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[Supra renal metastases. The rôle of angiography (author's transl)].

Fifteen cases of metastatic involvement of the adrenal glands are described. There are three groups of metastatic lesions: 1. metastases of distant tumors 2. metastases of malignant tumors of the ipsilateral kidney 3. direct extension of tumor to the adrenals Neovascularity was angiographically demonstrated in all cases. 13 of 15 patients had hypervascular metastases and 12 showed enlarged adrenal arteries. The angiographic findings are discussed and compared to those found in the literature.

Adrenal Gland Neoplasms↗

Cushing's syndrome, nodular adrenal hyperplasia and virilizing carcinoma.

A 48-year-old hypertensive diabetic woman rapidly became virilized. Urine 17-oxo-and oxogenic steroids and plasma testosterone, androstenedione, DHEA, DHEA-sulphate and androstenediol were greatly elevated. Plasma cortisol was constantly high and was not suppressed by dexamethasone. Circulating immunoreactive ACTH was consistently detectable at 18-24 ng/l. A 450 g carcinoma arising from a nodular hyperplastic right adrenal gland was resected. Production by the tumour of 17a-hydroxypregnenolone, 17a-hydroxyprogesterone and five C-19 steroids, but very little prenenolone, progesterone or cortisol, was shown by blood sampling, tumour culture and dramatic falls after operation. The plasma cortisol fell to half, with no diurnal variation, consistent with persistent Cushing's syndrome, and the plasma ACTH rose to 55 ng/l. She died 3 months later from a myocardial infarction. Autopsy revealed a pituitary basophil adenoma at a site where radiologically there had been an indentation in the fossa floor for at least 7 years. The left adrenal gland showed nodular hyperplasia. Therefore we conclude that mild pituitary-dependent Cushing's syndrome may have been present for many years before development of a virilizing carcinoma. This case demonstrates that adrenal carcinoma in man can sometimes develop as a consequence of nodular adrenal hyperplasia which may in turn be due to long-standing trophic hyper-stimulation.

Adenocarcinoma↗

Contralateral adrenal metastasis in renal cell cancer.

A 60-year-old female patient presenting with anemia was found to have a left-sided renal tumor and a contralateral adrenal mass of 2 cm in diameter. Imaging studies for metastases were negative. Nephrectomy along with contralateral adrenalectomy was performed and histology disclosed renal cell carcinoma stage pT3a pNO G2 with solitary contralateral adrenal metastasis. In a survey of the literature, 24 previous cases of renal cancer with solitary contralateral adrenal metastasis were identified. The most probable biological pathway to explain this peculiar metastatic pattern is transpulmonal passage of circulating cancer cells and seeding in the adrenal gland on the basis of a particular susceptibility of adrenal tissue to circulating renal cancer cells. The case illustrates that surgery of solitary metastases from renal cell carcinoma may be beneficial to the patient. The case further highlights the caution that is required diagnostically in the interpretation of incidentally found adrenal masses when other malignancies are present.

Adrenal Gland Neoplasms↗

Human model for studying seed-soil factors in blood-borne metastasis.

The relationship between tumor "seed" and tissue "soil" in blood-borne metastasis is poorly understood. Therefore, an explanatory human model is proposed. It is based on the hypothesis that the spread of lung cancer cells to the adrenal vein provides in man not only a variable attribute, lung cancer seed, but also a constant attribute, adrenal venous soil, as in a scientific experiment. Out of 100 cases of lung cancer, four histologic types proved their invasive potentiality in 45 subjects by colonizing the adrenal parenchyma proper and yet differed appreciably in their ability to grow in the adrenal venous blood. Hence, in all probability, the systematic study of venous blood will help in the discovery of the potentialities and limitations of human blood in tumor metastasis.

Adenocarcinoma↗

[Utilization and effectiveness of radiological study methods in the diagnosis of adrenal diseases].

In recent years the construction and increase of sensitiveness of clinical and biochemical test methods resulted in an essential improvement of the functional diagnostics of adrenal diseases. For the objectivation of the findings and for the preoperative localisation radio-morphological, nuclear-medical and sonographic investigation methods are used. The greatest certainty in the diagnostics also of relatively small changes of the adrenal glands is at present achieved by means of the selective, retrograde venography of the adrenal glands in connection with a selective withdrawal of venous blood for the analysis of hormones. The most essential field of indication for this investigation technique are overfunctions of the adrenal cortex as well as hormone-active and hormone-inactive tumorous (benign and malignant) adrenal processes.

Adrenal Cortex Diseases↗

Patterning of B16 melanoma metastasis and colonization generally relates to tumor cell growth-stimulating or growth-inhibiting effects of organs and tissues.

The mouse B16 melanoma metastasizes first to the lungs and secondarily to systemic sites, involving mainly the adrenals, ovaries and pancreas. Systemic colonization effected by intracardiac injection of tumor cells establishes similar patterning, but in addition frequently colonizes the bones. To assess possible systemic site influences on metastasis and colony formation, the capacity of B16 melanoma cells to proliferate in these sites in vivo and in ex vivo explants following intracardiac injection was examined. Effects of cells isolated from these sites, and of organ- or tissue-conditioned medium, on growth of B16 cells in monolayer culture were also studied. Injected fluorochrome-labeled tumor cells initially distributed without site preference, but within 48 h had begun proliferating in the adrenals, ovaries and lungs, while remaining static in the pancreas and bones, and disappearing from the spleen, liver, kidneys, brain, and skeletal muscles. Mitogenic activity releasable in soluble form was associated with all favorable organs and tissues and was the predominant influence of those tissues on cultured tumor cells. In contrast, the overall effects of liver, spleen, kidney, and brain tissues were to inhibit tumor cell growth. Soluble growth-promoting activity enhanced clonogenic growth of isolated tumor cells stimulated by mouse serum, suggesting that metastasis or colony formation might be stimulated in favorable sites by those factors together with blood-borne growth factors. The observed effects of organ- and tissue-derived cells and soluble factors on tumor cells generally reflected the in vivo consequences of tumor cell entrapment in the corresponding sites. However, the failure of metastases to develop in the bones, which are favorable sites for colonization by the same cells, remains puzzling.

Adrenal Gland Neoplasms↗

[Is adrenalectomy an indispensable part of nephrectomy? Results of a multivariate statistical analysis].

Since in the absence of clinically overt metastatic disease tumorous lesions within the adrenal gland are found in only 2-10% of cases, the majority of renal cell cancer patients are overtreated by adrenalectomy as an integral part of nephrectomy. The medical records of 847 patients undergoing adrenalectomy in combination with nephrectomy irrespective of the local extent of the primary tumor or the clinical stage at first diagnosis were reviewed to determine the reliability of currently available imaging modalities regarding the prediction of adrenal gland metastases. Several patient and tumor characteristics correlated with the presence of intra-adrenal metastases, and their prognostic value was determined by a multivariate logistic regression model. Metastatic spread into the adrenal gland was observed in 27 of 847 (3%) patients. In only three of eight patients in whom the adrenal was identified as the only metastatic site, preoperative abdominal CT scans were interpreted as false negative. During multivariate statistical analysis, only the presence of distant metastases, vascular invasion within the primary tumor, and multifocal growth of renal cell cancer within the tumor-bearing kidney were identified to independently predict the likelihood for the presence of intra-adrenal metastases. None of the patient or tumor characteristics evaluated reliably predicted the likelihood for the presence of adrenal metastases in patients without evidence of disseminated metastatic spread. As we believe and as the current investigation demonstrates, routine adrenalectomy should not be recommended in cases of preoperatively normal radiological examinations.

Adrenal Gland Neoplasms↗

Correlation between radiologic and pathologic dimensions of adrenal masses.

The size of adrenal tumors has been shown to be a good predictor of malignancy. There is still some controversy about the concordance between radiologic and real pathologic measurements. The aim of this study is to determine the correlation between direct and corrected radiologic computed tomography scan dimensions and the measurements of the resected specimen. A total of 41 adrenal tumors were included. Direct and corrected measurements of the largest diameter were contrasted with the pathologic dimensions. The Linos formula was used for the corrected measurements. Proper statistics were used considering a two-tailed significance level of 0.05. The intraclass correlations using direct and corrected measurements were 0.89 [95% confidence interval (95%CI) 0.81-0.94, p = 0.00001) and 0.90 (95%CI 0.82-0.95, p = 0.00001), respectively. The bivariate analysis using Pearson's correlation between two-dimensional group variables showed r = 0.82 (p < 0.0001) when direct and pathologic measurements were compared and r = 0.83 (p < 0.0001) when the corrected values were compared with the real dimensions. In this study, we demonstrate good correlation between radiologic and pathologic measurements of adrenal tumors. The Linos formula turned out to be significantly more accurate than direct radiologic measurements when means of the groups were compared, whereas when individual correlations were determined the two were similar. The Linos formula and radiologic measurements can be used to determine the proper management of adrenal incidentalomas in individual patients.

Adolescent↗

Metastatic malignant phaeochromocytoma: A rare entity that underlies a therapeutic quandary.

Phaeochromocytoma is a rare condition that provides a diagnostic challenge as a result of its variable presentation. Treatment of metastatic malignant phaeochromocytoma is also not well defined owing to its rarity. We present four such cases and a review of the literature. The database of the Singapore Cancer Registry was used to trace all cases of metastatic malignant phaeochromocytoma from 1984 to 2004, and the case records were then reviewed retrospectively. There were four patients with metastatic malignant phaeochromocytoma seen in Singapore in the last 20 years. Their variable clinical courses were reviewed and compared with current knowledge and overseas experience in the literature. We further discuss the difficulties in diagnosis, and the dilemma in appropriate management of such cases. Phaeochromocytoma remains a commonly missed diagnosis unless a high index of suspicion is maintained. Malignant phaeochromocytoma has a variable clinical course. There is a place for radical surgery if this can render the patient free of gross disease, or when it can achieve symptom control for palliation and improvement in quality of life. In the metastatic context, debulking surgery does not appear to be of curative benefit, although it may be undertaken for good palliation.

Adrenal Gland Neoplasms↗

Metastatic phaeochromocytoma: risks of diagnostic needle puncture and treatment by arterial embolisation.

A 62-year-old man had an acute episode of hypertension 72 h after fine needle aspiration biopsy of an intra- hepatic nodule. The patient had been operated 3 years previously for a right adrenal phaeochromocytoma with no evidence of metastases at that time. Thus, a relapse of the tumour was postulated and confirmed by raised levels of urinary metanephrines. The extent of the metastases precluded surgical intervention and thus localised embolisation was proposed and permitted a clinical stabilisation over 8 months. This case indicates the necessity of long-term post-operative follow-up of phaeochromocytoma as well as the dangers of fine needle aspiration biopsy of metastases from this kind of tumour. Treatment of malignant phaeochromocytoma is difficult and embolisation was a useful therapeutic alternative in this case where the metastases were well defined.

Adrenal Gland Neoplasms↗

Laparoscopic adrenalectomy for large-volume (> or = 5 cm) adrenal masses.

BACKGROUND AND PURPOSE: Laparoscopic adrenalectomy has emerged as the standard of care at many centers for small surgical adrenal masses. However, the role of laparoscopic adrenalectomy in the treatment of large adrenal masses has not been specifically addressed. Our aim was to evaluate the outcome of laparoscopic v open adrenalectomy for large-volume (> or =5 cm) adrenal masses and to compare laparoscopic adrenalectomy for large- and small-volume (<5 cm) masses. PATIENTS AND METHODS: Data from 14 patients with large adrenal masses undergoing laparoscopic adrenalectomy between February 1998 and March 1999 (Group I) were retrospectively compared with 14 contemporary large-volume open adrenalectomies between December 1992 and May 1998 (Group II) and 45 small-volume laparoscopic adrenalectomies between July 1997 and November 1998 (Group III). RESULTS: In Group I and Group II, the mean surgical time (205 min v 216 min) and blood loss (400 mL v 584 mL) were similar. Although the mean adrenal size was also comparable (8 cm v 7.8 cm), the specimen weight of the en bloc adrenal gland and periadrenal fat was greater in Group I (168 g v 106 g). The hospital stay was shorter in Group I (2.4 days v 7.7 days). Minor complications occurred in 21.4% of Group I and 50% of Group II patients. On comparing Group I and Group III (laparoscopic <5 cm), Group I had larger specimen weight (168 g v 51.4 g), longer surgical time (205 min v 158 min), greater blood loss (400 mL v 113 mL), longer hospital stay (2.4 days v 1.5 days), a higher complication rate (21.4% v 8.9%), and a higher incidence of open surgical conversion (14.3% v 2.2%). Over a mean follow-up of 9.9 months, no local or port-site recurrences have been noted in Group I. CONCLUSIONS: Laparoscopic adrenalectomy for large-volume adrenal masses is technically feasible and seems to replicate open surgical oncologic principles of achieving a wide-margin, en bloc excision of the adrenal gland and periadrenal fat. Successful laparoscopic resection is not impacted by the large size of the adrenal mass per se but rather by the presence of local invasion and poorly defined tissue planes that may be encountered in adrenal malignancy. As such, laparoscopic adrenalectomy for large masses should be attempted only by experienced laparoscopic surgeons and then with a low threshold for open conversion.

Adrenal Gland Neoplasms↗

Case report: bilateral adrenal pheochromocytoma.

Pheochromocytoma remains a clinical challenge to diagnose and manage. In addition, the association of multiple endocrine neoplasia syndromes with pheochromocytoma require the clinician's awareness to evaluate patients with pheochromocytoma (especially when bilateral) for abnormalities in thyroidal C-cell function with serum calcitonin determinations. The authors present a case of a 42-year-old woman initially diagnosed with, and treated for, cranial artery vasculitis because she had a stroke and a history of rheumatoid arthritis and asthma. Subsequent evaluation of episodic blood pressure increases, headache, and tachycardia revealed biochemical evidence of catecholamine overproduction. Bilateral adrenal masses were found on computed tomography scanning, and the functional nature of the adrenal masses was confirmed by a meta-Iodobenzylguanidine scan. Upon further evaluation, an elevated serum calcitonin concentration was demonstrated, which increased greatly with pentagastrin stimulation. C-cell hyperplasia was demonstrated by subsequent thyroidectomy, confirming the diagnosis of multiple endocrine neoplasia 2A. The difficulty in arriving at a correct diagnosis, the subsequent management, including bilateral adrenalectomy and thyroidectomy, and newer insight into the genetic abnormalities of multiple endocrine neoplasia 2A are discussed.

Adrenal Gland Neoplasms↗

Imaging and pathologic features of myelolipoma.

Myelolipoma is a benign tumor consisting of mature fat interspersed with hematopoietic elements resembling bone marrow. Imaging findings in a large series of pathologically proved cases of myelolipoma were correlated with the pathologic and histologic features of the lesions. Myelolipoma manifests in four distinct clinicopathologic patterns: isolated adrenal myelolipoma, adrenal myelolipoma with hemorrhage, extraadrenal myelolipoma, and myelolipoma associated with other adrenal disease. Myelolipoma is difficult or impossible to detect at plain radiography unless the lesion is large and predominantly fatty. At ultrasound, myelolipoma often has heterogeneous echogenicity due to its typically nonuniform architecture. Computed tomography (CT) frequently demonstrates large amounts of fat with areas of interspersed higher-attenuation tissue. At magnetic resonance imaging, predominantly fatty areas usually have increased signal intensity on T1-weighted images and moderate hyperintensity complicated by the presence of marrowlike elements in the corresponding regions on T2-weighted images. The imaging appearance of myelolipoma is altered by the presence of hemorrhage. In such cases, CT is the most accurate method for evaluation. Knowledge of the imaging characteristics of myelolipoma usually allows presumptive diagnosis, although percutaneous needle biopsy may be needed to confirm the diagnosis in cases of extraadrenal myelolipoma. Surgical excision is unnecessary unless the diagnosis is unclear or the lesion is symptomatic. Asymptomatic, nonhemorrhagic myelolipomas do not require therapy.

Adrenal Gland Diseases↗

Abnormal regulation of adenosine 3',5'-monophosphate and corticosterone formation in an adrenocortical carcinoma.

A spontaneously occurring rat adrenocortical carcinoma which produces corticosterone was maintained by transplantation. The carcinoma appeared to utilize corticosterone biosynthetic steps similar to those of the normal adrenal, but the tumor produced only about 1-10% as much corticosterone per unit tissue weight as nontumorous adrenal glands. The tumor demonstrated little or no increase in corticosterone production in response to adrenocorticotropic hormone (ACTH) either in vivo or in vitro. In normal adrenals, ACTH increases the activity of adenyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to adenosine-3',5'-monophosphate (cyclic AMP), the latter then serving as an intracellular regulator of steroidogenesis. ACTH failed to increase cyclic AMP levels in the tumor in vivo or in slices in vitro, conditions under which there were 50- and 20-fold increases in nontumorous adrenals. However, in homogenates fortified with exogenous ATP, adenyl cyclase activity was comparable in the tumor and adrenals, and cyclic AMP formation was increased 3-fold by ACTH in each. As measured in homogenates, the tumor did not possess a greater ability to destroy cyclic AMP than did normal adrenals. Although ATP levels in the carcinoma were found to be considerably lower than those in normal adrenals, it was not clear that this finding can explain the inability of ACTH to increase cyclic AMP levels in intact tumor cells. While the failure to normally influence cyclic AMP levels in the carcinoma cells could be an important factor in the lack of a steroid response to ACTH, several lines of evidence suggest that the tumor possesses one or more additional abnormalities in the regulation of steroidogenesis. First, in the absence of ACTH stimulation, the tissue concentrations of cyclic AMP were comparable in the tumor and in nontumorous adrenals, but these cyclic AMP levels were associated with a lower level of steroidogenesis in the tumor. Second, tumor slices failed to increase corticosterone production when incubated with cyclic AMP, in contrast to 5-fold increases observed with nontumorous adrenals.

Adenine Nucleotides↗

High epinephrine content in the adrenal tumors from Sipple's syndrome.

Percent of epinephrine content to total catecholamine is low in pheochromocytomas irrespective of unilateral or bilateral adrenal origin when they have no medullary carcinoma of the thyroid. However, epinephrine content higher than norepinephrine has been noted in the adrenal tumors from the patients with Sipple's syndrome. Although an exact reason for this remained unknown, our data could suggest that the adrenal tumors in Sipple's syndrome are primarily different from other types of pheochromocytoma, and thorough examinations for detecting the thyroid carcinoma should be necessary when the adrenal tumor is rich in epinephrine.

Adolescent↗