cortodoxone and Adrenocortical-Hyperfunction

Topics: Adrenal Hyperplasia, Congenital; Adrenocortical Hyperfunction; Cortodoxone; Female; Humans; Male

Trilostane is thought to be a competitive inhibitor of the 3beta-hydroxysteroid dehydrogenase (3beta-HSD), an essential enzyme system for the synthesis of cortisol, aldosterone and androstenedione. Due to its reliable clinical efficacy, trilostane is increasingly used to treat dogs with pituitary-dependant hyperadrenocorticism (PDH). The objective of our study was to investigate the effect of trilostane on precursor concentrations located before (17alpha-OH-pregnenolone, dehydroepiandrostenedione) and after (17alpha-OH-progesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol) the proposed enzyme inhibition, on end products of steroid biosynthesis (cortisol and aldosterone) and on endogenous adrenocorticotrophic hormone (ACTH) concentrations in dogs with PDH. Hormones of the steroid biosynthesis pathway were evaluated in 15 dogs before and 1h after injection of synthetic ACTH prior to (t(0)), in weeks 1-2 (t(1)) and in weeks 3-7 (t(2)) of trilostane treatment. Endogenous ACTH concentrations were measured at the same time points before performing the ACTH stimulation test. During trilostane treatment baseline and post-stimulation cortisol concentrations decreased significantly. Baseline serum aldosterone levels showed a significant increase; post-stimulation values decreased. Baseline and post-stimulation 17alpha-OH-pregnenolone and dehydroepiandrostenedione concentrations increased significantly. 17alpha-OH-progesterone and androstenedione levels did not change. Post-stimulation 21-deoxycortisol concentrations decreased significantly, baseline 11-deoxycortisol concentrations increased significantly. Endogenous ACTH levels showed a significant increase. The significant increase in 17alpha-OH-pregnenolone and dehydroepiandrostenedione concentrations confirms an inhibitory effect of trilostane on the 3beta-HSD. Since 17alpha-OH-progesterone concentrations did not change, but cortisol concentrations markedly decreased, trilostane seems to influence additional enzymes of the hormone cascade, like the 11beta-hydroxylase and possibly the 11beta-hydroxysteroid dehydrogenase.

Topics: 17-alpha-Hydroxypregnenolone; 3-Hydroxysteroid Dehydrogenases; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Aldosterone; Androstenedione; Animals; Cortodoxone; Dehydroepiandrosterone; Dihydrotestosterone; Dog Diseases; Dogs; Enzyme Inhibitors; Female; Hydrocortisone; Male; Prospective Studies; Statistics, Nonparametric

Topics: 17-Hydroxycorticosteroids; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Chromatography, High Pressure Liquid; Cortodoxone; Dexamethasone; Gas Chromatography-Mass Spectrometry; Humans; Metyrapone; Radioimmunoassay

Topics: 17-Hydroxycorticosteroids; Adrenal Cortex Function Tests; Adrenal Insufficiency; Adrenocortical Hyperfunction; Chromatography, High Pressure Liquid; Cortodoxone; Humans; Metyrapone; Radioimmunoassay; Reference Values

A 47-year-old female presented with hypertension, hypokalaemia, low plasma renin, high plasma aldosterone and was found to have a left adrenal tumour 4 cm in diameter by computerized tomography. Detailed biochemical studies showed high plasma levels of 11-deoxycorticosterone and corticosterone in addition to aldosterone and 18-hydroxycorticosterone. Basal 11-deoxycorticosterone levels were particularly high. Corticosterone, 18-hydroxycorticosterone and aldosterone concentrations were abnormally sensitive to infusions of ACTH and angiotensin II. Plasma cortisol and assays for sex hormones were normal although there was evidence that cortisol derived from the neoplasm. At operation a well-differentiated adrenocortical carcinoma weighing 50 g (56 X 30 X 36 mm) was removed. There was no evidence of metastases following surgery. Adrenal function returned to normal. Review of the literature suggests that adrenocortical carcinoma should be suspected in patients who otherwise have typical features of Conn's syndrome, but whose tumours are more than 3 cm in diameter. Measurement of steroids such as 11-deoxycorticosterone in addition to aldosterone is recommended since abnormally high values may also help to distinguish between hyperaldosteronism due to adenoma and carcinoma. Previously reported cases of isolated aldosterone production by a carcinoma cannot be substantiated.

Topics: 18-Hydroxycorticosterone; Adrenal Cortex Hormones; Adrenal Cortex Neoplasms; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Angiotensin II; Corticosterone; Cortodoxone; Dexamethasone; Female; Humans; Hyperaldosteronism; Hypokalemia; Middle Aged

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Corticosterone; Cortodoxone; Cushing Syndrome; Cyclic AMP; Humans; Hydrocortisone

Topics: Adrenocortical Hyperfunction; Child; Cortodoxone; Humans; Male; Mixed Function Oxygenases

Topics: 17-Hydroxycorticosteroids; Adrenal Hyperplasia, Congenital; Adrenocortical Hyperfunction; Adult; Child; Child, Preschool; Cortisone; Cortodoxone; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Infant; Infant, Newborn; Isomerism; Male; Radioimmunoassay

Topics: 17-Hydroxycorticosteroids; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Adult; Child; Cortodoxone; Female; Heterozygote; Humans; Hydroxyprogesterones; Isomerism; Male

Plasma cortisol values in seven patients with the 21-hydroxylase variant of CAH ranged from 9 to 35 micron/100 ml. (mean+/-S.E.=22+/-4) as determined fluorimetrically and from 22 to 35 microng/100 ml. (26+/-2) by competitive protein-binding radioassay. In these same patients the cortisol values obtained after Sephadex LH-20 column chromatography were much lower, ranging from 1 to 12.5 microng/100 ml. (5+/-2, p less than 0.01). In six normal subjects, cortisol values were similar before and after chromatography. Plasma concentrations of progesterone, 17alpha-hydroxyprogesterone, and 21-deoxycortisol in the CAH patients were increased 10 to 100-fold. The elevated cortisol values determined by customary methods were shown to be due to cross-interference of these and other steroids in the assays. Plasma cortisol values obtained routinely are falsely elevated and therefore misleading as a gauge of adrenal insufficiency in CAH.

Topics: Adolescent; Adrenocortical Hyperfunction; Child; Cortodoxone; Female; Fluorometry; Humans; Hydrocortisone; Hydroxyprogesterones; Infant; Infant, Newborn; Male; Progesterone; Radioligand Assay

Topics: 17-Hydroxycorticosteroids; Adolescent; Adrenocortical Hyperfunction; Child; Child, Preschool; Circadian Rhythm; Cortodoxone; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Infant; Infant, Newborn; Isomerism; Male

One of the first described cases of hypertensive virilizing adrenal hyperplasia (VAH) (Pediatrics 8: 805, 1951) has been followed from age 2 1/2 until age 26. Blood pressure as an infant was 150/90, and at age 25 was 220/160. During childhood the patient was lost to follow-up for prolonged periods, and received no therapy from age 20 to 25. At this time 24 h urinary excretion of 17-ketosteroids was 89 mg; tetrahydro 11-deoxycortisol (tetrahydro S), 47 mg and pregnanetriol 5.7 mg. Hourly measurements of several plasma steroids utilizing sephadex LH 20 chromatography and competitive protein binding were made during 24 h; concentration ranges were made during 24 h; concentration ranges were as follows (mug/100 ml): 11-deoxycortisol 8-40; cortisol 0-48; corticosterone 0-15; deoxycorticosterone 1-18. Plasma cortisol, especially showed a significiant morning impairment, but reached normal and even markedly elevated levels during the day and early evening. Urinary cyclic AMP per 24 h ranged from 5.3 to 11.6 n mol/mg creatinine before therapy, and was 1.9 n mol after therapy. The results suggest either the formation of an alternate pathway to cortisol synthesis, or the existence of a form of VAH with two independent 11-B hydroxylating systems, exhibiting only minimal impairment of the synthetic route to cortisol. The latter would support the presence of two independent 11-B hydroxylating systems in the normal human adrenal. This has been suggested by Zachmann et al. (J Clin Endocrinol Metab 33: 501, 1971) to be true in infancy. Our observations on an adult indicate that these two systems may not be transitory, but persist into adulthood.

Topics: Adrenocortical Hyperfunction; Adult; Child, Preschool; Circadian Rhythm; Corticosterone; Cortodoxone; Cyclic AMP; Desoxycorticosterone; Follow-Up Studies; Humans; Hydrocortisone; Hypertension; Male

Topics: Adolescent; Adrenal Hyperplasia, Congenital; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Adult; Child; Child, Preschool; Cortisone; Cortodoxone; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Immune Sera; Infant; Male; Mixed Function Oxygenases; Prednisone; Pregnadienediols; Radioimmunoassay; Tritium