Therapy of adrenocortical cancer: present and future

Adrenocortical carcinoma is a rare endocrine malignancy with an estimated worldwide incidence of 0.5 - 2 per million/year. This neoplasm is characterized by a high risk of recurrence and a dismal prognosis owing to unsatisfactory overall survival. Surgery represents the cornerstone of adrenocortical carcinoma therapy, which can be associated to radiotherapy and adjuvant mitotane administration. In advanced cases, different chemotherapy regimens are used, but their relative efficacy is still unknown until the results of clinical trials under way will be published. Novel drugs have been recently developed based on the discovery of molecular pathways that trigger development and evolution of these tumors. More efficient treatments are widely expected in the future from these new targeted therapies as a hope of cure for patients affected with this aggressive malignancy.     

普米克令舒和博利康尼联合雾化吸入治疗慢性阻塞性肺病急性加重期的临床观察

目的观察普米克令舒和博利康尼联合雾化吸入对慢性阻塞性肺病急性加重期(AECOPD)的临床疗效。方法58例AECOPD住院患者随机分为两组:观察组30例给予普米克令舒1mg和博利康尼雾化液5mg联合雾化吸入治疗,2次/日;对照组28例给予博利康尼雾化液5mg雾化吸入,甲基强的松龙40mg/日静滴。记录两组患者用药7天前后PaO2、PaCO2、FEV1变化,同时观察不良反应及疗效分析。结果观察组总有效率86.67%,对照组总有效率89.29%,两组疗效相比无显著性差异(P>0.05);两组患者治疗前后PaO2、PaCO2、FEV1均有改善,治疗前后相比有显著性差异(P<0.05),但两组间相互比较无显著性差异(P>0.05);观察组副作用明显少于对照组。结论普米克令舒和博利康尼联合雾化吸入能够改善AECOPD患者肺功能及临床症状,与全身使用糖皮质激素疗效相近,但副作用明显减少。     

慢性肾上腺皮质功能减退症临床分析

目的分析近5年来原发性和继发性慢性肾上腺皮质功能减退症的病因、诊断和替代治疗情况。方法回顾性分析2002年1月～2007年12月67例原发性和继发性慢性肾上腺皮质功能减退症的临床资料,并进行治疗追踪。结果原发性的主要病因是结核(26.87%)、恶性肿瘤治疗后(16.42%)、自身免疫疾病(4.48%),继发病因主要是各种原因长期应用糖皮质激素停药后(37.31%)、席汉氏综合征(14.93%)。两者共有表现为精神差、食欲减退、容易疲乏、体重减轻、低血压、贫血、低钠血症、低血糖。原发性者伴色素沉着,高钾血症;继发性者则皮肤颜色变浅,常有伴有甲状腺和性腺激素水平低的表现,无高钾血症。正规糖皮质激素替代治疗者占22.39%,部分正规替代治疗者占34.33%,不正规替代治疗者占43.28%。结论近年来结核、恶性肿瘤治疗后和长期应用糖皮质激素停药后成为最主要导致慢性肾上腺皮质功能减退症的原因,替代治疗很不理想。     

构建人类肾上腺皮质腺癌细胞系并用其验证过继免疫细胞治疗效果

Objective To establish a human adrenocortical carcinoma (ACC)cell line ACC-LWL, and investigate its cell phenotypes and expression of tumor associated antigens, to detect sensitivity of ACC-LWL against adoptive immune cells. Methods Fresh tumor tissues from the resection of a human ACC were primary cultured and passed generation to generation so as to achieve stable growth in vitro. For analyzing its biological characteristic, the cell cloning formation in soft agar, chromosome and tumorigenesis were tested. Flow cytometric analysis was carried out for phenotype analysis and RT-PCR examination for MN/CA9 and HLA-A2 genes expression. PBMC from 4 healthy donors (2 HLA-A2+ or 2 HLA-A3+) co-cultured with IL-2 (200 U/ml)and the tumor cell lysate of ACC-LWL (20 μg/ml) in vitro to generate CTL. After 14 day stimulation, CTLs were incubated with ACC-LWL with a E/T ratio of 10:1 for 4 hours at 37 ℃. Cytotoxicity was measured with MTr assay. Results One human ACC cell line had been established that showed the characteristics of malignant cells. The cells grew a solid tumor in nude mice. ACC-LWL had a high expression of MHC-Ⅰ, weakly expression of Her2/neu and MHC-Ⅱ, no expression of CD80 or CD86. RT-PCR showed that ACC-LWL expressed MN/CA9 and HLA-A2 genes. CTL, either HLA-A2+ or HLA-A3+, had the capability of killing ACC-LWL in vitro. Conclusion This newly established ACC would provide a useful target in vitro and in vivo for investigations related to human ACC.     

Remission of Cushing's syndrome during pregnancy

We present the first report of pregnancy with Cushing's syndrome due to an adrenal cortical adenoma, in which the hypercortisolemia disappeared during the third trimester of pregnancy, but recurred following the delivery of a normal male infant at 38 weeks by Cesarean section. The case is also unique because plasma ACTH levels were elevated during gestation and postpartum. Also, urinary estriol excretion was very low during the third trimester of pregnancy. The relationship of Cushing's syndrome and pregnancy are reviewed. This study points up some of the limitations of the routinely used dynamic tests of pituitary-adrenal function in Cushing's syndrome, and emphasizes the importance of various radiologic procedures in evaluation of patients with Cushing's syndrome.     

A Child with Adrenocortical Adenoma Accompanied by Congenital Hemihypertrophy: Report of a Case

We report herein the findings of a 7-year-old male child with a ruptured adrenocortical adenoma and congenital hemihypertrophy which was incidentally detected after suffering a trauma. A review of 21 pediatric cases of adrenocortical neoplasms in the literature was made. The patient showed precocious puberty such as pubis and advanced bone age, but an endocrinological examination revealed no definite abnormalities. The right adrenal tumor with hematoma was resected after these evaluations. Adrenocortical adenoma is considered to occur more frequently in female children. However, the incidence of adrenocortical tumors accompanied by congenital hemihypertrophy does not differ between males and females. The outcomes were relatively good, although the observation periods were short in some patients. A large number of patients presented with a tumor and hemihypertrophy on the same side. This finding is of interest when considering the possible association between hemihypertrophy of the organs and tumor proliferation. However, their association in terms of development was unclear. It is necessary for patients with hemihypertrophy to have regular examinations for the possible development of malignant tumors, especially in the kidney, adrenal gland, and liver. Received: November 1, 1999 / Accepted: March 24, 2000     

Paediatric adrenocortical neoplasia — a study of 25 cases

We reviewed our experience of 25 children with adrenocortical tumours from January 1980 to December 1994. Their ages ranged from 7 months to 15 years; there were 16 girls and 9 boys. Truncal obesity, moon facies, hypertension, and virilisation were the most common clinical features. Establishment of the diagnosis of Cushing's syndrome was accomplished by hormonal and radiological studies. Eighteen patients had adrenocortical carcinomas, but 2 of them refused operation; 7 had adrenocortical adenomas. Twenty-three patients were treated by surgery; 6 with carcinomas are still alive after periods of 6 months to 3 years. The results of treatment of adrenocortical carcinoma have been poor, but the prognosis is excellent for benign lesions.     

Kombination von Morbus Addison und Morbus Schilder bei einer 43 jährigen Frau

Summary A singular case of Schilder's diffuse cerebral sclerosis associated with adrenocortical atrophy (Addison's disease) and hyperplasie of the thymus is reported in a women aged 43 years. This appears to be the first observation of diffuse sclerosis with adrenal insufficiency in a female.

     

Histopathological diagnosis and prognostic factors in adrenocortical carcinoma

A great majority of adrenocortical tumors are benign, and many adrenocortical carcinomas (ACC) are obviously malignant at presentation. The histopathological diagnosis of ACC is occasionally difficult, particularly with stage I and stage II disease. The prognosis of ACC is generally poor. Surgery is the major treatment, with chemotherapy and radio-therapy being applicable to only restricted patients. The Weiss criteria are useful in diagnosing the common adult type of ACC. Histopathological prognostic factors of ACC have not been fully established because of the rarity of the disease. In this article, we first describe the current histopathological diagnostic and prognostic factors of ACC, highlighting the special types of ACC to which Weiss’s criteria are not fully applicable. These special type tumors include pediatric adrenocortical tumors, oncocytomas, and aldosterone-producing tumors of pure zona glomerulosa type. Then we present three cases with unusual small adrenocortical tumors. One patient had an unequivocal ACC showing metastatic disease. One had a histologically defined ACC with no metastasis or macroscopic invasion. The third was a pediatric patient with a tumor showing a nodule-in-nodule pattern with insulin-like growth factor II expression.     

Necrosis of granule cells of hippocampus in adrenocortical failure

Summary A case of untreated and rapidly progressive Addison's disease in a 23-year old woman showed selective necrosis with karyorhexis of the granule cells in the hippocampus. We suggest that this unique lesion was caused by a severe adrenocortical insufficiency. This explanation is in accordance with a recent report of selective loss of hippocampal granule cells after complete adrenalectomy in rats. No evidence of nerve cell loss was found in three cases of Addison's disease that had received cortisone treatment, which is consistent with the experimental observation that even very low levels of cortisone in adrenalectomized rats are sufficient to prevent granule cell loss.