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Sample records for hyperaldosteronism

  1. Familial hyperaldosteronism.

    PubMed

    Stowasser, M; Gordon, R D

    2001-09-01

    Primary aldosteronism (PAL) may be as much as ten times more common than has been traditionally thought, with most patients normokalemic. The study of familial varieties has facilitated a fuller appreciation of the nature and diversity of its clinical, biochemical, morphological and molecular aspects. In familial hyperaldosteronism type I (FH-I), glucocorticoid-remediable PAL is caused by inheritance of an ACTH-regulated, hybrid CYP11B1/CYP11B2 gene. Genetic testing has greatly facilitated diagnosis. Hypertension severity varies widely, demonstrating relationships with gender, affected parent's gender, urinary kallikrein level, degree of biochemical disturbance and hybrid gene crossover point position. Analyses of aldosterone/PRA/cortisol 'day-curves' have revealed that (1) the hybrid gene dominates over wild type CYP11B2 in terms of aldosterone regulation and (2) correction of hypertension in FH-I requires only partial suppression of ACTH, and much smaller glucocorticoid doses than those previously recommended. Familial hyperaldosteronism type II is not glucocorticoid-remediable, and is clinically, biochemically and morphologically indistinguishable from apparently sporadic PAL. In one informative family available for linkage analysis, FH-II does not segregate with either the CYP11B2, AT1 or MEN1 genes, but a genome-wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH-I, elucidation of causative mutations is likely to facilitate earlier detection of PAL and other curable or specifically treatable forms of hypertension. PMID:11595502

  2. Hyperaldosteronism - primary and secondary

    MedlinePlus

    ... JavaScript. Hyperaldosteronism is a disorder in which the adrenal gland releases too much of the hormone aldosterone into ... hyperaldosteronism is due to a problem of the adrenal glands themselves, which causes them to release too much ...

  3. Genetics Home Reference: familial hyperaldosteronism

    MedlinePlus

    ... and Advocacy Resources (1 link) Hormone Health Network: Primary Hyperaldosteronism Genetic Testing Registry (2 links) Familial hyperaldosteronism type 3 Hyperaldosteronism, familial, type I ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific articles on PubMed (1 link) PubMed OMIM (3 links) ...

  4. Genetics of primary hyperaldosteronism.

    PubMed

    Dutta, Ravi Kumar; Söderkvist, Peter; Gimm, Oliver

    2016-10-01

    Hypertension is a common medical condition and affects approximately 20% of the population in developed countries. Primary aldosteronism is the most common form of secondary hypertension and affects 8-13% of patients with hypertension. The two most common causes of primary aldosteronism are aldosterone-producing adenoma and bilateral adrenal hyperplasia. Familial hyperaldosteronism types I, II and III are the known genetic syndromes, in which both adrenal glands produce excessive amounts of aldosterone. However, only a minority of patients with primary aldosteronism have one of these syndromes. Several novel susceptibility genes have been found to be mutated in aldosterone-producing adenomas: KCNJ5, ATP1A1, ATP2B3, CTNNB1, CACNA1D, CACNA1H and ARMC5 This review describes the genes currently known to be responsible for primary aldosteronism, discusses the origin of aldosterone-producing adenomas and considers the future clinical implications based on these novel insights. PMID:27485459

  5. An Update on Familial Hyperaldosteronism.

    PubMed

    Korah, H E; Scholl, U I

    2015-12-01

    Familial forms of primary aldosteronism have been suggested to account for up to 6% of cases in referral centers. For many years, the genetics of familial hyperaldosteronism remained unknown, with the notable exception of glucocorticoid-remediable aldosteronism, due to unequal crossing over and formation of a chimeric 11β-hydroxylase/aldosterone synthase gene. Over the past 5 years, mutations in 3 additional genes have been shown to cause familial forms of primary aldosteronism. Gain-of-function heterozygous germline mutations in KCNJ5, which encodes an inward rectifier potassium channel, cause autosomal dominant syndromes of PA and hypertension with or without adrenal hyperplasia. Germline mutations in CACNA1D, which codes for an L-type calcium channel, have so far only been found in 2 cases with a syndrome of primary aldosteronism, seizures, and neurologic abnormalities. Both KCNJ5 and CACNA1D mutations in familial hyperaldosteronism were only discovered following identification of similar or identical somatic mutations in aldosterone-producing adenomas. In contrast, a recent exome sequencing study identified germline mutations in CACNA1H (a T-type calcium channel), previously undescribed in adenomas, in 5 unrelated families with early-onset primary aldosteronism and hypertension, without any additional shared symptoms. Future exome or genome sequencing studies are expected to shed light on the genetic basis of many cases of familial hyperaldosteronism that remain unexplained. PMID:26445452

  6. An Association of Chronic Hyperaldosteronism with Medullary Nephrocalcinosis

    PubMed Central

    Mittal, Kartik; Anandpara, Karan; Dey, Amit K.; Sharma, Rajaram; Thakkar, Hemangini; Hira, Priya; Deshmukh, Hemant

    2015-01-01

    Summary Background An association between chronic hyperaldosteronism and medullary nephrocalcinosis has rarely been made, with only a handful of cases described in literature. Case Report We describe five cases of hyperaldosteronism with a long- standing history in whom associated medullary nephrocalcinosis was established. Conclusions We infer that a chronic hyperaldosteronic status, whether primary or secondary, is a causal factor in the etiopathogenesis of medullary nephrocalcinosis. This article illustrates and summarizes various postulated theories that support our proposed association between hyperaldosteronism and nephrocalcinosis. We conclude that chronic hyperaldosteronism should be included as one of the causes of nephrocalcinosis and that our case series emphasizes the need of a well-organized retrospective study to prove it further. PMID:26413177

  7. Primary hyperaldosteronism, a mediator of progressive renal disease in cats.

    PubMed

    Javadi, S; Djajadiningrat-Laanen, S C; Kooistra, H S; van Dongen, A M; Voorhout, G; van Sluijs, F J; van den Ingh, T S G A M; Boer, W H; Rijnberk, A

    2005-01-01

    In recent years, there has been renewed interest in primary hyperaldosteronism, particularly because of its possible role in the progression of kidney disease. While most studies have concerned humans and experimental animal models, we here report on the occurrence of a spontaneous form of (non-tumorous) primary hyperaldosteronism in cats. At presentation, the main physical features of 11 elderly cats were hypokalemic paroxysmal flaccid paresis and loss of vision due to retinal detachment with hemorrhages. Primary hyperaldosteronism was diagnosed on the basis of plasma concentrations of aldosterone (PAC) and plasma renin activity (PRA), and the calculation of the PAC:PRA ratio. In all animals, PACs were at the upper end or higher than the reference range. The PRAs were at the lower end of the reference range, and the PAC:PRA ratios exceeded the reference range. Diagnostic imaging by ultrasonography and computed tomography revealed no or only very minor changes in the adrenals compatible with nodular hyperplasia. Adrenal gland histopathology revealed extensive micronodular hyperplasia extending from zona glomerulosa into the zona fasciculata and reticularis. In three cats, plasma urea and creatinine concentrations were normal when hyperaldosteronism was diagnosed but thereafter increased to above the upper limit of the respective reference range. In the other eight cats, urea and creatinine concentrations were raised at first examination and gradually further increased. Even in end-stage renal insufficiency, there was a tendency to hypophosphatemia rather than to hyperphosphatemia. The histopathological changes in the kidneys mimicked those of humans with hyperaldosteronism: hyaline arteriolar sclerosis, glomerular sclerosis, tubular atrophy and interstitial fibrosis. The non-tumorous form of primary hyperaldosteronism in cats has many similarities with "idiopathic" primary hyperaldosteronism in humans. The condition is associated with progressive renal disease

  8. Adrenal Diagnostics: An Endocrinologist’s Perspective focused on Hyperaldosteronism

    PubMed Central

    Fuller, Peter J

    2013-01-01

    The era of sophisticated high resolution imaging with the consequent identification of previously unrecognised adrenal masses (adrenal incidentalomas), has emphasised the need for an appropriate biochemical approach to define adrenal function. The focus of this testing is on catecholamines from the adrenal medulla (testing that has been rendered relatively straightforward by plasma metanephrine measurements) and the physiological corticosteroids, cortisol and aldosterone, synthesised by the adrenal cortex. The diagnosis of hypercortisolism remains a challenge and has been extensively reviewed. In the context of hypertension and an adrenal incidentaloma, the exclusion of hyperaldosteronism has an importance beyond simple blood pressure control. This review focuses on the recommended approaches to both the diagnosis of hyperaldosteronism and the characterisation of its aetiology. Monogenetic causes of mineralocorticoid hypertension are discussed as are recent developments with respect to both the molecular aetiology and the differential diagnosis of aldosterone-producing adenomas. PMID:24353356

  9. Surgical treatment of posterior nutcracker syndrome presented with hyperaldosteronism.

    PubMed

    Deser, Serkan Burc; Onem, Kadir; Demirag, Mustafa Kemal; Buyukalpelli, Recep

    2016-05-01

    Posterior nutcracker syndrome is caused by the compression of left renal vein between the abdominal aorta and the vertebral body. Most seen symptoms are haematuria, left flank pain, abdominal pain and varicocele. The nutcracker syndrome may lead to left renal vein thrombosis due to blood congestion within compression of the vessel. Both endovascular and open surgical interventions can relieve symptoms; however, traditional surgical repair is still considered as the gold standard. Here, we present the surgical treatment of a 36-year old female with complaints of hypertension, hyperaldosteronism and diagnosed with posterior nutcracker syndrome. PMID:26892192

  10. Hypokalemic paralysis due to primary hyperaldosteronism simulating Gitelman's syndrome.

    PubMed

    Kasifoglu, Timucin; Akalin, Aysen; Cansu, Dondu Uskudar; Korkmaz, Cengiz

    2009-03-01

    Some diseases, such as Gitelman's syndrome, Bartter's syndrome, and primary hyperaldosteronism (Conn's syndrome), may bear some similar clinical and laboratory findings. Their treatment modalities being different from one another, the need for a scrupulous diagnostic evaluation arises as far as clinical practice is concerned. In this report, we present a patient with Conn's syndrome who was initially considered to have Gitelman's syndrome due to displaying a few overlapping features of both diseases. We also give an account of the hardships encountered during the diagnostic evaluation. PMID:19237821

  11. Primary hyperaldosteronism: comparison of CT, adrenal venography, and venous sampling

    SciTech Connect

    Geisinger, M.A.; Zelch, M.G.; Bravo, E.L.; Risius, B.F.; O'Donovan, P.B.; Borkowski, G.P.

    1983-08-01

    Twenty-nine patients with primary hyperaldosteronism were evaluated with computed tomography (CT), adrenal venous sampling, and adrenal venography. Twenty-three patients had aldosteronomas and six had bilateral adrenocortical hyperplasia. Sixteen (70%) of the adenomas were accurately located by CT. All nodules of 1.5 cm or larger diameter and 50% of nodules 1.0 to 1.4 cm in diameter were demonstrated. Nodules of less than 1.0 cm in diameter generally were not detected. High-resolution CT appeared more sensitive than standard CT (75% vs 58%). Adrenal venous sampling for aldosterone assay was the most sensitive of the three methods, localizing 22 (96%) of the 23 adenomas. Eighteen (78%) of the adenomas were identified by adrenal venography, although two patients with bilateral cortical hyperplasia were mistakenly diagnosed as having a small adenoma. No such false-positive studies were encountered with CT or adrenal venous sampling.

  12. [Hypokalemia, a key clinical data for diagnosing primary hyperaldosteronism].

    PubMed

    Rodríguez Maya, B; Rodríguez Goncer, I; Diego Hernández, C

    2016-01-01

    We report a case of a 37 year-old man with a long history of hypertension under treatment, who was admitted at our institution with intense fatigue and weakness of lower limbs. The laboratory results at Emergency Department showed severe hypokalemia. A study of secondary hypertension was carried out. With the initial suspicion of primary hyperaldosteronism, complete blood test was done including plasma renine activity, which was completely suppressed, and plasma aldosterone concentration, which resulted normal. Likewise, an abdomen CT was performed and revealed a left adrenal mass consistent of suprarrenal adenoma. Therefore, a salt loading suppression test was done with subsequent measure of plasmatic renine activity, which was still suppressed, plasma aldosterone concentration, that persisted normal, and a 24-h urinary aldosterone excretion rate, which was clearly high, supporting the suspected diagnosis. After the adrenalectomy, the patient remained asymptomatic with normal blood pressure without treatment and with normal serum potassium levels. PMID:26869044

  13. KCNK3 Variants Are Associated With Hyperaldosteronism and Hypertension.

    PubMed

    Manichaikul, Ani; Rich, Stephen S; Allison, Matthew A; Guagliardo, Nick A; Bayliss, Douglas A; Carey, Robert M; Barrett, Paula Q

    2016-08-01

    Blood pressure (BP) is a complex trait that is the consequence of an interaction between genetic and environmental determinants. Previous studies have demonstrated increased BP in mice with global deletion of TASK-1 channels contemporaneous with diverse dysregulation of aldosterone production. In humans, genome-wide association studies in ≈100 000 individuals of European, East Asian, and South Asian ancestry identified a single nucleotide polymorphism (SNP) in KCNK3 (the gene encoding TASK-1) associated with mean arterial pressure. The current study was motivated by the hypotheses that (1) association of KCNK3 SNPs with BP and related traits extends to blacks and Hispanics, and (2) KCNK3 SNPs exhibit associations with plasma renin activity and aldosterone levels. We examined baseline BP measurements for 7840 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), and aldosterone levels and plasma renin activity in a subset of 1653 MESA participants. We identified statistically significant association of the previously reported KCNK3 SNP (rs1275988) with mean arterial pressure in MESA blacks (P=0.024) and a nearby SNP (rs13394970) in MESA Hispanics (P=0.031). We discovered additional KCNK3 SNP associations with systolic BP, mean arterial pressure, and hypertension. We also identified statistically significant association of KCNK3 rs2586886 with plasma aldosterone level in MESA and demonstrated that global deletion of TASK-1 channels in mice produces a mild-hyperaldosteronism, not associated with a decrease in renin. Our results suggest that genetic variation in the KCNK3 gene may contribute to BP variation and less severe hypertensive disorders in which aldosterone may be one of several causative factors. PMID:27296998

  14. Hyperaldosteronism after decreased renal K+ excretion in KCNMB2 knockout mice.

    PubMed

    Larsen, Casper K; Jensen, Iben S; Sorensen, Mads V; de Bruijn, Pauline I; Bleich, Markus; Praetorius, Helle A; Leipziger, Jens

    2016-05-15

    The kidney is the primary organ ensuring K(+) homeostasis. K(+) is secreted into the urine in the distal tubule by two mechanisms: by the renal outer medullary K(+) channel (Kir1.1) and by the Ca(2+)-activated K(+) channel (KCa1.1). Here, we report a novel knockout mouse of the β2-subunit of the KCa1.1 channel (KCNMB2), which displays hyperaldosteronism after decreased renal K(+) excretion. KCNMB2(-/-) mice displayed hyperaldosteronism, normal plasma K(+) concentration, and produced dilute urine with decreased K(+) concentration. The normokalemia indicated that hyperaldosteronism did not result from primary aldosteronism. Activation of the renin-angiotensin-aldosterone system was also ruled out as renal renin mRNA expression was reduced in KCNMB2(-/-) mice. Renal K(+) excretion rates were similar in the two genotypes; however, KCNMB2(-/-) mice required elevated plasma aldosterone to achieve K(+) balance. Blockade of the mineralocorticoid receptor with eplerenone triggered mild hyperkalemia and unmasked reduced renal K(+) excretion in KCNMB2(-/-) mice. Knockout mice for the α-subunit of the KCa1.1 channel (KCNMA1(-/-) mice) have hyperaldosteronism, are hypertensive, and lack flow-induced K(+) secretion. KCNMB2(-/-) mice share the phenotypic traits of normokalemia and hyperaldosteronism with KCNMA1(-/-) mice but were normotensive and displayed intact flow-induced K(+) secretion. Despite elevated plasma aldosterone, KNCMB2(-/-) mice did not display salt-sensitive hypertension and were able to decrease plasma aldosterone on a high-Na(+) diet, although plasma aldosterone remained elevated in KCNMB2(-/-) mice. In summary, KCNMB2(-/-) mice have a reduced ability to excrete K(+) into the urine but achieve K(+) balance through an aldosterone-mediated, β2-independent mechanism. The phenotype of KCNMB2 mice was similar but milder than the phenotype of KCNMA1(-/-) mice. PMID:26962098

  15. Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism.

    PubMed

    Ilias, Chatziioannidis; Evgenia, Babatseva; Aikaterini, Patsatsi; Asimina, Galli-Tsinopoulou; Constantina, Sarri; Maria, Lithoxopoulou; George, Mitsiakos; Paraskevi, Karagianni; Christos, Tsakalidis; Zissis, Mamuris; Nikolaos, Nikolaidis

    2015-01-01

    Netherton syndrome, a rare autosomal recessive genetic disorder, is classified as an ichthyosiform syndrome. In this report we present the case of a neonate with erythroderma shortly after birth, accompanied by severe hypernatremia, recurrent infections, transient hyperaldosteronism, and signs of growth hormone (GH) deficiency. DNA molecular analysis in the SPINK5 gene revealed heterozygosity in our index patient for 238insG and 2468delA frameshift mutations in exons 4 and 26, respectively, in the maternal allele and 1431-12G>A splice-site mutation in intron 15 in the paternal allele as well as the missense variation E420K in homozygous state. Combination of the identified mutations along with transient hyperaldosteronism and possible GH deficiency have not been described before. Accordingly, the importance of early multidisciplinary approach is highlighted, in order to reach accurate diagnosis, initiate prompt treatment, and ensure survival with fewer disease complications. PMID:26229701

  16. Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism

    PubMed Central

    Ilias, Chatziioannidis; Evgenia, Babatseva; Aikaterini, Patsatsi; Asimina, Galli-Tsinopoulou; Constantina, Sarri; Maria, Lithoxopoulou; George, Mitsiakos; Paraskevi, Karagianni; Christos, Tsakalidis; Zissis, Mamuris; Nikolaos, Nikolaidis

    2015-01-01

    Netherton syndrome, a rare autosomal recessive genetic disorder, is classified as an ichthyosiform syndrome. In this report we present the case of a neonate with erythroderma shortly after birth, accompanied by severe hypernatremia, recurrent infections, transient hyperaldosteronism, and signs of growth hormone (GH) deficiency. DNA molecular analysis in the SPINK5 gene revealed heterozygosity in our index patient for 238insG and 2468delA frameshift mutations in exons 4 and 26, respectively, in the maternal allele and 1431-12G>A splice-site mutation in intron 15 in the paternal allele as well as the missense variation E420K in homozygous state. Combination of the identified mutations along with transient hyperaldosteronism and possible GH deficiency have not been described before. Accordingly, the importance of early multidisciplinary approach is highlighted, in order to reach accurate diagnosis, initiate prompt treatment, and ensure survival with fewer disease complications. PMID:26229701

  17. Iatrogenic myxoedema madness following radioactive iodine ablation for Graves' disease, with a concurrent diagnosis of primary hyperaldosteronism

    PubMed Central

    Snell, L; Morris, D V

    2015-01-01

    Summary Myxoedema madness was first described as a consequence of severe hypothyroidism in 1949. Most cases were secondary to long-standing untreated primary hypothyroidism. We present the first reported case of iatrogenic myxoedema madness following radioactive iodine ablation for Graves' disease, with a second concurrent diagnosis of primary hyperaldosteronism. A 29-year-old woman presented with severe hypothyroidism, a 1-week history of psychotic behaviour and paranoid delusions 3 months after treatment with radioactive iodine ablation for Graves' disease. Her psychiatric symptoms abated with levothyroxine replacement. She was concurrently found to be hypertensive and hypokalemic. Primary hyperaldosteronism from bilateral adrenal hyperplasia was diagnosed. This case report serves as a reminder that myxoedema madness can be a complication of acute hypothyroidism following radioactive iodine ablation of Graves' disease and that primary hyperaldosteronism may be associated with autoimmune hyperthyroidism. Learning points Psychosis (myxoedema madness) can present as a neuropsychiatric manifestation of acute hypothyroidism following radioactive iodine ablation of Graves' disease.Primary hyperaldosteronism may be caused by idiopathic bilateral adrenal hyperplasia even in the presence of an adrenal adenoma seen on imaging.Adrenal vein sampling is a useful tool for differentiating between a unilateral aldosterone-producing adenoma, which is managed surgically, and an idiopathic bilateral adrenal hyperplasia, which is managed medically.The management of autoimmune hyperthyroidism, iatrogenic hypothyroidism and primary hyperaldosteronism from bilateral idiopathic adrenal hyperplasia in patients planning pregnancy includes delaying pregnancy 6 months following radioactive iodine treatment and until patient is euthyroid for 3 months, using amiloride as opposed to spironolactone, controlling blood pressure with agents safe in pregnancy such as nifedipine and avoiding

  18. Hypokalemic periodic paralysis in primary hyperaldosteronism. Subclinical myopathy with atrophy of the type 2A muscle fibers.

    PubMed

    Bautista, J; Gil-Neciga, E; Gil-Peralta, A

    1979-01-01

    A case of a patient suffering from primary hyperaldosteronism is reported. In this case the disease is manifested clinically by periodic paralysis and hypopotasemia without permanent myopathy. The morphological study of the muscle demonstrates selective atrophy of the type 2A fibers as the most pronounced alteration. These findings suggest a chronic myopathic process. PMID:546663

  19. Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (Primary Aldosteronism in TOrino-GENetic forms).

    PubMed

    Mulatero, Paolo; Tizzani, Davide; Viola, Andrea; Bertello, Chiara; Monticone, Silvia; Mengozzi, Giulio; Schiavone, Domenica; Williams, Tracy Ann; Einaudi, Silvia; La Grotta, Antonio; Rabbia, Franco; Veglio, Franco

    2011-11-01

    Primary aldosteronism (PA) is the most frequent cause of secondary hypertension, and patients display an increased prevalence of cardiovascular events compared with essential hypertensives. To date, 3 familial forms of PA have been described and termed familial hyperaldosteronism types I, II, and III (FH-I to -III). The aim of this study was to investigate the prevalence and clinical characteristics of the 3 forms of FH in a large population of PA patients. Three-hundred consecutive PA patients diagnosed in our unit were tested by long-PCR of the CYP11B1/CYP11B2 hybrid gene that causes FH-I, and all of the available relatives of PA patients were screened to confirm or exclude PA and, thus, FH-II. Urinary 18-hydroxycortisol and 18-oxocortisol were measured in all of the familial PA patients. Two patients were diagnosed with FH-I (prevalence: 0.66%), as well as 21 of their relatives, and clinical phenotypes of the 2 affected families varied markedly. After exclusion of families who refused testing and those who were not informative, 199 families were investigated, of which 12 were diagnosed with FH-II (6%) and an additional 15 individuals had confirmed PA; clinical and biochemical phenotypes of FH-II families were not significantly different from sporadic PA patients. None of the families displayed a phenotype compatible with FH-III diagnosis. Our study demonstrates that familial forms of hyperaldosteronism are more frequent than previously expected and reinforces the recommendation of the Endocrine Society Guidelines to screen all first-degree hypertensive relatives of PA patients. PMID:21876069

  20. Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension.

    PubMed

    Martínez-Martínez, Ernesto; Calvier, Laurent; Fernández-Celis, Amaya; Rousseau, Elodie; Jurado-López, Raquel; Rossoni, Luciana V; Jaisser, Frederic; Zannad, Faiez; Rossignol, Patrick; Cachofeiro, Victoria; López-Andrés, Natalia

    2015-10-01

    Hypertensive cardiac remodeling is accompanied by molecular inflammation and fibrosis, 2 mechanisms that finally affect cardiac function. At cardiac level, aldosterone promotes inflammation and fibrosis, although the precise mechanisms are still unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, is associated with inflammation and fibrosis in the cardiovascular system. We herein investigated whether Gal-3 inhibition could block aldosterone-induced cardiac inflammation and fibrosis and its potential role in cardiac damage associated with hypertension. Aldosterone-salt-treated rats presented hypertension, cardiac inflammation, and fibrosis that were prevented by the pharmacological inhibition of Gal-3 with modified citrus pectin. Cardiac inflammation and fibrosis presented in spontaneously hypertensive rats were prevented by modified citrus pectin treatment, whereas Gal-3 blockade did not modify blood pressure levels. In the absence of blood pressure modifications, Gal-3 knockout mice were resistant to aldosterone-induced cardiac inflammation. In human cardiac fibroblasts, aldosterone increased Gal-3 expression via its mineralocorticoid receptor. Gal-3 and aldosterone enhanced proinflammatory and profibrotic markers, as well as metalloproteinase activities in human cardiac fibroblasts, effects that were not observed in Gal-3-silenced cells treated with aldosterone. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac inflammation and fibrosis, alterations that were prevented by Gal-3 blockade independently of blood pressure levels. These data suggest that Gal-3 could be a new molecular mechanism linking cardiac inflammation and fibrosis in situations with high-aldosterone levels, such as hypertension. PMID:26238446

  1. Plasma immunoreactive gamma melanotropin in patients with idiopathic hyperaldosteronism, aldosterone-producing adenomas, and essential hypertension.

    PubMed Central

    Griffing, G T; Berelowitz, B; Hudson, M; Salzman, R; Manson, J A; Aurrechia, S; Melby, J C; Pedersen, R C; Brownie, A C

    1985-01-01

    A non-ACTH aldosterone-stimulating factor(s) has been implicated in the pathogenesis of idiopathic hyperaldosteronism (IHA). Although this factor has not been fully characterized, some evidence suggests that it may be related to a pro-gamma-melanotropin (pro-gamma-MSH), derived from the NH2-terminal region of pro-opiomelanocortin. In the present study, plasma immunoreactive (IR-) gamma-MSH levels at 0800 h in patients with IHA were evaluated (90 +/- 17 fmol/ml; range: 13-173 fmol/ml) and found to be significantly higher (P less than 0.05) than those in subjects with aldosterone-producing adenomas (33 +/- 8 fmol/ml), essential hypertension (33 +/- 6 fmol/ml), and normotensive controls (19 +/- 2 fmol/ml). Seven of nine IHA subjects had circulating IR-gamma-MSH levels above the normal range (greater than 35 fmol/ml). In plasmas sampled at 1200 h, IR-gamma-MSH was significantly higher in patients with IHA (95 +/- 26 fmol/ml) and adenomas (63 +/- 23 fmol/ml), as compared with essential hypertensives (31 +/- 6 fmol/ml) and normotensives (19 +/- 3 fmol/ml). Mean plasma IR-ACTH, plasma cortisol, and urinary cortisol levels did not differ significantly between any of these groups. In order to evaluate the effect of a pro-gamma-MSH in vitro, adrenal adenoma tissue was obtained from two patients, one with elevated IR-gamma-MSH (61 fmol/ml) and a second with low IR-gamma-MSH (12 fmol/ml). Aldosterone secretion by dispersed adenoma cells from the former, but not the latter, underwent a fourfold dose-dependent (10(-14)-10(-9) M) increase in response to human Lys-gamma 3-MSH. These data suggest that a pro-gamma-MSH may be implicated as a pathogenic factor in a subset of patients with primary aldosteronism, particularly among those differentially diagnosed as having IHA. Images PMID:4019776

  2. Hyperaldosteronism and cardiovascular risk in patients with autosomal dominant polycystic kidney disease.

    PubMed

    Lai, Silvia; Petramala, Luigi; Mastroluca, Daniela; Petraglia, Emanuela; Di Gaeta, Alessandro; Indino, Elena; Panebianco, Valeria; Ciccariello, Mauro; Shahabadi, Hossein H; Galani, Alessandro; Letizia, Claudio; D'Angelo, Anna Rita

    2016-07-01

    Hypertension is commonly associated with autosomal dominant polycystic kidney disease (ADPKD), often discovered before the onset of renal failure, albeit the pathogenetic mechanisms are not well elucidated. Hyperaldosteronism in ADPKD may contribute to the development of insulin resistance and endothelial dysfunction, and progression of cardiorenal disease. The aim of study was to evaluate the prevalence of primary aldosteronism (PA) in ADPKD patients and identify some surrogate biomarkers of cardiovascular risk.We have enrolled 27 hypertensive ADPKD patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, evaluating the renin-angiotensin-aldosterone system (RAAS), inflammatory indexes, nutritional status, homocysteine (Hcy), homeostasis model assessment-insulin resistance (HOMA-IR), mineral metabolism, microalbuminuria, and surrogate markers of atherosclerosis [carotid intima media thickness (cIMT), ankle/brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI) and left ventricular mass index (LVMI)]. Furthermore, we have carried out the morpho-functional magnetic resonance imaging (MRI) with high-field 3 T Magnetom Avanto.We have divided patients into group A, with normal plasma aldosterone concentration (PAC) and group B with PA, present in 9 (33%) of overall ADPKD patients. Respect to group A, group B showed a significant higher mean value of LVMI, HOMA-IR and Hcy (P = 0.001, P = 0.004, P = 0.018; respectively), and a lower value of FMD and 25-hydroxyvitamin D (25-OH-VitD) (P = 0.037, P = 0.019; respectively) with a higher prevalence of non-dipper pattern at Ambulatory Blood Pressure Monitoring (ABPM) (65% vs 40%, P < 0.05) at an early stage of the disease.In this study, we showed a high prevalence of PA in ADPKD patients, associated to higher LVMI, HOMA-IR, Hcy, lower FMD, and 25-OH-VitD, considered as surrogate markers of atherosclerosis, compared to ADPKD patients with normal PAC values. Our

  3. Idiopathic primary hyperaldosteronism: normalization of plasma aldosterone after one month withdrawal of long-term therapy with aldosterone-receptor antagonist potassium canrenoate.

    PubMed

    Armanini, D; Scaroni, C; Mattarello, M J; Fiore, C; Albiger, N; Sartorato, P

    2005-03-01

    We have re-evaluated 15 patients with idiopathic primary aldosteronism one month after withdrawal of therapy with aldosterone-receptor antagonist potassium canrenoate. Therapy had lasted for 3 to 24 yr. Median blood pressure (BP) in the sitting position at the time of diagnosis was 160/100 (ranges 150-200/95-110 mmHg); while 1 month after withdrawal of therapy median BP was 145/90 (ranges 125-160/80-100 mmHg). One month after withdrawal, the ratio aldosterone (ng/dl)/plasma renin activity (ng/ml/h) in the upright position was increased only in 3 cases (median 18, range 6.1-125). We found a significant inverse correlation between the upright aldosterone/plasma renin activity (aldo/PRA) ratio, 1 month after withdrawal, and the number of years of therapy with potassium canrenoate. We conclude that long-term therapy with the aldosterone-receptor blocker, potassium canrenoate, can normalize the aldo/PRA ratio in many cases of idiopathic primary hyperaldosteronism after one-month withdrawal of the drug. These data are consistent with possible regression of idiopathic primary hyperaldosteronism after long-term therapy with potassium canrenoate, or in alternative to a persistent effect of potassium canrenoate, on aldosterone synthesis. PMID:15952408

  4. Hyperaldosteronism: Screening and Diagnostic Tests.

    PubMed

    Sabbadin, Chiara; Fallo, Francesco

    2016-06-01

    Primary aldosteronism (PA) is the most common secondary cause of hypertension, accounting for 10 % of hypertensives and 20 % of those with drug-resistant hypertension. Aldosterone excess is associated with the development of adverse cardiovascular, renal and metabolic effects that are partly independent of its effect on blood pressure. Guidelines recommended wider screening for PA in an effort to maximize detection of patients who may benefit from optimal, specific management. All patient groups with increased prevalence of PA, including hypertensive patients with type 2 diabetes mellitus and those with obstructive sleep apnea, should be carefully screened for PA. Screening with aldosterone-to-renin ratio (ARR) is the most practical and informative initial test. Subsequent confirmatory tests are: (1) oral salt loading; (2) saline infusion; (3) captopril challenge and (4) fludrocortisone suppression test. Confirmation of PA can avoid that patients with a false positive ARR would inappropriately undergo costly and harmful lateralization procedures. If confirmatory testing is positive, further investigations are directed toward determining the subtype of PA, as the treatment differs for each subtype. PMID:26971505

  5. Hypokalemic quadriparesis with normotensive primary hyperaldosteronism.

    PubMed

    Talib, Abu; Mahmood, Khalid; Jairamani, Krishan Lal; Samo, Akhtar; Shakoor, Asima; Ghanghro, Imran; Mehar, Saeed

    2004-08-01

    This case report describe a 45 years old female who presented with hypotonia, hyporeflexia, and motor weakness of all four limbs with bilateral flexor planter response due to severe hypokalemia. The patient was finally diagnosed as a case of normotensive primary aldosteronism. Her CT scan abdomen was done which excluded adrenal adenoma. Aldosterone antagonist led to excellent response and recovery. PMID:15321042

  6. Novel Somatic Mutations in Primary Hyperaldosteronism are related to the Clinical, Radiological and Pathological Phenotype

    PubMed Central

    Scholl, Ute I.; Healy, James M.; Thiel, Anne; Fonseca, Annabelle L.; Brown, Taylor C.; Kunstman, John W.; Horne, Matthew J.; Dietrich, Dimo; Riemer, Jasmin; Kücükköylü, Seher; Reimer, Esther N.; Reis, Anna-Carinna; Goh, Gerald; Kristiansen, Glen; Mahajan, Amit; Korah, Reju; Lifton, Richard P.; Prasad, Manju L.; Carling, Tobias

    2016-01-01

    Summary Aldosterone-producing adenomas (APAs) and bilateral adrenal hyperplasia are important causes of secondary hypertension. Somatic mutations in KCNJ5, CACNA1D, ATP1A1, ATP2B3 and CTNNB1 have been described in APAs. Objective To characterize clinical-pathological features in APAs and unilateral adrenal hyperplasia, and correlate them with genotypes. Design Retrospective study. Subjects and Measurements Clinical and pathological characteristics of 90 APAs and 7 diffusely or focally hyperplastic adrenal glands were reviewed, and samples were examined for mutations in known disease genes by Sanger or exome sequencing. Results Mutation frequencies were: KCNJ5, 37.1%; CACNA1D, 10.3%; ATP1A1, 8.2%; ATP2B3, 3.1%; CTNNB1, 2.1%. Previously unidentified mutations included I157K, F154C and 2 insertions (I150_G151insM and I144_E145insAI) in KCNJ5, all close to the selectivity filter, V426G_V427Q_A428_L433del in ATP2B3, and A39Efs*3 in CTNNB1. Mutations in KCNJ5 were associated with female, and other mutations with male gender (p=0.007). On computed tomography, KCNJ5-mutant tumors displayed significantly greater diameter (p=0.023), calculated area (p=0.002) and lower pre-contrast Hounsfield Units (p=0.0002) vs. tumors with mutations in other genes. Accordingly, KCNJ5-mutant tumors were predominantly comprised of lipid-rich fasciculata-like clear cells, whereas other tumors were heterogeneous (p=5×10−6 vs. non-KCNJ5 mutant and p=0.0003 vs. wild type tumors, respectively). CACNA1D mutations were present in two samples with hyperplasia without adenoma. Conclusions KCNJ5 mutant tumors appear to be associated with fasciculata-like clear cell predominant histology and tend to be larger with a characteristic imaging phenotype. Novel somatic KCNJ5 variants likely cause adenomas by loss of potassium selectivity, similar to previously described mutations. PMID:26252618

  7. Resolution of Hyperreninemia, Secondary Hyperaldosteronism, and Hypokalemia With 177Lu-DOTATATE Induction and Maintenance Peptide Receptor Radionuclide Therapy in a Patient With Pancreatic Neuroendocrine Tumor.

    PubMed

    Makis, William; McCann, Karey; Riauka, Terence A; McEwan, Alexander J B

    2015-11-01

    A 54-year-old woman presented with a history of nausea, vomiting, diarrhea, and recurrent episodes of severe hypokalemia requiring hospitalization. Imaging revealed a pancreatic mass with liver metastases, histologically confirmed to be a neuroendocrine tumor. Elevated active renin and aldosterone levels were identified, and the patient was treated with 4 induction cycles of Lu-DOTATATE, which resolved the diarrhea, nausea, and hypokalemia, and normalized the renin and aldosterone levels. After 3 additional maintenance Lu-DOTATATE treatments, the pancreatic tumor had decreased in size, was deemed operable, and was resected. She remains on maintenance Lu-DOTATATE therapy with progression-free survival of 45 months thus far. PMID:26359564

  8. How Is Adrenal Surgery Performed?

    MedlinePlus

    HOME ADRENAL GLANDS Background Where are the adrenal glands? What do the adrenal glands do? Is this adrenal tumor a genetic problem? Primary hyperaldosteronism (aldosterone-producing tumor) What is primary hyperaldosteronism? Signs ...

  9. High prevalence of thyroid ultrasonographic abnormalities in primary aldosteronism.

    PubMed

    Armanini, Decio; Nacamulli, Davide; Scaroni, Carla; Lumachi, Franco; Selice, Riccardo; Fiore, Cristina; Favia, Gennaro; Mantero, Franco

    2003-11-01

    The study was performed to evaluate the prevalence of thyroid abnormalities detected by ultrasonography and, in particular, of multinodular nontoxic goiter in primary aldosteronism. We analyzed 80 consecutive of patients with primary hyperaldosteronism (40 with unilateral adenoma and 40 with idiopathic hyperaldosteronism) and 80 normotensive healthy controls, comparable for age, sex, iodine intake, and geographical area. Blood pressure, thyroid palpation, thyroid function, and ultrasonography were evaluated. The prevalence of ultrasonographic thyroid abnormalities was 60% in primary aldosteronism and 27% in controls (p < 0.0001). There was a statistically significant difference in prevalence of these abnormalities in unilateral adenoma and idiopathic hyperaldosteronism with respect to controls (p < 0.05 and p < 0.0001, respectively). The prevalence of multinodular nontoxic goiter in idiopathic hyperaldosteronism was higher than in controls (p < 0.001) and, in particular, in female patients. From these data it seems to be worth considering the existence of primary hyperaldosteronism in patients with multinodular goiter and hypertension. PMID:14665720

  10. Aldosterone blood test

    MedlinePlus

    ... hypotension) Aldosterone is a hormone released by the adrenal glands . It helps the body regulate blood pressure. Aldosterone ... may be due to Bartter syndrome (extremely rare) Adrenal glands release too much aldosterone hormone ( primary hyperaldosteronism - usually ...

  11. Spironolactone

    MedlinePlus

    ... potassium levels; heart failure; and in patients with edema (fluid retention) caused by various conditions, including liver, ... increase your dose.Spironolactone controls high blood pressure, edema, heart failure, and hyperaldosteronism, but does not cure ...

  12. Aldosterone and type 2 diabetes mellitus.

    PubMed

    Zavatta, Guido; Casadio, Elena; Rinaldi, Eleonora; Pagotto, Uberto; Pasquali, Renato; Vicennati, Valentina

    2016-04-01

    Primary hyperaldosteronism (PA) has recently been demonstrated to be strictly associated to metabolic syndrome as compared with essential hypertension (EH). Besides, the characteristics of metabolic syndrome are different in PA compared to EH, as high fasting glucose is more frequent in the former condition. The adverse effect of excess aldosterone on insulin metabolic signaling has generated increasing interest in the role of hyperaldosteronism in the pathogenesis of insulin resistance and resistant hypertension. Moreover, aldosterone receptor antagonist therapy in diabetic and cardiopathic patients improved coronary flow. The aim of this review is to present recent knowledge about the relationship between aldosterone, insulin resistance and diabetes. PMID:26876814

  13. Impairment of endothelial progenitor cell function and vascularization capacity by aldosterone in mice and humans

    PubMed Central

    Thum, Thomas; Schmitter, Kerstin; Fleissner, Felix; Wiebking, Volker; Dietrich, Bernd; Widder, Julian D.; Jazbutyte, Virginija; Hahner, Stefanie; Ertl, Georg; Bauersachs, Johann

    2011-01-01

    Aims Hyperaldosteronism is associated with vascular injury and increased cardiovascular events. Bone marrow-derived endothelial progenitor cells (EPCs) play an important role in endothelial repair and vascular homeostasis. We hypothesized that hyperaldosteronism impairs EPC function and vascularization capacity in mice and humans. Methods and results We characterized the effects of aldosterone and mineralocorticoid receptor (MR) blockade on EPC number and function as well as vascularization capacity and endothelial function. Treatment of human EPC with aldosterone induced translocation of the MR and impaired multiple cellular functions of EPC, such as differentiation, migration, and proliferation in vitro. Impaired EPC function was rescued by pharmacological blockade or genetic ablation of the MR. Aldosterone protein kinase A (PKA) dependently increased reactive oxygen species formation in EPC. Aldosterone infusion in mice impaired EPC function, EPC homing to vascular structures and vascularization capacity in a MR-dependent but blood pressure-independent manner. Endothelial progenitor cells from patients with primary hyperaldosteronism compared with controls of similar age displayed reduced migratory potential. Impaired EPC function was associated with endothelial dysfunction. MR blockade in patients with hyperaldosteronism improved EPC function and arterial stiffness. Conclusion Endothelial progenitor cells express a MR that mediates functional impairment by PKA-dependent increase of reactive oxygen species. Normalization of EPC function may represent a novel mechanism contributing to the beneficial effects of MR blockade in cardiovascular disease prevention and treatment. PMID:20926363

  14. [Hypokalaemic paralysis as a presentation of adrenal tumor].

    PubMed

    Briere, C; Milhaud, D; Heroum, C; Ringeard, I; Blard, J-M; Pagès, M

    2003-12-01

    A 24-year-old patient presented with flaccid quadriplegia due to severe hypokaliemia, initially presumed to have been induced by glycyrrhizin. Persistence of low potassium levels and hypertension led to the diagnosis of primary hyperaldosteronism related to an adrenal cortical tumor. After surgery, the patient recovered from hypertension and hypokaliemia. PMID:14978420

  15. Some considerations about evolution of idiopathic primary aldosteronism.

    PubMed

    Armanini, D; Fiore, C

    2009-07-01

    The prevalence of primary aldosteronism has increased since many patients who were previously considered as being affected by low renin essential hypertension are actually satisfying the new diagnostic criteria using plasma aldosterone/ plasma renin activity (PRA) ratio. Many of these cases could be classified as subclinical hyperaldosteronism, having normal aldosterone and low PRA, or in alternative the normal range of aldosterone should be revised. Idiopathic hyperaldosteronism can, in many cases, be considered as an evolutive disease: it can be hypothesized that the biochemical picture can be preceded by essential hypertension and that, after several years, primary aldosteronism can evolve back to essential hypertension due to age-related reduced vascular and adrenal sensitivity to angiotensin II. This effect is also evident after longterm treatment with aldosterone receptors blockers and therefore it possible that aldosterone-receptors blockers are able to normalize the sensitivity of glomerulosa to angiotensin II even after long-term withdrawal. The use of aldosterone receptors blockers prevents cardiovascular complications due to local aldosterone effect at the level of endothelium and mononuclear leukocytes; therefore, these drugs should be also considered for therapy of patients with hypertension. It is not excluded that aldosterone receptor blockers could prevent the onset of idiopathic hyperaldosteronism and its complications in patients with hypertension without primary hyperaldosteronism. From all these considerations it follows that the concept of normal range of aldosterone should be revised and the use of aldosterone receptor blockers should be revisited. PMID:19893360

  16. Impact of Aldosterone-Producing Adenoma on Endothelial Function and Rho-Associated Kinase Activity in Patients With Primary Aldosteronism

    PubMed Central

    Matsumoto, Takeshi; Oki, Kenji; Kajikawa, Masato; Nakashima, Ayumu; Maruhashi, Tatsuya; Iwamoto, Yumiko; Iwamoto, Akimichi; Oda, Nozomu; Hidaka, Takayuki; Kihara, Yasuki; Kohno, Nobuoki; Chayama, Kazuaki; Goto, Chikara; Aibara, Yoshiki; Noma, Kensuke; Liao, James K.; Higashi, Yukihito

    2016-01-01

    The purpose of this study was to evaluate vascular function and activity of Rho-associated kinases in patients with primary aldosteronism. Vascular function, including flow-mediated vasodilation and nitroglycerine-induced vasodilation, and Rho-associated kinase activity in peripheral leukocytes were evaluated in 21 patients with aldosterone-producing adenoma, 23 patients with idiopathic hyperaldosteronism, and 40 age-, gender-, and blood pressure-matched patients with essential hypertension. Flow-mediated vasodilation was significantly lower in the aldosterone-producing adenoma group than in the idiopathic hyperaldosteronism and essential hypertension groups (3.2±2.0% vs. 4.6±2.3% and 4.4±2.2%, P<0.05, respectively), whereas there was no significant difference in flow-mediated vasodilation between the idiopathic hyperaldosteronism and essential hypertension groups. There was no significant difference in nitroglycerine-induced vasodilation in the three groups. Rho-associated kinase activity was higher in the aldosterone-producing adenoma group than in the idiopathic hyperaldosteronism and essential hypertension groups (1.29±0.57 vs. 1.00±0.46 and 0.81±0.36, P<0.05, respectively), whereas there was no significant difference in Rho-associated kinase activity between the idiopathic hyperaldosteronism and essential hypertension groups. Flow-mediated vasodilation correlated with age (r=−0.31, P<0.01), plasma aldosterone concentration (r=−0.35, P<0.01) and aldosterone to renin ratio (r=−0.34, P<0.01). Rho-associated kinase activity correlated with age (r=−0.24, P=0.04), plasma aldosterone concentration (r=0.33, P<0.01) and aldosterone to renin ratio (r=0.46, P<0.01). After adrenalectomy, flow-mediated vasodilation and Rho-associated kinase activity were restored in aldosterone-producing adenoma patients. Aldosterone-producing adenoma was associated with both endothelial dysfunction and increased Rho-associated kinase activity compared with those in

  17. Laparoscopic Single Site Adrenalectomy Using a Conventional Laparoscope and Instrumentation

    PubMed Central

    Colon, Modesto J; LeMasters, Patrick; Newell, Phillipa; Divino, Celia; Weber, Kaare J.

    2011-01-01

    Background and Objectives: We present a case of Laparoendoscopic Single Site Surgery (LESS) left adrenalectomy performed with a conventional laparoscope and instruments. Methods: A 45-year-old male was diagnosed with hyperaldosteronism. Computed tomography detected a left adrenal nodule. Bilateral adrenal vein sampling was consistent with a left-sided source for hyperaldosteronism. Results: Total operative time for LESS left adrenalectomy was 120 minutes. The surgery was performed with conventional instruments, a standard 5-mm laparoscope, and a SILS port, with no additional incisions or trocars needed. No complications occurred, and the patient reported an uneventful recovery. Conclusions: LESS adrenalectomy is a feasible procedure. Although articulating instruments and laparoscopes may offer advantages, LESS adrenalectomy can be done without these. PMID:21902983

  18. Mineralocorticoid receptor antagonists as diuretics: Can congestive heart failure learn from liver failure?

    PubMed Central

    Ortiz, Fernando; Radhakrishnan, Jai; Schrier, Robert W.; Colombo, Paolo C.

    2014-01-01

    Despite significant improvements in diagnosis, understanding the pathophysiology and management of the patients with acute decompensated heart failure (ADHF), diuretic resistance, yet to be clearly defined, is a major hurdle. Secondary hyperaldosteronism is a pivotal factor in pathogenesis of sodium retention, refractory congestion in heart failure (HF) as well as diuretic resistance. In patients with decompensated cirrhosis who suffer from ascites, similar pathophysiological complications have been recognized. Administration of natriuretic doses of mineralocorticoid receptor antagonists (MRAs) has been well established in management of cirrhotic patients. However, this strategy in patients with ADHF has not been well studied. This article will discuss the potential use of natriuretic doses of MRAs to overcome the secondary hyperaldosteronism as an alternative diuretic regimen in patients with HF. PMID:25447845

  19. Use of computed tomography in diagnosing the cause of primary aldosteronism

    SciTech Connect

    White, E.A.; Schambelan, M.; Rost, C.R.; Biglieri, E.G.; Moss, A.A.; Korobkin, M.

    1980-12-25

    Computed tomography (CT) was performed in 22 consecutive patients with primary aldosteronism to evaluate the usefulness of this technique in diagnosing and locating aldosterone-producing adenomas. Sixteen patients had severe hypokalemia, hyperaldosteronism, and elevated plasma levels of 18-hydroxycorticosterone suggestive of an adenoma. In 12 of these 16, a unilateral adrenal mass was demonstrated clearly, and in all 11 who had surgery an adenoma was confirmed. In the other four patients in this group, one adrenal gland was normal and the other was either not seen adequately or had minor abnormalities that could not be definitely classified; and adenoma was found in the poorly visualized gland in each of the two patients who had surgery. The remaining six patients, who had milder biochemical abnormalities suggestive of idiopathic hyperaldosteronism, had bilateral adrenal enlargement or normal-appearing glands on scan and were not surgically explored.

  20. Functioning unilateral adrenocortical carcinoma in a dog

    PubMed Central

    Gójska-Zygner, Olga; Lechowski, Roman; Zygner, Wojciech

    2012-01-01

    An 11-year-old, 24-kg, intact female Siberian husky dog in anestrus had a 2-month history of polyuria and polydipsia. The dog had signs of mineralocorticoid excess such as hypertension and hypokalemia refractory to potassium supplementation. Abdominal ultrasound revealed an irregular mass in the left adrenal gland. The ACTH stimulation test for aldosterone concentration did not reveal hyperaldosteronism. Unilateral adrenalectomy was performed and histopathology identified adrenal cortical carcinoma. All clinical signs of mineralocorticoid excess ceased after surgery. PMID:23204580

  1. Nephrocalcinosis as adult presentation of Bartter syndrome type II.

    PubMed

    Huang, L; Luiken, G P M; van Riemsdijk, I C; Petrij, F; Zandbergen, A A M; Dees, A

    2014-02-01

    Bartter syndrome consists a group of rare autosomal-recessive renal tubulopathies characterised by renal salt wasting, hypokalaemic metabolic alkalosis, hypercalciuria and hyperreninaemic hyperaldosteronism. It is classified into five types. Mutations in the KCNJ1 gene (classified as type II) usually cause the neonatal form of Bartter syndrome. We describe an adult patient with a homozygous KCNJ1 mutation resulting in a remarkably mild phenotype of neonatal type Bartter syndrome. PMID:24659592

  2. Plasma aldosterone levels are elevated in patients with pulmonary arterial hypertension in the absence of left ventricular heart failure: a pilot study

    PubMed Central

    Maron, Bradley A.; Opotowsky, Alexander R.; Landzberg, Michael J.; Loscalzo, Joseph; Waxman, Aaron B.; Leopold, Jane A.

    2013-01-01

    Aims Elevated levels of the mineralocorticoid hormone aldosterone are recognized as a modifiable contributor to the pathophysiology of select cardiovascular diseases due to left heart failure. In pulmonary arterial hypertension (PAH), pulmonary vascular remodelling induces right ventricular dysfunction and heart failure in the absence of left ventricular (LV) dysfunction. Hyperaldosteronism has emerged as a promoter of pulmonary vascular disease in experimental animal models of PAH; however, the extent to which hyperaldosteronism is associated with PAH in patients is unknown. Thus, the central aim of the current study is to determine if hyperaldosteronism is an unrecognized component of the PAH clinical syndrome. Methods and results Plasma aldosterone levels and invasive cardiopulmonary haemodynamic measurements were obtained for 25 patients referred for evaluation of unexplained dyspnoea or pulmonary hypertension. Compared with controls (n = 5), patients with PAH (n = 18) demonstrated significantly increased plasma aldosterone levels (1200.4 ± 423.9 vs. 5959.1 ± 2817.9 pg/mL, P < 0.02), mean pulmonary artery pressure (21.4 ± 5.0 vs. 45.5 ± 10.4 mmHg, P < 0.002), and pulmonary vascular resistance (PVR) (1.41 ± 0.6 vs. 7.3 ± 3.8 Wood units, P < 0.003) without differences in LV ejection fraction or pulmonary capillary wedge pressure between groups. Among patients not prescribed PAH-specific pharmacotherapy prior to cardiac catheterization, a subgroup of the cohort with severe pulmonary hypertension, aldosterone levels correlated positively with PVR (r = 0.72, P < 0.02) and transpulmonary gradient (r = 0.69, P < 0.02), but correlated inversely with cardiac output (r = –0.79, P < 0.005). Conclusions These data demonstrate a novel cardiopulmonary haemodynamic profile associated with hyperaldosteronism in patients: diminished cardiac output due to pulmonary vascular disease in the absence of LV heart failure. PMID:23111998

  3. Liquorice Health Check, Oro-Dental Implications, and a Case Report

    PubMed Central

    Touyz, Louis Z. G.

    2009-01-01

    Liquorice has an active substance, Glycyrrhizin which inhibits the conversion of precursor cortisol to cortisone by inhibiting the enzyme 11-betahydroxysteroid dehydrogenase. When imbibed, liquorice acts like hyperaldosteronism which presents with typical symptoms including high blood pressure, low blood potassium, and muscle pain and weakness. This article appraises physiological and pharmacological effects on health of liquorice, critiques products containing liquorice, describes a typical case report of liquorice-induced hypertension, and appraises oral effects from consumption of liquorice products. PMID:19707475

  4. Small-Conductance Ca2+-Activated Potassium Channels Negatively Regulate Aldosterone Secretion in Human Adrenocortical Cells.

    PubMed

    Yang, Tingting; Zhang, Hai-Liang; Liang, Qingnan; Shi, Yingtang; Mei, Yan-Ai; Barrett, Paula Q; Hu, Changlong

    2016-09-01

    Aldosterone, which plays a key role in maintaining water and electrolyte balance, is produced by zona glomerulosa cells of the adrenal cortex. Autonomous overproduction of aldosterone from zona glomerulosa cells causes primary hyperaldosteronism. Recent clinical studies have highlighted the pathological role of the KCNJ5 potassium channel in primary hyperaldosteronism. Our objective was to determine whether small-conductance Ca(2+)-activated potassium (SK) channels may also regulate aldosterone secretion in human adrenocortical cells. We found that apamin, the prototypic inhibitor of SK channels, decreased membrane voltage, raised intracellular Ca(2+) and dose dependently increased aldosterone secretion from human adrenocortical H295R cells. By contrast, 1-Ethyl-2-benzimidazolinone, an agonist of SK channels, antagonized apamin's action and decreased aldosterone secretion. Commensurate with an increase in aldosterone production, apamin increased mRNA expression of steroidogenic acute regulatory protein and aldosterone synthase that control the early and late rate-limiting steps in aldosterone biosynthesis, respectively. In addition, apamin increased angiotensin II-stimulated aldosterone secretion, whereas 1-Ethyl-2-benzimidazolinone suppressed both angiotensin II- and high K(+)-stimulated production of aldosterone in H295R cells. These findings were supported by apamin-modulation of basal and angiotensin II-stimulated aldosterone secretion from acutely prepared slices of human adrenals. We conclude that SK channel activity negatively regulates aldosterone secretion in human adrenocortical cells. Genetic association studies are necessary to determine whether mutations in SK channel subtype 2 genes may also drive aldosterone excess in primary hyperaldosteronism. PMID:27432863

  5. Familial varieties of primary aldosteronism.

    PubMed

    Stowasser, M; Gunasekera, T G; Gordon, R D

    2001-12-01

    1. Improved approaches to screening and diagnosis have revealed primary aldosteronism (PAL) to be much more common than previously thought, with most patients normokalaemic. The spectrum of this disorder has been further broadened by the study of familial varieties. 2. Familial hyperaldosteronism type I (FH-I) is a glucocorticoid-remediable form of PAL caused by the inheritance of an adrenocorticotrophic hormone (ACTH)- regulated, hybrid CYP11B1/CYP11B2 gene. Diagnosis has been greatly facilitated by the advent of genetic testing. The severity of hypertension varies widely in FH-I, even among members of the same family, and has demonstrated relationships with gender, degree of biochemical disturbance and hybrid gene crossover point position. Hormone "day curve" studies show that the hybrid gene dominates over wild-type CYP11B2 in terms of aldosterone regulation. This may be due, in part, to a defect in wild-type CYP11B2-induced aldosterone production. Control of hypertension in FH-I requires only partial suppression of ACTH and much smaller glucocorticoid doses than previously recommended. 3. Familial hyperaldosteronism type II (FH-II) is not glucocorticoid remediable and is not associated with the hybrid gene mutation. Familial hyperaldosteronism type II is clinically, biochemically and morphologically indistinguishable from apparently non-familial PAL. Linkage studies in one informative family did not show segregation of FH-II with the CYP11B2, AT1 or MEN1 genes, but a genome-wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH-I, elucidation of causative mutations is likely to facilitate earlier detection of PAL. PMID:11903322

  6. Mineralocorticoid receptor antagonists and endothelial function

    PubMed Central

    Maron, Bradley A.; Leopold, Jane A.

    2010-01-01

    Hyperaldosteronism has been associated with endothelial dysfunction and impaired vascular reactivity in patients with hypertension or congestive heart failure. The mineralocorticoid receptor (MR) antagonists spironolactone and eplerenone have been shown to reduce morbidity and mortality, in part, by ameliorating the adverse effects of aldosterone on vascular function. Although spironolactone and eplerenone are increasingly utilized in patients with cardiovascular disease, widespread clinical use is limited by the development of gynecomastia with spironolactone and hyperkalemia with both agents. This suggests that the development of newer agents with favorable side effect profiles is warranted. PMID:18729003

  7. Hypertensive Crisis and Left Ventricular Thrombi after an Upper Respiratory Infection during the Long-term Use of Oral Contraceptives.

    PubMed

    Suzuki, Natsuko; Suzuki, Keisuke; Mizuno, Tomofumi; Kato, Yukari; Suga, Norihiro; Yoshino, Masabumi; Miura, Naoto; Banno, Shogo; Imai, Hirokazu

    2016-01-01

    A 34-year-old woman who had been using oral contraceptives for 10 years developed hypertensive crisis with papilloedema after an upper respiratory infection. Laboratory data showed hyperreninemic hyperaldosteronism and elevated levels of fibrinogen, fibrin, and fibrinogen degradation products. Echocardiography demonstrated two masses (18 mm) in the left ventricle. On the fourth hospital day, cerebral infarction, renal infarction, and upper mesenteric artery occlusion suddenly occurred despite the blood pressure being well-controlled using anti-hypertensive drugs. Echocardiography revealed the disappearance of the left ventricular masses, which suggested left ventricular thrombi. Cessation of the contraceptives and administration of heparin, warfarin, and anti-platelets drugs improved her general condition. PMID:26726092

  8. An unusual case of self-induced electrolyte depletion

    PubMed Central

    Love, D. R.; Brown, J. J.; Fraser, R.; Lever, A. F.; Robertson, J. I. S.; Timbury, G. C.; Thomson, Sheena; Tree, M.

    1971-01-01

    A case of anorexia nervosa, presenting with unexplained hypokalaemia, is described. The patient was also secretly addicted to purgatives and diuretics. During an attempted metabolic balance study she secretly disposed of food and excreta, which were smuggled from the hospital by her sister. The patient induced her husband to bring his own stools into the ward, these then being substituted for her own. The interrelationships of the electrolyte disturbances, elevation of plasma renin, renin substrate, and hyperaldosteronism are discussed, particularly in connexion with the pathogenesis of peripheral oedema in anorexia nervosa. PMID:5574799

  9. An unusual case of self-induced electrolyte depletion.

    PubMed

    Love, D R; Brown, J J; Fraser, R; Lever, A F; Robertson, J I; Timbury, G C; Thomson, S; Tree, M

    1971-04-01

    A case of anorexia nervosa, presenting with unexplained hypokalaemia, is described. The patient was also secretly addicted to purgatives and diuretics. During an attempted metabolic balance study she secretly disposed of food and excreta, which were smuggled from the hospital by her sister. The patient induced her husband to bring his own stools into the ward, these then being substituted for her own. The interrelationships of the electrolyte disturbances, elevation of plasma renin, renin substrate, and hyperaldosteronism are discussed, particularly in connexion with the pathogenesis of peripheral oedema in anorexia nervosa. PMID:5574799

  10. Adrenal venous sampling in a patient with adrenal Cushing syndrome

    PubMed Central

    Villa-Franco, Carlos Andrés; Román-Gonzalez, Alejandro; Velez-Hoyos, Alejandro; Echeverri-Isaza, Santiago

    2015-01-01

    The primary bilateral macronodular adrenal hyperplasia or the independent adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause hypercortisolism, its diagnosis is challenging and there is no clear way to decide the best therapeutic approach. Adrenal venous sampling is commonly used to distinguish the source of hormonal production in patients with primary hyperaldosteronism. It could be a useful tool in this context because it might provide information to guide the treatment. We report the case of a patient with ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with some modifications radically modified the treatment and allowed the diagnosis of a macronodular adrenal hyperplasia. PMID:26309345

  11. The Current Role of Venous Sampling in the Localization of Endocrine Disease

    SciTech Connect

    Lau, Jeshen H. G. Drake, William; Matson, Matthew

    2007-07-15

    Endocrine venous sampling plays a specific role in the diagnosis of endocrine disorders. In this article, we cover inferior petrosal sinus sampling, selective parathyroid venous sampling, hepatic venous sampling with arterial stimulation, adrenal venous sampling, and ovarian venous sampling. We review their indications and the scientific evidence justifying these indications in the diagnosis and management of Cushing's syndrome, hyperparathyroidism, pancreatic endocrine tumors, Conn's syndrome, primary hyperaldosteronism, pheochromocytomas, and androgen-secreting ovarian tumors. For each sampling technique, we compare its diagnostic accuracy with that of other imaging techniques and, where possible, look at how it impacts patient management. Finally, we incorporate venous sampling into diagnostic algorithms used at our institution.

  12. Hypokalemic paralysis due to thyrotoxicosis accompanied by Gitelman's syndrome.

    PubMed

    Baldane, S; Ipekci, S H; Celik, S; Gundogdu, A; Kebapcilar, L

    2015-01-01

    A 35-year-old male patient was admitted with fatigue and muscle weakness. He had been on methimazole due to thyrotoxicosis for 2 weeks. Laboratory tests showed overt hyperthyroidism and hypokalemia. Potassium replacement was started with an initial diagnosis of thyrotoxic hypokalemic periodic paralysis. Later on, despite the euthyroid condition and potassium chloride treatment, hypokalemia persisted. Further investigations revealed hyperreninemic hyperaldosteronism. The patient was considered to have Gitelman's syndrome (GS) and all genetic analysis was done. A c. 1145C>T, p. Thr382Met homozygote missense mutation located on solute carrier family 12, member gene 3, exon 9 was detected and GS was confirmed. PMID:25838649

  13. Hypokalemic paralysis due to thyrotoxicosis accompanied by Gitelman's syndrome

    PubMed Central

    Baldane, S.; Ipekci, S. H.; Celik, S.; Gundogdu, A.; Kebapcilar, L.

    2015-01-01

    A 35-year-old male patient was admitted with fatigue and muscle weakness. He had been on methimazole due to thyrotoxicosis for 2 weeks. Laboratory tests showed overt hyperthyroidism and hypokalemia. Potassium replacement was started with an initial diagnosis of thyrotoxic hypokalemic periodic paralysis. Later on, despite the euthyroid condition and potassium chloride treatment, hypokalemia persisted. Further investigations revealed hyperreninemic hyperaldosteronism. The patient was considered to have Gitelman's syndrome (GS) and all genetic analysis was done. A c. 1145C>T, p. Thr382Met homozygote missense mutation located on solute carrier family 12, member gene 3, exon 9 was detected and GS was confirmed. PMID:25838649

  14. A Rare Presentation of Primary Hyperparathyroidism with Concurrent Aldosterone-Producing Adrenal Carcinoma

    PubMed Central

    Molina-Ayala, Mario; Ramírez-Rentería, Claudia; Manguilar-León, Analleli; Paúl-Gaytán, Pedro; Ferreira-Hermosillo, Aldo

    2015-01-01

    Aldosterone-producing adrenocortical carcinomas are an extremely rare cause of hyperaldosteronism (<1%). Coexistence of different endocrine tumors warrants additional screening for multiple endocrine neoplasia syndromes, especially in young patients with large or malignant masses. We present the case of a 40-year-old man with a history of hypertension that presented with an incidental left adrenal tumor during an ultrasound performed for nephrolithiasis. Biochemical assessment showed a mildly elevated calcium (11.1 mg/dL), high parathyroid hormone, and a plasma aldosterone concentration/plasma renin activity ratio of 124.5 (normal < 30), compatible with primary hyperparathyroidism with a concomitant primary hyperaldosteronism. A Tc99m-MIBI scintigraphy showed an abnormally increased tracer uptake in the right superior parathyroid and abdominal computed tomography confirmed a left adrenal tumor of 20 cm. The patient underwent parathyroidectomy and adrenalectomy with final pathology reports of parathyroid hyperplasia and adrenal carcinoma with biochemical remission of both endocrinopathies. He was started on chemotherapy, but the patient developed a frontal cortex and an arm metastasis and finally died less than one year later. PMID:26161274

  15. Up-regulation of FGF23 release by aldosterone.

    PubMed

    Zhang, Bingbing; Umbach, Anja T; Chen, Hong; Yan, Jing; Fakhri, Hajar; Fajol, Abul; Salker, Madhuri S; Spichtig, Daniela; Daryadel, Arezoo; Wagner, Carsten A; Föller, Michael; Lang, Florian

    2016-02-01

    The fibroblast growth factor (FGF23) plasma level is high in cardiac and renal failure and is associated with poor clinical prognosis of these disorders. Both diseases are paralleled by hyperaldosteronism. Excessive FGF23 levels and hyperaldosteronism are further observed in Klotho-deficient mice. The present study explored a putative aldosterone sensitivity of Fgf23 transcription and secretion the putative involvement of the aldosterone sensitive serum & glucocorticoid inducible kinase SGK1, SGK1 sensitive transcription factor NFκB and store operated Ca(2+) entry (SOCE). Serum FGF23 levels were determined by ELISA in mice following sham treatment or exposure to deoxycorticosterone acetate (DOCA) or salt depletion. In osteoblastic UMR106 cells transcript levels were quantified by qRT-PCR, cytosolic Ca(2+) concentration utilizing Fura-2-fluorescence, and SOCE from Ca(2+) entry following store depletion by thapsigargin. As a result, DOCA treatment and salt depletion of mice elevated the serum C-terminal FGF23 concentration. In UMR106 cells aldosterone enhanced and spironolactone decreased SOCE. Aldosterone further increased Fgf23 transcript levels in UMR106 cells, an effect reversed by mineralocorticoid receptor blockers spironolactone and eplerenone, SGK1 inhibitor EMD638683, NFκB-inhibitor withaferin A, and Ca(2+) channel blocker YM58483. In conclusion, Fgf23 expression is up-regulated by aldosterone, an effect sensitive to SGK1, NFκB and store-operated Ca(2+) entry. PMID:26773502

  16. Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently.

    PubMed

    Lee, Seung Eun; Kim, Jae Hyeon; Lee, You Bin; Seok, Hyeri; Shin, In Seub; Eun, Yeong Hee; Kim, Jung Han; Oh, Young Lyun

    2015-12-01

    A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses. PMID:26248855

  17. Pathogenetic role of cyclooxygenase-2 in hyperprostaglandin E syndrome/antenatal Bartter syndrome: therapeutic use of the cyclooxygenase-2 inhibitor nimesulide.

    PubMed

    Nüsing, R M; Reinalter, S C; Peters, M; Kömhoff, M; Seyberth, H W

    2001-10-01

    Patients with hyperprostaglandin E syndrome/antenatal Bartter syndrome typically have renal salt wasting, hypercalciuria with nephrocalcinosis, and secondary hyperaldosteronism. Antenatally, these patients have fetal polyuria, leading to polyhydramnios and premature birth. Hyperprostaglandin E syndrome/antenatal Bartter syndrome is accompanied by a pathologically elevated synthesis of prostaglandin E(2), thought to be responsible for aggravation of clinical symptoms such as salt and water loss, vomiting, diarrhea, and failure to thrive. In this study administration of the cyclooxygenase-2 (COX-2) specific inhibitor nimesulide to patients with hyperprostaglandin E syndrome/antenatal Bartter syndrome blocked renal prostaglandin E(2) formation and relieved the key parameters hyperprostaglandinuria, secondary hyperaldosteronism, and hypercalciuria. Partial suppression of serum thromboxane B(2) synthesis resulting from platelet COX-1 activity and complete inhibition of urinary 6-keto-prostaglandin F(1alpha), reflecting endothelial COX-2 activity, indicate preferential inhibition of COX-2 by nimesulide. Amelioration of the clinical symptoms by use of nimesulide indicates that COX-2 may play an important pathogenetic role in hyperprostaglandin E syndrome/antenatal Bartter syndrome. Moreover, on the basis of our data we postulate that COX-2-derived prostaglandin E(2) is an important mediator for stimulation of the renin-angiotensin-aldosterone system in the kidney. PMID:11673754

  18. A decreased metabolic clearance rate of aldosterone in benign essential hypertension

    PubMed Central

    Nowaczynski, W.; Kuchel, O.; Genest, J.

    1971-01-01

    Aldosterone secretion rate, metabolic clearance rate, and/or plasma concentration were determined in 16 patients with benign, uncomplicated essential hypertension and compared with those of control subjects. The mean metabolic clearance rate of aldosterone in 10 patients was significantly (P < 0.001) lower (mean 867 liters of plasma/day per m2 ±270 SD) than in a group of 7 healthy subjects (mean 1480 liters/day per m2 ±265 SD). Secretion rates in 13 patients (including the 10 already mentioned) tended to be low (83 ±43 vs. 109 ±54 μg/day) and plasma concentrations tended to be high (13.6 ±4.6 vs. 7.5 ±4.8 ng/100 ml), but neither of these differences was statistically significant. The lower metabolic clearance rate could account for elevated plasma concentrations of aldosterone even when the secretion rate is normal or low. Measurement of secretion rate or urinary excretion only is therefore insufficient to establish the presence and/or mode of evolution of hyperaldosteronism. Failure of the aldosterone secretion to adapt fully to a decreased aldosterone metabolic clearance rate (MCR) could explain the state of relative hyperaldosteronism in patients with benign essential hypertension, even when the secretion rate and the urinary excretion rate are in the normal range. PMID:5116208

  19. Effects of aldosterone on insulin sensitivity and secretion

    PubMed Central

    Luther, James M.

    2014-01-01

    Dr. Conn originally reported an increased risk of diabetes in patients with hyperaldosteronism in the 1950’s, although the mechanism remains unclear. Aldosterone-induced hypokalemia was initially described to impair glucose tolerance by impairing insulin secretion. Correction of hypokalemia by potassium supplementation only partially restored insulin secretion and glucose tolerance, however. Aldosterone also impairs glucose-stimulated insulin secretion in isolated pancreatic islets via reactive oxygen species in a mineralocorticoid receptor-independent manner. Aldosterone-induced mineralocorticoid receptor activation also impairs insulin sensitivity in adipocytes and skeletal muscle. Aldosterone may produce insulin resistance secondarily by altering potassium, increasing inflammatory cytokines, and reducing beneficial adipokines such as adiponectin. Renin-angiotensin system antagonists reduce circulating aldosterone concentrations and also the risk of type 2 diabetes in clinical trials. These data suggest that primary and secondary hyperaldosteronism may contribute to worsening glucose tolerance by impairing insulin sensitivity or insulin secretion in humans. Future studies should define the effects of MR antagonists and aldosterone on insulin secretion and sensitivity in humans. PMID:25194457

  20. Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently

    PubMed Central

    Lee, Seung-Eun; Lee, You-Bin; Seok, Hyeri; Shin, In Seub; Eun, Yeong Hee; Kim, Jung-Han; Oh, Young Lyun

    2015-01-01

    A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses. PMID:26248855

  1. Aldosterone-secreting adrenal cortical carcinoma. A case report and review of the literature.

    PubMed

    Griffin, Adrienne Carruth; Kelz, Rachel; LiVolsi, Virginia A

    2014-09-01

    Adrenal cortical carcinomas (ACC) are rare, typically aggressive malignant neoplasms with a reported incidence of 1-2 cases per 1 million population and account for 0.05-0.2 % of all malignancies. The majority of these tumors are functional with approximately 60 % of patients experiencing endocrine symptomatology typically characterized by Cushing's syndrome (40 %) or a mixed hormonal picture of Cushing syndrome seen in association with virilization. Rarely, patients present with a pure hormonal syndrome of feminization or hyperaldosteronism, 6 and 2.5 %, respectively. We report a case of a 76-year-old woman presenting with recently diagnosed hypertension secondary to primary hyperaldosteronism. The patient underwent laparoscopic converted to an open adrenalectomy and a diagnosis of adrenocortical carcinoma (aldosteronoma clinical) was rendered. This case and review of the literature highlight that while rare, aldosterone-secreting adrenal cortical carcinomas may occur. In this case report, we discuss the clinical presentation, pathologic findings, and review the literature for adrenal cortical carcinomas and aldosterone-secreting adrenal cortical carcinomas. PMID:24682757

  2. Ultrasonographic appearance of adrenal glands in healthy and sick cats.

    PubMed

    Combes, Anaïs; Pey, Pascaline; Paepe, Dominique; Rosenberg, Dan; Daminet, Sylvie; Putcuyps, Ingrid; Bedu, Anne-Sophie; Duchateau, Luc; de Fornel-Thibaud, Pauline; Benchekroun, Ghita; Saunders, Jimmy H

    2013-06-01

    The first part of the study aimed to describe prospectively the ultrasonographic features of the adrenal glands in 94 healthy cats and 51 chronically sick cats. It confirmed the feasibility of ultrasonography of adrenal glands in healthy and chronically sick cats, which were not statistically different. The typical hypoechoic appearance of the gland surrounded by hyperechoic fat made it recognisable. A sagittal plane of the gland, not in line with the aorta, may be necessary to obtain the largest adrenal measurements. The reference intervals of adrenal measurements were inferred from the values obtained in the healthy and chronically sick cats (mean ± 0.96 SD): adrenal length was 8.9-12.5 mm; cranial height was 3.0-4.8 mm; caudal height was 3.0-4.5 mm. The second part of the study consisted of a retrospective analysis of the ultrasonographic examination of the adrenal glands in cats with adrenal diseases (six had hyperaldosteronism and four had pituitary-dependent hyperadrenocorticism) and a descriptive comparison with the reference features obtained in the control groups from the prospective study. Cats with hyperaldosteronism presented with unilateral severely enlarged adrenal glands. However, a normal contralateral gland did not preclude a contralateral infiltration in benign or malignant adrenal neoplasms. The ultrasonographic appearance of the adrenal glands could not differentiate benign and malignant lesions. The ultrasonographic appearance of pituitary-dependent hyperadrenocorticism was mainly a symmetrical adrenal enlargement; however, a substantial number of cases were within the reference intervals of adrenal size. PMID:23234721

  3. The McKittrick–Wheelock syndrome: a rare cause of curable diabetes

    PubMed Central

    Lim, Chung Thong; Cluroe, Alison; Cameron, Ewen; O’Rahilly, Stephen

    2016-01-01

    Summary McKittrick–Wheelock syndrome (MWS) is a rare consequence of severe dehydration and electrolyte depletion due to mucinous diarrhoea secondary to a rectosigmoid villous adenoma. Reported cases of MWS commonly describe hypersecretion of mucinous diarrhoea in association with dehydration, hypokalaemia, hyponatraemia, hypochloraemia and pre-renal azotemia. Hyperglycaemia and diabetes are rarely reported manifestations of MWS. Herein we describe the case of a 59-year-old woman who presented with new-onset diabetes and severe electrolyte derangement due to a giant rectal villous adenoma. Subsequent endoscopic resection of the tumour cured her diabetes and normalised electrolytes. This case describes a rare cause of ‘curable diabetes’ and indicates hyperaldosteronism and/or whole-body potassium stores as important regulators of insulin secretion and glucose homeostasis. Learning points McKittrick–Wheelock syndrome (MWS) is typically characterised by the triad of pre-renal failure, electrolyte derangement and chronic diarrhoea resulting from a secretory colonic neoplasm. Hyperglycaemia and new-onset diabetes are rare clinical manifestations of MWS. Hyperaldosteronism and/or hypokalaemia may worsen glucose tolerance in MWS. Aggressive replacement of fluid and electrolytes is the mainstay of acute management, with definitive treatment and complete reversal of the metabolic abnormalities being achieved by endoscopic or surgical resection of the neoplasm. PMID:27252863

  4. Estimation of urinary aldosterone using thin-layer chromatography and fluorimetry.

    PubMed Central

    Mattingly, D; Martin, H; Tyler, C M

    1993-01-01

    AIMS--To develop a fluorimetric method for the estimation of urinary aldosterone; to establish a normal range in 24 hour and overnight urine samples; and to investigate the use of overnight urines for detecting hyperaldosteronism. METHODS--Essential steps include hydrolysis of the 18 conjugate to release aldosterone and its oxidation with Benedict's solution, followed by thin-layer chromatography on silica gel and development of fluorescence on the plate with sulphuric acid. RESULTS--There was a linear correlation between the amount of aldosterone and the area under the peak on the chromatogram. The mean intra-assay and interassay coefficients of variation were 4.4% and 6.8%, respectively. The mean aldosterone excretion in 67 adults was 15.7 (SD 8.1) nmol/24 hours. The mean overnight excretion in 65 adults was 2.6 (1.4) nmol/8 hours. The method detected raised concentrations in patients with primary and secondary aldosteronism. CONCLUSIONS--This technique provides an accurate means of assaying urinary aldosterone. Overnight estimations seem to be as effective as 24 hour assays for identifying patients with hyperaldosteronism. PMID:8282834

  5. Myocardial pathology induced by aldosterone is dependent on non-canonical activities of G protein-coupled receptor kinases

    PubMed Central

    Cannavo, Alessandro; Liccardo, Daniela; Eguchi, Akito; Elliott, Katherine J.; Traynham, Christopher J.; Ibetti, Jessica; Eguchi, Satoru; Leosco, Dario; Ferrara, Nicola; Rengo, Giuseppe; Koch, Walter J.

    2016-01-01

    Hyper-aldosteronism is associated with myocardial dysfunction including induction of cardiac fibrosis and maladaptive hypertrophy. Mechanisms of these cardiotoxicities are not fully understood. Here we show that mineralocorticoid receptor (MR) activation by aldosterone leads to pathological myocardial signalling mediated by mitochondrial G protein-coupled receptor kinase 2 (GRK2) pro-death activity and GRK5 pro-hypertrophic action. Moreover, these MR-dependent GRK2 and GRK5 non-canonical activities appear to involve cross-talk with the angiotensin II type-1 receptor (AT1R). Most importantly, we show that ventricular dysfunction caused by chronic hyper-aldosteronism in vivo is completely prevented in cardiac Grk2 knockout mice (KO) and to a lesser extent in Grk5 KO mice. However, aldosterone-induced cardiac hypertrophy is totally prevented in Grk5 KO mice. We also show human data consistent with MR activation status in heart failure influencing GRK2 levels. Therefore, our study uncovers GRKs as targets for ameliorating pathological cardiac effects associated with high-aldosterone levels. PMID:26932512

  6. Juxtaglomerular cell tumor--a rare cause of secondary hypertension.

    PubMed

    Dolezel, Z; Starha, J; Pavlovsky, Z; Skotakova, J; Dostalkova, D

    2010-01-01

    Secondary hypertension (SH) is much more common in children than in adults. We report a 17-year-old girl with severe hypertension, hypokalemia and metabolic alkalosis. Because of these findings, primary or secondary hyperaldosteronism was suspected. Her initial treatment with spironolactone and ACE inhibitor was unsuccessful. With consideration of high plasma renin activity, the renal computed tomography angiography was performed and showed tumor mass in the left kidney. An uncomplicated partial left nephrectomy was performed. Histopathological examination and electron microscopy showed typical features of juxtaglomerular cell tumor (JCT). Imunohistochemistry of tumor was positive for CD34 and CD117 and this finding is effective in the diagnosis of JCT if immunostain for renin is unavailable. After the resection of JCT, the patient's blood pressure and hypokalemia returned to normal range. JCT is a rare renal neoplasm and an unusual cause of SH in children or adolescents (Fig. 2, Ref. 12). PMID:21384734

  7. [Diuretic-Abuse in Chronic Bulimia Nervosa--Case Report and Clinical Management].

    PubMed

    Greetfeld, Martin; Bröckel-Ristevski, Nicole; Fumi, Markus; Cuntz, Ulrich; Voderholzer, Ulrich

    2015-09-01

    We give account of a patient, who works in health care, with bulimia nervosa (BN) and a long term abuse of Furosemide. Due to patients' tendency to conceal addictive behavior and symptoms of BN, the prevalence of purging behavior caused by the intake of diuretics is difficult to quantify 10% of BN patients exhibit a long-term harmful abuse. Discontinuation of diuretics causes the development of edema, attributable to pathophysiological changes with hyperaldosteronism. These can lead to renewed escalation of purging behaviour, provoked either by phobia of weight gain or by unbearable feelings of tension in the facial area or in the legs. For an adequate clinical management, it is vital to have thorough knowledge of the pathophysiological context which consists of psychoeducation, provision of information, treatment of water-electrolyte imbalance and, in individual cases, the administration of aldosterone antagonists. PMID:26039368

  8. The role of cyclooxygenases and prostanoid receptorsin furosemide-like salt losing tubulopathy: the hyperprostaglandin E syndrome.

    PubMed

    Nüsing, R M; Seyberth, H W

    2004-08-01

    Hyperprostaglandin E syndrome/antenatal Bartter syndrome is characterized by NaCl wasting and volume depletion, juxtaglomerula hypertrophy, hyperreninism and secondary hyperaldosteronism. Primary causes are mutations in the gene for Na-K-2Cl-cotransporter, NKCC2, or for potassium channel, ROMK, responsible for medullary NaCl malabsorption. Most intriguing aspect of the syndrome is the association with a massively increased renal prostaglandin production which contributes substantially to the clinical picture of the patients. Therefore the term hyperprostaglandin E syndrome has been introduced. It is unclear how prostaglandins aggravate the NaCl transport deficiency. Aspects to prostaglandin synthesis and receptor-mediated function within the kidney in patients suffering from hyperprostaglandin E syndrome/antenatal Bartter syndrome will be discussed. PMID:15283766

  9. Bilateral Adrenal Adenoma Presented As Multiple Metatarsal And Phalangeal Fractures

    PubMed Central

    LiYeung, L L; Lui, T H

    2015-01-01

    Introduction: Symptomatic adrenal adenoma usually presents with systemic symptoms. Depending on the function of the adenoma, the patient can present with pheochromocytoma-like symptoms; primary hyperaldosteronism and Cushing syndrome (weight gain, weakness, depression, and bruising). Case report: A 41 year-old lady presented with multiple metatarsal and phalangeal fractures of the both feet without significant injury. DEXA scan showed evidence of osteoporosis. Investigations showed that the picture was compatible with adrenal Cushing syndrome. Computed tomogram showed bilateral adrenal adenoma. Adrenal cortex scintigraphy with NP-59 scan showed hyperfunctioning right adrenal adenoma. Laproscopic R adrenalectomy was performed and histological study confirmed adrenal cortical adenoma with adjacent cortical atrophy suggestive of a functioning adenoma. Post-operatively, she was put on hydrocortisone replacement and recovered well. Conclusion: Adrenal adenoma can present with insufficiency fractures of the feet. PMID:27299107

  10. Advances in WNK signaling of salt and potassium metabolism: clinical implications.

    PubMed

    Arroyo, Juan Pablo; Gamba, Gerardo

    2012-01-01

    Recent evidence due to the discovery of a family of kinases implicated in arterial hypertension now points to the underlying molecular mechanisms that dictate Na(+), K(+) and water handling in the nephron. These new key players need to be understood in order to fully comprehend the pathophysiology, manifestations, and treatment of common clinical entities such as hypovolemic shock, congestive heart failure, primary hyperaldosteronism, nephrotic syndrome and hypertension. It is through the analysis of the volume status and electrolyte abnormalities that commonly present with these diseases that we can begin to create a link between the abstract concept of a kinase regulation and how a patient will respond to a particular treatment. This review is an attempt to bridge that gap. PMID:22508439

  11. Genetic analysis in Bartter syndrome from India.

    PubMed

    Sharma, Pradeep Kumar; Saikia, Bhaskar; Sharma, Rachna; Ankur, Kumar; Khilnani, Praveen; Aggarwal, Vinay Kumar; Cheong, Hae

    2014-10-01

    Bartter syndrome is a group of inherited, salt-losing tubulopathies presenting as hypokalemic metabolic alkalosis with normotensive hyperreninemia and hyperaldosteronism. Around 150 cases have been reported in literature till now. Mutations leading to salt losing tubulopathies are not routinely tested in Indian population. The authors have done the genetic analysis for the first time in the Bartter syndrome on two cases from India. First case was antenatal Bartter syndrome presenting with massive polyuria and hyperkalemia. Mutational analysis revealed compound heterozygous mutations in KCNJ1(ROMK) gene [p(Leu220Phe), p(Thr191Pro)]. Second case had a phenotypic presentation of classical Bartter syndrome however, genetic analysis revealed only heterozygous novel mutation in SLC12A gene p(Ala232Thr). Bartter syndrome is a clinical diagnosis and genetic analysis is recommended for prognostication and genetic counseling. PMID:24696311

  12. Hypokalaemic periodic paralysis in rural northern India--most have secondary causes.

    PubMed

    Kumar, Vinod; Armstrong, Lois; Seshadri, M S; Finny, Philip

    2014-01-01

    Hypokalaemic periodic paralysis (HPP) is a life-threatening condition. Our aim was to study the clinical profile and laboratory parameters of HPP patients and to develop an algorithm to determine the causes of HPP. 84 patients presented with HPP over a 3 year period. 58 (69.0%) were found to have renal tubular acidosis (RTA). The other causes were idiopathic HPP (8 (9.5%)), acute gastroenteritis (4 (4.8%)), suspected primary hyperaldosteronism and familial HPP (2 each (2.4%)) and suspected Gitelman/Bartter Syndrome and thyrotoxic periodic paralysis (1 each (1.2%)). The number of cases peaks in the hot season. Over a third of the patients (35.7%) had recurrent episodes. 80% had secondary HPP and therefore a biochemical evaluation is mandatory. A simple algorithm was developed. Both health professionals and patients need further education regarding this problem in order to improve diagnosis and treatment and to improve compliance. PMID:24275360

  13. Hypokalemic paralyses: a review of the etiologies, pathophysiology, presentation, and therapy.

    PubMed

    Stedwell, R E; Allen, K M; Binder, L S

    1992-03-01

    Acute hypokalemic paralysis is an uncommon cause of acute weakness. Morbidity and mortality associated with unrecognized disease include respiratory failure and death. Hence, it is imperative for physicians to be knowledgeable about the causes of hypokalemic paralysis, and consider them diagnostically. The hypokalemic paralyses represent a heterogeneous group of disorders with a final common pathway presenting as acute weakness and hypokalemia. Most cases are due to familial hypokalemic paralysis; however, sporadic cases are associated with diverse underlying etiologies including thyrotoxic periodic paralysis, barium poisoning, renal tubular acidosis, primary hyperaldosteronism, licorice ingestion, and gastrointestinal potassium losses. The approach to the patient with hypokalemic paralysis includes a vigorous search for the underlying etiology and potassium replacement therapy. Further therapy depends on the etiology of the hypokalemia. Disposition depends on severity of symptoms, degree of hypokalemia, and chronicity of disease. PMID:1586409

  14. An Adolescent with Tingling and Numbness of Hand: Gitelman Syndrome

    PubMed Central

    Poudel, Atul

    2015-01-01

    Context: Gitelman syndrome is an inherited autosomal recessive disorder. It is usually diagnosed incidentally during adolescence or early adulthood based on clinical and biochemical findings. Case Report: We present a case of 16 years old adolescent female presenting with recurrent chest pain, tingling, and numbness of bilateral hands. Diagnosis was established by the typical biochemical abnormalities with hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis, and hyperreninemic hyperaldosteronism. Genetic diagnosis was confirmed by sequence analysis of the SLC12A3 gene showing the compound heterozygous mutation encoding the thiazide-sensitive sodium chloride co-transporter. The patient was treated with oral potassium, magnesium, and amiloride with complete improvement of symptoms and biochemical profile. Conclusion: Gitelman syndrome should be considered as a differential diagnosis in work up of hypokalemia, especially in adolescent age group. The presence of hypokalemia, metabolic alkalosis, hypomagnesaemia, hypocalciuria, and mutation analysis provides the final diagnosis. PMID:25709976

  15. [The renin-angiotensin-aldosterone system during the extraction, concentration and reinfusion of ascitic fluid in cirrhotic patients].

    PubMed

    Giorcelli, V; Fossale, P G

    1983-01-01

    The course of hepatic cirrhosis involves alterations to the sodium-water balance, the aetiopathogenetic causes of which are still not entirely known. At first major importance was assigned to the role of secondary hyperaldosteronism which develops during the ascitic phase. This was subsequently recognised to have only a permissive rather than determinant function. Changes in the renin-angiotensin-aldosterone (RAA) system and variations in hydrosaline balance as the extracellular volume (ECV) expands during the reinfusion of concentrated ascitic fluid have been studied. The data reported show that ECV expansion causes increased diuresis, natriuresis and osmolar clearance. The RAA system is suppressed and at the same time kaliuresis increases. The latter factor points up the role played by increased solute flow to the distal tube in the diuretico-metabolic response, where aldosterone plays a purely permissive part. PMID:6675585

  16. Overview of the genetic determinants of primary aldosteronism

    PubMed Central

    Al-Salameh, Abdallah; Cohen, Régis; Desailloud, Rachel

    2014-01-01

    Primary aldosteronism is the most common cause of secondary hypertension. The syndrome accounts for 10% of all cases of hypertension and is primarily caused by bilateral adrenal hyperplasia or aldosterone-producing adenoma. Over the last few years, the use of exome sequencing has significantly improved our understanding of this syndrome. Somatic mutations in the KCNJ5, ATP1A1, ATP2B3 or CACNA1D genes are present in more than half of all cases of aldosterone-producing adenoma (~40%, ~6%, ~1% and ~8%, respectively). Germline gain-of-function mutations in KCNJ5 are now known to cause familial hyperaldosteronism type III, and an additional form of genetic hyperaldosteronism has been reported in patients with germline mutations in CACNA1D. These genes code for channels that control ion homeostasis across the plasma membrane of zona glomerulosa cells. Moreover, all these mutations modulate the same pathway, in which elevated intracellular calcium levels lead to aldosterone hyperproduction and (in some cases) adrenal cell proliferation. From a clinical standpoint, the discovery of these mutations has potential implications for patient management. The mutated channels could be targeted by drugs, in order to control hormonal and overgrowth-related manifestations. Furthermore, some of these mutations are associated with high cell turnover and may be amenable to diagnosis via the sequencing of cell-free (circulating) DNA. However, genotype-phenotype correlations in patients harboring these mutations have yet to be characterized. Despite this recent progress, much remains to be done to elucidate the yet unknown mechanisms underlying sporadic bilateral adrenal hyperplasia. PMID:24817817

  17. Inhibition of Galectin-3 Pathway Prevents Isoproterenol-Induced Left Ventricular Dysfunction and Fibrosis in Mice.

    PubMed

    Vergaro, Giuseppe; Prud'homme, Mathilde; Fazal, Loubina; Merval, Regine; Passino, Claudio; Emdin, Michele; Samuel, Jane-Lise; Cohen Solal, Alain; Delcayre, Claude

    2016-03-01

    Galectin-3 (Gal-3) is involved in inflammation, fibrogenesis, and cardiac remodeling. Previous evidence shows that Gal-3 interacts with aldosterone in promoting macrophage infiltration and vascular fibrosis and that Gal-3 genetic and pharmacological inhibition prevents remodeling in a pressure-overload animal model of heart failure. We aimed to explore the contribution of Gal-3 and aldosterone in mechanisms leading to heart failure in a murine model. Male mice with cardiac-specific hyperaldosteronism underwent isoproterenol subcutaneous injections, to be then randomized to receive placebo, a Gal-3 inhibitor (modified citrus pectin [MCP]), an aldosterone antagonist (potassium canrenoate), or MCP+canrenoate for 14 days. Isoproterenol induced a rapid and persistent decrease in left ventricular fractional shortening (-20% at day 14); this was markedly improved by treatment with either MCP or canrenoate (both P<0.001 versus placebo). MCP and canrenoate also reduced cardiac hypertrophy and fibrosis and the expression of genes involved in fibrogenesis (Coll-1 and Coll-3) and macrophage infiltration (CD-68 and MCP-1). After isoproterenol, Gal-3 gene expression (P<0.05 versus placebo) and protein levels (-61% and -69% versus placebo) were decreased by both canrenoate and MCP. The combined use of antagonists of Gal-3 and aldosterone resulted in more pronounced effects on cardiac hypertrophy, inflammation, and fibrosis, when compared with either MCP or canrenoate alone. Inhibition of Gal-3 and aldosterone can reverse isoproterenol-induced left ventricular dysfunction, by reducing myocardial inflammation and fibrogenesis. Gal-3 likely participates in mechanisms of aldosterone-mediated myocardial damage in a heart failure murine model with cardiac hyperaldosteronism. Gal-3 inhibition may represent a new promising therapeutic option in heart failure. PMID:26781273

  18. Increased aldosterone-dependent Kv1.5 recycling predisposes to pacing-induced atrial fibrillation in Kcne3-/- mice.

    PubMed

    Lisewski, Ulrike; Koehncke, Clemens; Wilck, Nicola; Buschmeyer, Bastian; Pieske, Burkert; Roepke, Torsten K

    2016-07-01

    Hyperaldosteronism is associated with an increased prevalence of atrial fibrillation (AF). Mutations in KCNE3 have been associated with AF, and Kcne3(-/-) mice exhibit hyperaldosteronism. In this study, we used recently developed Kcne3(-/-) mice to study atrial electrophysiology with respect to development of aldosterone-dependent AF. In invasive electrophysiology studies, Kcne3(-/-) mice displayed a reduced atrial effective refractory period (AERP) and inducible episodes of paroxysmal AF. The cellular arrhythmogenic correlate for AF predisposition was a significant increase in atrial Kv currents generated by the micromolar 4-aminopyridine-sensitive Kv current encoded by Kv1.5. Electrophysiological alterations in Kcne3(-/-) mice were aldosterone dependent and were associated with increased Rab4, -5, and -9-dependent recycling of Kv1.5 channels to the Z-disc/T-tubulus region and lateral membrane via activation of the Akt/AS160 pathway. Treatment with spironolactone inhibited Akt/AS160 phosphorylation, reduced Rab-dependent Kv1.5 recycling, normalized AERP and atrial Kv currents to the wild-type level, and reduced arrhythmia induction in Kcne3(-/-) mice. Kcne3 deletion in mice predisposes to AF by a heretofore unrecognized mechanism-namely, increased aldosterone-dependent Kv1.5 recycling via Rab GTPases. The findings uncover detailed molecular mechanisms underpinning a channelopathy-linked form of AF and emphasize the inevitability of considering extracardiac mechanisms in genetic arrhythmia syndromes.-Lisewski, U., Koehncke, C., Wilck, N., Buschmeyer, B., Pieske, B., Roepke, T. K. Increased aldosterone-dependent Kv1.5 recycling predisposes to pacing-induced atrial fibrillation in Kcne3(-/-) mice. PMID:26985008

  19. Mild Adrenal Steroidogenic Defects and ACTH-Dependent Aldosterone Secretion in High Blood Pressure: Preliminary Evidence

    PubMed Central

    Martin Martins, João; do Vale, Sónia; Martins, Ana Filipa

    2014-01-01

    Introduction. Adrenal glands play a major role in the control of blood pressure and mild defects of steroidogenesis and/or inappropriate control of mineralocorticoid production have been reported in high blood pressure (HBP). Patients and Methods. We used a specific protocol for the evaluation of 100 consecutive patients with inappropriate or recent onset HBP. Specific methods were used to confirm HBP and to diagnose secondary forms of HBP. In addition we tested adrenal steroidogenesis with the common cosyntropin test, modified to include the simultaneous measurement of renin and aldosterone besides 17-hydroxyprogesterone (17OHP) and 11-deoxycortisol (S). Results. Secondary forms of HBP were diagnosed in 32 patients, including 14 patients with primary hyperaldosteronism (PA) (14%) and 10 patients with pheochromocytoma (10%). Mild defects of the 21-hydroxylase (21OHD) and 11-hydroxylase (11OHD) enzymes were common (42%). ACTH-dependent aldosterone secretion was found in most patients (54%) and characteristically in those with mild defects of adrenal steroidogenesis (>60%), PA (>75%), and otherwise in patients with apparent essential HBP (EHBP) (32%). Discussion. Mild defects of adrenal steroidogenesis are common in patients with HBP, occurring in almost half of the patients. In those patients as well as in patients with apparent EHBP, aldosterone secretion is commonly dependent on ACTH. PMID:25580122

  20. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity

    PubMed Central

    Leopold, Jane A.; Dam, Aamir; Maron, Bradley A.; Scribner, Anne W.; Liao, Ronglih; Handy, Diane E.; Stanton, Robert C.; Pitt, Bertram; Loscalzo, Joseph

    2013-01-01

    Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanism by which aldosterone promotes endothelial dysfunction remains unknown. Glucose-6-phosphate dehydrogenase (G6pd), the principal source of Nadph, modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO•). In these studies, we show that aldosterone (10−9-10−7 mol/l) decreases endothelial G6pd expression and activity in vitro resulting in increased oxidant stress and decreased cGMP levels similar to what is observed in G6pd-deficient cells. Aldosterone decreases G6pd expression by protein kinase A activation to increase expression of Crem, which interferes with Creb binding to the G6pd promoter. In vivo, infusion of aldosterone decreases vascular G6pd expression and impairs vascular reactivity. These effects are abrogated by spironolactone or vascular gene transfer of G6pd. These studies demonstrate that aldosterone induces a G6pd-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6pd activity. PMID:17273168

  1. Altered potassium homeostasis in cirrhosis of the liver and Crohn's disease

    SciTech Connect

    Schober, O.; Bossaller, C.

    1984-01-01

    In the course of patients (pts) with cirrhosis of the liver (Ci) and Crohn's disease (CD) frequently noticed arrhythmias of the heart, weakness and adynamic ileus suggest alterations in the potassium (K) homeostasis. It is the purpose of the study to assess the role of Na/sup +/-K/sup +/ pump mechanism in intracellular and extracellular K homeostasis. Relative total body potassium (TBK), serum potassium (K-S), and the number of red blood cell ouabain binding sites (n-ATPase) was studied in 21 pts with Ci, 31 pts with CD and in 31 controls (C), all were not on digitalis. TBK was measured by equilibrium binding of H-3-ouabain. A significant reduction in TBK was accompanied by normal serum potassium levels, whereas the number of Na-K pumps is increased. The results support the suggestion that changes in TBK may regulate the synthesis of Na-K pump molecules. Secondary hyperaldosteronism and diarrhea e.g. may be responsible for chronic potassium depletion. The need for a nutritional support is discussed.

  2. Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension.

    PubMed

    Leung, Alexander A; Nerenberg, Kara; Daskalopoulou, Stella S; McBrien, Kerry; Zarnke, Kelly B; Dasgupta, Kaberi; Cloutier, Lyne; Gelfer, Mark; Lamarre-Cliche, Maxime; Milot, Alain; Bolli, Peter; Tremblay, Guy; McLean, Donna; Tobe, Sheldon W; Ruzicka, Marcel; Burns, Kevin D; Vallée, Michel; Prasad, G V Ramesh; Lebel, Marcel; Feldman, Ross D; Selby, Peter; Pipe, Andrew; Schiffrin, Ernesto L; McFarlane, Philip A; Oh, Paul; Hegele, Robert A; Khara, Milan; Wilson, Thomas W; Penner, S Brian; Burgess, Ellen; Herman, Robert J; Bacon, Simon L; Rabkin, Simon W; Gilbert, Richard E; Campbell, Tavis S; Grover, Steven; Honos, George; Lindsay, Patrice; Hill, Michael D; Coutts, Shelagh B; Gubitz, Gord; Campbell, Norman R C; Moe, Gordon W; Howlett, Jonathan G; Boulanger, Jean-Martin; Prebtani, Ally; Larochelle, Pierre; Leiter, Lawrence A; Jones, Charlotte; Ogilvie, Richard I; Woo, Vincent; Kaczorowski, Janusz; Trudeau, Luc; Petrella, Robert J; Hiremath, Swapnil; Drouin, Denis; Lavoie, Kim L; Hamet, Pavel; Fodor, George; Grégoire, Jean C; Lewanczuk, Richard; Dresser, George K; Sharma, Mukul; Reid, Debra; Lear, Scott A; Moullec, Gregory; Gupta, Milan; Magee, Laura A; Logan, Alexander G; Harris, Kevin C; Dionne, Janis; Fournier, Anne; Benoit, Geneviève; Feber, Janusz; Poirier, Luc; Padwal, Raj S; Rabi, Doreen M

    2016-05-01

    Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force provides annually updated, evidence-based recommendations to guide the diagnosis, assessment, prevention, and treatment of hypertension. This year, we present 4 new recommendations, as well as revisions to 2 previous recommendations. In the diagnosis and assessment of hypertension, automated office blood pressure, taken without patient-health provider interaction, is now recommended as the preferred method of measuring in-office blood pressure. Also, although a serum lipid panel remains part of the routine laboratory testing for patients with hypertension, fasting and nonfasting collections are now considered acceptable. For individuals with secondary hypertension arising from primary hyperaldosteronism, adrenal vein sampling is recommended for those who are candidates for potential adrenalectomy. With respect to the treatment of hypertension, a new recommendation that has been added is for increasing dietary potassium to reduce blood pressure in those who are not at high risk for hyperkalemia. Furthermore, in selected high-risk patients, intensive blood pressure reduction to a target systolic blood pressure ≤ 120 mm Hg should be considered to decrease the risk of cardiovascular events. Finally, in hypertensive individuals with uncomplicated, stable angina pectoris, either a β-blocker or calcium channel blocker may be considered for initial therapy. The specific evidence and rationale underlying each of these recommendations are discussed. Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force will continue to provide annual updates. PMID:27118291

  3. Urinary Aldosterone/Creatinine Ratio After Fludrocortisone Suppression Consistent with PHA in a Cat.

    PubMed

    Koutinas, Christos K; Soubasis, Nektarios C; Djajadiningrat-Laanen, Sylvia C; Kolia, Elissavet; Theodorou, Konstantina

    2015-01-01

    A 9 yr old cat was presented with clinical signs and laboratory abnormalities attributed to arterial hypertension (mean systolic arterial pressure, 290 mm Hg). Plasma aldosterone concentration was increased at the time of admission (651 pmol/L), but serum creatinine and potassium concentrations were within the reference range. A second increased aldosterone (879 pmol/L) and normal plasma renin activity (1.85 ng/mL/hr) resulted in an increased aldosterone/renin ratio, which was suggestive of primary hyperaldosteronism (PHA). To further support the diagnosis of PHA, the urinary aldosterone/creatinine ratio was calculated both before and after oral administration of fludrocortisone acetate (0.05 mg/kg q 12 hr for 4 consecutive days). The urinary aldosterone/creatinine ratio was 92.6 × 10(-9) before fludrocortisone administration and 155.8 × 10(-9) 4 days later. Absence of suppression was typical of PHA. The cat had a limited response to antihypertensive medication and died before treatment for PHA could be instituted. A necropsy was not permitted by the owner. PMID:26355586

  4. Interactions Between Adrenal and Calcium-Regulatory Hormones in Human Health

    PubMed Central

    Brown, Jenifer M.; Vaidya, Anand

    2014-01-01

    Purpose of Review To summarize evidence characterizing the interactions between adrenal- and calcium-regulating hormones, and the relevance of these interactions to human cardiovascular and skeletal health. Recent Findings Human studies support the regulation of parathyroid hormone (PTH) by the renin-angiotensin-aldosterone system (RAAS): angiotensin II may stimulate PTH secretion via an acute and direct mechanism, whereas aldosterone may exert a chronic stimulation of PTH secretion. Studies in primary aldosteronism, congestive heart failure, and chronic kidney disease have identified associations between hyperaldosteronism, hyperparathyroidism, and bone loss, which appear to improve when inhibiting the RAAS. Conversely, elevated PTH and insufficient vitamin D status have been associated with adverse cardiovascular outcomes, which may be mediated by the RAAS. Studies of primary hyperparathyroidism implicate PTH-mediated stimulation of the RAAS, and recent evidence shows that the vitamin D-vitamin D receptor (VDR) complex may negatively regulate renin expression and RAAS activity. Ongoing human interventional studies are evaluating the influence of RAAS inhibition on PTH and the influence of VDR agonists on RAAS activity. Summary While previously considered independent endocrine systems, emerging evidence supports a complex web of interactions between adrenal and calcium-regulating hormones, with implications for human cardiovascular and skeletal health. PMID:24694551

  5. ARMC5 mutation analysis in patients with primary aldosteronism and bilateral adrenal lesions.

    PubMed

    Mulatero, P; Schiavi, F; Williams, T A; Monticone, S; Barbon, G; Opocher, G; Fallo, F

    2016-06-01

    Idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia is the most common subtype of primary aldosteronism (PA). The pathogenesis of IHA is still unknown, but the bilateral disease suggests a potential predisposing genetic alteration. Heterozygous germline mutations of armadillo repeat containing 5 (ARMC5) have been shown to be associated with hypercortisolism due to sporadic primary bilateral macronodular adrenal hyperplasia and are also observed in African-American PA patients. We investigated the presence of germline ARMC5 mutations in a group of PA patients who had bilateral computed tomography-detectable adrenal alterations. We sequenced the entire coding region of ARMC5 and all intron/exon boundaries in 39 patients (37 Caucasians and 2 black Africans) with confirmed PA (8 unilateral, 27 bilateral and 4 undetermined subtype) and bilateral adrenal lesions. We identified 11 common variants, 5 rare variants with a minor allele frequency <1% and 2 new variants not previously reported in public databases. We did not detect by in silico analysis any ARMC5 sequence variations that were predicted to alter protein function. In conclusion, ARMC5 mutations are not present in a fairly large series of Caucasian patients with PA associated to bilateral adrenal disease. Further studies are required to definitively clarify the role of ARMC5 in the pathogenesis of adrenal nodules and aldosterone excess in patients with PA. PMID:26446392

  6. Regulation of aldosterone secretion by Cav1.3

    PubMed Central

    Xie, Catherine B.; Haris Shaikh, Lalarukh; Garg, Sumedha; Tanriver, Gizem; Teo, Ada E. D.; Zhou, Junhua; Maniero, Carmela; Zhao, Wanfeng; Kang, Soosung; Silverman, Richard B.; Azizan, Elena A. B.; Brown, Morris J.

    2016-01-01

    Aldosterone-producing adenomas (APAs) vary in phenotype and genotype. Zona glomerulosa (ZG)-like APAs frequently have mutations of an L-type calcium channel (LTCC) CaV1.3. Using a novel antagonist of CaV1.3, compound 8, we investigated the role of CaV1.3 on steroidogenesis in the human adrenocortical cell line, H295R, and in primary human adrenal cells. This investigational drug was compared with the common antihypertensive drug nifedipine, which has 4.5-fold selectivity for the vascular LTCC, CaV1.2, over CaV1.3. In H295R cells transfected with wild-type or mutant CaV1.3 channels, the latter produced more aldosterone than wild-type, which was ameliorated by 100 μM of compound 8. In primary adrenal and non-transfected H295R cells, compound 8 decreased aldosterone production similar to high concentration of nifedipine (100 μM). Selective CaV1.3 blockade may offer a novel way of treating primary hyperaldosteronism, which avoids the vascular side effects of CaV1.2-blockade, and provides targeted treatment for ZG-like APAs with mutations of CaV1.3. PMID:27098837

  7. Regulation of aldosterone secretion by Cav1.3.

    PubMed

    Xie, Catherine B; Haris Shaikh, Lalarukh; Garg, Sumedha; Tanriver, Gizem; Teo, Ada E D; Zhou, Junhua; Maniero, Carmela; Zhao, Wanfeng; Kang, Soosung; Silverman, Richard B; Azizan, Elena A B; Brown, Morris J

    2016-01-01

    Aldosterone-producing adenomas (APAs) vary in phenotype and genotype. Zona glomerulosa (ZG)-like APAs frequently have mutations of an L-type calcium channel (LTCC) CaV1.3. Using a novel antagonist of CaV1.3, compound 8, we investigated the role of CaV1.3 on steroidogenesis in the human adrenocortical cell line, H295R, and in primary human adrenal cells. This investigational drug was compared with the common antihypertensive drug nifedipine, which has 4.5-fold selectivity for the vascular LTCC, CaV1.2, over CaV1.3. In H295R cells transfected with wild-type or mutant CaV1.3 channels, the latter produced more aldosterone than wild-type, which was ameliorated by 100 μM of compound 8. In primary adrenal and non-transfected H295R cells, compound 8 decreased aldosterone production similar to high concentration of nifedipine (100 μM). Selective CaV1.3 blockade may offer a novel way of treating primary hyperaldosteronism, which avoids the vascular side effects of CaV1.2-blockade, and provides targeted treatment for ZG-like APAs with mutations of CaV1.3. PMID:27098837

  8. Hypokalemic paralysis in a professional bodybuilder.

    PubMed

    Mayr, Florian B; Domanovits, Hans; Laggner, Anton N

    2012-09-01

    Severe hypokalemia is a potentially life-threatening disorder and is associated with variable degrees of skeletal muscle weakness, even to the point of paralysis. On rare occasions, diaphragmatic paralysis from hypokalemia can lead to respiratory arrest. There may also be decreased motility of smooth muscle, manifesting with ileus or urinary retention. Rarely, severe hypokalemia may result in rhabdomyolysis. Other manifestations of severe hypokalemia include alteration of cardiac tissue excitability and conduction. Hypokalemia can produce electrocardiographic changes such as U waves, T-wave flattening, and arrhythmias, especially if the patient is taking digoxin. Common causes of hypokalemia include extrarenal potassium losses (vomiting and diarrhea) and renal potassium losses (eg, hyperaldosteronism, renal tubular acidosis, severe hyperglycemia, potassium-depleting diuretics) as well as hypokalemia due to potassium shifts (eg, insulin administration, catecholamine excess, familial periodic hypokalemic paralysis, thyrotoxic hypokalemic paralysis). Although the extent of diuretic misuse in professional bodybuilding is unknown, it may be regarded as substantial. Hence, diuretics must always be considered as a cause of hypokalemic paralysis in bodybuilders. PMID:21871759

  9. The Role of Aldosterone in Obesity-Related Hypertension.

    PubMed

    Kawarazaki, Wakako; Fujita, Toshiro

    2016-04-01

    Obese subjects often have hypertension and related cardiovascular and renal diseases, and this has become a serious worldwide health problem. In obese subjects, impaired renal-pressure natriuresis causes sodium retention, leading to the development of salt-sensitive hypertension. Physical compression of the kidneys by visceral fat and activation of the sympathetic nervous system, renin-angiotensin systems (RAS), and aldosterone/mineralocorticoid receptor (MR) system are involved in this mechanism. Obese subjects often exhibit hyperaldosteronism, with increased salt sensitivity of blood pressure (BP). Adipose tissue excretes aldosterone-releasing factors, thereby stimulating aldosterone secretion independently of the systemic RAS, and aldosterone/MR activation plays a key role in the development of hypertension and organ damage in obesity. In obese subjects, both salt sensitivity of BP, enhanced by obesity-related metabolic disorders including aldosterone excess, and increased dietary sodium intake are closely related to the incidence of hypertension. Some salt sensitivity-related gene variants affect the risk of obesity, and together with salt intake, its combination is possibly associated with the development of hypertension in obese subjects. With high salt levels common in modern diets, salt restriction and weight control are undoubtedly important. However, not only MR blockade but also new diagnostic modalities and therapies targeting and modifying genes that are related to salt sensitivity, obesity, or RAS regulation are expected to prevent obesity and obesity-related hypertension. PMID:26927805

  10. The renin-angiotensin-aldosterone system and calcium-regulatory hormones.

    PubMed

    Vaidya, A; Brown, J M; Williams, J S

    2015-09-01

    There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium-regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis, while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control. Hyperaldosteronism and hyperparathyroidism represent pathophysiologic conditions that may contribute to or perpetuate each other; aldosterone regulates parathyroid hormone and associates with adverse skeletal complications, and parathyroid hormone regulates aldosterone and associates with adverse cardiovascular complications. As dysregulation in both systems is linked to poor cardiovascular and skeletal health, it is increasingly important to fully characterize how they interact to more precisely understand their impact on human health and potential therapies to modulate these interactions. This review describes the known clinical interactions between these two systems including observational and interventional studies. Specifically, we review studies describing the inhibition of renin activity by calcium and vitamin D, and a potentially bidirectional and stimulatory relationship between aldosterone and parathyroid hormone. Deciphering these relationships might clarify variability in outcomes research, inform the design of future intervention studies and provide insight into the results of prior and ongoing intervention studies. However, before these opportunities can be addressed, more effort must be placed on shifting observational data to the proof of concept phase. This will require reallocation of resources to conduct interventional studies and secure the necessary talent. PMID:25631218

  11. Physiologic Tailoring of Treatment in Resistant Hypertension

    PubMed Central

    Spence, J. David

    2010-01-01

    Resistant hypertension is a major opportunity for prevention of cardiovascular disease. Despite widespread dissemination of consensus guidelines, most patients are uncontrolled with approaches that assume that all patients are the same. Causes of resistant hypertension include 1) non-compliance 2) consumption of substances that aggravate hypertension (such as salt, alcohol, nonsteroidal anti-inflammatory drugs, licorice, decongestants) and 3) secondary hypertension. Selecting the appropriate therapy for a patient depends on finding the cause of the hypertension. Once rare causes have been eliminated (such as pheochromocytoma, licorice, adult coarctation of the aorta), the cause will usually be found by intelligent interpretation (in the light of medications then being taken) of plasma renin and aldosterone. If stimulated renin is low and the aldosterone is high, the problem is primary aldosteronism, and the best treatment is usually aldosterone antagonists (spironolactone or eplerenone; high-dose amiloride for men where eplerenone is not available). If the renin is high, with secondary hyperaldosteronism, the best treatment is angiotensin receptor blockers or aliskiren. If the renin and aldosterone are both low the problem is over-activity of renal sodium channels and the treatment is amiloride. This approach is particularly important in patients of African origin, who are more likely to have low-renin hypertension. PMID:21532778

  12. Channelopathies

    PubMed Central

    Kim, June-Bum

    2014-01-01

    Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases. PMID:24578711

  13. Identification of compound heterozygous KCNJ1 mutations (encoding ROMK) in a kindred with Bartter's syndrome and a functional analysis of their pathogenicity.

    PubMed

    Srivastava, Shalabh; Li, Dimin; Edwards, Noel; Hynes, Ann-M; Wood, Katrina; Al-Hamed, Mohamed; Wroe, Anna C; Reaich, David; Moochhala, Shabbir H; Welling, Paul A; Sayer, John A

    2013-11-01

    A multiplex family was identified with biochemical and clinical features suggestive of Bartter's syndrome (BS). The eldest sibling presented with developmental delay and rickets at 4 years of age with evidence of hypercalciuria and hypokalemia. The second sibling presented at 1 year of age with urinary tract infections, polyuria, and polydipsia. The third child was born after a premature delivery with a history of polyhydramnios and neonatal hypocalcemia. Following corrective treatment she also developed hypercalciuria and a hypokalemic metabolic alkalosis. There was evidence of secondary hyperreninemia and hyperaldosteronism in all three siblings consistent with BS. Known BS genes were screened and functional assays of ROMK (alias KCNJ1, Kir1.1) were carried out in Xenopus oocytes. We detected compound heterozygous missense changes in KCNJ1, encoding the potassium channel ROMK. The S219R/L220F mutation was segregated from father and mother, respectively. In silico modeling of the missense mutations suggested deleterious changes. Studies in Xenopus oocytes revealed that both S219R and L220F had a deleterious effect on ROMK-mediated potassium currents. Coinjection to mimic the compound heterozygosity produced a synergistic decrease in channel function and revealed a loss of PKA-dependent stabilization of PIP2 binding. In conclusion, in a multiplex family with BS, we identified compound heterozygous mutations in KCNJ1. Functional studies of ROMK confirmed the pathogenicity of these mutations and defined the mechanism of channel dysfunction. PMID:24400161

  14. Resistant hypertension in office practice: a clinical approach.

    PubMed

    Siyam, Fadi; Brietzke, Stephen A; Sowers, James R

    2010-11-01

    Resistant hypertension is defined as blood pressure uncontrolled to guideline levels despite the use of ≥3 antihypertensive medications. When evaluating patients with resistant hypertension, it is important to consider issues such as blood pressure measurement technique, lifestyle, other comorbid conditions and medications, and the white coat effect. To this point, potential contributing factors include obstructive sleep apnea, excess alcohol intake, and use of blood pressure-elevating medications, such as nonsteroidal anti-inflammatory drugs, sympathomimetics, certain anorexic agents, and oral contraceptives. Secondary causes of hypertension are common in patients with resistant hypertension and appropriate screening tests should be performed as suggested by signs, symptoms, and laboratory abnormalities. In this regard, there is increasing evidence that hyperaldosteronism is common in the resistant hypertensive patient group. Pharmacologic therapy in patients with resistant hypertension is centered on drug combinations that have different mechanisms of action, including diuretics, which are essential in maximizing antihypertensive effects. The role of mineralocorticoid receptor antagonists is expanding, especially in patients with the metabolic syndrome, where aldosterone excess is increasingly recognized as an etiology of resistant hypertension. Finally, when appropriate, specialist referral may be necessary to appropriately assess and treat these patients. PMID:21068532

  15. The spironolactone renaissance.

    PubMed

    Doggrell, S A; Brown, L

    2001-05-01

    Until recently, spironolactone was considered only as an antagonist at the aldosterone receptors of the epithelial cells of the kidney and was used clinically in the treatment of hyperaldosteronism and, occasionally, as a K(+)-sparing diuretic. The spironolactone renaissance started with the experimental finding that spironolactone reversed aldosterone-induced cardiac fibrosis by a cardiac action. Experimentally, spironolactone also has direct effects on blood vessels. Spironolactone reduces vascular fibrosis and injury, inhibits angiogenesis, reduces vascular tone and reduces portal hypertension. The rationale for the Randomized Aldactone Evaluation Study (RALES) of spironolactone in heart failure was that 'aldosterone escape' occurred through non-angiotensin II mechanisms. The RALES clinical trial was stopped early when it was shown that there was a 30% reduction in risk of death among the spironolactone patients. In RALES, spironolactone also reduced hospitalisation for worsening heart failure and improved the symptoms of heart failure. Other recent clinical trials have shown that spironolactone reduces cardiac and vascular collagen turnover, improves heart variability, reduces ventricular arrhythmias, improves endothelial dysfunction and dilates blood vessels in human heart failure and these effects probably all contribute to the increased survival in heart failure. Spironolactone may also be useful in the treatment of left ventricular hypertrophy, portal hypertension and cirrhosis. There have also been some recent small clinical trials of spironolactone as an anti-androgen showing potential in acne, hirsutism and precocious puberty. PMID:11322868

  16. Channelopathies.

    PubMed

    Kim, June-Bum

    2014-01-01

    Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases. PMID:24578711

  17. An additional child case of an aldosterone-producing adenoma with an atypical presentation of peripheral paralysis due to hypokalemia.

    PubMed

    Dinleyici, E C; Dogruel, N; Acikalin, M F; Tokar, B; Oztelcan, B; Ilhan, H

    2007-11-01

    Aldosterone-producing adenoma, which is characterized by hypertension, hypokalemia, and elevated aldosterone levels with suppressed plasma renin activity, is a rare condition during childhood and is also potentially curable. To the best of our knowledge, nearly 25 cases of childhood aldosterone-secreting adenoma have been reported in the literature to date. Here we describe a 13-yr-old girl with primary hyperaldosteronism secondary to aldosterone-secreting adenoma. The patient was admitted to our hospital with the neuromuscular complaints of muscle weakness and inability to walk due to hypokalemia. She had been misdiagnosed as having hypokalemic periodic paralysis 2 months before admission and her symptoms had radically improved with potassium supplementation. However, her blood pressure levels had increased and her symptoms reappeared 2 days prior to being observed during hospitalization in our institution. Laboratory examinations revealed hypokalemia (2.1 mEq/l), and increased serum aldosterone levels with suppressed plasma renin activity. Abdominal ultrasonography and abdominal magnetic resonance imaging revealed left adrenal mass. Laparoscopic adrenalectomy was performed and histopathological examinations showed benign adrenal adenoma. Serum aldosterone levels and blood pressure levels returned to normal after surgical intervention. This case demonstrates the importance of a systemic evaluation including blood pressure monitorization of children with hypokalemia as intermittent hypertension episodes may be seen; cases without hypertension may be misdiagnosed as rheumatological or neurological disorders such as hypokalemic periodic paralysis, as in our case. PMID:18075291

  18. Endothelial metabolism of angiotensin II to angiotensin III, not angiotensin (1-7), augments the vasorelaxation response in adrenal cortical arteries.

    PubMed

    Kopf, Phillip G; Campbell, William B

    2013-12-01

    Hyperaldosteronism is linked to the development and progression of several different cardiovascular diseases. Angiotensin (Ang) II increases aldosterone secretion and adrenal blood flow. Ang II peptide fragments are produced by various peptidases, and these Angs have diverse and vital physiologic roles. Due to the uncharacteristic vasorelaxation of adrenal arteries by Ang II, we tested the hypothesis that Ang II metabolism contributes to its relaxant activity in adrenal arteries. Metabolism of Angs by bovine adrenal cortical arteries and isolated bovine adrenal vascular cells was measured by liquid chromatography-mass spectrometry. The primary Ang metabolites of adrenal arteries are Ang III and Ang (1-7), with Ang IV produced to a lesser extent. Bovine microvascular endothelial cells produced a similar metabolic profile to adrenal arteries, whereas bovine adrenal artery smooth muscle cells exhibited less metabolism. In preconstricted adrenal arteries, Ang II caused relaxation in picomolar concentrations and constrictions at 10nM. Ang-converting enzyme 2 inhibition augmented this relaxation response, whereas aminopeptidase inhibition did not. Ang III was equipotent to Ang II in relaxing adrenal arteries. Ang IV did not cause relaxation. Nitric oxide synthase inhibition enhanced Ang II-induced constriction of adrenal arteries. Aminopeptidase inhibition increased the concentration range for Ang II-induced constriction of adrenal arteries. Ang III and Ang IV did not change the basal tone but caused constriction of adrenal arteries with nitric oxide synthase inhibition. These data indicate that Ang II metabolism modulates the vascular effects of Ang II in the adrenal vasculature. PMID:24092640

  19. Adrenal Venous Sampling: Where Is the Aldosterone Disappearing to?

    SciTech Connect

    Solar, Miroslav; Ceral, Jiri; Krajina, Antonin; Ballon, Marek; Malirova, Eva; Brodak, Milos; Cap, Jan

    2010-08-15

    Adrenal venous sampling (AVS) is generally considered to be the gold standard in distinguishing unilateral and bilateral aldosterone hypersecretion in primary hyperaldosteronism. However, during AVS, we noticed a considerable variability in aldosterone concentrations among samples thought to have come from the right adrenal glands. Some aldosterone concentrations in these samples were even lower than in samples from the inferior vena cava. We hypothesized that the samples with low aldosterone levels were unintentionally taken not from the right adrenal gland, but from hepatic veins. Therefore, we sought to analyze the impact of unintentional cannulation of hepatic veins on AVS. Thirty consecutive patients referred for AVS were enrolled. Hepatic vein sampling was implemented in our standardized AVS protocol. The data were collected and analyzed prospectively. AVS was successful in 27 patients (90%), and hepatic vein cannulation was successful in all procedures performed. Cortisol concentrations were not significantly different between the hepatic vein and inferior vena cava samples, but aldosterone concentrations from hepatic venous blood (median, 17 pmol/l; range, 40-860 pmol/l) were markedly lower than in samples from the inferior vena cava (median, 860 pmol/l; range, 460-4510 pmol/l). The observed difference was statistically significant (P < 0.001). Aldosterone concentrations in the hepatic veins are significantly lower than in venous blood taken from the inferior vena cava. This finding is important for AVS because hepatic veins can easily be mistaken for adrenal veins as a result of their close anatomic proximity.

  20. Recent Developments in Primary Aldosteronism.

    PubMed

    Asbach, E; Williams, T A; Reincke, M

    2016-06-01

    Primary aldosteronism (PA) is the most frequent endocrine cause of secondary arterial hypertension. Sporadic forms of PA caused mainly by an aldosterone producing adenoma (APA) or idiopathic adrenal hyperplasia (IAH) predominate; in contrast, familial forms (familial hyperaldosteronism types I, II and III) affect only a minor proportion of PA patients. Patient based registries and biobanks, international networks and next generation sequencing technologies have emerged over recent years. Somatic hot-spot mutations in the potassium channel GIRK4 (encoded by KCNJ5), in ATPases and a L-type voltage-gated calcium-channel correlate with the autonomous aldosterone production in approximately half of all APAs. The recently discovered form FH III is caused by different germline KCNJ5 mutations with variable clinical presentations and severity. Autoantibodies to the angiotensin II Type 1 receptor have been identified in patients with PA and possibly play a pathophysiological role in the development of PA. Adrenal vein sampling (AVS) represents the gold standard in differentiating unilateral and bilateral forms of PA. Recent consensus papers have tried to implement current guidelines in order to standardise the technique of AVS. New techniques like segmental AVS might allow a finer mapping of the aldosterone production within the adrenal gland. The measurement of the steroids 18-hydroxycortisol and 18-oxocortisol by liquid chromatography tandem mass spectrometry has been shown to be useful to distinguish between unilateral and bilateral forms of PA. PMID:27219889

  1. Blood pressure in patients with primary aldosteronism is influenced by bradykinin B(2) receptor and alpha-adducin gene polymorphisms.

    PubMed

    Mulatero, Paolo; Williams, Tracy A; Milan, Alberto; Paglieri, Cristina; Rabbia, Franco; Fallo, Francesco; Veglio, Franco

    2002-07-01

    Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA is most frequently presented as moderate to severe hypertension, but the clinical and biochemical features vary widely. The aim of our study was to identify genetic variants that influence the phenotype of patients with PA. We hypothesized that genetic variants potentially affecting aldosterone production (aldosterone synthase, CYP11B2), renal proximal tubule reabsorption (alpha-adducin), or the mechanisms of counterbalance leading to vasodilatation and sodium excretion (bradykinin B(2)-receptor, B(2)R) could influence the clinical and biochemical characteristics of patients with PA. We studied three polymorphisms of these genes (C-344T of CYP11B2, G460W of alpha-adducin, and C-58T of B(2)R) in 167 primary aldosteronism patients (56 with aldosterone-producing adenoma and 111 with idiopathic hyperaldosteronism). B(2)R and alpha-adducin genotypes were strong independent predictors of both systolic and diastolic blood pressure levels; plasma renin activity and aldosterone also play a marginal role on BP levels. Body mass index, age, sex, and CYP11B2 genotype displayed no significant effect on the clinical parameters of our population. In particular, alpha-adducin and B(2)R polymorphisms accounted for 13.2% and 11.0% of the systolic and diastolic blood pressure variance, respectively. These data suggest that genetic variants of alpha-adducin and the bradykinin B(2)-R influence the blood pressure levels in patients with primary aldosteronism. PMID:12107246

  2. Ambulatory Blood Pressure Monitoring-Derived Short-Term Blood Pressure Variability in Primary Aldosteronism.

    PubMed

    Grillo, Andrea; Bernardi, Stella; Rebellato, Andrea; Fabris, Bruno; Bardelli, Moreno; Burrello, Jacopo; Rabbia, Franco; Veglio, Franco; Fallo, Francesco; Carretta, Renzo

    2015-08-01

    The aim of this study was to investigate the short-term blood pressure (BP) variability (BPV) derived from ambulatory blood pressure monitoring (ABPM) in patients with primary aldosteronism (PA), either idiopathic hyperaldosteronism (IHA) or aldosterone-producing adenoma (APA), in comparison with patients with essential hypertension (EH) and normotensive (NT) controls. Thirty patients with PA (16 with IHA and 14 with APA), 30 patients with EH, and 30 NT controls, matched for sex, age, body mass index, and antihypertensive therapy, were studied. The standard deviation (SD) of 24-hour, daytime, and nighttime BP; 24-hour weighted SD of BP; and 24-hour BP average real variability were not different between patients with PA and those with EH (P=not significant). All BPV indices were higher in patients with PA, either IHA or APA subtypes, and patients with EH, compared with NT controls (P<.001 to P<.05). ABPM-derived short-term BPV is increased in patients with PA, and it may represent an additional cardiovascular risk factor in this disease. The role of aldosterone excess in BPV has to be clarified. PMID:25880017

  3. Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22(phox) in human mononuclear leukocytes.

    PubMed

    Calò, Lorenzo A; Zaghetto, Francesca; Pagnin, Elisa; Davis, Paul A; De Mozzi, Paola; Sartorato, Paola; Martire, Giuseppe; Fiore, Cristina; Armanini, Decio

    2004-04-01

    Aldosterone excess can produce heart and kidney fibrosis, which seem to be related to a direct effect of aldosterone at the level of specific receptors. We report a direct, mineralocorticoid-mediated effect on the protein expression of two markers of oxidative stress after incubation of mononuclear leukocytes with 1 x 10(-8) M aldosterone (p22(phox)/beta-actin = 1.38 +/- 0.05 and PAI-1/beta-actin = 1.80 +/- 0.05). The same effect was also found with 3 x 10(-5) M glycyrrhetinic acid, the principal constituent of licorice root (p22(phox)/beta-actin = 1.37 +/- 0.97 and PAI-1/beta-actin = 1.80 +/- 0.04). The effect of both aldosterone and glycyrrhetinic acid is blocked by incubation with added 1 x 10(-6) M of receptor-antagonist canrenone. Canrenone alone did not show any effect. PAI-1 related protein was also found using 4 x 10(-9) M aldosterone. Incubations with 1 x 10(-9) M for 3 hours as well as 1 x 10(-8) M aldosterone for 5, 10, and 20 minutes were ineffective for both proteins. These data support the previous finding of an involvement of mononuclear leukocytes in the pathogenesis of the oxidative stress induced by hyperaldosteronism. In addition, the results confirm our previous data on a direct effect of glycyrrhetinic acid at the level of mineralocorticoid receptors. PMID:15070972

  4. Pseudohyperaldosteronism: pathogenetic mechanisms.

    PubMed

    Armanini, Decio; Calò, Lorenzo; Semplicini, Andrea

    2003-06-01

    Pseudohyperaldosteronism is characterized by a clinical picture of hyperaldosteronism with suppression of plasma renin activity and aldosterone. Pseudohyperaldosteronism can be due to a direct mineralocorticoid effect, as with desoxycorticosterone, fluorohydrocortisone, fluoroprednisolone, estrogens, and the ingestion of high amounts of glycyrrhetinic acid. A block of 11-hydroxysteroid-dehydrogenase type 2 (11HSD2), the enzyme that converts cortisol into cortisone, at the level of epithelial target tissues of aldosterone, is involved in other cases. This mechanism is related either to a mutation of the gene, which encodes 11HSD2 (apparent mineralocorticoid excess syndrome and some cases of low renin hypertension) or to an acquired reduction of the activity of the enzyme due to glycyrrhetinic acid, carbenoxolone, and grapefruit juice. In other cases saturation of 11HSD2 may be involved as in severe Cushing's syndrome and chronic therapy with some corticosteroids. Recently, an activating mutation of the mineralocorticoid receptor gene has been described. Another genetic cause of pseudohyperaldosteronism is the syndrome of Liddle, which is due to a mutation of the gene encoding for beta and gamma subunits of the sodium channels. PMID:12892318

  5. Mineralocorticoid hypertension

    PubMed Central

    Gupta, Vishal

    2011-01-01

    Hypertension affects about 10 – 25% of the population and is an important risk factor for cardiovascular and renal disease. The renin-angiotensin system is frequently implicated in the pathophysiology of hypertension, be it primary or secondary. The prevalence of primary aldosteronism increases with the severity of hypertension, from 2% in patients with grade 1 hypertension to 20% among resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of disorders ranging from renin-producing pathologies (renin-secreting tumors, malignant hypertension, coarctation of aorta), aldosterone-producing pathologies (primary aldosteronism – Conns syndrome, familial hyperaldosteronism 1, 2, and 3), non-aldosterone mineralocorticoid producing pathologies (apparent mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting tumors, ectopic adrenocorticotropic hormones (ACTH) syndrome, congenitalvadrenal hyperplasia), and drugs with mineraocorticoid activity (locorice, carbenoxole therapy) to glucocorticoid receptor resistance syndromes. Clinical presentation includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of plasma aldosterone concentraion to plasma renin activity remains the best screening tool. Bilateral adrenal venous sampling is the best diagnostic test coupled with a CT scan. Treatment is either surgical (adrenelectomy) for unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or bilateral disease. Medical therapy focuses on blood pressure control and correction of hypokalemia using a combination of anti-hypertensives (calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers) and potassium-raising therapies (mineralcorticoid receptor antagonist or potassium sparing diuretics). Direct aldosterone synthetase antagonists represent a promising future therapy. PMID:22145132

  6. Mouse Models Recapitulating Human Adrenocortical Tumors: What Is Lacking?

    PubMed Central

    Leccia, Felicia; Batisse-Lignier, Marie; Sahut-Barnola, Isabelle; Val, Pierre; Lefrançois-Martinez, A-Marie; Martinez, Antoine

    2016-01-01

    Adrenal cortex tumors are divided into benign forms, such as primary hyperplasias and adrenocortical adenomas (ACAs), and malignant forms or adrenocortical carcinomas (ACCs). Primary hyperplasias are rare causes of adrenocorticotropin hormone-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely “functional,” i.e., producing steroids. When functional, adenomas result in endocrine disorders, such as Cushing’s syndrome (hypercortisolism) or Conn’s syndrome (hyperaldosteronism). By contrast, ACCs are extremely rare but highly aggressive tumors that may also lead to hypersecreting syndromes. Genetic analyses of patients with sporadic or familial forms of adrenocortical tumors (ACTs) led to the identification of potentially causative genes, most of them being involved in protein kinase A (PKA), Wnt/β-catenin, and P53 signaling pathways. Development of mouse models is a crucial step to firmly establish the functional significance of candidate genes, to dissect mechanisms leading to tumors and endocrine disorders, and in fine to provide in vivo tools for therapeutic screens. In this article, we will provide an overview on the existing mouse models (xenografted and genetically engineered) of ACTs by focusing on the role of PKA and Wnt/β-catenin pathways in this context. We will discuss the advantages and limitations of models that have been developed heretofore and we will point out necessary improvements in the development of next generation mouse models of adrenal diseases. PMID:27471492

  7. When normal is abnormal: keys to laboratory diagnosis of hidden endocrine disease.

    PubMed

    Graves, Thomas K

    2011-05-01

    Although veterinary clinicians commonly rely on panels of laboratory tests with individual results flagged when abnormal, care should be taken in interpreting normal test results as well. There are several examples of this in evaluating patients with endocrine disease. The finding of a normal leukogram (absence of a stress leukogram) can be indicative of adrenal insufficiency in dogs, and this disorder can be especially elusive when there are no overt indicators of mineralocorticoid deficiency. Cats with hyperthyroidism can have normal serum thyroid hormone concentrations, normal hematocrits, and normal serum concentrations of creatinine despite the presence of disease that affects these parameters. A normal serum phosphorus concentration, in the face of azotemia, isosthenuria, and hypertension can point a clinician toward a diagnosis of primary hyperaldosteronism rather than primary renal disease. A normal serum parathyroid hormone concentration in the face of hypercalcemia is inappropriate and can indicate the presence of primary hyperparathyroidism. Similarly, hypoglycemia accompanied by a normal serum insulin concentration can be found in cases of hyperinsulinism. These normal findings in abnormal patients, and their mechanisms, are reviewed. PMID:21596344

  8. Ultrasonographical examination of feline adrenal glands: intra- and inter-observer variability.

    PubMed

    Combes, Anaïs; Stock, Emmelie; Van der Vekens, Elke; Duchateau, Luc; Van Ryssen, Bernadette; Saunders, Jimmy H

    2014-12-01

    Interpretation of ultrasonographical measurements requires an understanding of the source and the magnitude of variation. A substantial part of the variation can be attributed to the observer, the equipment or the animal. The aim of this study was to evaluate which adrenal gland measurement is the least variable within and between observers. Three experienced ultrasonographers examined six cats at three different times on the same day, more than 1 h apart, according to a strict scanning protocol. Seven ultrasonographical measurements were performed on each adrenal gland (maximal length on sagittal images, maximal height at the cranial and caudal poles on sagittal and transverse images, and maximal width of the cranial and caudal poles on transverse images). Height measurements in both planes showed the lowest variability within and between observers compared with length and width measurements. Descriptive ultrasonographical features, such as echogenicity of the gland, presence of hyperechoic spots or layering assessment, demonstrated satisfactory-to-good intra- and inter-observer agreement, whereas the shape assessment showed very poor inter-observer agreement. The results of this study describe a reliable scanning protocol that can be the basis for future adrenal ultrasonographical examinations for cats suspected of adrenal disease (eg, hyperaldosteronism, hyperadrenocorticism, sex hormone-producing tumours). PMID:24518254

  9. VLDL-activated cell signaling pathways that stimulate adrenal cell aldosterone production.

    PubMed

    Tsai, Ying-Ying; Rainey, William E; Johnson, Maribeth H; Bollag, Wendy B

    2016-09-15

    Aldosterone plays an important role in regulating ion and fluid homeostasis and thus blood pressure, and hyperaldosteronism results in hypertension. Hypertension is also observed with obesity, which is associated with additional health risks, including cardiovascular disease. Obese individuals have high serum levels of very low-density lipoprotein (VLDL), which has been shown to stimulate aldosterone production; however, the mechanisms underlying VLDL-induced aldosterone production are still unclear. Here we demonstrate in human adrenocortical carcinoma (HAC15) cells that submaximal concentrations of angiotensin II and VLDL stimulate aldosterone production in an additive fashion, suggesting the possibility of common mechanisms of action. We show using inhibitors that VLDL-induced aldosterone production is mediated by the PLC/IP3/PKC signaling pathway. Our results suggest that PKC is upstream of the extracellular signal-regulated kinase (ERK) activation previously observed with VLDL. An understanding of the mechanisms mediating VLDL-induced aldosterone production may provide insights into therapies to treat obesity-associated hypertension. PMID:27222295

  10. Diagnostic Value of I-131 NP-59 SPECT/CT Scintigraphy in Patients with Subclinical or Atypical Features of Primary Aldosteronism

    PubMed Central

    Chen, Yi-Chun; Su, Yu-Chieh; Wei, Chang-Kuo; Chiu, Jainn-Shiun; Tseng, Chih-En; Chen, Shao-Jer; Wang, Yuh-Feng

    2011-01-01

    Accumulating evidence has shown the adverse effect of long-term hyperaldosteronism on cardiovascular morbidity that is independent of blood pressure. However, the diagnosis of primary aldosteronism (PA) remains a challenge for patients who present with subtle or atypical features or have chronic kidney disease (CKD). SPECT/CT has proven valuable in the diagnosis of a number of conditions. The aim of this study was to determine the usefulness of I-131 NP-59 SPECT/CT in patients with atypical presentations of PA and in those with CKD. The records of 15 patients with PA were retrospectively analyzed. NP-59 SPECT/CT was able to identify adrenal lesion(s) in CKD patients with suspected PA. Patients using NP-59 SPECT/CT imaging, compared with those not performing this procedure, significantly featured nearly normal serum potassium levels, normal aldosterone-renin ratio, and smaller adrenal size on CT and pathological examination and tended to feature stage 1 hypertension and non-suppressed plasma renin activity. These findings show that noninvasive NP-59 SPECT/CT is a useful tool for diagnosis in patients with subclinical or atypical features of PA and those with CKD. PMID:21541242

  11. Novel Therapeutic Strategies for Reducing Right Heart Failure Associated Mortality in Fibrotic Lung Diseases

    PubMed Central

    Adegunsoye, Ayodeji; Levy, Matthew; Oyenuga, Olusegun

    2015-01-01

    Fibrotic lung diseases carry a significant mortality burden worldwide. A large proportion of these deaths are due to right heart failure and pulmonary hypertension. Underlying contributory factors which appear to play a role in the mechanism of progression of right heart dysfunction include chronic hypoxia, defective calcium handling, hyperaldosteronism, pulmonary vascular alterations, cyclic strain of pressure and volume changes, elevation of circulating TGF-β, and elevated systemic NO levels. Specific therapies targeting pulmonary hypertension include calcium channel blockers, endothelin (ET-1) receptor antagonists, prostacyclin analogs, phosphodiesterase type 5 (PDE5) inhibitors, and rho-kinase (ROCK) inhibitors. Newer antifibrotic and anti-inflammatory agents may exert beneficial effects on heart failure in idiopathic pulmonary fibrosis. Furthermore, right ventricle-targeted therapies, aimed at mitigating the effects of functional right ventricular failure, include β-adrenoceptor (β-AR) blockers, angiotensin-converting enzyme (ACE) inhibitors, antioxidants, modulators of metabolism, and 5-hydroxytryptamine-2B (5-HT2B) receptor antagonists. Newer nonpharmacologic modalities for right ventricular support are increasingly being implemented. Early, effective, and individualized therapy may prevent overt right heart failure in fibrotic lung disease leading to improved outcomes and quality of life. PMID:26583148

  12. The Kidney Is the Principal Organ Mediating Klotho Effects

    PubMed Central

    Lindberg, Karolina; Amin, Risul; Moe, Orson W.; Hu, Ming-Chang; Erben, Reinhold G.; Östman Wernerson, Annika; Lanske, Beate; Olauson, Hannes

    2014-01-01

    Klotho was discovered as an antiaging gene, and α-Klotho (Klotho) is expressed in multiple tissues with a broad set of biologic functions. Membrane-bound Klotho binds fibroblast growth factor 23 (FGF23), but a soluble form of Klotho is also produced by alternative splicing or cleavage of the extracellular domain of the membrane-bound protein. The relative organ-specific contributions to the levels and effects of circulating Klotho remain unknown. We explored these issues by generating a novel mouse strain with Klotho deleted throughout the nephron (Six2-KL−/−). Klotho shedding from Six2-KL−/− kidney explants was undetectable and the serum Klotho level was reduced by approximately 80% in Six2-KL−/− mice compared with wild-type littermates. Six2-KL−/− mice exhibited severe growth retardation, kyphosis, and premature death, closely resembling the phenotype of systemic Klotho knockout mice. Notable biochemical changes included hyperphosphatemia, hypercalcemia, hyperaldosteronism, and elevated levels of 1,25-dihydroxyvitamin D and Fgf23, consistent with disrupted renal Fgf23 signaling. Kidney histology demonstrated interstitial fibrosis and nephrocalcinosis in addition to absent dimorphic tubules. A direct comparative analysis between Six2-KL−/− and systemic Klotho knockout mice supports extensive, yet indistinguishable, extrarenal organ manifestations. Thus, our data reveal the kidney as the principal contributor of circulating Klotho and Klotho-induced antiaging traits. PMID:24854271

  13. Narrative Review: The Emerging Clinical Implications of the Role of Aldosterone in the Metabolic Syndrome and Resistant Hypertension

    PubMed Central

    Sowers, James R.; Whaley-Connell, Adam; Epstein, Murray

    2010-01-01

    The prevalence of obesity, diabetes, hypertension, and cardiovascular and chronic kidney disease is increasing in developed countries. Obesity, insulin resistance, and hypertension commonly cluster with other risk factors for cardiovascular and chronic kidney disease to form the metabolic syndrome. Emerging evidence supports a paradigm shift in our understanding of the renin–angiotensin–aldosterone system and in aldosterone's ability to promote insulin resistance and participate in the pathogenesis of the metabolic syndrome and resistant hypertension. Recent data suggest that excess circulating aldosterone promotes the development of both disorders by impairing insulin metabolic signaling and endothelial function, which in turn leads to insulin resistance and cardiovascular and renal structural and functional abnormalities. Indeed, hyperaldosteronism is associated with impaired pancreatic β-cell function, skeletal muscle insulin sensitivity, and elevated production of proinflammatory adipokines from adipose tissue, which results in systemic inflammation and impaired glucose tolerance. Accumulating evidence indicates that the cardiovascular and renal abnormalities associated with insulin resistance are mediated in part by aldosterone acting on the mineralocorticoid receptor. Although we have known that mineralocorticoid receptor blockade attenuates cardiovascular and renal injury, only recently have we learned that mineralocorticoid receptor blockade improves pancreatic insulin release, insulin-mediated glucose utilization, and endothelium-dependent vasorelaxation. In summary, aldosterone excess has detrimental metabolic effects that contribute to the metabolic syndrome and endothelial dysfunction, which in turn contribute to the development of resistant hypertension as well as cardiovascular disease and chronic kidney disease. PMID:19487712

  14. The diagnosis of Liddle syndrome by identification of a mutation in the beta subunit of the epithelial sodium channel.

    PubMed Central

    Jackson, S N; Williams, B; Houtman, P; Trembath, R C

    1998-01-01

    Hypertension is a common multifactorial disorder associated with considerable morbidity and mortality. The kidney plays a major role in the long term regulation of blood pressure. Liddle syndrome (pseudo-hyperaldosteronism) is one of a number of monogenic disorders of salt and water transport. In a kindred with at least four affected members suffering from Liddle syndrome, we confirmed by direct DNA sequencing the identity of a novel heterozygous mutation in h betaENaC, the gene encoding the beta subunit of the amiloride sensitive epithelial sodium channel which is expressed in the distal nephron. Single stranded conformational polymorphism analysis showed cosegregation of the mutant allele within the kindred with the Liddle phenotype. An insertion of an additional cytosine into a string of six located between codons 593 and 595 results in a sequence frameshift and is predicted to produce a protein truncated by 34 amino acids. The availability of a molecular diagnostic tool has implications for the management of hypertension and genetic counselling in families with Liddle syndrome. Images PMID:9643296

  15. Aldosterone Activates Transcription Factor Nrf2 in Kidney Cells Both In Vitro and In Vivo

    PubMed Central

    Oteiza, Patricia I.; Link, Samuel; Hey, Valentin; Stopper, Helga; Schupp, Nicole

    2014-01-01

    Abstract Aims: An increased kidney cancer risk was found in hypertensive patients, who frequently exhibit hyperaldosteronism, known to contribute to kidney injury, with oxidative stress playing an important role. The capacity of kidney cells to up-regulate transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2), a key regulator of the cellular antioxidative defense, as a prevention of aldosterone-induced oxidative damage was investigated both in vitro and in vivo. Results: Aldosterone activated Nrf2 and increased the expression of enzymes involved in glutathione (GSH) synthesis and detoxification. This activation depended on the mineralocorticoid receptor (MR) and oxidative stress. In vitro, Nrf2 activation, GSH amounts, and target gene levels decreased after 24 h, while oxidant levels remained high. Nrf2 activation could not protect cells against oxidative DNA damage, as aldosterone-induced double-strand breaks and 7,8-dihydro-8-oxo-guanine (8-oxodG) lesions steadily rose. The Nrf2 activator sulforaphane enhanced the Nrf2 response both in vitro and in vivo, thereby preventing aldosterone-induced DNA damage. In vivo, Nrf2 activation further had beneficial effects on the aldosterone-caused blood pressure increase and loss of kidney function. Innovation: This is the first study showing the activation of Nrf2 by aldosterone. Moreover, the results identify sulforaphane as a substance that is capable of preventing aldosterone-induced damage both in vivo and in vitro. Conclusion: Aldosterone-induced Nrf2 adaptive response cannot neutralize oxidative actions of chronically increased aldosterone, which, therefore could be causally involved in the increased cancer incidence of hypertensive individuals. Enhancing the cellular antioxidative defense with sulforaphane might exhibit beneficial effects. Antioxid. Redox Signal. 21, 2126–2142. PMID:24512358

  16. Aldosterone Increases Oxidant Stress to Impair Guanylyl Cyclase Activity by Cysteinyl Thiol Oxidation in Vascular Smooth Muscle Cells*S⃞

    PubMed Central

    Maron, Bradley A.; Zhang, Ying-Yi; Handy, Diane E.; Beuve, Annie; Tang, Shiow-Shih; Loscalzo, Joseph; Leopold, Jane A.

    2009-01-01

    Hyperaldosteronism is associated with impaired endothelium-dependent vascular reactivity owing to increased reactive oxygen species and decreased bioavailable nitric oxide (NO·); however, the effects of aldosterone on vasodilatory signaling pathways in vascular smooth muscle cells (VSMC) remain unknown. Soluble guanylyl cyclase (GC) is a heterodimer that is activated by NO· to convert cytosolic GTP to cGMP, a second messenger required for normal VSMC relaxation. Here, we show that aldosterone (10-9-10-7 mol/liter) diminishes GC activity by activating NADPH oxidase in bovine aortic VSMC to increase reactive oxygen species levels and induce oxidative posttranslational modification(s) of Cys-122, a β1-subunit cysteinyl residue demonstrated previously to modulate NO· sensing by GC. In VSMC treated with aldosterone, Western immunoblotting detected evidence of GC β1-subunit disulfide bonding, whereas mass spectrometry analysis of a homologous peptide containing the Cys-122-bearing sequence exposed to conditions of increased oxidant stress confirmed cysteinyl sulfinic acid (m/z 435), sulfonic acid (m/z 443), and disulfide (m/z 836) bond formation. The functional effect of these modifications was examined by transfecting COS-7 cells with wild-type GC or mutant GC containing an alanine substitution at Cys-122 (C122A). Exposure to aldosterone or hydrogen peroxide (H2O2) significantly decreased cGMP levels in cells expressing wild-type GC. In contrast, aldosterone or H2O2 did not influence cGMP levels in cells expressing the mutant C122A GC, confirming that oxidative modification of Cys-122 specifically impairs GC activity. These findings demonstrate that pathophysiologically relevant concentrations of aldosterone increase oxidant stress to convert GC to an NO·-insensitive state, resulting in disruption of normal vasodilatory signaling pathways in VSMC. PMID:19141618

  17. Aldosterone Inactivates the Endothelin-B Receptor via a Cysteinyl Thiol Redox Switch to Decrease Pulmonary Endothelial Nitric Oxide Levels and Modulate Pulmonary Arterial Hypertension

    PubMed Central

    Maron, Bradley A.; Zhang, Ying-Yi; White, Kevin; Chan, Stephen Y.; Handy, Diane E.; Mahoney, Christopher E.; Loscalzo, Joseph; Leopold, Jane A.

    2012-01-01

    Background Pulmonary arterial hypertension (PAH) is characterized, in part, by decreased endothelial nitric oxide (NO•) production and elevated levels of endothelin-1. Endothelin-1 is known to stimulate endothelial nitric oxide synthase (eNOS) via the endothelin-B receptor (ETB), suggesting that this signaling pathway is perturbed in PAH. Endothelin-1 also stimulates adrenal aldosterone synthesis; in systemic blood vessels, hyperaldosteronism induces vascular dysfunction by increasing endothelial reactive oxygen species (ROS) generation and decreasing NO• levels. We hypothesized that aldosterone modulates PAH by disrupting ETB-eNOS signaling through a mechanism involving increased pulmonary endothelial oxidant stress. Methods and Results In rats with PAH, elevated endothelin-1 levels were associated with elevated aldosterone levels in plasma and lung tissue and decreased lung NO• metabolites in the absence of left heart failure. In human pulmonary artery endothelial cells (HPAECs), endothelin-1 increased aldosterone levels via PGC-1α/steroidogenesis factor-1-dependent upregulation of aldosterone synthase. Aldosterone also increased ROS production, which oxidatively modified cysteinyl thiols in the eNOS-activating region of ETB to decrease endothelin-1-stimulated eNOS activity. Substitution of ETB-Cys405 with alanine improved ETB-dependent NO• synthesis under conditions of oxidant stress, confirming that Cys405 is a redox sensitive thiol that is necessary for ETB-eNOS signaling. In HPAECs, mineralocorticoid receptor antagonism with spironolactone decreased aldosterone-mediated ROS generation and restored ETB-dependent NO• production. Spironolactone or eplerenone prevented or reversed pulmonary vascular remodeling and improved cardiopulmonary hemodynamics in two animal models of PAH in vivo. Conclusions Our findings demonstrate that aldosterone modulates an ETB cysteinyl thiol redox switch to decrease pulmonary endothelium-derived NO• and promote PAH

  18. Upregulation of Steroidogenic Acute Regulatory Protein by Hypoxia Stimulates Aldosterone Synthesis in Pulmonary Artery Endothelial Cells to Promote Pulmonary Vascular Fibrosis

    PubMed Central

    Maron, Bradley A.; Oldham, William M.; Chan, Stephen Y.; Vargas, Sara O.; Arons, Elena; Zhang, Ying-Yi; Loscalzo, Joseph; Leopold, Jane A.

    2014-01-01

    Background The molecular mechanism(s) regulating hypoxia-induced vascular fibrosis are unresolved. Hyperaldosteronism correlates positively with vascular remodeling in pulmonary arterial hypertension (PAH), suggesting that aldosterone may contribute to the pulmonary vasculopathy of hypoxia. The hypoxia-sensitive transcription factors c-Fos/c-Jun regulate steroidogenic acute regulatory protein (StAR), which facilitates the rate-limiting step of aldosterone steroidogenesis. We hypothesized that c-Fos/c-Jun upregulation by hypoxia activates StAR-dependent aldosterone synthesis in human pulmonary artery endothelial cells (HPAECs) to promote vascular fibrosis in PAH. Methods and Results Patients with PAH, rats with Sugen/hypoxia-PAH, and mice exposed to chronic hypoxia expressed increased StAR in remodeled pulmonary arterioles, providing a basis for investigating hypoxia-StAR signaling in HPAECs. Hypoxia (2.0% FiO2) increased aldosterone levels selectively in HPAECs, which was confirmed by liquid chromatography-mass spectrometry. Increased aldosterone by hypoxia resulted from enhanced c-Fos/c-Jun binding to the proximal activator protein (AP-1) site of the StAR promoter in HPAECs, which increased StAR expression and activity. In HPAECs transfected with StAR-siRNA or treated with the AP-1 inhibitor, SR-11302, hypoxia failed to increase aldosterone, confirming that aldosterone biosynthesis required StAR activation by c-Fos/c-Jun. The functional consequences of aldosterone were confirmed by pharmacological inhibition of the mineralocorticoid receptor with spironolactone or eplerenone, which attenuated hypoxia-induced upregulation of the fibrogenic protein connective tissue growth factor and collagen III in vitro, and decreased pulmonary vascular fibrosis to improve pulmonary hypertension in Conclusions Our findings identify autonomous aldosterone synthesis in HPAECs due to hypoxia-mediated upregulation of StAR as a novel molecular mechanism that promotes pulmonary vascular

  19. [Hypotension from endocrine origin].

    PubMed

    Vantyghem, Marie-Christine; Douillard, Claire; Balavoine, Anne-Sophie

    2012-11-01

    Hypotension is defined by a low blood pressure either permanently or only in upright posture (orthostatic hypotension). In contrast to hypertension, there is no threshold defining hypotension. The occurrence of symptoms for systolic and diastolic measurements respectively below 90 and 60 mm Hg establishes the diagnosis. Every acute hypotensive event should suggest shock, adrenal failure or an iatrogenic cause. Chronic hypotension from endocrine origin may be linked to adrenal failure from adrenal or central origin, isolated hypoaldosteronism, pseudohypoaldosteronism, pheochromocytoma, neuro-endocrine tumors (carcinoïd syndrome) or diabetic dysautonomia. Hypotension related to hypoaldosteronism associates low blood sodium and above all high blood potassium levels. They are generally classified according to their primary (hyperreninism) or secondary (hyporeninism) adrenal origin. Isolated primary hypoaldosteronisms are rare in adults (intensive care unit, selective injury of the glomerulosa area) and in children (aldosterone synthase deficiency). Isolated secondary hypoaldosteronism is related to mellitus diabetes complicated with dysautonomia, kidney failure, age, iatrogenic factors, and HIV infections. In both cases, they can be associated to glucocorticoid insufficiency from primary adrenal origin (adrenal failure of various origins with hyperreninism, among which congenital 21 hydroxylase deficiency with salt loss) or from central origin (hypopituitarism with hypo-reninism). Pseudohypoaldosteronisms are linked to congenital (type 1 pseudohypoaldosteronism) or acquired states of resistance to aldosterone. Acquired salt losses from enteric (total colectomy with ileostomy) or renal (interstitial nephropathy, Bartter and Gitelman syndromes…) origin might be responsible for hypotension and are associated with hyperreninism-hyperaldosteronism. Hypotension is a rare manifestation of pheochromocytomas, especially during surgical removal when the patient has not been

  20. Structure-activity relationship study of angiotensin II analogs in terms of β-arrestin-dependent signaling to aldosterone production.

    PubMed

    Valero, Thairy Reyes; Sturchler, Emmanuel; Jafferjee, Malika; Rengo, Giuseppe; Magafa, Vassiliki; Cordopatis, Paul; McDonald, Patricia; Koch, Walter J; Lymperopoulos, Anastasios

    2016-04-01

    The known angiotensin II (AngII) physiological effect of aldosterone synthesis and secretion induction, a steroid hormone that contributes to the pathology of postmyocardial infarction (MI) heart failure (HF), is mediated by both Gq/11 proteins and β-arrestins, both of which couple to the AngII type 1 receptors (AT1Rs) of adrenocortical zona glomerulosa (AZG) cells. Over the past several years, AngII analogs with increased selectivity ("bias") toward β-arrestin-dependent signaling at the AT1R have been designed and described, starting with SII, the gold-standard β-arrestin-"biased" AngII analog. In this study, we examined the relative potencies of an extensive series of AngII peptide analogs at relative activation of G proteins versus β-arrestins by the AT1R. The major structural difference of these peptides from SII was their varied substitutions at position 5, rather than position 4 of native AngII. Three of them were found biased for β-arrestin activation and extremely potent at stimulating aldosterone secretion in AZG cells in vitro, much more potent than SII in that regard. Finally, the most potent of these three ([Sar(1), Cys(Et)(5), Leu(8)]-AngII, CORET) was further examined in post-MI rats progressing to HF and overexpressing adrenal β-arrestin1 in vivo. Consistent with the in vitro studies, CORET was found to exacerbate the post-MI hyperaldosteronism, and, consequently, cardiac function of the post-MI animals in vivo. Finally, our data suggest that increasing the size of position 5 of the AngII peptide sequence results in directly proportional increases in AT1R-dependent β-arrestin activation. These findings provide important insights for AT1R pharmacology and future AngII-targeted drug development. PMID:27069636

  1. Characterization of aldosterone-induced potassium secretion in rat distal colon.

    PubMed Central

    Sweiry, J H; Binder, H J

    1989-01-01

    The role of apical and basolateral membranes in aldosterone-induced active potassium (K) secretion in rat distal colon was investigated by measuring mucosal-to-serosal (Jms) and serosal-to-mucosal (Jsm) 42K fluxes (mueq.h-1.cm-2) across isolated stripped mucosa under short-circuit conditions in normal and secondary-hyperaldosterone animals. In normal colons mucosal tetraethylammonium (TEA; 30 mM) or barium (Ba; 5 mM), but not cesium (Cs; 15 mM), reduced Jsm without affecting Jms. In aldosterone animals (a) net K secretion (-0.54 +/- 0.11) was converted to net K absorption (0.63 +/- 0.15) by mucosal TEA, which produced a marked reduction in Jsm (0.82 +/- 0.07) and an increase in Jms (0.35 +/- 0.07). In contrast mucosal Ba resulted in a relatively smaller reduction in JK(sm) without altering JK(ms), whereas mucosal Cs was ineffective; (b) serosal bumetanide or the removal of serosal Na or Cl markedly inhibited JK(sm and abolished net K secretion; and (c) serosal ouabain (1 mM) produced qualitatively similar effects to those of serosal bumetanide. These results demonstrate that (a) normal rat distal colon contains apical TEA- and Ba-sensitive K channels; (b) aldosterone induces TEA-sensitive and Ba-sensitive apical K channels; (c) aldosterone-induced K secretion requires both the Na,K-pump and Na-K-2Cl cotransport for K uptake across the basolateral membrane; and (d) alteration of any of these processes results in inhibition of aldosterone-induced active K secretion simultaneously with stimulation of K absorption. Images PMID:2921323

  2. Uncoupling of Secretion From Growth in Some Hormone Secretory Tissues

    PubMed Central

    2014-01-01

    Context: Most syndromes with benign primary excess of a hormone show positive coupling of hormone secretion to size or proliferation in the affected hormone secretory tissue. Syndromes that lack this coupling seem rare and have not been examined for unifying features among each other. Evidence Acquisition: Selected clinical and basic features were analyzed from original reports and reviews. We examined indices of excess secretion of a hormone and indices of size of secretory tissue within the following three syndromes, each suggestive of uncoupling between these two indices: familial hypocalciuric hypercalcemia, congenital diazoxide-resistant hyperinsulinism, and congenital primary hyperaldosteronism type III (with G151E mutation of the KCNJ5 gene). Evidence Synthesis: Some unifying features among the three syndromes were different from features present among common tumors secreting the same hormone. The unifying and distinguishing features included: 1) expression of hormone excess as early as the first days of life; 2) normal size of tissue that oversecretes a hormone; 3) diffuse histologic expression in the hormonal tissue; 4) resistance to treatment by subtotal ablation of the hormone-secreting tissue; 5) causation by a germline mutation; 6) low potential of the same mutation to cause a tumor by somatic mutation; and 7) expression of the mutated molecule in a pathway between sensing of a serum metabolite and secretion of hormone regulating that metabolite. Conclusion: Some shared clinical and basic features of uncoupling of secretion from size in a hormonal tissue characterize three uncommon states of hormone excess. These features differ importantly from features of common hormonal neoplasm of that tissue. PMID:25004249

  3. Laboratory investigation of primary aldosteronism.

    PubMed

    Stowasser, Michael; Taylor, Paul J; Pimenta, Eduardo; Ahmed, Ashraf H Al-Asaly; Gordon, Richard D

    2010-05-01

    Availability and wider application of the plasma aldosterone/renin ratio (ARR) as a screening test for primary aldosteronism (PA) has led to the recognition that PA is the most common potentially curable and specifically treatable form of hypertension, possibly accounting for as many as 5-13% of patients. Aldosterone excess also has adverse cardiovascular consequences that go above and beyond hypertension development. These findings support the concept that PA plays an important role in cardiovascular disease states and should be systematically sought and specifically treated, and have led to the development of a US Endocrine Society clinical guideline for the detection, diagnosis and management of this condition. Reliable detection requires that interfering factors (including medications known to alter the ratio) are controlled before ARR measurement (or their effects taken into account), and reliable methods such as fludrocortisone suppression testing are used to confirm PA. Because computed tomography frequently misses aldosterone-producing adenomas yet demonstrates non-functioning nodules, adrenal venous sampling is the only dependable way to differentiate unilateral (surgically correctable) from bilateral (usually treated with aldosterone antagonist medications) forms of PA. For the glucocorticoid-remediable form of PA (familial hyperaldosteronism type I), genetic testing for the causative 'hybrid' 11beta-hydroxylase/aldosterone synthase gene has greatly facilitated detection. Laboratory assessment (including suppression testing post-operatively, and renin measurement during treatment with aldosterone antagonist medications) can assist in assessing therapeutic responses and in guiding ongoing management. Development of new, highly reliable high-throughput mass spectrometric methods for measuring aldosterone and renin should further enhance detection and reliability of diagnostic workup for PA. PMID:20498828

  4. A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery.

    PubMed

    Morimoto, R; Satani, N; Iwakura, Y; Ono, Y; Kudo, M; Nezu, M; Omata, K; Tezuka, Y; Seiji, K; Ota, H; Kawasaki, Y; Ishidoya, S; Nakamura, Y; Arai, Y; Takase, K; Sasano, H; Ito, S; Satoh, F

    2016-06-01

    Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl(-1) and aldosterone renin activity ratio of 90.2 (ng dl(-1) per ng ml(-1 )h(-1)), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl(-1) confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production. PMID:26538381

  5. Aldosterone, Parathyroid Hormone, and the Use of Renin-Angiotensin-Aldosterone System Inhibitors: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Brown, Jenifer; de Boer, Ian H.; Robinson-Cohen, Cassianne; Siscovick, David S.; Kestenbaum, Bryan; Allison, Matthew

    2015-01-01

    Context: Aldosterone and PTH are implicated in the pathogenesis of cardiovascular and skeletal diseases. An expanding body of evidence supports a bidirectional and positive physiologic relationship between aldosterone and PTH. Large population-based studies confirming this relationship, and whether it may be targeted as a potential method to mitigate the clinical consequences associated with excess aldosterone and PTH, are needed. Objective: We hypothesized that higher aldosterone levels would associate with higher PTH, and that the use of renin-angiotensin-aldosterone system (RAAS) inhibitors would predict lower PTH in a large, multi-ethnic, community-based cohort. Design, Setting, Participants: We conducted cross-sectional analyses of participants in the Multi-Ethnic Study of Atherosclerosis without apparent primary hyperparathyroidism or chronic kidney disease (n = 5668). We evaluated associations of RAAS inhibitor use with PTH concentration among 1888 treated hypertensive participants. We also tested associations of serum aldosterone concentration with PTH concentration among 1547 participants with these measurements. Outcome: Serum PTH concentration. Results: Higher aldosterone associated with higher PTH (β = 0.19 pg/ml per 1 ng/dl of aldosterone, P < .0001), and this finding was most pronounced among those with a primary hyperaldosteronism-like phenotype. There was a stepwise increment in PTH when comparing untreated normotensives, hypertensives using RAAS inhibitors, untreated hypertensives, and treated hypertensives using non-RAAS inhibitors (40.8, 45.0, 46.2, 47.1 pg/ml, respectively). The use of any RAAS inhibitor independently associated with lower PTH (β = −2.327 pg/ml per use of RAAS inhibitor, P = .006), when compared with the use of any non-RAAS inhibitor medication. Conclusions: Higher serum aldosterone concentration is associated with higher serum PTH concentration, and the use of RAAS inhibitors is associated with lower PTH concentration

  6. Reduced parenteral nutrition requirements following anastomosis of a short residual colonic segment to a short jejunum.

    PubMed

    Smith, Katherine H; Saunders, John A; Nugent, Karen P; Jackson, Alan A; Stroud, Michael A

    2011-11-01

    A 22-year-old man suffered an acute small bowel infarct leading to extensive bowel resection, resulting in only 20 cm of jejunum to a jejunostomy, although he also had 50 cm of residual colon with a mucous fistula. The patient was out on long-term home parenteral nutrition (PN) but endured high stomal losses of 5-6 L per day and, despite all conventional measures, required 6.1 L of fluid (including PN) and 555 mmol sodium per day. Although body mass index was maintained, he suffered debilitating malaise and recurrent episodes of catheter-related sepsis and also developed persistently abnormal liver function tests. He was considered a potential intestinal transplant patient, but before taking that step, he opted for reanastomosis of his residual colon to his jejunum, ending in a colostomy. At surgery, only 30 cm of additional bowel lengthening could be achieved, but despite this, the patient's stomal losses reduced to 2.5 L per day, intravenous fluid requirements reduced to 4.1 L per day, and liver function normalized. The patient also gained 7.5 kg despite no change in PN caloric prescription, and his quality of life was dramatically enhanced. The case illustrates that even a small length of colon can grant significant improvements, probably via improvements in small bowel transit and adaptive changes, better sodium and water resorption with decreased hyperaldosteronism, and enhanced energy and nitrogen recovery. Reanastomosis of defunctioned colon should therefore always be considered a management option in short bowel syndrome. PMID:22042049

  7. Aldosterone induces fibrosis, oxidative stress and DNA damage in livers of male rats independent of blood pressure changes

    SciTech Connect

    Queisser, Nina; Happ, Kathrin; Link, Samuel; Jahn, Daniel; Zimnol, Anna; Geier, Andreas; Schupp, Nicole

    2014-11-01

    Mineralocorticoid receptor blockers show antifibrotic potential in hepatic fibrosis. The mechanism of this protective effect is not known yet, although reactive oxygen species seem to play an important role. Here, we investigated the effects of elevated levels of aldosterone (Ald), the primary ligand of the mineralocorticoid receptor, on livers of rats in a hyperaldosteronism model: aldosterone-induced hypertension. Male Sprague–Dawley rats were treated for 4 weeks with aldosterone. To distinguish if damage caused in the liver depended on increased blood pressure or on increased Ald levels, the mineralocorticoid receptor antagonist spironolactone was given in a subtherapeutic dose, not normalizing blood pressure. To investigate the impact of oxidative stress, the antioxidant tempol was administered. Aldosterone induced fibrosis, detected histopathologically, and by expression analysis of the fibrosis marker, α-smooth muscle actin. Further, the mRNA amount of the profibrotic cytokine TGF-β was increased significantly. Fibrosis could be reduced by scavenging reactive oxygen species, and also by blocking the mineralocorticoid receptor. Furthermore, aldosterone treatment caused oxidative stress and DNA double strand breaks in livers, as well as the elevation of DNA repair activity. An increase of the transcription factor Nrf2, the main regulator of the antioxidative response could be observed, and of its target genes heme oxygenase-1 and γ-glutamylcysteine synthetase. All these effects of aldosterone were prevented by spironolactone and tempol. Already after 4 weeks of treatment, aldosteroneinfusion induced fibrosis in the liver. This effect was independent of elevated blood pressure. DNA damage caused by aldosterone might contribute to fibrosis progression when aldosterone is chronically increased. - Highlights: • Aldosterone has direct profibrotic effects on the liver independent of blood pressure. • Fibrosis is mediated by the mineralocorticoid receptor and

  8. Effect of aldosterone-producing adenoma on endothelial function and Rho-associated kinase activity in patients with primary aldosteronism.

    PubMed

    Matsumoto, Takeshi; Oki, Kenji; Kajikawa, Masato; Nakashima, Ayumu; Maruhashi, Tatsuya; Iwamoto, Yumiko; Iwamoto, Akimichi; Oda, Nozomu; Hidaka, Takayuki; Kihara, Yasuki; Kohno, Nobuoki; Chayama, Kazuaki; Goto, Chikara; Aibara, Yoshiki; Noma, Kensuke; Liao, James K; Higashi, Yukihito

    2015-04-01

    The purpose of this study was to evaluate vascular function and activity of Rho-associated kinases (ROCKs) in patients with primary aldosteronism. Vascular function, including flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation, and ROCK activity in peripheral leukocytes were evaluated in 21 patients with aldosterone-producing adenoma (APA), 23 patients with idiopathic hyperaldosteronism (IHA), and 40 age-, sex-, and blood pressure-matched patients with essential hypertension (EHT). FMD was significantly lower in the APA group than in the IHA and EHT groups (3.2±2.0% versus 4.6±2.3% and 4.4±2.2%; P<0.05, respectively), whereas there was no significant difference in FMD between the IHA and EHT groups. There was no significant difference in nitroglycerine-induced vasodilation in the 3 groups. ROCK activity was higher in the APA group than in the IHA and EHT groups (1.29±0.57 versus 1.00±0.46 and 0.81±0.36l; P<0.05, respectively), whereas there was no significant difference in ROCK activity between the IHA and EHT groups. FMD correlated with age (r=-0.31; P<0.01), plasma aldosterone concentration (r=-0.35; P<0.01), and aldosterone:renin ratio (r=-0.34; P<0.01). ROCK activity correlated with age (r=-0.24; P=0.04), plasma aldosterone concentration (r=0.33; P<0.01), and aldosterone:renin ratio (r=0.46; P<0.01). After adrenalectomy, FMD and ROCK activity were restored in patients with APA. APA was associated with both endothelial dysfunction and increased ROCK activity compared with those in IHA and EHT. APA may have a higher risk of future cardiovascular events. PMID:25624340

  9. Mutated KCNJ5 activates the acute and chronic regulatory steps in aldosterone production.

    PubMed

    Hattangady, Namita G; Karashima, Shigehiro; Yuan, Lucy; Ponce-Balbuena, Daniela; Jalife, José; Gomez-Sanchez, Celso E; Auchus, Richard J; Rainey, William E; Else, Tobias

    2016-07-01

    Somatic and germline mutations in the inward-rectifying K(+) channel (KCNJ5) are a common cause of primary aldosteronism (PA) in aldosterone-producing adenoma and familial hyperaldosteronism type III, respectively. Dysregulation of adrenal cell calcium signaling represents one mechanism for mutated KCNJ5 stimulation of aldosterone synthase (CYP11B2) expression and aldosterone production. However, the mechanisms stimulating acute and chronic production of aldosterone by mutant KCNJ5 have not been fully characterized. Herein, we defined the effects of the T158A KCNJ5 mutation (KCNJ5(T158A)) on acute and chronic regulation of aldosterone production using an adrenal cell line with a doxycycline-inducible KCNJ5(T158A) gene (HAC15-TRE-KCNJ5(T158A)). Doxycycline incubation caused a time-dependent increase in KCNJ5(T158A) and CYP11B2 mRNA and protein levels. Electrophysiological analyses confirm the loss of inward rectification and increased Na(+) permeability in KCNJ5(T158A)-expressing cells. KCNJ5(T158A) expression also led to the activation of CYP11B2 transcriptional regulators, NURR1 and ATF2. Acutely, KCNJ5(T158A) stimulated the expression of total and phosphorylated steroidogenic acute regulatory protein (StAR). KCNJ5(T158A) expression increased the synthesis of aldosterone and the hybrid steroids 18-hydroxycortisol and 18-oxocortisol, measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS). All of these stimulatory effects of KCNJ5(T158A) were inhibited by the L-type Ca(2+) channel blocker, verapamil. Overall, KCNJ5(T158A)increases CYP11B2 expression and production of aldosterone, corticosterone and hybrid steroids by upregulating both acute and chronic regulatory events in aldosterone production, and verapamil blocks KCNJ5(T158A)-mediated pathways leading to aldosterone production. PMID:27099398

  10. Hyperplasia in glands with hormone excess.

    PubMed

    Marx, Stephen J

    2016-01-01

    Five syndromes share predominantly hyperplastic glands with a primary excess of hormones: neonatal severe primary hyperparathyroidism, from homozygous mutated CASR, begins severely in utero; congenital non-autoimmune thyrotoxicosis, from mutated TSHR, varies from severe with fetal onset to mild with adult onset; familial male-limited precocious puberty, from mutated LHR, expresses testosterone oversecretion in young boys; hereditary ovarian hyperstimulation syndrome, from mutated FSHR, expresses symptomatic systemic vascular permeabilities during pregnancy; and familial hyperaldosteronism type IIIA, from mutated KCNJ5, presents in young children with hypertension and hypokalemia. The grouping of these five syndromes highlights predominant hyperplasia as a stable tissue endpoint and as their tissue stage for all of the hormone excess. Comparisons were made among this and two other groups of syndromes, forming a continuum of gland staging: predominant oversecretions express little or no hyperplasia; predominant hyperplasias express little or no neoplasia; and predominant neoplasias express nodules, adenomas, or cancers. Hyperplasias may progress (5 of 5) to neoplastic stages while predominant oversecretions rarely do (1 of 6; frequencies differ P<0.02). Hyperplasias do not show tumor multiplicity (0 of 5) unlike neoplasias that do (13 of 19; P<0.02). Hyperplasias express mutation of a plasma membrane-bound sensor (5 of 5), while neoplasias rarely do (3 of 14; P<0.002). In conclusion, the multiple distinguishing themes within the hyperplasias establish a robust pathophysiology. It has the shared and novel feature of mutant sensors in the plasma membrane, suggesting that these are major contributors to hyperplasia. PMID:26407873

  11. [Effect of bradykinin on systemic and pulmonary hemodynamics in the human].

    PubMed

    Bönner, G; Schunk, U; Preis, S; Wambach, G; Toussaint, T

    1989-11-01

    In our studies we investigated the vasodepressor effects of bradykinin in vivo in normotensive and hypertensive subjects. Bradykinin was injected intravenously and intraarterially (40-6050 pM/kg) respectively was infused intraarterially (40-6050 pM/kg/min). The investigations were performed in 21 normotensives and 15 hypertensives. Bradykinin injections were performed after the following pharmacological interventions: salt restriction (10 mmol Na/d), salt loading (300 mmol Na/d), captopril (50 mg), ramipril (5 mg), lisinopril (20 mg), ketotifen (2 x 1 mg), indomethacin (2 x 50 mg), and propranolol (80 mg). The results show that bradykinin lowers blood pressure dose related by marked reduction in peripheral vascular resistance. The blood pressure reduction was strongly correlated with the increase in kinin concentration. This effect of bradykinin appears to be independent of changes in sodium metabolism, of beta adrenoceptors, of histamine-1 receptors, and of prostaglandins. ACE-inhibitors potentiate the blood pressure lowering effect of bradykinin about 20- to 50-fold. In case of an intraarterial injection of bradykinin in only 2-5% o the intravenously used dose of bradykinin are needed to produce an identical fall in blood pressure. From this experiments a pulmonary clearance rate of bradykinin over 95% can be calculated. In the pulmonary arteries bradykinin has no effect on the vascular resistance. In patients suffering from primary or renovascular hypertension the blood pressure response to bradykinin was enhanced. The bradykinin potentiating effect of the ACE-inhibitors was not altered in the hypertensives. In patients suffering from bradykinin hypertension or primary hyperaldosteronism bradykinin developed the same blood pressure lowering effect as in the normotensives. PMID:2586015

  12. A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery

    PubMed Central

    Morimoto, R; Satani, N; Iwakura, Y; Ono, Y; Kudo, M; Nezu, M; Omata, K; Tezuka, Y; Seiji, K; Ota, H; Kawasaki, Y; Ishidoya, S; Nakamura, Y; Arai, Y; Takase, K; Sasano, H; Ito, S; Satoh, F

    2016-01-01

    Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl−1 and aldosterone renin activity ratio of 90.2 (ng dl−1 per ng ml−1 h−1), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl−1 confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production. PMID:26538381

  13. Activation of mTORC1 in collecting ducts causes hyperkalemia.

    PubMed

    Chen, Zhenguo; Dong, Heling; Jia, Chunhong; Song, Qiancheng; Chen, Juan; Zhang, Yue; Lai, Pinglin; Fan, Xiaorong; Zhou, Xuan; Liu, Miao; Lin, Jun; Yang, Cuilan; Li, Ming; Gao, Tianming; Bai, Xiaochun

    2014-03-01

    Mutation of TSC (encoding tuberous sclerosis complex protein) and activation of mammalian target of rapamycin (mTOR) have been implicated in the pathogenesis of several renal diseases, such as diabetic nephropathy and polycystic kidney disease. However, the role of mTOR in renal potassium excretion and hyperkalemia is not known. We showed that mice with collecting-duct (CD)-specific ablation of TSC1 (CDTsc1KO) had greater mTOR complex 1 (mTORC1) activation in the CD and demonstrated features of pseudohypoaldosteronism, including hyperkalemia, hyperaldosteronism, and metabolic acidosis. mTORC1 activation caused endoplasmic reticulum stress, columnar cell lesions, and dedifferentiation of CD cells with loss of aquaporin-2 and epithelial-mesenchymal transition-like phenotypes. Of note, mTORC1 activation also reduced the expression of serum- and glucocorticoid-inducible kinase 1, a crucial regulator of potassium homeostasis in the kidney, and decreased the expression and/or activity of epithelial sodium channel-α, renal outer medullary potassium channel, and Na(+), K(+)-ATPase in the CD, which probably contributed to the aldosterone resistance and hyperkalemia in these mice. Rapamycin restored these phenotypic changes. Overall, this study identifies a novel function of mTORC1 in regulating potassium homeostasis and demonstrates that loss of TSC1 and activation of mTORC1 results in dedifferentiation and dysfunction of the CD and causes hyperkalemia. The CDTsc1KO mice provide a novel model for hyperkalemia induced exclusively by dysfunction of the CD. PMID:24203997

  14. Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations.

    PubMed

    Al Shibli, Amar; Narchi, Hassib

    2015-06-26

    Bartter and Gitelman syndromes (BS and GS) are inherited disorders resulting in defects in renal tubular handling of sodium, potassium and chloride. Previously considered as genotypic and phenotypic heterogeneous diseases, recent evidence suggests that they constitute a spectrum of disease caused by different genetic mutations with the molecular defects of chloride reabsorption originating at different sites of the nephron in each condition. Although they share some characteristic metabolic abnormalities such as hypokalemia, metabolic alkalosis, hyperplasia of the juxtaglomerular apparatus with hyperreninemia, hyperaldosteronism, the clinical and laboratory manifestations may not always allow distinction between them. Diuretics tests, measuring the changes in urinary fractional excretion of chloride from baseline after administration of either hydrochlorothiazide or furosemide show very little change (< 2.3%) in the fractional excretion of chloride from baseline in GS when compared with BS, except when BS is associated with KCNJ1 mutations where a good response to both diuretics exists. The diuretic test is not recommended for infants or young children with suspected BS because of a higher risk of volume depletion in such children. Clinical symptoms and biochemical markers of GS and classic form of BS (type III) may overlap and thus genetic analysis may specify the real cause of symptoms. However, although genetic analysis is available, its use remains limited because of limited availability, large gene dimensions, lack of hot-spot mutations, heavy workup time and costs involved. Furthermore, considerable overlap exists between the different genotypes and phenotypes. Although BS and GS usually have distinct presentations and are associated with specific gene mutations, there remains considerable overlap between their phenotypes and genotypes. Thus, they are better described as a spectrum of clinical manifestations caused by different gene mutations. PMID:26140272

  15. Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations

    PubMed Central

    Al Shibli, Amar; Narchi, Hassib

    2015-01-01

    Bartter and Gitelman syndromes (BS and GS) are inherited disorders resulting in defects in renal tubular handling of sodium, potassium and chloride. Previously considered as genotypic and phenotypic heterogeneous diseases, recent evidence suggests that they constitute a spectrum of disease caused by different genetic mutations with the molecular defects of chloride reabsorption originating at different sites of the nephron in each condition. Although they share some characteristic metabolic abnormalities such as hypokalemia, metabolic alkalosis, hyperplasia of the juxtaglomerular apparatus with hyperreninemia, hyperaldosteronism, the clinical and laboratory manifestations may not always allow distinction between them. Diuretics tests, measuring the changes in urinary fractional excretion of chloride from baseline after administration of either hydrochlorothiazide or furosemide show very little change (< 2.3%) in the fractional excretion of chloride from baseline in GS when compared with BS, except when BS is associated with KCNJ1 mutations where a good response to both diuretics exists. The diuretic test is not recommended for infants or young children with suspected BS because of a higher risk of volume depletion in such children. Clinical symptoms and biochemical markers of GS and classic form of BS (type III) may overlap and thus genetic analysis may specify the real cause of symptoms. However, although genetic analysis is available, its use remains limited because of limited availability, large gene dimensions, lack of hot-spot mutations, heavy workup time and costs involved. Furthermore, considerable overlap exists between the different genotypes and phenotypes. Although BS and GS usually have distinct presentations and are associated with specific gene mutations, there remains considerable overlap between their phenotypes and genotypes. Thus, they are better described as a spectrum of clinical manifestations caused by different gene mutations. PMID:26140272

  16. Characterization of right ventricular remodeling and failure in a chronic pulmonary hypertension model.

    PubMed

    Aguero, Jaume; Ishikawa, Kiyotake; Hadri, Lahouaria; Santos-Gallego, Carlos; Fish, Kenneth; Hammoudi, Nadjib; Chaanine, Antoine; Torquato, Samantha; Naim, Charbel; Ibanez, Borja; Pereda, Daniel; García-Alvarez, Ana; Fuster, Valentin; Sengupta, Partho P; Leopold, Jane A; Hajjar, Roger J

    2014-10-15

    In pulmonary hypertension (PH), right ventricular (RV) dysfunction and failure is the main determinant of a poor prognosis. We aimed to characterize RV structural and functional differences during adaptive RV remodeling and progression to RV failure in a large animal model of chronic PH. Postcapillary PH was created surgically in swine (n = 21). After an 8- to 14-wk follow-up, two groups were identified based on the development of overt heart failure (HF): PH-NF (nonfailing, n = 12) and PH-HF (n = 8). In both groups, invasive hemodynamics, pressure-volume relationships, and echocardiography confirmed a significant increase in pulmonary pressures and vascular resistance consistent with PH. Histological analysis also demonstrated distal pulmonary arterial (PA) remodeling in both groups. Diastolic dysfunction, defined by a steeper RV end-diastolic pressure-volume relationship and longitudinal strain, was found in the absence of HF as an early marker of RV remodeling. RV contractility was increased in both groups, and RV-PA coupling was preserved in PH-NF animals but impaired in the PH-HF group. RV hypertrophy was present in PH-HF, although there was evidence of increased RV fibrosis in both PH groups. In the PH-HF group, RV sarcoplasmic reticulum Ca(2+)-ATPase2a expression was decreased, and endoplasmic reticulum stress was increased. Aldosterone levels were also elevated in PH-HF. Thus, in the swine pulmonary vein banding model of chronic postcapillary PH, RV remodeling occurs at the structural, histological, and molecular level. Diastolic dysfunction and fibrosis are present in adaptive RV remodeling, whereas the onset of RV failure is associated with RV-PA uncoupling, defective calcium handling, and hyperaldosteronism. PMID:25158063

  17. Repeated resections for liver metastasis from primary adrenocortical carcinoma: A case report

    PubMed Central

    Nakano, Ryosuke; Satoh, Daisuke; Nakajima, Hirochika; Yoshimura, Yuri; Miyoshi, Hisanobu; Yoshida, Kazuhiro; Matsukawa, Hiroyoshi; Shiozaki, Shigehiro; Ichimura, Kouichi; Okajima, Masazumi; Ninomiya, Motoki

    2015-01-01

    Introduction Adrenal cortical carcinoma (ACC) is a very rare type of tumor that generally has a poor prognosis. Little has been reported on repeated liver resections with recurrent metastasis still confined to the liver. In this report, we describe a case of functioning ACC in a 65-year-old woman with 2 liver metastases of the ACC (at 1.5 and 4 years) after the right adrenalectomy. Presentation of case A 65-year-old woman was referred to our hospital based on a suspicion of hyperaldosteronism. Abdominal computed tomography revealed a lesion at the right adrenal gland; therefore, we performed right adrenalectomy and subsequently diagnosed the lesion as ACC. However, follow-up computed tomography at 1.5 and 4 years after the right adrenalectomy revealed liver metastasis of ACC; liver resection was performed for both metastases. Discussion Complete surgical resection is the established approach for the treatment of ACC. The prognosis of ACC is usually dismal, and recurrence rates of up to 85% have been reported. However, the appropriate treatment for recurrent ACC is not well established, and the effectiveness of other modalities, such as chemotherapy and radiotherapy, is not proven. Therefore, surgical resection may currently be the most appropriate treatment modality, as the patient achieved a disease-free interval of 2.5 years after the first liver resection. Conclusion In selected patients with recurrent or metastatic ACC, resection is likely to be associated with prolonged survival. However, a full cure is generally not achievable, and a multidisciplinary approach is likely needed to achieve long-term disease-free status and survival. PMID:25765741

  18. Severe hypokalemic paralysis as a manifestation of a mitochondrial disorder.

    PubMed

    Finsterer, Josef; Lässer, Stefan

    2013-01-01

    Mitochondrial disorder (MtD) is usually a multisystem disease due to impaired mitochondrial energy production. Severe hypokalemia resulting in muscle weakness and rhabdomyolysis has not been reported as a phenotypic feature of MtD. Here we describe a 60-year-old male patient who developed myalgias followed by generalized muscle weakness a few days before admission. Symptoms were attributed to severe hypokalemia that occurred after the patient had discontinued spironolactone, a competitive antagonist of the aldosterone receptor, four months earlier on his own judgment. Spironolactone was given for 10 years to treat suspected primary hyperaldosteronism (Conn's syndrome). He presented with myopathic face, bilateral ptosis, hypertelorism, brachydactylia, weakness of the axial and limb muscles, and bilateral leg edema. Hypertelorism and brachydactylia are known as physical traits of MtD. Laboratory investigations revealed hypokalemia of 1.7 mmol/l and elevated serum levels of creatine kinase (2,772 U/l). Electrocardiogram showed sinus rhythm, left bundle-branch-block, repolarization abnormalities, and prolonged QTc (571 ms), which is associated with a propensity to ventricular arrhythmias. Diagnostic work-up revealed bilateral adenomas of the suprarenal glands. Conn's syndrome was regarded as a manifestation of MtD, since MtDs are frequently associated with endocrine abnormalities. The patient also presented with occasional double vision, ptosis, renal insufficiency, bilateral renal cysts, hypertriglyceridemia, arterial hypertension, and hypertrophic cardiomyopathy. Taken together, we have made the diagnosis of MtD. In conclusion, MtD may be associated with adrenal adenomas, which may cause severe symptomatic hypokalemia, manifesting as generalized weakness and myalgias due to rhabdomyolysis. Endocrine involvement may be a phenotypic feature of MtD. PMID:23985882

  19. Classification and surgical treatment for 180 cases of adrenocortical hyperplastic disease

    PubMed Central

    Zhang, Yushi; Li, Hanzhong

    2015-01-01

    Objective: To review and discuss the diagnostic and surgical therapeutic methods of adrenocortical hyperplastic disease. Methods: A retrospective analysis was done to 180 adrenocortical hyperplasia patients (74 males, 109 females, aged 6~76 (average 40.1). Studies were done to the relationship between patients’ clinical characteristics, biochemical, endocrinological and imaging examination results, the therapeutic effects. Results: Among all 180 cases, there are 107 Cushing disease (CD), 19 ectopic adrenocorticotropin adrenal hyperplasia (EAAH), 28 adrenocorticotropin independent macronodular adrenal hyperplasia (AIMAH), 4 primary pigmented nodular adrenocortical hyperplasia (PPNAH), and 28 Idiopathic Hyperaldosteronism (IHA). Twenty-four-hour urinary free cortisol (24 h UFC) excretion of CD, EAAH, AIMAH and PPNAH patients were 95.2~535.7 µg (average 287.6 µg), 24.8~808.2 µg (average 307.9 µg), 102.5~3127.0 µg (average 852.5 µg), and 243.8~1124.6 µg (average 564.3 µg). Both low and high-dose dexamethasone suppression tests (DDST) were not suppressed in AIMAH, PPNAH and EAAH groups, but HDDST was suppressed in CD group. CT thin scanning results of 180 patients all showed enlargements in the affected side adrenal gland. Unilateral adrenalectomies were performed in 102 hypercortisolism cases. Local lesion excisions were done to 21 IHA patients. 57 patients had surgeries in both sides of the adrenal glands (39 bilateral total adrenalectomies, 16 total adrenalectomy in one side andsubtotal adrenalectomy in the other, 2 bilateral subtotal adrenalectomies). 106 (59%) patients were followed up for 4~158 (average 32) months. Conclusion: Unilateral adrenalectomy was the first choice for operable adrenocortical hyperplasia patients. The operation mode for the other adrenal gland should be based on the type of hyperplasia and clinical observation. PMID:26770569

  20. A 5-Year Prospective Follow-Up Study of Lipid-Rich Adrenal Incidentalomas: No Tumor Growth or Development of Hormonal Hypersecretion

    PubMed Central

    Raade, Merja; Hämäläinen, Esa; Sane, Timo

    2015-01-01

    Background Current guidelines for follow-up of adrenal incidentalomas are extensive and hampered by lack of follow-up studies. We tested the hypothesis that small lipid-rich adrenal incidentalomas, initially characterized by tumor size <40 mm and <10 Hounsfield units (HUs) on unenhanced computed tomography (CT) may not demonstrate excessive growth/hormonal hypersecretion on follow-up. Methods Sixty-nine incidentalomas in 56 patients were restudied with unenhanced CT and screening for hypercortisolism (dexamethasone suppression test [DST], plasma adrenocorticotropic hormone) and pheochromocytoma (24-hour urinary metanephrines and normetanephrines) 5 years later. Primary hyperaldosteronism was excluded at base-line. Results Tumor (n=69) size was similar before and after 5 years follow-up (19±6 mm vs. 20±7 mm). Mean tumor growth was 1±2 mm. Largest increase in tumor size was 8 mm, this tumor was surgically removed and histopathology confirmed cortical adenoma. DST was normal in 54 patients and two patients (3.6%) were still characterized by subclinical hypercortisolism. Initial tumor size was >20 mm for the patient with largest tumor growth and those with subclinical hypercortisolism. All patients had normal 24-hour urinary metanephrines and normetanephrines. Low attenuation (<10 HU) was demonstrated in 97% of 67 masses re-evaluated with unenhanced CT. Conclusion None of the patients developed clinically relevant tumor growth or new subclinical hypercortisolism. Biochemical screening for pheochromocytoma in incidentalomas demonstrating <10 HU on unenhanced CT is not needed. For such incidentalomas <40 mm, it seems sufficient to perform control CT and screen for hypercortisolism after 5 years. PMID:26354488

  1. Syndromes that Mimic an Excess of Mineralocorticoids.

    PubMed

    Sabbadin, Chiara; Armanini, Decio

    2016-09-01

    Pseudohyperaldosteronism is characterized by a clinical picture of hyperaldosteronism with suppression of renin and aldosterone. It can be due to endogenous or exogenous substances that mimic the effector mechanisms of aldosterone, leading not only to alterations of electrolytes and hypertension, but also to an increased inflammatory reaction in several tissues. Enzymatic defects of adrenal steroidogenesis (deficiency of 17α-hydroxylase and 11β-hydroxylase), mutations of mineralocorticoid receptor (MR) and alterations of expression or saturation of 11-hydroxysteroid dehydrogenase type 2 (apparent mineralocorticoid excess syndrome, Cushing's syndrome, excessive intake of licorice, grapefruits or carbenoxolone) are the main causes of pseudohyperaldosteronism. In these cases treatment with dexamethasone and/or MR-blockers is useful not only to normalize blood pressure and electrolytes, but also to prevent the deleterious effects of prolonged over-activation of MR in epithelial and non-epithelial tissues. Genetic alterations of the sodium channel (Liddle's syndrome) or of the sodium-chloride co-transporter (Gordon's syndrome) cause abnormal sodium and water reabsorption in the distal renal tubules and hypertension. Treatment with amiloride and thiazide diuretics can respectively reverse the clinical picture and the renin aldosterone system. Finally, many other more common situations can lead to an acquired pseudohyperaldosteronism, like the expansion of volume due to exaggerated water and/or sodium intake, and the use of drugs, as contraceptives, corticosteroids, β-adrenergic agonists and FANS. In conclusion, syndromes or situations that mimic aldosterone excess are not rare and an accurate personal and pharmacological history is mandatory for a correct diagnosis and avoiding unnecessary tests and mistreatments. PMID:27251484

  2. Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications

    PubMed Central

    Polizzi, Agata; Di Rosa, Gabriella; Romeo, Anna Claudia; Dipasquale, Valeria; Chirico, Valeria; Arrigo, Teresa; Ruggieri, Martino

    2014-01-01

    Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency) has been reported with neurological and magnetic resonance imaging (MRI) abnormalities (e.g., delayed myelination and brain atrophy) due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH), a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF) pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS) through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric) CNS seems to be particularly vulnerable to alterations induced by adrenal

  3. Effectiveness of Spironolactone Plus Ambrisentan for Treatment of Pulmonary Arterial Hypertension (from the [ARIES] Study 1 and 2 Trials)

    PubMed Central

    Maron, Bradley A.; Waxman, Aaron B.; Opotowsky, Alexander R.; Gillies, Hunter; Blair, Christiana; Aghamohammadzadeh, Reza; Loscalzo, Joseph; Leopold, Jane A.

    2014-01-01

    In translational models of pulmonary arterial hypertension (PAH), spironolactone improves cardiopulmonary hemodynamics by attenuating the adverse effects of hyperaldosteronism on endothelin type-B receptor function in pulmonary endothelial cells. This observation suggests that coupling spironolactone with inhibition of endothelin type-A receptor—mediated pulmonary vasoconstriction may be a useful treatment strategy for patients with PAH. We examined clinical data from patients randomized to placebo or the selective endothelin type-A receptor antagonist ambrisentan (10 mg/day) and in whom spironolactone use was reported during ARIES-1 and -2, which were randomized, double-blind, placebo-controlled trials assessing the effect of ambrisentan for 12 weeks on clinical outcome in PAH. From patients randomized to placebo (n = 132) or ambrisentan (n = 67), we identified concurrent spironolactone use in 21 (15.9%) and 10 (14.9%) patients, respectively. Compared with patients treated with ambrisentan alone (n = 57), therapy with ambrisentan D spironolactone improved change in 6-minute walk distance by 94% at week 12 (mean ± SE, +38.2 ± 8.1 vs +74.2 ± 27.4 m, p = 0.11), improved plasma B-type natriuretic peptide concentration by 1.7-fold (p = 0.08), and resulted in a 90% relative increase in the number of patients improving ≥1 World Health Organization functional class (p = 0.08). Progressive illness, PAH-associated hospitalizations, or death occurred as an end point for 5.3% of ambrisentan-treated patients; however, no patient treated with ambrisentan + spironolactone reached any of these end points. In conclusion, these pilot data suggest that coupling spironolactone and endothelin type-A receptor antagonism may be clinically beneficial in PAH. Prospective clinical trials are required to further characterize our findings. PMID:23751938

  4. Effectiveness of spironolactone plus ambrisentan for treatment of pulmonary arterial hypertension (from the [ARIES] study 1 and 2 trials).

    PubMed

    Maron, Bradley A; Waxman, Aaron B; Opotowsky, Alexander R; Gillies, Hunter; Blair, Christiana; Aghamohammadzadeh, Reza; Loscalzo, Joseph; Leopold, Jane A

    2013-09-01

    In translational models of pulmonary arterial hypertension (PAH), spironolactone improves cardiopulmonary hemodynamics by attenuating the adverse effects of hyperaldosteronism on endothelin type-B receptor function in pulmonary endothelial cells. This observation suggests that coupling spironolactone with inhibition of endothelin type-A receptor-mediated pulmonary vasoconstriction may be a useful treatment strategy for patients with PAH. We examined clinical data from patients randomized to placebo or the selective endothelin type-A receptor antagonist ambrisentan (10 mg/day) and in whom spironolactone use was reported during ARIES-1 and -2, which were randomized, double-blind, placebo-controlled trials assessing the effect of ambrisentan for 12 weeks on clinical outcome in PAH. From patients randomized to placebo (n = 132) or ambrisentan (n = 67), we identified concurrent spironolactone use in 21 (15.9%) and 10 (14.9%) patients, respectively. Compared with patients treated with ambrisentan alone (n = 57), therapy with ambrisentan + spironolactone improved change in 6-minute walk distance by 94% at week 12 (mean ± SE, +38.2 ± 8.1 vs +74.2 ± 27.4 m, p = 0.11), improved plasma B-type natriuretic peptide concentration by 1.7-fold (p = 0.08), and resulted in a 90% relative increase in the number of patients improving ≥1 World Health Organization functional class (p = 0.08). Progressive illness, PAH-associated hospitalizations, or death occurred as an end point for 5.3% of ambrisentan-treated patients; however, no patient treated with ambrisentan + spironolactone reached any of these end points. In conclusion, these pilot data suggest that coupling spironolactone and endothelin type-A receptor antagonism may be clinically beneficial in PAH. Prospective clinical trials are required to further characterize our findings. PMID:23751938

  5. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 5: Genetic diagnosis of primary aldosteronism.

    PubMed

    Zennaro, Maria-Christina; Jeunemaitre, Xavier

    2016-07-01

    While the majority of cases of primary aldosteronism (PA) are sporadic, four forms of autosomal-dominant inheritance have been described: familial hyperaldosteronism (FH) types I to IV. FH-I, also called glucocorticoid-remediable aldosteronism, is characterized by early and severe hypertension, usually before the age of 20 years. It is due to the formation of a chimeric gene between the adjacent CYP11B2 and CYP11B1 genes (coding for aldosterone synthase and 11β-hydroxylase, respectively). FH-I is often associated with family history of stroke before 40years of age. FH-II is clinically and biochemically indistinguishable from sporadic forms of PA and is only diagnosed on the basis of two or more affected family members. No causal genes have been identified so far and no genetic test is available. FH-III is characterized by severe and early-onset hypertension in children and young adults, resistant to treatment and associated with severe hypokalemia. Mild forms, resembling FH-II, have been described. FH-III is due to gain-of-function mutations in the KCNJ5 gene. Recently, a new autosomal-dominant form of familial PA, FH-IV, associated with mutations in the CACNA1H gene, was described in patients with hypertension and PA before the age of 10years. In rare cases, PA may be associated with complex neurologic disorder involving epileptic seizures and cerebral palsy (Primary Aldosteronism, Seizures, and Neurologic Abnormalities [PASNA]) due to de novo germline CACNA1D mutations. PMID:27315758

  6. Resistant hypertension with adrenal nodule: are we removing the right gland?

    PubMed Central

    Taylor, Peter N; Tabasum, Arshiya; Rao Bondugulapati, L N; Parker, Danny; Baglioni, Piero; Okosieme, Onyebuchi E; Scott Coombes, David

    2015-01-01

    hyperaldosteronism. Adrenal incidentalomas and UAH may coexist and the latter may often be the sole cause of excess aldosterone secretion. Decisions about adrenalectomy should be made only after integrating and interpreting radiological and biochemical test findings properly. PMID:26527194

  7. Inflammatory markers in primary aldosteronism.

    PubMed

    Šomlóová, Z; Petrák, O; Rosa, J; Štrauch, B; Indra, T; Zelinka, T; Haluzík, M; Zikán, V; Holaj, R; Widimský, J

    2016-06-20

    Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. The unfavorable cardiometabolic profile may be due to aldosterone-mediated activation of inflammatory cells, circulatory cytokines and activation of collagen synthesis in the vessel wall. Aim of our study was to evaluate differences in the levels of hsCRP, IL-6, TNF-alpha and N-terminal propeptide of collagen I (PINP) in patients with PA and essential hypertension (EH) as a control group, and between the subtypes of PA (aldosterone producing adenoma - APA, idiopathic hyperaldosteronism - IHA). We studied 28 patients with PA (IHA - 10 patients, APA - 12 patients, 6 unclassified) and 28 matched patients with EH. There were no differences in the levels of inflammatory markers between the followed groups [EH vs. PA: TNF-alpha (5.09 [3.68-6.32] vs. 4.84 [3.62-6.50] pg/ml), IL-6 (0.94 [0.70-1.13] vs. 0.97 [0.71-1.28] pg/ml), hsCRP (0.53 [0.25-1.54] vs. 0.37 [0.31-0.61] mg/l), leukocytes (6.35+/-1.42 vs. 5.97+/-1.29 10(9) l); APA vs. IHA: TNF-alpha (4.54 [3.62-7.03] vs. 5.19 [4.23-5.27] pg/ml), IL-6 (0.96 [0.63-1.21] vs. 0.90 [0.65-1.06] pg/ml), hsCRP (0.34 [0.29-0.47] vs. 0.75 [0.36-1.11] mg/l), leukocytes (6.37+/-1.41 vs. 5.71+/-1.21 10(9) l)]. Significant differences in the levels of PINP between PA and EH group were observed (35.18 [28.46-41.16] vs. 45.21 [36.95-62.81] microg/l, p

  8. Different effects of progesterone and estradiol on chimeric and wild type aldosterone synthase in vitro

    PubMed Central

    2013-01-01

    Background Familial hyperaldosteronism type I (FH-I) is caused by the unequal recombination between the 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, resulting in the generation of a CYP11B1/B2 chimeric gene and abnormal adrenal aldosterone production. Affected patients usually show severe hypertension and an elevated frequency of stroke at a young age. Aldosterone levels rise during pregnancy, yet in pregnant women with FH-1, their hypertensive condition either remains unchanged or may even improve. The purpose of this study was to investigate in vitro whether female sex steroids modulate the activity of chimeric (ASCE) or wild type (ASWT) aldosterone synthase enzymes. Methods We designed an in vitro assay using HEK-293 cell line transiently transfected with vectors containing the full ASCE or ASWT cDNAs. Progesterone or estradiol effects on AS enzyme activities were evaluated in transfected cells incubated with deoxycorticosterone (DOC) alone or DOC plus increasing doses of these steroids. Results In our in vitro model, both enzymes showed similar apparent kinetic parameters (Km = 1.191 microM and Vmax = 27.08 microM/24 h for ASCE and Km = 1.163 microM and Vmax = 36.98 microM/24 h for ASWT; p = ns, Mann–Whitney test). Progesterone inhibited aldosterone production by ASCE- and ASWT-transfected cells, while estradiol demonstrated no effect. Progesterone acted as a competitive inhibitor for both enzymes. Molecular modelling studies and binding affinity estimations indicate that progesterone might bind to the substrate site in both ASCE and ASWT, supporting the idea that this steroid could regulate these enzymatic activities and contribute to the decay of aldosterone synthase activity in chimeric gene-positive patients. Conclusions Our results show an inhibitory action of progesterone in the aldosterone synthesis by chimeric or wild type aldosterone synthase enzymes. This is a novel regulatory mechanism of progesterone

  9. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension.

    PubMed

    Aghamohammadzadeh, Reza; Zhang, Ying-Yi; Stephens, Thomas E; Arons, Elena; Zaman, Paula; Polach, Kevin J; Matar, Majed; Yung, Lai-Ming; Yu, Paul B; Bowman, Frederick P; Opotowsky, Alexander R; Waxman, Aaron B; Loscalzo, Joseph; Leopold, Jane A; Maron, Bradley A

    2016-07-01

    Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10(-9) to 10(-7) M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor-small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.-Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth