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The biochemical assessment of sympathoadrenal activity in man.

Sympathoadrenal activity in man can be assessed by measuring catecholamines in plasma or by recording impulses in sympathetic nerves to skin and muscles by microneurography. Several studies have indicated that forearm venous plasma noradrenaline concentration and muscle sympathetic nerve activity are closely correlated in normal subjects at rest as well as during various conditions with increased or decreased sympathetic activity. Both parameters are influenced by baroreceptors and increase with age. Plasma adrenaline should preferably be measured in arterial blood because the extraction of adrenaline in organs and tissues may increase considerably when plasma adrenaline increases. The problem of studying the metabolic clearance rate of noradrenaline but not of adrenaline is discussed. It is emphasized that sympathetic activity is highly differentiated and it should therefore be measured in specific organs and tissues. Sympathetic activity in internal organs can be studied by measuring the release of noradrenaline from these organs. Imaging technique may, however, prove useful in future studies. The significance of microdialysis, measurements of plasma catecholamine metabolites, dopa and dopamine, plasma neuropeptide Y, catecholamines in urine and in the cerebrospinal fluid is discussed. Furthermore, it is emphasized that adrenergic agonist and antagonist drugs are important tools to study sensitivity and responsiveness to catecholamines preferably in specific organs and tissues. Finally, a few examples are given of the values in human research of the techniques described.

Adrenal Cortex Function Tests

Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production.

Isolated glucocorticoid failure associated with achalasia of the cardia is described in two pairs of siblings in separate families. Defective tear production is also present in three of the patients, and one shows other signs of autonomic dysfunction. Two other families with adrenal insufficiency and achalasia are known. This unusual association probably represents a familial disorder of as yet unknown aetiology.

Adrenal Cortex Function Tests

[Role of vitamin C on adrenocortical effects of etomidate].

This study was carried out to assess whether the adrenal inhibition induced by etomidate could be prevented by associating ascorbic acid with etomidate, as a protective effect of ascorbic acid administered three hours after etomidate has been described. Sixteen ASA 1 or 2 patients, less than 65 years old, free of endocrine disease, were included. At induction of anaesthesia, eight of them (group B) were given an infusion of ascorbic acid 1 g, in 500 ml of 5% glucose. Group A patients (n = 8) were given 500 ml of 5% glucose. Anaesthesia was induced with etomidate 0.3 mg.kg-1, fentanyl 0.005 mg.kg-1 and vecuronium 0.1 mg.kg-1. Maintenance was carried out using a continuous infusion of etomidate (0.1 mg.kg-1.h-1 for 10 min, followed by 0.01 to 0.02 mg.kg-1.h-1). Additional boluses of fentanyl or diazepam (10 mg) were administered when arterial blood pressure or heart rate were 20% greater than preanaesthetic values. The number of injections required was the same in both groups. Plasma cortisol concentrations were measured by radioimmunoassay (RIA) before anaesthesia (T0), 4 h (T4) and 24 h (T24) after the end of surgery. Blood ACTH levels were also assessed by RIA at T0 and T4. The adrenal insufficiency at T4 had completely ended at T24. In fact, the relative decrease in cortisol levels was greater in patients treated with ascorbic acid (T4/T0: 47.6 +/- 9% in group A vs 76.5 +/- 33% in group B, p less than 0.05); this was suggestive of a higher degree of adrenal inhibition in patients receiving ascorbic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex

Adrenal-cortical function in patients with medullary carcinoma of the thyroid and pheochromocytoma.

Medullary carcinoma of the thyroid (MCT) is reported to synthesize ACTH. This ACTH is believed to be responsible for the development of Cushing's syndrome in some patients with MCT. To determine the frequency of occurrence of adrenal cortical overactivity in patients with MCT, we measured plasma cortisol concentration and the urinary excretion of 17-hydroxycorticosteroids, 17-ketosteroids and urinary free cortisol in 22 patients with MCT and 7 patients with MCT plus pheochromocytomas. The patients with MCT and MCT plus pheochromocytoma had similar adrenal cortical function to age and sex matched normal subjects. We conclude that adrenal cortical function is usually normal in patients with MCT.

17-Hydroxycorticosteroids

Two cases of adrenal myelolipoma.

We report myelolipoma found in two patients, of whom one had hormonal abnormalities related to adrenal function. The first patient was a 36-year-old woman, who was found incidentally to have a left adrenal tumor by CT scan during admission for treatment of Guillain-Barré syndrome. Obesity, hirsutism and osteoporosis were also evident, and the patient was forwarded for additional endocrine function analysis, which revealed elevation of serum cortisol, urine 17-OHCS and 17-KS, and a decreased level of ACTH. These abnormalities returned to normal after excision of the tumor. Pathologically, the tumor was composed of mature fat cells and hematopoietic components, and was diagnosed as myelolipoma. The second patient was a 63-year-old woman, who was receiving follow-up care for hyperthyroidism. A right adrenal tumor was noted incidentally in a routine examination by CT scan. Endocrinologically, she was found to have no abnormalities of adrenal function. The tumor was excised, and diagnosed pathologically as myelolipoma, being composed of mature fat cells and hematopoietic components. Generally, although most myelolipomas have no endocrine function, our first patient showed features of Cushing's syndrome. Thus it is suggested that an interrelationship may exist between myelolipoma and endocrinological alteration.

Adrenal Cortex Function Tests

Effect on adrenal function of topically applied clobetasol propionate (Dermovate).

Thirty-nine patients (15 outpatients and 24 inpatients) with a variety of skin diseases affecting variable areas of the body surface were treated with clobetasol propionate ointment (Dermovate). Before and after treatment the adrenal response to an intramuscular injection of tetracosactrin was rested and additional 9 am plasma cortisol levels were measured at intervals during treatment. A satisfactory initial therapeutic response was achieved in almost all cases during the trial period. When more than 50 g of ointment a week was used a significant number of patients developed adrenal suppression. WHen less than 50 g per week was used any suppression tended to be transtion. These cysts may be the cause of this condition, producing abnormal amounts of ovarian steroids which modify the pituitary response. Futher studies are needed, however, to determine this possibility.

Adolescent

Urinary free 11-hydroxycorticosteroid/creatinine ratios in early morning urine samples as an index of adrenal function.

Urinary free 11-hydroxycorticosteroid/creatinine ratios were determined in early morning urine samples from 113 females (age range 20-45 years) and 65 males (age range 22-45 years). Basal values in normal subjects fluctuated between 5 and 55 mumol/mol creatinine. In four patients in whom Cushing's syndrome was diagnosed, urinary free 11-hydroxycorticosteroid/creatinine ratios were greater than 85 mumol/mol creatinine. Administration of dexamethasone (0.5 mg/q.i.d.) to nine normal laboratory staff for two days resulted in a suppression of the urinary free 11-hydroxycorticosteroid/creatinine ratio to less than 50% of the mean basal value in all cases. This degree of suppression did not occur in two cases of Cushing's syndrome due to adrenal tumours.

11-Hydroxycorticosteroids

Alterations in adrenal growth and corticosteroid content in foetal and neonatal rats developing at high altitude.

To study the effects of chronic maternal hypoxia on the growth and functional development of foetal and neonatal adrenal glands, Long-Evans rats were acclimatized to high altitude (3800 m) before mating and were maintained at this height throughout gestation. The body growth of the progeny at high altitude was essentially normal during the perinatal period, but adrenal weight and adrenocortical function showed marked differences from those of control rats maintained at sea level. The adrenal glands were larger in foetuses but smaller in neonates, compared with the adrenal glands of control animals maintained at sea level. Differences in the protein content of the adrenal glands between the two groups paralleled differences in adrenal weight. The concentration and content of corticosterone in the adrenal glands of both foetuses and neonates kept at high altitude were markedly lower than values in animals kept at sea level. The lower adrenal corticosterone content was not reflected in the concentration of the hormone in the peripheral plasma, since this was essentially the same at high altitude and at sea level in both mothers and perinatal animals. The reduction in the adrenal corticosterone content was accompanied by and may have resulted from, a reduction in the concentration of cytochrome P-450 in the adrenal tissue of foetuses maintained at high altitude. Possible explanations for the dichotomous results are discussed.

Adrenal Cortex Function Tests

[Indications for study of adrenal function by measurement of the cortisol secretion rate].

Results of routine methods for measurements of plasma cortisol and his urinary metabolites have been comparated with those of cortisol secretion rate (CSR) measured by simple isotopic dilution; the latter appears for his specify and precision, to be the most suitable for an exact evaluation of cortisol production by the adrenals. In normal subjects CSR resulted slightly lower than those reported in the literature; in obese subjects CSR was slightly higher than in normals, also when it was related to the urinary creatinine. In the patients with Cushing's syndrome, CSR was considerably higher, with no overlap with the obese subjects. The CSR was also useful in showing values lower than normal, in hypopituitarism, and in confirming hormone abnormal findings in thyroid diseases.

Adolescent

[Relationship between accumulation of o,p'-dichlorodiphenyl-dichloroethane in the adrenal glands and their function and structure].

Over a periof of 12 days following introduction of o'p-dichlordiphenyl-chlorethane to dogs in a dose of 25 mg/kg a sizable accumulation of the compound in the adrenal tissue, a drastic inhibition of its function and deragment of the suprarenal cortex structure are observed. After a 28-day administration of the compound the functional and structural upsets in the adrenals gain in strength, whereas it concentration in this organ declines.

Adrenal Cortex

[Adrenal function in chronic myeloid leukemia].

Adrenal function was studied in patients with chronic myeloid leukaemia treated in the past or presently with Busulphan. Adrenocortical function was determined by means of 24-hour profile of 11-hydroxysteroids (11-OHCS) in plasma, and urinary 24-hour 17 hydrocorticosteroids (17-OHCS) and 17-ketosteroids (17-KS). The adrenomedullary function was determined measuring VMA level in 24-hour urine. In most patients normal 24-hour 11-OHCS profiles and 24-levels of 17-OHCS, 17-KS and VMA. Only in some cases these levels were raised. This rise was observed more frequently in patients with blastic crisis of myeloid leukaemia which may indicate that the adrenal reserve was maintained in these patients. The investigations failed to show that the disease itself or Busulphan treatment impaired adrenal function. The possibility of a direct effect of Busulphan on melanin metabolism in the organism is discussed.

Adrenal Cortex Function Tests