Recurrent Hypokalemia Research Articles

Gitelman syndrome, a rare cause of refractory hypokalemia. A case repor

Introduction: Gitelman syndrome is a rare hereditary primary renal tubular disorder, with a prevalence of approximately 1 to 10 cases per 40 000 people. It does not have specific symptoms, so its diagnosis depends on high clinical suspicion by the treating physical and a sequential approach to hypokalemia, especially in young patients. Thus, a diagnostic algorithm is proposed at the end of this report. Case presentation: A 23-year-old woman with a history of hospitalization due to hypokalemia presented to the emergency service with intermittent cramping in her lower limbs, which was exacerbated by gastrointestinal symptoms. Laboratory tests reported the following findings: metabolic alkalosis, elevated levels of potassium, magnesium, chloride and sodium in urine, and reduced levels of calcium in urine. Thus, potassium supplementation and eplerenone administration were started, obtaining the complete resolution of symptoms. At her last follow-up appointment, the patient was asymptomatic, and her serum electrolyte levels were normal. In addition, during her hospital stay and due to the high suspicion of Gitelman syndrome, a genetic study was performed, which reported a mutation of the SCL12A3 gene, confirming the diagnosis. Conclusion: The sequential approach to a patient with recurrent hypokalemia is very important to reach an accurate diagnosis among a wide range of differential diagnoses.

Normotensive presentation in primary aldosteronism: A report of two cases

Normotensive patients with primary aldosteronism (PA) are relatively rare. Herein, we report two patients with normotensive PA and present a literature review to improve an understanding of the disease. Patient 1, a 56-year-old man, presented with recurrent hypokalemia that lasted for more than 2 years. Patient 2 was a 33-year-old man who presented with sexual dysfunction and was diagnosed with a prolactinoma combined with adrenal insufficiency and hypogonadism. Neither of these patients had hypertension that was detectable on repeated manual measurements. In both patients, a typical biological profile of PA was demonstrated that included hypokalemia with kaliuresis, elevated plasma aldosterone concentration (PAC), suppressed plasma renin concentration, and a high aldosterone-to-renin ratio. Both patients did not have sufficiently suppressed PAC on the saline infusion test, confirming the diagnosis of PA. Computed tomography of the adrenal gland and adrenal venous sampling suggested an aldosteronoma, which was confirmed by lateralized hypersecretion of aldosterone. After removal of the benign adenoma, the biochemical abnormalities were corrected. As hypertension is not necessarily a sign of PA, we propose that all patients with hypokalemia should be screened for PA in order to prevent cardiovascular complications while balancing economics and effectiveness.

Primary Sjogren’s syndrome manifesting as recurrent hypokalemia with distal renal tubular acidosis

Sjogren’s syndrome is an autoimmune disease with both glandular and extraglandular manifestations. We report a rare case of primary Sjogren syndrome without sicca symptoms presenting with renal tubular acidosis and recurrent hypokalaemia.

P0800PROFILING HYPOKALAEMIC AND HYPERKALAEMIC STATES IN THE IRISH HEALTH SYSTEM: TESTING RATES, INCIDENCE AND DETERMINANTS

Abstract Background and Aims Hypo- and hyperkalaemia are potentially life-threatening electrolyte abnormalities often associated with severe adverse clinical outcomes. Real-world incidence and determinants of hypo- and hyperkalaemia in clinical settings are poorly characterised. We studied incidence and determinants of these abnormalities in the Irish healthcare system Method Data from the Irish National Kidney Disease Surveillance and Quality Assurance Programme were used to construct a retrospective observational study. We identified all adult individuals (age > 18 years) who accessed health care from 2006 and 2010 in a regional health system (n = 205,334). Cumulative incidence of hypokalaemia (K+ < 3.5 mmol/L), hyperkalaemia (K+> 5 mmol/L), and moderate/severe hyperkalaemia (K+> 5.5 mmol/L) was estimated over a 3-year period. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Multinomial logistic regression explored associations of baseline patient characteristics with dyskalaemia states. Results Of 205,334 participants, 85.2% had 1–2 potassium tests, 5.8% had 2–3 tests, 2.7% had 3-4 tests and the remaining 6.4% had > 4 potassium tests/year. Hypokalaemia occurred in 17,145 (8.35%) individuals, of these 43.8% had recurrent hypokalaemia (>1 event). Hyperkalaemia occurred in 44,283 (21.6%) individuals, with 29.7% recurrence. Moderate/severe hyperkalaemia occurred in 9,672 (4.71%) with 18.0% recurrence. The frequency of potassium testing was an important determinant of dyskalaemia risk. In adjusted analyses, advancing age profile, women, inpatients, outpatients and emergency department patients (vs general practice), and frequency of tests had significantly higher risks of hypokalaemia. Additionally, advancing age, men, poorer kidney function, and frequency of potassium testing, and general practice were associated with significantly higher risk of hyperkalaemia. Conclusion Both hypo- and hyperkalaemic states are common in the Irish healthcare system with high rates of recurrence. Surveillance strategies should be put in place to allow timely detection and treatment of potassium disturbances in these high-risk groups.

Gitelman Syndrome: A Cause for Recurrent Hypokalaemia with Tetany

Gitelman Syndrome: A Cause for Recurrent Hypokalaemia with Tetany

Intraoperative Hypertensive Crisis in a Patient with Normotensive Primary Aldosteronism. Lessons from a Clinical Case

Primary hyperaldosteronism is the most frequent cause of secondary hypertension. However, it can also be found in apparently normotensive patients, often associated with recurrent hypokalemia and isolated hypertensive episodes.
 We hereby present the case of a normotensive 50-year-old female patient with a surgical left kidney mass; however, after anaesthetic induction, surgery was aborted due to a severe hypertensive crisis. She was referred to our Hypertension Outpatient Clinic to rule out pheochromocytoma/ paraganglioma. The anamnesis revealed unexplained episodes of hypokalemia. Ambulatory blood pressure monitoring showed normal mean values of blood pressure and heart rate, with an isolated hypertensive peak. Plasma glucose, ions, creatinine, lipids, metanephrines and chromogranin A were normal, but plasma aldosterone was clearly elevated with suppressed plasma renin activity and high aldosterone/renin activity ratio. Primary aldosteronism was confirmed by the captopril test. Abdominal CT was compatible with left adrenal hyperplasia. Treatment with low-dose spironolactone was well tolerated and resulted in normal blood pressure, normokalemia and unsuppressed plasma renin activity. The patient underwent successful laparoscopic removal of a renal oncocytoma. 
 We conclude that normotensive primary aldosteronism is not harmless; it can be associated with severe hypokalemia, anxiety, depression, hypertensive crisis and cardiovascular damage. Patients can also develop resistant hypertension. Adequate treatment can decisively improve the survival and quality of life of the patients with primary aldosteronism, but a correct diagnosis is needed first. Therefore, it must be considered as a diagnostic possibility in normotensive patients with unexplained hypokalemia or isolated hypertensive episodes.

SUN-460 Anticipating Hypokalemia in Patients With ACTH-Dependent Cushing Syndrome Treated With Mifepristone: Utilization of Cortisol and ACTH Levels to Identify At-Risk Patients

Background: Hypokalemia (K+ level <3.5 mEq/L) is common in patients with hypercortisolism. Treatment with mifepristone, a glucocorticoid receptor antagonist, can exacerbate hypokalemia due to the mineralocorticoid effects produced by the rapid and significant increase in cortisol levels that result from the loss of negative feedback of the HPA axis. Correction of hypokalemia is required prior to initiating mifepristone and K+ levels must be closely monitored during treatment. However, there is little guidance to help clinicians identify patients who may be at a greater risk for developing hypokalemia during mifepristone therapy and who may benefit from prophylactic treatment (eg, mineralocorticoid antagonists, potassium replacement). Method: Using data from the 24-week, open-label, phase 3 SEISMIC study, this report investigated associations between cortisol and adrenocorticotropic hormone (ACTH) levels and the development of hypokalemia in patients with ACTH-dependent Cushing syndrome treated with mifepristone. Data from 47 patients were retrospectively analyzed using logistic regressions and receiver operating characteristic (ROC) curves. Analyses were performed to identify factors associated with early-onset hypokalemia (occurring within the first 2 weeks of mifepristone treatment during doses of 300 mg/day) and late-onset hypokalemia (occurring after 2 weeks of mifepristone treatment during dose escalation). Results: Nineteen patients (40.4%) developed hypokalemia at least once during mifepristone treatment. Of these 19 patients, 10 (52.6%) developed hypokalemia by day 14. Early-onset hypokalemia was significantly related to baseline serum cortisol levels (P=.0155). Baseline serum cortisol levels >27 µg/dL (>750 nmol/L) were associated with a 6.8-fold increase in the occurrence of early-onset hypokalemia vs patients with cortisol ≤27 µg/dL (≤750 nmol/L) (58.3% vs 8.6%, P<.0011). Late-onset hypokalemia was significantly related to the 2-week ACTH levels (P=.0032). At 2 weeks, ACTH levels >112 pg/mL (>25 pmol/L) were associated with a 5.64-fold higher risk of late-onset hypokalemia vs patients with ACTH ≤112 pg/mL (≤25 pmol/L) (75% vs 13.3%; P<.0001). ACTH levels >112 pg/mL (>25 pmol/L) at 2 weeks were also associated with a greater risk of severe (K+ ≤2.5 mEq/L) or recurrent hypokalemia. Conclusions: Serum cortisol and ACTH levels may be useful in identifying patients at risk for developing hypokalemia while being treated with mifepristone. Patients with serum cortisol levels >27 µg/dL (>750 nmol/L) assessed before mifepristone initiation had a 6.8-fold increase in occurrence of early-onset hypokalemia. Patients with ACTH levels >112 pg/mL (>25 pmol/L) at 2 weeks after initiation of mifepristone (prior to dose escalation) had a 5.64-fold higher risk of late-onset hypokalemia.

Novel compound heterozygous ATP6V1B1 mutations in a Chinese child patient with primary distal renal tubular acidosis: a case report

BackgroundDistal renal tubular acidosis (dRTA) is a heterogeneous disorder characterized by normal anion gap metabolic acidosis. Autosomal recessive dRTA is usually caused by mutations occurring in ATP6V1B1 and ATP6V0A4 genes,encoding subunits B1 and a4 of apical H+-ATPase, respectively. The heterogeneous clinical manifestations of dRTA have been described in different ethnic groups harboring distinct mutations. Most of the reported cases are from Europe and Africa. At present, the prevalence of primary dRTA is still poorly elucidated in Chinese population.Case presentationA 2-year and six-month-old female patient was hospitalized because of recurrent hypokalemia, hyperchloremic metabolic acidosis and growth retardation. Laboratory investigations presented a normal anion gap hyperchloremic metabolic acidosis, hypokalemia, and inappropriate alkaline urine. Renal ultrasound indicated bilateral nephrocalcinosis. Bilateral sensorineural hearing loss (SNHL) was confirmed with moderately severe (45 dB) on the left ear and severe (80 dB) on the right ear, which was accompanied with enlarged vestibular aqueduct (EVA) on both sides. According to these findings, a diagnosis of dRTA was made. To identify the pathogenic gene mutation, all coding regions of ATP6V1B1 and ATP6V0A4 gene, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. The splicing variants were verified in peripheral blood leucocytes of the patient by RT-PCR. As a result, two novel heterozygous mutations in ATP6V1B1 were identified in the child. One mutation was a successive 2-nucleotide deletion in exon 2(c.133-134delTG), which caused a marked nonsense mediated mRNA decay. The other was a guanine to adenine substitution of the first nucleotide of intron 8(c.785 + 1 G > A), which led to the exclusion of exon 8. After treatment with sodium citrate, potassium citrateand citric acid, metabolic acidosis and hypokalemia were corrected, but her hearing decreased gradually during the 2 years and had to accept the use of bilateral hearing aids.ConclusionsWe described two novel dRTA associated mutations in ATP6V1B1 identified in a Chinese child patient accompanying with SNHL and EVA. Our study will help to expand the understanding of this rare disease in Chinese population.

Hypertension and Recurrent Hypokalaemia in Young Woman - A Case Report of Primary Hyperaldosteronism (Conn’s Syndrome)

Primary hyperaldosteronism is caused by most commonly due to aldosterone producing adenoma(conn’s syndrome) or bilateral adrenal hyperplasia. Clinical features may be of different type which includes hypertension in young age or resistant hypertension, recurrent hypokalaemia and characterized by increased ratio of plasma aldosterone (ng/dl) to rennin (ng/ml per hour) activity. We report a case of young woman presented with hypertension and recurrent hypokalaemia.University Heart Journal Vol. 12, No. 2, July 2016; 102-104

A Patient with Recurrent Hypokalaemia

Abstract not availableJ Bangladesh Coll Phys Surg 2016; 34(4): 228-230

Bartter Syndrome Represented by Recurrent Hypokalemia Attacks: A Case Report

Bartter Syndrome Represented by Recurrent Hypokalemia Attacks: A Case Report

A Middle Aged Man Presented with Recurrent Hypokalaemia and Basal Ganglia Calcification

Abstract not availableJ MEDICINE January 2016; 17 (1) : 57-58

Recurrent Hypokalemia, Hypomagnesemia and Metabolic Alkalosis Following Preemptive Renal Transplantation: Bartter Syndrome

Native kidney function can still contribute to the total renal function after preemptive renal transplantation, and the primary problems of native kidneys such as tubular disorders may persist or reappear in the post-transplantation period. Bartter syndrome is a rare hereditary tubulopathy characterized by renal salt wasting, hypokalemia, metabolic alkalosis, and normotensive hyperreninemic hyperaldosteronism. In this case report, we described a patient who presented with episodes of recurrent hypokalemia, hypomagnesemia, and metabolic alkalosis in the post-transplantation period, probably due to the tubular disorder of the native kidneys. The primary kidney disease had not been adequately investigated in the pre-transplant period, and Bartter syndrome was the most likely diagnosis. Identifying primary kidney disease in the pre-transplantation period is important for patient follow-up.

Biochemical munchausen’s - a “baffling” case of recurrent hypokalemia and lactic acidosis - secondary to surreptitious salbutamol abuse in a 36-year-old female

Factitious medical disorders with the well-known eponym of Munchausen’s syndrome represent a challenge in both diagnosis and management for the clinician. Here, we report a case of “Biochemical Munchausen’s” in a 36-year-old female, characterised by recurrent and multiple presentations with symptomatic hypokalaemia, supraventricular tachycardia and lactic acidosis that required the use of biochemical laboratory expertise and liquid chromatography/mass spectrophotometry to unravel and break the cycle of costly investigations and hopefully contain the risk of potential harm. We also highlight the evolution of various stages of generating factitious illness in this 36-year-old female with the crucial breakthrough being made only by proof of the biochemical exposure through the close collaboration of biochemist and clinicians.

Bartter syndrome represented by recurrent hypokalemia atttacs: A case report

Bartter syndrome represented by recurrent hypokalemia atttacs: A case report

Idiopathic Intractable Diarrhoea Leading to Torsade de Pointes.

An 81-year-old lady was admitted to our hospital with a 3-year history of noninfective diarrhoea and recurrent syncopal events over the last 3 months. Her initial electrocardiogram (ECG) revealed trigeminy and prolonged QTc interval. She had a structurally normal heart with no coronary artery disease. Investigations revealed low potassium at 3.0 mmol/L. Sigmoidoscopy and colonoscopy suggested a possible diagnosis of diverticulitis. Soon after admission she had an unresponsive episode with spontaneous recovery. Telemetry and Holter analysis confirmed multiple episodes of polymorphic ventricular tachycardia (Torsade de Pointes). Following electrolyte supplementation the episodes of polymorphic VT improved. Due to the protracted nature of the diarrhoea, the recurrent syncopal events, and recurrent hypokalaemia documented over recent years, an Implantable Cardioverter Defibrillator (ICD) was sanctioned by the multidisciplinary team (MDT). In summary, chronic diarrhoea may result in life threatening polymorphic VT due to hypokalaemia and QTc prolongation. In these patients an ICD may be considered.

Brugada phenocopy: A new electrocardiogram phenomenon

Brugada phenocopies (BrP) are clinical entities that are etiologically distinct from true congenital Brugada syndrome. BrP are characterized by type 1 or type 2 Brugada electrocardiogram (ECG) patterns in precordial leads V1-V3. However, BrP are elicited by various underlying clinical conditions such as myocardial ischemia, pulmonary embolism, electrolyte abnormalities, or poor ECG filters. Upon resolution of the inciting underlying pathological condition, the BrP ECG subsequently normalizes. To date, reports have documented BrP in the context of singular clinical events. More recently, recurrent BrP has been demonstrated in the context of recurrent hypokalemia. This demonstrates clinical reproducibility, thereby advancing the concept of this new ECG phenomenon. The key to further understanding the pathophysiological mechanisms behind BrP requires experimental model validation in which these phenomena are reproduced under strictly controlled environmental conditions. The development of these validation models will help us determine whether BrP are transient alterations of sodium channels that are not reproducible with a sodium channel provocative test or alternatively, a malfunction of other ion channels. In this editorial, we discuss the conceptual emergence of BrP as a new ECG phenomenon, review the progress made to date and identify opportunities for further investigation. In addition, we also encourage investigators that are currently reporting on these cases to use the term BrP in order to facilitate literature searches and to help establish this emerging concept.

低カリウム血性ミオパチーにより首下がりを呈した２症例

We reported two women (78 and 85 years of age) with dropped head syndrome caused by hypokalemic myopathy restricted to the posterior cervical muscles. Both presented with relatively rapid onset of severe neck extensor weakness. Needle EMG demonstrated myogenic changes in the cervical paraspinal muscles and there were high intensity signals in the posterior cervical muscles on the neck MRI. Dropped head syndrome resolved in both patients as potassium normalized. One of the patients relapsed 11 months later with recurrent hypokalemia, but recovered rapidly with supplementation of potassium. Focal myopathy localized in the posterior cervical muscles due to hypokalemia should be considered as one of the possible causes of dropped head syndrome.

Apparently Persistent Weakness After Recurrent Hypokalemic Paralysis: A Tale of Two Disorders

A 19-year-old woman presented with recurrent hypokalemic paralysis, followed by apparently persistent symptoms due to coexisting osteomalacia. Distal renal tubular acidosis type 1 (dRTA1) linked the metabolic abnormalities and occurred as an extraglandular feature of Sjögren syndrome (SS). This case highlights the fact that in the setting of recurrent hypokalemia, apparently progressive weakness should be distinguished from primary hypokalemic paralysis and evaluated for dRTA1, as the metabolic alterations are potentially treatable. Further dRTA1 may precede the occurrence of sicca syndrome in SS.

Ibuprofen codeine combination precipitating severe hypokalaemia in a patient with pre-existing type 1 renal tubular acidosis.

Sir, A 36-year-old lady presented to the A&E with a 2-day history of generalized, severe progressive weakness of her limbs. Two days prior to her presentation, she had been exercising vigorously at the gym and subsequently developed muscle pain. In the hours following, she developed progressive weakness in her upper and lower limbs. She became unable to walk or stand. She described several previous episodes of leg weakness and numbness, especially at night, over a few months. On further questioning, she stated that she had been taking up to eight tablets of an ibuprofen codeine combination (200 mg + 12.8 mg respectively) everyday for 3 months for backache. She had been admitted previously with profound iron deficiency anaemia and weakness but mild hypokalaemia 19 months before, which had resolved completely with oral supplementation. There was no other relevant family or drug history. On examination, the patient was dehydrated, afebrile (37.4°C), with a regular pulse rate of 90 bpm and blood pressure 123/83 mmHg. She had decreased power in all four limbs (MRC score of 3/5 in the lower limbs and 4/5 in the upper limbs). Blood tests on admission showed a serum potassium of 1.7 mmol/L and a high serum creatinine level of 282 mmol/L and urea 12.8 mmol/L (sodium 130 mmol/L, chloride 95 mmol/L, creatinine kinase 289 i.u./mL). Arterial blood gas sampling revealed a metabolic acidosis (pH 7.20, pCO2 3.04 kPa (23 mmHg), pO2 15.7 kPa (118 mmHg), HCO3 11.0 mmol/L, base deficit 18) with an anion gap of 25 mmol/L. Serum lactate was normal (0.9 mmol/L) and salicylate was undetected. An E. coli UTI was discovered and treated. ECG changes were consistent with severe hypokalaemia. Her urine sodium at presentation was 42 mmol/L, potassium 12.4 mmol/L, urea 27 mmol/L and osmolality of 134 mOsm/kg. The urine osmolal gap was −1.8, making recent toluene abuse unlikely. Immunological tests were negative (inter alia, Hep 2 cells, ANA, and autoimmune profile negative). Subsequent investigations showed transient polyuria (urine volume up to 4.3 L/day), high 24-h urinary K+ wasting (175 mmol/day). CT scan of the abdomen showed marked bilateral nephrocalcinosis, but no other abnormalities. The patient re-presented to the emergency department with similar symptoms a month later. On this occasion, she was also found to be hypokalaemic (2.1 mmol/L) with hyperchloraemic metabolic acidosis (pH 7.23, HCO3 14.7 mmol/L, base deficit 12.6). Her serum anion gap was normal (13 mmol/L). Whilst acidotic, her urine anion gap was + 7 mmol/L and urine pH 6.52. She was again treated with fluid resuscitation and potassium repletion. She denied further NSAID or diuretic use. In view of the recurrent hypokalaemia, advanced nephrocalcinosis, urine pH, positive urine anion gap and normal anion gap metabolic acidosis, a diagnosis of longstanding type 1 RTA was made. She made a full recovery and was discharged 5 days later on potassium citrate supplementation, and remained potassium replete on follow-up. There have been reports of ibuprofen codeine combination, particularly in excess doses, causing acute and transient RTA [1–4]; when characterized it has been reported to be type 2. Our patient now meets criteria for a diagnosis of type 1 RTA. This pre-existing condition was not diagnosed until her admission with life-threatening hypokalaemia, after taking an ibuprofen codeine combination for 3 months. This presentation with far graver hypokalaemia than before was accompanied by no alternative explanation for the development of 0.76 mol potassium deficit, and was associated with transient hypophosphataemia. We speculate that at the time of presentation she had developed a proximal tubulopathy, attributable to the ibuprofen codeine combination, resulting in a combined renal tubular acidosis with dramatic consequences. Vigilance in eliciting a detailed analgesic history remains important in patients with acute acidoses, especially in patients with pre-existing renal conditions. Conflict of interest statement. None declared.