Adrenal cortex tumors

Fig. 1. Pertussis toxin-mediated ADP ribosylation of membrane G proteins. Isolated cell membranes (50 ng of protein) from N1E 115 cells (mouse neuroblastoma cell line), N2A cells (mouse neuroblastoma cell line), S49-1 eye cells (S49(-) mutated mouse lymphoma cell line deficient in Ga ), 549 wt cells (wild-type mouse lymphoma cell line), RBL (RBL 2H3 rat basophilic leukemia cell line), GH3 cells (GH3 rat hypophyseal tumor cell line), PC-12 (rat pheochromocytoma cell line), HIT-T15 cells (hamster insulinoma cell line), Y-1 cells (mouse adrenal cortex tumor cell line), 108 cc 15 cells (mouse/rat neuroblastoma x glioma hybrid cell line), HL-60 cells (DMSO-differentiated human leukemia cell line), HL-60 (+PT) cells (HL-60 cells pretreated with 25 ng/ml of pertussis toxin for 24 h prior to preparation of membranes), RINm5F cells (rat insulinoma cell line), and C6-2 cells (rat glioma cell line) were subjected to P-ADP-ribosylation as described in section 4.3.3. Samples were precipitated as outlined in section 4.3.5 and subjected to SDS-PAGE with separating gels containing 8% acrylamide (w/v). An autoradiogram of the dried gel is shown. Molecular masses of marker proteins are indicated (kDa). Modified Ga proteins migrate at approximately 40 kDa. Radioactivity running in front of the 30 kDa marker protein comigrates with the dye front...

Cloned mouse adrenal cortex tumor cells respond to ACTH with an increased output of steroids which is independent of the growth phase T. v fithin 5 minutes the cells retract from the surface of the vessel and from each other and within 1 hour a rounded-up morphology is seen. This cell line is unable to hydroxylate position 21 but has a high ability to reduce the 20-keto group. 

The remaining 18% of Cushing s syndrome cases are ACTH-independent and are almost equally divided between adrenal adenomas and adrenal carcinomas, with rare cases caused by micronodular or macronodular hyperplasia." The majority of adrenal cortex tumors are benign adenomas. Adrenal carcinoma is found more often in children than in adults with Cushing s syndrome. 

Conditions of this type, generally referred to as hypoadrenalism, may result from several causes, including destruction of the cortex by tuberculosis or atrophy or decreased secretion of adrenocorticotropin (adenocorticotropic hormone [ACTH]) because of diseases of the anterior pituitary (adenohypophysis). Cushing s disease, or hyperadrenalism, on the other hand, may result from adrenal cortex tumors or increased production of ACTH caused by pituitary carcinoma. Cushing s syndrome also is rare, occurring in only two to five people for every 1 million people each year. Approximately 10 percent of newly diagnosed cases are observed in children and teenagers. 

Metyrapone is commonly used in tests of adrenal function. The blood levels of 11-deoxycortisol and the urinary excretion of 17-hydroxycorticoids are measured before and after administration of the compound. Normally, there is a twofold or greater increase in the urinary 17-hydroxycorticoid excretion. A dose of 300-500 mg every 4 hours for six doses is often used, and urine collections are made on the day before and the day after treatment. In patients with Cushing s syndrome, a normal response to metyrapone indicates that the cortisol excess is not the result of a cortisol-secreting adrenal carcinoma or adenoma, since secretion by such tumors produces suppression of ACTH and atrophy of normal adrenal cortex. 

Mitotane (Figure 39-5), a drug related to the DDT class of insecticides, has a nonselective cytotoxic action on the adrenal cortex in dogs and to a lesser extent in humans. This drug is administered orally in divided doses up to 12 g daily. About one third of patients with adrenal carcinoma show a reduction in tumor mass. In 80% of patients, the toxic effects are sufficiently severe to require dose reduction. These... 

Several relatively common disorders result in aldosterone secretion abnormalities and aberrations of electrolyte status. In Addison s disease, the adrenal cortex is often destroyed through autoimmune processes. One of the effects is a lack of aldosterone secretion and decreased Na+ retention by the patient. In a typical Addison s disease patient, serum [Na+] and [CL] are 128 and 96 meq/L, respectively (see Table 16.2 for normal values). Potassium levels are elevated, 6 meq/L or higher, because the Na+ reabsorption system of the kidney, which is under aldosterone control, moves K+ into the urine just as it moves Na+ back into plasma. Thus, if more Na+ is excreted, more K+ is reabsorbed. Bicarbonate remains relatively normal. The opposite situation prevails in Cushing s disease, however, in which an overproduction of adrenocorticosteroids, especially cortisol, is present. Glucocorticoids have mild mineralocorticoid activities, but ACTH also increases aldosterone secretion. This may be caused by an oversecretion of ACTH by a tumor or by adrenal hyperplasia or tumors. Serum sodium in Cushing s disease is slightly elevated, [K+] is below normal (hypokalemia), and metabolic alkalosis is present. The patient is usually hypertensive. A more severe electrolyte abnormality is seen in Conn s syndrome or primary aldosteronism, usually caused by an adrenal tumor. Increased blood aldosterone levels result in the urinary loss of K+ and H+, retention of Na+ (hypernatremia), alkalosis, and profound hypertension. 

Both type I and type II cyclic AMP-dependent protein kinase forms are found in the adrenal cortex [8]. The predominant form in the Y1 adrenocortical tumor cell line is type I [2], Yl(Kin) mutants with RI subunits which have a much lower affinity for cyclic AMP lack ACTH-stimulated cyclic AMP production, thus demonstrating the involvement of the type I form of cyclic AMP-dependent protein kinase in the action of ACTH. 

Cushing s syndrome is caused by the hypersecretion of cortisol by cells in the adrenal cortex. Hypersecretion can be due to overstimulation of cortisol-releasing mechanisms by excess ACTH, a pituitary hormone. Cushing s can result from pituitary or adrenal tumors. It is further characterized by obesity, a rounded face, muscle weakness, a tendency to bruise easily, and numerous other complications. 

E. ACTH levels were low, so the elevated cortisol levels were most likely caused by a secretory tumor of the adrenal cortex. The elevated cortisol levels caused the elevation of blood glucose. 

Cortisol. Cortisol, secreted by the adrenal cortex in response to adrenocorticotropic hormone (ACTH), stimulates gluconeogenesis and increases the breakdown of protein and fat. Patients with Cushing s syndrome have increased cortisol owing to a tumor or hyperplasia of the adrenal cortex and may become hyperglycemic. In contrast, people with Addisons disease have adrenocortical insufficiency because of destruction or atrophy of the adrenal cortex and may exhibit hypoglycemia. ... 

Munro LM, Kennedy A, McNicol AM. The expression of inhib-in/activin subunits in the human adrenal cortex and its tumors. J Endocrinol. 1999 161 341-347. 

Miettinen M, Lehto V-P, Virtanen 1. Immunofluorescence microscopic evaluation of the intermediate filament expression of the adrenal cortex and medulla and their tumors. Am J Pathol. 

Cote RJ, Cardon-Cardo C, Reuter VE, Rosen PP. Immuno-pathology of adrenal and renal cortical tumors Coordinated change in antigen expression is associated with neoplastic conversion in the adrenal cortex. Am J Pathol. 1990 136 1077-1084. 

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