100 Case Report Olgu Sunumu

Rhabdomyolysis Secondary to Severe : Case Report Ciddi Hipokalemiye Ba¤l› Rabdomiyoliz: Olgu Sunumu

Özlem Çelik, Ifl›l Bavuno¤lu*, Mehmet Yürüyen*, A. Sadi Gündo¤du, P›nar Kad›o¤lu

Division of and Metabolism, Department of Internal Medicine, Cerrahpasa Medical School, University of Istanbul, ‹stanbul, Turkey *Department of Internal Medicine, Cerrahpasa Medical School, University of ‹stanbul, Turkey

Abstract Primary hyperaldosteronism is an endocrine disorder characterized by an increased excretion from the adrenal glands, which causes , hypokalemia, and suppressed plasma activity. It can be difficult to diagnose until hypokalemic manifestations, such as rhabdomyolysis, occur, and also these subjects may be treated as essential hypertensive patients. Here, we report a 51-year-old woman who presented with rhabdomyolysis caused by severe hypokalemia and was diagnosed with Conn’s syndrome.Turk Jem 2010; 14: 100-2 Key words: Primary hyperaldosteronism, hypokalemia, rhabdomyolysis

Özet Primer hiperaldosteronizm adrenal bezlerden aldosteron sekresyonunun art›fl›na ba¤l› hipertansiyon, hipokalemi, plazma renin aktivitesinin bask›lanmas›na neden olan endokrin bir hastal›kt›r. Rabdomiyoliz gibi hipokalemik belirtiler olufluncaya kadar tan›nmayabilir ve bu hastalar esansiyel hipertansiyon gibi tedavi edilebilirler. Biz bu yaz›da hipokalemiye sekonder rabdomyoliz ile gelen Conn’s syndrome tan›s› alan 51 yafl›nda kad›n hastay› tart›flaca¤›z. Türk Jem 2010; 14: 100-2 Anahtar kelimeler: Primer hiperaldosteronizm, hipokalemi, rabdomiyoliz

Introduction Case Report

Primary hyperaldosteronism (PA) is characterized by hypertension, A 51-year-old woman was admitted to our hospital with severe hypokalemia, metabolic , suppressed plasma renin activity weakness and muscle cramps. She had a history of hypertension (PRA) and increased aldosterone excretion. With current screening for nine years and had been treated with indapamide for the last methods, it appears that PA may be the most common form two years. Three months ago, her routine biochemical tests of accounting for up to 5-10% of all revealed hypokalemia and normal creatine phosphokinase (CPK) hypertensives. The two major subtypes of primary hyperaldosteronism levels. At that time, she had no complaints and her examination are bilateral idiopathic hyperaldosteronism and aldosterone- was normal. The patient had been operated on for parathyroid producing adenoma (APA) (1,2). It is has been recently recognized adenoma in 2002. At admission, she was visibly unwell. The that most patients with PA are not hypokalemic. Plasma aldosterone pressure was 150/80 mm/Hg, pulse rate was 76/min. concentration (PAC) to PRA ratio is currently the most reliable Cardiovascular, pulmonary and abdominal examinations were method of screening for PA (1-5). Clinically, hyperaldosteronism is unremarkable. She had paresthesia and muscle cramps, but mostly asymptomatic, but some patients may present with severe musculoskeletal examination revealed normal muscle strength. hypokalemia, , unusual sensations (paresthesias), Her neurological examination was normal. muscle cramps, tetany, and in severe cases, transient . Initial laboratory tests showed severe hypokalemia (1.58 mmol/L, We present a patient with PA associated with severe rhabdomyolysis normal reference range: 3.6-5.1 mmol/L), extreme elevation of the due to profound hypokalemia. serum CPK levels (22 230 IU/L, normal reference range: 29-200

Address for Correspondence: P›nar Kad›o¤lu MD, Division of Endocrinology and Metabolism, Department of Internal Medicine, Cerrahpasa Medical School, University of ‹stanbul, Turkey Gsm: +90 532 404 10 40 E-mail: [email protected] Recevied: 02.12.2010 Accepted: 26.12.2010 Turkish Journal of Endocrinology and Metabolism, published by Galenos Publishing. Çelik et al. Turk Jem 2010; 14: 100-2 Rhabdomyolysis Secondary to Severe Hypokalemia: Case Report 101

IU/L), and (bicarbonate 29 mmol/L, normal are a few reports of cases of PA complicated by hypokalemia and reference range: 22-26 mmol/L ). Other laboratory analysis rhabdomyolysis (6,7). The mechanism of the hypokalemia-induced showed: urea nitrogen 53 mg/dL (10-50 mg/dL), creatinine 1.5 rhabdomyolysis in PA is still not clear, but some reports suggest (0.6-1.2 mg/dL) mg/dL, sodium 145 mmol/L (136-144 mmol/L), that the enhanced muscle sodium- pump (ATPase) calcium 7.4 mg/dL (8.5-10.6 mg/dl), magnesium 1.9 mg/dL, glucose activity may cause an increased potassium entry into the cells. Hypokalemia may induce muscle injury or frank necrosis as a 104 mg/dL, uric acid 6.9 mg/dL, aspartate aminotransferase (AST) consequence of relative ischemia (3,7). If hypokalemia is not 279 IU/L (15-41 IU/L) , alanine aminotransferase (ALT) 76 IU/L(15-41 treated early, it may lead to worsening of mild myalgia to tetraplegia IU/L). Complete blood count, urine examination and chest X-ray or severe acute renal failure because of the release of intracellular were normal. Electrocardiogram revealed a normal sinus rhythm muscle constituents such as CPK and myoglobulin into the with non-diagnostic T-wave changes consistent with hypokalemia. circulation (7). PA should be suspected in a hypertensive patient There was no history of crush injury, intense physical exercise, fever, with hypokalemia and metabolic alkalosis. However, hyperaldos- seizures, diabetes mellitus, recent viral illness, alcohol and drug teronism may also present with normokalemia, especially in the abuse or musculoskeletal , which can cause rhabdomyol- early phase of the disease, and after taking potassium-wasting ysis. Based on these findings, the patient was diagnosed with diuretics, hypokalemia occurs, as seen in this case. hypokalemic rhabdomyolysis. Due to the possibility of drug-induced Because of the severe hypokalemia, rhabdomyolysis, hypertension hypokalemia, indapamide was discontinued. Potassium and fluid and metabolic alkalosis, the patient was screened for secondary causes of hypertension. There was no history of crush injury, replacement therapies were initiated. Two weeks later, the intense physical exercise, fever, seizures, diabetes mellitus, musculoskeletal symptoms resolved and the serum CPK levels, recent viral illness, licorice, laxatives, alcohol and drug abuse or renal and hepatic function tests returned to normal ranges (Table 1). musculoskeletal disease, which are causes of rhabdomyolysis. Because of the severe hypokalemia, the patient was screened for and Gitelman syndrome were excluded, secondary causes of hypertension. The morning supine PAC because the patient had a history of hypertension for nine years. was elevated at 38.6 ng/dL (supine normal range: 2.9-16.1). The Biochemical diagnosis of PA was made by measuring a high level simultaneous PRA was low at 0.16 ng/mL/h (supine normal range: of PAC (≥ 15 ng/dL) in the setting of low PRA (< 1ng/mL/h). If the 0.2-2.8), giving a calculated supine aldosterone-to-renin ratio (ARR) of 241.2. PAC was 33 ng/dL, remained high in response to a saline load, and ARR was calculated as 100. Abdominal computed tomography (CT) showed a low-density left adrenal mass measuring 2.5x1.5 cm in diameter (Figure 1). Also the laboratory analysis of thyroid function, urinary metanephrine, normetanephrine, vanilmandelic acid and levels, and renal Doppler ultrasound were normal. PA was suspected and the patient was referred to surgery service for laparoscopic adrenalectomy. A solitary adenoma was removed surgically and pathologic examination revealed a benign . After surgery, she had no complaints and did not need any antihypertensive medication or potassium replacement therapy.

Discussion

Here, we report the case of a patient with rhabdomyolysis who was admitted to our hospital with diffuse myalgia, cramps and Figure 1. CT scan on admission showed a low-density left adrenal mass weakness caused by severe diuretic-induced hypokalemia. There measuring 2,5x1,5 cm in diameter (arrow).

Table 1. Serum biochemistry profile of the patient on admission, on the third day, 1th week, 2nd week, 4th week (post-operative)

Reference range Admission 3th day 1th week 2nd week 4th week (post-op) Sodium (136-144 mmol/L) 145 145 143 137 143 Potassium (3.6-5.1 mmol/L) 1.58 3.6 4.1 4.6 3.8 CPK (29-200 U/L) 22230 18305 2022 94 55 Urea (10-50 mg/dL) 53 15 25 33 41 Creatinine (0.6-1.2 mg/dL) 1.5 1.2 1.2 1.2 1.2 AST (15-41 U/L) 279 601 140 24 16 ALT (10-40 U/L) 76 271 168 29 12 Bicarbonate (22-26 mmol/L) 29.3 - - 23.6 22.8 Çelik et al. 102 Rhabdomyolysis Secondary to Severe Hypokalemia: Case Report Turk Jem 2010; 14: 100-2 results are high (ARR≥20 ng/dL per ng/mL per hour), then Also, physicians should be aware of hypokalemia-induced confirmation is required. These tests are available: [1] the saline rhabdomyolysis among patients with PA. suppression test, [2] the dietary sodium loading test, [3] the Acknowledgement fludrocortisone suppression test, and [4] the captopril suppression Written consent for publication was obtained from the patient. test (1,2,4). The most commonly used confirmatory test is the saline suppression test. Patient with inappropriate aldosterone secretion References will not have a suppression of aldosterone (4,8,9). The next step of the diagnosis is to perform a CT imaging. If there is an adrenal 1. Young WF. -treatment options. Growth Horm IGF Res 2003;13:102-8. mass, adrenal vein sampling (AVS) should be tested. But, for 2. Cecilia Mattson, William F. Young Jr. Primary aldosteronism: diagnostic cases, in which APA is identified with high prevalence (patients and treatment strategies. Nat Clin Pract Nephrol 2006;4:198-208. ≤40 years of age with marked PA, e.g. PAC ≥30 ng/d L and a 3. Chuang HT, Wang HC, Tseng YB, Hsu HY, Tsai PJ, Hsu GB, Fang CT. Conn’s syndrome with an unusual presentation of rhabdomyolysis well-defined hypodense adrenal mass), AVS can be bypassed secondary to severe hypokalemia. Tzu Chi Med J 2008;20:327-33. and unilateral adrenalectomy can be performed (2,10). In our case, 4. Funder JW, Carey RM, Fardella C, Gomez-Sanchez E, Mantero F, biochemical and clinical evidence of aldosterone excess was Stowasser M, Young WF, Montori VM. Case Detection, Diagnosis and Treatment of Patinets with Primary Aldosteronsim: Endocrine Society clear. The presence of a left-sided adenoma (size >1 cm, uniform, Clinical Practice Guideline. J Clin Endocrinol Metab 2008;93:3266-81. round, hypodense, e.g. Hounsfield unit score ≤10) was confirmed 5. Carey RM. Primary aldosteronism. Horm Res 2009;1:8-12. with CT imaging. Thus, AVS was not necessary. 6. Freel EM, Connell JMC. Diagnosis of adenomatous primary aldosteronism in a patient with severe hypertension. Nat Clin Pract Treatment for PA can be surgical or medical, which depends on Endocrinol Metab 2005;2:111-5. the subtype of the disease. Most functional adrenal tumours are 7. Goto A, Takahashi Y, Kishimoto M, Minowada S, Aibe H, Hasuo K, benign and surgery is the main treatment modality for Conn’s Hiroshi K, Noda M. Primary aldosteronism associated with severe syndrome (2). In the majority of patients with surgically managed rhabdomyolysis due to profound hypokalemia. Intern Med 2009;48:219-23. APA, and serum potassium levels improve (2,10). 8. Mulatero P, Rabbia F, Milan A, Paglieri C, Morello F, Chiandussi L, Veglio PA is a common and potentially curable cause of secondary F. Drug effects on aldosterone/plasma renin activity ratio in primary hypertension. This case showed us that PA may not be diagnosed aldosteronism. Hypertension 2002;40:897-902. until hypokalemic manifestations, such as rhabdomyolysis, occur. 9. Schirpenbach C, Reincke M. Screening for primary aldosteronism. Best Pract Res Clin Endocrinol Metab 2006;20:369-84. In hypertensive patients, the serum potassium concentration 10. Martinez DG. Adrenalectomy for primary aldosteronism; authors’ reply. should be determined prior to the initiation of diuretic therapy. Ann Intern Med 2003;138:157-9.