cortodoxone and Hyperplasia

The article considers the technique of high-performance liquid chromatography making it possible simultaneously detect cortisol, cortisone and secondary steroids in serum for consequent analysis of common reversed-phase high-performance liquid chromatography with ultraviolet under 240 nm. The liquid-liquid extraction from alkaline medium in diethyl ether The separation using column of 150x4.6 size ODS 3.5 mkm in isocratic mode. The eluent acetonitrile--0.02 M phosphate buffer pH 8.0--isopropanol (40:60:1). The application of proposed technique managed to separate cortisol, cortisone, dexamethasone, corticosterone, 11-desoxicortisol, testosterone, desoxicorticosterone, 17α-gidroxiprogesterone and androstendion in 20 minutes. The simplicity, reproducibility and sufficient selectivity and sensitivity of technique permit implement it in clinical practice for simultaneous diagnostic of inherent hyperplasia of adrenal glands type I and II.

Topics: Acetonitriles; Adrenal Glands; Androstenedione; Chromatography, High Pressure Liquid; Corticosterone; Cortisone; Cortodoxone; Desoxycorticosterone; Dexamethasone; Humans; Hydrocortisone; Hydroxyprogesterones; Hyperplasia; Reproducibility of Results; Sensitivity and Specificity; Testosterone

ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) is a rare cause of Cushing's syndrome in which adrenal glands become very enlarged, occupied and distorted by multiple cortical nodules. We report on such two patients, a 44-year-old man and a 40-year-old woman. Physical examination revealed in both cases a classic cushingoid habit. Laboratory studies showed overt hypercortisolism with high urinary free cortisol excretion and elevated serum cortisol with loss of the circadian rhythm. Serum cortisol levels were not modified after high dose dexamethasone. ACTH levels were undetectable both in baseline conditions and following CRH or metyrapone. In both cases, abdominal CT demonstrated bilaterally enlarged adrenal glands which were distorted by multiple bumps. 131I-Norcholesterol scintiscan showed bilateral uptake of the radionuclide. Pituitary region was normal at neuroradiologic imaging. Bilateral adrenalectomy was performed in both cases. In patient I, adrenal glands weighted 77 and 90 g, respectively, while in patient II they were of 90 and 55 g, respectively. At histological examination, the adrenal cortex was occupied by multiple nodular lesions composed mostly of clear cells. In the internodular regions, no evidence of cortical architecture was observed. At the immunohistochemical evaluation, both cases displayed KI-67 staining comparable with that of ACTH-dependent diffuse hyperplasia. Postoperative course was uneventful and signs of Cushing's syndrome resolved in about three months. At the last follow up, the patients are going well on glucocorticoid and mineralocorticoid supplementation. Plasma ACTH levels are 65 and 107 pg/ml, respectively.

Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Adrenalectomy; Adrenocorticotropic Hormone; Adult; Circadian Rhythm; Cortodoxone; Cushing Syndrome; Female; Follow-Up Studies; Humans; Hydrocortisone; Hyperplasia; Male; Radionuclide Imaging; Tomography, X-Ray Computed

We report a patient with Cushing's syndrome in whom the etiology of the hypercortisolemia could not be definitely established despite extensive biochemical investigations. Results included raised basal serum cortisol, plasma ACTH, and urinary free cortisol; failure to suppress even a paradoxical rise in serum cortisol after dexamethasone (1 mg overnight, 2, 8, and 16 mg/day); and a definite but not exaggerated rise in 11-deoxycortisol after metyrapone. After iv CRF, plasma ACTH rose from 22 to 30 pmol/L. Abdominal computed tomographic scanning showed adrenal hyperplasia; the presence of an adrenal adenoma, although suspected, was not established. An unusual finding was the presence in the urine of large amounts of 21-deoxycortisol metabolites, including 3 alpha,11 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one and 5 beta-pregnane 3 alpha,11 beta,17 alpha,20 alpha-tetrol. On the basis of preoperative biochemical/radiological findings, a provisional diagnosis of ACTH-dependent Cushing's syndrome associated with autonomous bilateral adrenal hyperplasia was made. Incomplete bilateral adrenalectomy was performed; adrenal hyperplasia was histologically confirmed, but no tumor was found. However, ACTH was measured 1) just before operation when the patient was receiving treatment with metyrapone, and 2) postoperatively when the patient was receiving steroid replacement only, and on these occasions ACTH levels were lower than during the initial investigations. Pituitary scans before and after adrenalectomy were similar, offering no evidence of pituitary infarction. We propose that abnormal production of 21-deoxycortisol contributed to the aberrant regulation of ACTH and cortisol in this case, providing an example of a previously unreported cause of hypercortisolemia.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Adult; Cortodoxone; Cushing Syndrome; Dimethyl Sulfoxide; Female; Humans; Hydrocortisone; Hyperplasia

to determine the 11-deoxycortisol (S) response and incidence of 11 beta-hydroxylase deficiency in hyperandrogenism.. Hyperandrogenic women prospectively and consecutively underwent acute adrenal stimulation studies.. Tertiary institution.. Two hundred sixty women complaining of hirsutism and/or hyperandrogenic oligomenorrhea were studied, excluding five unrelated families (1.9% of total) suffering from 21-hydroxylase deficient late-onset adrenal hyperplasia. Forty-one healthy premenopausal eumenorrheic women served as controls.. Only two unrelated women (0.8%) had a poststimulation or net increment S level value greater than or equal to threefold the upper 95th percentile of controls and were presumed to suffer from 11 beta-hydroxylase deficient late-onset adrenal hyperplasia. One hundred nine (42%) of hyperandrogenic women had at least one S value above the 95th percentile of controls. These women also demonstrated higher basal (F0) and stimulated cortisol levels, but a similar increment compared with controls.. Patients with high S measures had higher testosterone, dehydroepiandrosterone sulfate, and androstenedione levels, but similar luteinizing hormone/follicle-stimulating hormone ratios, than hyperandrogenic cohorts with no abnormal S measures. Basal values of S (S0), F0, or S0/F0 were not useful to predict an abnormal S response to stimulation.. Although adrenocortical hyperactivity was present in 42% of our hyperandrogenic patients, only 0.8% were presumed to suffer from 11 beta-hydroxylase deficient late-onset adrenal hyperplasia. A systemic search for this deficiency in hyperandrogenism is probably unwarranted.

Topics: Adrenal Glands; Adrenal Hyperplasia, Congenital; Adult; Androgens; Cortodoxone; Female; Hirsutism; Hormones; Humans; Hyperplasia; Menstruation Disturbances; Predictive Value of Tests; Prospective Studies; Reference Values

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