Rapid Protein-Ligand Affinity Determination by Photoinduced Hyperpolarized NMR.

The binding affinity determination of protein-ligand complexes is a cornerstone of drug design. State-of-the-art techniques are limited by lengthy and expensive processes. Building upon our recently introduced novel screening method utilizing photochemically induced dynamic nuclear polarization (photo-CIDNP) NMR, we provide the methodological framework to determine binding affinities within 5-15 min using 0.1 mg of protein. The accuracy of our method is demonstrated for the affinity constants of peptides binding to a PDZ domain and fragment ligands binding to the protein PIN1. The method can also be extended to measure the affinity of nonphoto-CIDNP-polarizable ligands in competition binding experiments. Finally, we demonstrate a strong correlation between the ligand-reduced signals in photo-CIDNP-based NMR fragment screening and the well-established saturation transfer difference (STD) NMR. Thus, our methodology measures protein-ligand affinities in the micro- to millimolar range in only a few minutes and informs on the binding epitope in a single-scan experiment, opening new avenues for early stage drug discovery approaches.

Ultrafast Fragment Screening Using Photo-Hyperpolarized (CIDNP) NMR.

While nuclear magnetic resonance (NMR) is regarded as a reference in fragment-based drug design, its implementation in a high-throughput manner is limited by its lack of sensitivity resulting in long acquisition times and high micromolar sample concentrations. Several hyperpolarization approaches could, in principle, improve the sensitivity of NMR also in drug research. However, photochemically induced dynamic nuclear polarization (photo-CIDNP) is the only method that is directly applicable in aqueous solution and agile for scalable implementation using off-the-shelf hardware. With the use of photo-CIDNP, this work demonstrates the detection of weak binders in the millimolar affinity range using low micromolar concentrations down to 5 µM of ligand and 2 µM of target, thereby exploiting the photo-CIDNP-induced polarization twice: (i) increasing the signal-to-noise by one to two orders in magnitude and (ii) polarization-only of the free non-bound molecule allowing identification of binding by polarization quenching, yielding another factor of hundred in time when compared with standard techniques. The interaction detection was performed with single-scan NMR experiments of a duration of 2 to 5 s. Taking advantage of the readiness of photo-CIDNP setup implementation, an automated flow-through platform was designed to screen samples at a screening rate of 1500 samples per day. Furthermore, a 212 compounds photo-CIDNP fragment library is presented, opening an avenue toward a comprehensive fragment-based screening method.

A Benchmark Study of Protein-Fragment Complex Structure Calculations with NMR2.

Protein-fragment complex structures are particularly sought after in medicinal chemistry to rationally design lead molecules. These structures are usually derived using X-ray crystallography, but the failure rate is non-neglectable. NMR is a possible alternative for the calculation of weakly interacting complexes. Nevertheless, the time-consuming protein signal assignment step remains a barrier to its routine application. NMR Molecular Replacement (NMR2) is a versatile and rapid method that enables the elucidation of a protein-ligand complex structure. It has been successfully applied to peptides, drug-like molecules, and more recently to fragments. Due to the small size of the fragments, ca < 300 Da, solving the structures of the protein-fragment complexes is particularly challenging. Here, we present the expected performances of NMR2 when applied to protein-fragment complexes. The NMR2 approach has been benchmarked with the SERAPhic fragment library to identify the technical challenges in protein-fragment NMR structure calculation. A straightforward strategy is proposed to increase the method's success rate further. The presented work confirms that NMR2 is an alternative method to X-ray crystallography for solving protein-fragment complex structures.

Fragment Screening and Fast Micromolar Detection on a Benchtop NMR Spectrometer Boosted by Photoinduced Hyperpolarization.

Fragment-based drug design is a well-established strategy for rational drug design, with nuclear magnetic resonance (NMR) on high-field spectrometers as the method of reference for screening and hit validation. However, high-field NMR spectrometers are not only expensive, but require specialized maintenance, dedicated space, and depend on liquid helium cooling which became critical over the recurring global helium shortages. We propose an alternative to high-field NMR screening by applying the recently developed approach of fragment screening by photoinduced hyperpolarized NMR on a cryogen-free 80 MHz benchtop NMR spectrometer yielding signal enhancements of up to three orders in magnitude. It is demonstrated that it is possible to discover new hits and kick-off drug design using a benchtop NMR spectrometer at low micromolar concentrations of both protein and ligand. The approach presented performs at higher speed than state-of-the-art high-field NMR approaches while exhibiting a limit of detection in the nanomolar range. Photoinduced hyperpolarization is known to be inexpensive and simple to be implemented, which aligns greatly with the philosophy of benchtop NMR spectrometers. These findings open the way for the use of benchtop NMR in near-physiological conditions for drug design and further life science applications.

Biometric Registration to an HIV Research Study may Deter Participation.

Biometric registration may improve services associated with HIV research. A cross-sectional, observational survey was used to evaluate biometric fingerprint scanning for identification (ID) verification in the setting of an HIV prevention study. Survey outcomes were dichotomized (discouraged or not discouraged) by biometric scanning and statistical analyses were used to determine if participation decreased by greater than 10% overall and after stratifying by demographic variables and risk behaviors. 206 participants were recruited from a community-based HIV and sexual health research screening program. Participants completed a quantitative survey to assess their perceptions of biometric scanning for ID verification. The majority of participants (n = 160; 77.7%) indicated no deterrence from testing due to biometric scanning, yet a significant number (n = 45; 23.3%, P < .001) reported at least partial deterrence. Research using biometric scanning for ID verification may significantly limit access to HIV prevention services and may risk reducing meaningful participation among marginalized populations.

Molecular features toward high photo-CIDNP hyperpolariztion explored through the oxidocyclization of tryptophan.

Photo-chemically induced dynamic nuclear polarization (photo-CIDNP) is a promising solution to the inherent lack of sensitivity in NMR spectroscopy. It is particularly interesting in biological systems since it operates in water, at room temperature, and it can be repeated if the bleaching of the system can be controlled. However, the photo-CIDNP signal enhancement is well below those of other hyperpolarization techniques. While DNP, PHIP, and SABRE reach polarization enhancements of 103 to 104-fold, photo-CIDNP enhancement is typically only one order of magnitude for 1H and two orders of magnitude for 13C in the amino-acids tryptophan and tyrosine. Here we report on a photo-oxidation product of tryptophan that is strongly photo-CIDNP active under continuous wave light irradiation. In conjunction with the dye Atto Thio 12, a 1H signal enhancement of 120-fold was observed on a 600 MHz spectrometer, while at 200 MHz the enhancement was 380-fold. These enhancements in signal to noise correspond to a reduction in measurement time of 14 400-fold and 144 400-fold, respectively. The enhancement for 13C is estimated to be over 1200-fold at 600 MHz which corresponds to an impressive measurement time reduction of 1 440 000-fold. This photo-CIDNP active oxidation product of tryptophan has been identified to be 3α-hydroxypyrroloindole. The reasons for its improved signal enhancement compared to tryptophan have been further investigated.

Exploring Urological Experience in the COVID-19 Outbreak: American Confederation of Urology (CAU) Survey.

PURPOSE: To explore the current situation faced by Latin American urology departments during the COVID-19 Outbreak in terms of knowledge, actions, prioritization of urology practices, and implementation of internal clinical management protocols for inpatients and outpatients. MATERIAL AND METHODS: A non-validated, structured, self-administered, electronic survey with 35 closed multiple choice questions was conducted in Spanish, Portuguese, Italian, and English and Deutsch versions from April 1st to April 30th, 2020. The survey was distributed through social networks and the official American Confederation of Urology (CAU) website. It was anonymous, mainly addressed to Latin American urologists and urology residents. It included 35 questions exploring different aspects: 1) Personal Protective Equipment (PPE) and internal management protocols for healthcare providers; 2) Priority surgeries and urological urgencies and 3) Inpatient and outpatient care. RESULTS: Of 864 surveys received, 846 had at least 70% valid responses and were included in the statistical analyses. Surveys corresponded to South America in 62% of the cases, Central America and North America in 29.7%. 12.7% were residents. Regarding to PPE and internal management protocols, 88% confirmed the implementation of specific protocols and 45.4% have not received training to perform a safe clinical practice; only 2.3% reported being infected with COVID-19. 60.9% attended urgent surgeries. The following major uro-oncologic surgeries were reported as high priority: Radical Nephrectomy (RN) 58.4%, and Radical Cystectomy (RC) 57.3%. When we associate the capacity of hospitalization (urologic beds available) and percentage of high-priority surgery performed, we observed that centers with fewer urological beds (10-20) compared to centers with more urological beds (31-40) performed more frequently major urologic cancer surgeries: RN 54.5% vs 60.8% (p=0.0003), RC 53.1% vs 64.9% (p=0.005) respectively. CONCLUSIONS: At the time of writing (May 13th 2020) our data represents a snapshot of COVID-19 outbreak in Latin American urological practices. Our findings have practical implications and should be contextualized considering many factors related to patients and urological care: The variability of health care scenarios, institutional capacity, heterogeneity and burden of urologic disease, impact of surgical indications and decision making when prioritizing and scheduling surgeries in times of COVID-19 pandemic.

Atto Thio 12 as a promising dye for photo-CIDNP.

Photo-CIDNP is one among different promising techniques to improve nuclear magnetic resonance (NMR) sensitivity. Being sensitive to particular amino acids makes it a promising candidate with respect to biological NMR. Our goal is to exploit new sensitizers and compare them to the present working horses flavin mononucleotide, bipyridyl, and the recently applied fluorescein. Among the investigated dyes, we found a new and very efficient one, Atto Thio 12, conveniently used in fluorescence microscopy with 2-3 fold enhanced polarization when compared to the established ones. We also show that diode lasers which are now available from near UV to IR can be efficiently used in photo-CIDNP. Results are obtained with the amino acids tyrosine and tryptophan.

American Confederation of Urology (CAU) experience in minimally invasive partial nephrectomy.

PURPOSE: To describe the perioperative and oncology outcomes in a series of laparoscopic or robotic partial nephrectomies (PN) for renal tumors treated in diverse institutions of Hispanic America from the beginning of their minimally invasive (MI) PN experience through December 2014. METHODS: Seventeen institutions participated in the CAU generated a MI PN database. We estimated proportions, medians, 95 % confidence intervals, Kaplan-Meier curves, multivariate logistic and Cox regression analyses. Clavien-Dindo classification was used. RESULTS: We evaluated 1501 laparoscopic (98 %) or robotic (2 %) PNs. Median age: 58 years. Median surgical time, warm ischemia and intraoperative bleeding were 150, 20 min and 200 cc. 81 % of the lesions were malignant, with clear cell histology being 65 % of the total. Median maximum tumor diameter is 2.7 cm, positive margin is 8.2 %, and median hospitalization is 3 days. One or more postoperative complication was recorded in 19.8 % of the patients: Clavien 1: 5.6 %; Clavien 2: 8.4 %; Clavien 3A: 1.5 %; Clavien 3B: 3.2 %; Clavien 4A: 1 %; Clavien 4B: 0.1 %; Clavien 5: 0 %. Bleeding was the main cause of a reoperation (5.5 %), conversion to radical nephrectomy (3 %) or open partial nephrectomy (6 %). Transfusion rate is 10 %. In multivariate analysis, RENAL nephrometry score was the only variable associated with complications (OR 1.1; 95 % CI 1.02-1.2; p = 0.02). Nineteen patients presented disease progression or died of disease in a median follow-up of 1.37 years. The 5-year progression or kidney cancer mortality-free rate was 94 % (95 % CI 90, 97). Positive margins (HR 4.98; 95 % CI 1.3-19; p = 0.02) and females (HR 5.6; 95 % CI 1.7-19; p = 0.005) were associated with disease progression or kidney cancer mortality after adjusting for maximum tumor diameter. CONCLUSION: Laparoscopic PN in these centers of Hispanic America seem to have acceptable perioperative complications and short-term oncologic outcomes.

An improved, time-efficient approach to extract accurate distance restraints for NMR2 structure calculation.

Exact nuclear Overhauser enhancement (eNOE) yields highly accurate, ensemble averaged 1H-1H distance restraints with an accuracy of up to 0.1 Šfor the multi-state structure determination of proteins as well as for nuclear magnetic resonance molecular replacement (NMR2) to determine the structure of the protein-ligand interaction site in a time-efficient manner. However, in the latter application, the acquired eNOEs lack the obtainable precision of 0.1 Šbecause of the asymmetrical nature of the filtered nuclear Overhauser enhancement spectroscopy (NOESY) experiment used in NMR2. This error is further propagated to the eNOE equations used to fit and extract the distance restraints. In this work, a new analysis method is proposed to obtain inter-molecular distance restraints from the filtered NOESY spectrum more accurately and intuitively by dividing the NOE cross peak by the corresponding diagonal peak of the ligand. The method termed diagonal-normalised eNOEs was tested on the data acquired by on the complex of PIN1 and a small, weak-binding phenylimidazole fragment. NMR2 calculations performed using the distances derived from diagonal-normalised eNOEs yielded the right orientation of the fragment in the binding pocket and produced a structure that more closely resembles the benchmark X-ray structure (2XP6) with an average heavy-atom root-mean-square deviation (RMSD) of 1.681 Šwith respect to it, when compared to the one produced with traditional NMR2 with an average heavy atom RMSD of 3.628 Å. This is attributed to the higher precision of the evaluated distance restraints.

Effect of HIV suppression on the cytokine network in blood and seminal plasma.

OBJECTIVE: HIV infection disrupts the cytokine network and this disruption is not completely reversed by antiretroviral therapy (ART). Characterization of cytokine changes in blood and genital secretions is important for understanding HIV pathogenesis and the mechanisms of HIV sexual transmission. Here, we characterized the cytokine network in individuals longitudinally sampled before they began ART and after achieving suppression of HIV RNA. METHODS: We measured concentrations of 34 cytokine/chemokines using multiplex bead-based assay in blood and seminal plasma of 19 men with HIV-1 prior to and after viral suppression. We used Partial Least Squares Discriminant Analysis (PLS-DA) to visualize the difference in cytokine pattern between the time points. Any cytokines with VIP scores exceeding 1 were deemed important in predicting suppression status and were subsequently tested using Wilcoxon Signed Rank Tests. RESULTS: PLS-DA projections in blood were fairly similar before and after viral suppression. In contrast, the difference in PLS-DA projection observed in semen emphasizes that the immunological landscape and immunological needs are very different before and after ART in the male genital compartment. When tested individually, four cytokines were significantly different across time points in semen (MIG, IL-15, IL-7, I-TAC), and two in blood (MIG and IP-10). CONCLUSION: Viral suppression with ART impacts the inflammatory milieu in seminal plasma. In contrast, the overall effect on the network of cytokines in blood was modest but consistent with prior analyses. These results identify specific changes in the cytokine networks in semen and blood as the immune system acclimates to chronic, suppressed HIV infection.

NMR Molecular Replacement Provides New Insights into Binding Modes to Bromodomains of BRD4 and TRIM24.

Structure-based drug discovery (SBDD) largely relies on structural information from X-ray crystallography because traditional NMR structure calculation methods are too time consuming to be aligned with typical drug discovery timelines. The recently developed NMR molecular replacement (NMR2) method dramatically reduces the time needed to generate ligand-protein complex structures using published structures (apo or holo) of the target protein and treating all observed NOEs as ambiguous restraints, bypassing the laborious process of obtaining sequence-specific resonance assignments for the protein target. We apply this method to two therapeutic targets, the bromodomain of TRIM24 and the second bromodomain of BRD4. We show that the NMR2 methodology can guide SBDD by rationalizing the observed SAR. We also demonstrate that new types of restraints and selective methyl labeling have the potential to dramatically reduce "time to structure" and extend the method to targets beyond the reach of traditional NMR structure elucidation.

Analysis of the diversity of Megachilidae bees on the northern subplateau of the Iberian Peninsula.

In the western Mediterranean, 772 species of bees in the family Megachilidae have been reported. Special emphasis has been placed on the Iberian Peninsula, where to date 218 species are known. However, few intensive studies providing information about communities of Megachilidae have been carried out. Two earlier works cite 70 species; almost one third of those known on the Peninsula. With an aim of gaining insight into the structure of the communities of Megachilidae and the factors influencing them, an analysis was made of the alpha and beta diversity of different localities in the northern subplateau. Malaise traps (black and white) were used, and 559 specimens belonging to 55 species were identified of which most exhibited a nest-holder-type nesting habit. Abundance and richness were higher for white traps, although a considerable degree of complementarity was observed with the black traps. In the study zone, diversity can be considered medium-high with a phylogenetic diversity corresponding to stable populations. Regarding the composition of the Megachilidae communities, the influence of the landscape structure, of the microhabitat, and of the colour of the trap used to collect the specimens was detected. The following are recommended: (1) the use of both black and white traps, since they show high complementarity and offer different information about community structure, (2) homogenization of the samples in comparisons among communities, owing to the influence of the color of the trap, which masks the importance of ecological factors in community structuring, and (3) the collection of samples from at least two years previous, in view of the elevated "replacement" of species observed with species richness estimators.

Protein-fragment complex structures derived by NMR molecular replacement.

Recently we have established an NMR molecular replacement method, which is capable of solving the structure of the interaction site of protein-ligand complexes in a fully automated manner. While the method was successfully applied for ligands with strong and weak binding affinities, including small molecules and peptides, its applicability on ligand fragments remains to be shown. Structures of fragment-protein complexes are more challenging for the method since fragments contain only few protons. Here we show a successful application of the NMR molecular replacement method in solving structures of complexes between three derivatives of a ligand fragment and the protein receptor PIN1. We anticipate that this approach will find a broad application in fragment-based lead discovery.

Decoding New York State's Prescription Monitoring Program.

This column describes the Internet System for Tracking Over-Prescribing (I-STOP), New York State's prescription monitoring program, and its compatibility with HIPAA and Part 2 of Volume 42 of the Code of Federal Regulations (CFR). The authors review use of information that is permitted by I-STOP and CFR for health care operations, including disclosure, and present information from the state Bureau of Narcotics Enforcement about appropriate use of the program. Physicians are permitted, for example, to contact other prescribers in I-STOP, even without explicit permission from the patient, an area in which physicians need more training. Common clinical scenarios encountered while navigating I-STOP are described.

Updated list of bumblebees (Hymenoptera: Apidae) from the Spanish Pyrenees with notes on their decline and conservation status.

The Pyrenees, where Euro-Siberian, Mediterranean and alpine faunas join together, have a large biodiversity of bumblebees. We compiled historical literature records of bumblebee species from the Spanish Pyrenees, and then compared these to contemporary surveys to assess trends in elevational distribution. Twenty-eight species (including thirty-five subspecies) were found in the contemporary survey. Nine species and two subspecies previously present were not detected, some included on the Spanish Red List. With the exception of a few species, a reduction of the altitudinal range and an orophilous tendency was observed at both upper and lower elevational levels, suggesting an upward trend towards better-preserved high areas. Our results reinforce the need to develop new protection programs and more restrictive conservation measures for bumblebee populations, species and their habitats.

Exploring Urological Experience in the COVID-19 Outbreak: American Confederation of Urology (CAU) Survey

ABSTRACT Purpose: To explore the current situation faced by Latin American urology departments during the COVID-19 Outbreak in terms of knowledge, actions, prioritization of urology practices, and implementation of internal clinical management protocols for inpatients and outpatients. Material and Methods: A non-validated, structured, self-administered, electronic survey with 35 closed multiple choice questions was conducted in Spanish, Portuguese, Italian, and English and Deutsch versions from April 1st to April 30th, 2020. The survey was distributed through social networks and the official American Confederation of Urology (CAU) website. It was anonymous, mainly addressed to Latin American urologists and urology residents. It included 35 questions exploring different aspects: 1) Personal Protective Equipment (PPE) and internal management protocols for healthcare providers; 2) Priority surgeries and urological urgencies and 3) Inpatient and outpatient care. Results: Of 864 surveys received, 846 had at least 70% valid responses and were included in the statistical analyses. Surveys corresponded to South America in 62% of the cases, Central America and North America in 29.7%. 12.7% were residents. Regarding to PPE and internal management protocols, 88% confirmed the implementation of specific protocols and 45.4% have not received training to perform a safe clinical practice; only 2.3% reported being infected with COVID-19. 60.9% attended urgent surgeries. The following major uro-oncologic surgeries were reported as high priority: Radical Nephrectomy (RN) 58.4%, and Radical Cystectomy (RC) 57.3%. When we associate the capacity of hospitalization (urologic beds available) and percentage of high-priority surgery performed, we observed that centers with fewer urological beds (10-20) compared to centers with more urological beds (31-40) performed more frequently major urologic cancer surgeries: RN 54.5% vs 60.8% (p=0.0003), RC 53.1% vs 64.9% (p=0.005) respectively. Conclusions: At the time of writing (May 13th 2020) our data represents a snapshot of COVID-19 outbreak in Latin American urological practices. Our findings have practical implications and should be contextualized considering many factors related to patients and urological care: The variability of health care scenarios, institutional capacity, heterogeneity and burden of urologic disease, impact of surgical indications and decision making when prioritizing and scheduling surgeries in times of COVID-19 pandemic.

[Chest pain units. Organization and protocol for the diagnosis of acute coronary syndromes]. / Unidades de dolor torácico. Organización y protocolo para el diagnóstico de los síndromes coronarios agudos.

The two main goals of chest pain units are the early, accurate diagnosis of acute coronary syndromes and the rapid, efficient recognition of low-risk patients who do not need hospital admission. Many clinical, practical, and economic reasons support the establishment of such units. Patients with chest pain account for a substantial proportion of emergency room turnover and their care is still far from optimal: 8% of patients sent home are later diagnosed of acute coronary syndrome and 60% of admissions for chest pain eventually prove to have been unnecessary.We present a systematic approach to create and manage a chest pain unit employing specialists headed by a cardiologist. The unit may be functional or located in a separate area of the emergency room. Initial triage is based on the clinical characteristics, the ECG and biomarkers of myocardial infarct. Risk stratification in the second phase selects patients to be admitted to the chest pain unit for 6-12 h. Finally, we propose treadmill testing before discharge to rule out the presence of acute myocardial ischemia or damage in patients with negative biomarkers and non-diagnostic serial ECGs.

The subgenus Andrena (Micrandrena) (Hymenoptera: Andrenidae) in the Iberian Peninsula.

This work presents the results obtained after a revision of the current species of the subgenus Andrena (Micrandrena) Ashmead, 1899 that appear in the Iberian Peninsula. It provides a key to the species, diagnosis, biological data, and comments about the 19 species and 5 subspecies. Additionally, it includes a redescription of five species because their original descriptions were inadequate. Newly reported for the Iberian Peninsula are Andrena floricola Eversmann, 1852 and Andrena strohmella Stöckhert, 1928. This study is the first contribution to resolve certain taxonomic problems in the subgenus Andrena (Micrandrena); however, the use of additional tools like morphometric and molecular characters are recommended in the future to confirm the taxonomic status of Andrena spreta Pérez, 1895. 

[Rosai-Dorfman disease presented with involvement of the adrenal gland. A clinical case reported]. / Enfermedad de Rosai-Dorfman en glándula suprarrenal. Informe de un caso clínico.

BACKGROUND: Adrenal gland involvement is a very rare extranodal presentation of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Its pathogenesis still remains unknown with many theories about its probable cause. Symptoms and signs of adrenal involvement presentation are uncertain. Although, it is a disease with a good prognosis and a favorable clinical course in most cases, the low index of suspicion and difficulty in radiological differential diagnosis lead to radical treatment. CLINICAL CASE: We present a case of Rosai-Dorfman disease with right adrenal plus left infrahiliar nodal involvement. It was treated with adrenalectomy and node exeresis. The infrahilial involvement evolution was appropriate. CONCLUSIONS: Rosai-Dorfman disease is a rare disease and the extra-nodal presentation is even more rare. The incidence and evolution of this disease in the adrenal gland is unknown. The presence of this pathology should be considered if the patient shows adrenal gland affected and lymph node growth, in order to consider the individualized treatment, which may vary (treatment with corticosteroids, chemotherapy and/or radiotherapy).

INTRODUCCIÓN: la afectación extranodal de la glándula suprarrenal es una forma infrecuente de la histiocitosis sinusal con linfadenopatía masiva o enfermedad de Rosai-Dorfman. Aún se desconoce la etiopatogenia de esta enfermedad. Los síntomas y signos de presentación en la afectación adrenal son inciertos. Aunque es una enfermedad de buen pronóstico y curso clínico favorable, el bajo índice de sospecha y el difícil diagnóstico radiológico diferencial llevan a tratamiento radical en la mayoría de los casos. CASO CLÍNICO: se describe el caso de una paciente con enfermedad de Rosai-Dorfman en quien se identificó tumor adrenal derecho de 97 × 99 × 68 mm y tumor nodal infrahiliar izquierdo de 61 × 58 × 57 mm. El tratamiento incluyó adrenalectomía y vigilancia activa del tumor infrahilial mediante tomografía y gammagrama renal. La evolución de la paciente fue adecuada. CONCLUSIONES: la enfermedad de Rosai-Dorfman es una patología poco común y su presentación extranodal es todavía más extraña. La incidencia y evolución de la enfermedad en glándula suprarrenal se desconocen. Esta patología debe ser considerada en glándula suprarrenal cuando hay afección adrenal y crecimiento nodal, para plantear el tratamiento individualizado que puede variar entre vigilancia activa, tratamiento con corticosteroides, quimioterapia y radioterapia.