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Outcomes of adrenal cortical carcinoma in the United States.

BACKGROUND: Improvements in the sensitivity of radiographic imaging have lead to an increase in the number of adrenal masses diagnosed. The purpose of this study is to determine if technologic advancements have resulted in the diagnosis of earlier-staged adrenal cortical cancer (ACC) and to determine if the survival of patients with ACC has improved over the past 15 years. METHODS: Patients with ACC were identified in the Surveillance, Epidemiology, and End Results database between 1988 and 2002. Changes in demographics, stage, size, and treatment were analyzed by standard statistical testing. RESULTS: We identified 602 patients with a mean age of 53 years and an average tumor size of 11.8 cm. Two hundred thirty-eight (39.5%) patients presented with localized disease (stages I and II), and 311 (52%) patients presented with advanced disease (stages III and IV). The comparison of smaller lesions and number of patients were 5 to 6 cm in 24 (4%) patients, 4 to 5 cm in 27 (4.5%) patients, and <4 cm in 19 (3.1%) patients. Patients with masses less than 5 cm were statistically more likely to have localized disease (P <. 001). Age (P = .10), tumor size (P = .85), tumor stage (P = .45), and 5-year survival (P = .5) did not change over the 15-year study. CONCLUSIONS: Over the 15-year study, patients with ACC were not diagnosed at an earlier stage or with tumors smaller, and survival did not improve.

Adrenal Cortex Neoplasms↗

Analysis of genomic alterations in sporadic adrenocortical lesions. Gain of chromosome 17 is an early event in adrenocortical tumorigenesis.

Genetic changes underlying the tumorigenesis of sporadic adrenocortical tumors are poorly characterized. To search for characteristic genomic imbalances involved in adrenocortical tumors, we examined 41 adrenocortical lesions (12 carcinomas, 23 adenomas, and 6 hyperplasias) by comparative genomic hybridization. Our results show that genetic alterations are more frequent in malignant than in benign lesions and that they rarely occur in hyperplastic lesions. The most frequent DNA copy number changes in adrenocortical carcinomas included losses of 1p21-31, 2q, 3p, 3q, 6q, 9p, and 11q14-qter, as well as gains and amplifications of 5q12, 9q32-qter, 12q, and 20q. The genomic aberrations prevalently occurring in adrenocortical adenomas were gains of 17q, 17p, and 9q32-qter. Gains found in 2 of 6 adrenocortical hyperplastic lesions involved chromosome 17 or 17q only. These data indicate that oncogenes determining the early tumorigenesis of adrenocortical tumors may exist on chromosome 17 and that the number of genomic alterations is closely associated with tumor behavior in adrenocortical tumors.

Adolescent↗

Laparoscopic ultrasound imaging of adrenal tumors during laparoscopic adrenalectomy.

BACKGROUND: The purpose of this study was to determine the usefulness of laparoscopic ultrasound (LUS) during laparoscopic adrenalectomy (LA) and to define the ultrasound imaging characteristics of various adrenal tumors. METHODS: LUS was utilized in 27 patients who underwent LA (including one bilateral adrenalectomy) from May 1994 to October 1998. Tumor size ranged from 1.0 to 5.5 cm (mean 3.3 cm), and a transabdominal lateral approach to LA was used. RESULTS: LUS localized the adrenal gland and tumor in all 28 adrenalectomies and demonstrated the relationship of the tumor to the kidney and adjacent vascular structures (renal artery/vein and inferior vena cava). The adrenal vein was visualized sonographically in only six cases (21 %). Pheochromocytomas were mild to markedly heterogenous, whereas most aldosteronomas and cortical adenomas were homogenous. LUS provided useful information to the surgeon in 11 of 28 cases (39%) by: 1) localizing the adrenal gland and tumor and/or guiding the dissection; 2) demonstrating that tumors > or =4 cm were confined to the adrenal gland; and 3) investigating suspected pathology in other organs. Mean operating time for LUS was 10.9 min (range 5 to 24 min) and calculated hospital charges were $602. CONCLUSIONS: LUS accurately localizes adrenal tumors, helps define their relationship to adjacent structures, and provides confirmation that larger tumors are amenable to laparoscopic resection. LUS is a useful adjunct to laparoscopic adrenalectomy in selected patients.

Adrenal Cortex Neoplasms↗

Fine structure of a virilizing adrenocortical adenoma.

An adrenocortical adenoma associated with adrenogenital syndrome in a two-year-old boy was investigated light and electron microscopically. Urinary 17-ketosteroid excretion was considerably elevated and unresponsive to dexamethasone administration. The level returned to normal after surgical removal of the tumour. Adenomatous cells display striking cellular and nuclear pleomorphism. Megalocytes with huge nuclei and nucleoli frequently occur. Deep cytoplasmic indentations cause nuclear pseudoinclusions and bizarre shape of the nuclei. True nuclear inclusions are also seen, as well as nuclear fragmentation. Cytoplasmic organelles show striking morphological alterations. Mitochondria with lamellar and tubular cristae are transformed into round or ovoid organelles of vesicular type. Their internal compartment is reduced, matrix material increases relatively, and mitochondrial inclusion bodies develop. Mitochondrial inclusions are identified as corresponding to fuchsinophil (siderophil or argyrophil) granules seen in the light microscope. Their staining properties indicate their glycoprotein nature. Vesicular profiles of smooth endoplasmic reticulum predominate and stacks of rough endoplasmic reticulum are transformed into tubules and vesicles. In Golgi regions, only vesicular elements are enriched. Lipid droplets are scarce. It was not possible to demonstrate histochemically catalase activity in microbodies. Dense bodies only occur in small, undifferentiated tumour cells. Multivesicular bodies, autophagosomes and residual bodies are rare. Lipofuscin is absent. Tumour cells are thought to derive from a population of undifferentiated cells ("germinative tumour cells"). Their morphological features and organelle equipment during a hypothetical course of differentiation and following dedifferentiation is described and discussed with respect to exceeding androgen synthesis.

Adenoma↗

Lack of toxic effects of F 12511, a novel potent inhibitor of acyl-coenzyme A: cholesterol O-acyltransferase, on human adrenocortical cells in culture.

Inhibition of acyl-coenzyme A: cholesterol O-acyltransferase (EC 2.3.1.26; ACAT) reduces intracellular cholesteryl esters that are substrates for steroidogenesis in adrenal cells. The adrenal side effects of ACAT inhibitors remain a key point for their development as antiatherosclerotic agents. The aim of this study was to characterize the effects of a novel and powerful ACAT inhibitor, F 12511 (S)-2',3',5'-trimethyl-4'-hydroxy-alpha-dodecylthio-phenylacetanilide, on the NCI-H295R cell line, which has functional properties comparable to those of normal human adrenal cells. F 12511 incubated with cultured cells for 4-72 hr strongly inhibited cholesteryl oleate formation. The concentrations required to produce 50% inhibition (IC50) values) ranged from 20 to 50 nM; in the presence of low-density lipoproteins (LDL), this effect was paralleled by a decrease in cholesteryl ester mass and an increase in intracellular free cholesterol. At concentrations 100-fold larger than the IC(50) value for up to 48 hr, F 12511 reduced neither the basal release of cortisol and aldosterone nor the production of cortisol stimulated by forskolin. F 12511 did not modify the mRNA levels of the steroidogenic enzyme genes cytochrome P450 cholesterol side-chain cleavage (P450scc), cytochrome P450 17alpha-hydroxylase (P450c17), or cytochrome P450 21-hydroxylase (P450c21) or those of the LDL receptor and high-density lipoprotein scavenger receptor class B, type I (SR-BI) genes, either in the presence or absence of adenosine 3',5'-cyclic monophosphate stimulation for 24 hr. Exposure to F 12511 at up to 3 microM for 24 or 48 hr did not result in significant change in morphological and ultrastructural characteristics; the cytoplasm contained large numbers of mitochondria with intact crystae, and the same typical features of secretory activity were observed in NCI-H295R control cells. Exposure to 3 microM of F 12511 for 96 hr also did not affect cell viability. These data demonstrate that reduction of the substrate for steroidogenesis by the ACAT inhibitor F 12511 impairs neither steroid production nor transcription of genes involved in steroidogenesis and lipoprotein uptake in the pluripotent human adrenal cell line NCI-H295R.

Adrenal Cortex Neoplasms↗

Cloning of a novel kinase (SIK) of the SNF1/AMPK family from high salt diet-treated rat adrenal.

PCR-coupled cDNA subtraction hybridization was adapted to identify the genes expressed in the adrenocortical tissues from high salt diet-treated rat. A novel cDNA clone, termed salt-inducible kinase (SIK), encoding a polypeptide (776 amino acids) with significant similarity to protein serine/ threonine kinases in the SNF1/AMPK family was isolated. An in vitro kinase assay demonstrated that SIK protein had autophosphorylation activity. Northern blot revealed that SIK mRNA levels were markedly augmented by ACTH treatment both in rat adrenal glands and in Y1 cells. SIK may play an important role in the regulation of adrenocortical functions in response to high plasma salt and ACTH stimulation.

AMP-Activated Protein Kinase Kinases↗

Adrenocortical tumor in a patient with untreated congenital adrenocortical hyperplasia owing to 21-hydroxylase deficiency: characterization of steroidogenic lesions.

We report a case of congenital adrenal hyperplasia complicated by a right adrenal adenoma. The congenital adrenal hyperplasia was confirmed by extremely high levels of basal serum 17 alpha-hydroxy-progesterone and urinary pregnantriol as well as an exaggerated response of 17 alpha-hydroxyprogesterone to adrenocorticotropic hormone. On roentogenographic examinations and an echogram a huge calcified tumor was seen in the right adrenal gland. Histological findings indicated an adrenocortical adenoma. Culture of the tumor cells showed an accentuated response in the ratio of 17 alpha-hydroxy-progesterone to desoxycortisol with adrenocorticotropic hormone as a stimulator, suggesting that such adenoma cells also lack 21-hydroxylase activity. Our study clearly demonstrates that tumor cells have the same steroidogenic lesions as hyperplasia.

Adenoma↗

Usefulness of adrenal venography and iodocholesterol scan in adrenal surgery.

Adrenal scintiscanning and venography with sampling of adrenal venous blood are valuable methods to localize adrenal cortical lesions of Cushing's syndrome and primary aldosteronism. Adrenal scintiscanning with dexamethasone suppression is most useful in differentiating adenoma from hyperplasia of primary aldosteronism.

19-Iodocholesterol↗

Adrenal surgery for hypercortisolism--surgical aspects.

BACKGROUND: Patients with endogenous hypercortisolism are thought to be at high risk for adrenalectomy and may experience significant postoperative surgical mortality/morbidity. METHODS: From 1981 through 1991, 91 patients underwent adrenal resection for endogenous hypercortisolism. Causes were adrenal-dependent Cushing's syndrome (50%), pituitary-dependent Cushing's syndrome (27%), and an ectopic adrenocorticotropic hormone-secreting tumor (23%). Causes of adrenal-dependent Cushing's syndrome were adrenocortical adenoma (72%), bilateral nodular hyperplasia (20%), and adrenocortical carcinoma (8%). Comparative mean length of hospitalization for patients undergoing unilateral anterior versus posterior approach was 8 versus 6 days, and bilateral anterior versus posterior was 11 versus 6 days. RESULTS: Operative mortality was 2.6%. Only one patient had a wound infection, and no patient had either a venous thrombosis or a pulmonary embolism. Delayed wound healing occurred in three patients. CONCLUSIONS: (1) Adrenal surgery can be performed today with low morbidity/mortality. (2) Although there is an effect of hypercortisolism on wound healing, infection, diabetes, hypertension, coronary artery disease, and pulmonary embolism, it was possible to perform adrenalectomy surgically with acceptable morbidity and mortality. (3) These results may serve as a standard against which laparoscopic adrenalectomy may be compared.

Adenoma↗

Pediatric endocrine surgery.

The pediatric surgeon is in a unique position to understand endocrine surgery and, therefore, is expected to develop considerable expertise in this area. In recent years numerous advances and changes have occurred in pediatric endocrine surgery that have led to greater understanding of the disease processes and syndromes and the development of new diagnostic techniques and surgical approaches.

Adolescent↗