Corrigendum: Maternal and offspring sugar consumption increases perigonadal adipose tissue hypertrophy and negatively affects the testis histological organization in adult rats.

[This corrects the article DOI: 10.3389/fcell.2022.893099.].

[Erdheim-Chester disease: a rare histiocytosis with outstanding response to cobimetinib.] / Enfermedad de Erdheim-Chester: una rara histiocitosis con excelente respuesta a cobimetinib.

Introduction: Erdheim-Chester Disease (ECD) is a rare form of histiocytosis, characterized by xanthogranulomatous infiltration of multiple organs by lipid-laden histiocytes. It is considered a myeloid inflammatory clonal disorder that mainly affects men with a mean age of 55 years. Methods: We present the case of a 65-year-old man who consulted our Endocrinology Unit because of polyuria and polydipsia of 4 months of evolution, diagnosing central diabetes insipidus associated with pituitary infiltration. Physical examination showed skin lesions he has had for several years, that were papules-nodules in the anterior chest and xantelasma-like in the face and neck, with biopsy compatible with non-Langerhans histiocytosis. The genetic study of the skin biopsy showed the presence of a mutation in MAP2K1, confirming the ECD. Results: The patient started treatment with interferon alfa, but the response was incomplete and associated with severe intolerance, so given the findings of the genetic study, we decided to indicate treatment with cobimetinib, a potent and selective inhibitor of MEK. After 8 months of treatment, skin lesions have disappeared, as has the pituitary infiltration, with a remarkable improvement in his quality of life. Conclusions: We present a 65-year-old patient with a rare form of histiocytosis (ECD) who in turn presented an atypical form of ECD and, where the genetic study allowed us to confirm the diagnosis and use targeted therapy with cobimetinib with outstanding results.

Introducción: La Enfermedad de Erdheim-Chester (ECD) es una rara forma de histiocitosis, caracterizada por la infiltración xantogranulomatosa de múltiples órganos por histiocitos cargados de lípidos. Se la considera un trastorno clonal inflamatorio mieloide que afecta principalmente a hombres con una edad media de 55 años. Métodos: Presentamos el caso de un hombre de 65 años que consultó a nuestro Servicio de Endocrinología por poliuria y polidipsia de 4 meses de evolución diagnosticándose diabetes insípida central asociada a infiltración hipofisaria. El paciente presentaba lesiones cutáneas pápulo-nodulares en tórax y xantelasma-símiles en cuello y cara de varios años de evolución, con biopsia compatible con histiocitosis no-Langerhans. El estudio genético de la biopsia cutánea detectó la mutación MAP2K1 confirmando la ECD. Resultados: El paciente inició tratamiento con interferón alfa con respuesta incompleta y mala tolerancia por lo que cambiamos el tratamiento a un inhibidor potente y selectivo de MEK, el cobimetinib. Tras 8 meses de tratamiento presenta desaparición de lesiones cutáneas y de la infiltración hipofisaria con notable mejoría de su calidad de vida. Conclusión: Presentamos el caso de un paciente adulto con una forma rara de histiocitosis (ECD) que a su vez presentó una forma atípica de ECD y, donde el estudio genético nos permitió confirmar el diagnóstico e introducir una terapia dirigida con cobimetinib con excelentes resultados.

[Surgical treatment in acromegaly: experience in Córdoba]. / Tratamiento quirúrgico en acromegalia: experiencia en Córdoba

Introduction: Acromegaly prevalence is 35-70 / million. Transsphenoidal surgery is the first-line treatment, with a remission rate of 80% for microadenomas and 50% for macroadenomas. Our aim was to evaluate the surgical results in Córdoba and determine predictive remission factors due to the lack of records. Methods: Retrospective-descriptive study of patients with surgery as the first therapeutic line. Remission criteria: IGF1 normalization for age/sex, with GH ≤1.0 g/L. Test X2 and Fisher's exact test with p<0.05. Results: 38 patients were included: 61% women and 39% men; Average age 45 years. Most frequent chief complaint: headache and acral growth (26%), visual disturbances (20%). Macroadenomas were the 84% of the tumors. Of 37 patients, 54% underwent microscopic surgery, 38% endoscopic and 8% transcranial. The 29% of patients showed post-operative complications and diabetes insipidus was the most frequent (10%). The percentage of them was: 33% transcranial surgery, 29% endoscopic and 25% microscopic (p = 0.557). The biochemical remission at 6 months was 34% and at 12 months 55% (p= 0.0001). No significant differences between the endoscopic and microscopic approach (p = 0.071). Of 36 patients, 31% showed complete tumor resection. The subjective clinical improvement was 88%. There weren´t predictive remission factors with significant differences. Conclusion: The surgical biochemical remission was similar to the bibliography. We didn´t find predictive remission factors but a larger number of patients could modify these results.

Introducción: La acromegalia tiene una prevalencia de 35-70/millón. La cirugía transesfenoidal es el tratamiento de elección, siendo la tasa de remisión del 80% en microadenomas y 50% en macroadenomas. Debido a la falta de registros, nos propusimos evaluar los resultados quirúrgicos en Córdoba y determinar factores predictivos de remisión. Métodos: Estudio retrospectivo-descriptivo de pacientes con cirugía como primera línea terapéutica. Criterios de remisión: normalización de IGF1 para edad/sexo, con GH ≤1,0 g/L.Test X2 y test exacto de Fisher y p<0,05. Resultados: Se incluyeron 38 pacientes: 61% mujeres y 39% hombres; edad promedio 45 años. Motivos de consulta más frecuentes: cefalea y crecimiento acral (26%), alteraciones visuales (20%). El 84% de los tumores fueron macroadenomas. De 37 pacientes, 54% se sometieron a cirugía microscópica, 38% endoscópica y 8% transcraneal. El 29% evidenció complicaciones postquirúrgicas, siendo la diabetes insípida la más frecuente (10%). El porcentaje de las mismas fue: cirugía transcraneal el 33%, endoscópica 29% y microscópica 25% (p= 0,557). La remisión bioquímica a los 6 meses fue de 34% y a los 12 meses 55% (p=0,0001). Sin diferencias significativas entre la vía endoscópica y microscópica (p=0,071). De 36 pacientes el 31% evidenció resección tumoral completa. La mejoría clínica subjetiva fue del 88%. No hubo factores predictivos de remisión bioquímica estadísticamente significativos. Conclusión: La remisión bioquímica con la cirugía fue similar a la bibliografía. No encontramos factores predictivos de remisión pero un número mayor de casos podría modificar estos resultados.

[Anti-estreptavidin antibodies. Diagnostic confusion by biochemical interference]. / Anticuerpos anti-estreptavidina. Confusión diagnóstica por interferencia bioquímica.

We present the case of a patient who, during studies for fertility and subsequent pregnancy, showed an altered thyroid profile with elevated levels of free T4 and normal TSH. After ruling out a thyrotropic adenoma and in the absence of clinical symptoms of hyperthyroidism, the possibility of analytical interference in the immunoassays used to measure hormones was investigated. Interferences caused by heterophile antibodies, macro TSH, anti-thyroid antibodies, biotin, and to a lesser extent anti-streptavidin and anti-ruthenium antibodies have been described. The analysis of the patient was carried out in a self-analyzer whose platform uses the streptavidin-biotin system that is very susceptible to several interferents. A proposed algorithm includes a series of simple tests to perform and interpret that allow detecting or ruling out the presence of interferents. Accordingly, a comparison was made with a different analytical platform (which does not use the streptavidin-biotin system), serial dilutions, precipitation with polyethylene glycol 6000 and treatment with microparticles coated with streptavidin. Results obtained confirmed the presence of anti-streptavidin antibodies in the patient's serum. In the case of disagreements between clinical manifestations and laboratory results, the possibility of methodological interferences should be investigated in order to avoid the potential iatrogenic risk involved in an erroneous biochemical interpretation.

Se presenta el caso de una paciente que, durante los estudios por búsqueda de fertilidad y posterior embarazo, mostraba un perfil tiroideo alterado con niveles elevados de T4 libre y TSH normal. Luego de descartar un adenoma tirotropo y ante la ausencia de sintomatología clínica de hipertiroidismo, se investigó la posibilidad de interferencias analíticas en los inmunoensayos utilizados para la medición de las hormonas. Se han descrito interferencias causadas por anticuerpos heterófilos, macro TSH, anticuerpos anti-tiroideos, biotina, y en menor medida anticuerpos anti-estreptavidina y anti-rutenio. Los análisis de la paciente se realizaron en autoanalizador cuya plataforma emplea el sistema estreptavidina-biotina que es muy susceptible a varios interferentes. Un algoritmo propuesto incluye una serie de pruebas simples de realizar e interpretar que permiten detectar o descartar la presencia de interferentes. De acuerdo al mismo, se efectuó la comparación con una plataforma analítica diferente (que no utiliza el sistema estreptavidina-biotina), diluciones seriadas, precipitación con polietilenglicol 6000 y tratamiento con micropartículas recubiertas con estreptavidina. Los resultados obtenidos confirmaron la presencia de anticuerpos anti-estreptavidina en el suero de la paciente. Ante discordancias entre las manifestaciones clínicas y los resultados de laboratorio, se debe investigar la posibilidad de interferencias metodológicas para evitar el riesgo iatrogénico potencial que implica una interpretación bioquímica errónea.

Anticuerpos anti-estreptavidina: Confusión diagnóstica por interferencia bioquímica / Anti-estreptavidin antibodies. Diagnostic confusion by biochemical interference

Se presenta el caso de una paciente que, durante los estudios por búsqueda de fertilidad y posterior embarazo, mostraba un perfil tiroideo alterado con niveles elevados de T4 libre y TSH normal. Luego de descartar un adenoma tirotropo y ante la ausencia de sintomatología clínica de hipertiroidismo, se investigó la posibilidad de interferencias analíticas en los inmunoensayos utilizados para la medición de las hormonas. Se han descrito interferencias causadas por anticuerpos heterófilos, macro TSH, anticuerpos anti-tiroideos, biotina, y en menor medida anticuerpos anti-estreptavidina y anti-rutenio. Los análisis de la paciente se realizaron en autoanalizador cuya plataforma emplea el sistema estreptavidina-biotina que es muy susceptible a varios interferentes. Un algoritmo propuesto incluye una serie de pruebas simples de realizar e interpretar que permiten detectar o descartar la presencia de interferentes. De acuerdo al mismo, se efectuó la comparación con una plataforma analítica diferente (que no utiliza el sistema estreptavidina-biotina), diluciones seriadas, precipitación con polietilenglicol 6000 y tratamiento con micropartículas recubiertas con estreptavidina. Los resultados obtenidos confirmaron la presencia de anticuerpos anti-estreptavidina en el suero de la paciente. Ante discordancias entre las manifestaciones clínicas y los resultados de laboratorio, se debe investigar la posibilidad de interferencias metodológicas para evitar el riesgo iatrogénico potencial que implica una interpretación bioquímica errónea.

We present the case of a patient who, during studies for fertility and subsequent pregnancy, showed an altered thyroid profile with elevated levels of free T4 and normal TSH. After ruling out a thyrotropic adenoma and in the absence of clinical symptoms of hyperthyroidism, the possibility of analytical interference in the immunoassays used to measure hormones was investigated. Interferences caused by heterophile antibodies, macro TSH, anti-thyroid antibodies, biotin, and to a lesser extent anti-streptavidin and anti-ruthenium antibodies have been described. The analysis of the patient was carried out in a self-analyzer whose platform uses the streptavidin-biotin system that is very susceptible to several interferents. A proposed algorithm includes a series of simple tests to perform and interpret that allow detecting or ruling out the presence of interferents. Accordingly, a comparison was made with a different analytical platform (which does not use the streptavidin-biotin system), serial dilutions, precipitation with polyethylene glycol 6000 and treatment with microparticles coated with streptavidin. Results obtained confirmed the presence of anti-streptavidin antibodies in the patient's serum. In the case of disagreements between clinical manifestations and laboratory results, the possibility of methodological interferences should be investigated in order to avoid the potential iatrogenic risk involved in an erroneous biochemical interpretation.

[IgG4 related disease presenting as panhypopituitarism and perimacular scotoma]. / Panhipopituitarismo y escotoma perimacular como presentación de enfermedad relacionada a IgG4.

IgG4-related disease (IgG4-RD) is a recently described systemic entity of unknown origin. It predominantly affects older men and has distinctive histopathologic features as storiform fibrosis, obliterative phlebitis, dense lymphoplasmacytic infiltrate with immunostaining for IgG4, and it may be associated with elevated serum levels of IgG4. Although any organ can be affected, pituitary gland is rarely involved. We describe the case of a 36-year-old man who presented with headaches, impaired vision, panhypopituitarism with diabetes insipidus and an infiltrative lesion mainly of infundibulum and pituitary. We arrived at diagnosis of IgG4-RD by pituitary biopsy. A successful response to treatment with immunosuppressive doses of corticosteroids was achieved.

Panhipopituitarismo y escotoma perimacular como presentación de enfermedad relacionada a IgG4 / IgG4 related disease presenting as panhypopituitarism and perimacular scotoma

La enfermedad relacionada a IgG4 (IgG4-RD) constituye una entidad sistémica recientemente descrita, de causa desconocida. Afecta predominantemente a hombres mayores y presenta características histopatológicas distintivas, como fibrosis estoriforme, flebitis obliterante y denso infiltrado linfoplasmocitario con inmunomarcación para IgG4, pudiendo estar asociada a elevación sérica de dicha inmunoglobulina. Si bien cualquier órgano puede estar afectado, el compromiso de la hipófisis es infrecuente. Describimos el caso de un hombre de 36 años que se presentó con cefaleas, alteración del campo visual, panhipopituitarismo, diabetes insípida y una imagen que mostraba una lesión infiltrativa infundíbulo-panhipofisaria extendida. Arribamos al diagnóstico de IgG4-RD a través de biopsia hipofisaria. La respuesta al tratamiento con dosis inmunosupresoras de corticoides fue exitosa.

IgG4-related disease (IgG4-RD) is a recently described systemic entity of unknown origin. It predominantly affects older men and has distinctive histopathologic features as storiform fibrosis, obliterative phlebitis, dense lymphoplasmacytic infiltrate with immunostaining for IgG4, and it may be associated with elevated serum levels of IgG4. Although any organ can be affected, pituitary gland is rarely involved. We describe the case of a 36-year-old man who presented with headaches, impaired vision, panhypopituitarism with diabetes insipidus and an infiltrative lesion mainly of infundibulum and pituitary. We arrived at diagnosis of IgG4-RD by pituitary biopsy. A successful response to treatment with immunosuppressive doses of corticosteroids was achieved.

Chronic cluster-like headache in a patient with a macroprolactinoma presenting with falsely low prolactin levels: bromocriptine versus cabergoline?

Cluster-like headache may be associated with pituitary tumors, mostly prolactinomas. Pituitary imaging and prolactin measurement should be assessed in patients presenting with cluster-like headaches with atypical features or unsatisfactory response to treatment. Furthermore, large pituitary adenomas with moderate increase in prolactin levels should prompt prolactin dilutions to avoid "hook effect".

Hipofisitis linfoplasmocitaria con expresión de IgG4 / IgG4- related lymphoplasmacytic hypophysitis

La hipofisitis linfoplasmocitaria con expresión de inmunoglobulina G4 (IgG4) es una entidad de reciente conocimiento. Pertenece al grupo de enfermedades relacionadas a IgG4 (IgG4-RD, del inglés: IgG4-related disease), donde uno o varios órganos pueden estar comprometidos, con síntomas compresivos u obstructivos, o disfuncionalidad por infiltración celular. La hipófisis puede estar afectada en forma aislada. Clínicamente, se presentan con diabetes insípida, hipopituitarismo y/o síntomas de masa ocupante selar, siendo los principales diagnósticos diferenciales los adenomas selares no secretantes, y otros tipos de hipofisitis. Para arribar al diagnóstico de este tipo patología es necesaria la presencia de una imagen de agrandamiento selar o engrosamiento del tallo pituitario en la resonancia magnética nuclear, una histopatología característica con inmunomarcación positiva para IgG4 en más de 10 células plasmáticas por campo de gran aumento y la presencia de IgG4 sérica elevada. Tienen una excelente respuesta a glucocorticoides, por lo que una sospecha diagnóstica oportuna evitaría una cirugía innecesaria en la mayoría de los pacientes con esta entidad.

Immunoglobulin G4 (IgG4)-related lymphoplasmacytic hypophysitis is a recently known entity. It belongs to the IgG4-related diseases (IgG4-RD), in which one or more organs may be involved, with compressive or obstructive symptoms, or dysfunctionality due to cellular infiltration. The pituitary gland can be isolatedly affected. Clinically, lymphoplasmacytic hypophysitis presents with diabetes insipidus, hypopituitarism and/or symptoms of an occupying sellar mass, being the non-secreting sellar adenomas and other types of hypophysitis the main differential diagnosis. In order to reach the diagnosis, the presence of pituitary enlargement or pituitary stalk thickening on an MRI scan, a distinctive histopathology with positive for IgG4 immunostaining in more than 10 plasma cells per high-powerfield, and elevated serum IgG4 levels, confirms this type of hypophysitis. As this entity has an excellent response to glucocorticoids, the diagnosis suspicion may avoid an unnecessary surgery in most patients.

Thyroid lipomatosis in a 36-year-old patient with rheumatoid arthritis and a kidney transplant.

UNLABELLED: Thyroid lipomatosis is a rare disease, as a total of 20 cases have been described in the literature. It is characterized by diffuse infiltration of the stroma by mature adipose tissue and by progressive growth that produces different degrees of compressive symptoms. Our aim is to present the case of a 36-year-old woman who consulted because of dyspnea caused by a multinodular goiter. She underwent surgery with the presumptive diagnosis of a malignant neoplasia, but the pathological examination of the surgical specimen established the diagnosis of thyroid lipomatosis. LEARNING POINTS: Thyroid lipomatosis is a rare, benign disease characterized by diffuse infiltration of the stroma by mature adipose tissue.The pathophysiology of diffuse proliferation of adipose tissue in the thyroid gland is unclear.Thyroid lipomatosis is clinically manifested by a progressive enlargement of the thyroid that can involve the airway and/or upper gastrointestinal tract, producing dyspnea, dysphagia, and changes in the voice.Given the rapid growth of the lesion, the two main differential diagnoses are anaplastic carcinoma and thyroid lymphoma.Imaging studies may suggest a differential diagnosis, but a definitive diagnosis generally requires histopathological confirmation after a thyroidectomy.

Histologically confirmed isolated IgG4-related hypophysitis: two case reports in young women.

UNLABELLED: IgG4-related hypophysitis is a recently described entity belonging to the group of IgG4-related diseases. Many other organs can also be affected, and it is more common in older men. To date, 32 cases of IgG4-related hypophysitis have been reported in the literature, 11 of which included confirmatory tissue biopsy and the majority affecting multiple organs. The aim of this report is to present two cases of biopsy-proven IgG4-related hypophysitis occurring in two young female patients with no evidence of involvement of other organs at the time of diagnosis. LEARNING POINTS: IgG4-related hypophysitis belongs to the group of IgG4-related diseases, and is a fibro-inflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells and storiform fibrosis.It is more common in older men, but young women may also present this type of hypophysitis.Although involvement of other organs is frequent, isolated pituitary disease is possible.Frequent clinical manifestations include anterior hypopituitarism and/or diabetes insipidus.THE DIAGNOSIS MAY BE CONFIRMED WITH ANY OF THE FOLLOWING CRITERIA: a pituitary biopsy with lymphoplasmacytic infiltrates, with more than ten IgG4-positive cells; a sellar mass and/or thickened pituitary stalk and a biopsy-proven involvement of another organ; a sellar mass and/or thickened pituitary stalk and IgG4 serum levels >140 mg/dl and sellar mass reduction and symptom improvement after corticosteroid treatment.Glucocorticoids are recommended as first-line therapy.

Clinical features of the hospitalized patients with 2009 pandemic influenza A (H1N1) in Santa Fe, Argentina.

BACKGROUND: During 2009 occurred the emergence and global spread of a novel influenza A (H1N1) virus. We describe the clinical and epidemiologic features of hospitalized patients who survived and patients who died because of pandemic 2009 influenza A (H1N1) infection reported in Santa Fe, Argentina, from May to July 2009. METHODS: Using medical charts, we collected data on 242 patients who were hospitalized with confirmed laboratory results (defined as positive by specific PCR for pandemic 2009 influenza A H1N1). RESULTS: During the study period, there were 242 cases of hospitalization or death. Of the 242, 46% were admitted to an intensive care unit (ICU) and 33·5% died. The mean age was 27·8 years for surviving and 39·6 for those who died. Twenty-eight percent of hospitalizations involved persons under the age of 15 years; 33% of the patients were between the age of 15 and 44 years; and only 3·3% were 65 years of age or older. Sixty-seven percent had an underlying medical conditions, including diabetes, obesity, heart and lung diseases, and pregnancy. Of the 242 patients, 68% had findings consistent with pneumonia. Treatment with oseltamivir was administered to 227 (93·8%) patients from which 38 received oseltamivir within 48 hours after the onset of symptoms. CONCLUSIONS: The pandemic strain caused severe illness, including pneumonia and acute respiratory distress syndrome, and resulted in ICU admissions in 46% of patients and death in 33·5%. The mean age of hospitalized infected cases was lower than is common with seasonal influenza. Underlying medical conditions were common in the 67% the evaluated patients. Patients who died had a higher prevalence of comorbidities (86·4%) than those who survived (57%), suggesting that the presence of chronic illness may increase the likelihood of death. However, the severe illness was also identified among young, healthy persons.

Alergia respiratoria inducida por hongos / Respiratory hypersensibility induced by fungi

Se realizó una revisión retrospectiva de 152 expedientes de niños con alergia respiratoria, que acudieron al Hospital del Niño "Dr. Rodolfo Nieto Padrón" de Villahermosa, Tabasco, México, entre junio de 1984 y abril de 1986. El grupo estuvo formado por 85 niños (55.9%) y 67 niñas (44.1%) con una edad promedio de 7.3 años. Llamó la atención que la reactividad cutánea a hongos (88.1% fue más importante que a pólenes (69.0%), siendo los alérgenos más frecuentes: Curvularia (31.5%), Penicillium (31.5%) y Rhizopus (30.9%). Al analizarlos por padecimientos encontramos que el 95.6% de los asmáticos, el 90.8% de los riníticos y el 80.6% de los niños con ambos padecimientos fueron alérgicos a hongos, en tanto que la hiperreactividad a pólenes fue de 67.3%, 68.0% y 70.9% respectivamente. No observamos diferencias en la frecuencia de reactividad cutánea entre hongos y pólenes en relación con la edad