Caffeine-induced hypokalemia: a case report.

BACKGROUND: With an increase in the global popularity of coffee, caffeine is one of the most consumed ingredients of modern times. However, the consumption of massive amounts of caffeine can lead to severe hypokalemia. CASE PRESENTATION: A 29-year-old man without a specific past medical history was admitted to our hospital with recurrent episodes of sudden and severe lower-extremity weakness. Laboratory tests revealed low serum potassium concentration (2.6-2.9 mmol/L) and low urine osmolality (100-130 mOsm/kgH2O) in three such prior episodes. Urinary potassium/urinary creatinine ratio was 12 and 16 mmol/gCr, respectively. The patient was not under medication with laxatives, diuretics, or herbal remedies. Through an in-depth interview, we found that the patient consumed large amounts of caffeine-containing beverages daily, which included > 15 cups of coffee, soda, and various kinds of tea. After the cessation of coffee intake and concomitant intravenous potassium replacement, the symptoms rapidly resolved, and the serum potassium level normalized. CONCLUSIONS: An increased intracellular shift of potassium and increased loss of potassium in urine due to the diuretic action have been suggested to be the causes of caffeine-induced hypokalemia. In cases of recurring hypokalemia of unknown cause, high caffeine intake should be considered.

Acute Kidney Injury Impacts on Hypokalemia Associated with Yokukansan Preparation: A Retrospective Observational Study.

The time course of acute kidney injury and hypokalemia remains unelucidated. We investigated whether altered renal function impacts hypokalemia and clinical predictors for acute kidney injury in patients who used Yokukansan preparation. We performed a secondary analysis of retrospective observational cohort data from adult patients who started Yokukansan preparation. The study was conducted from June 2015 to May 2019 at Tokyo Women's Medical University, Medical Center East. The effect of acute kidney injury (>1.5-fold increase from baseline serum creatinine level) or renal function recovery on hypokalemia (serum potassium level <3.0 mEq/L) was investigated. The clinical predictors for acute kidney injury were determined using a multivariate Cox proportional hazard analysis. Out of 258 patients, 12 patients had both outcomes, and all but one patient experienced in the order of acute kidney injury and hypokalemia. Excluding one patient, hypokalemia occurred in 11/34 (32%) patients after acute kidney injury and 27/223 (12%) patients without acute kidney injury (p = 0.005). Hypokalemia occurred in 9/25 (36%) of acute kidney injury with recovery, 2/9 (22%) of acute kidney injury without recovery, and 27/223 (12%) of no acute kidney injury (p = 0.014). Patients with acute kidney injury showed a late onset of hypokalemia compared with those without acute kidney injury (p = 0.001). In 258 patients, multivariate Cox proportional hazard analysis showed that high systolic blood pressure and mean arterial pressure increased the risk of acute kidney injury. Clinicians should remember that hypokalemia developed after acute kidney injury while Yokukansan preparation treatment.

Ectopic ACTH syndrome of different origin-Diagnostic approach and clinical outcome. Experience of one Clinical Centre.

PURPOSE: Ectopic Cushing Syndrome (EAS) is a rare condition responsible for about 5-20% of all Cushing syndrome cases. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The aim of this study is to present a 20-year experience in the diagnosis and clinical course of patients with EAS in a single Clinical Centre in Southern Poland as well as a comparison of clinical course and outcomes depending on the source of ectopic ACTH production-especially neuroendocrine tumors with other neoplasms. METHODS: Twenty-four patients were involved in the clinical study with EAS diagnosed at the Department of Endocrinology between years 2000 and 2018. The diagnosis of EAS was based on the clinical presentation, hypercortisolemia with high ACTH levels, high dose dexamethasone suppression test and/or corticotropin-releasing hormone tests. To find the source of ACTH various imaging studies were performed. RESULTS: Half of the patients were diagnosed with neuroendocrine tumors, whereby muscle weakness was the leading symptom. Typical cushingoid appearance was seen in merely a few patients, and weight loss was more common than weight gain. Patients with neuroendocrine tumors had significantly higher midnight cortisol levels than the rest of the group. Among patients with infections, we observed a significantly higher concentrations of cortisol 2400 levels in gastroenteropancreatic neuroendocrine tumors. Chromogranin A correlated significantly with potassium in patients with neuroendocrine tumors and there was a significant correlation between ACTH level and severity of hypokalemia. CONCLUSION: EAS is not common, but if it occurs it increases the mortality of patients; therefore, it should be taken into consideration in the case of coexistence of severe hypokalemia with hypertension and muscle weakness, especially when weight loss occurs. Because the diagnosis of gastroenteropancreatic neuroendocrine tumor worsens the prognosis-special attention should be paid to these patients.

Type 2 diabetes mellitus caused by Gitelman syndrome-related hypokalemia: A case report.

INTRODUCTION: Gitelman syndrome (GS) is an autosomal-recessive disease caused by SLC12A3 gene mutations. It is characterized by hypokalemic metabolic alkalosis in combination with hypomagnesemia and hypocalciuria. Recently, patients with GS are found at an increased risk for developing type 2 diabetes mellitus (T2DM). However, diagnosis of hyperglycemia in GS patients has not been thoroughly investigated, and family studies on SLC12A3 mutations and glucose metabolism are rare. Whether treatment including potassium and magnesium supplements, and spironolactone can ameliorate impaired glucose tolerance in GS patients, also needs to be investigated. PATIENT CONCERNS: We examined a 55-year-old Chinese male with intermittent fatigue and persistent hypokalemia for 17 years. DIAGNOSES: Based on the results of the clinical data, including electrolytes, oral glucose tolerance test (OGTT), and genetic analysis of the SLC12A3 gene, GS and T2DM were newly diagnosed in the patient. Two mutations of the SLC12A3 gene were found in the patient, one was a missense mutation p.N359K in exon 8, and the other was a novel insert mutation p.I262delinsIIGVVSV in exon 6. SLC12A3 genetic analysis and OGTT of 9 other family members within 3 generations were also performed. Older brother, youngest sister, and son of the patient carried the p.N359K mutation in exon 8. The older brother and the youngest sister were diagnosed with T2DM and impaired glucose tolerance by OGTT, respectively. INTERVENTIONS: The patient was prescribed potassium and magnesium (potassium magnesium aspartate, potassium chloride) oral supplements and spironolactone. The patient was also suggested to maintain a high potassium diet. Acarbose was used to maintain the blood glucose levels. OUTCOMES: The electrolyte imbalance including hypokalemia and hypomagnesemia, and hyperglycemia were improved with a remission of the clinical manifestations. CONCLUSION: GS is one of the causes for manifestation of hypokalemia. SLC12A3 genetic analysis plays an important role in diagnosis of GS. Chinese male GS patients characterized with heterozygous SLC12A3 mutation should be careful toward occurrence of T2DM. Moreover, the patients with only 1 SLC12A3 mutant allele should pay regular attention to blood potassium and glucose levels. GS treatment with potassium and magnesium supplements, and spironolactone can improve impaired glucose metabolism.

A complicated chinese herbal medicine nephrotoxicity.

Chinese herbal medicine is widely used globally. In many instances, it is associated with severe adverse outcomes. We report case of a Chinese herbal nephropathy occurring in a 43-year-old woman showing renal impairment, metabolic acidosis, Stokes - Adams syndrome, hypernatremia, and hypokalemia, characteristics not usually encountered in published cases.

Thyrotoxic Periodic Paralysis with Hypokalemia in an Adult Male from Nepal: A Case Report.

Thyrotoxic periodic paralysis is rare complication of hyperthyroidism characterized by the sudden onset of hypokalemia and muscle paralysis. It is typically present in young Asian males. There are very few literatures regarding the occurrence of thyrotoxic hypokalemic periodic paralysis in Nepal. We reported a case of a 35-year-old male presented with the chief complaints of weakness of all four limbs of 1 day duration. He was diagnosed as a case of hyperthyroidism in the past, received treatment for 6 months and left medications on his own 6 months ago. Evaluation during admission revealed severe hypokalemia with serum potassium level 1.3mEq/l and high serum Triiodothyronine (>20.00µg/L) and low serum Thyroid Stimulating Hormone (<0.01µg/L). Potassium supplements resolved muscle weakness and the patient was restarted with anti-thyroid drugs. Hence, hypokalemic paralysis is a reversible cause of paralysis and high index of suspicion as well as timely interventions are required to prevent potential harm. Keywords: hyperthyroidism; hypokalemia; muscle paralysis; thyrotoxic periodic paralysis.

Dyskalemia in Chronic Kidney Disease: How Concerned Should We Be?

CONTEXT: The widespread use of diuretics, potassium supplements, and medications that block renin angiotensin system puts the chronic kidney disease (CKD) population at high risk for dyskalemia, both hyperkalemia and hypokalemia. The optimal potassium level in a CKD patient is unknown. Subject of review: Two recent studies found conflicting results on the association of dyskalemia with outcomes. The Renal Research Institute CKD study [Clin J Am Soc Nephrol 2010; 5: 762-769] found increased mortality and incidence of end-stage renal disease (ESRD) with mild to moderate hypokalemia, whereas hyperkalemia was not significantly associated, compared to eukalemia. On the other hand, the Multi-Ethnic Study of Atherosclerosis (MESA)/Cardiovascular Health Study [Clin J Am Soc Nephrol 2017; 12: 245-252] showed both cardiovascular and noncardiovascular mortality to be higher with hyperkalemic patients, whereas associations with hypokalemic patients were statistically nonsignificant. Second opinion: If mild hypo- or hyperkalemia is associated with adverse outcomes, is it related to the hyperkalemia per se or to conditions associated with dyskalemia, such as kidney disease or cardiovascular disease? We interpret these articles in the context of criteria to support causality in epidemiologic studies. The cardiovascular effects of dyskalemia is well described and there is biological plausibility for increased cardiovascular mortality but the association of increased non-cardiovascular mortality with dyskalemia has little mechanistic basis. The explanation for a causal association of dyskalemia with ESRD is not adequate. Based on current evidence, targeting a potassium level of 4-5 mmol/L can be considered safe.

Licorice-induced apparent mineralocorticoid excess compounded by excessive use of terbutaline and high water intake.

This case highlights the clinical course of a 54-year-old male patient presenting with hypertension and long-term refractory hypokalaemia. He reported long-term malaise, fatigue and physical discomfort. Diarrhoea, vomiting, over-the-counter drugs, dietary supplements and any kind of medical abuse were all denied. Physical examination was normal. Suppressed plasma renin activity along with a low aldosterone level and elevated urinary cortisone/cortisol metabolite excretion ratio raised the suspicion of apparent mineralocorticoid excess (AME). The patient started treatment with spironolactone, but serum potassium levels were persistently fluctuating and the patient was hospitalised for further evaluation. During hospitalisation, repeated medical history and diagnostic examinations revealed licorice-induced AME complicated by excessive use of terbutaline and massive water intake. Licorice discontinuation, reduction of terbutaline and normalisation of water intake led to fully normalised potassium levels. Despite careful clinical history and diagnostic work-up, hospitalisation may be necessary in selected patients with long-term hypokalaemia.

Etiologic and therapeutic analysis in patients with hypokalemic nonperiodic paralysis.

BACKGROUND: Hypokalemic nonperiodic paralysis represents a group of heterogeneous disorders with a large potassium (K(+)) deficit. Rapid diagnosis of curable causes with appropriate treatment is challenging to avoid the sequelae of hypokalemia. We prospectively analyzed the etiologies and therapeutic characteristics of hypokalemic nonperiodic paralysis. METHODS: Over an 8-year period, patients with hypokalemic nonperiodic paralysis were enrolled by excluding those with hypokalemic periodic paralysis due to acute shift of K(+) into cells. Blood and spot urine samples were collected for the measurements of electrolytes, pH, and biochemistries. Intravenous potassium chloride (KCl) at a rate of 10-20 mmol/h was administered until muscle strength recovered. RESULTS: We had identified 58 patients with hypokalemic nonperiodic paralysis from 208 consecutive patients with hypokalemic paralysis, and their average K(+) concentration was 1.8 ± 0.2 mmol/L. Among patients with low urinary K(+) excretion (n = 17), chronic alcoholism, remote diuretic use, and anorexia/bulimia nervosa were the most common causes. Among patients with high urinary K(+) excretion (n = 41) and metabolic acidosis, renal tubular acidosis and chronic toluene abuse were the main causes, while primary aldosteronism, Gitelman syndrome, and diuretics were the leading diagnoses with metabolic alkalosis. The average KCl dose needed to restore muscle strength was 3.8 ± 0.8 mmol/kg. Initial lower plasma K(+), volume depletion, and high urinary K(+) excretion were associated with higher recovery KCl dosage. During therapy, patients with paradoxical hypokalemia (n = 32) who required more KCl supplementation than patients without (4.1 ± 0.7 vs 3.4 ± 0.7 mmol/kg, P < 0.001) often exhibited significantly higher plasma renin activity and received a higher volume of normal saline before its appearance. CONCLUSIONS: Understanding the common etiologies of hypokalemic nonperiodic paralysis may aid in early diagnosis. Patients with initial lower plasma K(+), renal K(+) wasting, and hypovolemia required higher recovery K(+) dosage. Paradoxical hypokalemia is prone to develop in hypovolemic patients even during K(+) supplementation with volume repletion.

Indomethacin, amiloride, or eplerenone for treating hypokalemia in Gitelman syndrome.

Patients with Gitelman syndrome (GS), an inherited salt-losing tubulopathy, are usually treated with potassium-sparing diuretics or nonsteroidal anti-inflammatory drugs and oral potassium and magnesium supplementations. However, evidence supporting these treatment options is limited to case series studies. We designed an open-label, randomized, crossover study with blind end point evaluation to compare the efficacy and safety of 6-week treatments with one time daily 75 mg slow-release indomethacin, 150 mg eplerenone, or 20 mg amiloride added to constant potassium and magnesium supplementation in 30 patients with GS (individual participation: 48 weeks). Baseline plasma potassium concentration was 2.8±0.4 mmol/L and increased by 0.38 mmol/L (95% confidence interval [95% CI], 0.23 to 0.53; P<0.001) with indomethacin, 0.15 mmol/L (95% CI, 0.02 to 0.29; P=0.03) with eplerenone, and 0.19 mmol/L (95% CI, 0.05 to 0.33; P<0.01) with amiloride. Fifteen patients became normokalemic: six with indomethacin, three with eplerenone, and six with amiloride. Indomethacin significantly reduced eGFR and plasma renin concentration. Eplerenone and amiloride each increased plasma aldosterone by 3-fold and renin concentration slightly but did not significantly change eGFR. BP did not significantly change. Eight patients discontinued treatment early because of gastrointestinal intolerance to indomethacin (six patients) and hypotension with eplerenone (two patients). In conclusion, each drug increases plasma potassium concentration in patients with GS. Indomethacin was the most effective but can cause gastrointestinal intolerance and decreased eGFR. Amiloride and eplerenone have similar but lower efficacies and increase sodium depletion. The benefit/risk ratio of each drug should be carefully evaluated for each patient.

Hypokalemia: a potent risk for QTc prolongation in clarithromycin treated rats.

Clarithromycin belongs to macrolide group of antibiotics commonly known for their proarrhythmic potency. Besides agents interfering with CYP 3A, electrolyte imbalance might influence repolarization problems of clarithromycin. The proarrhythmic tendency of clarithromycin particularly in association with hypokalemia manifested a change in QT interval in rat electrocardiogram (ECG). Varying degree of hypokalemia was induced by intraperitoneal injection of furosemide (50, 30, and 10 mg/kg, for seven days). The serum electrolyte levels confirmed that hypokalemia was established in the groups receiving furosemide. Simultaneously, clarithromycin was orally administered in the doses of 100 and 80 mg/kg for seven days. ECG was measured for 5 min in anaesthetised rat before and after 2 h of treatment. The QT interval was corrected for heart rate and reported as corrected QT (QTc). Distinct QTc interval prolongation was observed in groups receiving furosemide (50 and 30 mg/kg) alone and in all the groups receiving clarithromycin alongside furosemide. Neither, clarithromycin (80 mg/kg) nor furosemide (10 mg/kg) exhibited any significant change in the QTc interval but in combination these drugs led to a significant increase in the QTc interval. Most interestingly, potassium supplementation was found to reduce QTc interval in the group presenting with maximum QTc prolongation. These results suggest that hypokalemic condition potentiates the clarithromycin induced QTc prolongation, thereby indicating the importance of monitoring serum electrolyte during clarithromycin therapy. Although, selection of rat for examination of proarrhythmic liability is controversial, this report may be considered as an evidence of hypokalemia potentiating clarithromycin induced QTc prolongation.

Refeeding syndrome in children in developing countries who have celiac disease.

OBJECTIVES: The clinical presentations of celiac crisis and refeeding syndrome in celiac disease are almost similar, but information about refeeding syndrome is scarce. We are reporting for the first time 5 cases of refeeding syndrome in children with celiac disease that could have otherwise been labeled as celiac crisis. METHODS: From January to December 2010, a chart review of hospital records of all celiac disease cases was performed, and refeeding syndrome was ascribed in those celiac patients who deteriorated clinically after initiation of a gluten-free diet and had biochemical parameters suggestive of refeeding syndrome such as hypophosphatemia, hypokalemia, hypocalcemia, and hypoalbuminemia. RESULTS: Of the total 35 celiac disease patients, 5 (median age 6.5 [range 2.2-10] years, 3 boys) were identified as having refeeding syndrome. All 5 children were severely malnourished (body mass index <14 kg/m) and all of them had anemia, hypophosphatemia, hypokalemia, hypoalbuminemia, and hypocalcemia, meaning that they had the perfect setting for developing refeeding syndrome. At the same time, their clinical features fulfilled the criteria for celiac crisis except that their symptoms have worsened after the introduction of a gluten-free diet. Nevertheless, instead of using steroids, they were managed as refeeding syndrome in terms of correction of electrolytes and gradual feeding, and that led to a successful outcome in all of them. CONCLUSIONS: Severely malnourished patients with celiac disease are at risk of developing potentially life-threatening refeeding syndrome, which may mimic celiac crisis, especially in developing countries. Early recognition and appropriate treatment are the keys to a successful outcome.

Resistant hypertension in an aged woman presenting with clinical features simulating ectopic ACTH syndrome--response to spironolactone--.

A 91-year-old depressed woman had resistant hypertension despite a triple combination of anti-hypertensives, including a Ca-antagonist, an angiotensin receptor blocker, and a thiazide diuretic at optimal doses. She had hypokalemic metabolic alkalosis, elevated plasma cortisol and ACTH, and elevated urinary cortisol. The high-dose dexamethasone did not suppress the elevated ACTH and cortisol. The addition of spironolactone to her previous medications controlled and normalized hypertension, hypokalemia, and hormonal abnormalities within 4 months. Her blood pressure, serum electrolytes, and the hormonal states remained normalized for more than a year thereafter. Her depressed mental state also improved after spironolactone.

Hypokalaemia and failure to thrive: report of a misleading onset.

AIM: We report a case of Gitelman Syndrome (GS) in a 9-year-old girl, previously diagnosed as a Bartter syndrome at one year of life. METHODS: She had been treated with potassium, for over 8 years and was admitted because of fatigue, numbness and weakness of both legs. The patient has typical laboratory findings, including hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria, thus GS was suspected. RESULTS: Genetic analysis was performed two mutations IVS9(+1)G>T were detected in the thiazide-sensitive Na-Cl cotransporter (TSC) gene (SLC12A3), thus she was diagnosed as having GS. She was treated with oral potassium and magnesium supplements with resolution of the symptoms. CONCLUSION: This case reminded us that doctors should be alert to the initial presentation of renal tubular diseases. Detailed electrolyte analysis, hormone evaluations and clinic follow-up are mandatory for their correct differential diagnosis.

Longitudinal growth in chronic hypokalemic disorders.

Growth retardation remains a major complication in children with primary tubular disorders, despite adequate supplemental treatment with electrolytes, water and bicarbonate. Chronic hypokalemia, characteristic of some tubulopathies, impairs growth by mechanisms that are not well known. Association with growth hormone deficiency has been reported in patients with Bartter's or Gitelman's syndrome. Tissue-specific alterations of growth hormone and insulin-like growth factor I axis have been described in experimental models of potassium depletion. Hypokalemic rats gain less body length and weight than pair-fed normokalemic animals and, by contrast, develop renal hypertrophy. These rats have low circulating concentrations of insulin-like growth factor I, depressed messenger ribonucleic acid (mRNA) levels of this peptide in the tibial growth plate, and they are resistant to the longitudinal growth-promoting effects of exogenous growth hormone. The reason for this resistance remains to be defined. No alterations in the intracellular signaling for growth hormone have been found in the liver of hypokalemic rats. However, treatment with high doses of growth hormone is unable to normalize hypertrophy of the epiphyseal cartilage chondrocytes, which are severely disturbed in potassium depletion and likely play an important role in the pathogenia of growth impairment in this condition.

A sweet tooth as the root cause of cardiac arrest.

A 71-year-old woman was admitted with hypotension and bradycardia. An electrocardiogram showed flattened T waves and increased U wave prominence, resulting in a long QT(U) syndrome. Her initial serum potassium level was 1.6 mmol/L (all other electrolytes, including magnesium, were normal). She suffered recurrent ventricular tachycardia and ventricular fibrillation arrest requiring direct current cardioversion and high-dose intravenous potassium chloride replacement. Systematic enquiry revealed that she had been constipated for a number of months and had resorted to consuming large quantities of liquorice on a daily basis for its laxative effects. Endocrinology review identified no primary abnormality of the renin- angiotensin- aldosterone axis, and the patient was diagnosed with hypokalemia secondary to liquorice overindulgence. Liquorice has a mineralocorticoid effect. If chronically consumed in large quantities, this effect may lead to severe depletion of whole-body potassium stores. The present case highlights a rare but important cause of hypokalemic cardiac arrest of which all acute care physicians should be aware.

Miocardiopatía hipertrófica y alteraciones electrocardiográficas / No disponible

Presentamos un caso clínico que muestra una mujer de 66 años diagnosticada de miocardiopatía hipertrófica obstructiva y fibrilación auricular paroxística, remitida desde la consulta de Atención Primaria al Servicio de Urgencias por insuficiencia cardiaca izquierda aguda. El electrocardiograma muestra ondas U prominentes e hipopotasemia, alteraciones que tras la suplementación de potasio mejoran o se normalizan

We present a clinical case of a 66-year-old woman diagnosed of obstructive hypertrophic cardiomyopathy and paroxysmal atrial fibrillation referred from the Primary Care medical site to the emergency service due to acute left-sided heart failure. The electrocardiogram showed prominent U waves accompanied of hypokaliemia who improved or in whom the disorder normalized after potassium supplementation+

Severe hypokalemia, rhabdomyolysis, muscle paralysis, and respiratory impairment in a hypertensive patient taking herbal medicines containing licorice.

A 93 year-old hypertensive woman was found to have severe hypokalemia (as low as 1.3 mEq/L) and developed paralysis of the all extremities associated with metabolic alkalosis, hypoxemia, hypercapnea, extremely high levels of creatine phosphokinase (up to 9280 U/L), myoglobin and myoglobinuria compatible with rhabdomyolysis. Plasma renin activity and aldosterone levels were below normal. She was found to have been taking licorice-containing herbal medicines for the last 7 years. With the discontinuation of the licorice-containing medicines and administration of spironolactone together with intravenous and oral potassium supplement, her serum potassium level was normalized and her clinical symptoms and hypertension improved within 2 weeks.

Hypocalciuria in patients with Gitelman syndrome: role of blood volume.

BACKGROUND: Hypocalciuria is common in patients with Gitelman syndrome (GS), and its cause primarily is enhanced renal reabsorption of calcium in the proximal tubule in response to hypovolemia, judged by recent studies in animals. STUDY DESIGN: Uncontrolled trial in cases and controls to evaluate the effect of acute reexpansion of extracellular fluid volume (ECFV) on urine calcium excretion in patients with GS. SETTING & PARTICIPANTS: 8 patients with GS and 8 sex- and age-matched healthy control subjects (CSs) were enrolled in an academic medical center. PREDICTOR: ECFV expansion with isotonic saline at 1 L/h for 3 hours. OUTCOMES & MEASUREMENTS: Urinary calcium excretion was measured hourly for 6 hours, and subsequent 18-hour urine was analyzed as a single collection; hormones and electrolytes were measured. RESULTS: Patients with GS had hypokalemia, metabolic alkalosis, hypomagnesemia, severe hypocalciuria (urine calcium-creatinine ratio, 0.006 +/- 0.002 versus 0.08 +/- 0.02 mg/mg [0.02 +/- 0.01 versus 0.22 +/- 0.05 mmol/mmol]; P < 0.005), and a mild degree of ECFV contraction. Sodium excretion and creatinine clearance rates were similar to those in CSs. In patients with GS, saline infusion increased ECFV, which caused a significantly greater sodium excretion rate, but there was only a small increase in calcium excretion rate, in both the first 6 hours (0.04 +/- 0.02 mg/min [1.0 +/- 0.6 micromol/min]) and subsequent 18-hour period (0.02 +/- 0.01 mg/min [0.4 +/- 0.2 micromol/min]), as in CSs. Notwithstanding, their calcium excretion rate was still much less than that in CSs before volume repletion (0.13 +/- 0.04 mg/min [3.2 +/- 1.0 micromol/min]). LIMITATION: Patients with GS did not become euvolemic on a long-term sodium chloride supplementation because they excreted sodium chloride so rapidly. CONCLUSION: Hypovolemia is not the sole cause of hypocalciuria in patients with GS.