Biomedical subjects
Z Barrou
Publications and source records attributed to Z Barrou.
[Assay of salivary cortisol. An interesting method for exploring the adrenal cortex].
AN INTERESTING METHOD FOR PATIENTS AND PHYSICIANS: Measurement of salivary cortisol has not modified the investigation of hospitalized patients but offers very original possibilities for exploring outpatients. REPEAT MEASUREMENTS AND STIMULATION TESTS: As for serum cortisol levels, repeat measurements or stimulation tests are required for reliable evaluation of salivary cortisol. SEVERAL APPLICATIONS: Salivary cortisol level can be an appropriate tool in screening for adrenal insufficiency, using the short ACTH injection test, evaluating hypercorticism through the circadian cycle of cortisol and overnight dexamethasone suppression test either at the physician's office or in the patient's home. In addition, long-term follow-up is possible for outpatients investigated or treated for Cushing's syndrome.
[Actions of dehydroepiandrosterone: possible links with aging].
Dehydroepiandrosterone (DHEA) and its sulfo-conjugated derivative (SDHEA), secreted by the adrenal glands, are the most abundant circulating steroids in the human organism. The well-established fact that levels decrease progressively with age suggests a role in the aging process. They could also play a preventive role via an antitumoral action, stimulation of the immune system, an antiosteoporotic effect, a neuropsychologic action and cardiovascular protection. Nevertheless, it is not certain that evidence obtained from animal models can be transposed to man due to the specific nature of adrenal secretion of steroids in the human species. Epidemiological studies have often provided conflicting results. There have been few trials of administration in man, mostly aimed at studying the metabolic effects of DHEA. There is no evidence of secondary effects. Inversely, high-doses lead to transformation into active androgens with deleterious metabolic effects. Consequently, the current trend is to use low doses. Body weight, body composition, and sensitivity to insulin are not modified although variable effects on the lipid profile have been observed. Finally one study has produced much debate: a randomized trial demonstrating an improvement in wellbeing... Confirmation of this effect is certainly needed. In the absence of a satisfactory animal model, randomized prospective studies versus placebo are required to study the effect of substitution therapy in elderly subjects.
[Lymphocytic hypophysitis: a reality].
Lymphocytic hypophysitis is a rare entity; we report here three cases. This condition usually occurs in women during pregnancy or in the post-partum period. Pituitary enlargement is associated with complete or partial hypopituitarism. The difficulty in diagnosis is well illustrated by our cases and results from the similarity between the clinical and biological signs of adenoma and hypophysitis. Circulating antipituitary antibodies are not constantly found and are nonspecific, evidence only of the autoimmune nature of hypophysitis. Thus the diagnosis has to be undertaken in all suspected cases in pregnant women or during the post-partum period. The clinical course may be very long, emphasizing the need for rigorous long-term observation. The pituitary gland is commonly enlarged and homogenous in lymphocytic hypophysitis, but in our third case the enlargement was heterogeneous with associated cyst formation. We suggest that the inflammatory process could have been maintained by the presence of cysts. Finally, corticosteroids are the therapy of choice in the inflammatory stage and should be undertaken as soon as the diagnosis has been established. Regular surveillance is required.
Overnight dexamethasone suppression test: comparison of plasma and salivary cortisol measurement for the screening of Cushing's syndrome.
The overnight 1-mg dexamethasone suppression test is a very good screening test for subjects suspected of having Cushing's syndrome. To simplify the procedure, we evaluated the 1-mg dexamethasone suppression test with measurement of salivary cortisol. We performed this test with plasma and salivary cortisol measurements in 27 patients with Cushing's syndrome and 64 normal controls. The sensitivity and specificity of plasma cortisol measurements were 100% and 87%, respectively, for a cut-off point of 100 nmol/l, in accordance with previous studies. The results of salivary cortisol showed the absence of overlap between the two groups, with a sensitivity and specificity of 100% for a cut-off point of 2.8 nmol/l. On a larger series, however, one might occasionally miss the diagnosis of a patient with Cushing's syndrome. Therefore, we favor a cut-off point of 1.9 nmol/l, the sensitivity remaining at 100% and the specificity being 94%. In conclusion we recommend the overnight dexamethasone suppression test with measurement of salivary cortisol as a screening test for Cushing's syndrome.
[Function of pancreas transplants in increased metabolic stress].
Patients undergoing successful pancreas transplantation have normal glucose levels in the fasting and fed states and normal levels of hemoglobin A1c without use of exogenous inulin or any other medications for diabetes. In some of these patients, these measures have remained stable for more than 10 years. Additionally pancreas transplant recipients recover from short-term hypoglycemia produced by an intravenous pulse of insulin. However, metabolic success has been determined by relatively routine, unsophisticated tests such as oral and intravenous glucose tolerance tests or stimulation with intravenous arginine. These tests may not provide measures of the functional reserve of the pancreas, which is called on during periods of maximal stress. Consequently, we designed studies to ascertain beta and alpha cell performance in recipients of whole pancreas transplants and recipients of a segment of a living related donor. All recipients were recruited from the University of Minnesota Transplant Registry, Minneapolis, Minnesota. Successfully transplanted recipients were subjected to prolonged hyperglycemia to assess insulin secretory reserve using the method of glucose potentiation of arginine induced insulin secretion and to prolonged hypoglycemia to assess glucagon responsiveness and hepatic glucose production using the technique of the hyperinsulinemic hypoglycemic clamp. Our studies show that pancreas transplant recipients have markedly diminished insulin secretory reserve, a defect not evident with conventional tests of beta-cell function. No difference was found between the whole graft and segmental graft recipients. Pancreas transplantation restores the defective glucagon secretory response and enhances hepatic glucose production during prolonged hypoglycemia in subjects with type I diabetes. We conclude that pancreas transplantation does not completely restore beta-cell secretory reserve. This defect might be probably caused in part by cyclosporine and by the procedure involved in transplanting a cadaveric pancreas. Pancreas transplantation normalizes hypoglycemia-induced glucagon secretion and hepatic glucose production, thereby allowing for normalization of glucose recovery from hypoglycemia.
Pancreas transplantation in diabetic humans normalizes hepatic glucose production during hypoglycemia.
Although successful pancreas transplantation in humans with type I diabetes mellitus restores glucose-induced insulin secretion, provides freedom from insulin treatment, and normalizes fasting glucose levels, much less is known about its effects on counterregulation of hypoglycemia. To determine whether pancreas transplantation normalizes glucagon secretion and hepatic glucose production (HGP) during hypoglycemia, we performed hyperinsulinemic hypoglycemic clamps in successful recipients of pancreas allografts. Recipients were found to have glucagon secretory responses during hypoglycemia that were similar to those of control subjects (incremental glucagon response: recipients, 147 +/- 34 ng/L; control subjects, 161 +/- 43 ng/L, NS) but were significantly higher than those of matched subjects with type I diabetes (23 +/- 9 ng/L, P < 0.01). HGP rates at the end of 120 min of hypoglycemia were also significantly higher in recipients and control subjects than in subjects with diabetes (pancreas recipients, 1.92 +/- 0.33 mg.kg-1.min-1; control subjects, 2.05 +/- 0.18 mg.kg-1.min-1; subjects with type I diabetes, 0.58 +/- 0.12 mg.kg-1.min-1). A comparison with a third group of nondiabetic kidney transplant recipients demonstrated that the beneficial effects on glucose counterregulation were a result of pancreas transplantation and not the associated immunosuppressive therapy. We conclude that pancreas transplantation restores hypoglycemia-induced glucagon secretion and HGP, thereby allowing for normalization of glucose recovery from hypoglycemia.
Probability of retaining endocrine function (insulin independence) after definitive loss of exocrine function in bladder-drained pancreas transplants.
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[Nodular adrenomegalies in congenital adrenal hyperplasia in adults. Implications].
The presence of adrenal nodules in patients with congenital adrenal hyperplasia seems to be relatively frequent but is seldom reported. We observed such nodular formations in 3 women and 2 men aged from 19 to 71 years. Four patients had enzyme deficiency revealed in childhood (3 were deficient in 21-hydroxylase and 1 in 11-hydroxylase); the fifth patient had a virilizing form of an unrecognized 21-hydroxylase deficiency. In 3 patients the nodular formations had a diameter of 10 millimetres or less. In the other 2 patients the diameter was greater than 30 millimetres, and an adrenocortical adenoma was found at surgery. In one case a preoperative increase of medical treatment resulted in partial regression of the nodules. Our findings show that young subjects may have adrenal nodules, and their dependence on ACTH is discussed. We also discuss the possible influence of these nodules on the difficulty of medical treatment, the need for a life-long therapy and the necessity to look for a congenital adrenal hyperplasia when confronted with an "incidentaloma".
[Polyendocrinopathy combined with primary pulmonary arterial hypertension].
We report the case of a woman who had premature menopause, adrenal insufficiency and hypothyroidism by peripheral gland lesion, all most probably due to an autoimmune disorder, and who subsequently developed primary pulmonary arterial hypertension. The causes of this hypertension are ill-defined, but an autoimmune origin has often been envisaged since primary pulmonary arterial hypertension is not unfrequently associated with connective tissue diseases. Its association with an autoimmune polyendocrinopathy has only been reported, to our knowledge, on four occasions; in all 4 cases the thyroid gland was involved, and a connective tissue disease was present in 3 of them. Our case, which includes adrenal insufficiency and premature menopause is, as far as we know, unique. The possible link between these various diseases is their autoimmune nature, in which case primary pulmonary arterial hypertension would belong to the category of organ-specific autoimmune diseases. Our case supports the hypothesis that a number of isolated primary pulmonary arterial hypertensions could be of autoimmune origin.
[The effects of inhibition of converting enzyme by perindopril on renal hemodynamics and natriuresis in essential arterial hypertension].
Renal hemodynamics and natriuresis have been studied before and 6 hours after oral intake of perindopril (8 mg) in 8 hypertensive patients without renal failure. Then, the patients were treated with perindopril (8 mg per day) and renal hemodynamics was repeated on the fifth day, 6 hours after the morning intake of the substance. Sodium diet was controlled during the study (100 mmol sodium per day). Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by the clearance method using 131I-hippuran and 125I-iothalamate respectively. The results are as follows: (table; see text) Perindopril produced a potent renal vasodilatation after the first intake and the following days without any change in GFR. A significant decrease in FF was observed indicating that efferent as well as afferent arteriolar vasodilatation was induced. Perindopril produced an increase in natriuresis after the first intake and at D5; this natriuretic effect may be related to the changes in renal hemodynamics inducing a decreased sodium reabsorption in the proximal tubule.
Effects of perindopril on renal haemodynamics and natriuresis in essential hypertension.
Renal haemodynamics and natriuresis were studied before and 6 h after oral intake of perindopril (8 mg) in eight hypertensive patients without renal failure. The patients were then treated with perindopril (8 mg per day) and renal haemodynamics were measured on the fifth day, 6 h after the morning intake. Sodium intake was controlled during the study (100 mmol sodium per day). Renal blood flow and the glomerular filtration rate were measured by the clearance method using 131I-hippuran and 125I-iothalamate, respectively. Mean blood pressure decreased from 135 to 110 after 6 h, and was 118 mmHg on the fifth day (P less than 0.001, respectively). Renal vascular resistance decreased significantly after acute drug intake from 0.19 to 0.15 arbitrary units (P less than 0.001) and on the fifth day to 0.16 arbitrary units (P less than 0.001). Renal blood flow rose from 708 to 723 after 6 h, and to 750 ml/min per 1.73 m2 on the fifth day but the change was no significant. There was no alteration in the glomerular filtration rate so that the filtration fraction decreased from 0.27 to 0.26 (after 6 h), and to 0.25 on the fifth day (P less than 0.02). Natriuresis increased after the first intake between the first and tenth hours. On the fifth day, maximum natriuresis was observed between the fourth and sixth hours. Perindopril caused strong renal vasodilation after the first intake and during the following days, with no change in the glomerular filtration rate. There was a significant decrease in the filtration fraction, indicating efferent, as well as afferent, arteriolar vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
[Magnetic resonance imaging in Cushing disease. Prediction of surgical results].
OBJECTIVES: The purpose of the study is to determine if pituitary Magnetic Resonance Imaging (MRI) can predict the outcome of transsphenoidal surgery in patients with Cushing's disease. METHODS: Fifty four patients were divided in three groups according to MRI findings: those with a well circumscribed focal lesion clearly separated from the cavernous sinus (group 1, n = 24), those with adenomas in close contact with the cavernous sinus (group 2, n = 18), and those with no identified lesion (group 3, n = 12). RESULTS: The adenoma is found on the predicted side in 97,6% of the cases with positive MRI. A histologically proven adenoma is found in 96, 100 and 33% of the cases in groups 1, 2 and 3, with successful outcome in 91, 94 and 58% of the patients respectively. In group 2, surgery failed in a patient in whom tumoral tissue surrounded the internal carotid artery, but succeeded in two other cases in whom a MRI involvement of the cavernous sinus was suspected. CONCLUSION: We confirm the excellent localization value of MRI. Failure due to cavernous sinus involvement can be predicted only when MRI shows that the adenomatous tissue surrounds the carotid artery. In cases of negative MRI, the outcome is less favorable.