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PubMed1975

An application of neuroendocrinological studies in autistic children and Heller's syndrome.

The response of plasma 11-hydroxycorticosteroids (11-OHCS) to intravenous pyrogen as well as the circadian rhythm of plasma 11-OHCS levels were investigated in seven autistic children and in two children with Heller's syndrome. In autistic children, the stress response, which is acquired in an earlier stage of development, was adequately sustained. However, the circadian rhythm, which seems to appear at a later stage with the maturity of the CNS, frequently revealed abnormal patterns. Similar findings were obtained in the Heller's syndrome cases, indicating organic changes in the brain. On the basis of these results, it is postulated that in early infantile autism there exist some functional changes in the CNS that show a close correlation to the regulatory mechanism of ACTH secretion.

11-Hydroxycorticosteroids↗
PubMed1984

Urinary androgen and 17-hydroxylated corticosteroid metabolites and their relation to recurrence rates in early breast cancer.

The amounts of urinary androsterone and etiocholanolone are highly correlated with recurrence rates in patients with early breast cancer after treatment by mastectomy. A more efficient means of predicting the clinical course of the disease is obtained by using a ratio of these compounds to the amounts of individual 17-hydroxycorticosteroids in the urine. For instance, the ratio of androsterone to alpha-cortolone is particularly effective in identifying women with a high rate of recurrence, and this is largely independent of pathological stage and tumor grade.

17-Hydroxycorticosteroids↗
PubMedDate not supplied

Ranitidine treatment and cortisol metabolism in man.

Experimental evidence suggested that H2-receptor antagonists may inhibit not only hepatic but also adrenal cytochrome P-450 dependent monooxygenases. Therefore, the effects of ranitidine (150 mg b.i.d. over 14 days) on cortisol metabolism and antipyrine clearance have been investigated in nine healthy volunteers. Urinary excretion of 6 beta-hydroxycortisol (6 beta-OHC) and 17-hydroxycorticosteroids (17-OHCS) remained unaffected by ranitidine pretreatment, as did the calculated 6 beta-OHC/17-OHCS ratio. Only marginal effects were observed on antipyrine kinetics and metabolite formation. We conclude that neither adrenal production of corticosteroids nor their hepatic metabolism is affected by ranitidine administration.

17-Hydroxycorticosteroids↗
PubMed1999

Increased sensitivity to thyroid hormone replacement therapy followed by hyponatremia and eosinophilia in a patient with long-standing young-onset primary hypothyroidism.

We describe a 51-year-old woman with long-standing young-onset primary hypothyroidism. Serum cortisol, adrenocorticotropin, and arginine vasopressin levels were normal, but urinary excretion of 17-hydroxycorticosteroid was decreased. Administration of a very small initial dose of thyroid hormone induced severe acute complications including fever, palpitation, and sweating associated with a rapid decrease in serum thyrotropin level, a dramatic increase in serum alkaline-phosphatase level, and a decrease in serum total cholesterol level. A week later, the late complications of nausea, severe hyponatremia, and eosinophilia occurred. Serum cortisol level decreased slightly but remained within normal limits during this hyponatremic period. This rare case suggests that increased sensitivity to thyroid hormone can occur in long-standing primary hypothyroidism with biphasic clinical course of acute thyrotoxic complications followed by severe hyponatremia resembling hypoadrenocorticism.

17-Hydroxycorticosteroids↗
PubMed1992

The silent corticotropinoma: is clinical diagnosis possible?

Up to now, the diagnosis of silent corticotroph cell pituitary adenomas has been made only on histopathological basis. In this paper we describe 6 women affected with pituitary adenomas, without evident clinical features of hypercortisolism, in whom retrospective data suggested the possibility of clinically diagnosing silent corticotropinomas in vivo. In all patients basal ACTH and cortisol levels were normal, and the low-dose dexamethasone test constantly suppressed serum cortisol and urinary 17-hydroxycorticosteroid levels. The CRH and/or lysine-vasopressin tests, performed in five patients, always induced exaggerated ACTH/cortisol rises. In three cases the response to the opiate agonist loperamide was assessed and no inhibition of ACTH/cortisol levels was found. All patients underwent pituitary surgery. In five cases evidence of corticotropinoma was obtained by immunohistochemistry or immunofluorescence studies; moreover, in one adenoma ACTH was secreted into the culture medium, and in another one CRH and arginine-vasopressin induced a marked intracellular [Ca++] rise. Electron microscopy study of the adenoma, removed from three patients, showed the presence of adenomatous corticotroph cells. Finally, in another woman no hormonal abnormalities were initially observed and she was operated for a "nonfunctioning" pituitary adenoma, but four years later an overt Cushing's disease appeared, suggesting that a silent corticotropinoma subsequently became functional, although the formation of a different adenoma cannot be excluded. In conclusion, the occurrence of ACTH/cortisol hyperresponsiveness to CRH and/or lysine-vasopressin and the lack of suppression of ACTH/cortisol secretion to opioid agonists in patients with apparently "nonfunctioning" pituitary tumors might allow the in vivo recognition of silent corticotropinomas.

17-Hydroxycorticosteroids↗
PubMed1984

Cushing's disease: clinical and laboratory response to bromocriptine therapy.

Four patients with Cushing's disease were treated with bromocriptine, administered three times daily, in doses ranging from 7.5 to 15 mg/day, during an average period of 80 days. Daily urinary 17-hydroxycorticosteroids (17-OHCS) and 17-ketosteroids (17-KS) excretion was measured during dynamic tests and at two-week intervals. Plasma adrenocorticotropic hormone (ACTH) and cortisol levels were also assayed before and after therapy. A marked clinical and laboratory improvement was noted in two patients, in another some clinical and laboratory improvement was obtained only after bromocriptine dosage was increased to 15 mg/day. There was no effect in the fourth patient. Thus, at least for a short period of time, bromocriptine may be useful therapy for some patients with Cushing's disease.

17-Hydroxycorticosteroids↗
PubMed1980

Cushing's syndrome with small cell carcinoma of the uterine cervix.

A 28 year old white women was found to have a cervical tumor in the 25th week of pregnancy. Pathologic examination revealed a nonkeratinizing small cell carcinoma. After delivery by cesarean section, pelvic lymph node exploration was carried out, and all 15 nodes were free of tumor. Her condition was staged as II-A, and she was treated with local radiation. Metastatic disease became manifest almost a year later and was histologically similar to her primary disease. A Cushingoid appearance was noticed and plasma cortisol levels were elevated. Twenty-four hour urinary 17-hydroxycorticosteroid (17-OHCS) and 17-ketosteroid (17-KS) levels were elevated and failed to suppress with dexamethasone. Plasma adrenocorticotropin (ACTH) level was elevated. Electron microscopic examination of the tumor tissue revealed neurosecretory granules. Immunoperoxidase stains for ACTH were positive. The patient's course was one of progressive decline and eventual death. A literature review revealed two other cases in which carcinoma of the uterine cervix was considered to be the source of ectopic ACTH. Some small cell carcinomas of the cervix may arise from cells of the APUD series. Small cell carcinoma of the uterine cervix may behave differently from the more commonly encountered keratinizing and large cell nonkeratinizing carcinomas of the cervix and may not respond as well to standard therapy. Ectopic hormone production, production of abnormal peptides or of vasoactive amines may be more common in small cell carcinoma of the cervix than is currently recognized, and these products may be clinically useful as tumor markers.

17-Hydroxycorticosteroids↗
PubMed1978

Analysis of glucocorticoid metabolites in the neonatal period: catabolism of cortisone acetate by an infant with 21-hydroxylase deficiency.

The urinary excretion of 27 individual 17-hydroxycorticosteroids by a female infant with 21-hydroxylase deficiency was studied using gas chromatography on an open-tubular column and combined gas chromatography-mass spectrometry. Samples were analysed from days 1, 3 and 4 of life, before cortisone acetate treatment commenced on day 6, and on days 9 and 192, during treatment. The pattern of metabolites before and after treatment showed similarities with extensive reductions at positions 3 and 20 of the steroid nucleus and hydroxylations at positions 1 and 6. The following new glucocorticoid metabolites were identified: 1beta,3alpha,17alpha,21-tetrahydroxy-5alpha(andbeta)-pregnane-11,20-dione; 3alpha,6xi,17alpha,21-tetrahydroxy-5xi-pregnane-11,20-dione (2 epimers); 1beta,3alpha,17alpha,20alpha(andbeta),21-pentahydroxy-5beta-pregnan-11-one, and 3alpha,6xi,17alpha,20alpha (andbeta),21-pentahydroxy-5beta-pregnan-11-one. These steroids comprised 50% of the total metabolites on day 9, but only 20% on day 192. They have also been detected in the urine of normal neonates.

17-Hydroxycorticosteroids↗
PubMed1986

ELISA of 6-beta-hydroxycortisol in human urine: diurnal variations and effects of antiepileptic therapy.

An enzyme-linked immunosorbent assay for urinary 6-beta-hydroxycortisol (6-beta-OHF) was developed. A highly specific antiserum against 6-beta-OHF-21-hemisuccinate bovine serum albumin (6-beta-OHF-21-HS-BSA) raised in rabbit was used. The enzyme-labelled hapten was prepared by the mixed anhydride method using horse radish peroxidase (HRP). The limit of detection is very low (10 pg), the intra-assay variation ranges from 5.2-6.6%, the inter-assay variation is 8.2-8.3%. Cross reactivities of various steroids are very low. The diurnal variations in urinary 6-beta-OHF and it's ratio to 17-hydroxycorticosteroids (17-OHCS) were studied in six healthy volunteers. No significant difference was found within the 24 h for the ratio of 6-beta-OHF to 17-OHCS. A large increase of 8-12 h urinary 6-beta-OHF was observed in patients receiving chronic treatment with antiepileptics.

17-Hydroxycorticosteroids↗
PubMed1980

Human sleep and adrenal individual reactions to exercise.

Six fit men, aged 20, participated in the 16 day experiment. After a 5 day control period, the subjects marched on 6 consecutive days (from 09:00 h to 17:00 h) for 34 km/day at a speed of 6 km/h, with a backpack adjusted to complete a 35% of individual VO2 max energy expenditure. Control conditions were resumed for a 5 day recovery period. Sleep records were taken every night from 22:00 h to 06:00 h. Urinary 17-hydroxycorticosteroids (17-OHCS) were analysed from a 09:00 h to 17:00 h sample and from overnight urines. Two groups of subjects were defined by their responses to exercise. Four subjects exhibited an increase in stage 3 during the last third of the exercise nights (mean: 163.8 +/- 7.3% of control values) without any change in their adrenal response. Two subjects had no change or a slight decrease in stage 3 but showed increased 09:00--17:00 h 17-OHCS urine excretion (mean: 147 +/- 13% of control values). Sleep latencies were decreased in both groups. However, the 2 subjects of the second group exhibited increased restlessness as measured by the levels of wakefulness, stage 1 and EMG activity. In all subjects, paradoxical sleep was not altered, along with an unchanged all-night excretion of 17-OHCS. It is suggested that differences in adrenal responses to exercise may be responsible for differences in sleep quality. This could explain the discrepancies encountered in the literature about sleep variations after physical exercise.

17-Hydroxycorticosteroids↗
PubMed1976

Steroidogenic responses to varying parenteral routes of administered (alpha 1-18) ACTH.

In healthy human subjects, the steroidogenic responses to a single injection of alpha 1-18 ACTH by the subcutaneous, intramuscular, and intravenous (IV) routes were assessed by measurement of plasma cortisol levels, 17-hydroxycorticosteroid excretion, and cortisol secretion rates. Results showed that regardless of the parenteral route used, alpha 1-18 ACTH at doses of 1.0 and 0.5 mg was an effective adrenocorticotropic agent; however, with the IV route, the effect was considerably prolonged. The patterns of disappearance within the plasma of alpha 1-18 ACTH and alpha 1-24 ACTH were compared following a single IV injection of these compounds labeled with 125I. ALPHa 1-18 acth produced only a slight initial rise and a slower decline in plasma radioactivity compared to alpha 1-24 ACTH, suggesting slower degradation of alpha 1-18 ACTH. Administered as a single IV injection, alpha 1-18 ACTH has a prolonged effect on steroidogenesis and has potential for being a useful diagnostic and therapeutic ACTH preparation.

17-Hydroxycorticosteroids↗
PubMed1975

Candicidin: physiologic effect on prostate.

In a double-blind study, candicidin therapy resulted in over-all clinical improvement of benign prostatic hypertrophy symptoms in 78.1 per cent of treated patients compared with 10 per cent for patients given a placebo. Histologic review of prostates of candicidin-treated patients showed more stroma relative to the epithelium. The epithelium was less active with more cuboidal than columnar cells. There were fewer papillary infoldings, and the epithelium contained more true cysts than did the prostates of patients given a placebo. Urinary testosterone, 17-ketosteroids, 17-hydroxycorticosteroids, and serum androgen, follicle-stimulating hormones, and corticosteroid levels ramained within normal values with candicidin therapy.

17-Hydroxycorticosteroids↗
PubMed1985

Primary aldosteronism treated by trilostane (3 beta-hydroxysteroid dehydrogenase inhibitor).

The practicability and tolerability of trilostane, a competitive inhibitor of 3 beta-hydroxysteroid-delta 5-dehydrogenase, for the therapy of primary aldosteronism was assessed in 1 patient with aldosterone-producing adenoma (APA) and 3 subjects with idiopathic adrenal hyperplasia (IHA). Trilostane afforded reduction of plasma levels of aldosterone, progesterone, deoxycorticosterone, 17-OH progesterone, cortisol, delta 4-androstenedione, and urinary excretion of 17-hydroxycorticosteroid. Conversely, circulating levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, and urinary excretion of 17-ketosteroids were increased following this drug therapy. Suppression of mineralo- or glucocorticoid biosynthesis was accompanied by an increase in plasma renin activity. One patient with APA or 3 subjects with IHA showed slight or remarkable improvement of hypertension and hypokalemia. Based on these findings, efficacy and tolerability of trilostane appear to aid in the treatment of IHA.

17-Hydroxycorticosteroids↗
PubMedDate not supplied

Recent advances in the physiology of whole body immersion.

Recent investigations have furnished a complete analysis of the hemodynamic events accompanying whole-body immersion. About 700 ml of blood are translocated into the intrathoracic circulation, and heart volume increases by 180 +/- 62 ml. These changes are followed by an increase in stroke volume and cardiac output of over 30%. At the same time a reflex reduction of total peripheral resistance and venous tone occurs. Renin and aldosterone activity are reduced while the 17-hydroxycorticosteroid is not affected. Treatment of the subject with DOCA attenuates but does not extinguish the excess sodium excretion of immersion. This finding strengthens the arguments in favor of an unknown factor enhancing sodium excretion. Finally, the relative activation of the three factors that serve volume control, the excretory function of the kidney, capillary filtration pressure, and the thirst mechanism, is discussed.

17-Hydroxycorticosteroids↗
PubMedDate not supplied

Elevated urinary free cortisol in patients with dementia.

Urinary free cortisol (UFC), 17-hydroxycorticosteroids (17-OHCS) in urine and dexamethasone suppression test (DST) were examined in patients with dementia of Alzheimer type (DAT) and multi-infarct dementia (MID), and nondemented elderly. Eight of 19 patients (42.1%) were DST nonsuppressor. UFC was significantly elevated in patients with dementia, compared with that in nondemented elderly. There was no difference in UFC levels between DAT and MID. The UFC level correlated with post-DST plasma cortisol level at 1600 in demented patients. The mean level of 17-OHCS in demented patients was increased, although the difference was not significant statistically. In demented patients, UFC levels, not 17-OHCS levels in urine were correlated with Mini-Mental State Examination scores. These results suggest that a hypothalamo-pituitary-adrenal axis function is activated in demented patients and that this activation relates generally to dementation itself, not to an etiology of dementia. Measurement of UFC might be a biological marker of dementia and may have a value in diagnosis of dementia.

17-Hydroxycorticosteroids↗
PubMed1993

Clinical experience of incidentally discovered adrenal tumor with particular reference to cortical function.

We reviewed 14 male and 9 female patients with adrenal tumor discovered incidentally by imaging studies in an attempt to assess adrenal function, mainly cortical function. Pathological diagnosis consisted of cortical adenoma in 12 patients, cortical nodular hyperplasia in 2, medullary hyperplasia in 1, cavernous hemangioma in 1, metastatic tumor in 4 and cyst in 2. Another adrenal cyst was diagnosed by percutaneous puncture. In all patients peripheral levels of plasma cortisol and aldosterone were normal. Plasma catecholamine levels were also normal except for 1 patient with medullary hyperplasia who had equivocal elevation. Among the patients with cortical adenoma and hyperplasia, however, 5 of 10 (50%) had excessive excretion of 24-hour urinary 17-hydroxycorticosteroids, 4 of 13 (31%) had a loss of plasma cortisol circadian rhythm and 7 of 14 (50%) had insufficient suppression on the dexamethasone test. Furthermore all patients had an increased ipsilateral uptake that was not suppressed after dexamethasone on 131iodine-adosterol scintigraphy, while a diminished contralateral uptake was noted in 5 of 15 (33%). Postoperatively, hypertension decreased to normal in 2 of 3 patients and impaired glucose tolerance was improved in 1 of 2. Two patients with cortical adenoma who exhibited a loss of plasma cortisol circadian rhythm experienced postoperative adrenal insufficiency. These data indicate that a considerable number of incidentally discovered adrenal tumors are not nonfunctioning particularly in reference to glucocorticoid secretion, and adrenalectomy seems to be beneficial in some of those patients with hypertension or impaired glucose tolerance.

17-Hydroxycorticosteroids↗
PubMed1997

Endocrine functions in young men exposed for one night to a 50-Hz magnetic field. A circadian study of pituitary, thyroid and adrenocortical hormones.

In recent years, some epidemiologic studies have suggested that extremely low frequency magnetic and electric fields might affect human health, and, in particular, that the incidence of certain types of cancer, depression, and miscarriage might increase among individuals living or working in environments exposed to such fields. Work in our laboratory studies whether and how changes in the electromagnetic environment might affect human health. The study presented here was designed to look for possible effects of acute exposure to 50-Hz linearly polarized magnetic fields (10 microT) on the hormones of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes. Thirty-two young men (20-30 years old) were divided into two groups (sham-exposed or control group, and exposed group) of 16 subjects each. All subjects participated in two 24-hour experiments to evaluate the effects of both continuous and intermittent (one hour "off" and one hour "on" with the field switched "on" and "off" every 15 seconds) exposure to linearly polarized magnetic fields. The subjects were exposed to the magnetic field (generated by three Helmholtz coils per bed) from 2300 to 0800 while recumbent. Blood samples were collected during each session at 3 hour intervals from 1100 to 2000 and hourly from 2200 to 0800. Total urine was collected every 3 hours from 0800 to 2300 and then again at 0800. No significant differences were observed between sham-exposed and exposed men for any of the parameters measured: thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, triiodothyronine, thyroxine, free triiodothyronine, free thyroxine, thyroxine-binding globulin, cortisol, 17-hydroxycorticosteroids (17-OH-CS) and TBK. These results suggest that acute exposure to either continuous or intermittent 50-Hz linearly polarized magnetic fields of 10 microT does not affect, at least under our experimental conditions, these endocrine functions or their circadian rhythmicity in healthy young men.

17-Hydroxycorticosteroids↗
PubMed1994

Endocrinological and clinical evaluation of two doses of formestane in advanced breast cancer.

Formestane is a selective inhibitor of oestrogen synthesis by aromatase enzymes and induces disease regression in breast cancer patients. This phase II randomised study was carried out to determine whether there were any differences in the effects of two different doses of formestane on oestradiol (E2) serum levels and to evaluate the corresponding clinical activity in post-menopausal patients with positive or unknown oestrogen receptor status pretreated or not for advanced disease. Furthermore, possible drug interference with adrenal steroidogenesis was assessed by measuring 17-hydroxycorticosteroid (17-OHCS) urinary levels. A total of 143 patients entered the study and were randomly assigned to receive formestane 250 mg (72 patients) or formestane 500 mg (71 patients), both given i.m. every 2 weeks. In comparison with baseline, E2 serum levels decreased by an average of 40% after only 15 days and remained unchanged thereafter, with no difference being observed between the two doses. The values of 17-OHCS remained unchanged during treatment in both groups. Objective responses were 28% (19/69) in the 250 mg and 46% (31/68) in the 500 mg group. In conclusion, the two formestane doses were equally effective in reducing E2 levels without affecting adrenal function, and in inducing a considerable percentage of clinical responses.

17-Hydroxycorticosteroids↗