Corticosterone Methyl Oxidase Deficiency Type 1 with Normokalemia in an Infant.

Isolated aldosterone synthase deficiency may result in life-threatening salt-wasting and failure to thrive. The condition involves hyperkalemia accompanying hyponatremia. Two types of aldosterone synthase deficiency may be observed depending on hormone levels: corticosterone methyl oxidase type 1 (CMO 1) and CMO 2. Herein, we describe a Turkish infant patient with aldosterone synthase deficiency who presented with failure to thrive and salt wasting but with normal potassium levels. Urinary steroid characteristics were compatible with CMO I deficiency. Diagnosis of aldosterone synthase deficiency was confirmed by mutational analysis of the CYP11B2 gene which identified the patient as homozygous for two mutations: c.788T>A (p.Ile263Asn) and c.1157T>C (p.Val386Ala). Family genetic study revealed that the mother was heterozygous for c.788T>A and homozygous for c.1157T>C and the father was heterozygous for both c.788T>A and c.1157T>C. To the best of our knowledge, this is only the second Turkish case with a confirmed molecular basis of type 1 aldosterone synthase deficiency. This case is also significant in showing that spot urinary steroid analysis can assist with the diagnosis and that hyperkalemia is not necessarily part of the disease.

Persistent hyperkalaemia.

BACKGROUND: Persistent hyperkalaemia in elderly patients caused by hyporeninaemic hypoaldosteronism is relatively common and often under recognised in the general practice setting. OBJECTIVE: This article highlights the importance of suspecting hyporeninaemic hypoaldosteronism in any elderly patient with persistent hyperkalaemia and provides an outline of investigation and management of the condition. DISCUSSION: Elderly patients with persistent hyperkalaemia may have hyporeninaemic hypoaldosteronism. The diagnosis is made by calculating the transtubular potassium concentration gradient, and then measuring the serum aldosterone level. Hyporeninaemic hypoaldosteronism is managed with a low potassium diet and a low dose loop or thiazide diuretic.

Utilidad del laboratorio clínico en la evaluación del sistema renina-angiotensin-aldosterona / Utility of the clinical laboratory in the evaluation of renin-angiotensin-aldosterone system

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A 12-lipoxygenase product, 12-hydroxyeicosatetraenoic acid, is increased in diabetics with incipient and early renal disease.

Earlier studies in diabetic animal models or ex vivo from diabetics suggest a deficiency in prostacyclin (PGI2) production and an increase in an alternate arachidonic acid metabolite, 12-hydroxyeicosatetraenoic acid (12-HETE), which stimulates angiogenesis, mitogenesis, and inhibits renin secretion. We studied the urinary excretion rate of 6-keto-PGF1 alpha (a stable metabolite of PGI2) and 12-HETE in controls and 42 noninsulin-dependent diabetes mellitus (NIDDM) patients with normal renal function and those with micro- or macroalbuminuria/hyporeninemic hypoaldosteronism (HH). The 2 eicosanoids were measured in urine using previously described high pressure liquid chromatography and RIA methods. Normal subjects and patients with NIDDM and microalbuminuria were infused with low dose calcium infusions that stimulate prostacyclin production in normal subjects. The PGI2 excretion rate of NIDDM patients with normal renal function was not different from that of controls (143 +/- 17 vs. 118 +/- 34 ng/g creatinine), but was reduced in those with microalbuminuria (75 +/- 10) and in macroalbuminuria patients (48 +/- 7; P < 0.01). In contrast, 12-HETE was increased in diabetics with normal renal function as well as in those with micro- or macroalbuminuria patients (69 +/- 18 vs. 250 +/- 62 vs. 226 +/- 60 and 404 +/- 131 ng/g creatinine; P < 0.01). Calcium did not stimulate PGI2, but increased 12-HETE in diabetics with microalbuminuria in contrast to levels in normal subjects. HH patients excreted less PGI2 (as previously reported), but had increased 12-HETE. HETE/PGI2 ratios further demonstrated these changes in the various groups. In a nondiabetic hypertensive microalbuminuria group, 12-HETE excretion was normal (73 +/- 28 ng/g creatinine). We conclude that the lipoxygenase product 12-HETE is increased early in the diabetic process, whereas PGI2 production is progressively impaired in NIDDM. These changes may play a role in the vascular disease of diabetes and partially explain the HH syndrome.

Urinary prostaglandins (PGE2 and PGI2) in hyporeninaemic hypoaldosteronism in diabetic patients with chronic renal failure.

The present work studies the urinary excretion of PGE2 and PGI2 (6-keto PGF 1 alpha) in 11 insulin-dependent diabetic patients with chronic renal failure with a glomerular filtration rate of 33.9 +/- 9.03 ml/min who had hyporeninaemic hypoaldosteronism to evaluate the influence of these prostaglandins on the appearance of this latter process. The results obtained in this group of patients were compared with those of a control group of healthy individuals, another group of nine non-diabetic patients with CRF, and a last group of eight insulin-dependent diabetic patients with normal renal function to evaluate to what extent the possible variations in prostaglandin excretion could be related to the diabetes, CRF, or a conjunction of both processes. The results of the groups of diabetic patients with CRF were Ccr 33.9 +/- 9.03 ml/min, decreased (P < 0.0001) with respect to the control group and with no difference with the CRF group without diabetes; plasma potassium (4.7 +/- 0.4 mEq/l), increased (P < 0.005) with respect to the values found in the control group; plasma bicarbonate (17.8 +/- 1.8 mEq/l), decreased (P < 0.005) with respect to the control group and also, though not significantly, with respect to the group of non-diabetic patients with CRF. Plasma aldosterone (pg/ml): resting 44.3 +/- 14.9; standing 65.7 +/- 63.5 and post-frusemide 65.5 +/- 58.6, decreased (P < 0.01) with respect to the other three groups. Plasma renin activity (PRA) (ng/ml/h): resting 0.34 +/- 0.3; standing 0.6 +/- 0.4, post-frusemide 0.9 +/- 0.5, decreased significantly with respect to the other three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis.

We evaluated the use of the urinary anion gap (sodium plus potassium minus chloride) in assessing hyperchloremic metabolic acidosis in 38 patients with altered distal urinary acidification and in 8 patients with diarrhea. In seven normal subjects given ammonium chloride for three days, the anion gap was negative (-27 +/- 9.8 mmol per liter) and the urinary pH under 5.3 (4.9 +/- 0.03). In the eight patients with diarrhea the anion gap was also negative (-20 +/- 5.7 mmol per liter), even though the urinary pH was above 5.3 (5.64 +/- 0.14). In contrast, the anion gap was positive in all patients with altered urinary acidification, who were classified as having classic renal tubular acidosis (23 +/- 4.1 mmol per liter, 11 patients), hyperkalemic distal renal tubular acidosis (30 +/- 4.2, 12 patients), or selective aldosterone deficiency (39 +/- 4.2, 15 patients). When the data on all subjects studied were pooled, a negative correlation was found between the urinary ammonium level and the urinary anion gap. We conclude that the use of the urinary anion gap, as a rough index of urinary ammonium, may be helpful in the initial evaluation of hyperchloremic metabolic acidosis. A negative anion gap suggests gastrointestinal loss of bicarbonate, whereas a positive anion gap suggests the presence of altered distal urinary acidification.