BACKGROUND: Traditional testing of the hypothalamic-pituitary-adrenal axis function has essentially relied upon the insulin tolerance test or the metyrapone test(both tests are not only uncomfortable, but are also dangerous). The standard ACTH stimulation test uses an extremely supra-physiologic amount(250f microgram) of ACTH to evaluate a physiological response, which may result in a false normal response. The 1microgram rapid ACTH stimulation test is more physiological and more sensitive than the standard test, but there exist much controversy about when the serum cortisol should be measured or what the most appropriate cut-off point is for normality or whether the 1microgram ACTH commercial solution is needed. The aims of this study were to investigate 1) whether 1microgram of ACTH is an appropriate amount to stimulate the adrenal gland of patients that have suspected central adrenal insufficiency compared with insulin tolerance test(ITT) and 2) the diagnostic value of the 1microgram rapid ACTH stimulation test according to timing of sampling of serum cortisol. METHODS: In order to evaluate the dose-response relationship between ACTH and cortisol, we performed the ITT in 77 patients with suspected central adrenal insufficiency with serial measurements of serum cortisol and plasma ACTH. We drew the blood samples in 10 min intervals between 10 and 60 min after the administration of 1microgram ACTH in 39 patients with central adrenal insufficiency and in 38 pituitary control patients with pituitary. ITT was used to confirm the diseases for the patients of central adrenal insufficiency, but for pituitary control patients, the ITT indicated normality in the patients. Also, all subjects underwent the 250microgram rapid ACTH stimulation test, and we compared the diagnostic value of the 1microgram ACTH stimulation test with the 250microgram test. RESULTS: 1) The plasma ACTH level after the 1microgram ACTH stimulation test, even if it was be assumed as approximately 300pg/mL, was expected to be sufficient enough to stimulate the adrenal cortex normally(serum cortisol levels >18microgram/dL) compared to the plasma ACTH level in the ITT. 2) The sensitivity and specificity of the 1microgram rapid ACTH stimulation test was highest with 92.3% and 84.2%, respectively, when serum cortisol levels were measured at 20, 30, and 40 min after the ACTH injection. The 1microgram rapid ACTH stimulation test was more sensitive than the 250microgram ACTH test(sensitivity: 92.3%, specificity: 71.8%). CONCLUSION: The 1microgram rapid ACTH stimulation test was more sensitive test in patients with suspected central adrenal insufficiency, and blood samples for cortisol levels should be drawn at 20, 30, and 40 min after ACTH administration.
Adrenal Cortex ; Adrenal Glands ; Adrenal Insufficiency* ; Adrenocorticotropic Hormone* ; Axis, Cervical Vertebra ; Humans ; Hydrocortisone* ; Insulin ; Metyrapone ; Plasma ; Sensitivity and Specificity

Pregnancy is rare in women with Cushing's syndrome, as the associated infertility is related to excess cortisol and/or androgen. However, approximately 100 such cases have been reported, with 50% due to an adrenal cortical adenoma. Establishing a diagnosis and cause can be difficult. Clinically, striae, hypertension and gestational diabetes are common features in pregnancy, with hypertension and diabetes being the most common signs of Cushing's syndrome in pregnant women. Furthermore, biochemically, a normal pregnancy is associated with a several fold increase in plasma cortisol, as the increased cortisol production rate also increases the cortisol binding protein. Untreated, the condition results in high maternal and fetal morbidity and mortality. An adrenal or pituitary adenoma should be excised, but a metyrapone, which is not teratogenic, has been effective in controlling many cases of excess cortisol. Here, a case of Cushing's syndrome, complicating a pregnancy due to an adrenal cortical adenoma, with thorough obstetric and medical management, including a metyrapone, which was adrenalectomized after delivery, is reported.
Adrenocortical Adenoma ; Carrier Proteins ; Cushing Syndrome* ; Diabetes, Gestational ; Diagnosis ; Female ; Humans ; Hydrocortisone ; Hypertension ; Infertility ; Metyrapone ; Mortality ; Pituitary Neoplasms ; Plasma ; Pregnancy* ; Pregnant Women

This woman was a secondary infertile patient with amenorrhea, hirsutism, and hyperprolactinemia due to excessive secretion of androgen. We had an impression that her disease was polycystic ovary syndrome, and she became pregnant after ovulation induction. Complications arised, such as hypertension, diabetes and pulmonary edema at 23rd week of pregnancy and physical findings of Cushing's syndrome were observed. Cushing's syndrome caused by adrenal cortical adenoma was diagnosed through endocrine and radiologic examination. We let her keep pregnancy through adjusting hypercorticolism with metyrapone to restrain abnormal steroidogenesis during pregnancy. After delivery, we carried out adrenalectomy through laparoscopic surgery and then can't find out any problem to be appeared to the mother and her neonate. We report this case with brief discussion.
Adrenalectomy ; Adrenocortical Adenoma* ; Amenorrhea ; Cushing Syndrome* ; Female ; Glycogen Storage Disease Type VI ; Hirsutism ; Humans ; Hyperprolactinemia ; Hypertension ; Infant, Newborn ; Laparoscopy ; Linear Energy Transfer ; Metyrapone ; Mothers ; Ovulation Induction* ; Ovulation* ; Polycystic Ovary Syndrome ; Pregnancy* ; Pulmonary Edema

Animals ; Brain ; metabolism ; Dehydroepiandrosterone ; therapeutic use ; Depressive Disorder, Major ; drug therapy ; metabolism ; physiopathology ; Humans ; Metyrapone ; therapeutic use ; Mifepristone ; therapeutic use ; Psychotic Disorders ; drug therapy ; metabolism ; physiopathology ; Pyrimidines ; therapeutic use ; Receptors, Corticotropin-Releasing Hormone ; antagonists & inhibitors ; Receptors, Glucocorticoid ; antagonists & inhibitors ; metabolism

The characteristics of uptake, transepithelial transport and efflux of Z- and E-ajoenes isolated from the bulbs of Allium sativum were studied. A human colon cell model Caco-2 cell monolayers in vitro cultured had been applied to study the characteristics of uptake, transepithelial transport and efflux of Z- and E-ajoenes. The quantitative determination of Z- and E-ajoenes was performed by high-performance liquid chromatography. Z- and E-Ajoenes can be detected only in the apical side and can be metabolized, but both compounds can not be transported from apical-to-basolateral and basolateral-to-apical directions in cultured Caco-2 cell monolayers. The metabolism of Z- and E-ajoenes in Caco-2 cell monolayers can be partially inhibited by vitamin C as an anti-oxidant, metyrapone as an inhibitor to subtype CYP3A of cytochrome P450 drug metabolism enzymes, and sodium azide as an inhibitor to ATP production. It is shown that neither Z-ajoene nor E-ajoene can pass through Caco-2 cell monolayers, and that they can be metabolized by the cells. The metabolism might be in correlation with cytochrome P450 drugs metabolism enzymes in Caco-2 cell monolayers.
Antioxidants ; pharmacology ; Ascorbic Acid ; pharmacology ; Biological Transport ; drug effects ; Caco-2 Cells ; Cell Membrane ; drug effects ; metabolism ; Cytochrome P-450 CYP3A ; metabolism ; Cytochrome P-450 CYP3A Inhibitors ; Disulfides ; chemistry ; isolation & purification ; pharmacokinetics ; Enzyme Inhibitors ; pharmacology ; Garlic ; chemistry ; Humans ; Metyrapone ; pharmacology ; Plants, Medicinal ; chemistry ; Sodium Azide ; pharmacology ; Stereoisomerism