor são submetidos a tratamento, ignorando os aspectos-chave da ética na experimentação animal. A proliferação de esquemas SOV e SR pretendem melhorar as taxas de resposta na produção de embriões qualidade I e II (transferíveis ou congeladas) eu aumento das taxas de gravidez de embriões transferidos, mas os resultados não têm melhorado significativamente ao longo dos últimos 20, uma situação comum em todos os países do mundo. Neste documento é uma revisão sobre o uso de hormônios nas formas de SOV e sincronização de receptores, com ênfase na utilização racional das hormonais e os resultados obtidos. Por último, propomos vários elementos de juízo para levantar uma discussão sobre a racionalidade e bioética dos esquemas utilizados na TE.

Quistes esplénicos no parasitarios / Nonparasitic splenic cysts

Los quistes esplénicos no parasitarios son poco frecuentes. Sin embargo, es posible clasificarlos en primarios y secundarios dependiendo de la presencia o ausencia de revestimiento epitelial. Los síntomas tienen relación con el tamaño del quiste. Aunque no hay información basada en la evidencia que defina el manejo quirúrgico óptimo, se recomiendan las técnicas de cirugía conservadora (preservación del bazo) en quistes no parasitarios. En la actualidad, la cirugía por laparoscopia es una alternativa. Se informan dos casos de quiste esplénico no parasitario. Ninguna de las pacientes registra antecedente de trauma. Se practica esplenectomía total por un quiste central y esplenectomía parcial por un quiste en el polo superior. Una de las pacientes presentó trombosis de la vena porta y esplénica posoperatoria.

Manejo de la insuficiencia adrenal / Approach to the handling of adrenal insufficiency

La insuficiencia adrenal (IA) se refiere a la hipofunción de dicha glándula debida a causas tanto primarias como secundarias, que resultan en niveles plasmáticos inadecuados de cortisol, andrógenos adrenales y adicionalmente, en la falla primaria de mineralocorticoides. Sus manifestaciones inespecíficas dificultan o retrasan con frecuencia el diagnóstico y tratamiento oportuno, lo cual incrementa la morbilidad y eventualmente la mortalidad de estos pacientes.Se incluyen en este artículo: definición, epidemiología, causas, fisiopatología, clasificación, manifestaciones clínicas, diagnóstico y tratamiento de la IA. Además se consideran algunas situaciones especiales como la IA en el paciente críticamente enfermo y en la mujer gestante. Finalmente se hace especial énfasis en un algoritmo diagnóstico, con la finalidad de facilitarle al médico general un enfoque ágil y oportuno de los pacientes con este problema endocrino.

The term adrenal insufficiency refers to the hypofunction of this gland. From the etiologic point of view it may be either primary or secondary. This insufficiency manifests as inadequate serum levels of cortisol and adrenal androgens in the secondary form and of these and mineralocorticoids in the primary one. Clinical manifestations are often nonspecific and, consequently, diagnosis may be difficult to establish and treatment may be delayed with increased morbidity and mortality. This article on adrenal insufficiency includes its definition, epidemiology, etiology, physiopathology, classification, clinical presentation, diagnostic criteria and treatment guidelines. Besides, some special situations like critically ill patients and pregnant women are given special consideration. Emphasis is done on a diagnostic algorithm to make it easier for general practitioners the approach to patients with this endocrine disorder.