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Biochemical characterization of pituitary-dependent hyperadrenocorticism in the dog.

The biochemical characterization of 22 cases of pituitary-dependent hyperadrenocorticism in the dog, is reported. The principal characteristics of the disease include excessive and non-rhythmic production of cortisol, decreased sensitivity of the hypothalamic-pituitary system to the suppressive effects of dexamethasone, decreased responsiveness of the pituitary-adrenocortical system to the stimulus of insulin-induced hypoglycaemia and increased responsiveness of the system to stimulation with lysine-vasopressin. From these observations it is concluded that pituitary-dependent hyperadrenocorticism in the dog is a valid model for study of the pathogenesis of the disease in man. For the diagnosis of hyperadrenocorticism itself, the measurement of the concentration of corticosteroids in a single sample of plasma obtained 8 h after intravenous injection of 0.01 mg dexamethasone/kg was sufficient. The level of 11-hydroxycorticosteroids was less than 140 nmol/1 plasma in normal dogs, whereas higher values were found in dogs with hyperadrenocorticism. For purposes of differential diagnosis, measurement of the level of corticosteroids in the plasma both before and 4 h after intravenous injection of 0.05 mg dexamethasone/kg is adequage: suppression is obtained only in cases of pituitary-dependent hyperadrenocorticism.

11-Hydroxycorticosteroids↗

Adrenal circadian system in young and elderly human subjects: a comparative study.

Circadian changes in plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), total and unbound cortisol were studied in four groups: seven healthy young men, six elderly men, six elderly women and six elderly demented patients of both sexes. The daily activities of the subjects were synchronous; blood samples were taken every 4 h and 4 hourly urine samples were collected only from the young men. A circadian rhythm was defined for plasma 18-OH-DOC, total and unbound cortisol in all groups; the secretory patterns of these steroids were parallel, as were the profiles of urinary 18-OH-DOC and unconjugated cortisol. When compared with respect to sex, the 24-h mean level of total cortisol was higher in women; that of unbound cortisol was higher in the three groups of elderly patients than in the young men. No major changes in plasma steroids were observed between elderly demented patients (mainly women) and healthy elderly women. The phasing of total and unbound cortisol showed no major modifications with age, sex or senile dementia. Acrophases of 18-OH-DOC were earlier in elderly patients than in young men. Amplitudes were not modified with sex in elderly patients but were always lower in the demented patients. A circadian rhythm was defined for 18-OH-DOC, unconjugated cortisol, 17-hydroxycorticosteroids (17-OH-CS) and 17-ketosteroids in the urine of the young men. The acrophases of 18-OH-DOC and unbound cortisol were close, as were those of 17-OH-CS and 17-ketosteroids. The lag was short between the acrophases of 18-OH-DOC in plasma and urine and between those of plasma unbound cortisol and urinary unconjugated cortisol; it was much larger between the acrophases of plasma total cortisol and 17-OH-CS. Thus, the process of ageing, and the possible alterations in the central nervous system which are often seen in normal ageing, induced no major modifications in the temporal organization of adrenocortical function, even in subjects who were very advanced in age.

17-Hydroxycorticosteroids↗

Thyroid storm associated with probable subclinical hypoadrenocorticism in an elderly woman.

A 73-year-old woman was admitted to the hospital for severe persistent vomiting with fever, drowsiness, and weight loss. Elevated serum levels of thyroid hormones and the presence of a consciousness disorder with fever and vomiting led to the diagnosis of thyroid storm. A low normal concentration of serum cortisol, urinary 17-hydroxycorticosteroids and an elevated plasma level of corticotropin suggest that an inadequate adrenal reserve have been involved in the pathogenesis of the thyroid storm in this patient. She responded to the administration of intravenous methimazole and oral supersaturated potassium iodide solution.

17-Hydroxycorticosteroids↗

Cushing's syndrome due to unilateral adrenocortical hyperplasia.

A 49-year-old woman with Cushing's syndrome due to unilateral adrenal hyperplasia is presented. She had developed obesity and menopause for 2 years, but no hypertension or hypertrichosis was observed. Although plasma adrenocorticotropin and serum cortisol levels were within normal ranges, the circadian rhythm has completely disappeared. Free thyroxine and triiodothyronine levels were decreased. Adrenocorticotropin did not respond to corticotropin-releasing hormone, and urinary excretion of 17-hydroxycorticosteroids was not suppressed by dexamethasone. Abdominal computed tomography and 131I-Adosterol scintigraphy demonstrated a unilateral functioning mass in the left adrenal gland. The resected left adrenal mass was pathologically diagnosed as the rare condition of adrenocortical nodular hyperplasia.

17-Hydroxycorticosteroids↗

An overnight high-dose dexamethasone suppression test for rapid differential diagnosis of Cushing's syndrome.

We have developed a high-dose dexamethasone suppression test that can be administered overnight with a single 8-mg dose and used the new procedure in the differential diagnosis of 83 patients with Cushing's syndrome. In 76 patients with surgically or pathologically proven cause--60 with Cushing's disease, 7 with the ectopic adrenocorticotrophic hormone syndrome, and 9 with adrenal tumors--suppression of plasma cortisol levels to less than 50% of baseline indicated a diagnosis of Cushing's disease. The test had a sensitivity of 92%, a specificity of 100%, and a diagnostic accuracy of 93%. These values equal or exceed those of the standard 2-day test whether based on suppression of urinary 17-hydroxycorticosteroids or plasma cortisol. We conclude that this overnight, high-dose dexamethasone suppression test is practical and reliable in the differential diagnosis of Cushing's syndrome.

17-Hydroxycorticosteroids↗

Paradoxical response to dexamethasone in the diagnosis of primary pigmented nodular adrenocortical disease.

BACKGROUND: Primary pigmented nodular adrenocortical disease causes the Cushing syndrome in children and young adults and is most frequently associated with the Carney complex. OBJECTIVE: To evaluate diagnostic tests for primary pigmented nodular adrenocortical disease. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: 21 patients with primary pigmented nodular adrenocortical disease. The control groups consisted of 9 patients with macronodular adrenocortical disease and 15 patients with primary unilateral adrenocortical disease (single adenomas). MEASUREMENTS: Clinical characteristics, radiologic imaging, and a 6-day Liddle test with determination of urinary free cortisol and 17-hydroxycorticosteroid excretion. RESULTS: Adrenal imaging and other tests were of limited value for the diagnosis of primary pigmented nodular adrenocortical disease. The Liddle test, however, distinguished patients with this disorder from those with other primary adrenocortical lesions. An increase of 50% or more in urinary free cortisol levels on day 6 of the Liddle test identified 9 of 13 patients (69.2% [95% CI, 46.6% to 91.8%]) with primary pigmented nodular adrenocortical disease, excluded all patients with macronodular adrenocortical disease, and was present in only 3 of the 15 patients with single adrenocortical adenomas (20% [CI, 0% to 40.2%]). An increase in urinary free cortisol excretion of 100% or more on day 6 of the Liddle test identified only patients with primary pigmented nodular adrenocortical disease. CONCLUSIONS: Patients with primary pigmented nodular adrenocortical disease responded to dexamethasone with a paradoxical increase in glucocorticoid excretion during the Liddle test. This feature distinguishes such patients from those who have the Cushing syndrome caused by other primary adrenal disorders and may lead to timely detection of the Carney complex (a potentially fatal disorder) in asymptomatic patients.

17-Hydroxycorticosteroids↗

Serum cortisol levels in Cushing's syndrome after low- and high-dose dexamethasone suppression.

To standardize the cutoff points of serum cortisol values in the evaluation of Cushing's syndrome during a low- and high-dose dexamethasone suppression test, daily serum cortisol measurements (0800 hours and 1600 hours) and urinary 17-hydroxycorticosteroids were compared (Study A). Forty-seven subjects were studied (11 normal subjects, 15 patients with Cushing's disease, five patients with adrenal adenoma, and 16 subjects with suspected Cushing's syndrome). A serum cortisol measurement at 1600 hours of more than 5 micrograms/dL on low-dose dexamethasone suppression and more than 10 micrograms/dL on high-dose dexamethasone were ascertained to be nonsuppressed values. A baseline dehydroepiandrosterone-sulfate value less than 0.4 microgram/mL indicated patients with an adrenocorticol adenoma. Study B was a prospective study of 17 patients in which no urine samples were collected. Serum cortisol levels, obtained in 1600 hours on the second day of low- and high-dose dexamethasone, accurately allowed a differential diagnosis of suspected Cushing's syndrome. Serum cortisol measurements can replace the urinary 17-hydroxycorticoid measurements in a cost-effective manner without a decrease in the degree of accuracy.

17-Hydroxycorticosteroids↗

[Effect of noise on the physiological functions in fowl. 1. Effect of primary strong noise on the 11-OHKS level in broilers and leghorns].

The effects of first noises on broilers and white leghorns were tested by plasma levels on 11-hydroxycorticosteroid (11-OHKS). The noises were 100 dB, 60 to 8,00 Hz, and applied 30 minutss to one group of broilers, aged 14, 28, and 56 days, and to another group of broilers and white leghorns in adult age. The reactions were compared. Acoustic stimulation was followed by temporary activation of the hypothalamic pituitary-suprarenal system. The rise of the plasma glucocorticosteroid level in leghorns was three times as high as that in adult broilers, which was interpreted as a reflection of stronger organic stress. Reactions differed in intensity, depending on age as well. Plasma-11-OHKS levels went up by 32 per cent maximum in broilers aged 56 days or by 73 per cent in animals aged 14 days or 120 per cent in those aged 28 days. The above results seemed to support the conclusion that noises of the above quantity and quality represented stress on fowl.

11-Hydroxycorticosteroids↗

[Effect of noise on the physiological functions in fowl. 2. Adaptation to noise of white leghorns and broilers].

Two experimental groups and series were compared (leghorns and broilers as well as two age groups of broilers) for their adaptive responses to repeated noise application. The noise was 100 dB and applied daily 30 minutes. The reference for comparison was the plasma-11-hydroxycorticosteroid concentration (11-OHKS). The results differed somewhat from those obtained earlier from one first short-time noise application, in that the rise in plasma glucocorticosteroid concentrations dropped from 431 to 210 per cent of the initial values in adult leghorns exposed to repeated noise stress over seven days. Adult broilers, however, did not exhibit any difference in the magnitude of rise of 11-OHKS concentrations by comparison between first and seven days of repeated stress. The initial values, however, were reached earlier by repeated noise application.

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Endocrine patterns of the mare at term.

The levels of progesterone and total progestins increased during late pregnancy and then fell dramatically during the last few days before parturition, although birth occurred in the presence of significant amounts of plasma progesterone. Oestrogen levels decreased slowly but insignificantly until birth occurred, and then remained at a low level until the post-partum oestrus 10 to 12 days later. Total 11beta-hydroxycorticosteroids were unchanged from Day 45 before to Day 15 after birth. The endocrine pattern of one ovariectomized pregnant mare during the last month of gestation was similar to that of the intact mares. A normal cyclic progesterone and total progestin pattern was observed at the post-partum ovulation. Oestrogen levels did not change significantly but corticosteroid levels increased significantly between Days 15 and 22 post partum. Progestin, oestrogen and corticosteroid levels during the first 24 hr after birth were consistently higher in the foal than in the maternal plasma.

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[Biochemical and hematological changes in sows during estrus].

After the second and fourth parturition of piglets, ten clinically healthy sows, weaned on the second day of life, were subjected to examination two to three days before heat, during heat (defined by typical changes on the outer genitals and immobilization in the presence of a boar) and two days after insemination. During the morning hours, four hours after the last feeding, blood was taken from V. cava cranialis. Seventeen parameters were determined in whole blood and in the blood serum. In the period of oestrus, compared with the period two to three days before this period and two days after insemination, a marked increase was observed in the concentration of the serum levels of 11-hydroxycorticosteroids, iron, and in the activity of alanine aminotransferase. The activity of aspartate aminotransferase was increased in heat only in comparison with the period of the two days after insemination. The concentration of haemaglobin in whole blood was significantly increased in comparison with the period before oestrus and after insemination. Further, in the heat period -- as compared with the time before it -- a considerable drop was observed in the content of inorganic phosphorus and vitamin A. The possible mechanism of the occurrence of other changes is discussed.

Animals↗

Psychological stress induced by 20 days bed rest.

We investigated the changes of the psychological state during 20 days bed rest (BR) in 10 young participants,(5 males and 5 females, age; 19-24 yrs). Psychological assessment was accomplished by the following authorized 3 indices: 1) Zung's Self-rating Depression Scale, 2) Cornell Medical Index, and 3) Goldberg's General Health Questionnaire. Zung's Self-rating Depression Scale is a indicator for depression, and the other two indices were used for detecting signs of neurosis. The results from Zung's Self-rating Depression Scale and the General Health Questionnaire in this study indicated a tendency toward depression and neurosis developing during BR, respectively. The scores in the Cornell Medical Index did not change. Urinary excretion of 17-hydroxycorticosteroid increased significantly, indicating that BR immobilization induced an important psychological stress. We were unable to determine which factors caused the changes in psychological state during BR, immobilization insert or personal problems.

17-Hydroxycorticosteroids↗

Evaluation of psychological effects due to bed rest.

The psychological condition of astronauts is an important factor for ensuring mission success in limited space. Head-down tilting bed rest is a well-accepted method by which to simulate an acute stage of human adaptation to the weightless state in space flight. In our previous studies, the enhancement of depressive and neurotic levels occurred during a 20-day horizontal bed rest. In this study, we attempted to examine the depressive and neurotic levels, the mood status, and behavioral tendency of the subjects and to analyze the changes of 24-hour urinary excretion of 17-hydroxycorticosteroid-glucronides (17-OHCS) for an indicator of changes in the endocrine system due to physical and psychological stress during a 20-day 6-degrees head-down tilting bed rest (BR).

17-Hydroxycorticosteroids↗

Further examination of a biochemical test for suicide potential.

The use of biological data, especially adrenal cortical activity, to enhance the assessment of suicide potential has been suggested and briefly argued in the literature. In this report data is presented on two suicide patients. One patient suicided 8 months after her 4-month hospitalization during which time her 17-hydroxycorticosteroid (17-OHCS) excretion remained at low levels. The second patient suicided on his thirteenth hospital day; his 17-OHCS excretion was moderately elevated, but consistent with his high anxiety and depression ratings. One case is used to support the previous findings that low 17-OHCS affords the clinician no reassurance regarding suicidal risk in the future. The other case illustrates the difficulty in interpreting moderate elevation in arousal sensitive endocrine systems in light of clinically manifest anxiety and/or depression.

17-Hydroxycorticosteroids↗

Effect of insulin hypoglycaemia on adrenocortical function and blood plasma vitamin E and cholesterol levels in suckling and weaned piglets.

Suckling piglets aged 28-31 days and weaned piglets aged 46-60 days were injected with insulin at a rate of 1 U/kg body weight to induce hypoglycaemia. All the animals were blood-sampled before and 45 and 90 minutes after the insulin injection. Both groups developed a marked adrenocortical response without any significant differences, though the rise in plasma 17-hydroxycorticosteroid (17-OHCS) levels of weaned piglets was slightly delayed. Plasma vitamin E concentration showed a significant rise in suckling piglets and a slight rise in weaned animals; it was not accompanied by an increase in total cholesterol levels. The results suggest that glucocorticoids affect vitamin E metabolism. The values of plasma 17-OHCS, cholesterol and vitamin E levels as well as of blood glucose levels and circulating eosinophil leucocyte counts confirmed differences in these parameters between suckling and weaned piglets.

17-Hydroxycorticosteroids↗

[Clinical experience with a test of pituitary reserve].

A test of pituitary reserve was used in the investigation of 14 children with retarded growth and 15 adults with endocrine disorders. Mepyrapone (Metopiron), 500 mg. every four hours, was administered orally for 48 hours. The pituitary response was determined by the amount of 17-hydroxycorticosteroid in a 24-hour urine sample (by a modification by Peterson of the Porter-Silber method). Pituitary reserve was decreased in four patients who were pituitary dwarfs, one who had retarded growth, two patients with Sheehan's syndrome, three with pituitary tumours, one who had panhypopituitarism without a tumour, and one case of limited adrenal reserve (confirmed by a negative response to ACTH stimulation). The pituitary reserve was normal in three patients with gonadal dysgenesis, three who exhibited retarded growth, one case of diabetes insipidus, one cretin, one patient treated by steroids, three with psychogenic amenorrhea, and five normal controls. It is concluded that this test of pituitary reserve is useful in the assessment of children with growth retardation and in establishing the diagnosis of pituitary insufficiency in adults.

17-Hydroxycorticosteroids↗

KORSAKOFF'S SYNDROME ASSOCIATED WITH ADRENAL VIRILISM.

Korsakoff's syndrome of obscure etiology was observed in a 34-year-old single woman with an 11-year history of hirsutism and mood swings, and previous hospitalizations for mania three years ago and depression 11 years ago.Recently the virilism had intensified with increased muscularity and coarsening of facial features. The 24-hour urinary 17-ketosteroids ranged between 14.4 mg. and 21.5 mg. and were suppressed by dexamethasone. The 17-hydroxycorticosteroid excretion was normal. These and other findings suggested a diagnosis of adrenal virilism due to adrenocortical hyperplasia. In the absence of other discernible causes it appeared that the adrenal pathology was responsible for the Korsakoff's syndrome. Both conditions responded well to glucocorticoid therapy although low doses were necessary to avoid mania.It is speculated that the encephalopathy was due to an associated adrenal insufficiency. Although hypoadrenalism is accepted as a complication of only the infant form of adrenal virilism, it is noteworthy that this patient had pathological pigmentation of her skin.

17-Hydroxycorticosteroids↗

[Participation of the adrenals in the pathogenesis of metabolic acid-base disorders].

The authors examined in dynamics the changes in the functional state of the adrenals on 240 rabbits, which served as models for acute metabolic deviations in the acid-base balance. The obtained results showed that the acute metabolic acidosis increased moderately the values of ACTH and 17-hydroxycorticosteroids in blood without changing their concentration on the adrenal tissue. It lowered strongly the content of catecholamines (adrenaline and noradranaline) in the adrenal medular part. The metabolic alkalosis raised the concentration of ACTH in blood plasma and increased the amount of corticosteroids in blood and adrenals. There was no well formed parallelism in normalizing acid-base and hormonal indices. As a consequence of this a stage of postaciodotic catecholamine adrenal deficit was formed as well as metabasic hypercorticism in the experimental animals.

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