ABSTRACT
Immunochemical methods of analysis are traditionally used for diagnosis of various forms of Cushing's syndrome (CS). In the presence of boundary values of hormonal parameters, doubtful situations, a combination of changes both in pituitary and in adrenal glands, it is useful to determine additional differential diagnostic criteria for the diagnosis of various forms of CS. Urinary steroid profiles (USP) were analyzed by gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) for 38 females with adrenal Cushing's syndrome (CSA), 42 females with pituitary CS (CSP) and 25 healthy females (control group). An increase of free cortisol/free cortisone ratio in the urine (UFF/UFE) for CSP patients in comparison of CSA was obtained by HPLC method. Decreased urinary excretion of UFF and UFE by more than 60% after the 8 mg dexamethasone suppression test had 100% sensitivity and specificity of more than 90% for the diagnosis of CSP. GC-MS method in patients with CSA and CSG revealed the peculiarities of androgens, progestins and glucocorticoids metabolism which leaded to obtain specific USP for CS of different genesis. Increased urinary excretions of dehydroepiandrosterone and its metabolites, metabolites of androstenedione, the ratio of sum of cortisol and cortisone tetrahydrometabolites to tetrahydro-11-deoxycortisol (more then 36) in CSP patients compared with CSA are additional signs for differential diagnosis of these diseases. The combination of classical tests and USP obtained by HPLC and GC-MS methods increased the sensitivity and specificity of differential diagnosis of CSA and CSP.
Subject(s)
Chromatography, High Pressure Liquid , Cortisone , Cushing Syndrome , Cortisone/analysis , Cushing Syndrome/diagnosis , Dexamethasone , Diagnosis, Differential , Female , Gas Chromatography-Mass Spectrometry , Humans , HydrocortisoneABSTRACT
Urinary steroid profiling (USP) was studied using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) methods in 108 patients with adrenocortical adenoma (ACA) and in 31 patients with adrenocortical carcinoma (ACC). Thirteen ACC and Cushing's syndrome (ACC-CS) patients had two types of USP as well as 18 ACC patients without hypercortisolism. These four types differed by androgen and glucocorticoid secretion of the adrenal cortex. Fifteen main ACC features were observed by GC-MS. Urinary excretion of dehydroepiandrosterone (DHEA) was increased in 67.7 % of ACC patients and tetrahydro-11-deoxycortisol (THS) in 74.2 %. By combination of the following parameters: THS >900 µg/24 h and/or DHEA >1500 µg/24 h with ratios of 3α,16,20-pregnentriol/3ß,16,20-pregnentriol (3α,16,20dP3/3ß,16,20dP3) less than 6.0 and 3α,17,20dP3/3ß,17,20dP3 less than 9.0 and the detection of "non-classical" 5-en-pregnens, not found in ACA and healthy persons, 100 % sensitivity and specificity of ACC and ACA differential diagnosis were achieved. Features of 21-hydroxylase and 11ß-hydroxylase deficiency were observed by GC-MS in 32.2 and 61.3 % of the ACC patients, respectively. Additional features for ACC-CS diagnostic were increased urinary excretion of 6ß-hydroxycortisol, 18-hydroxycorticosterone, the sum (UFF + UFE) obtained by HPLC, tetrahydrocorticosterone, and the sum (THF + THE + allo-THF) obtained by GC-MS.
Subject(s)
Adrenal Cortex Neoplasms/urine , Adrenocortical Adenoma/urine , Adrenocortical Carcinoma/urine , Chromatography, High Pressure Liquid/methods , Gas Chromatography-Mass Spectrometry/methods , Steroids/urine , Adrenal Cortex Neoplasms/diagnosis , Adrenocortical Adenoma/diagnosis , Adrenocortical Carcinoma/diagnosis , Adult , Cortodoxone/analogs & derivatives , Cortodoxone/urine , Cushing Syndrome/urine , Dehydroepiandrosterone/urine , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Steroid 11-beta-Hydroxylase/metabolism , Steroid 21-Hydroxylase/metabolism , Young AdultABSTRACT
Forty-two patients with classical forms of congenital adrenal cortical dysfunction (CACD) (22 patients with salt-loosing form and 20 patients with simple virile form) caused by 21-hydroxylase deficiency and 29 female with an obscure form of the disease were examined. The patients with classical CACD received therapy with gluco- and mineralocorticoids. Radioimmunoassay and enzyme immunoassay were employed to estimate the levels of 17-OH-progesterone and the activities of plasma renin and serum corticotropin, aldosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione. High performance liquid chromatography (HPLC) was used to measure the blood levels ofcortisol, cortisone, corticosterone (B), 11-deoxycorticosterone (DOC), and 11-deoxycortisol (S). There were increases in the levels of Ð and DOC in patients with the simple form at the decompensation stage and in those of DOC in patients with the simple form at the compensation stage, which is indicative of activation of the renin-angiotensin system. There were also rises in Ð and DOC in 35.8 and 33.0% of the patients with obscure CACD, respectively, as well as a significant elevation of the content of S. A study of the profiles of corticosteroids by HPLC in patients with 21-hydroxylase deficiency-related CACD is an additional method for assessing the compensation of the disease in patients with classical CACD and for diagnosing the obscure form of the disease.
