cortodoxone and Carcinoma

Radiological examination may unexpectedly reveal an adrenal mass. Current algorithms for differentiating between benign and malignant lesions mainly rely on size and densitometry on unenhanced CT, which have limited specificity. We examined the diagnostic value of urinary steroid profiling by gas chromatography/mass-spectrometry (GC/MS) in differentiating between benign and malignant adrenal tumors. A retrospective study in two referral centers for patients with adrenal disease was performed. All urinary steroid profiles ordered for evaluation of an adrenal tumor between January 2000 and November 2011 were examined. Patients were diagnosed with adrenal cortical carcinoma (ACC), adrenal cortical adenoma (ACA), or other adrenal mass. Results of hormonal measurements, imaging studies, pathology reports, and clinical outcome were retrieved from medical records. The diagnostic value of individual urinary steroid metabolites was determined by receiver operating characteristics analysis. Cut-off values were compared to reference values from an age and gender-standardized population of healthy controls. Eighteen steroid metabolites were excreted in significantly higher concentrations in patients with ACC (n = 27) compared to patients with ACA (n = 107) or other adrenal conditions (n = 18). Tetrahydro-11-deoxycortisol (THS) at a cut-off value of 2.35 μmol/24 h differentiated ACC from other adrenal disorders with 100% sensitivity and 99% specificity. Elevated urinary excretion of THS was associated with a very high sensitivity and specificity to differentiate between an ACC and a benign adrenal mass. Urinary steroid profiling might be a useful diagnostic test for the evaluation of patients with an adrenal incidentaloma.

Topics: Adrenal Cortex Neoplasms; Adult; Aged; Carcinoma; Cohort Studies; Cortodoxone; Female; Humans; Male; Middle Aged; Prognosis; Steroids

Adrenocortical carcinoma is a rare malignancy in children, with a high mortality. Little is known about long-term outcome, especially in infants treated with mitotane. We report the successful long-term outcome of a case of metastatic adrenocortical carcinoma presenting in infancy treated with surgical resection and mitotane. The patient presented at 2 months of age with Cushing's syndrome, a large adrenal mass, and elevated adrenal steroid levels. The tumor was removed surgically. Intraoperative findings included an adrenal tumor (confirmed malignant pathologically) invading the adrenal vein and vena cava. After surgery he was treated with mitotane at a dose of 2 g/d. Six months after surgery 11-deoxycortisol levels increased, and a computed tomography scan showed a pulmonary metastasis. Mitotane was increased to 2.5 g/d, and the metastasis was removed surgically. Plasma mitotane levels ranged 10-15 micro g/ml. Tumor markers remained normal, and mitotane was discontinued at 18 months. During therapy the patient's somatic growth was poor. His motor and speech development was delayed. After mitotane was discontinued he demonstrated catch-up growth. This case shows successful long-term outcome and recovery from the toxic effects of mitotane.

Topics: Adrenal Cortex Neoplasms; Antineoplastic Agents, Hormonal; Carcinoma; Cortodoxone; Growth Disorders; Humans; Infant; Lung Neoplasms; Male; Mitotane; Neoplasm Metastasis; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography

To analyse the clinical and biochemical effects of metyrapone in the treatment of Cushing's syndrome.. An evaluation of the standard clinical practice at one institution.. Ninety-one patients with Cushing's syndrome: 57 pituitary-dependent Cushing's disease, 10 adrenocortical adenomas, six adrenocortical carcinomas and 18 ectopic ACTH syndrome.. The acute response to metyrapone was assessed by measuring cortisol, 11-desoxycortisol and ACTH at 0, 1, 2, 3, 4 hours after a test dose of 750 mg of metyrapone. The longer-term effect of metyrapone was judged by measuring serum cortisol at 0900, 1200, 1500, 1800, 2100 and sometimes 2400 h and calculating a mean.. A test dose of 750 mg of metyrapone decreased serum cortisol levels within 2 hours in all groups of patients and this effect was sustained at 4 hours. At the same time, serum 11-desoxycortisol levels increased in all patients, while plasma ACTH increased in patients with pituitary Cushing's disease and the ectopic ACTH-syndrome. Fifty-three patients with Cushing's disease were followed on short-term metyrapone therapy (1 to 16 weeks) before other more definitive therapy. Their mean cortisol levels (median 654 nmol/l, range 408-2240) dropped to the target range of less than 400 nmol/l in 40 patients (75%) on a median metyrapone dose of 2250 mg/day (range 750-6000). Metyrapone was given long term in 24 patients with Cushing's disease who had been given pituitary irradiation, for a median of 27 months (range 3-140) with adequate control of hypercortisolaemia in 20 (83%). In 10 patients with adrenocortical adenomas and six with adrenocortical carcinomas, metyrapone in a median dose of 1750 mg/day (range 750-6000) reduced their mean cortisol levels (median 847 nmol/l, range 408-2000) to less than 400 nmol/l in 13 patients (81%). In 18 patients with the ectopic ACTH-syndrome the 'mean cortisol levels', obtained from five or six samples on the test day (median 1023 nmol/l, range 823-6354) were reduced to less than 400 nmol/l in 13 patients (70%), on a median dose of 4000 mg/day (range 1000-6000). Reduction of cortisol levels was clearly associated with clinical and biochemical improvement. The medication was well tolerated. Transient hypoadrenalism and hirsutism were unusual but were the most common side-effects.. In our experience metyrapone remains a most useful agent for controlling cortisol levels in the management of Cushing's syndrome of all types.

Topics: ACTH Syndrome, Ectopic; Adenoma; Adolescent; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Adult; Aged; Carcinoma; Cortodoxone; Cushing Syndrome; Depression, Chemical; Female; Humans; Hydrocortisone; Male; Metyrapone; Middle Aged; Time Factors

The urinary steroid profile was determined in 24 patients with adrenocortical carcinoma. Seventeen of the patients had Cushing's syndrome, virilization or feminization, and 7 had no signs of endocrine disease. Seven of the 11 patients still alive are free of disease, after a follow-up period of 5-75 months. The steroid profile varied widely between the patients with adrenocortical carcinoma. Patients with Cushing's syndrome had increased levels of cortisol metabolites and those with virilism had raised excretion of androgen metabolites. Six of the patients with adrenocortical carcinoma showed normal values of these metabolites. In 23 of the 24 patients the excretion of 3 beta-hydroxy-5-ene steroids and/or metabolites of cortisol precursors, such as tetrahydro-11-deoxycortisol, were significantly increased, compared with healthy controls or patients with adrenal adenomas. These findings suggest a relative deficit or low activity of 3 beta-hydroxysteroid dehydrogenase/delta isomerase and/or 11 beta-hydroxylase in tumour tissue. In the single patient where the steroid profile failed to indicate malignancy, hypercortisolism was seen and the tumour mass was small. The steroid excretion normalized after radical surgery and decreased in patients responding to chemotherapy. During recurred disease the metabolites of 3 beta-hydroxy-5-ene steroids and/or cortisol precursors increased, but in some patients the excretory pattern then was different from that seen before treatment.

Topics: Adrenal Cortex Neoplasms; Adult; Aged; Biomarkers, Tumor; Carcinoma; Child; Child, Preschool; Cortodoxone; Dehydroepiandrosterone; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Steroids

Selective adrenal vein catheterization was done preoperatively in 11 patients with Cushing's syndrome owing to either an adrenal adenoma (6) or an adrenal carcinoma (5). Peripheral and adrenal venous blood (tumor side) was analyzed for progesterone, 17-hydroxyprogesterone, testosterone, delta-4-androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, cortisol and 11-deoxycortisol. Comparisons were made of the ratios of precursors to products in the androgen and cortisol production pathways. In adrenal vein samples, cortisol levels were higher in the adenoma patients (p equals 0.06). These patients had a higher ratio of 17-hydroxyprogesterone to delta-4-androstenedione (p less than 0.04). The ratio of 11-deoxycortisol to cortisol was higher in the carcinoma patients (p less than 0.02). In the peripheral samples, the carcinoma patients had higher levels of testosterone and 11-deoxycortisol (p less than 0.02) and progesterone (p equals 0.05). The most striking differences were in the peripheral levels of 17-hydroxyprogesterone, delta-4-androstenedione and dehydroepiandrosterone, which were 10 to 20 times higher in the carcinoma group (p less than 0.005). The ratios of progesterone to 17-hydroxyprogesterone and 17-hydroxyprogesterone to 11-deoxycortisol were higher in the adenoma group (p less than 0.005 and p equals 0.06, respectively). The peripheral blood ratio of 11-deoxycortisol to cortisol was higher in the carcinoma group (p less than 0.03). These data indicate that peripheral and adrenal venous steroid levels and ratios of precursors to products are significantly different in the 2 groups. The carcinomas have a block in the conversion of 11-deoxycortisol to cortisol with a subsequent accumulation in androgen and cortisol precursors. The elevations in 17-hydroxyprogesterone, delta-4-androstenedione and dehydroepiandrosterone, and in the ratio of 11-deoxycortisol to cortisol in the carcinoma group are most striking in the periphery. Peripheral blood steroid measurement in patients with Cushing's syndrome and an adrenal mass aids in the preoperative differentiation of carcinoma from adenoma.

Topics: 17-alpha-Hydroxyprogesterone; Adenoma; Adrenal Cortex Hormones; Adrenal Gland Neoplasms; Androstenedione; Carcinoma; Cortodoxone; Cushing Syndrome; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Male; Progesterone; Testosterone

In search for a biochemical marker to differentiate between adrenocortical carcinoma (AC) and adenoma (AA), plasma levels of the following steroids were studied preoperatively and postoperatively: 11-deoxycorticosterone (DOC), corticosterone (B), 11-deoxycortisol (S), and cortisol (F). Levels were measured by Sephadex LH-20 chromatography and specific radioimmunoassays. The subjects included eight children ages 2 years, 5 months to 9 years, 10 months. There were three girls and 5 boys with pseudoprecocious puberty due to adrenocortical tumors (histologically, four were AC and four, AA). The preoperative showed that DOC and S levels were elevated in all patients, F levels were elevated in four of eight children when compared with age-matched controls, whereas B was normal. Postoperatively, all levels returned to normal. The ratios of B/DOC and F/S as an index of adrenal 11 beta-hydroxylase activity were calculated. The preoperative ratios of B/DOC were markedly decreased in all patients with AC compared to controls (7.7,4.1,5.9,1.9 versus 23.5, median), but normal in three of four patients with AA (16.2, 29.6, 16.1). The F/S ratios were significantly lower in AC and AA when compared with controls. The data indicate a deficiency in 11 beta-hydroxylation in cases of adrenocortical tumors. Despite a still limited number of patients, the decreased B/DOC ratios may possibly indicate malignancy and could be helpful in distinguishing by biochemical means between benign and malignant adrenocortical tumors.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenal Hyperplasia, Congenital; Carcinoma; Child; Child, Preschool; Chromatography, Gel; Corticosterone; Cortodoxone; Desoxycorticosterone; Female; Humans; Hydrocortisone; Male; Puberty, Precocious; Radioimmunoassay; Steroid Hydroxylases

o,p'-DDD is an inhibitor of adrenal steroid synthesis currently used for therapy of Cushing's syndrome. Conflicting data have been published on the relationship between the plasma level of the drug and its clinical and biological effects. The levels of o,p'-DDD and o,p'-DDE in various tissues obtained from treated patients have been measured and are compared with data on in vitro steroidogenesis in adrenal tissues from the same patients. o,p'-DDD was found in all samples and o,p'-DDE in half of them, both levels being high when the tissue lipid concentration was high. There was considerable variability in lipid content from one tissue to another and within a tissue from one sample to another; only the drug to lipid ratio seems able to provide a reproducible index of drug entry into a tissue. No relationship was found between the tissue concentration of the drug and the total dose administered or inhibition of the steroid biosynthetic step studied.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Gland Neoplasms; Adrenal Glands; Adult; Carcinoma; Child; Cortodoxone; Cushing Syndrome; Desoxycorticosterone; Dichlorodiphenyl Dichloroethylene; Female; Humans; Hydroxyprogesterones; Hyperplasia; In Vitro Techniques; Male; Middle Aged; Mitotane; Steroids

Four post-menopausal women had Cushing's syndrome due to adrenal cortical carcinomas. Comprehensive analyses of blood and urinary steroids showed that although the steroid profiles differed between patients, the pattern in each patient remained almost constant as the disease progressed, or remitted due to therapy. Elevations of serum testosterone and oestradiol were commensurate with the extent of virilisation, and the urinary output of aldosterone was associated with the severity of hypertension. A new finding was that all had substantially increased urinary free deoxycorticosterone. Complete surgical removal of the primary tumours was impossible but when most of the tumour tissue was removed, full clinical and biochemical remissions were obtained for a short time in 2 patients. One patient obtained a clinical and biochemical remission from op'DDD. In another patient the drug caused reduction both in blood pressure and in urinary aldosterone excretion, but there were unpleasant side effects. A third patient could not tolerate op'DDD. Metyrapone therapy produced neither clinical nor biochemical improvement in 3 patients. The mean duration of survival was 17 months after the first symptoms and 10 months from the date of operation. Despite advances in drug therapy, adrenal cortical carcinoma remains a lethal disease. Biochemical screening of multiple steroids offers a means of early diagnosis and disease monitoring. Extensive surgical removal of the tumour offers the best chance of a clinical and biochemical remission.

Topics: 17-Ketosteroids; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Aldosterone; Carcinoma; Cortodoxone; Cushing Syndrome; Desoxycorticosterone; Electrolytes; Estradiol; Female; Humans; Hydrocortisone; Luteinizing Hormone; Metyrapone; Middle Aged; Mitotane; Pregnanetriol; Testosterone

The case of a young boy who had Cushing's syndrome and severe hypertension in association with metastatic adrenal carcinoma is described. Marked elevation of the mineralocorticoid 11-deoxycorticosterone was demonstrated in the plasma. 11-Deoxycortisol, 17alpha-hydroxyprogesterone, and urinary tetrahydro-11-deoxycortisol and pregnanetriol were also elevated. Aldosterone excretion was low. The data implicate defective 11beta hydroxylation and suggest that excessive 11-deoxycorticosterone production may have been responsible for the hypertension.

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Cortex Hormones; Adrenal Gland Neoplasms; Aldosterone; Carcinoma; Child; Cortodoxone; Desoxycorticosterone; Humans; Hydrocortisone; Hydroxyprogesterones; Hypertension; Male; Pregnanetriol