1/4. Transient pseudo-hypoaldosteronism following resection of the ileum: normal level of lymphocytic aldosterone receptors outside the acute phase.Pseudo-hypoaldosteronism (PHA) is due to mineralocorticoid resistance and manifests as hyponatremia and hyperkalemia with increased plasma aldosterone levels. It may be familial or secondary to abnormal renal sodium handling. We report the case of a 54-year-old woman with multifocal cancer of the colon, who developed PHA after subtotal colectomy, ileal resection and jejunostomy. She was treated with 6 g of salt daily to prevent dehydration, which she stopped herself because of reduced fecal losses. One month later she was admitted with signs of acute adrenal failure, i.e. fatigue, severe nausea, blood pressure of 80/60 mmHg, extracellular dehydration, hyponatremia (118 mmol/l); hyperkalemia (7.6 mmol/l), increased blood urea nitrogen (BUN) (200 mg/dl) and creatininemia (2.5 mg/dl), and decreased plasma bicarbonates level (HCO3-: 16 mmol/l; N: 27-30). However, the plasma cortisol was high (66 microg/100 ml at 10:00 h; N: 8-15) and the ACTH was normal (13 pg/ml, N: 10-60); there was a marked increase in plasma renin activity (>37 ng/ml/h; N supine <3), active renin (869 pg/ml; N supine: 1.120), aldosterone (>2000 pg/ml; N supine <150) and plasma AVP (20 pmol/l; N: 0.5-2.5). The plasma ANH level was 38 pmol/l (N supine: 5-25). A urinary steroidogram resulted in highly elevated tetrahydrocortisol (THF: 13.3 mg/24h; N: 1.4 /-0.8) with no increase in tetrahydrocortisone (THE: 3.16 mg/24h; N: 2.7 /-2.0) excretion, and with low THE/THF (0.24; N: 1.87 /-0.36) and alpha THF/THF (0.35; N: 0.92 /-0.42) ratios. The number of mineralocorticoid receptors in mononuclear leukocytes was in the lower normal range for age, while the number of glucocorticoid receptors was reduced. Small-bowel resection in ileostomized patients causes excessive fecal sodium losses and results in chronic sodium depletion with contraction of the plasma volume and severe secondary hyperaldosteronism. Nevertheless, this hyperaldosteronism may be associated with hyponatremia and hyperkalemia suggesting PHA related to the major importance of the colon for the absorption of sodium. In conclusion, this case report emphasizes 1) the possibility of a syndrome of acquired PHA with severe hyperkalemia after resection of the ileum and colon responding to oral salt supplementation; 2) the major increase in AVP and the small increase in ANH; 3) the strong increase in urinary THF with low THE/THF and alpha THF/THF ratios; 4) the normal number of lymphocytic mineralocorticoid receptors outside the acute episode.- - - - - - - - - - ranking = 1keywords = hyperaldosteronism (Clic here for more details about this article) |
2/4. Heterozygous mutations of the gene for Kir 1.1 (ROMK) in antenatal bartter syndrome presenting with transient hyperkalemia, evolving to a benign course.Bartter-like syndrome encompasses a set of inherited renal tubular disorders associated with hypokalemic metabolic alkalosis, renal salt wasting, hyperreninemic hyperaldosteronism, and normal blood pressure. Antenatal bartter syndrome, a subtype of Bartter-like syndrome, is characterized by polyhydramnios, premature delivery, life-threatening episodes of fever and dehydration during the early weeks of life, growth retardation, hypercalciuria, and early-onset nephrocalcinosis. Mutations in the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) and ATP-sensitive inwardly rectifying potassium channel (ROMK) of the thick ascending limb of Henle's loop have been identified in the antenatal bartter syndrome. We report the identification of two heterozygous mutations of the gene for Kir 1.1 (ROMK) from an antenatal bartter syndrome patient who presented at birth with mild salt wasting and a biochemical findings that mimicked primary pseudohypoaldosteronism type 1, such as hyperkalemia and hyponatremia, and evolved to a relatively benign course. We have identified amino acid exchanges Arg338Stop and Met357Thr in the gene exon 5 for ROMK by PCR and direct sequencing. Both mutations alter the C-terminus of the ROMK protein, and can affect channel function.- - - - - - - - - - ranking = 0.5keywords = hyperaldosteronism (Clic here for more details about this article) |
3/4. Erythrocyte transmembrane Na and K fluxes in pseudohypoaldosteronism.pseudohypoaldosteronism (PHA) is a disease characterized by hyponatremia, hypotension, and dehydratation, despite the presence of hyperreninemic hyperaldosteronism. The membrane-bound Na,K ATPase activity and the transmembrane Na and K transport systems have been studied in vitro in red blood cells of two subjects, son and mother, affected by pseudohypoaldosteronism with different degrees of clinical involvement. Both parameters were significantly altered suggesting that the refractory response to mineralocorticoids is detectable, not only in kidneys and salivary and sweat glands, but also in red blood cells. Since pseudohypoaldosteronism, in its asymptomatic form, may be much more common than expected, we suggest the use of the tests described herein as a practical approach to the early diagnosis of pseudohypoaldosteronism in the investigation of sodium wasting syndromes.- - - - - - - - - - ranking = 0.5keywords = hyperaldosteronism (Clic here for more details about this article) |
4/4. Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects.Type I pseudohypoaldosteronism (PHA) is a hereditary disease characterized by salt wasting resulting from target organ unresponsiveness to mineralocorticoids. We have studied two kindreds including a total of nine patients with PHA. In kindred I, the propositus presented with renal salt wasting in infancy (vomiting, failure to thrive, short stature, hyponatremia, hyperkalemia) and responded dramatically to a high salt diet (2.5 g/day). sodium supplementation was discontinued at the age of two. In seven additional family members from three generations, clinical expression of PHA varied from asymptomatic to moderate. In affected members (propositus, mother, and two brothers), hyperaldosteronism persisted over 13 yr; however, the PRA decreased gradually to near normal values. Persistent hyperaldosteronism in the face of a decrease in PRA indicated the development of tertiary hyperaldosteronism due to autonomously functioning zona glomerulosa. The pedigree was consistent with an autosomal dominant mode of transmission with variable expression. In kindred II, the propositus, who was the product of a consanguineous marriage, developed severe renal salt losing at age 9 days. She had also increased salivary and sweat electrolytes consistent with PHA resulting from multiple organ unresponsiveness to mineralocorticoids. life threatening episodes of salt wasting recurred beyond the age of 2 yr. At 5 yr of age she still requires high amounts of salt supplements (14 g/day). A sister died at 9 days of age with PHA symptoms. Six close relatives (parents, three siblings, maternal uncle) showed no biochemical abnormalities. This pedigree was consistent with an autosomal recessive mode of inheritance. In view of the findings on these two kindreds and the analysis of those in the literature, we conclude that type I PHA includes two clinically and genetically distinct entities with either renal or multiple target organ defects.- - - - - - - - - - ranking = 1.5keywords = hyperaldosteronism (Clic here for more details about this article) |