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37 year-old man presented to our clinic because of tetany that occurred during driving a car in the morning. He had no anorexia, chronic diarrhea or vomiting. He was normotensive and no edema was noted. On neurological examination, he was rather apprehensive and Trousseau sign was mildly positive. No muscle weakness was noted except for the moderate atrophies of bilateral anterior tibial muscles as a sequela of Guillain-Barré syndrome that he suffered at the age of 7. The results of laboratory studies included hypokalemia, metabolic alkalosis, hyperuricemia, increased plasma renin activity, increased plasma aldosterone concentration, reduced pressor response to infusion of angiotensin II. Based on these clinical and laboratory findings, the diagnosis of Bartter's syndrome was made. As far as we know, it is extremely rare that Bartter's syndrome manifests tetany alone as in the present case. The exacerbation of preexisting alkalosis by hyperventilation during driving might be the cause of tetany. Tetany was easily provoked by hyperventilation, during which serum ionized calcium remained in normal level despite the exacerbation of alkalosis. The results suggest that alkalosis per se can cause tetany in Bartter's syndrome. Indomethacin, 75 mg daily, effectively prevented tetany from recurring for nearly 4 years without any side effect.

This report deals with three cases of Bartter's syndrome whose symptomatology was associated with indirect hyperbilirubinemia. The bilirubin disorder was suggestive of Gilbert's syndrome, with no pathological findings being detected as far as the liver function was concerned. Furthermore, the unconjugated fraction of bilirubin increased after fasting. The therapy with indomethacin exerted beneficial effects on both electrolytes and bilirubin disorders, and the patients recovered a good healthy state. These findings suggest the possibility that Bartter's syndrome may coexist in a variety associated with indirect hyperbilirubinemia.

A 34-year-old female complaining of numbness and weakness of the extremities was examined. Consanguineous marriage was contracted between mother and father. She was of short stature (149 cm), and her blood pressure was normal (118/60 mmHg). Her serum potassium concentration had decreased to a level between 2.5 and 3.2 mEq/L, and hypokalemic alkalosis was present. Potassium clearance had increased and urinary concentrating capacity was impaired. Plasma renin activity was high at 25 ng/ml/hr but plasma aldosterone concentration was normal. Hypertensive response to angiotensin II (50 ng/kg/min) was weak but improved to nearly the normal value after the administration of indomethacin for 17 days at a dose of 50 mg/day. A slight elevation in blood pressure was observed during the infusion of norepinephrine (250 ng/kg/min). A decrease in blood pressure was observed during the infusion of 1-sarcosine, 8-isoleucine angiotensin II (600 ng/kg/min) with concomitant increase of plasma renin activity. Twenty-four hour urinary excretion of prostaglandin E decreased somewhat (225 approximately 252 ng/day), and hyperplasia of the juxtaglomerular cells and increased JG index were demonstrated in the biopsy specimens of the right kidney. From the findings, the present case were diagnosed as Bartter's syndrome. Although mild enlargement of the sella turcica was found in skull x-ray films, no abnormalities in pituitary function were demonstrated. Other unusual complications, i.e. hyperlipidemia (type II, beta-dominant) and abnormal configuration of peripheral erythrocytes, were demonstrated. Phospholipid composition of the erythrocyte membrane was normal. The fluidity of plasma VLDL examined by electron spin resonance was increased. Hypokalemia and hyperreninemia were improved through the administration of indomethacin. However, because of headache as an adverse effect, further administration could not be accepted. The patient's complaints were resolved by the rectal application of indomethacin with oral administrations of spironolactone and triamterene. Changes in serum lipid levels did not occur with the above mentioned treatment. alpha-tocopheryl nicotinate lowered the levels of serum lipids and normalized the configuration of peripheral erythrocytes. But increased fluidity of plasma VLDL remained, and phospholipid composition of erythrocyte membrane was also unchanged. The relationship between the rare complications mentioned above and the pathophysiology of Bartter's syndrome is still obscure.

Seventy-seven patients with nephrocalcinosis as revealed by X-ray studies over a 10-year period are reviewed. A programmed clinical and metabolic study was performed on each case; the author's criteria included the different pathogenic factors considered in the etiologic definition of the disease. There were 22 cases with primary hyperparathyroidism, 19 with spongy kidney, nine with tubulointerstitial nephropathy, five with hyperoxaluria, five with distal renal tubular acidosis, four with esential hypomagnesemia, and three cases of miscellaneous etiology (vitamin D intoxication, Fanconi's syndrome, Bartter's disease). Ten other cases were classified as idiopathic nephrocalcinosis since no definite cause could be found. The clinical characteristics (symptoms, associated diseases, diet and medication intake, family history) and the biochemical findings are analysed for each group. The physiopathologic mechanisms, comparisons between each etiologic group, treatment, clinical course, and prognosis are commented on. The conclusion drawn is that nephrocalcinosis is a clinical syndrome of various etiologies which in most cases arises from an underlying metabolic disease.

A 24-yr-old male patient that suffered from chronic tetany since school age. At the age of 20 tetanic convulsions occurred due to hypocalcemia. His mother also had chronic tetany due to pseudohypoparathyroidism. At the age of 24, hypocalcemia caused by pseudohypoparathyroidism was noted. Hypopotassemia persisted even when the hypocalcemia improved with the administration of 1 alpha-hydroxycholecalciferol and calcium lactate. Other findings were normal blood pressure, high levels of plasma renin activity and serum aldosterone, a fall in blood pressure after angiotensin II antagonist infusion, blunted pressor response to angiotensin II infusion and hyperplasia of the juxtaglomerular cells. These results were compatible with Bartter's syndrome. Plasma prostaglandins E2 and F2 alpha in standing position were suppressed after indomethacin administration. To our knowledge this is thought to be the first report of a case of pseudohypoparathyroidism associated with probable Bartter's syndrome.

The relationship between renal prostaglandins (PG) and electrolyte transport in the thick ascending limb of Henle's loop (TALH) was examined in 8 normal subjects and in 7 patients with hypokalemia, the latter including 4 cases of Bartter's syndrome. Distal fractional delivery and distal reabsorption of chloride and sodium were determined using clearance techniques under maximal volume expansion, and urinary excretion rates of PGE2 and PGF2 alpha were measured. In the normal subjects, suppression of PG synthesis by indomethacin decreased distal delivery without changing distal reabsorption, suggesting that PG may influence solute transport at a site proximal to the diluting segment. In the subjects with Bartter's syndrome, however, distal reabsorption was impaired, this defect being apparently independent of PG as it was unaffected by inhibition of PG synthesis. In the patients with hypokalemia due to non-renal causes, distal reabsorption of chloride was increased, resulting in a decreased chloride clearance. These results suggest a link between renal PG and solute transport in normal man and also provide evidence that Bartter's syndrome is characterized by a prostaglandin-independent defect in distal reabsorption which is not found in hypokalemia due to other causes.

A 5.5-month-old male infant with hypokalaemia and gall bladder dilatation is reported. The child was shown to have Bartter syndrome. After oral treatment with potassium and indomethacin, serum potassium levels became low normal and the gall bladder enlargement resolved. This entity should be included in the clinical spectrum of neuromuscular disturbances resulting from hypokalaemia and should be considered in a hypokalaemic infant with a right-sided abdominal mass.

A case of an adult with Bartter's syndrome (hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis) is described; the patient had the unusual manifestation of cardiomyopathy, probably secondary to severe hypokalemia. Results of metabolic studies and kidney biopsy were consistent with Bartter's syndrome; angiographic and hemodynamic findings were abnormal. The cardiomyopathy was confirmed at autopsy after the patient's sudden death. Conclusions from this case are that severe hypokalemia can pose a serious threat both immediately in the form of dangerous arrhythmias and in the long term in the form of cardiomyopathy.

The case of a woman with recurrent hydramnios in three pregnancies, from which the only surviving infant was later found to have Bartter's syndrome, is described. Analysis of electrolytes, renin activity, and aldosterone levels in amniotic fluid from this pregnancy are presented. The finding of maternal hydramnios in the present and 12 other reported cases of Bartter's syndrome suggests that increased fetal voiding is the most likely causative factor in the development of increased amniotic fluid volume. Early onset hydramnios might signify Bartter's syndrome in the offspring in families with an index case. In cases of hydramnios of unknown etiology, appropriate investigations might lead to early diagnosis and treatment of Bartter's syndrome.

In 2 adult patients with Bartter's syndrome, in whom chloride reabsorption at the diluting segment of the nephron was markedly reduced, serum potassium concentration could be improved with oral administration of a large amount of potassium chloride. In both cases, improvement of serum potassium levels with oral potassium load resulted in an increase in plasma renin activity (PRA) and plasma aldosterone concentration (PAC), a decrease in urinary excretion of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha), and an improvement of pressor responsiveness to angiotensin II and norepinephrine. Treatment with indomethacin also improved the pressor responsiveness to angiotensin II and norepinephrine, but this occurred in association with a decrease in PRA, PAC and urinary excretion of PGE2 and PGF2 alpha. These results indicated that an event at the renal tubular level leading to potassium depletion is the most proximal pathogenetic defect in Bartter's syndrome, and that this in turn contributes to excessive prostaglandin production leading further to the decreased pressor responsiveness to vasoactive substances.

A prevalence of hyperuricemia of 50% and of acute gouty arthritis of 20% has been observed in a group of patients with Bartter's syndrome. All patients except one presented initially with complaints unrelated to uric acid metabolism. The cause of their hyperuricemia and subnormal clearance of uric acid is unexplained. Systemic alkalosis, a prominent feature of Bartter's syndrome, can decrease the clearance of uric acid and may contribute to the hyperuricemia and gout that have been observed. Physicians should be aware of the possibility of gout as a clinical complication of Bartter's syndrome and of the inhibitory effects of alkalosis on urate clearance.

The authors report two cases of the articular chondrocalcinosis associated with a laboratory profile compatible with Bartter's syndrome and masked diuretic intoxication in 2 women aged 31 and 59 years. An extensive study of the literature revealed 7 similar cases. The pathogenic relationship between the two conditions could be the hypomagnesemia. 5 other reports concerning young patients presenting the association of chondrocalcinosis and hypomagnesemia, not part of Bartter's syndrome, add further support to this hypothesis. This study suggests that the serum electrolytes and the serum magnesium should be assayed routinely in cases of chondrocalcinosis, especially in young patients.

Six interrelated abnormalities of Bartter's syndrome are analyzed-juxtaglomerular hyperplasia, angiotensin resistance, altered kallikrein-kinin system, hyperprostaglandinuria, hypokalemia, and chloride-losing nephropathy. Arguments are advanced that any one of these could be the proximate cause and result in all the others. By the same token, each abnormality could be a consequence of any of the others and, furthermore, modulate the others by negative or positive feedback. Despite many recent insights, available data do not permit a definitive conclusion as to the locus of the primary abnormality. Rather, the syndrome presents as a remarkable biological counterpart to an electronic integrated circuit. The altered physiology of Bartter's syndrome is reviewed and the pathogenesis of the syndrome analyzed in the light of recent literature.

A case of pseudo-Bartter's syndrome associated with hypokalemic myopathy was presented. A 37-year-old housewife was admitted to our hospital because of muscle cramps with muscle weakness and tetany. There was a history of facial edema and constipation, which have been managed with "Kanpo medicine (Chinese medicine)" and laxatives for several years. The patient was amenorrhea 3 months before entry. She began to experience muscle weakness and muscle cramps associated with gait disturbance 2 or 3 months before admission. On physical examination, she was thin with positive Trousseau's and Chvostek's signs. Laboratory studies revealed hypokalemia, low urinary excretion of potassium, hypocalcemia, metabolic alkalosis, elevated creatine phosphokinase (CPK), increased levels of plasma renin activity and plasma aldosterone concentration, and decreased sensitivity to pressor effect of angiotensin II. Potassium supplementation resulted in restoration of her symptoms and normalization of low serum calcium and elevated CPK levels. She was diagnosed to be pseudo-Bartter's syndrome due to anorexia nervosa. The mechanism(s) of hypokalemia in our case was discussed.

In an 18-year-old boy with Bartter's syndrome, hypophosphatemia was discovered (2.4 mg/100 ml) with normal serum calcium concentration (9.7 mg/100 ml) and elevated alkaline phosphatase level: 528 mU/ml (normal less than or equal to 150). Skeleton X-rays showed osteomalacia on the pelvic bones and metaphyseal rickets on the wrists. Plasma 25-hydroxycholecalciferol (25-OHCC) concentration was 7.2 ng/ml (normal = 13 +/- 4.4), and serum immunoreactive parathyroid hormone (iPTH) concentration 160 micron1Eq/ml (normal less than or equal to 150). Ca infusion (1500 mg/m2/12 h) induced an increase in serum P level to 3.2 mg/100 ml, in tubular phosphate reabsorption from 72 to 90%, while serum iPTH decreased to 33 micron1Eq/ml. Vitamin D2 administration (45 mg) resulted in increased 25-OHCC concentration to 28 ng/ml and in healing of pelvic osteomalacia. However, there was little change of the radiological aspect of the wrist and of serum phosphorus and iPTH concentrations. In a control 6-year-old hypokalemic girl, administration of parathyroid hormone (8 USP/kg) produced a marked phosphaturic response and an increase in urinary cyclic AMP excretion. These data suggest that hypophosphatemia can be attributed to secondary hyperparathyroidism in the patient with Bartter's syndrome. Hypokalemia does not impair the renal activity of parathyroid hormone.

A description is given of a girl with the non-salt-losing type of congenital adrenal hyperplasia (CAH) and with Bartter's syndrome. In addition, the patient had a balanced translocation between 6q and 9p. Although the possibility cannot be ruled out fully that an excess of progesterone might modify the renin-aldosterone axis to some extent, the finding that dexamethasone therapy improved the clinical features of CAH but failed to correct metabolic disorders in electrolyte balance strongly suggests the coexistence of the two clinical entities. Chloride transport at the distal tubule was impaired moderately in the patient, which suggests that her defective reabsorption of chloride was responsible for the impaired renal handling of sodium that is often observed in patients with Bartter's syndrome. It appears that the reciprocal translocation is unrelated to both CAH and Bartter's syndrome since the same translocation was found in her healthy mother and siblings.

A case of early onset Bartter's syndrome associated with hydramnios, prematurity, hypercalciuria and nephrocalcinosis is reported. A literature review of Bartter's syndrome supports the hypothesis that the findings in this infant constitute a specific variant of Bartter's syndrome inherited in an autosomal recessive mode. Fetal polyuria in Bartter's syndrome leads to hydramnios, and the excess fluid causes premature birth. This variant of Bartter's syndrome should be included in the differential diagnosis of hydramnios, especially if the woman has had previous hydramnios resulting in a perinatal death. The disorder responds to treatment with indomethacin.

The present authors observed and treated a siblings case of normocalcemic tetany, which is considered as belonging to Bartter's syndrome. As far as we know, there are a number of familial cases of tetany in literature, but none of them spreads over more than two generations, so that the tetany appears to be recessive in hereditary characters including our patients. Both of them presented tetanic seizures in the course of Bartter's syndrome and they were regarded as one of various manifestations of the syndrome. In other words, the Bartter's syndrome or the hypopotassemia should be one of the fundamental disorders for developing tetanic symptom. The tetanic symptoms became extinct during the treatment with spironolactone against hypopotassemia. Of the two patients, younger sister had shown an agitated depression developed on her childish and over-sensitive personality, but the depression was improved in parallel to the recovery from tetany and hypopotassemia. Therefore, it appears to be certain that the patients would have some premorbid deviation of personality traits, where symptomatic psychoses could be attributed, in the case of Bartter's syndrome. Generally speaking the psychic disorders, such as personality deviation and psychotic episode, seem to by very important symptoms in patient with Bartter's syndrome as well as in patient with hypocalcemia or hypoparathyroidism.

A case of maternal Bartter's syndrome is reported and prenatal management discussed. Close monitoring of serum potassium levels is essential. Patients with this syndrome may have an increased risk of developing intrauterine growth retardation.

A new case of association between Bartter's syndrome and chondrocalcinosis is reported. The patient was shown to have marked hypomagnesemia. Indomethacin and magnesium therapy was started and resulted in increased magnesemia, even if it did not reach normal levels. There was complete remission of articular symptoms and no progression on the radiological picture after 2 years of continuous magnesium and indomethacin therapy. The 7 available family members were studied to assess the possible presence of a familial form of chondrocalcinosis and/or hypomagnesemia. The literature is reviewed and reports of previously described associations between Bartter's syndrome and chondrocalcinosis are summarized. The possible role of hypomagnesemia in predisposing to deposition of calcium pyrophosphate dihydrate crystal in cartilagine is also discussed.

Studies on the growth and development of patients with Bartter's syndrome indicate that severe growth retardation occurs during infancy and early childhood. Delayed adolescent growth spurt has occurred in all patients studied thus far who had manifested the syndrome during infancy. Normal stature is eventually attained. Mental development ranges from normal to brain damage and dysfunction; however, the majority of patients show some degree of mental retardation. The coexistence of Leigh's encephalopathy with Bartter's syndrome in one patient and the finding of severe motor and congnitive retardation with communicating hydrocephalus in another indicate that the prognosis of mental development in some cases of Bartter's syndrome is guarded. Particular attention should be given to maintaining normal nutritional status in all patients, particularly during infancy and early childhood.

A new case of Bartter's syndrome is described. There is a context of other cases of familial renal tubular disease with a sex-linked heredity. In this case, the Bartter's syndrome is associated with magnesium deficiency and hypomagnesemia, with a ricket and severe phosphate deficiency, and finally with an hypercorticism. The basal secretion rate of cortisol agree with a Cushing's syndrome. This hypercorticism is corrected by aminogluthetimide. The influence of the hyperreninism on the hypercorticism is discussed.

In 1962 Bartter et al. described a clinical syndrome characterized by growth and mental retardation, hypokalemic alkalosis, increased aldosterone secretion rate and increased plasma angiotensin II concentration in the presence of normal blood pressure. The inheritance pattern has been reported as autosomal recessive or as sporadic. Since that time 37 cases have been reported in pediatric age, describing a wide spectrum of clinical and biochemical features. For the diagnosis the following criteria must be present: hypokalemia, hypochloremia, alkalosis, hyperreninemia in the presence of a normal blood pressure and elevated urinary K and Cl excretion, in the absence of other conditions that might cause similar features. A case of Bartter's disease is herein reported with our experience in the diagnosis, treatment and follow-up.

In two cases of Bartter's syndrome with hypomagnesaemia the authors report radiological findings typical of chondrocalcinosis associated with joint symptoms corresponding to this condition. In Bartter's syndrome there is, in addition to hypokalaemic alkalosis, often concomitant magnesium depletion which has marked repercussions with respect to both physiopathology and symptomatology. In particular, hypomagnesaemia could well be important in the pathogenesis of chondrocalcinosis through two simultaneous mechanisms: by reducing the activity of pyrophosphatases and by facilitating the crystallisation of pyrophosphates. These mechanisms could explain the association of Bartter's syndrome and chondrocalcinosis, which is described here for the first time.

Bartter's syndrome, chondrocalcinosis and nephrogenic hypomagnesemia in an adult. Bartter's syndrome, chondrocalcinosis and nephrogenic hypomagnesemia in an adult. Bartter's syndrome, initially described in children, becomes a controversial entity when it is observed in adults, as it cannot be dissociated easily from the pseudo Bartter's syndrome caused by an abuse of diuretics or provoked by surreptitious vomiting. Yet its association with chondrocalcinosis, about ten cases of which have already been published and which is not reproducible by prolonged diuretic treatment, seems to give it some authenticity. The link between the two conditions might well be the low blood magnesium level observed significantly in both diseases and constantly when they are associated. This hypomagnesaemia is of renal origin and it may reflect a complex tubular disorder which also includes a defect of chloride reabsorption by the tubule. We report here a case of diffuse chondrocalcinosis and Bartter-like syndrome in a 38-year old woman, leading to the discovery of nephrogenic hypomagnesaemia.