Thyrotoxic periodic paralysis complicated by life-threatening acute hypercapnic respiratory failure in a Chinese male with painless thyroiditis.

CONTEXT: Thyrotoxic periodic paralysis (TPP) is a relatively common complication seen in Asian hyperthyroid patients. However, it is a rare occurrence to find a TPP case comprised of acute hypercapnic respiratory failure in patients with painless thyroiditis. PATIENT: A 29-year-old Chinese man presented with flaccid paralysis of all four limbs and he was brought to emergency room. Severe hypokalemia was found on admission. Although treatment had been initiated with potassium chloride supplementation, he went on to develop acute hypercapnic respiratory failure likely due to muscle fatigue. The patient was intubated for mechanical ventilatory support. Once his serum potassium levels were normalized, he was able to be weaned off ventilator support. Thyroid function tests showed elevated free thyroxine concentration and low thyroid-stimulating hormone concentration. He underwent a thyroid uptake scan with 131I which revealed decreased uptake rate of thyroid area. Based on the patient's clinical presentation and associated findings, we diagnosed him with TPP due to painless thyroiditis. We have reviewed TPP cases caused by painless thyroiditis and TPP cases associated with acute hypercapnic respiratory failure. CONCLUSION: It is important to note that potentially fatal complications such as acute hypercapnic respiratory failure might occur in acute attacks of TPP even in cases of TPP due to painless thyroiditis.

Evaluation of the Saline Infusion Test and the Captopril Challenge Test in Chinese Patients With Primary Aldosteronism.

Context: The aim of this study was to determine whether the diagnosis cutoff values associated with the saline infusion test (SIT) and captopril challenge test (CCT) in the Endocrine Society guidelines are applicable to Chinese subjects. Objective and Design: We performed a head-to-head comparison of the SIT and CCT among Chinese subjects with primary aldosteronism (PA) and essential hypertension (EH). Participants and Setting: One hundred sixty-four hypertensive patients were enrolled. Intervention: All participants underwent both the SIT and CCT. Main Outcome Measures: The plasma aldosterone concentration (PAC) and plasma renin activity were measured before and after the SIT and CCT. The degree of PAC decline after CCT was calculated. Results: This study included 115 PA and 49 EH subjects. The prevalence of hypokalemia was 74.8% in the PA group. Supine PACs in the EH and PA groups were 15.1 ± 4.7 mmol/L and 30.4 ± 12.1 mmol/L. Post-SIT PACs were 8.8 ± 1.7 ng/dL and 22.7 ± 10.2 ng/dL in the EH and PA groups. The degree of PAC decline after CCT was 17.7% and 14.2% in the EH and PA groups; post-CCT PACs were 11.7 ± 3.3 ng/dL and 25.9 ± 10.6 ng/dL. PAC values of 11.2 ng/dL and 16.7 ng/dL after the SIT and CCT represented the optimal cutoff values for PA diagnosis. The post-SIT and post-CCT area under the receiver operating characteristic curve values were 0.972 [95% confidence interval (CI) = 0.934 to 0.991] and 0.933 (95% CI = 0.883 to 0.966). Conclusions: Post-SIT and post-CCT PACs, but not the degree of PAC suppression, were both reliable for PA diagnosis. However, the optimal cutoffs were slightly higher in Chinese subjects than those recommended by the Endocrine Society.

Hyperkalemia and Hypokalemia in CKD: Prevalence, Risk Factors, and Clinical Outcomes.

Abnormalities of serum potassium are common in patients with CKD. Although hyperkalemia is a well-recognized complication of CKD, the prevalence rates of hyperkalemia (14%-20%) and hypokalemia (12%-18%) are similar. CKD severity, use of medications such as renin-angiotensin-aldosterone system inhibitors and diuretics, and dietary potassium intake are major determinants of serum potassium concentration in CKD. Demographic factors, acid-base status, blood glucose, and other comorbidities contribute as well. Both hyperkalemia and hypokalemia are associated with similarly increased risks of death, cardiovascular disease, and hospitalization. On the other hand, limited evidence suggests a link between hypokalemia, but not hyperkalemia, and progression of CKD. This article reviews the prevalence rates and risk factors for hyperkalemia and hypokalemia, and their associations with adverse outcomes in CKD.

Serum Potassium, End-Stage Renal Disease and Mortality in Chronic Kidney Disease.

BACKGROUND/AIMS: Hypokalemia and hyperkalemia are often noted in chronic kidney disease (CKD) patients, but their impact on mortality and end-stage renal disease (ESRD) is less well understood. We aimed at studying the associations between potassium disorders, and mortality and progression to ESRD in a CKD population. METHODS: Using our electronic health record-based CKD registry, 36,359 patients with eGFR <60 ml/min/1.73 m(2) and potassium levels measured from January 1, 2005 to September 15, 2009 were identified. We examined factors associated with hypokalemia (<3.5 mmol/l) and hyperkalemia (>5.0 mmol/l) using logistic regression models and associations between serum potassium levels (both as continuous and categorical variables) and all-cause mortality or ESRD using Cox-proportional hazards models. RESULTS: Serum potassium <3.5 mmol/l was noted among 3% and >5.0 mmol/l among 11% of the study population. In the multivariable logistic regression analysis, lower eGFR, diabetes and use of ACE inhibitors or Angiotensin-Receptor Blockers were associated with higher odds of having hyperkalemia. Heart failure and African American race were factors associated with higher odds of hypokalemia. After adjustment for covariates including kidney function, serum potassium <4.0 and >5.0 mmol/l were significantly associated with increased mortality risk, but there was no increased risk for progression to ESRD. Time-dependent repeated measures analysis confirmed these findings. When potassium was examined as a continuous variable, there was a U-shaped association between serum potassium levels and mortality. CONCLUSION: In patients with stage 3-4 CKD, serum potassium levels <4.0 and >5.0 mmol/l are associated with higher mortality but not with ESRD.

Race influences the safety and efficacy of spironolactone in severe heart failure.

BACKGROUND: The incidence of hyperkalemia caused by mineralocorticoid receptor antagonists may vary by race, but whether race influences efficacy of mineralocorticoid receptor antagonists in heart failure (HF) is unknown. METHODS AND RESULTS: We assessed hyperkalemia and outcomes in African Americans (AAs; n=120) and non-AAs (n=1543; white 93%) with New York Heart Association (NYHA) class III or IV HF and left ventricular dysfunction who were randomized to spironolactone, titrated to 25 or 50 mg daily or placebo, in the Randomized Aldactone Evaluation Study (RALES). AA participants were significantly younger, less likely to have an ischemic HF pathogenesis, more likely to be NYHA functional class IV, and more likely to have a higher estimated glomerular filtration rate and heart rate, less hypertension, diabetes mellitus, or history of myocardial infarction compared with non-AA participants. Potassium increased with spironolactone in non-AAs (4.29±0.5-4.55±0.49 mmol/L) but not in AAs (4.32±0.54-4.31±0.49 mmol/L; race by treatment interaction, P=0.03) during the first month and remained higher throughout the trial. Compared with AAs, non-AAs were more likely to attain maximal spironolactone dose (13.9% versus 5.8%; P=0.04) and had higher rates of hyperkalemia (potassium>5.5 mmol/L; 9.7% versus 4.2%; P<0.046), as well as lower rates of hypokalemia (potassium<3.5 mmol/L; 5.6% versus 17.9%; P<0.001). After adjustment for differences in baseline characteristics and achieved study drug dose, spironolactone reduced the combined end point of death or hospitalization for HF in non-AAs (hazard ratio, 0.63; 95% confidence interval, 0.55-0.73) but not in AAs (hazard ratio, 1.07; 95% confidence interval, 0.67-1.71; P value for interaction=0.032). CONCLUSIONS: AAs with HF exhibited less hyperkalemia and more hypokalemia with spironolactone compared with non-AAs and seemed to derive less clinical benefit. These hypothesis-generating findings suggest that safety and efficacy of mineralocorticoid receptor antagonists may differ by race.

Serum potassium and the racial disparity in diabetes risk: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Low serum potassium appears to be independently associated with incident type 2 diabetes, and low dietary potassium is more common in African Americans than in whites. OBJECTIVE: We hypothesized that low serum potassium contributes to the excess risk of diabetes in African Americans. DESIGN: We analyzed data collected from 1987 to 1996 from the Atherosclerosis Risk in Communities (ARIC) Study. At baseline, we identified 2716 African American and 9493 white participants without diabetes. We used multivariate Cox models to estimate the relative hazards (RHs) of incident diabetes related to baseline serum potassium during 9 y of follow-up. RESULTS: Mean serum potassium concentrations were lower in African Americans than in whites at baseline (4.2 compared with 4.5 mEq/L; P < 0.01), and African Americans had a greater incidence of diabetes than did whites (26 compared with 13 cases/1000 person-years). The adjusted RHs (95% CI) of incident diabetes for those with serum potassium concentrations of <4.0, 4.0-4.4, and 4.5-4.9 mEq/L, compared with those with serum potassium concentrations of 5.0-5.5 mEq/L (referent), were 2.28 (1.21, 4.28), 1.97 (1.06, 3.65), and 1.85 (0.99, 3.47) for African Americans and 1.53 (1.14, 2.05), 1.49 (1.19, 1.87), and 1.27 (1.02, 1.58) for whites, respectively. Racial differences in serum potassium appeared to explain 18% of the excess risk of diabetes in African Americans, which is comparable with the percentage of risk explained by racial differences in body mass index (22%). CONCLUSIONS: Low serum potassium concentrations in African Americans may contribute to their excess risk of type 2 diabetes relative to whites. Whether interventions to increase serum potassium concentrations in African Americans might reduce their excess risk deserves further study. The ARIC Study is registered at clinicaltrials.gov as NCT00005131.

Ethnicity and unprovoked hypokalemia in the Atherosclerosis Risk in Communities Study.

BACKGROUND: Hypertension is more prevalent in the African American population when compared with the European American population in the United States. Unprovoked hypokalemia may lead to hypertension and is associated with several forms of recognized secondary hypertension. METHODS: We investigated the association of ethnicity with unprovoked hypokalemia in the second Atherosclerosis Risk in Communities (ARIC) study examination. Hypokalemia was defined as serum potassium <3.5 mmol/L. RESULTS: A statistically significant association was detected between ethnicity and unprovoked hypokalemia (odds ratio = 5.3; 95% confidence interval = 3.6, 7.7) with unprovoked hypokalemia more prevalent in African Americans both before and after adjustment for important covariates. The unadjusted prevalence for unprovoked hypokalemia was 2.6% for African Americans and 0.5% for European Americans. CONCLUSIONS: We found that the prevalence of unprovoked hypokalemia for African Americans in the ARIC cohort was more than five times that for European Americans. These data suggest that an increased awareness of hypokalemia and its etiology may be indicated for African Americans.

Intestinal permeability and diarrhoeal disease in Aboriginal Australians.

BACKGROUND: Northern Territory Aboriginal children hospitalised with acute gastroenteritis have high rates of acidosis, hypokalaemia, and dehydration. AIMS: To determine whether Aboriginal children with and without diarrhoea have greater impairment in intestinal function than non-Aboriginal children, as assessed by increased permeability ratios. METHODS: A descriptive study of 124 children (96 Aboriginal and 28 non-Aboriginal) hospitalised with and without diarrhoea. Intestinal permeability was assessed by the lactulose to rhamnose (L-R) ratio from a five hour urine collection. RESULTS: In Aboriginal children, mean L-R ratios (95% confidence intervals) were 18.3 (17.1 to 19.6) with diarrhoea and 9.0 (7.3 to 11.0) without diarrhoea, and in non-Aboriginal children they were 5.9 (2.8 to 12. 3) and 4.2 (3.3 to 5.2), respectively. In patients with diarrhoea, L-R ratios were significantly raised when accompanied by acidosis (mean, 22.8; 95% CI, 17.0 to 30.5), hypokalaemia (mean, 20.7; 95% CI, 15.4 to 27.9), and >/= 5% dehydration (mean, 24.3; 95% CI, 19.0 to 29.6) compared with none of these complications (mean, 7.0; 95% CI, 3.5 to 13.8). CONCLUSION: The high incidence of acidosis, hypokalaemia, and dehydration in Aboriginal children admitted with diarrhoeal disease is related to underlying small intestinal mucosal damage.

Thyrotoxic periodic paralysis in Mexican mestizo patients: a clinical, biochemical and HLA-serological study.

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is characterized by episodes of neuromuscular weakness occurring in the context of hypokalemia and hyperthyroidism and has been predominantly described in Oriental populations. Whereas it is uncommon in Caucasians and Blacks, TPP does occur in individuals of Native American descent. The objective was to analyze the clinical, biochemical, and HLA characteristics of a group of Mexican mestizo patients with TPP. METHODS: The sample was comprised of 14 men with TPP diagnosed since January 1990, based on one or more episodes of flaccid paralysis, accompanied by hypokalemia and occurring in the context of clinical and biochemical hyperthyroidism. Eight were available for HLA testing. RESULTS: Hyperthyroidism was diagnosed before the development of periodic paralysis in five of the patients, whereas in six it occurred afterward. The severity of paralysis did not correlate with the degree of either hypokalemia or hyperthyroidism. An increased frequency of HLA-DR3 was found in Graves' patients without paralysis but not in those with paralysis, as compared to the general population. CONCLUSIONS: TPP is more common than previously thought in Mexicans, in whom it behaves as in other Native American groups. The lack of HLA-DR3 association in Graves' patients with TPP is interesting, but at the moment has no pathophysiological implications.

Thyrotoxic periodic paralysis in mexican mestizo patients: a clinical, biochemical and HLA-Serological study

Background. Thyrotoxic periodic paralysis (TPP) is characterized by episodes of neuromuscular weakness occurring in the context of hypokalemia and hyperthyroidism and has been predominantly described in Oriental populations. Whereas it is uncommon in Caucasians and Blacks, TPP does occur in individuals of Native American descent. The objective was to analyze the clinical, biochemical, and HLA characteristics of group of Mexican mestizo patients with TPP. Methods. The sample was comprised of 14 men with TPP diagnosed since january 1990, based on one or more episodes of flaccid paralysis, accompanied by hypokalemia and occurring in the context of clinical and biochemical hyperthyroidism. Eight were available HLA testing. Results. Hyperthyroidsm was diagnosed before the development of periodic paralysis in five of the patients, whereas in six it occurred afterward. The severity of paralysis did not correlate with the degree of either hypokalemia or hyperthyroidism. An increased frequency of HLA-DR3 was found in Graves' patients without paralysis but not in those with paralysis, as compared to the general population. Conclusions. TPP is more common than previously thoought in Mexicans, in whom it behaves as in other Native American groups. The lack of HLA-DR3 association in Graves' patients with TPP is interesting, but at the moment has no pathophysiological implications

Sudden periodic paralysis: rare manifestation of thyrotoxicosis.

Nonfamilial hypokalemic thyrotoxic periodic paralysis is rarely diagnosed among Caucasians and blacks in the western world but it is relatively common among Asiatics. Sudden paralysis occurring while at rest after a large carbohydrate meal or strenuous exercise in an undiagnosed mild thyrotoxic patient is a common presentation. A case illustrating such presentation is reported. Intracellular shifts of potassium triggered or facilitated by hyperthyroidism and hyperinsulinemia are the biochemical features. Correction of the thyrotoxic state is the definitive treatment for this disorder. Judicious administration of potassium is indicated during the hypokalemic episode to prevent life-threatening arrhythmias.

Use of indapamide in hospital and community clinics and its effect on plasma potassium in Chinese patients.

OBJECTIVES: To investigate the usage pattern of indapamide and other antihypertensive drugs in patients attending a community-based government outpatient clinic (GOPC) or a hospital-based specialist clinic (SC). The plasma potassium concentrations of patients receiving indapamide and other diuretics were also examined. METHOD: Prescriptions from the SC and the GOPC were reviewed and collected during January 1998. Patients' plasma potassium concentrations and the date of initiation of each medication were retrieved from the hospital computer databases at SC. An age- and sex-matched control group of patients on non-diuretic antihypertensive drugs was identified. RESULTS: A total of 1648 and 773 prescriptions were collected from the SC during a 1-week period and GOPC during a 1-month period, respectively. Approximately half (45%) of the patients received antihypertensive treatment. Indapamide was five times more frequently prescribed in GOPC than SC (84.7 vs. 17.7%, P<0.001). Calcium channel blocking agents were the commonest antihypertensive drugs used in both clinics. The mean plasma potassium concentration of patients taking indapamide was lower than that of the control group (P = 0.037). Multiple linear regression analysis showed that consumption of indapamide (P =0.002) and duration of diuretic therapy (P = 0.023) were significantly related to changes in plasma potassium concentrations [multiple regression equation for potassium level = 4.09-0.145 (thiazide = 1)-0.377 (indapamide = 1) -0.00468 (duration of diuretic therapy in months)]. CONCLUSION: Indapamide was used extensively in the community clinic and less in the hospital-based outpatient clinic. Patients receiving indapamide had a significantly lower plasma potassium concentration as compared to other diuretics or antihypertensive groups and this was predicted by a multiple linear regression model. Monitoring plasma electrolytes before initiation of indapamide treatment and at regular intervals thereafter is essential for detecting the hypokalaemia that may occur in Chinese patients.

Sudden periodic paralysis: rare manifestation of thyrotoxicosis

Nonfamilial hypokalemic thyrotoxic periodic paralysis is rarely diagnosed among Caucasians and blacks in the western world but it is relatively common among Asiatics. Sudden paralysis occurring while at rest after a large carbohydrate meal or strenuous exercise in an undiagnosed mild thyrotoxic patient is a common presentation. A case illustrating such presentation is reported. Intracellular shifts of potassium triggered or facilitated by hyperthyroidism and hyperinsulinemia are the biochemical features. Correction of the thyrotoxic state is the definitive treatment for this disorder. Judicious administration of potassium is indicated during the hypokalemic episode to prevent life-threatening arrhythmias

Thyrotoxic periodic paralysis in a Chinese population.

We retrospectively evaluated the characteristics of adult patients admitted with thyrotoxic hypokalaemic periodic paralysis in Hong Kong. From 1984 to 1993, 45 Chinese adult patients were admitted with acute limb weakness, plasma potassium < or = 3.5 mmol/l and thyrotoxicosis confirmed by laboratory investigations. All but one were male. Seventy-five percent of attacks occurred between 9pm and 9am. Half of the attacks occurred between July and October (49.1%), most commonly in August (20%). Mean (+/- SEM) plasma potassium on admission was 2.17 +/- 0.08 mmol/l (range 1.1-3.5). In 15 episodes (27.3%), plasma potassium on recovery exceeded 5.0 mmol/l, while in three episodes (5.5%), potassium exceeded 6.0 mmol/l. No patient had a positive family history of thyrotoxic periodic paralysis. Only 28.9% had a known history of thyrotoxicosis before their first presentation with periodic paralysis. Twenty-seven (60%) had clinical evidence of thyrotoxicosis. Although all were biochemically thyrotoxic, 11.4% had only a mild degree of thyrotoxicosis (suppressed thyroid-stimulating hormone, high free thyroxine, but normal free triiodothyronine). One quarter of the patients had a normal erythrocyte zinc concentration, indicating either a short history of thyrotoxicosis or transient thyrotoxicosis. The diagnosis of thyrotoxic hypokalaemic paralysis should always be considered in Chinese patients with acute muscle weakness, especially in young males. Absence of clinical thyrotoxicosis does not exclude the diagnosis. Plasma potassium should be monitored carefully during treatment to prevent rebound hyperkalaemia.

Liddle's syndrome, an underrecognized entity: a report of four cases, including the first report in black individuals.

Liddle's syndrome, a rare cause of hypokalemic hypertension, is characterized by a renal tubular sodium channel defect resulting in excessive sodium absorption and concomitant potassium wasting. In this disorder, although the clinical manifestations resemble primary aldosteronism, serum and urine aldosterone are suppressed. The syndrome is transmitted in an autosomal dominant pattern. It has been reported previously in white and oriental populations but not in the black individuals. We identified four patients (two of whom are black) in our nephrology clinic, with severe hypokalemic hypertension not correctly diagnosed for several years. All patients underwent an extensive work-up for secondary hypertension because of persistent severe hypertension (average blood pressure, 210/130 mm Hg) despite high-dose multi-drug therapy. Primary aldosteronism was excluded because of low serum aldosterone. Cushing's syndrome, pheochromocytoma, renal artery stenosis, and enzymatic deficiencies of cortisol synthesis (11 beta-hydroxylase, 17 alpha-hydroxylase, 5 beta-reductase, and 11 beta-hydroxysteroid dehydrogenase) were ruled out with extensive endocrine and radiologic studies. Once the diagnosis of Liddle's syndrome was suspected, all patients were treated with either triamterene or ameloride, with resolution of hypokalemia and correction of hypertension occurring within 5 to 7 days. Our findings suggest that Liddle's syndrome can occur in the black population. Although the actual incidence of this syndrome remains unknown, it may be significantly more common than we are led to believe since it is inherited in a Mendelian pattern. Whether there is a subset of low-renin, salt-sensitive black hypertensive patients who have the same or similar sodium channel defect remains to be elucidated.

Thyrotoxic hypokalemic periodic paralysis: report of four cases in black American males.

Thyrotoxic periodic paralysis (TPP) is an unusual complication of a fairly common disease affecting mostly Asian males. In the United States, there have been several reports of TPP in different ethnic populations and it appears that the incidence is approximately one-tenth of that found in Asian countries. Only six reports of TPP in African-Americans could be found in the literature; however, we are reporting four cases diagnosed within a 13-year period at our institution. We conclude that TPP may occur more often in Blacks than previously suspected and should be considered when patients present with unexplained hypokalemia, muscular weakness and rhabdomyolysis. The epidemiology, clinical manifestations, pathophysiology, and treatment of TPP are reviewed.

Changes in red cell sodium content and blood pressure levels with potassium supplementation in black hypertensive patients

Red cell sodium and potassium content were measured in 24 black hypertensive patients while they were hypokalemic on thiazide diuretic therapy and again after potassium supplements (48 meq elemental K+/day). Mean and diastolic blood pressure levels fell by 4.1-4.4 and 4.5-5.2 mm. hg respectively with potassium supplementation, while both urinary excretion of potassium and serum potassium rose. Urinary sodium excretion was unchanged. Rd cell potassium remained within the normal range but red cell sodium, initially high, fell with potassium therapy. This study confirms the importance of potassium supplementation where hypokalemia results from diuretic therapy(AU)