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Cyclic AMP response of isolated Snell adrenocortical carcinoma 494 cells to trophic hormones and other substances.

Suspensions of viable cells were prepared from solid tumor of the Snell adrenocortical carcinoma 494 without the use of proteolytic enzymes. Cyclic AMP formation in these cells was stimulated by ACTH, LH, FSH and TSH but not by prostaglandins (E1, E2, F1alpha and F2alpha), insulin and secretin. Glucagon tested at a single dose level of 50 mug increased cyclic AMP to about 65% of the maximum amounts obtained with ACTH. When Ca++ was omitted from the incubation medium, the response to ACTH was considerably reduced while that to LH was essentially unchanged. Low concentrations of EGTA (0.3 MM) abolished the ACTH response almost completely but caused only a partial reduction in the response to LH; as much as 10 mM EGTA was required to obtain complete inhibition of the latter.

Adrenal Cortex Neoplasms↗

Molecular mechanisms of cell cycle control in the mouse Y1 adrenal cell line.

Y1 adrenocortical tumor cells possess amplified and overexpressed c-Ki-ras proto-oncogene, displaying chronic high levels of the c-Ki-Ras-GTP protein. Despite this oncogenic lesion, we previously reported that Y1 cells retain tight regulatory mechanisms of cell cycle control typified by the mitogenic response triggered by FGF2 in G0/G1-arrested cells. ACTH, on the other hand, elicits cAMP/PKA-mediated antimitogenic mechanisms involving Akt/PKB dephosphorylation/deactivation and c-Myc protein degradation, blocking G1 phase progression stimulated by FGF2. In this paper we report that ACTH does not directly antagonize any of the early or late sequential steps comprising the mitogenic response triggered by FGF2. In effect, ACTH targets deactivation of constitutively phosphorylated-Akt, restraining the potential of c-Ki-Ras-GTP to subvert Y1 cell cycle control. Thus, we can consider ACTH a tumor suppressor rather than an antimitogenic hormone. In addition, we present initial results showing that high constitutive levels of c-Ki-Ras-GTP render Y1 cells susceptible to dye upon FGF2 treatment. This surprising FGF2 death-effect, that is independent of the well known FGF2-mitogenic activity, might involve a natural unsuspected mechanism for restraining oncogene-induced proliferation.

Adrenal Cortex Neoplasms↗

FDG-PET in adrenocortical carcinoma.

Adrenal cortical carcinoma (ACC) is a rare malignant neoplasm with a poor prognosis. Radical surgery of the primary tumor and of local as well as of distant recurrence is the only effective treatment, and requires accurate and early localization of recurrent tumors. In this regard, we prospectively scanned 10 patients with ACC, 8 during follow-up and 2 at primary work-up. In all patients PET scans from the neck to the upper thighs were obtained 45 minutes after injection of 370 MBq [18F]FDG. Reading was done visually, with the investigator blinded to the results of other diagnostic modalities. All known sites of ACC lesions showed markedly increased FDG uptake. In 3 patients, previously unknown lesions were identified by PET in the lung (one lesion), the abdomen (3 lesions), and the skeleton (multiple), respectively. One false positive liver focus was shown by PET aside from the true positive lung metastases in the same patient. The sensitivity/specificity of PET based on different organs was 100/97%, that based on the number of PET-detected lesions (N = 23) was 100/95%. PET altered or influenced the tumor stage in 3/10 patients, modifying the subsequent therapeutic management in 2/10 patients. We conclude that FDG-PET is highly useful in ACC and should be included in the work-up for initial staging as well as for follow-up.

Abdominal Neoplasms↗

Laparoscopic adrenal surgery: new frontiers.

After about 10 years of experience, laparoscopic adrenalectomy has become the gold standard for the treatment of adrenal lesions. Here, we describe the presenting features, imaging methods, and current surgical approaches to diseases of the adrenal gland. There is general agreement on the suitability of the laparoscopic approach for benign adrenal lesions, but controversy exists about using laparoscopy for suspected adrenal malignancy, metastasis, and partial adrenalectomy. This article reviews the literature on laparoscopic adrenalectomy. In particular, we focus our attention on the new surgical approaches to the gland. We evaluate the indications, operative techniques, and tools for partial adrenalectomy, and we discuss new surgical strategies such as cryosurgery and radiofrequency ablation.

Adrenal Cortex Neoplasms↗

Laparoscopic approach to the adrenal tumors.

Over the years, a number of different surgical approaches to the adrenal glands have been devised. The anterior transabdominal approach is considered to be a source of postoperative morbidity. However, this conviction can be changed. The laparoscopic approach was used in four patients. One had a right 5 cm nonfunctioning tumor, the second had a 1.8 cm right aldosterone-producing adenoma, the third patient had a 4 cm adrenocortical adenoma, and the fourth patient had a bilateral pheochromocytoma (tumor size was 3.5 cm and 4.5 cm in the right and left adrenals, respectively). Carbon dioxide pneumoperitoneum was used in three patients, but helium pneumoperitoneum was used in the patient with bilateral pheochromocytoma to prevent CO2 retention. Single right adrenalectomy lasted between 2 h and 2 h 30 min, and bilateral adrenalectomy lasted 5 h 30 min. The hospital stay was between 3 and 4 days. Unilateral or bilateral adrenalectomy through laparoscopy can be performed safely and has the advantage of avoiding the muscular trauma related to laparotomy or rib resection necessary for the extraperitoneal approach.

Adolescent↗

Genetic changes in human adrenocortical carcinomas.

Recent studies have suggested that loss of heterozygosity at loci on the short arm of human chromosome 11 (11p) may be important in the pathogenesis of benign and malignant adrenal cortical tumors. To test this concept, adrenocortical carcinomas from nine patients and benign adrenal cortical lesions from eight patients were tested for loss of alleles at loci on human chromosomes 11, 13, and 17. All patients with adrenocortical carcinoma whose normal somatic tissues were heterozygous for a locus on chromosome 17p had lost alleles in the tumor. Four of six patients with adrenocortical carcinoma who were heterozygous for one or more alleles on chromosome 11p in normal tissues had lost 11p alleles in the tumor. Three of six patients with adrenocortical carcinoma showed loss of 13q alleles in the tumor. Loss of alleles on chromosomes 11p, 13q, and 17p was observed in primary tumors and metastases but not in adrenocortical adenomas or hyperplastic lesions of the adrenal cortex. One patient with adrenocortical carcinoma had a somatic mutation in the HRAS1 gene in the normal adrenal gland. The consistency of the genetic changes on chromosomes 11p, 13q, and 17p suggests that they are important in the pathogenesis of adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗

Adrenal carcinosarcoma presenting in a woman with clinical signs of virilization. A case report with immunohistochemical and ultrastructural findings.

An adrenal carcinosarcoma is reported in a 29-year-old female presenting with clinical signs of virilization. This is the first reported case of a functioning adrenal carcinosarcoma in the English language literature. The tumor measured 12.5 cm in greatest dimension, weighed 610 g, and consisted of large areas of typical adrenal cortical carcinoma that was, however, interspersed with multiple foci of sarcoma. Rhabdomyosarcomatous elements were identified and confirmed both immunohistochemically and ultrastructurally. After radical resection, the patient received adjuvant mitotane therapy but developed rapid local and metastatic recurrence. Systemic chemotherapy was unsuccessful, and the patient died 8 months after surgery.

Adrenal Cortex Neoplasms↗

Selection of patients and operative approach in primary aldosteronism.

A system for discriminating between adrenal adenoma and hyperplasia based on the levels of aldosterone production, plasma renin concentration, severity of electrolyte disturbances, plasma aldosterone patterns during recumbency and after assuming erect posture, and 131I-19-iodocholesterol scan has been developed. Indicated for operation are patients with adenomas whose elevated blood pressure cannot be continuously controlled with usual doses of medication and patients with documented deterioration of target organ function. Adrenalectomy has been performed 83 times in 81 patients with a diagnosis of primary hyperaldosteronism. Results of excision of adrenal adenomas have been excellent with significant lowering of blood pressure in all cases and cure of hypertension in over 60%. Results of total or subtotal adrenalectomy for hyperplasia have been poor with almost all patients still requiring medication for hypertension. Adenomas have always been unilateral, and usually can be localized so that unilateral exploration is curative. Therefore, we have tried to distinguish preoperatively between adenoma and hyperplasia. Anterior transperitoneal adrenalectomy has been effective with few complications, and no postoperative hypercortisolism after unilateral adrenalectomy for adenoma. The unilateral extraperitoneal approach gives shorter morbidity and potentially fewer serious complications.

Adenoma↗

Surgical management of Cushing's syndrome with emphasis on adrenal autotransplantation.

Cushing's syndrome may be caused by pituitary ACTH, ectopically produced ACTH, adrenocortical tumor or medication. Cushing's disease, due to excessive pituitary ACTH resulting in adrenocortical hyperplasia, remains a complex endocrine disorder for which no single treatment is wholly satisfactory. Twenty-two patients with surgically treated Cushing's syndrome are presented: Four with benign adrenocortical adenoma, two with adrenocortical carcinoma and 16 with adrenocortical hyperplasia. The four benign adenomas were excised with the one death due to respiratory failure and sepsis. Both patients with carcinoma and liver metastases died of their tumors. Of the 16 patients with adrenocortical hyperplasia and Cushing's disease, eight underwent subtotal adrenalectomy and thereafter eight had total intra-abdominal adrenalectomy with autotransplantation of adrenal tissue to the thigh. There was one operative death. Total adrenalectomy has now replaced subtotal resection in most clinics. All eight of the patients who had adrenal autotransplantation exhibited biopsy or functional evidence of some degree of graft survival. On patient stopped steroid replacement permanently and another developed recurrent Cushing's syndrome from the grafts. Of a total of 26 reported patients with adrenal autotransplants surveyed, 22 exhibited evidence of graft survival, 16 were able to discontinue steroid replacement therapy and three eventually developed recurrent Cushing's syndrome from the transplants. There is now strong evidence that most patients with Cushing's disease harbor a pituitary basophil ademona, and in the future the initial surgical attack may be directed to the pituitary rather than to the adrenals.

Adenoma↗

The incidentally discovered adrenal mass.

With the wider application of increasingly sensitive computed tomographic scans, more adrenal masses will be discovered incidentally. Because benign lesions of the adrenal are much commoner than malignant ones, an approach is needed to determine which incidentally discovered masses should be removed. The history and physical examination may guide the evaluation. Imaging studies and needle biopsies have limited value. If the history and physical findings do not suggest a diagnosis, an approach using the size of the mass, results of any cyst puncture, and a biochemical assessment may determine which patients should have surgery. This approach is based on the relative prevalence of benign and malignant clinically silent adrenal tumors.

17-Hydroxycorticosteroids↗

Advances in the management of adrenal tumors.

Adrenal tumors are very common, with the majority being nonhypersecretory and benign and less than 1% being malignant. Most primary adrenal tumors are sporadic, but may be associated with other endocrine and familial disorders, especially pheochromocytoma. All patients with "sporadic" pheochromocytoma should be screened for MEN-2 and Von Hippel-Lindau disease. As in many endocrine tumors, there are no uniform definitive histologic criteria to distinguish malignancy, which is dependent on the clinical behavior of the tumor and is accurately diagnosed in the presence of adjacent organ invasion, recurrence, or distant metastasis. Surgery remains the cornerstone and the treatment of choice for functional and primary malignant adrenal tumors, both for cure and palliation, with low morbidity and mortality.

Adrenal Cortex Neoplasms↗

Adrenal incidentalomas.

The term adrenal incidentaloma refers to an adrenal mass occasionally and unexpectedly discovered by an abdominal imaging procedure performed for reasons a priori unrelated to adrenal dysfunction. The prevalence of adrenal incidentalomas as discovered by computed tomographic scan examination is estimated to be between 1% and 4%. The vast majority of these lesions are of adrenocortical origin, most often adenomas. Identification of steroid or catecholamine-secreting tumors is important but usually solved with appropriate endocrinologic investigations. A difficult problem, however, is to distinguish between benign and malignant primary or secondary tumors. Size less than 4 cm and an unenhanced computed tomographic attenuation under 10 Hounsfield Units (HU) are findings in favor of a benign adrenocortical adenoma, as is a positive NP 59 scintigraphic examination. The pathogenesis of adrenal tumors is not well understood. However, alterations of the cyclic AMP signalling pathway have recently been observed in benign adrenocortical lesions and molecular defects associated with insulin-like growth factor-II overexpression in malignant adrenocortical tumors.

Adenoma↗

Adrenal scintigraphy in low renin essential hypertension.

Adrenal scintigraphy was performed on 23 patients with low renin essential hypertension (LREH). After baseline scintigraphy was shown not to be helpful, 13 of these 23 patients underwent dexamethasone suppression adrenal scintigraphy. Four adrenal imaging patterns were observed: unilateral imaging with adenoma; bilateral early or late imaging with hyperplasia; no uptake with normal adrenals. These imaging patterns were shown to be predictive of the individual patient's response to spironolactone administration of functional adrenal cortical abnormalities in LREH supplies direct evidence for the hypothesis that LREH has an adrenal mineralocorticoid etiology.

Adenoma↗

Computed tomography and scintigraphy of aldosteronoma. A comparative study.

Twelve cases of aldosteronoma were evaluated with CT and radioisotope scintigraphy to compare the diagnostic capability of both methods. All cases were diagnosed with scintigraphy, while six of 12 cases were diagnosed with CT. However, considering that nuclear imaging requires seven or eight days for evaluation, and the radiation dose is relatively high, it seems reasonable to perform CT scans initially in the localization of an aldosteronoma and to include scintigraphy in those cases in which aldosteronoma is not demonstrated by CT.

19-Iodocholesterol↗