Free cortisol/cortisone ratio in pooled urine was increased after rapid-ACTH stimulation test under dexamethasone suppression.
ABSTRACT We employ rapid-ACTH stimulation test under dexamethasone (DEX) suppression to assess the adrenal function in daily clinic. However, we have little knowledge about the excretion of urinary free cortisol (FF) and cortisone (FE) in pooled urine in this setting. The purpose was to examine the changes of FF and FE as well as FF/FE ratio in pooled urine after rapid-ACTH stimulation test under DEX suppression using stable isotope dilution-gas chromatography/mass spectrometry (SID-GC/MS). Pooled urine samples were collected from 8 patients (age 33-71 years) who were suspected to have primary aldsteronism. They all were finally diagnosed as having normal glucocorticoid secretion. We performed rapid-ACTH stimulation test with DEX suppression for consecutive 4 days as follows. (1) 24 hour urine samples were serially collected from 2300 h on day 1 for 72 hours (Basal, DEX1mg, and DEX8mg-ACTH). (2) 1 and 8 mg DEX was given at 2300 h on day 2 and 3, respectively. (3) 250 µg of ACTH was given at 0900 h on day 4. Urine free steroids were delivered with bismethylenedioxy-heptafluorobutyric anhydride and analyzed by SID-GC/MS (µg/day). From DEX1mg to DXE8mg-ACTH, (1) FF and FE were significantly increased (3.9±1.3 to 21.3±14.6 and 12.4±4.8 to 26.1±11.0 µg/day, respectively), but (2) FF/FE ratio significantly increased (0.32±0.05 to 0.77±0.23). These data suggested that newly synthesized cortisol by ACTH stimulation was not efficiently metabolized to cortisone.
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ABSTRACT: Urinary steroid profile analysis using gas chromatography/mass spectrometry (GC/MS) has been reported for the diagnosis of abnormal steroidogenesis in newborn infants with some success. We tried to establish the reference values of 63 urinary steroids in Japanese newborn infant, using GC/MS in selected ion monitoring (SIM) that utilizes two characteristic mass ions for each steroid for definitive identification. We studied 36 healthy full-term newborn infants (1-56 days of age) on spot urine samples to define the reference values (mg/g creatinine, median and 10-90 percentile range) and to investigate the possible difference between daytime and nighttime levels. We also studied 23 healthy adult females (20-24 years of age) on 24-hour-urine for the comparison of the reference values of newborn infants. Fifty metabolites of DHEA, pregnenolone, 17-hydroxypregnenolone, androstenedione, progesterone, 17-hydroxyprogesterone, 21-deoxycortisone, corticosterone, 18-hydroxycorticosterone, aldosterone, 18-hydroxycortisol, 11-deoxycortisol, cortisone, cortisol, and estrogen in each infant were measurable without interference, but 13 metabolites of 11-hydroxyandrostenedione, pregnenolone, 11-deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, 21-deoxycortisol, 11-deoxycortisol and cortisol were unmeasurable in each infant due to the interference of fetal cortex steroids as confirmed by abnormal peak area ratios of two mass ions. All 63 metabolites in each control adult were measurable without interference. 16alpha-, 16beta-, and 15beta-hydroxy metabolites of 3beta-hydroxy-5-en-steroids, and 6beta-, 18-hydroxy and 11-oxo-metabolites of corticosteroids were significantly higher in full-term newborn infants than those in adults as previously reported. Urinary steroids showed little circadian variation in the newborn infants, indicating that spot urine can substitute for 24-hour urine.Endocrine Journal 01/2004; 50(6):783-92. · 2.23 Impact Factor
Article: Adrenal insufficiency.[show abstract] [hide abstract]
ABSTRACT: Adrenal insufficiency is caused by either primary adrenal failure (mostly due to autoimmune adrenalitis) or by hypothalamic-pituitary impairment of the corticotropic axis (predominantly due to pituitary disease). It is a rare disease, but is life threatening when overlooked. Main presenting symptoms such as fatigue, anorexia, and weight loss are non-specific, thus diagnosis is often delayed. The diagnostic work-up is well established but some pitfalls remain, particularly in the identification of secondary adrenal insufficiency. Despite optimised life-saving glucocorticoid-replacement and mineralocorticoid-replacement therapy, health-related quality of life in adrenal insufficiency is more severely impaired than previously thought. Dehydroepiandrosterone-replacement therapy has been introduced that could help to restore quality of life. Monitoring of glucocorticoid-replacement quality is hampered by lack of objective methods of assessment, and is therefore largely based on clinical grounds. Thus, long-term management of patients with adrenal insufficiency remains a challenge, requiring an experienced specialist. However, all doctors should know how to diagnose and manage suspected acute adrenal failure.The Lancet 06/2003; 361(9372):1881-93. · 39.06 Impact Factor
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ABSTRACT: Our objective was to develop clinical practice guidelines for the diagnosis and treatment of patients with primary aldosteronism. The Task Force comprised a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, six additional experts, one methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. Systematic reviews of available evidence were used to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group criteria to describe both the quality of evidence and the strength of recommendations. We used "recommend" for strong recommendations and "suggest" for weak recommendations. Consensus was guided by systematic reviews of evidence and discussions during one group meeting, several conference calls, and multiple e-mail communications. The drafts prepared by the task force with the help of a medical writer were reviewed successively by The Endocrine Society's CGS, Clinical Affairs Core Committee (CACC), and Council. The version approved by the CGS and CACC was placed on The Endocrine Society's Web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes. We recommend case detection of primary aldosteronism be sought in higher risk groups of hypertensive patients and those with hypokalemia by determining the aldosterone-renin ratio under standard conditions and that the condition be confirmed/excluded by one of four commonly used confirmatory tests. We recommend that all patients with primary aldosteronism undergo adrenal computed tomography as the initial study in subtype testing and to exclude adrenocortical carcinoma. We recommend the presence of a unilateral form of primary aldosteronism should be established/excluded by bilateral adrenal venous sampling by an experienced radiologist and, where present, optimally treated by laparoscopic adrenalectomy. We recommend that patients with bilateral adrenal hyperplasia, or those unsuitable for surgery, optimally be treated medically by mineralocorticoid receptor antagonists.Journal of Clinical Endocrinology & Metabolism 07/2008; 93(9):3266-81. · 6.43 Impact Factor