Phenotype and genotype of patients with multiple endocrine neoplasia type 1 studied in Argentina.

INTRODUCTION: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant inherited disease with an estimated prevalence of 2-10:100 000. The main locations of tumors are parathyroid glands (HPT), gastroenteropancreatic tract (GEPT), and anterior pituitary gland (PT). The aim of our investigation was to describe the phenotype and genotype of Argentinian patients with MEN1. METHODS: A total of 68 index patients diagnosed with at least two of the three main tumors or one tumor and a relative with MEN1, and 84 first-degree relatives were studied. We sequenced the coding region (exons 2-10); the promoter, exon 1; and the flanking intronic regions of the MEN1 gene, following the Sanger method. We used MLPA in index patients without mutation. RESULTS: Prevalence of tumors: HPT 87.5%, GEPT 49% (p< 0.001). No statistical differences in the prevalence of HPT vs. PT (68%). Prevalence of pathogenic variants: 90% in familial cases and 51% in sporadic cases. Of the different 36 pathogenic variants, 13 (36.2%) were frameshift micro-rearrangement, 8 (22.2%) were missense, 9 (25%) were nonsense, 3 (8.3%) were mutations in splicing sites, 2 (5.5%) were large deletions and, 1 in-frame micro-rearrangement. We found 7 novel pathogenic variants. Thirty-nine percent (n = 33) of first-degree relatives of 23 families were found to be mutation carriers. CONCLUSION: The phenotype and genotype of Argentinian patients was similar to other MEN1 populations. A high frequency of PT and the identification of seven novel mutations are underscored.

Introducción: La neoplasia endocrina múltiple tipo 1 (NEM1) es una enfermedad hereditaria autosómica dominante con una prevalencia estimada de 2-10:100 000. Las localizaciones principales de los tumores son glándulas paratiroides (HPT), tracto gastroenteropancreático (TGEP) y glándula pituitaria (TP). El objetivo de nuestra investigación fue describir el fenotipo y genotipo de pacientes argentinos con NEM1. Métodos: Estudiamos 68 casos índices diagnosticados por presentar al menos dos de los tres tumores principales, o un tumor y un pariente con NEM1, y 84 familiares de primer grado. Secuenciamos la región codificante (exones 2-10); el promotor, exón 1; y las regiones intrónicas flanqueantes del gen MEN1 siguiendo el método de Sanger. Utilizamos MLPA en pacientes índice sin mutación. Resultados: Prevalencia de tumores: HPT 87.5%, TGEP 49% (p < 0.001), sin diferencias estadísticas entre las prevalencias de HPT vs TP (68%). Prevalencia de variantes patogénicas: 90% en casos familiares y 51% en esporádicos. Hallamos 36 variantes patogénicas, 7 (20%) fueron noveles. Fueron 13 (36.2%) microarreglos con cambio en el marco de lectura, 9 (25%) variantes sin sentido, 8 (22.2%) con cambio de sentido, 3 (8.3%) en sitio de unión de empalme, 2 (5.5%) grandes deleciones y 1 microarreglo sin cambio en el marco de lectura. El 39 % (n = 33) de los parientes de primer grado en 23 familias fueron portadores de mutaciones. Conclusión: El fenotipo y genotipo de los pacientes argentinos con NEM1 fue similar al de otras poblaciones. Destacamos una alta frecuencia de TP y de variaciones patogénicas noveles.

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.

Venous thromboprophylaxis in general surgery ward admissions: strategies for improvement.

OBJECTIVE: To estimate the adherence to institutional venous thromboprophylaxis clinical practice guidelines (CPGs) in general surgery patients and to assess the effectiveness of a multi-strategy improvement intervention. DESIGN: A prospective before-after study. SETTING: Two teaching hospitals located in the city of Buenos Aires, Argentina. PARTICIPANTS: Prescriptions belonging to patients admitted to the general surgery wards were evaluated. INTERVENTION: A multi-strategy intervention that included (i) simplification of institutional CPGs for venous thromboprophylaxis using a single drug at a single dose, based on the American College of Chest Physicians recommendations, (ii) distribution of pocket cards with an algorithm for the implementation of new recommendations to both, physicians and nurses, working in the general surgery units, (iii) educational talks, (iv) paper-based reminders and (v) audit and feedback. MAIN OUTCOME MEASURE: The adherence of the venous thromboprophylaxis prescription to the institutional recommendations. RESULTS: The prescriptions of 100 admitted patients before and 90 after the intervention were included in the analysis. The initial rate of adherence was 31%. After the intervention this rate rose to 71.1% (P< 0.001). The major improvement observed was the reduction in omitted prophylaxis in patients at risk of venous thromboembolism from 45 to 13.3% (P< 0.001). In the adjusted model, prescribing compliance with CPGs was five times more likely during the second stage than during the first stage (OR = 5.60, 95% CI = 2.92-10.74). CONCLUSIONS: Simple and economical interventions such as those described in this study can improve general surgeons compliance with the institutional and international guidelines, thus assuring patient safety and quality of health care.