Allelic Variants of ARMC5 in Patients With Adrenal Incidentalomas and in Patients With Cushing's Syndrome Associated With Bilateral Adrenal Nodules.

Objective: Germline ARMC5 mutations are considered to be the main genetic cause of primary macronodular adrenal hyperplasia (PMAH). PMAH is associated with high variability of cortisol secretion caused from subclinical hypercortisolism to overt Cushing's syndrome (CS), in general due to bilateral adrenal nodules and rarely could also be due to non-synchronic unilateral adrenal nodules. The frequency of adrenal incidentalomas (AI) associated with PMAH is unknown. This study evaluated germline allelic variants of ARMC5 in patients with bilateral and unilateral AI and in patients with overt CS associated with bilateral adrenal nodules. Methods: We performed a retrospective multicenter study involving 123 patients with AI (64 bilateral; 59 unilateral). We also analyzed 20 patients with ACTH pituitary independent overt CS associated with bilateral adrenal nodules. All patients underwent germline genotyping analysis of ARMC5; abdominal CT and were classified as normal, possible or autonomous cortisol secretion, according to the low doses of dexamethasone suppression test. Results: We identified only one pathogenic allelic variant among the patients with bilateral AI. We did not identify any pathogenic allelic variants of ARMC5 in patients with unilateral AI. Thirteen out of 20 patients (65%) with overt CS and bilateral adrenal nodules were carriers of pathogenic germline ARMC5 allelic variants, all previously described. The germline ARMC5 mutation was observed in only one patient with bilateral AI; it was associated with autonomous cortisol secretion and showed to be a familial form. Conclusion: The rarity of germline ARMC5 mutations in AI points to other molecular mechanisms involved in this common adrenal disorder and should be investigated. In contrast, patients with overt Cushing's syndrome and bilateral adrenal nodules had the presence of ARMC5 mutations that were with high prevalence and similar to the literature. Therefore, we recommend the genetic analysis of ARMC5 for patients with established Cushing's syndrome and bilateral adrenal nodules rather than patients with unilateral AI.

Experiência de 20 anos em adrenalectomia videolaparoscópica / Twenty-year experience in laparoscopic adrenalectomy

Introdução: As operações na glândula adrenal são realizadas para determinados cânceres, todas as massas biologicamente ativas, metástases, massas com mais de 4-5 cm encontradas incidentalmente e hiperplasia adrenal primária. Métodos: Estudo transversal e descritivo. Foram analisados os prontuários dos pacientes submetidos a adrenalectomia videolaparoscópica entre agosto de 1994 e novembro de 2014. Resultados: Foram realizadas 146 adrenalectomias videolaparoscópicas. Em 134 casos, foi realizada com sucesso, mas em 12 casos (8,2%), o procedimento foi convertido. Foram 97 pacientes do sexo feminino e 49 do sexo masculino, com idade variando de 9 a 81 anos (média de 46,7 anos). Foram removidas 56 adrenais direitas, 75 esquerdas e 15 bilaterais. O tamanho médio das adrenais foi de 5,7 cm, variando de 0,9 a 15 cm. A mediana do tempo de internação hospitalar pós-operatória foi de 4,5 dias. A mediana do tempo de cirurgia foi de 144 minutos. Houve complicações em 22,5% dos casos (maiores ­ casos em que houve conversão para cirurgia aberta, necessidade de reinternação hospitalar e óbito­ e menores), sendo 10,9% complicações intraoperatórias e 11,6% pós-operatórias. Apenas sete (4,7%) pacientes foram considerados complicações maiores. Conclusão: A cirurgia realizada em nosso serviço está de acordo com o descrito na literatura, com taxas aceitáveis de complicações, com motivos de conversão compatíveis e com as indicações totalmente aceitáveis e condizentes. A adrenalectomia videolaparoscópica é a cirurgia de escolha para patologias cirúrgicas da glândula adrenal, exceto em casos de carcinoma adrenal localmente invasivo com comprometimento de outras estruturas (AU)

Introduction: Adrenal gland surgery is performed for some types of cancer, all biologically active masses, metastases, masses larger than 4-5 cm found incidentally, and primary adrenal hyperplasia. Methods: A cross-sectional, descriptive study. Medical records of patients who underwent laparoscopic adrenalectomy from August 1994 to November 2014 were analyzed. Results: A total of 146 laparoscopic adrenalectomies were performed. In 134 cases, laparoscopic adrenalectomy was successfully performed, but in 12 cases (8.2%), the procedure was converted. There were 97 female patients and 49 male patients. Fifty-six right adrenal glands and 75 left adrenal glands were removed, and 15 patients had both of them removed. The average size of adrenal glands was 5.7 cm, ranging from 0.9 to 1.5 cm. The median length of postoperative hospital stay was 4.5 days, ranging from 1 to 55 days. The median surgery time was 144 minutes. There were 22.5% of complications (major ones ­ cases that required conversion to open surgery, hospital readmission, and death ­ and minor ones), of which 10.9% were intraoperative and 11.6% were postoperative. Only seven (4.7%) patients were classified as having major complications. Conclusion: The surgery performed in our department is consistent with the literature, showing acceptable rates of complications, compatible reasons for conversion, and completely acceptable and consistent indications. Laparoscopic adrenalectomy is the surgery of choice for diseases of the adrenal gland, except for locally invasive adrenal carcinoma compromising other structures (AU)

Adrenalectomía laparoscópica: lecciones aprendidas en 110 procedimientos consecutivos / Lapararoscopic adrenalectomy: lessons learned from 110 consecutive procedures

Objetivo: Se presenta una serie personal de 110 adrenalectomías laparoscópicas efectuadas en forma consecutiva, destacando las indicaciones, técnica quirúrgica, complicaciones y resultados. Material y Método: Entre Junio de 1993 y Junio del 2003, se realizaron 110 adrenalectomías laparoscópicas en 102 pacientes, 62 mujeres y 40 hombres con una edad promedio de 47,2 años (8-78 años). Las indicaciones más frecuentes fueron: incidentaloma 23,6 por ciento, cáncer metastásico 22,7 por ciento, hiperaldosteronismo 17,3 por ciento,feocromocitoma 15,5 por ciento, síndrome de Cushing 7,3 por ciento, quiste adrenal 6,4 por ciento, mielolipoma 3,6 por ciento y teratoma 1,8 por ciento. Resultados: El tiempo operatorio promedio fue 94.2 minutos (25-240 minutos), el sangrado intraoperatorio fue de 116,9 mL (0-2500 mL), la conversión a cirugía abierta fue necesaria en 1 paciente (0,9 por ciento) debido a sangrado. La estadía hospitalaria fue de 2,5 días (1-10 días). Se registró complicación en 3 pacientes (2,7 por ciento) y hubo una muerte (0,9 por ciento) durante la cirugía. El tamaño promedio fue de 4,2 cm (1,5- 14 cm) y los diagnósticos anatomopatológicos más frecuentes fueron: adenoma 27,3 por ciento, hiperplasia nodular 18,2 por ciento, cáncer metastático 17,3 por ciento y feocromocitoma 14,5 por ciento. Conclusiones: La adrenalectomía laparoscópica evolucionó durante la década pasada hasta establecerse como la técnica de elección para la cirugía adrenal. Basado tanto en la experiencia personal como en los artículos aparecidos en la literatura, este abordaje reporta resultados quirúrgicos comparables a cirugía abierta, pero con claras ventajas para la cirugía laparoscópica en lo que se refiere a complicaciones, estadía hospitalaria, período de convalecencia y resultado cosmético.

[Casuistic revision of adrenal pathology during last 23 years]. / Revisión casuística de la patología adrenal durante los últimos 23 años.

We present a casuistic revision of adrenal pathology, which was studied in our service during the period January 1977-July 2000. We reviewed 59.069 biopsies and 2.674 autopsies and we 84 cases. founded with the following findings: Primary tumors 25% Secundary tumors 51% Infectious diseases 11% Miscellaneous 12% Unsuitable for diagnosis 1% Hyperplasias, adenomas, pheochromocy-tomas, neuroblastoma, adenocarcinoma are included within primary tumors. The metastasic tumors corresponded to: lung, pancreas, mammary gland, kidney and carcinomas; endometrial adenocarcinoma, lymphoma, melanoma, hepatocarcinoma, gastric carcinoma, testicular teratocarcinoma, skin epidermoid carcinoma, uterus choriocarcinoma and a primary germinal tumor of the thymus. Within infectious diseases we founded tuberculosis, histoplasmosis, cryptococosis, hydatidosis. Miscellaneous included hematoma, hemorrhage, pseudocyst, Disseminated Intravascular Coagulation (DIC), athrophy, Wegener's granulomatosis, myelolipoma, hemorrhagic necrosis. There was only one case which was unsuitable for diagnosis due to insufficient material.

Revisión casuística de la patología adrenal durante los últimos 23 años / Casuistic revision of adrenal pathology during last 23 years

Se presenta una revisión casuística de patología adrenal estudiada durante el período comprendido entre Enero de 1977 y Julio del 2000. Se revisaron 59.069 biopsias y 2.674 autopsias y se encontraron 84 casos con los siguientes hallazgos: Tumores primarios 25 por ciento, Tumores secundarios 51 por ciento, Patología infecciosa 11 por ciento, Misceláneas 12 por ciento, No apto para diagnóstico 1 por ciento. Los tumores primarios comprendieron hiperplasias, adenomas, feocromocitomas, neuroblastomas y adenocarcinomas. Los tumores metastásicos correspondieron a carcinomas de pulmón, páncreas, glándula mamaria, riñón, adenocarcinomas de endometrio, linfomas, melanomas, hepatocarcinoma, carcinoma de estómago, teratocarcinoma de testículo, carcinoma epidermoide de piel, coriocarcinoma uterino, y germinoma primitivo de timo. La patología infecciosa hallada fue: Tuberculosis, histoplasmosis, criptococcosis, e hidatidosis. Dentro del grupo "Misceláneas" Se incluyeron: hematomas, hemorragias, pseudoquiste, Coagulación Intravascular Diseminada (CID), atrofia suprarrenal, granulomatosis de Wegener, mielolipoma, necrosis hemorrágica. Hubo un caso no apto para diagnóstico debido a material insuficiente. (Au)

Experiencia en cirugía suprarrenal / Experience in adrenal surgery

Entre 1982 y 1995, nuestra unidad operó 42 pacientes con patología suprarrenal.Fueron 13 portadores de Enfermedad de Cushing, 11 con feocromocitomas, 6 con adenomas funcionantes, 5 neoplasias malignas, 5 tumores incidentales y 2 casos misceláneos. La vía de abordaje fue transperitoneal. Se efectuaron 14 adrenalectomías bilaterales y 27 unilaterales, incluidas 3 ampliadas por cáncer. La tasa de complicaciones postoperatorias fue de 20 por ciento, básicamente respiratorias. Un caso reoperado por hemoperitoneo, y 1 fallecido (2 por ciento). Otros 4 casos de cáncer suprarrenal fallecen dentro de 24 meses. Se mantienen en control actualmente, 33 de los 37 pacientes restantes, con sobrevida entre 2 y 13 años. La vía de abordaje abdominal es conveniente para el manejo de estas lesiones

Incidencia de adrenalites em material de necropsia / Incidence of adrenalitis in necropsy material

Foram estudados casos de adrenalites em material de necropsias efetuadas na Faculdade de Medicina da USP, entre os anos de 1931 a 1981. De 131.466 necropsias 0,2 por cento exibiam adrenalites: 185 homens e 69 mulheres. Ocorrencia bilateral foi observada em 161 casos e unilateral em 46 (47 casos sem essa informacao). Os achados histopatologicos revelaram: 111 casos de tuberculose (43,7 por cento), 86 de paracoccidioidomicose (33,8 por cento), 24 com adrenalites cronicas inespecificas (9,5 por cento), 25 com adrenalites agudas e abcessos (9,8 por cento), 3 casos de histoplasmoses (1,2 por cento), 2 com febre tifoide (0,8 por cento), 2 com citomegalovirus (0,8 por cento) e 1 caso de leishmaniose (0,4 por cento). A grande incidencia de tuberculose e paracoccidioidomicose em glandula adrenal pode ser explicada pela grande ocorrencia dessas patologias em nosso pais, e por suas afinidades em acometer as supra-renais.

[Incidence of adrenalitis in necropsy material]. / Incidência de adrenalites em material de necropsia.

In the necropsy material of the Medical School of the University of São Paulo, collected between 1931 and 1981, consisting of 131,466 post-mortem examinations, there were 254 (0.2%) cases of adrenalitis, 185 male and 69 female. In 161 of these cases the affection was bilateral, in 46 it was unilateral and in 47 cases this information is lacking. In 111 cases (43.7%), the adrenalitis was caused by tuberculosis, in 86 cases (33.8%), by South American blastomycosis, in three cases (1.2%) by histoplasmosis, in two (0.8%) by Salmonellosis, in two (0.8%) by cytomegalovirus infection and in one (0.4%) by leishmaniasis. The high number of cases with tuberculosis and paracoccidioidomycosis of adrenal glands is due to high incidence of these infections in Brazil.