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Korean J Intern Med > Volume 10(1); 1995 > Article
Park, Chung, Yeum, Lee, Yoo, Kim, Kim, Choi, and Kang: A Case of Adult-Onset Bartter’s Syndrome


Bartter’s Syndrome is characterized by renal potassium wasting with hypokalemia, metabolic alkalosis, increased renin-angiotensin-aldosterone system, normal blood pressure, resistance to the pressor effects of angiotensin II and juxtaglomerular cell hyperplasia. Most of the cases have been noted in the pediatric age group and adult-onset cases are very rare. We report a case of adult-onset Bartter’s syndrome.


In 1962, Bartter et al.1) described a clinical syndrome characterized by hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normal blood pressure. Further findings include a resistance to the pressor effects of norepinephrine and angiotensin II. Histologically, there is hyperplasia of the juxtaglomerular cell. It occurs mostly in childhood or adolescence, and initial presentation in patients over 40 years of age was very rare2). Bartter’s syndrome is a rare cause of chronic hypokalemic alkalosis in adults. Neverthless, Neverthless, the syndrome has aroused great interest in many clinical investigators because it may provide new insights in to renal electrolyte metabolism and the pathophysiology of hypertension3).
We recently experienced a case of adult-onset Bartter’s syndrome who showed hypokalemia, metabolic alkalosis, normotension, hyperreninemia, hyperaldosteronism and juxtaglomerular cell hyperplasia.


A 40-year-old woman was admitted to the Chonnam University Hospital, with a three months history of severe generalized weakness and fatigue.
The first episode occurred three years ago and spontaneously remitted from it following bed rest, she denied ingestion of licorice, diuretics, laxative or any other medication, and she had no significant nausea, vomiting or diarrhea.
The patient appeared relatively well and had a height of 154 cm and a weight of 52 kg. The pulse rate was 98/min, the blood pressure 100/70 mmHg, and the respiration rate 18/min. The remainder of her physical examination was within normal limits.
Laboratory findings included persistent hypokalemic alkalosis with 2.4 mEq/L for serum potassium, 32.7 mEq/L for serum bicarbonate, 86.1 mmHg for PaO2, 48 mmHg for PaCO2 and 32 mmol/L for total CO2 content. The pH of plasma was 7.44 and that of urine 7.0. Electrocardiography revealed PR prolongation and T wave - flattening. Serum sodium averaged 139 mEq/L, chloride 85 mEq/L, total calcium 5.1 mEq/L, ionized calcium 2.0 mEq/L, inorganic phosphorus 4.7 mg/dl, magnesium 1.6 mEq/L, uric acid 13.4 mg/dl and serum osmolality 289 mosl/kg. The blood urea nitrogen was 44.0 mg/dl, serum creatinine 1.7 mg/dl and creatinine clearance 35 ml/min. There were no proteinuria, hematuria and abnormality of the urinary sediment. Pertinent studies of the blood and serum revealed a normal hemoglobin level, hematocrit value, white blood cell count, total protein, albumin, alkaline phosphatase and transaminase levels. Twenty four-hour urinary excretion of sodium was 183 mEq, potassium 67 mEq, chloride 247 mEq, calcium 120 mg, protein 150 mg, glucose 30 mg and urine amounts 2,300 cc. The urinary specific gravity was 1.010 and osmolality 310 mosm/kg. The plasma renin activity was 48.2 ng/ml/hr and aldosterone level 34.4 ng/dl. FENa was 2.6%, FECl, 5.7%, FEK 55%, and FEUric acid 8.2%. Thiazide and furosemide were not detected in her urine by high-performance liquid chromatography at the Department of Pharmacology, Chonnam University Medical School, Kwangju, Korea.
The renal biopsy was performed without difficulty. The biopsy specimen contained up to 8 glomeruli per section. Some glomeruli revealed focal and segmental glomerulosclerotic changes. Juxtaglomerular hyperplasia of varying degrees and multiple vacuolization of proximal tubule due to chronic hypokalemia were noted (Fig. 1, 2). The tubules, interstitium and blood vessels were entirely normal with no scarring or atrophy. The constellation of hypokalemia, relative hypotension, increased renin activity, increased aldosterone level and juxtaglomerular hyperplasia substantiated the diagnosis of Bartter’s syndrome.
Following the renal biopsy, the patient had been treated with potassium chloride, 40 mEq twice a day, spironolactone, 50 mg three times a day, propranolol, 20 mg three times a day, enalapril, 2.5 mg a day and indomethacin, 25 mg three times a day. The administration of medications led to an increase in serum potassium to 3.5 to 4.5 mEg/L.
In association with this improvement in the serum potassium concentration, the patient’s muscle strength was rapidly recovered and the patient did well for the following two months (Table 1).


Bartter’s syndrome consists of hypokalemia due to renal potassium wasting, elevated plasma renin activity and aldosterone secretion, normal blood pressure, hyporesponsiveness of blood pressure to infused angiotensin II and hyperplasia of granular cells of the juxtaglomerular apparatus of the kidney1). The clinical symptoms of Bartter’s syndrome are dominated by hypokalemia3). Proximal muscle weakness may cause incapacity and force families to seek medical help.
Gastrointestinal symptoms include anorexia and constipation due to renal water loss and hypokalemic ileus. Clinically, Bartter’s syndrome can be divided into at least two groups: one group with an eary (infancy), and the other with a late onset of symptoms. Neonatal Bartter’s syndrome is characterized by the intrauterine onser of polyuria, leading to polyhydramnios between the 22nd and 24th weeks of gestation. In adults, fatigue, proximal muscle weakness and tetany are the most common presenting features4).
The primary etiolgy of Bartter’s syndrome is still unknown. With the findings of abnormalities in plasma and urinary prostaglandins, many investigators considered a defect in prostaglandin homeostasis as the primary defect5). Elevated prostaglandin levels could explain peripheral vasodilatation and a lack of responsiveness to pressors. The inhibition of chloride transport in the loop of Henle by prostaglandins, especially in the face of hyperaldosteronism, would lead to potassium wasting and alkalosis6). However, prostaglandin inhibition does not completely cure the defects in Bartter’s syndrome. Also, continued use of prostaglandin inhibitors may not result in continuous benefit to patients with Bartter’s syndrome7). Stein8) reviewed the published material and the data derived in his laboratory with Bartter’s syndrome, and concluded that Bartter’s syndrome may have more one underlying etiology.
Bartter9) and Baehler et al10) favored primary chloride wasting as the defect of Bartter’s syndrome. These hypotheses all consider the resulting potassium deficiency as the cause of the prostaglandin, bradykinin, kallikrein, and vasopressor abnormalities. Sodium, chloride, and potassium losses result in volume depletion, increased aldosterone levels, and metabolic alkalosis. Bartter’s syndrome may be mimicked by magnesium deficiency, diuretic use or vomiting. Magnesium depletion causes kaliuresis, diuretics cause potassium and volume depletion and vomiting causes renal potassium wasting and volume depletion.
Treatment is generally focused on the repair of hypokalemia by inhibition of the renin-angiotensin-aldosterone or the prostaglandin-kinin system. Potassium supplementation, magnesium repletion, propranolol, spironolactone, prostaglandin inhibitors and conventing enzyme inhibitors all have been advocated, but each has met with limited success8).
In this case, the patient was diagnosed to be adult-onset Bartter’s syndrome due to hypokalemia, relative hypotension, increased renin activity, increased aldosterone level and juxtaglomerular hyperplasia. In appropriate medical therapy, a positive potassium balance and an increase in serum potassium concentration. In association with this improvement in the serum potassium concentration, the patient’s muscle strength was rapidly recovered and the patient did well for the following two months.

Fig. 1.
Increased number of cells lie in the afferent arteriole at the hilum of the glomerulus and multiple vacuoles in the proximal tubules. Light microscopy, Homatoxylin and eosin stain, origisnal magnification × 200.
Fig. 2.
Varying sized multiple vacuoles in the proximal tuble. Electron microscopy. × 8000.
Table 1.
Clinical Manifestations Before and After Treatment
Before treatment After treatment
Muscle weakness +
Fatigue ++
Polyuria +
Polydipsia ++
Nocturia +
Enuresis +
Salt craving +
Dehydration +
Orthostatic hypotension +
Failure to thrive
Delayed growth
Short stature
Mental retardation


1. Bartter FC, Pronove P, Gill JR Jr, MacCardle RC. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis:a new syndrome. Am J Med 33:811. 1962.
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2. Tomko DJ, Yeh BPY, Falls WF Jr. Bartter’s syndrome, Study of a 52-year-old man with evidence for a defect in proximal tubular sodium resorption and comments on therapy. Am J Med 61:111. 1976.
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3. Gans ROB, Hoorntje SJ. Bartter’s syndrome. In: Cameron S, Davison AM, Grünfeld JP, Kerr D, Ritz E, eds. Oxford textbook of clinical nephrology. P. 782. Oxford University Press, 1992.

4. White MG. Bartter’s syndrome. Arch Intern Med 129:41. 1972.
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5. Schöter J, Timmermans G, Sexberth HW, Greven J, Bachmann S. Marked reduction of Tamm-Horsfall protein synthesis in hyperprostaglandin E-syndrome. Kidney Int 44:401. 1993.
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6. Strokes JB. Effect of prostaglandin E2 on chloride transport across the rabbit thick ascending loop of Henle. Selective inhibition of the medullary portion. J Clinn Invest 64:495. 1979.
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7. Halushka PV, Wohltmann H, Privitera Pj, Hurwitz G, Margolius HS. Bartter’s syndrome: urinary prostaglandin E-like material and kallikrein; Indomethacin effects. Ann Intern Med 87:281. 1977.
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8. Stein JH. The pathogenetic spectrum of Bartter’s syndrome. Kidney Int 28:85. 1985.
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9. Bartter FC. On the pathogenesis of Bartter’s syndrome. Miner Electrolyte Metab 3:61. 1980.

10. Baehler RW, Work J, Kotchen TA, McMorrow G, Guthrie G. Studies on the pathogensis of Bartter’s syndrome. Am J Med 69:933. 1980.
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