Plasma concentration of neuropeptide Y in patients with adrenal hypertension.

The mechanisms of hypertension during primary hyperaldosteronism and Cushing's syndrome are not completely understood. An enhanced vascular sensitivity to noradrenaline has been described in both situations. Neuropeptide Y (NPY) induces direct vasoconstriction and potentiates the action of noradrenaline. Sodium retention and dexamethasone have been shown to increase circulating NPY levels in animals and the expression of NPY in neuroendocrine cells. In order to determine if NPY could be involved in the enhanced vascular sensitivity to noradrenaline associated with adrenocortical hyperactivity, we measured plasma NPY in patients with Cushing's syndrome (n = 26) and primary hyperaldosteronism (n = 15) and compared it with that of hypertensive patients with pheochromocytomas (n = 13) or essential hypertension (n = 51) and with normotensive controls (n = 47). The concentration of NPY-Like immunoreactivity (NPY-Li) (mean +/- S.E.) in controls was 39.6 +/- 3.0 pg/ml. Elevated concentrations were found in 77% of the samples collected from pheochromocytoma patients (1180.4 +/- 394.0 pg/ml). NPY-Li levels in patients with essential hypertension (35.0 +/- 2.6 pg/ml), primary hyperaldosteronism (31.3 +/- 3.9 pg/ml) and Cushing's syndrome (33.1 +/- 4.8 pg/ml) were not different from that of controls. NPY-Li levels in hypertensive and normotensive patients with Cushing's syndrome were similar (38.5 +/- 7.5 vs 24.2 +/- 3.7 pg/ml). No correlation was found between the NPY-Li level and the mean blood pressure at the time of sampling. Our results suggest that NPY is unlikely to be involved in the pathogenesis of hypertension associated with primary hyperaldosteronism and Cushing's syndrome.     

Aldosterone synthase cytochrome P-450 expressed in the adrenals of patients with primary aldosteronism

A human cytochrome P-450 with aldosterone synthase activity was purified from the mitochondria of an aldosterone-producing adenoma. It was recognized by an anti-bovine cytochrome P-450(11 beta) IgG and by a specific antibody raised against a portion of the CYP11B2 gene product, one of the two putative proteins encoded by human cytochrome P-450(11 beta)-related genes (Mornet, E., Dupont, J., Vitek, A., and White, P. C. (1989) J. Biol. Chem. 264, 20961-20967). A similar and probably the same aldosterone synthase cytochrome P-450 was detected in the adrenal of a patient with idiopathic hyperaldosteronism. These aldosterone synthases were distinguishable from cytochrome P-450(11 beta), the product of another cytochrome P-450(11 beta)-related gene, i.e. CYP11B1, by their catalytic, molecular, and immunological properties and also by their localization. The latter enzyme was unable to produce aldosterone and did not react with the specific antibody against the CYP11B2 gene product. It was present both in tumor and non-tumor portions of the adrenals carrying the adenoma and in normal adrenal cortex. On the other hand, aldosterone synthase cytochrome P-450 localized in the tumor portions of the adrenals or in the adrenal of a patient with idiopathic hyperaldosteronism. Thus aldosterone synthase cytochrome P-450, a distinct species from cytochrome P-450(11 beta), is responsible for the biosynthesis of aldosterone in the human, at least in patients suffering from primary aldosteronism.     

Impaired insulin action in primary hyperaldosteronism

The presence of insulin resistance is frequently found in essential hypertension. There are, however, only sparse data with respect to the potential presence of insulin resistance in patients with secondary hypertension. We have therefore undertaken a study to reveal the potential occurrence of insulin resistance in primary hyperaldosteronism (PH). The hyperinsulinemic euglycemic clamp technique together with the evaluation of insulin receptor characteristics were used to study insulin resistance in 12 patients with PH. The measured parameters were compared to normal values in control subjects. We have found a significantly lower glucose disposal rate (M, micromol/kg/min) (18.7+/-6 vs. 29.3+/-4), decreased tissue insulin sensitivity index (M/I, micromol/kg/min per mU/l x100) (23.7+/-9.8 vs. 37.5+/-11.6) and also lower metabolic clearance rate of glucose (MCRg, ml/kg/min) (3.8+/-1.5 vs. 7.0+/-1.1) in patients with primary hyperaldosteronism. The insulin receptor characteristics on erythrocytes did not differ in primary hyperaldosteronism as compared to control healthy subjects. We thus conclude that insulin resistance is also present in secondary forms of hypertension (primary hyperaldosteronism) which indicates the heterogeneity of impaired insulin action in patients with arterial hypertension.     

Falsely High Plasma Potassium Values in Patients with Hyperaldosteronism

The common practice of encouraging forearm exercise as an aid to venepuncture is a potent source of erroneously high plasma potassium levels. This may be sufficient to obscure a suspicion of hyperaldosteronism, with possible serious repercussions in hypertensive patients, in whom the diagnosis of hyperaldosteronism has important therapeutic implications. Plasma is preferable to serum for potassium estimations, and forearm exercise should be avoided before venepuncture for potassium measurements.     

Presurgical functional localization of primary somatosensory cortex by dipole tracing method of scalp-skull-brain head model applied to somatosensory evoked potential

The aim of the present study was to explore the utility of dipole tracing (DT) of a scalp-skull-brain (SSB) head model in preoperative functional localization of the human brain. Nine patients who underwent surgery of mass lesions around the central sulcus (CS) were employed. By using SSB/DT, dipole source location of early cortical components of the somatosensory evoked potential (SEP) was estimated before surgery. Motor cortex, CS and primary somatosensory cortex were determined by cortical SEP during surgery. After surgery precise functional mapping was reproduced in MRI, and the accuracy of DT was evaluated by measuring the distance between estimated dipole source and the posterior bank of the CS. We defined this distance as localization error of DT. In 4 cases without structural change around the sensorimotor cortex, localization error ranged from 1 to 4 mm with an average of 2 mm. In 5 cases with structural alteration of sensorimotor cortex, localization error ranged from 6 to 10 mm with an average of 8 mm. The difference in localization error between the two groups was statistically significant, and may have been caused by changes of conductance near sensorimotor cortex in the latter group. Functional localization by DT was accurate and useful. But localization error could not be ignored in cases with structural alteration in the sensorimotor cortex.     

Multiple Unilateral adrenal Adenomas in a Patient with Primary Hyperaldosteronism

ObjectiveTo report a rare case of multiple unilateral adrenal adenomas in which immunohistochemistry results confirmed primary hyperaldosteronism in each of 3 adenomas.MethodsWe present the clinical, laboratory, radiographic, and pathologic findings of a case of multiple unilateral adrenal adenomas.ResultsAlthough multiple nodules in both adrenal glands are fairly common in patients with bilateral hyperplasia, multiple unilateral nodules are extremely rare. A 45-year-old woman with a long-standing history of severe hypertension was found to have biochemical parameters consistent with primary hyperaldosteronism, multiple unilateral adrenal adenomas, and immunohistochemical test results confirming primary hyperaldosteronism arising from each of 3 adrenal nodules (measuring 2.2 × 2.2 cm, 1.7 × 0.7 cm, and 0.5 × 0.5 cm).ConclusionThis case illustrates the rare presentation of primary hyperaldosteronism as multiple unilateral adrenal adenomas in which immunohistochemistry results can confirm the suspected preoperative diagnosis as suggested by biochemical and radiographic evidence. (Endocr Pract. 2008;14:76-79)     

Biochemical markers of endothelial dysfunction in patients with endocrine and essential hypertension

The aim of our study was to evaluate potential differences in the concentration of biochemical markers of endothelial dysfunction between essential hypertension, endocrine hypertension (pheochromocytoma, primary hyperaldosteronism) and control healthy group and to assess a potential relationship between these markers of endothelial dysfunction and vasopressor substances overproduced in endocrine hypertension. We have investigated 21 patients with moderate essential hypertension, 29 patients with primary hyperaldosteronism, 24 subjects with pheochromocytoma and 26 healthy volunteers. Following parameters of endothelial dysfunction were measured, von Willebrand factor (vWf), plasminogen activator (t-PA) and E-selectin (E-sel). Clinical blood pressure was measured according to the European Society of Hypertension recommendations. We found significantly higher levels of the von Willebrand factor in patients with essential hypertension in comparison with a control group (114+/-20 IU/dl vs 90+/-47 IU/dl; P=0.04) and patients with primary hyperaldosteronism (114+/-20 IU/dl vs 99+/-11 IU/dl; P=0.01). Patients with endocrine hypertension revealed increased levels of vWF compared to the control group, but these differences did not reach statistical significance. Levels of t-PA were increased in patients with pheochromocytoma in comparison with the control group (4.6+/-1.9 ng/ml vs 3.4+/-0.9 ng/ml; P=0.01) and with primary hyperaldosteronism (4.6+/-1.9 ng/ml vs 3.4+/-1.1 ng/ml; P<0.01). In case of E-selectin we found lower levels in patients with pheochromocytoma in comparison with other groups, but they differed significantly only with primary hyperaldosteronism (40.2+/-15.0 ng/ml vs 51.3+/-23.0 ng/ml; P=0.05). Our study did not reveal any convincing evidence of differences in the levels of biochemical markers of endothelial dysfunction between essential and endocrine hypertension. No correlation between the biochemical markers of endothelial dysfunction and vasopressor substances activated in endocrine hypertension was found.     

Genetic screening for glucocorticoid-remediable aldosteronism (GRA): experience of three clinical centres in Poland

Glucocorticoid-remediable aldosteronism (GRA), also known as familial hyperaldosteronism type I (FH-I, OMIM 103900), is a monogenic form of inherited hypertension caused by the presence of a chimaeric gene originating from an unequal cross-over between the CYP11B1 (11beta-hydroxylase) and CYP11B2 (aldosterone synthase) genes. The hybrid gene has the CYP11B1 sequence at the 5' end, including the promoter, and the CYP11B2 sequence at the 3' end. The aim of our study was to evaluate the prevalence of GRA in a Polish population of 129 patients with primary hyperaldosteronism (PHA) and 132 patients with essential hypertension (EH), through the use of a PCR-based test revealing the chimaeric gene. None of our PHA or EH patients was positive for the CYP11B1/CYP11B2 chimaeric gene. These data suggest that GRA is unlikely to be a common cause of hypertension in Polish subjects. However, the real prevalence of GRA in Poland, both in the high-risk group of individuals with primary hyperaldosteronism and in the general population, remains to be established.     

Adrenal cortical carcinoma: an unusual cause of hyperaldosteronism.

Although secondary hyperaldosteronism due to renal vein thrombosis may occur as a result of renal cell carcinoma or adrenal cortical carcinoma, primary hyperaldosteronism is rarely associated with the latter. This paper describes a patient with adrenal cortical carcinoma who presented with the clinical features of primary hyperaldosteronism 1 year after hypertension had been diagnosed; intravenous pyelography had not been done then. Drug therapy was ineffective, and the patient died 10 weeks after presentation.     

Can primary hyperaldosteronism be considered as a specific form of diabetes mellitus?

Aldosterone-producing adenoma (aldosteronoma)--the most frequent form of primary hyperaldosteronism (PH)--is considered a specific form of diabetes mellitus (DM). In a previous study we demonstrated insulin resistance in patients with PH. We have therefore undertaken a study to evaluate the incidence of abnormalities of glucose metabolism in patients with PH (36 subjects) compared to control subjects with essential hypertension (EH) (21 patients). The following parameters were measured in all studied subjects: office blood pressure (by mercury sphygmomanometer in the sitting position), body mass index (BMI), plasma potassium, plasma glucose and insulin levels during oral glucose tolerance test (OGTT) (0, 60, 120 min), plasma renin activity and plasma aldosterone. Although patients with PH tended to have higher stimulated plasma glucose levels after 60 and 120 min compared to EH, these differences did not attain statistical significance. Patients with EH tended to have higher insulin levels at each measured interval, but due to a high variability these differences were again not significant. There were no significant differences between PH and EH in the proportion of diabetics (20% vs. 14%) or patients with impaired glucose tolerance (18% vs. 10%). In conclusion, we have found the absence of significant differences in the frequency of diabetes mellitus, impaired glucose tolerance and insulin resistance in patients with EH and PH. Our data thus do not support the idea of primary hyperaldosteronism as a specific type of diabetes mellitus. Furthermore, our results indicate that glucose metabolic characteristics in essential hypertension and primary hyperaldosteronism tend to be similar. The definitive conclusion with respect to the possible causal relationship between DM and PH, however, can be obtained only on larger groups of subjects, in particular after the evaluation of the effect of surgical/pharmacological treatment of primary hyperaldosteronism.     

Beneficial Effect of Endocrinologist-Performed Ultrasonography on Preoperative Parathyroid Adenoma Localization

ObjectiveTo evaluate whether endocrinologist-performed ultrasonography improves the localization of parathyroid adenomas in patients with primary hyperparathyroidism.MethodsWe performed a retrospective analysis of consecutive patients with primary hyperparathyroidism due to a single adenoma who underwent surgery at the Dokuz Eylul University Hospital in Izmir, Turkey, between January 2000 and January 2008. Data regarding the localization of adenomas were obtained from surgical reports. Neck ultrasonography was performed in all patients as first-line imaging. Parathyroid ultrasonography was performed by a staff radiologist between January 2000 and December 2004. Beginning January 2005, parathyroid ultrasonography was performed blindly by an endocrinologist in addition to the staff radiologist. In the case of discordant preoperative localization between the endocrinologist- and radiologist-performed ultrasonography, surgery was performed according to the technetium Tc 99m sestamibi (MIBI) scan and endocrinologist-performed ultrasonography localization results.ResultsA total of 156 patients with primary hyperparathyroidism due to a single adenoma were included. Of the 156 patients, 139 also underwent MIBI scan. Ultrasonography localized 102 parathyroid adenomas (65%). The accuracy of the ultrasonography was improved in patients who underwent endocrinologist-performed ultrasonography. Endocrinologist-performed ultrasonography localized the adenoma correctly in 19 patients for whom the staff radiologist had reported a negative or unsuccessful localization. When ultrasonography results were combined with the MIBI scan findings, parathyroid adenomas were again more likely to be localized in patients who underwent operation after January 2005 and thus had endocrinologist-performed ultrasonography.ConclusionOur results suggest that endocrinologist-performed ultrasonography improves the preoperative localization of parathyroid adenoma. (Endocr Pract. 2009;15: 17-23)     

The visual cortex alpha-scanning: EEG and magnetic resonance tomography data

Exact localization of equivalent current dipoles (ECD) was obtained by combining the EEG and the MRI mapping allowing to trace the ECG displacement over the cortex. The data obtained corroborate localization of the alpha-rhythm ECD in the Gyrus Calcarina: the human primary visual cortex. Successive shifts of the ECD over this area during generation of each alpha-wave, were revealed. The data are discussed in the light of the "scanning hypothesis" that predicted a certain functional meaning of the alpha-wave spreading for cortical processing of sensory information.     

Peritoneal carcinomatosis following laparoscopic resection of an adrenocortical tumor causing primary hyperaldosteronism

A clinical syndrome combining hypertension and hypokalemic alkalosis led to the diagnosis of primary hyperaldosteronism, caused by a right-sided, 2 cm large, apparently benign aldosterone-producing adenoma. The adrenal tumor was completely resected by laparoscopic adrenalectomy. Six months after surgery, the patient exhibited a severe relapse of hyperaldosteronism. Extensive peritoneal metastases of a mixed aldosterone- and cortisol-secreting adrenocortical carcinoma were found at abdominal laparotomy. In the light of this case report, we discuss the possibility that laparoscopic resection of adrenocortical tumors might contribute to their subsequent peritoneal dissemination.     

低血钾对原发性醛固酮增多症诊断的影响

目的：探讨低血钾对原发性醛固酮增多症（原醛）患者醛固酮水平的影响.方法：回顾性分析29例原醛患者,这些患者均接受血、尿醛固酮测定及立卧位速尿激发试验,并进行手术治疗.观察原醛患者血钾与醛固酮分泌的关系.结果：原醛患者低血钾时出现醛固酮正常的比例（8/16,50%）较正常血钾组高（2/13,15.4%）,P〈0.05.结论：低血钾可以抑制原醛患者尤其是特发性醛固酮增多症患者的醛固酮水平.     

Invalidation of TASK1 potassium channels disrupts adrenal gland zonation and mineralocorticoid homeostasis

TASK1 (KCNK3) and TASK3 (KCNK9) are two-pore domain potassium channels highly expressed in adrenal glands. TASK1/TASK3 heterodimers are believed to contribute to the background conductance whose inhibition by angiotensin II stimulates aldosterone secretion. We used task1-/- mice to analyze the role of this channel in adrenal gland function. Task1-/- exhibited severe hyperaldosteronism independent of salt intake, hypokalemia, and arterial 'low-renin' hypertension. The hyperaldosteronism was fully remediable by glucocorticoids. The aldosterone phenotype was caused by an adrenocortical zonation defect. Aldosterone synthase was absent in the outer cortex normally corresponding to the zona glomerulosa, but abundant in the reticulo-fasciculata zone. The impaired mineralocorticoid homeostasis and zonation were independent of the sex in young mice, but were restricted to females in adults. Patch-clamp experiments on adrenal cells suggest that task3 and other K+ channels compensate for the task1 absence. Adrenal zonation appears as a dynamic process that even can take place in adulthood. The striking changes in the adrenocortical architecture in task1-/- mice are the first demonstration of the causative role of a potassium channel in development/differentiation.     

The effect of afferent subcortical conduction pathways on speech function status]

The combined analysis of neuropsychologic, electroencephalographic, and neurologic data as well as of the results of computerized and emission-computerized tomography in patients with ischemic stroke during the neurorehabilitation period made it possible to ascertain the correlation between the lesions of subcortical pathways and speech disorders. Besides the intracortical, the cortico-subcortical connections of the left associative cortex were demonstrated. The semantic aphasia was shown to be always associated with the dynamic aphasia; and each of these forms could be either primary or secondary depending on the lesion localization (from the EEG and neurophysiologic data). The incidence of local polymorphous delta and theta waves in the EEG is an unfavorable predictive sign for patients after ischemic stroke.     

Prognostic trees to aid prognosis in patients with cutaneous malignant melanoma. Scottish Melanoma Group.

OBJECTIVES--To design user friendly guides to prognosis for patients who have had invasive primary cutaneous malignant melanomas surgically excised. DESIGN--Adaptation of the classification tree method was used to derive prognostic trees for four different subgroups of malignant melanoma patients in whom known and possible prognostic variables interacted in different ways. SETTING--Scotland. SUBJECTS--Statistical modelling for prognostic trees was based on 1978 patients whose primary malignant melanoma was first diagnosed in 1979-86 for whom five year follow up and all relevant clinical pathological data were available. The resultant model was validated with 300 patients first diagnosed in 1987 for whom the same information was available. MAIN OUTCOME MEASURES--Actual and predicted rate of survival after diagnosis of primary cutaneous malignant melanoma. RESULTS--The four subgroups of patients were men and women with ulcerated and non-ulcerated cutaneous primary melanomas. Validation of the model showed excellent agreement between actual status of patients in the relevant subgroups and their status as predicted by the model. CONCLUSIONS--The prognostic trees are simple to use and give more accurate prognosis for individual patients than is currently available from tumour thickness alone.     

Localization of aldolase C mRNA in brain cells

The expression of aldolase C and aldolase A mRNA was assessed by Northern blot hybridization using RNAs purified from cultured rat and mouse brain neurons and astroglial cells. Neurons were found to contain about 4-fold more aldolase C mRNA and about twice as much aldolase A mRNA than astroglia. Analysis of the cellular localization of aldolase C mRNA by in situ hybridization to brain slices showed a predominantly neuronal labeling with an irregular distribution. A strong signal was observed in Purkinje cell somata and a weaker signal in subpopulations of neurons in cerebral cortex, striatum, hippocampus, hypothalamic nuclei and primary olfactory cortex.     

Comparative characteristics of spatial hearing of patients with different forms of cortical epilepsy

Perception of signals modeling directed movement of a sound source by three groups of patients with (1) temporal epilepsy, (2) epileptic foci in the frontal region, and (3) the epileptic syndrome due to local organic lesions in the temporal or frontal lobes was studied. It was established that the features and degree of spatial (binaural) hearing disorders in temporal epilepsy were determined not only by the localization and the extent of a lesion in the temporal lobe, but also by the areas beyond it that were involved in the epileptic process. Patients with organic lesions (tumors, cysts) involving the temporal lobe cortex may reveal more severe spatial hearing disorders than temporal epilepsy patients with the same localization of the foci of convulsive activity. A relatively isolated lesion of the frontal region cortex does not influence the assessment of the parameters of moving sound signals used. Possible neurophysiological mechanisms underlying the found spatial hearing disorders as well as the possibility of using the results obtained to solve the problems of differential diagnosis are considered.