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PubMed1995

Factitious hypercortisoluria.

A case of factitious hypercortisoluria due to the presumed addition of glucocorticoid to the urine collections is presented. The discrepancy between urine and blood steroid hormone levels first suggested that the patient had tampered with the urine collections. Plasma steroid hormone levels were normal, whereas the urinary free cortisol level fluctuated in a totally random fashion. Urinary 17-hydroxycorticosteroid and urinary free corticosterone levels were normal. Partition chromatography of the urine indicated that the cortisol immunoactivity coeluted with authentic cortisol. This study illustrates the value of multiple urinary and plasma steroid determinations, especially urinary or plasma corticosterone measurements, in suspected cases of factitious Cushing's syndrome.

Adrenal Cortex Hormones↗
PubMed1998

A single midnight serum cortisol measurement distinguishes Cushing's syndrome from pseudo-Cushing states.

Cushing's syndrome (CS) may be difficult to distinguish from pseudo-Cushing states (PCS) based on physical findings or urinary glucocorticoid excretion. As the lack of diurnal variation in serum cortisol is characteristic of CS, we studied whether diurnal cortisol determinations could discriminate CS from PCS. Two hundred and sixty-three patients were evaluated: 240 had CS, and 23 had PCS. Urine was collected for 24 h for measurement of cortisol and 17-hydroxycorticosteroids (17OHCS). Blood was drawn at 2300, 2330, 0000, 0030, and 0100 h and at 0600, 0630, 0700, 0730, and 0800 h the next morning for serum cortisol determination. The main outcome measure was the sensitivity of these parameters for the diagnosis of CS at 100% specificity. A midnight cortisol value greater than 7.5 microg/dL correctly identified 225 of 234 patients with CS and all PCS patients. This sensitivity (96%) was superior to that obtained for any other measure, including urinary cortisol (45%), 17OHCS (22%), any other individual cortisol time point (10-92%), the morning (23%) or the evening (93%) cortisol mean, and the ratio (11%) of morning to evening values. We conclude that at 100% specificity, a single serum cortisol value above 7.5 microg/dL at midnight discriminates CS from PCS with higher sensitivity than 24-h urinary cortisol or 17OHCS, or other individual or combined measures of serum cortisol.

Adolescent↗
PubMed1987

Effect of valproic acid on pharmacokinetics of active metabolites of cyclophosphamide in mice.

The effects of valproic acid (VPA) on pharmacokinetics of cyclophosphamide (CPM) alkylating metabolites were investigated in male BALB/c mice. The pharmacokinetics of CPM alkylating metabolites was found to be dose-dependent representing the decrease of formation and elimination rates of the metabolites. A nonlinear increase of area under blood concentration of CPM alkylating metabolites-time curve (AUC) occurred with increasing CPM dose of 100, 200, and 300 mg/kg body weight. The effects of VPA (100 mg/kg dose) coadministered with CPM were similar to those of the increase of the CPM dose in preventing the activation of CPM and the elimination of its alkylating metabolites. The delayed disposition of CPM alkylating metabolites resulted in a 1.5-fold increase (p less than 0.02) of AUC which was considered the most important pharmacokinetic parameter in the CPM therapy. VPA which was injected i.p. at a dose of 100, 200, or 300 mg/kg increased the pentobarbital induced-sleep time by 81, 138, or 192%, respectively. In order to assess the effect of VPA on drug metabolizing enzyme(s) activity in humans, the ratio of daily urinary 6-hydroxycortisol to 17-hydroxycorticosteroids, which can reflect cytochrome P-450 activity, was determined in 5 healthy volunteers. The ratio was rapidly and significantly decreased (p less than 0.05) and this reduction continued during VPA administration. These findings and those reported in the literature concerning CPM metabolism suggest that the delay of CPM alkylating metabolites elimination resulted in part from microsomal enzyme(s) inhibition by VPA.

Animals↗
PubMed2001

The masculinization of the fetus during pregnancy due to inhalation of diesel exhaust.

This study was conducted to determine the impact of diesel exhaust inhalation on the fetus. Seventy-two pregnant rats and 18 nonpregnant rats were divided into three groups: a group exposed to total diesel engine exhaust containing 5.63 mg/m(3) particulate matter, 4.10 ppm nitrogen dioxide, and 8.10 ppm nitrogen oxide; a group exposed to filtered exhaust without particulate matter; and a group exposed to clean air. The exposure period was from day 7 until day 20 of pregnancy. In addition, 15 pregnant rats were treated with aromatase inhibitors or testosterone to clarify the process by which diesel exhaust exerts its toxicity. The anogenital distance was significantly longer in male and female fetuses from both exhaust-exposed groups than in those of the control. Differentiation of the testis, ovary, and thymus was delayed and disturbed. Maternal testosterone and progesterone levels, which increased due to pregnancy whether or not the rats were exposed, were significantly higher and lower, respectively, in the pregnant rats exposed to total exhaust and filtered exhaust. The serum adrenocorticotropic hormone (ACTH) level and urinary excretion of 17-hydroxycorticosteroids (OHCS) did not differ among the pregnant groups. These results indicate that elevated testosterone did not result from elevated maternal adrenal function. The feto-placental-ovarian unit and inhibition of aromatase activity and synthesis caused by diesel exhaust inhalation might have played an essential role in the accumulation of testosterone. Since both exhaust-exposed groups showed almost the same reactions toward the inhalation, the gaseous phase must have included the relevant toxicants.

Adrenal Glands↗
PubMed1985

Polychlorinated biphenyl exposure and effects in transformer repair workers.

Fifty-five present and past transformer repair workers exposed to polychlorinated biphenyls (PCBs) and 56 unexposed comparison workers were evaluated in a clinical-epidemiologic study. The groups were similar in most demographic variables. Adipose tissue lipid and serum PCBs concentrations were higher in current exposed workers (geometric means adipose 2.1 ppm, serum 12.2 ppb). Concentrations in comparison (0.6 ppm and 4.6 ppb) and previously exposed (0.83 ppm and 5.9 ppb) workers were lower. Statistically significant differences in serum albumin and lactic dehydrogenase, but not in other liver function tests, were seen between the exposed and comparison groups; however, after adjustment for confounding variables, no correlations were observed between liver function tests and either adipose or serum PCBs concentrations. Statistically significant correlation both before and after adjustment for confounding variables were seen with adipose PCBs and 24-hr urinary 17-hydroxycorticosteroid excretion and with serum PCBs and serum gamma-glutamyl transpeptidase. Both associations could reflect microsomal enzyme induction among other possibilities. No differences were seen in fasting serum triglycerides, total cholesterol, LDL, HDL or VLDL cholesterol between the two exposure groups. A statistically significant correlation between serum PCBs and serum triglycerides, total cholesterol, and VLDL cholesterol was removed by adjusting for confounding variables. No correlation was seen between adipose PCBs concentrations and any serum lipid component. Partition phenomena could account for these findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1986

A case of partial hypopituitarism with empty sella following normal course of pregnancy and delivery.

A 28 year-old woman was admitted to Jichi Medical School Hospital because of amenorrhea, cold intolerance, easy fatigability and body weight loss. She was pregnant at the age of 26 years. She delivered a 3230 g healthy girl at full term without any complications. However, she did not have any lactation or recurrence of menstruation after the delivery. Serum cortisol was 0.7 micrograms/dl, and plasma adrenocorticotropic hormone (ACTH) was less than 10 pg/ml. Both hormones failed to increase in response to insulin-induced hypoglycemia or exogenous arginine vasopressin. However, serum cortisol and urinary excretion of 17-hydroxycorticosteroids (17-OHCS) were significantly increased by the repeated administration of ACTH. Serum prolactin was 2.2 ng/ml and the level did not rise after the administration of thyrotropin releasing hormone (TRH). Responses of release of adenohypophysial hormones including gonadotropins, growth hormone and thyroid stimulating hormone (TSH) were normal. Serological studies showed an antibody to the pituitary gland which was demonstrated by an indirect immunofluorescence technique. Plain skull X-ray film and brain computerized tomography revealed an empty sella of the normal size. These results indicate the presence of partial deficiency of ACTH and prolactin, and that autoimmune disorders may be involved in the pathogenesis of her hypopituitarism.

Adrenocorticotropic Hormone↗
PubMed1976

Co-existent primary hypothyroidism and isolated ACTH deficiency.

A 52 year old man is described in whom the simultaneous occurrence of isolated adrenocorticotrophin (ACTH) deficiency and primary hypothyroidism was documented by the determination of six anterior pituitary hormones by specific radioimmunoassays after suitable stimulations. The urinary 17-hydroxycorticosteroids excretion was persistently reduced and was increased by repeated ACTH injections. The low basal metabolic rate, reduced serum thyroid hormones and elevated serum thyrotrophic hormone were consistent with primary hypothyroidism. After resumption of euthyroidism, secretory reserves of growth hormone and ACTH were assessed. The growth hormone reponse to insulin-induced hypoglycaemic was normal. No rise in plasma cortisol and ACTH was observed following insulin-induced hypoglycaemia. Plasma ACTH was not augmented by iv infusion of metyrapone. The pathogenesis of two co-existent endocrine deficiencies was discussed.

17-Ketosteroids↗
PubMed1989

A case of normotensive primary aldosteronism with hypopituitarism, epilepsy, and medullary sponge kidney.

A 55-year-old man with normotensive primary aldosteronism, hypopituitarism, epilepsy, and medullary sponge kidney is reported. Seventeen years before admission, he had been noted to have hypokalemia associated with high potassium clearance, suppressed plasma renin activity, metabolic alkalosis, and normal blood pressure as well as low urinary excretion of 17-hydroxycorticosteroids. He kept normotensive in spite of hyperaldosteronism until nine months after the initiation of replacement therapy with glucocorticoid and thyroxine for hypopituitarism, when he became hypertensive. Hypopituitarism seemed to play a role in keeping a normal blood pressure despite long-standing hyperaldosteronism.

Adrenal Glands↗
PubMed1998

Identification of a single cytosine base insertion mutation at Arg-597 of the beta subunit of the human epithelial sodium channel in a family with Liddle's disease.

We describe a family with Liddle's disease caused by a novel mutation of the beta subunit of the human epithelial sodium channel (ENaC). A 15-year-old Japanese female was referred to our outclinic because of hypertension. The physical examination showed no abnormal findings except mild hypertension, but the laboratory data revealed low levels of plasma renin activity, plasma aldosterone and serum potassium. A comprehensive analysis of steroid hormones showed only high levels of urinary free cortisol and 17-hydroxycorticosteroids. During loading tests, blood pressure and serum potassium responded well to triamterene and slightly to spironolactone, but did not respond to dexamethasone. In addition, the normal ratio of tetrahydrocortisol plus 5alpha-tetrahydrocortisol to tetrahydrocortisone in a 24 h urinary excretion test strongly suggested a diagnosis of Liddle's disease rather than apparent mineralocorticoid excess syndrome. DNA sequence analysis of members of this family revealed a single cytosine base insertion at Arg-597 of the beta human ENaC in the proband and her mother, leading to a loss of the last 34 amino acids from the normally encoded protein as the result of a frameshift. We conclude that a de novo cytosine insertion into the final exon of the C-terminus of the beta human ENaC is responsible for Liddle's disease in this Japanese family.

Adolescent↗
PubMed2001

Acute fatty liver of pregnancy complicated with anterior pituitary insufficiency.

Acute fatty liver of pregnancy complicated with anterior pituitary insufficiency in a 24-year-old nullipara woman who presented fever and progressing liver damage after the delivery by Cesarean section is described. The liver biopsy revealed severe fatty changes with microvesicular fat drops in the hepatocytes. Serum growth hormone and adrenocorticotropic hormone levels were low, and did not respond to the stimulation. The daily urinary excretion of 17-hydroxycorticosteroid was also low. Acute fatty liver of pregnancy and antehypophyseal insufficiency were diagnosed. Secondary adrenal failure was also suspected. The co-existing hypercoagulable state could cause an ischemic attack on the pituitary gland.

Acute Disease↗
PubMed2002

Concomitant Cushing's syndrome due to adrenal adenoma in a patient with systemic lupus erythematosus.

A 51-year-old woman had been administered 5 mg/day of prednisolone due to systemic lupus erythematosus (SLE). She developed hypertension, hypokalemia and a pathologic pubic fracture during two years before admission. Although iatrogenic Cushing's syndrome was initially suspected, we diagnosed her as concomitant Cushing's syndrome due to a left adrenal tumor. The elevated endogeneous glucocorticoids were evaluated from urinary excretions of 17-hydroxycorticosteroids, which was 2-fold higher than normal and equivalent to 10 mg of prednisolone. After laparoscopic left adrenalectomy, SLE was favorably controlled with 15 mg of prednisolone, the dosage of which was equivalent to the estimated amount of preoperative glucocorticoids.

Adenoma↗
PubMed1994

Bilateral virilizing hilus (Leydig) cell tumors of the ovary.

A 72-year-old postmenopausal woman with high plasma testosterone levels and virilization, as demonstrated by hirsutism and balding, is presented. Urinary 17-ketosteroids and 17-hydroxycorticosteroids, as well as computed axial tomography scan of the adrenal glands were normal. Although no pelvic mass was detected by ultrasonography or pelvis examination, the patient was found to have small bilateral hilus cell tumors of the ovary. Following bilateral salpingo-oophorectomy the plasma testosterone dropped to normal level. This is the third case of bilateral hilus cell tumors of the ovary to be reported.

Aged↗
PubMed1994

Modulation of circadian rhythm of blood pressure by cortisol in patients with hypopituitarism.

We conducted a study to determine the effect of exogenous cortisol on circadian blood pressure changes in patients with hypopituitarism. Under replacement with hydrocortisone of 15 to 25mg either once (8:00) or twice a day (8:00 and 20:00), and with prednisolone of 3.75 to 5mg once a day, the patients underwent non-invasive ambulatory blood pressure monitoring for 24 hours. The average 24-hour blood pressure before hydrocortisone replacement was 92.9 +/- 1.0 (systolic)/53.2 +/- 0.8mmHg (diastolic), while that after hydrocortisone replacement once or twice a day and prednisolone replacement significantly increased to 108.2 +/- 1.4/63.5 +/- 0.9mmHg, 109.1 +/- 1.6/62.3 +/- 1.0mmHg, and 105.4 +/- 1.2/62.3 +/- 0.9mmHg, respectively. Hydrocortisone replacement once a day showed a significant increase in day-night differences of blood pressure, while hydrocortisone replacement twice a day did not. There were no differences in nocturnal decrease in pulse rate between these two replacements. The daytime and nighttime urinary excretions of 17-hydroxycorticosteroids in hydrocortisone replacement once a day were 7.7mg/12hr (daytime) and 1.4mg/12hr (nighttime), respectively, while those in hydrocortisone replacement twice a day were 3.9mg/12hr (daytime) and 3.6mg/12hr (nighttime), respectively. Urinary 17-ketosteroids, epinephrine and norepinephrine did not show any differences between hydrocortisone replacement once and twice a day. These results suggest that hydrocortisone administration is one of the factors which modulate the circadian variation of blood pressure in patients with hypopituitarism, and may also suggest that the circadian change of cortisol secretion participates, at least in part, in the formation of an intrinsic circadian rhythm of blood pressure.

Blood Pressure↗
PubMed2000

[Coping with stress in the elderly].

In terms of adaptability, unlike inanimate objects, living organisms exist in a dynamic balance between "wear and tear" and "repair and recovery". We regarded 17-hydroxycorticosteroids (17-OHCS) as a compound related to tissue "wear and tear" (Hans Selye) and sought for a compound related to tissue "repair and recovery". This led us to the discovery of 17-ketosteroid sulfates (17-KS-S) in urine. Elderly persons, unlike young adults, show low levels in 17-KS-S and little diurnal changes. In an elderly person 17-KS-S can decrease on significant life events (e.g. a spouse's death) and remain at low levels for a long time. Elderly persons with frailty need to improve their lifestyle (meals, exercise, rest, sleep, etc.) qualitatively and quantitatively to adapt themselves to stress adequately. Increased 17-KS-S levels were to be related to improvement in lifestyle.

17-Ketosteroids↗
PubMedDate not supplied

Intermittent hypercortisolism: a disorder strikingly prevalent after hypophysial surgical procedures.

OBJECTIVE: To determine the frequency of intermittent hypercortisolism in a consecutive series of patients with Cushing's disease who underwent hypophysial surgical treatment. METHODS: Thirty-three patients with hypercortisolism of central origin underwent follow-up at approximately annual intervals for prolonged periods after a transsphenoidal pituitary surgical procedure. Clinical evaluation was done, and urinary steroid measurements, as well as dexamethasone suppression tests in some patients, were performed. RESULTS: Frequently normal but intermittently increased urinary 17-hydroxycorticosteroid or cortisol excretion (or both) was found in six patients postoperatively, associated with intermittently severe hypertension, headaches, and weakness in only one patient. In a seventh patient, intermittently excessive cortisol excretion was clearly evident preoperatively. CONCLUSION: Because corticoid excretion was variable preoperatively in three of the seven study patients, we conclude that intermittent hypercortisolism is commoner than previous evidence has shown, constitutes an extremely difficult diagnostic problem, and did not result from but failed to be cured by pituitary surgical treatment in 6 of 33 patients (18%). The findings emphasize the need for regular follow-up for several years in all patients with Cushing's syndrome who have undergone a hypophysial surgical procedure. Variable consistency of follow-up might partly explain the wide discrepancies between reports of 80 to 90% and 40 to 60% cure rates after a single hypophysial adenomectomy.

Journal Article↗
PubMed1990

[Clinical experience of adrenal incidentaloma with particular reference to adrenal cortical function].

The adrenal function mainly cortical one, was evaluated in 16 patients with incidentally discovered adrenal masses. Pathological examination was possible in 15 cases. The finding consisted of adrenocortical adenoma in 9, adrenocortical nodular hyperplasia in 1, adrenal medullary hyperplasia in 1, metastatic tumor in 2 and adrenal cyst in 2. Another case of adrenal cyst was diagnosed by percutaneous puncture. In all cases peripheral levels of plasma cortisol, plasma aldosterone concentration and plasma renin activity were normal. Plasma catecholamine levels were also normal except in a case of adrenal medullary hyperplasia. On the other hand, the cases of adrenocortical adenoma displayed elevation of urinary 17-hydroxycorticosteroids in 6/9 (67%), a loss of plasma cortisol circadian rhythm in 3/7 (43%) and insufficient suppression on dexamethasone (DXM) suppression test in 6/9 (67%). Their adrenal scintigraphy (with 131I-6 beta-iodomethyl-9-nor-cholest-5 (10)-en-3 beta-ol) revealed an increased ipsilateral up-take and insufficient suppression after DXM in all, while a diminished contralateral up-take in 4/9 (44%). These data suggested that a considerable number of adrenal incidentalomas may not be truly "non-functioning". Two patients with cortical adenoma experienced post operative adrenal insufficiency (25%). It was suggested that a pre-operative loss of plasma cortisol circadian rhythm was the most prognosticating of the post operative adrenal insufficiency, rather than insufficient DXM suppression or scintigraphic absence of contralateral up-take. Among the patients with malignancy, differentiation of incidental adrenal adenoma from metastasis by size alone may not be reliable.

Adenoma↗
PubMed2004

[Clinical characteristics of 16 patients suspected preclinical Cushing's syndrome].

PURPOSE: In 1996, Japanese guidelines for the diagnosis of preclinical adrenal Cushing's syndrome were proposed. However, several patients with preclinical Cushing's syndrome (PCS) didn't clearly show that these diagnostic guidelines were universally applicable. The aim of the present study was to evaluate the validity of these diagnostic guidelines on the basis of our clinical experience. PATIENTS AND METHODS: We performed adrenalectomy for adrenal incidentaloma in 16 patients with suspected PCS at our university hospital from 1990 through 2002. Eight patients met the Japanese criteria for the diagnosis of PCS (PC group) and 8 did not (dexamethasone [DXM] suppression group). Clinical characteristics and pathology profiles were compared between the groups. RESULTS: No patients in the DXM suppression group showed responses of serum cortisol levels on a 1-mg overnight dexamethasone suppression test. Twenty-four-hour urinary levels of 17-hydroxycorticosteroids were significantly higher in the PC group than in the DXM suppression group. In all patients of both groups, adrenal scintigraphy showed marked accumulation of radioisotope in the adhesive, atrophic adrenal cortex. One patient of the DXM suppression group had severe adrenal symptoms after adrenalectomy. Several patients in the DMX suppression group showed clinical improvement after adrenalectomy, as well as did several patients in the PC group. CONCLUSION: Endocrine activity may have been higher in the PC group than in the DXM suppression group. However, because patients who failed a 1-mg DXM suppression test may in fact have autonomous cortisol secretion, adrenalectomy may still be indicated. Autonomous cortisol secretion might not be documented with the 1-mg overnight DXM suppression test; therefore, the results must be interpreted carefully.

Adrenocorticotropic Hormone↗