Types Of Adrenal Tumors Research Articles

Towards a Virtual Research Environment for International Adrenal Cancer Research

For many research areas, the need to collaborate across organizational and in certain cases national boundaries is essential. This is especially the case when dealing with rare diseases where a lack of data, information and/or sharing of expertise can cause delays in progressing the understanding and potential diagnosis/treatment of such diseases. Research into adrenal tumours is one such area where co-ordination of international cancer efforts is essential. The European Network for the Study of Adrenal Tumours - Structuring clinical research on adrenal cancers in adults (ENS@T-CANCER) project has recently been funded by the European Union to establish a state of the art Virtual Research Environment (VRE) supporting all aspects of international research and collaboration into the aetiology, diagnosis and establishing optimal treatment strategies for patients with adrenal cancer. It is envisaged that this VRE will comprise a portfolio of clinical databases for the different types of adrenal tumours that exist; support and integrate a seamless federation of adrenal tumour bio-banks with support for bio-sample tracking; support a wide range of – omics research into adrenal tumours and allow results to be shared amongst collaborators; offer advanced visualization services, and support several large-scale clinical trials comprising cohorts of patients with different kinds/treatments of adrenal tumours. This paper outlines the goals of the ENS@T-CANCER project and outlines the on-going implementation work. We show how security-oriented information can be collected and tracked through the VRE including supporting collection of clinical data sets and their linkage with associated bio-samples in an ethically-driven framework.

Clipless and Sutureless Laparoscopic Adrenalectomy Carried Out With the LigaSure Device in 32 Patients

Laparoscopic adrenalectomy has become the standard procedure for treating patents with adrenal masses. The purpose of this study was to evaluate the use of the LigaSure vessel closure system during laparoscopic adrenalectomy. The LigaSure device was used in 32 patients undergoing laparoscopic adrenalectomy for adrenal masses. Adrenalectomy was carried out without the use of clips or sutures for vessel closure. In 1 patient the adrenal tumor had invaded the ipsilateral kidney, so laparoscopic nephrectomy was also carried out during the same operation. In another patient, a renal cell carcinoma in the left kidney had metastasized to the right adrenal gland. Both the kidney and the contralateral adrenal gland were removed laparoscopically during the same operation. Adrenal masses had a mean greatest diameter of 3.48 cm (range 2 to 11 cm). Mean operative time was 83.2 minutes (range 30 to 190 min). Mean blood loss was 36.2 mL (range 10 to 140 mL). No conversions to open surgery were necessary. No patients experienced major bleeding intraoperatively or postoperatively. Adrenal tumor types included adrenocortical adenoma (16 patients), pheochromocytoma (13 patients), malignant pheochromocytoma (1 patient), chromophobic carcinoma (1 patient), and metastasis from a renal cell carcinoma (1 patient). For vessel closure during laparoscopic adrenalectomy, the LigaSure device seems to be safe and effective. For patients with conditions such as renal cell carcinoma combined with metastasis to the contralateral adrenal gland, nephrectomy, and contralateral adrenalectomy can be carried out during the same laparoscopic operation.

Presence of Kisspeptin-like Immunoreactivity in Human Adrenal Glands and Adrenal Tumors

Kisspeptins are neuropeptides which activate the hypothalamo-pituitary gonadal axis and are considered to play important physiological roles in the reproduction. Kisspeptins have also been reported to stimulate the aldosterone secretion from the adrenal cortex. However, the expression of kisspeptins in human adrenal glands and adrenal tumors has not been clarified yet. We, therefore, studied the presence of kisspeptin-like immunoreactivity (LI) in human adrenal glands and adrenal tumors (adrenocortical adenomas, adrenocortical carcinomas, and pheochromocytomas) by radioimmunoassay and immunocytochemistry. Kisspeptin-LI was detected in all the tissues examined; normal portions of adrenal glands (3.0 +/- 2.3 pmol/g wet weight, n = 21, mean +/- SD), aldosterone-producing adenomas (4.6 +/- 3.3 pmol/g wet weight, n = 10), cortisol-producing adenomas (2.7 +/- 1.4 pmol/g wet weight, n = 14), adrenocortical carcinomas (1.7 +/- 0.2 pmol/g wet weight, n = 4), and pheochromocytomas (1.8 +/- 0.8 pmol/g wet weight, n = 6). There was no significant difference in kisspeptin-LI levels among them. Immunocytochemistry showed positive kisspeptin-immunostaining in normal adrenal glands, with stronger immunostaining found in the medulla. Furthermore, positive kisspeptin-immunostaining was found in all types of adrenal tumors examined; adrenocortical adenomas, adrenocortical carcinomas, and pheochromocytomas. The intensity of kisspeptin-immunostaining in these adrenal tumors was, however, not so strong as that in normal adrenal medulla. The present study has shown for the first time the presence of kisspeptin-LI in adrenal glands and adrenal tumors.

Cardiovascular Risk in Patients with Nonfunctional Adrenal Incidentaloma: Myth or Reality?

It is not clear whether nonfunctional adrenal incidentaloma (NFA) increases the risk of atherosclerosis and metabolic syndrome or whether this type of adrenal tumor has been found more frequently in patients with cardiometabolic risk factors. We aimed to determine the effects of NFA on cardiometabolic risk factors and endothelial function and to compare the patients with a 1:1 cardiometabolic risk factor matched control group. Thirty-five patients with NFA were studied, and 35 body mass index-, age-, and sex-matched subjects were regarded as group 2 controls. Thirty-five cardiometabolic risk factors-matched subjects were then regarded as group 3 controls. Patients with NFA had significantly lower flow-mediated dilation (FMD)-a parameter for endothelial function-measurements compared with groups 2 and 3 (7.1 +/- 2.9% vs. 12.9 +/- 3.8% and 13.5 +/- 4.5%; P < 0.02). Frequency of metabolic syndrome was also significantly higher in NFA patients than in control groups 2 and 3 (31.4, 5.7, and 20.0%, respectively; P < 0.05). Age (Odds Ratio [OR] = 2.9), total cholesterol (OR = 2.3), and presence of adrenal incidentaloma (OR = 10) were significant independent predictors of lower FMD (P < 0.05 for all). Patients with NFA have increased prevalence of metabolic syndrome and impaired endothelial function compared with 1:1 cardiometabolic risk factor-matched controls.

Adrenal involvement in multiple endocrine neoplasia type 1: results of 7 years prospective screening

Adrenal tumors are a common manifestation of the multiple endocrine neoplasia type 1 (MEN-1) syndrome. Prevalence in recent studies varies between 9 and 45%. A genotype-phenotype correlation has been described as well as the development of adrenocortical carcinomas. Long-term prospective data are still lacking. Thirty-eight MEN-1 patients with proven germline mutations have been prospectively observed in a regular screening program in our hospital. Adrenal glands have been screened by biochemical analysis and either by endoscopic ultrasound (EUS) or computed tomography (CT) or both. Median follow-up was 48 months (12-108 months). Age at diagnosis of MEN-1, type of adrenal tumor, genotype, therapy, and clinical characteristics have been analyzed. In 21 (55%) patients, adrenal involvement of the disease was detected. Adrenal lesions were detected in average 6.9 years after the initial diagnosis of MEN-1. Median tumor size was 12 mm (5-40 mm). Tumor size smaller than 10 mm was observed in 11 patients. Twelve patients had unilateral while nine had bilateral adrenal lesions. EUS detected all adrenal tumors, whereas CT failed in seven cases. In three patients, functioning tumors (one pheochromocytoma, one bilateral Cushing adenoma, and one adrenocortical carcinoma) and one nonfunctioning adenoma were diagnosed by histology and biochemical assessment. Two laparoscopic adrenalectomies and one laparoscopic subtotal resection were performed. Nonfunctioning adrenal lesions, not characterized by histology yet, were found in 18 patients. There was no statistical difference with regard to adrenal involvement between patients with germline mutations in exons 2 and 10 (12/21) and those with mutations in exons 3-9 (6/11). MEN-1-associated adrenal tumors are mostly small, benign, and nonfunctioning and much more common than previously reported. EUS was the most sensitive imaging procedure. The genotype-pheotype correlation previously suggested by our group could not be confirmed.

Differential Expression of the Human Somatostatin Receptor Subtypes sst1 to sst5 in Various Adrenal Tumors and Normal Adrenal Gland

Somatostatin (SRIF) is a widely distributed peptide with growth-inhibiting effects in various tumors. So far, five distinct human SRIF receptor subtypes (sst1-sst5) have been identified. We investigated expression of the five ssts in various adrenal tumors and in normal adrenal gland. Tissue was obtained from ten pheochromocytomas (PHEOs), nine cortisol-secreting adenomas (CPAs), eleven aldosterone secreting adenomas (APAs) and eight non-functional adenomas (NFAs) after retroperitoneoscopic surgery, and used for RNA extraction. Adrenal tissue surrounding the tumor was available for analysis in twenty-seven cases. Receptor expression was studied by RT-PCR using sst-specific primers and subsequently confirmed by Southern blotting. Expression of all five receptor subtypes was observed in RNA obtained from normal adrenal gland. Furthermore, each receptor subtype was expressed in more than 50 % of all tumors analyzed. No sst5 expression was found in PHEOs, while sst1 was present in nearly all of these tumors. Only a few of the CPAs expressed subtypes sst1 and sst4. Expression of all five subtypes was distributed equally in APAs. No sst4 was found in any of the NFAs. Differential expression of ssts in various adrenal tumors may point to new aspects in the pathogenesis of these adenomas. Furthermore, the presence of specific ssts could expand the diagnostic and therapeutic strategies during management. New subtype specific analogues of SRIF may be used in the future depending on the type of adrenal tumor and receptor subtype expressed.

Adenomatoid of the adrenal gland

Adenomatoid tumors are common in the genital tract but rare in the adrenal gland. These tumors can be difficult to diagnose when present in extragenital sites. This type of adrenal tumor lacks specific radiographic features and can be confused preoperatively with more common adrenal gland tumors. We present the case of a 54-year-old man with an incidental right adrenal mass with calcified components and elevated urinary levels of homovanillic acid that was found to be an adenomatoid tumor of the adrenal gland.

Partial adrenalectomy in patients with multiple adrenal tumors.

Most adrenal tumors are found incidentally and appear as small solitary nodules on abdominal imaging. Occasionally, work-up demonstrates multifocal or bilateral adrenal tumors. Certain patients are predisposed to multiple lesions, such as those with hereditary forms of pheochromocytoma as seen in von Hippel-Lindau disease, multiple endocrine neoplasia type II, and von Recklinghausen's disease. Partial rather than total adrenalectomy should be considered for these patients in an attempt to preserve endogenous adrenocortical function. Partial adrenalectomy has also been used to resect other types of adrenal tumors, especially in patients with a solitary adrenal gland. A discussion of the indications for partial adrenalectomy and of the surgical technique follows.

P53 protein and its messenger ribonucleic acid in human adrenal tumors.

The role of p53 tumor suppressor gene in the pathomechanism of adrenal tumors was investigated by measuring p53 protein and its messenger ribonucleic acid (mRNA) in 12 normal human adrenals as well as in 56 adrenal tumors (7 aldosterone-producing adenomas, 5 adrenocortical adenomas causing Cushing's syndrome, 19 non-hyperfunctioning adrenocortical adenomas, 5 adrenocortical carcinomas, 12 pheochromocytomas, 3 myelolipomas, 4 ganglioneuromas and 1 hemangioma). The p53 protein concentration was significantly increased in aldosterone-producing adenomas (394+/-36 pg/mg cytosolic protein, mean+/-SE, vs 266+/-18 in normal human adrenals), whereas the concentration of this protein in Cushing's adenomas, non-hyperfunctioning adrenocortical adenomas, pheochromocytomas, and in all but one adrenocortical carcinomas was similar to that measured in normal human adrenal tissues. One adrenocortical carcinoma tissue showed very high p53 protein content (3000 pg/mg cytosolic protein). By contrast, myelolipomas (23+/-20) ganglioneuromas (43+/-15) and a hemangioma (11 pg/mg cytosolic protein) had very low p53 protein content. Northern blot analysis revealed the presence of p53 mRNA in each adrenal tissue examined with highest levels in aldosterone-producing and Cushing's adenomas. It is possible that the differences in p53 protein and/or mRNA contents reflect corresponding differences in the pathogenetic importance of p53 alterations in these types of adrenal tumors.

Imaging for adrenal tumours

Modern medical imaging has transformed the diagnosis and management of adrenal disease. The various types of adrenal tumours bear different aspects of problems in diagnostic imaging. The investigation used must be determined and monitored individually, as directed by the clinical and biochemical findings. CT plays a central role in the localization of the functioning adrenal tumours. It is regarded as the imaging modality of choice because it combines safety with a high rate of detection. It is highly sensitive in the localization of the large adrenal tumours that account for Cushing's syndrome and phaeochromocytomas, as well as the small tumours that account for primary hyperaldosteronism. It is, however, not reliable for the detection of adrenal hyperplasia, and does not yield functional imaging information. For small tumours not detectable by CT, and for ectopic tumours, complementary investigations with appropriate application of venous sampling, radionuclide scintigraphy and occasionally arteriography, will be very useful. CT-guided percutaneous biopsy is employed for the incidentalomas in oncologic patients. MRI appears to hold a great potential for the diagnosis of adrenal disorders, but this modality is awaiting wider availability of instrumentation and clearer documentation of techniques.

Black (or Brown) Adrenal Cortical Adenoma: Its Characteristic Features on Computed Tomography and Endocrine Data

Seventeen patients with adrenal adenoma causing Cushing's syndrome, eight patients with Cushing's disease due to hypersecretion of ACTH, and five patients with primary aldosteronism due to an aldosteronoma were studied for their computed tomographic (CT) patterns, hormonal profiles, and macroscopic and microscopic findings of the adrenal gland. Black (or brown) adrenal adenomas were found in 71% of the patients with Cushing's syndrome, but not in patients with aldosteronoma. The adrenal tissue of patients with Cushing's disease was predominantly yellow. The number of compact cells was larger in black or brown adenomas than in yellow tumors or hyperplastic adrenal tissue. In patients with Cushing's syndrome, urinary excretion of 17-ketosteroids (17-KS) and serum aldosterone concentrations were lower in those with black or brown adenomas than in those with yellow adenomas (P less than 0.05). Patients with Cushing's disease had even higher 17-KS and serum aldosterone levels. No difference was found in serum cortisol concentrations and dexamethasone suppressibility in two types of adenomas causing Cushing's syndrome. Visual estimation of radiological density of the adrenal tissue relative to the kidney on CT scan and quantitative measurement of it by CT number revealed a difference between the two types of adrenal tumors causing Cushing's syndrome. Adrenal tumors with decreased density on CT scan were yellow adenomas with predominantly clear cells, and those with equal or increased density were black or brown adenomas with predominantly compact cells. All aldosteronomas had decreased density and consisted of clear cells. It is suggested that black or brown adenomas of the adrenal gland have higher radiological density and accompanying lower serum aldosterone and urinary 17-KS levels than ordinary yellow tumors. The abundance of compact cells may have some significance for the development of this particular type of adrenal tumor.

A new type of adrenal tumor and its comparative histopathology

An undifferentiated adrenal tumor from a DMB-treated C3H (Jax) female mouse was found transplantable in about 50% male and 75% female homologous animals used. The “takes” were better and faster in the females; the sex in which the tumor had originated. The latent period shortened with successive passages and was shorter for females. Histologically, the transplanted tumors resembled the original tumor but tended to be more pleomorphic, highly vascular, and showed increased mitotic activity. Evidence was found to show that testosterone which inhibits induction of adrenal tumors cannot prevent their proliferation.

A new type of adrenal tumor and its comparative histopathology

A new type of adrenal tumor and its comparative histopathology

A new type of adrenal tumor and its comparative histopathology

A new type of adrenal tumor and its comparative histopathology

ADRENAL SYMPATHETIC SYNDROME WITH UNUSUAL VARIATIONS IN CARDIAC RHYTHM

Within the last few years a great deal of attention has been given to the relation of the adrenal glands to arterial hypertension. Both hyperplasia and tumor of these organs have been found in some instances to be associated with high blood pressure. In particular, a small number of instances of tumor arising from the chromaffin tissue of the adrenal medulla have been reported as characterized by an unusual clinical picture, the most striking feature of which is paroxysmal hypertension. It is the purpose of this communication to report an instance of this condition, including certain observations on the heart which are of interest. Among the published reports of instances of this type of adrenal tumor there have been several excellent descriptions of the associated clinical picture, of which condition our patient presented an extreme example. This symptom complex has been called the suprarenal sympathetic syndrome by Belt and Powell