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PubMed1970

Benign and malignant breast disease in South Wales: a study of urinary steroids.

The levels of aetiocholanolone, androsterone, and 17-hydroxycorticosteroids were measured in women without known disease of the breast, in women with benign breast disease, and in women with primary and advanced breast cancer. Statistical analysis showed there was no difference in the excretion of urinary 17-hydroxycorticosteroids in the various groups of patients. Detailed analysis of the aetiocholanolone and androsterone levels, however, indicated that patients with advanced localized disease excreted significantly less of these 11-deoxy-17-oxosteroids than those in the other groups.

17-Hydroxycorticosteroids↗
PubMed1976

Adrenosympathetic overactivity under conditions of work stress.

Serial measurements of urinary adrenaline, noradrenaline, and 11-hydroxycorticosteroid excretion were performed on 32 healthy men under two conditions of work stress; piecework and work on assembly line. A statistically significant increase in adrenaline, noradrenaline, and 11-hydroxycorticosteroids was observed for piecework and assembly line workers compared with salaried and 'ordinary' workers. The results support the assumption that psychosocial factors of an everyday type have significant effects on the sympathoadrenomedullary and adrenocortical function.

11-Hydroxycorticosteroids↗
PubMed1986

Ovine fetal adrenal maturation at term and during fetal ACTH administration: evidence that the modulating effect of cortisol may involve cAMP.

Exogenous ACTH1-24 promotes adrenal maturation in fetal sheep, and this effect appears to be modulated in part by cortisol (Challis et al. 1985). We have examined whether similar changes in adrenal metabolism of progesterone occur with ACTH-induced labour as at spontaneous term and whether the site of cortisol modulation is on adrenal steroidogenesis or at the level of cAMP generation. Chronically catheterized fetal sheep were infused in utero for 100 h between days 127 and 131 of pregnancy with P-ACTH, P-ACTH + metopirone, P-ACTH + metopirone + cortisol, or saline. After 100 h the metabolism of [3H]progesterone was measured in adrenal homogenates. Similar incubations were performed with adrenal tissue from fetal sheep at day 130 of pregnancy and at spontaneous labour. In the treatment groups of sheep, cAMP output by dispersed adrenal cells in response to ACTH added in vitro was also determined. Similar qualitative patterns of [3H]progesterone metabolism were found in adrenal homogenates after in vivo ACTH or at term. At both times there was an increase in cortisol and in total 17 alpha-hydroxycorticosteroid accumulation and also evidence for increased activity of 11 beta-hydroxylase enzyme. The formation of total 17 alpha-hydroxycorticosteroids was not affected significantly by concurrent treatment in vivo with metopirone +/- cortisol. The accumulation of cAMP in vitro was increased after in vivo ACTH, attenuated after ACTH + metopirone, but statistical significance over controls was restored after ACTH + metopirone + cortisol treatment. We conclude that ACTH-induced labour and spontaneous parturition in sheep is associated with qualitatively similar changes in progesterone metabolism by the fetal adrenal gland.(ABSTRACT TRUNCATED AT 250 WORDS)

17-Hydroxycorticosteroids↗
PubMed1976

The circadian periodicity of urinary 17-ketosteroids, corticosteroids, and electrolytes in congenital adrenal hyperplasia.

The circadian periodicity of adrenal function in patients with congenital virilizing adrenal hyperplasia (CAH) was examined by measuring the urinary 17-ketosteroids, 17-hydroxycorticosteroids, sodium, and potassium. Patients with the salt-losing and the non-salt-losing types were studied with and without treatment. Cosine curves were fitted to the data by the least-squares method to determine the mesors, amplitudes, and acrophases of the variable for each patient. The data reveal distinct circadian rhythms for all variables measured whether or not the patient was receiving treatment. The acrophases for 17-ketosteroids and 17-hydroxycorticosteroids were between 1500 and 1800 h. These acrophases are about 6 h later than those for normal subjects. The treatment on a fixed daytime schedule for many years may have shifted the natural rhythm.

17-Hydroxycorticosteroids↗
PubMed1980

Mineralocorticoid unresponsiveness with severe neonatal hyponatremia and hyperkalemia.

An infant with severe neonatal hyponatremia and hyperkalemia is described. Although marked elevations of urinary 17-hydroxycorticosteroids suggested an 18-dehydrogenase aldosterone biosynthetic defect, the infant proved to have mineralocorticoid unresponsiveness, or pseudohypoaldosteronism. Dietary sodium supplementation and ion exchange resin administration resulted in normalization of serum electrolytes and urinary 17-hydroxycorticosteroids. ACTH infusion produced natriuresis, suggesting the need for additional sodium supplementation during the stress of illness, with a resultant increase in ACTH secretion. Determinations of the relative amounts of urinary 18-hydroxy and aldosterone metabolites appear necessary for early definitive diagnosis of the disorder.

17-Hydroxycorticosteroids↗
PubMed1980

Pituitary carcinoma mimics the ectopic adrenocorticotropin syndrome.

A middle-aged man presented with weight loss, hypokalemic alkalosis, diabetes, hypertension, and generalized melanosis. Marked elevation of urinary free cortisol (655 micrograms/24 h) and plasma ACTH (2445 PG/ML) SUGGESTED THE DIAGNOSIS OF ECTOPIC ACTH syndrome. The plasma concentrations of cortisol and urinary 17-hydroxycorticosteroids increased paradoxically during the administration of dexamethasone without a corresponding change in the plasma ACTH level. Metyrapone administered over 24 h also markedly incrased both urinary free cortisol and 17-hydroxycorticosteroids. Selective venous sampling of plasma ACTH did not reveal a gradient between jugular vein and peripheral venous blood. The laboratory findings supported the diagnosis of ectopic ACTH syndrome. However, belated occurrence of visual changes necessitated surgical exploration, resulting in the diagnosis of pituitary carcinoma. A fluorescent antibody to ACTH reacted strongly with the atypical pituitary cells. This rare case documents that severe melanosis in Cushing's disease can occur without prior adrenalectomy and is consistent with the diagnosis of pituitary carcinoma. Furthermore, melanosis observed in patients with pituitary carcinoma is associated with ACTH levels similar to those occurrring in the ectopic ACTH or Nelson's syndrome.

17-Hydroxycorticosteroids↗
PubMed1983

The regulation of urinary free 19-nor-deoxycorticosterone and its relation to systemic arterial blood pressure in normotensive and hypertensive subjects.

19-Nor-deoxycorticosterone (19-nor-DOC) is a naturally occurring, potent mineralocorticoid present in hypertensive animal models as well as man. To investigate 19-nor-DOC's regulation and possible pathogenesis in hypertension, urinary free (UF) 19-nor-DOC was measured in 14 hypertensives, correlated with other corticosteroids and systemic arterial blood pressure (BP), and compared to basal and ACTH-stimulated values in 8 normotensive subjects. Seven of the 14 hypertensives had low-renin hypertension, 2 had primary aldosteronism, 1 had an adrenal carcinoma, and another had acromegaly. These studies determined that: 1) although the mean UF 19-nor-DOC was not increased in hypertensives (588 +/- 180 vs. 428 +/- 122 ng/day), 2 low-renin hypertensives had quite elevated levels (2186 and 2018); 2) the UF 19-nor-DOC in hypertensives was correlated with BP but not with PRA, aldosterone secretion, plasma potassium, basal plasma cortisol, or 17-hydroxycorticosteroids; 3) likewise, in normotensives, UF 19-nor-DOC did not correlate with basal plasma cortisol, cortisol secretion, or 17-hydroxycorticosteroids excretion but did correlate after ACTH stimulation. Therefore, although 19-nor-DOC is activated by ACTH administration, it is not correlated with basal parameters of cortisol production, suggesting that factors other than ACTH regulate basal 19-nor-DOC secretion. Furthermore 19-nor-DOC is elevated in some hypertensive patients, and it is directly related to the elevation of mean systemic BP. This suggests that, although 19-nor-DOC could contribute to hypertensive disease in some individuals, it does not appear to be due to excess ACTH.

17-Hydroxycorticosteroids↗
PubMed2001

A natural history of adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) from preclinical to clinically overt Cushing's syndrome.

A 49-year-old man was referred to our hospital for the treatment of gallstones in 1993. Bilateral adrenal nodular masses were detected incidentally by abdominal computed tomography. He had no clinical signs of Cushing's syndrome such as central obesity, striae of skin and diabetes mellitus. We performed cholecystectomy and partial adrenalectomy of right adrenal gland as a biopsy, and diagnosed him as preclinical Cushing's syndrome due to adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) based on endocrinological and histological examinations. We followed him up for 7 years. During the observation period, the sizes of both adrenal glands increased gradually, and finally serum cortisol level increased beyond normal range, and he showed a Cushingoid appearance such as moon face and central obesity. His skin became atrophic and very fragile, and the bone mineral density of his lumbar spine was extremely low. Serum cortisol level was elevated, and plasma ACTH level was always suppressed. Urinary excretion of 17-hydroxycorticosteroid and free cortisol were increased. Diurnal rhythm of cortisol and ACTH was completely lost and high dose (8 mg/day) dexamethasone did not suppress urinary 17-hydroxycorticosteroid excretion. He became clinically overt Cushing's syndrome. We recommended total adrenalectomy, but he refused it. It is important to know the natural history of preclinical Cushing's syndrome due to AIMAH when choosing an adequate treatment.

17-Hydroxycorticosteroids↗
PubMed1976

The insulin tolerance test after pre-treatment with dexamethasone.

The plasma 11-hydroxycorticosteroid and serum GH responses to insulin-induced hypoglycaemia were studied in 25 healthy volunteers. The results of a control insulin tolerance test were compared with those of 2 similar tests which were performed after pre-treatment with dexamethasone 0.5 and 1.0 mg, respectively. The GH response to hypoglycaemia was significantly lower in women than in men in all 3 tests. In men, but not in women, the GH response was lower after pre-treatment with 1 mg dexamethasone than in the other 2 tests. The plasma 11-hydroxycorticosteroid response was significantly greater after pre-treatment with 0.5 mg dexamethasone than in the control test, and was at least as good after 1 mg dexamethasone. After pre-treatment with dexamethasone the subjects experienced less discomfort and a shorter duration of sweating than in the control insulin tolerance test. Pre-treatment with 1 mg dexamethasone also has other advantages. Thus, the basal plasma cortisol level is low and stable, which facilitates estimation of the magnitude of the cortisol response. Furthermore, information is obtained about the dexamethasone suppression response.

11-Hydroxycorticosteroids↗
PubMed1981

Direct effect of histamine on the production of adrenocortical hormone by guinea-pig adrenal cells.

In trypsin-dispersed adrenal cells of the guinea-pig, the production of 11-hydroxycorticosteroids in vitro was found to be significantly stimulated by 10(-7) -10(-4)M histamine and the maximum steroidogenic response (1.7-fold increase in 11-hydroxycorticosteroid production) was observed at 10(-6)M. The stimulatory action of histamine on steroidogenesis was blocked by cycloheximide treatment.

11-Hydroxycorticosteroids↗
PubMed1975

Under-responsiveness of growth hormone secretion after L-dopa and deep sleep stimulation in obese subjects.

Plasma levels of glucose, free fatty acids and free 11-hydroxycorticosteroids, and serum levels of immunoreactive human growth hormone (HGH) and immunoreactive insulin were determined before and after L-dopa stimulation in 18 obese and six normal-weight subjects. A blunted response of HGH was found in the obese subjects who received 0.5 g L-dopa, but when the dose was doubled, a normal response was obtained in 7 of 13 of the obese subjects. No significant fluctuations in free 11-hydroxycorticosteroid, glucose or insulin levels were found in the obese and normal-weight groups and no increase in HGH was seen in the obese group after the subjects had been asleep for 90 min. In the obese subjects, the blunted response of HGH to stimulation with 0.5 g L-dopa and the lack of HGH increase during sleep are attributed to hypothalamic under-responsiveness, which is considered a basic disturbance in obesity.

11-Hydroxycorticosteroids↗
PubMed1965

Pituitary-adrenal function following topical triamcinolone acetonide and occlusion.

This study was undertaken to investigate the possible pituitary-adrenal suppressive effects of triamcinolone acetonide under occlusive dressings in six psoriatic patients. Forty-five grams of a cream containing 0.1% triamcinolone acetonide was applied daily to the psoriatic lesions of four patients and covered with an occlusive dressing. Two patients received daily applications of 45 gm of 0.01% triamcinolone acetonide cream and occlusive dressings. The four patients who received the 0.1% triamcinolone acetonide applications showed a marked decrease in the 24-hour urinary 17-hydroxycorticosteroids and no significant response to intravenous metyrapone testing. The two patients who were treated with 0.01% triamcinolone acetonide also showed a significant decrease in 24-hour urinary 17-hydroxycorticosteroids, but a partial response to metyrapone testing. Percutaneous absorption of as little as 1 to 2 mg of triamcinolone acetonide may affect pituitary-adrenal function.

17-Hydroxycorticosteroids↗
PubMed2004

Impact of amphotericin B on the cytochrome P450 system in HIV-infected patients.

OBJECTIVE: To investigate whether cytochrome P450-dependent enzymes are influenced by amphotericin B (Am-B) during the treatment of Candida oesophagitis in HIV-infected patients. METHODS: Twelve HIV-infected, antiretroviral-naive patients (CDC/WHO stage C3) with Candida oesophagitits were enrolled into a prospective clinical trial. The patients were treated with Am-B (0.4 mg/kg body weight) for two weeks. At baseline and after Am-B therapy the clearance of antipyrine and its metabolites were investigated by high-performance liquid chromatography. In addition, the urinary excretion of 6-beta-hydroxycortisol and 17-hydroxycorticosteroids was assessed by means of a radioimmunoassay. RESULTS: The following significant changes were observed after Am-B treatment (P < 0.01): increase of antipyrine half-life (12.4 h vs 16.8 h) and the area under the plasma concentration-time curve (27.9 mg min/ml vs 38.1 mg min/ml); decrease of the total body clearance (61.2 ml/min vs 43.7 ml/min); decrease of the renal clearance of antipyrine metabolites - norantipyrine (7.45 ml/min vs 5.31 ml/min), 4-hydroxyantipyrine (15.4 ml/min vs 10.3 ml/min), hydroxymethylantipyrine (4.31 ml/min vs 3.65 ml/min); decrease of urinary 6-beta-hydroxycortisol excretion (453 microg/24h vs 298 microg/24h) and the ratio of 6-beta-hydroycortisol to 17-hydroxycorticosteroids (8.8% vs 6.4%). CONCLUSIONS: Our data indicate that Am-B therapy has an inhibitory effect on cytochrome P450-dependent enzymes in HIV-infected patients. These results are of particular significance for HIV-infected patients who are concomitantly treated with drugs that are predominantly metabolised in the liver. A careful drug monitoring system seems advisable, especially for proteinase inhibitor experienced HIV-1-infected subjects.

17-Hydroxycorticosteroids↗
PubMed1975

The factors controlling stem cell recirculation. II. ACTH-induced inhibition of migration of hemopoietic stem cells.

Injections of ACTH of prolonged action (twice 1.5 units per mouse) given to lethally (800 R) irradiated mice with a hind limb shielded to the middle of the tibia brought about a twofold decrease in the number of spleen colonies. ACTH injections after sublethal whole-body irradiation (600 R) did not affect the number of endogenous spleen colonies. ACTH injection of normal mice brought about a substantial decrease in the CFU content in the circulating blood at the time of increased 11-hydroxycorticosteroid concentrations in the plasma. The results obtained are interpreted as inhibition of CFU migration from a shielded area of bone marrow induced by a high 11-hydroxycorticosteroid content in the plasma that followed ACTH injections which had no mitostatic effect on CFU proliferation.

11-Hydroxycorticosteroids↗
PubMedDate not supplied

[Use of circadian rhythms for analysis of the interrelationships between the concentration of glucocorticoids in the blood and the activity of key enzymes for gluconeogenesis in the liver and kidney of rats].

Circadian rhythms of alterations in content of 11-hydroxycorticosteroids and glucose in blood as well as in the activity of phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase in liver and kidney tissues were studied under normal and inverted luminous regimens in summer and winter seasons. These patterns were distinctly altered depending on circadian rhythms in the above-mentioned conditions. The maximal content of 11-hydroxycorticosteroids in blood did not correlate with the highest activity of the gluconeogenesis key enzymes in the periods studied. Daily alterations in the activity of phosphoemolpyruvate carboxykinase were shown to be similar to that of the fructose-1,6-diphosphatase in various tissues at different seasons. But glucose-6-phosphatase differed distinctly from these enzymes by the daily rhythm of activity. This suggests that glucose-6-phosphatase has the other mechanism for regulation of its daily rhythm.

11-Hydroxycorticosteroids↗
PubMed1990

The safety of halobetasol 0.05% ointment in the treatment of psoriasis.

The effects on the hypothalamic-pituitary-adrenal axis of the ultra-high potency corticosteroid halobetasol in the treatment of psoriasis were evaluated in seven patients with extensive, long-standing plaque psoriasis. Each patient applied 3.5 g halobetasol 0.05% ointment in the morning and evening for 7 days. Morning plasma cortisol levels and 24-hour urinary excretion of 17-hydroxycorticosteroid were determined before and on the last 2 days of treatment; plasma cortisol levels were also determined 4 and 5 days after completion of therapy. Morning plasma cortisol concentrations did not decrease significantly during treatment, and no values were below the normal range. Mean 24-hour urinary 17-hydroxycorticosteroid excretion fell from 6.6 +/- 1.4 mg to 5.1 +/- 1.4 mg. Two patients had mild, localized pruritus and stinging with the initial ointment application. No other adverse cutaneous effects were observed. Halobetasol was also clinically efficacious over the 7 days of treatment, based on evaluation of pruritus, erythema, scaling, and plaque elevation. These results demonstrate no adverse effects of the drug on the hypothalamic-pituitary-adrenal axis at doses that are clinically effective in the management of plaque psoriasis.

17-Hydroxycorticosteroids↗
PubMed1989

[Body weight, blood lipids, blood cortisol and prognosis of patients with cancer of the large intestine and breast].

Survival was evaluated in 121 patients with breast cancer and 114 with colorectal tumors versus overweight, body surface, preoperative blood-cholesterol level, cholesterol fraction profile and blood-triglyceride and -11-hydroxycorticosteroid levels. Survival was assessed by actuarial method. In breast cancer patients, prognosis inversely correlated with overweight and preoperative blood-cholesterol level whereas in colorectal cancer--with preoperative blood-triglyceride level, and--in males--with those of 11-hydroxycorticosteroids. The prognostic significance of cancrophilia factors in cancer as well as differences in said significance for colorectal and breast tumors are discussed.

11-Hydroxycorticosteroids↗
PubMedDate not supplied

[Evaluation of the secretory activity of the adrenal cortex and gonads in women with epilepsy. I. Urinary excretion of metabolites of adrenal cortex hormones in women with epilepsy during the 2 days preceding menstrual bleeding].

In 32 women with seizures occurring mainly in the premenstrual phase and during bleeding, (group A) and in 31 women with epilepsy without this relationship of the seizures to the menstrual cycle (group B) the metabolites of adrenocortical hormones (17-ketosteroids and 17-hydroxycorticosteroids) were determined in 24-hour urine. The investigations were done during 2 days preceding menstrual bleeding, in most cases during three menstrual cycles. A significant reduction of the excretion of 17-ketosteroids and total 17-hydroxycorticosteroids was found in both groups as compared to the accepted normal value (p less than 0.01). However, no significant difference was observed in the excretion of these hormones between these groups of patients, although in group A he values of 17-ketosteroids were lower than in group B. On the basis of these results it is suggested that deficiency of androgenic hormones may contribute to the occurrence of seizures on the days before the onset of menstrual bleeding, and the effect of anticonvulsant treatment on the decreased excretion of these hormones is discussed.

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