Interpretation of the 5th edition WHO classification of adrenal cortical tumors / 中华病理学杂志

Non-neoplastic lesions were added in the 5th edition WHO classification of adrenal cortical tumor based on the recent update, including adrenal rests, adrenal cysts, congenital adrenal hyperplasia and adrenocortical nodular disease. A range of tumor concepts were updated or refined based on tumor cell origin, histopathology, oncology and molecular biology. The most significant nomenclature change in the field of adrenal cortical pathology involves the refined classification of adrenal cortical nodular disease, which now includes sporadic nodular adrenocortical disease, bilateral micronodular adrenal cortical disease, and bilateral macronodular adrenal cortical disease. The 5th edition WHO classification endorses the nomenclature of the HISTALDO classification to help the classification of aldosterone producing adrenal cortical lesions, which uses CYP11B2 immunohistochemistry to identify functional sites of aldosterone production. The 5th edition WHO classification does not change the Weiss and Lin-Weiss-Bisceglia histopathologic criteria for diagnosing adrenal cortical carcinomas, and underscores the diagnostic and prognostic impact of angioinvasion in these tumors. Reticulin algorithm and Helsinki scoring system were added to assist the differential diagnosis of adrenal cortical neoplasms in adults. Pediatric adrenal cortical neoplasms are assessed using the Wieneke system. The 5th edition WHO classification places an emphasis on an accurate assessment of tumor proliferation rate using both the mitotic count (mitoses per 10 mm2) and Ki-67 labeling index which play an essential role in the dynamic risk stratification of affected patients. This review highlights advances in knowledge of histological features, ancillary studies, and associated genetic findings that increase the understanding of the adrenal cortex pathologies in the 5th edition WHO classification.

Adrenal cortical carcinoma in children: a clinicopathological analysis of 25 cases / 中华病理学杂志

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of adrenal cortical carcinoma (ACC) in children. Methods: Twenty-five children with ACC diagnosed in the Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from March 2014 to August 2022 were retrospectively analyzed. The related literature was reviewed. Results: A total of 25 children with ACC were collected, including 11 males and 14 females, with a male to female ratio of 1.0∶1.3. The patient ages ranged from 8 months to 14 years (median, 4 years). Eighteen cases with clinical data had functional tumors (18/22, 81.8%) presenting with virilization or precocious puberty (15/18), symptoms related to hypercortisolism (8/18) or endocrine symptoms mixed with both (5/18), while 3 cases (3/22, 13.6%) had unknown clinical data. The clinical manifestations of four patients with nonfunctional tumors were an abdominal mass and/or abdominal pain, walking instability and others. Grossly, the average maximum diameter of the tumor was 9.4 cm. Most of the tumors were nodular and partially encapsuled. The cut surfaces were gray or gray brown, soft with hemorrhage. Histologically, the tumor cells were diffusely distributed, separated by a vascular-rich network. The tumor cells were large, with distinct nucleoli, abundant eosinophilic or clear cytoplasm, and round or oval nuclei. The mitotic index was high, and atypical mitoses were common. Necrosis, calcification, capsule invasion or/and venous invasion were present. In some cases, the tumor invaded the surrounding soft tissues or kidneys. Immunohistochemically, the tumor cells were diffusely positive for syn and SF1 and focally positive for α-inhibin, Melan A and Calretinin, but negative for CgA. Ki-67 proliferation index ranged from 2%-90%. TP53 gene status was examined in 7 cases, in which mutations were detected in 4 cases. Follow-up data was obtained in 21 patients, among whom 18 received chemotherapy and 3 received radiotherapy. Distant metastasis occurred in 13 patients. Median progression-free survival (PFS) was 11.2 months and median overall survival (OS) was 54.7 months. Patients aged less than 5 years had a better prognosis for OS (P<0.05) than the older ones (≥5 years), but a similar PFS (P>0.05). Male patients and Ki-67 proliferation index <15% had a better prognosis tendency for OS, but there was no statistically significant difference (P>0.05). Conclusions: ACC in children is a rare, often functional tumor associated with Li-Fraumeni genetic syndrome and has a poor prognosis. Diagnosis and differential diagnosis require a combination of morphological, phenotypic and clinical analysis.

Comparison of coagulation function between adrenocorticotropic hormone independent Cushing syndrome and nonfunctional adrenal adenoma and its influence factors / 北京大学学报(医学版)

OBJECTIVE@#To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS).@*METHODS@#In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups.@*RESULTS@#In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001; (29.22±3.39) s vs. (31.86±3.63) s, P < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher (P < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% vs. 3.5%, P < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% vs. 6.6%, P=0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (r=-0.315, P < 0.001) and APTT (r=-0.410, P < 0.001), and positively associated with FDP (r=0.303, P < 0.001) and D-dimer levels (r=0.258, P < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients (P < 0.05).@*CONCLUSION@#ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.

Giant virilising adrenal cortical carcinoma

Androgen secreting adrenocortical carcinoma (ACC) is a very rare disease with a poor prognosis. Approximately 80% of tumors are functional, most commonly secreting glucocorticoids. We herewith report a case of a huge functional ACC of the right adrenal gland in a 33-year-old female who presented with complaints of hirsutism, amenorrhea and an abdominal lump. On abdominal examination a large lump was palpable in the right hypochondrium reaching up to the umbilicus. Contrast-enhance computed tomography (CECT) revealed a mass in the right suprarenal region. The tumor measured 29 cm × 20 cm × 12 cm and weighed 7.8 kg, the largest reported case of ACC in the world to the best of our knowledge.

Neoplasia oncocítica adrenocortical de potencial maligno incierto: reporte de un caso / Adrenocortical oncocytic neoplasm with uncertain malignant potential: a case report

Resumen Objetivo Describir el caso clínico de una paciente con neoplasia oncocitica adrenocortical, tratado quirúrgicamente en una clínica de Lima, Perú. Caso clínico Paciente mujer de 26 años ingresa a emergencia por dolor abdominal inespecífico. Se evidencia tumoración de 15x14x12 cm dependiente de glándula suprarrenal izquierda por lo que se decide tratamiento quirúrgico. Al análisis patológico se evidencia neoplasia oncocítica de potencial maligno incierto. Discusión Las neoplasias oncocíticas adrenocorticales son entidades poco frecuentes, con escasos reportes de casos de esta enfermedad. Para clasificarlas, se usa la escala de Weiss modificada. Obtenemos una neoplasia oncocítica de potencial maligno incierto, cuyo tratamiento incluye la cirugía de resección de tumor y observación. Conclusión Considerar a las neoplasias oncocíticas dentro del diagnóstico diferencial de incidentalomas adrenales.

Objective To describe a case report of a oncocytic adrenocortical neoplasm, treated surgically in a clinic in Lima, Peru. Case report A 26-year-old woman is admitted to the emergency due to nonspecific abdominal pain. A tumor measuring 15x14x12 cm dependent on left adrenal gland is evidenced, so surgical treatment is decided. Pathological analysis evidences oncocytic neoplasia of uncertain malignant potential. Discussion Oncocytic adrenocortical neoplasms are rare entities, with few case reports of this disease. To classify them, the modified Weiss scale is used. We obtain an oncocytic neoplasm of uncertain malignant potential, whose treatment includes surgery for tumor resection and observation. Conclusion Consider oncocytic neoplasms within the differential diagnosis of adrenal incidentalomas.

Predictors of complication after adrenalectomy

ABSTRACT Purpose: To investigate risk factors for complications in patients undergoing adrenalectomy. Materials and Methods: A retrospective search of our institutional database was performed of patients who underwent adrenalectomy, between 2014 and 2018. Clinical parameters and adrenal disorder characteristics were assessed and correlated to intra and post-operative course. Complications were analyzed within 30-days after surgery. A logistic regression was performed in order to identify independent predictors of morbidity in patients after adrenalectomy. Results: The files of 154 patients were reviewed. Median age and Body Mass Index (BMI) were 52-years and 27.8kg/m2, respectively. Mean tumor size was 4.9±4cm. Median surgery duration and estimated blood loss were 140min and 50mL, respectively. There were six conversions to open surgery. Minor and major post-operative complications occurred in 17.5% and 8.4% of the patients. Intra-operative complications occurred in 26.6% of the patients. Four patients died. Mean hospitalization duration was 4-days (Interquartile Range: 3-8). Patients age (p=0.004), comorbidities (p=0.003) and pathological diagnosis (p=0.003) were independent predictors of post-operative complications. Tumor size (p<0.001) and BMI (p=0.009) were independent predictors of intra-operative complications. Pathological diagnosis (p<0.001) and Charlson score (p=0.013) were independent predictors of death. Conclusion: Diligent care is needed with older patients, with multiple comorbidities and harboring unfavorable adrenal disorders (adrenocortical carcinoma and pheocromocytoma), who have greater risk of post-operative complications. Patients with elevated BMI and larger tumors have higher risk of intra, but not of post-operative complications.

Carcinoma adrenocortical oncocítico virilizante / Adrenal oncocytic virilizing carcinoma

Las neoplasias oncocíticas se encuentran raramente en la glándula suprarrenal. Suelen ser benignos y no funcionales. Existen informes extremadamente limitados de neoplasias oncocíticas suprarrenales. Alrededor del 20% de las neoplasias oncocíticas adrenocorticales muestran componentes malignos y el 10-20% produce hormonas que pueden causar desbalances hormonales. Se presenta un carcinoma adrenocortical oncocítico virilizante en mujer de 35 años de edad quien acudió a consulta por presentar hipomenorrea secundaria de seis meses de duración acompañada de hirsutismo y agravamiento del acné que afectaba principalmente la cara. El examen de laboratorio revela niveles elevados de testosterona libre. La tomografía computada mostró tumor multinodular en la glándula suprarrenal derecha con necrosis central y sin evidencia de linfadenopatía o invasión de estructuras que la rodeaban. Se programó la adrenalectomía derecha lográndose resección completa del tumor. Después de la cirugía, se normalizaron los ciclos menstruales, el hirsutismo, el acné y el resto de las pruebas. El examen histopatológico del tumor fue compatible con carcinoma adrenocortical oncocítico(AU)

Oncocytic neoplasms are found more rarely in the adrenal gland. They are usually benign and nonfunctional. There are limited reports of adrenal oncocytic neoplasms. About 20% of adrenocortical oncocytic neoplasms show malignant components and 10-20% produce hormones that can cause hormonal imbalances. We present a virilizing oncocytic adrenocortical carcinoma in a 35-year-old woman who consulted for hypomenorrhea accompanied by hirsutism and face acne worsening. Laboratory test revealed high levels of free testosterone. Computed tomography showed multinodular tumor of the right adrenal gland with central necrosis and without evidence of lymphadenopathy or invasion of surrounding structures. A right adrenalectomy was performed. After surgery, menstrual cycle, hirsutism and acne, as well as hormonal tests were normal. Histopathological examination of tumor showed an oncocytic adrenocortical carcinoma(AU)

Síndromes de neoplasia endocrina múltiple: revisión radiológica / Multiple Endocrine Neoplasia Syndromes: Radiological Review

Los síndromes de neoplasia endocrina múltiple (MEN), incluyen una serie de enfermedades con alteraciones genéticas que se caracterizan por la presencia de tumores que afectan a dos o más glándulas endocrinas. Son síndromes con una herencia autosómica dominante e incluyen tres patrones: MEN 1 (síndrome de Wermer), MEN 2 (que incluye MEN 2A o síndrome de Sipple y MEN 2B o síndrome de Wagenmann-Froboese) y MEN 4. Los adenomas paratiroideos y el carcinoma medular tiroideo, son los tumores más frecuentes del MEN tipo 1 y 2 respectivamente. Esos síndromes son más comunes en pacientes jóvenes, con patología de afectación bilateral, múltiple o multifocal y, sobre todo, en pacientes con antecedentes familiares. Es necesario el trabajo en equipo de endocrinólogos, cirujanos, oncólogos y radiólogos para optimizar el tratamiento de esos pacientes.

Multiple endocrine neoplasia (MEN) encompasses a serial of familial genetically disorders in wich tumors simultaneusly occur in two or more endocrine organs. MEN síndromes are autosomal-dominant disorders categorized into three main patterns: MEN 1 (Wermer syndrome), MEN 2 (includes MEN 2A o Sipple syndrome and MEN 2B o Wagenmann-Froboese syndrome) and MEN 4. Parathyroid adenomas and medullary thyroid carcinoma are the most frecuent tumors in MEN 1 and MEN 2 respectively. These entities will be suspected in younger patients, bilateral, multiple or multifocal disease and, specially, in patients with family background. Cooperation between endocrinologist, surgeons, oncologists and radiologists is pivotal for optimizing patient treatment.

Adrenocortical tumors associated with the TP53 p. R337H germline mutation can be identified during child-care consultations / Tumores adrenocorticais associados à mutação germinativa TP53 p. R337H podem ser identificados durante as consultas de puericultura

Abstract Objective: To evaluate the clinical features associated with adrenocortical hormone overexpression and familial cancer profiling as potential markers for early detection of adrenocortical tumors in children from South and Southeast Brazil. Methods: The clinical manifestations and anthropometric measurements of 103 children diagnosed with adrenocortical tumors were analyzed. Results: Between 1982 and 2011, 69 girls and 34 boys diagnosed with adrenocortical tumors were followed-up for a median time of 9.0 years (0-34 years). Signs of androgen overproduction alone (n = 75) or associated with cortisol (n = 18) were present in 90.3%. TP53 p.R337H mutation was found in 90.5% of patients. Stages I, II, III, and IV were observed in 45.6%, 27.2%, 19.4%, and 7.8% of patients, respectively. At diagnosis, there were no significant differences in height (p = 0.92) and weight (p = 0.22) among children with adrenocortical tumors, but children with virilization alone had significantly higher height-for-age Z-scores (0.92 ± 1.4) than children with hypercortisolism alone or combined (−0.32 ± 1,8; p = 0.03). The five-year overall survival was 76.7% (SD ± 4.2). Patients with advanced-stage disease had a significantly worse prognosis than those with limited disease (p < 0.001). During follow-up, ten of 55 p.R337H carrier parents developed cancer, whereas none of the 55 non-carriers did. Conclusions: Signs of adrenocortical hormone overproduction appear early, even in cases with early-stage. These signs can be identified at the physical examination and anthropometric measurements. In southern Brazil, pediatric adrenocortical tumor is a sentinel cancer for detecting families with germline p.R337H mutation in TP53 gene.

Resumo Objetivo: Avaliar as manifestações clínicas da hiperexpressão de hormônios do córtex da adrenal e câncer familiar como marcadores para a detecção precoce de tumores adrenocorticais em crianças do Sul e Sudeste do Brasil. Pacientes e métodos: Foram analisadas as manifestações clínicas e antropométricas de 103 crianças diagnosticadas com tumores adrenocorticais. Resultados: Entre 1982 e 2011, 69 meninas e 34 meninos diagnosticados com tumores adrenocorticais foram acompanhados por um tempo mediano de nove anos (0-34). Ao diagnóstico, sinais de virilização isolada (n = 75) ou associada ao cortisol (n = 18) estavam presentes em 90,3% dos pacientes; a mutação do gene TP53 p.R337H foi identificada em 90,5% dos pacientes. Os pacientes foram classificados em estádio I (45,6%), II (27,2%), III (19,4%) e IV (7,8%). Ao diagnóstico, não houve diferença significativa para as medidas de altura (p = 0,92) e de peso (p = 0,22) entre as crianças com tumores adrenocorticais, mas crianças com virilização tiveram escore-Z mais elevado para a idade (0,92 ± 1,4) do que aquelas com hipercortisolismo isolado ou combinado (−0,32 ± 1,8; p = 0,03). A sobrevida global de cinco anos foi de 76,7% (DP ± 4,2). Pacientes com estádios avançados tiveram pior prognóstico (p < 0,001). Durante o seguimento, 10 dos 55 genitores portadores da p.R337H desenvolveram câncer, enquanto que nenhum caso ocorreu entre os 55 não portadores. Conclusões: Os sinais de hiperprodução de hormônios adrenocorticais aparecem precocemente no desenvolvimento do tumor e podem ser identificados pelo exame físico e pelas medidas antropométricas na consulta pediátrica de rotina. O tumor adrenocortical pediátrico é sentinela para a detecção de câncer em famílias que segregam a mutação germinativa p.R337H do gene TP53.

Primary malignant tumors of the adrenal glands

Malignancy must be considered in the management of adrenal lesions, including those incidentally identified on imaging studies. Adrenocortical carcinomas (ACCs) are rare tumors with an estimated annual incidence of 0.7-2 cases per year and a worldwide prevalence of 4-12 cases per million/year. However, a much higher incidence of these tumors (>15 times) has been demonstrated in south and southeastern Brazil. Most ACCs cause hypersecretion of steroids including glucocorticoids and androgens. ACC patients have a very poor prognosis with a 5-year overall survival (OS) below 30% in most series. Pheochromocytoma or paraganglioma (PPGL) is a metabolically active tumor originating from the chromaffin cells of the adrenal medulla. The incidence of PPGL is 0.2 to 0.9 cases per 100,000 individuals per year. Pheochromocytomas are present in approximately 4-7% of patients with adrenal incidentalomas. Classically, PPGL manifests as paroxysmal attacks of the following 4 symptoms: headaches, diaphoresis, palpitations, and severe hypertensive episodes. The diagnosis of malignant PPGL relies on the presence of local invasion or metastasis. In this review, we present the clinical and biochemical characteristics and pathogenesis of malignant primary lesions that affect the cortex and medulla of human adrenal glands.

Adenoma corticoadrenal, presentándose como un incidentaloma: presentación de un caso y revisión de la literatura / Adrenocortical adenoma, presenting as an incidentaloma: case report and literature review

Resumen Objetivo: Presentamos un caso clínico con diagnóstico de incidentaloma adrenal no funcionante asintomático y analizamos las implicaciones clínicas y el abordaje realizado. Caso clínico: Se reporta el caso de un masculino de 53 años, asintomático, con hallazgo ecográfico accidental de imagen hipoecoica de contornos bien definidos en la glándula suprarrenal derecha que presentó incremento en su tamaño. Su estudio hormonal fue negativo para hiperfunción adrenal. Resultados: Se realizó suprarrenalectomía laparoscópica con técnica de 4 trocares con resección completa de la lesión. El paciente presentó buena evolución posquirúrgica. El estudio anatomopatológico concluyó el diagnóstico de adenoma corticoadrenal no funcionante. Conclusión: Ante el hallazgo de una masa adrenal mayor de 1 cm corresponde realizar una identificación hormonal y una evaluación del riesgo de malignidad en los pacientes, los cuales, junto con parámetros imagenológicos y los síntomas presentados, permitirán definir las complicaciones en el manejo y el pronóstico del paciente. El diagnóstico diferencial de los adenomas adrenales está basado en la identificación hormonal, el conocimiento radiológico y el grado de compromiso de la lesión. El abordaje laparoscópico es de elección en las lesiones pequeñas y sin sospecha de malignidad.

Objective: We present a clinical case with diagnosis of an asymptomatic nonfunctional adrenal incidentaloma, in which we discuss the clinical implications and the approach. Clinical case: Male patient, 53 years old with an accidental sonographic finding, characterized by a hypoechoic image of well-defined contours in the right adrenal gland of less than 2 cm. The hormonal test showed no adrenal hyperfunctioning. Laparoscopic adrenalectomy technique is performed with 4 trocars with complete excision of the lesion. The patient presented good postoperative evolution. Results: The pathology study showed a well-defined and benign tumor lesion of the adrenal gland, being similar to the fascicular zone and cortical hyperplasia next to it. The diagnosis is a non-functioning adenoma of the adrenal gland derived from the fascicular zone. Conclusion: Given the finding of an adrenal mass greater than 1 cm mass corresponds perform a hormonal identification and risk assessment of malignancy in patients, which with imaging parameters (echogenicity, bilateralism and the adjacent commitment) and symptoms presented allow to identify the complications in the management and prognosis of the patient. The differential diagnosis of adrenal adenomas is based on the hormonal evaluation, radiological knowledge and the commitment of the injury.

Adjuvant radiotherapy for the primary treatment of adrenocortical carcinoma: are we offering the best?

ABSTRACT Purpose: To evaluate the role of ARDT after surgical resection of ACC. Materials and Methods: Records of patients from our institutional ACC database were retrospectively assessed. A paired comparison analysis was used to evaluate the oncological outcomes between patients treated with surgery followed by ARDT or surgery only (control). The endpoints were LRFS, RFS, and OS. A systematic review of the literature and meta-analysis was also performed to evaluate local recurrence of ACC when ARDT was used. Results: Ten patients were included in each Group. The median follow-up times were 32 months and 35 months for the ARDT and control Groups, respectively. The results for LRFS (p=0.11), RFS (p=0.92), and OS (p=0.47) were similar among subsets. The mean time to present with local recurrence was significantly longer in the ARDT group compared with the control Group (419±206 days vs. 181±86 days, respectively; p=0.03). ARDT was well tolerated by the patients; there were no reports of late toxicity. The meta-analysis, which included four retrospective series, revealed that ARDT had a protective effect on LRFS (HR=0.4; CI=0.17-0.94). Conclusions: ARDT may reduce the chance and prolong the time to ACC local recurrence. However, there were no benefits for disease recurrence control or overall survival for patients who underwent this complementary therapy.

New evidences on the regulation of SF-1 expression by POD1/TCF21 in adrenocortical tumor cells

OBJECTIVES: Transcription Factor 21 represses steroidogenic factor 1, a nuclear receptor required for gonadal development, sex determination and the regulation of adrenogonadal steroidogenesis. The aim of this study was to investigate whether silencing or overexpression of the gene Transcription Factor 21 could modulate the gene and protein expression of steroidogenic factor 1 in adrenocortical tumors. METHODS: We analyzed the gene expression of steroidogenic factor 1 using qPCR after silencing endogenous Transcription Factor 21 in pediatric adrenal adenoma-T7 cells through small interfering RNA. In addition, using overexpression of Transcription Factor 21 in human adrenocortical carcinoma cells, we analyzed the protein expression of steroidogenic factor 1 using Western blotting. RESULTS: Transcription Factor 21 knockdown increased the mRNA expression of steroidogenic factor 1 by 5.97-fold in pediatric adrenal adenoma-T7 cells. Additionally, Transcription Factor 21 overexpression inhibited the protein expression of steroidogenic factor 1 by 0.41-fold and 0.64-fold in two different adult adrenocortical carcinoma cell cultures, H295R and T36, respectively. CONCLUSIONS: Transcription Factor 21 is downregulated in adrenocortical carcinoma cells. Taken together, these findings support the hypothesis that Transcription Factor 21 is a regulator of steroidogenic factor 1 and is a tumor suppressor gene in pediatric and adult adrenocortical tumors.

Long-term Results after CT-Guided Percutaneous Ethanol Ablation for the Treatment of Hyperfunctioning Adrenal Disorders

OBJECTIVES: To evaluate the safety and long-term efficacy of computed tomography-guided percutaneous ethanol ablation for benign primary and secondary hyperfunctioning adrenal disorders. METHOD: We retrospectively evaluated the long-term results of nine patients treated with computed tomography-guided percutaneous ethanol ablation: eight subjects who presented with primary adrenal disorders, such as pheochromocytoma, primary macronodular adrenal hyperplasia and aldosterone-producing adenoma, and one subject with Cushing disease refractory to conventional treatment. Eleven sessions were performed for the nine patients. The patient data were reviewed for the clinical outcome and procedure-related complications over ten years. RESULTS: Patients with aldosterone-producing adenoma had clinical improvement: symptoms recurred in one case 96 months after ethanol ablation, and the other patient was still in remission 110 months later. All patients with pheochromocytoma had clinical improvement but were eventually submitted to surgery for complete remission. No significant clinical improvement was seen in patients with hypercortisolism due to primary macronodular adrenal hyperplasia or Cushing disease. Major complications were seen in five of the eleven procedures and included cardiovascular instability and myocardial infarction. Minor complications attributed to sedation were seen in two patients. CONCLUSION: Computed tomography-guided ethanol ablation does not appear to be suitable for the long-term treatment of hyperfunctioning adrenal disorders and is not without risks.

Effect of Osthole on Adrenocortical Function in Y1 Mouse Adrenocortical Tumor Cells / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of osthole (Ost) on adrenocortical function in Y1 mouse adrenocortical tumor cells.</p><p><b>METHODS</b>Y1 mouse adrenocortical tumor cells were taken as subjects in this experiment. In 10.0%, 1.0%, and 0.1% serum DMEM-F12 medium, Y1 cells were treated with 1, 10, 25, 50, 100, and 200 micromol/L Ost for 24 and 48 h. 0.1% Dimethyl Sulfoxide (DMSO) was taken as negative control group and 1 mmol/L (Bu) 2cAMP as positive control group. Cell growth morphology was observed under inverted microscope. Contents of corticosterone were tested by ELISA. Expression levels of steroids synthase such as Star, Cyp11a1, Cyp21a1, Hsd3b2, Cyp11b1, Cyp11b2, Cyp17a1, and Hsd17b3 mRNA were detected by Real time quantitative PCR (RT-qPCR).</p><p><b>RESULTS</b>Y1 cell proliferation was obviously inhibited by 100 and 200 micromol/L Ost, and its inhibitory effect was more significant in 0.1% serum medium. Compared with the negative control group, gene expressions of Star, Cyp11a1 , Cyp21a1, Hsd3b2, Cyp11b1, Cyp17a1, and Hsd17b3 were significantly enhanced in the posi- tive control group (P < 0.05). Y1 cell corticosterone levels significantly increased in 50 micromol/L Ost treatment group after 24-and 48-h intervention (P < 0.05). Contents of corticosterone increased more obviously in 25 and 50 +/- mol/L Ost treatment groups after 48-h intervention, as compared with 24-h intervention (P < 0.01). After 24-h intervention, expression levels of Star, Cyp21a1, and Hsd3b2 genes were significantly up-regulated in 25 and 50 lLmol/L Ost groups (P < 0.05). Star gene expression was further enhanced after 48-h intervention (P < 0.05). However, Ost showed no effect on Cyp11a1 (P > 0.05). Additionally, gene expressions of Cyp11b1 and Cyp17a1 were significantly enhanced by 10, 25, and 50 pLmolIL Ost after treatment for 24 and 48 h (P < 0.05). Ost showed no obvious effect on Cyp11b2 and Hsd17b3 expressions.</p><p><b>CONCLUSION</b>Ost could regulate adrenal cortex function and promote corticosterone synthesis and secretion through strengthening gene expressions of steroidogenic enzymes.</p>

Tumores e hiperplasias adrenocorticais: identificação de possíveisdoenças hereditárias / Recognition of hereditary diseases related to adrenocortical tumors andhyperplasias

A alta prevalência de tumores da glândula adrenal deve-se, em parte, ao avanço dos métodos de imagem. Os adenomas, carcinomas e hiperplasias oriundos do córtex adrenal são responsáveis por 80 a 90% dos processos tumorais. Alguns casos são herdados e podem estar associados a efeito compressivo de massa tumoral, hipersecreção de esteroides ou manifestações clínicas em outros órgãos. Considerando as hiperplasias e tumores adrenocorticais, o objetivo desse trabalho foi auxiliar os médicos na identificação de pacientes que apresentem risco para doença hereditária. As neoplasias e hiperplasias adrenocorticais podem ser encontradas em síndromes hereditárias, como a síndrome de Li-Fraumeni, síndrome de Beckwith-Wiedemann, neoplasia endócrina múltipla do tipo I, síndrome de Gardner e no complexo de Carney. A hereditariedade também está associada com doenças adrenocorticais na hiperplasia adrenal congênita, no aldosteronismo primário e/ou na síndrome de Cushing (doença clínica ou subclínica) na hiperplasia adrenal macronodular primária. Essa revisão descreve as características clínicas e os defeitos genéticos responsáveis pelas síndromes hereditárias. Relacionamos também a classificação histopatológica dos processos expansivos com os principais sinais clínicos e os genes relacionados. A identificação de defeitos genéticos em células germinativas nessas doenças familiais permite o conhecimento de alterações somáticas em alguns tipos de processos tumorais adrenocorticais de etiologia esporádica. Considerando a prevalência dos tumores do córtex adrenal, a identificação de predisposição hereditária é essencial para assegurar a conduta clínica correta do paciente e o aconselhamento genético de seus familiares.

The adrenal gland tumors are prevalent due in part by the widespread use of imaging studies. Adenomas, carcinomas and hyperplasias, originating from the adrenal cortex, account for 80-90% of adrenal tumoral processes. Some cases are inherited and may be associated with local mass effect, steroid hypersecretion and/or clinical manifestation in other organs. In the context of adrenocortical tumors and hyperplasias, the purpose of this article is to assist physicians in identifying patients who may be at risk of hereditary diseases. Adrenocortical hyperplasias and neoplasias can be found in familial tumor syndromes, such as Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia type 1, Gardner syndrome and Carney complex. Heredity has been also associated with adrenocortical lesions in congenital adrenal hyperplasia, primary aldosteronism and/or Cushing syndrome (overt or subclinical disease) in primary macronodular adrenal hyperplasia (PMAH). This review describes the clinical recognition and genetic defects that have been found to be responsible for these hereditary diseases. Furthermore, we present the histopathologic classification of adrenocortical expansive processes in correlation to the main clinical features and related genes. The identification of germline genetic defects in such familial diseases lead to the identification of somatic alterations in a subgroup of sporadic adrenocortical lesions. Considering the prevalence of adrenocortical tumors, identification of a hereditary predisposition is essential to assure the adequate clinical management of the patient and to offer the genetic counselling to family members.

Beyond biology: the impact of marital status on survival of patients with adrenocortical carcinoma

Purpose: To analyze the association of marital status and survival of patients with ACC using a population-based database. Material and Methods: Patients with ACC were abstracted from the Surveillance Epidemiology and End Results (SEER) database from 1988-2010 (n=1271). Variables included marital status (married vs single/divorced/widowed (SDW)), gender, age, race, tumor (T) and node (N) classification, receipt of surgery, and SEER stage. Statistical analysis was performed using Cox proportional hazard models to generate hazard ratios and 95% confidence intervals. Results: There were 728 (57.3%) females and median age was 56 years (IQR 44-66). Patients who were alive were more frequently married (65.6% vs 61.6%, p=0.008), female (61.1% vs 58.0%, p=0.001), younger (median 51 vs 57 years, p=0.0001), submitted to adrenalectomy (88.6% vs 63.8%, p<0.0001), and more favorable SEER stage (localized-64.9% vs 29.9%; regional–25.1% vs 30.1%; distant 4.8% vs 31.5%, p<0.0001) compared to patients dead of disease (DOD). On multivariable analysis, factors significantly associated with all-cause mortality were SDW status (HR 1.28, 95% CI 1.091.51), age, non-operative management, and N+ disease. Risk factors for disease-specific mortality included SDW status (HR 1.30, 95% CI 1.07-1.56), age, non-operative management, T-classification, and N+ disease. Conclusions: Marital status is significantly associated with survival in patients with ACC. Our results suggest that the decreased survival seen among SDW individuals highlights an area for further research and needed intervention to reduce disparity.

Carcinoma de corteza suprarrenal simulando un carcinoma renal. Reporte de caso / Carcinoma of suprarenal bark simulating a renal carcinoma. Report of a case

Fundamento: El carcinoma de corteza suprarrenal es inusual su presentación, y menos con las características del caso que se presenta; además de no ser tenido en mente por la mayoría de los clínicos. Objetivo: Exponer un caso de carcinoma de corteza suprarrenal el cual clínicamente simulaba un carcinoma renal con un síndrome metastásico múltiple. Presentación de caso: Paciente de 63 años, diabético tipo I e hipertenso que se ingresó por dolor abdominal en epigastrio y mesogastrio acompañado de vómitos, diarreas, sensación de plenitud gástrica y pérdida de 10 kg de peso en los últimos meses. Tres días antes de su ingreso se constató diarreas abundantes, prurito, fiebre, hematuria múltiple, coluria, acolia e íctero. Al examen físico se observó mucosas deshidratadas y pálidas, íctero, deshidratación y pérdida de 10 kg de peso. Aparato respiratorio: Murmullo vesicular disminuido globalmente, estertores crepitantes aislados en ambos campos pulmonares. Aparato digestivo: hepatomegalia de 6 cm irregular y tumoración en flanco izquierdo de 10-12 cm con contacto lumbar. El estudio analítico mostró anemia, enzimas hepáticas elevadas, hematuria, velocidad de sedimentación globular, lactato deshidrogenasa y fosfatasa alcalina elevadas, con estudio imaginológico que señalaba un proceso metastásico en hígado, pulmón y ganglios con un posible origen renal. El paciente falleció a las 48 horas; se encontró un carcinoma de corteza suprarrenal en la necropsia y se confirmó en el estudio histopatológico. Conclusiones: Se presentó un paciente con carcinoma de corteza suprarrenal que simuló un carcinoma renal con manifestaciones clínicas sugestivas de proceso tumoral renal. El carcinoma de corteza suprarrenal es un tumor muy raro que puede evolucionar de forma asintomática, dando manifestaciones clínicas cuando adquiere gran tamaño o es hiperfuncionante. Frente a una tumoración de localización retroperitoneal o de clínica no característica, el clínico debe tener en cuenta esta enfermedad.

Background: The suprarenal cortex carcinoma has an unusual presentation and much less with the characteristics presented in this case, besides not being in the mind of the great majority of clinicians. Objective: To show a case of carcinoma of suprarenal cortex this clinically simulated a renal carcinoma with a multiple metastatic syndrome. Case presentation: A 63 year old diabetic type I and hypertensive patient, who was admitted due to abdominal pain in epigastrium and mesogaster accompanied by vomits, diarrheas, sensation of gastric fullness and loss of 10 kg of weight in the last months. Three days before his admission, it was found that he had had several episodes of diarrheas, pruritus, fever, multiple hematuria, choluria, acholia and jaundice. On physical examination it was observed that he had dehydrated mucous and paleness. Respiratory system: vesicular murmur diminished globally, isolated crepitants rale in both lung fields. Digestive system: hepatomegaly of 6 cm irregular and a tumor in left flank of 10-12 cm with lumbar contact. The analytic study showed anemia, elevated hepatic enzymes, hematuria, and rapid globular sedimentation, dehydrogenase lactate and elevated alkaline phosphatase, with imaging study which showed a metastatic process in liver, lung and ganglion with a possible renal origin. The patient died 48 hours after admission, on autopsy it was found that there was a carcinoma of suprarenal cortex which simulated a renal tumor confirmed in the histopathological study. Conclusiones: A patient with a suprarenal cortex carcinoma was admitted to a hospital simulating a renal carcinoma with clinical manifestations suggesting a renal tumoral process. This type of carcinoma is very weird and may evolve asymptomatically, showing clinical characteristics when they have a big size or it is hyperfunctioning. When facing a tumor like this of retroperitoneal location or non characteristic clinic, the doctor must bear in mind this disease.