A case of aldosterone-producing adenoma with severe postoperative hyperkalemia.
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It is known that some patients with primary aldosteronism show postoperative hyperkalemia, which is due to inability of the adrenal gland to secrete sufficient amounts of aldosterone. However, hyperkalemia is generally neither severe nor prolonged, in which replacement therapy with mineralocorticoid is seldom necessary. We report a case of a 46-year-old woman with an aldosterone-producing adenoma associated with severe postoperative hyperkalemia. After unilateral adrenalectomy, the patient showed episodes of severe hyperkalemia for four months, which required not only cation-exchange resin, but also mineralocorticoid replacement. Plasma aldosterone concentration (PAC) was low, although PAC was increased after rapid ACTH test. Histological examination indicated the presence of adrenocortical tumor and paradoxical hyperplasia of zona glomerulosa in the adjacent adrenal. Immunohistochemistry demonstrated that the enzymes involved in aldosterone synthesis, such as cholesterol side chain cleavage (P-450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), and 21-hydroxylase (P-450c21), or the enzyme involved in glucocorticoid synthesis, 11beta-hydroxylase (P-450c11beta), were expressed in the tumor, but they were completely absent in zona glomerulosa of the adjacent adrenal. These findings were consistent with the patterns of primary aldosteronism. Serum potassium level was gradually decreased with concomitant increase in PAC. These results suggest that severe postoperative hyperkalemia of the present case was attributable to severe suppression of aldosterone synthesis in the adjacent and contralateral adrenal, which resulted in slow recovery of aldosterone secretion. It is plausible that aldosterone synthesis of adjacent and contralateral adrenal glands is severely impaired in some cases with primary aldosteronism, as glucocorticoid synthesis in Cushing syndrome. (+info)
Raised aldosterone to renin ratio predicts antihypertensive efficacy of spironolactone: a prospective cohort follow-up study.
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AIMS: Aldosterone/renin ratio is an index for inappropriate aldosterone activity, and it is increasingly being used to screen for primary aldosteronism within the hypertensive population. It may also be a good index to help predict the response to spironolactone. To assess the blood pressure response to oral spironolactone in hypertensive patients with primary aldosteronism identified with raised aldosterone to renin ratio. METHODS: We conducted a prospective cohort study of hypertensive patients with raised aldosterone/renin ratio, who failed to suppress plasma aldosterone with salt loading and fludrocortisone suppression test. These patients were treated with spironolactone and were followed-up for a period of up to 3 years. RESULTS: We studied 28 (12 male) subjects with a mean age of 55 (s.d. 10) years who were followed up for a mean period of 12.9 (7) months. At baseline, the patients were taking a mean of 2.1 (1.2) antihypertensive drugs, but despite this 16/28 (57%) had diastolic BP >90 mmHg, 39% with systolic BP >160 mmHg. After commencing spironolactone, three patients complained of breast tenderness but continued treatment and one patient was intolerant of spironolactone and had to stop treatment. Of the remaining 27 patients, the mean number of antihypertensive drugs used dropped to spironolactone plus 0.7 (s.d. 0.9). All but one patient (96%) achieved a diastolic BP+info)
Aldosterone synthase deficiency type I with no documented homozygous mutations in the CYP11B2 gene.
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This case report concerns a girl born from non-consanguineous parents and hospitalized in another hospital at the age of 14 days because of a severe salt-losing syndrome (Na=125, K=8.6 mEq/l). In spite of normal genitalia, diagnosis of 21-hydroxylase deficiency was assessed on the basis of a slightly increased 17-OH-progesterone serum level (6.4 ng/ml). The onset of both hydrocortisone and 9alpha-fluorohydrocortisone therapy was followed by a resolution of the clinical picture. At the age of 60 days she was admitted to our clinic for a re-evaluation of the diagnosis. Steroid hormone serum levels were measured after withdrawal of therapy and diagnosis of corticosterone methyl oxidase (CMO) deficiency type I was definitely established in the light of the biochemical results: i.e. very low 18-hydroxycorticosterone (18-OH-B) serum levels (20 pg/ml), an abnormally high corticosterone/18-OH-B serum ratio (306.5) and an abnormally low 18-OH-B/aldosterone serum ratio (2.1). This autosomal recessively inherited disorder can be differentiated from CMO type II and other salt-wasting syndromes only on the basis of the serum steroid hormone pattern. After establishing the diagnosis of CMO I deficiency, hydrocortisone therapy was withdrawn whilst treatment with 9alpha-fluorohydrocortisone was begun again, with a satisfactory clinical and metabolic impact. Direct sequences of the patient's DNA were able to identify only a (heterozygous) amino acid substitution in exon 7 of that gene, which is known to have only a small effect on enzyme activity and cannot be the only cause of the patient's phenotype: valine-386-alanine (V386A) GTG-->GcG. No homozygous mutations in the CYP11B2 gene were observed. This is the first report of a patient with CMO type I who does not carry any homozygous mutation in the entire CYP11B2 alleles, whereas some cases with no mutations in this gene have already been reported in CMO II. The present study seems to be inconsistent with the previously reported correlation of the phenotype and genotype in CMO type I. A reasonable question that might be raised on the basis of our findings in this case report is whether other genes, apart from CYP11B2, are involved in the regulation of terminal aldosterone synthesis. (+info)
Adverse cardiac effects of salt with fludrocortisone in hypertension.
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The effect of salt on blood pressure (BP) is controversial. A more important question is whether salt can produce cardiac target-organ damage, irrespective of its effect on BP. We assessed the effect of salt with fludrocortisone on QT dispersion and echocardiographic left ventricular diastolic function in a prospective interventional study involving 29 hypertensive subjects with a raised aldosterone/renin ratio who were hospitalized for investigation of possible primary aldosteronism. Each subject over 4 days was given a total of 28.8 g (480 mmol) of sodium chloride and 1.5 mg of fludrocortisone with potassium supplementation. Baseline and posttreatment 12-lead ECGs and echocardiograms were obtained. There were no significant changes in body weight, pulse rate, or BP after treatment with salt and fludrocortisone. Plasma sodium was significantly increased from 141.4 (SD 2.1) to 142.6 (SD 2.4) mmol/L (P:=0.001). QT and QTc dispersion both significantly increased: +19.6 (SD 16.5) ms (95% CI, 13.4 to 25.9) (P:<0.001) and +19.8 (SD 20.9) ms (95% CI, 11.8 to 27.7) (P:<0.001), respectively. There were no significant changes in (n=15) left ventricular dimensions or systolic function, but all diastolic filling indexes, including the preload-independent index, flow propagation velocity (55.49 [SD 10.91] to 48.96 [SD 11.40] cm/s, P:=0.018) worsened, suggesting significant deterioration of left ventricular diastolic function with salt and fludrocortisone. In conclusion, a combination of salt with fludrocortisone increased QT dispersion and impaired left ventricular diastolic relaxation in hypertensive patients with high aldosterone/renin ratios. This raises the possibility that salt may have BP-independent adverse cardiac effects in susceptible hypertensive subjects. (+info)
Endothelial cell dysfunction in mice after transgenic knockout of type 2, but not type 1, 11beta-hydroxysteroid dehydrogenase.
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BACKGROUND: 11beta-Hydroxysteroid dehydrogenase (11betaHSD) isozymes catalyze the interconversion of active and inactive glucocorticoids, allowing local regulation of corticosteroid receptor activation. Both are present in the vessel wall; here, using mice with selective inactivation of 11betaHSD isozymes, we test the hypothesis that 11betaHSDs influence vascular function. METHODS AND RESULTS: Thoracic aortas were obtained from weight-matched male wild-type (MF1x129 cross(+/+)), 11betaHSD1(-/-), and 11betaHSD2(-/-) mice. mRNA for both isozymes was detected in wild-type aortas by RT-PCR. 11betaHSD activity in aortic homogenates (48.81+/-4.65% conversion) was reduced in both 11betaHSD1(-/-) (6.36+/-2.47% conversion; P<0.0002) and 11betaHSD2(-/-) (24.71+/-3.69; P=0.002) mice. Functional responses were unaffected in aortic rings isolated from 11betaHSD1(-/-) mice. In contrast, aortas from 11betaHSD2(-/-) mice demonstrated selectively enhanced constriction to norepinephrine (E(max) 4.28+/-0.56 versus 1.72+/-0.47 mN/mm; P=0.004) attributable to impaired endothelium-derived nitric oxide activity. Relaxation responses to endothelium-dependent and -independent vasodilators were also impaired. To control for chronic renal mineralocorticoid excess, MF1 mice were treated with fludrocortisone (16 weeks) but did not reproduce the functional changes observed in 11betaHSD2(-/-) mice. CONCLUSIONS: Although both 11betaHSD isozymes are present in the vascular wall, reactivation of glucocorticoids by 11betaHSD1 does not influence aortic function. Mice with 11betaHSD2 knockout, however, have endothelial dysfunction causing enhanced norepinephrine-mediated contraction. This appears to be independent of renal sodium retention and may contribute to hypertension in 11betaHSD2 deficiency. (+info)
An inhibitor of sodium transport in the urine of dogs with normal renal function.
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The urine and serum of chronically uremic patients and dogs contain an inhibitor of sodium transport that reduces short-circuit current (SCC) in the toad bladder and produces natriuresis in the rat. The present studies represent an effort to determine whether the same inhibitor is detectable in urine of normal dogs maintained on a dosium intake varying from 3 to 258 meq/day. Observations were made with and without fludrocortisone. The same Sephadex G-25 gel filtration fraction previously shown to contain the "uremic" inhibitor was tested in both the isolated toad bladder and rat bioassay systems. The fraction from dogs maintained on 258 meq qodium plus 0.2 mg fludrocortisone/day consistently inhibited SCC in the toad bladder and induced a natriuresis in the rat (P less than 0.001). The fraction from dogs on the same sodium intake without fludrocortisone was also natriuretic (P less than 0.01) but did not inhibit SCC significantly. In contrast, the fraction from dogs fed 3 meq sodium with fludrocortisone or 91 meq sodium without fludrocortisone had no significant effect in either assay system. Thus, an inhibitor of sodium transport has been found in the urine of nonuremic dogs. Both the degree of natriuresis in the rat and the degree of inhibition of SCC in the toad bladder correlated with the state of sodium balance which ensued in the dog. (+info)
Longitudinal analysis of growth and puberty in 21-hydroxylase deficiency patients.
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AIMS: To evaluate growth from diagnosis until final height (FH) in 21-hydroxylase deficiency patients. METHODS: A retrospective longitudinal study was performed. Only patients treated with hydrocortisone and fludrocortisone (in case of salt wasting) were evaluated. This resulted in a sample of 34 (21 male, 13 female) salt wasting patients (SW) and 26 (13 male, 13 female) non-salt wasting patients (NSW). Auxological data were compared to recent Dutch reference values. RESULTS: In the first three months of life, the mean length SDS decreased to -1.50, probably because of the high average glucocorticoid dose (40 mg/m2/day). FH corrected for target height (FH(corr)TH) was -1.25 and -1.27 SDS in females and males, respectively. Patients treated with salt supplements during the first year, had a better FH(corr)TH (-0.83 SDS). In NSW patients, FH(corr)TH was -0.96 and -1.51 SDS in females and males, respectively. In SW and NSW, age at onset of puberty was within normal limits, but bone age was advanced. Mean pubertal height gain was reduced in males. Body mass index was only increased in NSW females. CONCLUSION: In SW, loss of final height potential might be a result of glucocorticoid excess in the first three months and sodium depletion during infancy. In NSW, loss of FH potential was caused by the delay in diagnosis. In SW and NSW, the advanced bone age at onset of puberty (undertreatment in prebertal years) resulted in loss of height gain during puberty. The effect of intensive sodium chloride support in early infancy should be examined prospectively. Neonatal screening is required if the height prognosis in NSW patients is to be improved. (+info)
Yoghurt biotherapy: contraindicated in immunosuppressed patients?
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A fatal case of Lactobacillus rhamnosus septicaemia after prolonged oral vancomycin for recalcitrant Clostridium difficile infection is reported. The patient was immunosuppressed with cyclophosphamide and steroids for Sjogren's syndrome. The administration of Lactobacillus spp as "biotherapy" may be hazardous in such circumstances. (+info)