Case Report doi: 10.4183/aeb.2010.251 SEVERE HYPERKALEMIA WITHOUT ELECTROCARDIOGRAPHIC CHANGES IN A PATIENT WITH ADDISON DISEASE S. Isik 1, D. Berker* 1, Y. Aydin 2, U. Ozuguz 1, Y. Tutuncu 1, Y. Simsek 3, S. Guler 1 1 Ministry of Health, Ankara Numune Research and Training Hospital, Department of Endocrinology and Metabolism, Ankara,Turkey 2 Duzce University Faculty of Medicine - Department of Endocrinology and Metabolism, Duzce, Turkey, 3 Ministry of Health, Ankara Numune Research and Training Hospital, Department of Internal Medicine Ankara, Turkey Abstract Objective. Hyperkalemia is one of the most common acute life-threatening metabolic emergencies. Alterations in serum potassium (K + ) levels can have dramatic effects on cardiac cell conduction and may lead to electrocardiographic (ECG) changes. But in some patients ECG changes do not accompany serum K + abnormalities. Severe hyperkalemia secondary to Addison Disease (AD) is rare. Case. A 40-year-old woman with AD was admitted to emergency service with generalized pain. The patient s serum K + level was found to be at the highest level that can be detected in our laboratory (>10.0 mmol/l, normal 3.5-4.5 mmol/l) and repeated serum K + confirmed the previous result. Results of repeated ECGs have revealed a normal sinus rhythm. Our case is particularly interesting because it demonstrates an Addison patient that has an extremely high level of K + (>10 mmol/l) without any accompanying ECG changes. Conclusion. Our case confirms that diagnostic ECG changes do not always accompany severe hyperkalemia. Therefore, clinicians should be careful that ECG may look normal in the presence of severe hyperkalemia. Keywords: Hyperkalemia, Addison Disease, chronic renal failure, electrocardiography. *Correspondence to: Dilek Berker, MD, Ministry of Health, Ankara Numune Research and Training Hospital, Endocrinology and Metabolism Clinic, 23.Cad Simkent Sitesi No:8/11 Kirkkonaklar, Ankara, Turkey. Phone: +905056275953, fax: +903123093398 E-mail: dberker6@yahoo.com Acta Endocrinologica (Buc), vol. VI, no. 2, p. 251-255, 2010 251
S.Isik et al. INTRODUCTION Potassium (K + ) plays an important role in maintaining the electrical potential across the cellular membrane, as well as in depolarization and repolarization of the myocytes. These electrophysiological effects are reflected as some predictable electrocardiographic (ECG) manifestations (1, 2). Severe hyperkalemia induces fatal dysrhythmias, the recognition of its electrocardiographic manifestations is very important (3). We describe here a case of Addison Disease (AD) without any electrocardiographic abnormalities associated with severe hyperkalemia. CASE REPORT A 40-year-old woman with AD was admitted to the emergency service with generalized pain. Her medical history included autoimmune AD and urolithiasis. Her usual medications at the time of admission included prednisolon (7.5 mg/day) and fludrocortisone (0.1 mg/day). Vital signs showed a blood pressure of 100/60 mmhg, a heart rate of 80 beats/min and a respiratory rate of 24 breaths/min. Her physical examination was notable for mild weakness. The patient s serum K + level was found to be at the highest level that can be detected in our laboratory (>10.0 mmol/l, normal 3.5-4.5 mmol/l) and repeated serum K + confirmed the same result. Informed consent of the patient has been obtained. Other laboratory tests were creatinine 2.18 mg/dl, serum sodium level 128 mmol/l (normal 135-145 mmol/l), glucose 83 mg/dl (70-110 mg/dl) and ACTH 64.45 pg/ml (normal 4.7-48.8 pg/ml). In arterial blood gas analysis ph was 7.42, po 2 78 and pco 2 40. In our patients, leucocytosis, thrombocytosis or hemolysis were not present in the blood specimens, and there was no prolonged muscle ischemia during venipuncture. Results of multiple 12-lead ECGs have revealed a normal sinus rhythm with a rate of 75/min (Fig. 1). An ECG performed 15 minutes later demonstrated the same findings. 252 Figure 1. Patient s ECG in admission.
Severe hyperkalemia without ECG changes The patient was immediately treated with i.v. calcium gluconate, followed by glucose/insulin and sodium bicarbonate infusions. Because of severe hyperkalemia she underwent emergent hemodialysis and her K + level gradually returned to normal level. When patient s K + level was restored to normal ranges, her electrocardiographic findings were similar with the previous one (Fig. 2). Her medication doses were increased to prednisolon 15 mg/day and fludrocortisone 0.2 mg/day. Polystyrene sulfonate calcium 40 g/day was added to her treatment to maintain normal K + levels. Figure 2. Patient s ECG after potassium returned to normal levels. DISCUSSION Extracellular K + concentration is normally maintained between 3.5 and 4.5 mmol/l by the equilibrium between K + excretion and consumption. This equilibrium is modulated by insulin, catecholamines and, to a lesser extent, by acidbase balance, plasma tonicity, and several other factors (3). The average daily intake of potassium is 50-200 mmol K + /day and, after ingestion, monovalent K + ions are easily and actively absorbed into the small intestine and extremely rapidly transported into the intracellular space by means of the Na/K ATP-ase pump mediated by insulin (4). The ratio of intracellular to extracellular potassium is about 60:1. A very large amount of potassium (4000 mmol) may be accommodated within this space, whereas the acute addition of as little as 20-40 mmol of K + into the extracellular compartment may be lethal (3, 4). Potassium excretion is mainly through the kidney (90%) via the late distal and cortical collecting tubules and special potassium channels and depends on the activity of the ATP-ase pump, the electrochemical potassium gradient and membrane permeability (4). Increased extracellular potassium concentration is a potent stimulus to aldosterone secretion that in turn causes active sodium reabsorption (and cellular uptake of potassium) mediated through a sodium-potassium ATP-ase pump and increased permeability of the luminal membrane for potassium (5). 253
S.Isik et al. Among main causes of hyperkalemia are impaired excretion (renal impairment, aldosterone deficiency, drug action on renal excretion (heparin, NSAID agents, etc.), alteration in intra/extra cellular potassium distribution (acidosis, severe insulin deficiency (diabetic ketosis), cell lysis, etc.), and increased intake (3, 6). Experimental hyperkalemia and several retrospective human studies have demonstrated a close correlation between serum K + concentrations and its ECG effects (1,2). Predictable sequence of ECG changes with increasing hyperkalemia, usually seen when serum K + exceeds 6.5 to 6.7 mmol/l and it has been postulated that extremely high levels of serum K + ( > 8 mmol/l) are almost always associated with the classic ECG manifestations (7). Peaked T-waves in the precordial leads are among the most common and the most frequently recognized findings on the ECG. A tall peaked T wave with shortened QT interval is the first change seen on the ECG in a patient with hyperkalemia. This is followed by progressive prolongation of the PR interval and QRS duration. The P wave may disappear, and ultimately the QRS widens further to a sine wave. Ventricular fibrillation or standstill are the most severe consequences. Metabolic alterations such as alkalosis, hypernatremia, or hypercalcemia can antagonize the transmembrane effects of hyperkalemia and result in unremarkable ECG changes (8). There have been several reports in the literature of patients who had K + levels greater than 7.5 meq/l without electrocardiographic findings of hyperkalemia (9, 10). But previous reports of profound hyperkalemia (potassium 10 mmol/l) without the expected ECG findings are rare. Our case is particularly interesting because an extremely high level of serum K + may not always be associated without ECG changes. In uncomplicated AD, aldosterone deficiency leads to hyperkalemia that is typically moderate or mild but rarely severe. Therefore, in our case nephropathy can also contribute to severe hyperkalemia together with AD. Patients with chronic renal insufficiency frequently have an impaired kaliuretic response to exogenous mineralocorticoid administration, suggesting that enhanced distal chloride reabsorption may account for many of the findings of hyporeninemic hypoaldosteronism (11). Rapid increases in K + concentrations may potentiate the cardiotoxic effects of hyperkalemia, whereas if hyperkalemia develops slowly (e.g., chronic renal failure), cardiac manifestations may be attenuated. Chronic renal failure was present in our patient and may explain the lack of ECG changes. The ability to maintain potassium excretion at near normal levels is generally maintained in patients with renal disease as long as both aldosterone secretion and distal flow are maintained (12). Thus, hyperkalemia generally develops in the patient who is oliguric or who has an additional problem such as a high potassium diet, increased tissue breakdown, hypoaldosteronism (3, 13) In conclusion, our case confirms that diagnostic ECG changes do not always accompany severe hyperkalemia. Therefore, clinicians should be careful that ECG may look normal in the presence of severe hyperkalemia. 254
Severe hyperkalemia without ECG changes REFERENCES 1.Mattu A, Brady WJ, Robinson DA. Electrocardiographic manifestations of hyperkalemia. Am J Emerg Med 2000;18: 721-729. 2.Yu AS. Atypical electrocardiographic changes in severe hyperkalemia. Am J Cardiol 1990;77: 906-908. 3.Rose, BD, Post, TW, Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw- Hill, New York, 2001, pp. 383-396, 898-910. 4.Guyton AC, Hall JC. In: Textbook of Medical Physiology, 10th ed. 2000; p. 336-339. 5.Wang W. Regulation of renal K transport by dietary K intake. Annu Rev Physiol. 2004;66:547-569. 6.Adrogué, HJ, Lederer, ED, Suki, WN, Eknoyan, G. Determinants of plasma potassium levels in diabetic ketoacidosis. Medicine (Baltimore) 1986; 65:163. 7.Webster A, Brady W, Morris F. Recognising signs of danger: EKG changes resulting from an abnormal serum potassium concentration. Emerg Med J 2002;19:74-77. 8.Campistol JM, Almirall J, Montoliu J, Revert L. Electrographic alterations induced by hyperkalaemia simulating acute myocardial infarction. Nephrol Dial Transplant 1989;4:233-235. 9.Martinez-Vea A, Bardaji A, Garcia C, Oliver JA. Severe hyperkalemia with minimal electrocardiographic manifestations: a report of seven cases. J Electrocardiol 1999;32:45-49. 10.Gogas BD, Iliodromitis EK, Leftheriotis DI, Flevari PG, Rallidis LS, Kremastinos DT. Instantaneous electrocardiographic changes and transient sinus rhythm restoration in severe hyperkalaemia. Int J Cardiol 2009, 27 (Epub ahead of print). 11.Pelleya R, Oster JR, Perez GO. Hyporeninemic hypoaldosteronism, sodium wasting and mineralocorticoid-resistant hyperkalemia in two patients with obstructive uropathy. Am J Nephrol. 1983;3:223-227. 12.Gonick HC, Kleeman CR, Rubini ME, Maxwell MH. Functional impairment in chronic renal disease. 3. Studies of potassium excretion. Am J Med Sci 1971; 261:281-290. 13.Allon M. Hyperkalemia in end-stage renal disease: mechanisms and management. J Am Soc Nephrol 1995; 6:1134-1142. 255