Myasthenia Gravis Complicated with Primary Aldosteronism and Hypokalemic Myopathy

□ CASE REPORT □

Shu-ichi Yamashita, Wakaba Tsuchimochi, Tadato Yonekawa, Hideki Yamaguchi, Itaru Kyoraku, Kazutaka Shiomi and Masamitsu Nakazato

Abstract

A 34-year-old Japanese man was admitted to an outside hospital with an elevated creatinine kinase level and suspected myositis. He was treated with high dose methylprednisolone, which caused severe aggravation of muscle weakness. He was transferred to our hospital at that time. On admission, chest computed tomography (CT) and the presence of anti-acetylcholine receptor antibodies supported a diagnosis of myasthenia gravis and thymoma. Laboratory findings showed hypokalemia, low plasma renin activity and high serum aldosterone. Further studies, including abdominal CT and adrenal venous sampling suggested primary aldosteronism. At first, thymectomy was performed, and one month later, he was treated with laparoscopic adrenalectomy. Immediately after this procedure, he suffered from myasthenic crisis, which was successfully managed with mechanical ventilation and steroid pulse therapy followed by oral prednisolone. This case pre- sented a serious difficulty in differentiating from various myopathies and giving proper treatment because of a rare combination of independent diseases and their masquerading clinical features.

Key words: myasthenic crisis, hypokalemia, thymectomy, adrenalectomy, hypokalemia-induced rhabdomyolysis

(Inter Med 48: 1465-1469, 2009) (DOI: 10.2169/internalmedicine.48.2311)

mary aldosteronism. At first, he was considered to have Introduction myositis and was treated as such at his former hospital based on the high titer of creatinine kinase due to Myasthenic crisis is one of the most critical complications hypokalemia-induced rhabdomyolysis. of myasthenia gravis (MG). When a patient of MG shows an acute aggravation of muscle weakness, we have to con- Case Report sider the status of the condition and treat it immediately (1, 2). However, there remains the possibility that other disease A 34-year-old Japanese man was admitted to an outside entities happen to complicate it, rendering only slight differ- hospital with dropped head syndrome, limb muscle weak- ences in intricate clinical features. ness and dyspnea, which progressed sub-acutely over the The clinical characteristics of primary aldosteronism are course of 20 days prior to admission. Serum chemistry data treatment-resistant hypertension, hypokalemia, suppressed showed the elevation of creatinine kinase (CK) level (1,048 plasma renin activity and excessive aldosterone production. IU/L). Despite his low serum potassium level (3.1 mEq/L), Sometimes it can cause rhabdomyolysis due to severe hy- he was treated with a three-day course of 1.5 g/day methyl- pokalemia (3-5). If this condition supervenes MG, muscle prednisolone because the presence of myositis was sus- weakness can deteriorate and its clinical features become pected. After the treatment, his symptoms transiently confusing, which should be differentiated from myasthenic showed marked deterioration and then slightly improved af- crisis. Here, we present a case of MG complicated with pri- ter the treatment. He also started to suffer from dysphagia.

Neurology, Respirology, Endocrinology and Metabolism, Dapartment of Internal Medicine, Faculty of Medicine, University of Miyazaki, Mi- yazaki Received for publication March 30, 2009; Accepted for publication May 10, 2009 Correspondence to Dr. Shu-ichi Yamashita, [email protected]

1465 Inter Med 48: 1465-1469, 2009 DOI: 10.2169/internalmedicine.48.2311

He had no complaint of diplopia. He was transferred to our showed a left adrenal small mass without enhancement hospital. Physical examination on admission revealed (Fig. 2). Subsequently, adrenal venous sampling was per- marked obesity (BMI 35.7), a blood pressure of 144/86 formed. The ratio of aldosterone/cortisol in the blood from mmHg on anti-hypertensive medications and pulse rate of the left adrenal vein was much higher than that of the right 98/min, and mild bilateral blepharoptosis that worsened after adrenal vein (Fig. 3) (6). The diagnosis of MG with thy- a sustained upward gaze for 45 seconds. The proximal mus- moma complicated with primary aldosteronism was made. cles of both upper and lower limbs showed marked weak- Because high dose methylprednisolone could have aggra- ness with easy fatigabilty. Gowers’ sign was positive. The vated the high serum CK level (1,048 mEq/L) and low po- distal muscle groups were relatively spared. There was no tassium level (3.1 mEq/L) on admission to his former hospi- muscle tenderness. An edrophonium test showed transient tal, the acute deterioration of muscle power after steroid improvement of both blepharoptosis and muscle power. An pulse therapy was likely secondary to hypokalemia-induced abnormal decremental compound muscle action potential in rhabdomyolysis. the abductor digiti minimi of approximately 30% was ob- Oral administration of spironolactone was initiated imme- served in the repetitive nerve-stimulation test. Although diately, and oral and intravenous potassium supplementation laboratory findings showed severe hypokalemia (2.6 mEq/ was continued. After normalization of serum potassium, the L), the CK level was already normal (109 IU/L). Serum so- patient felt slight but definite improvement in muscle dium was 145 mEq/L, and immunologic test revealed the strength. Once stabilized, he underwent a thoracotomy for presence of acetylcholine receptor-binding antibodies (Ta- excision of the thymoma, which did not invade the wall of ble 1). Despite administration of oral and intravenous potas- aortic arch and was completely resected. Tissue specimens sium, the patient’s hypokalemia did not improve, and hor- showed an admixture of polygonal epithelial cells without monal test showed suppressed plasma renin activity and ex- apparent cellular atypia or high miotic activity, which was cessive aldosterone production (Table 1). No inflammation compatible with thymoma, type B2 by the classification of was detected in bilateral quadriceps muscles by fat- World Health Organization. After the operation, the patient’s suppressed T2-weighted magnetic resonance imaging. Com- condition including his limb weakness, dyspnea and puted tomography (CT) of the chest demonstrated an ante- dysphagia improved markedly without prednisolone. Then, rior mediastinal mass (Fig. 1). Additionally, abdominal CT he underwent laparoscopic adrenalectomy one month after the thymectomy. However, in the immediate post-operative period, the patient showed dramatic deterioration of his Table 1. Autoantibody and Endocrine Data symptoms (Fig. 4). He also suffered from severe dyspnea. It was difficult for him to swallow his saliva. His arterial

blood gas showed pH 7.31, PO2 49.1 mmHg and PCO2 62.3 mmHg. Both serum CK and potassium levels remained within normal limits (102 IU/L and 3.8 mEq/L, respec- tively). There was a transient increase in vital capacity from 300 mL to 600 mL following an edrophonium test, and the patient was immediately intubated and mechanically venti- lated. Treatment with 1.0 g/day of methylprednisolone for three days was started, and this was followed by 60 mg of

Figure 1. Axial (A) and coronal (B) views of plain computed tomography (CT) of the chest dem onstrate an anterior mediastinal mass (arrow).

1466 Inter Med 48: 1465-1469, 2009 DOI: 10.2169/internalmedicine.48.2311

Figure 2. Axial (A) and coronal (B) views of abdominal enhanced CT show a left adrenal small mass (arrow) without apparent enhancement.

Figure 3. Plasma aldosterone and cortisol concentrations were measured with adrenal venous sampling. There was excessive secretion of aldosterone from the left adrenal gland.

Figure 4. Clinical course after admission to our hospital.

1467 Inter Med 48: 1465-1469, 2009 DOI: 10.2169/internalmedicine.48.2311 prednisolone. His condition rapidly improved and mechani- of primary aldosteronism because of the continuation of hy- cal ventilation was discontinued after a few days. Oral pred- pertension and hypokalemia in spite of proper medications nisolone was tapered to a maintenance dose of 10 mg/day (3-5). Hypokalemia in patients with primary aldosteronism within two weeks. On this regimen, his symptoms including can cause muscle weakness. Furthermore, it can induce dropped head syndrome and generalized muscle weakness rhabdomyolysis by enhancing the muscle sodium-potassium resolved, and he was able to climb stairs without any aid. pump activity thereby causing an increase of potassium en- He was on ordinary diet, because there was no dysphagia try into cells. Impaired potassium release from skeletal mus- and his speech was normal. Pathological examination of the cle cells may promote muscle injury or rhabdomyolysis as a left adrenal mass confirmed the presence of a cortical ade- consequence of ischemia due to hypokalemia-induced de- noma. The patient was discharged to his former hospital. crease of blood flow (12, 13). Subsequently, the serum CK level could rise, completing the clinical features of this rare Discussion and complex presentation of diseases of this patient. The decision about which tumor should be operated on It might not have been difficult to diagnose this patient’s first must be a disputable problem. As far as we searched, MG because of the presence of relatively typical clinical we could not identify any published reports on a patient findings such as ptosis and easy fatigability of muscles (7). who had MG with thymoma and primary aldosteronism si- Nevertheless, his complicated clinical features including multaneously and the optimal sequence and timing of its high serum CK prompted the former doctors’ diagnosis of surgical treatment. There was only one report describing myositis and treatment with high dose steroids. Unfortu- successful sequential surgery of adrenalectomy and thymec- nately, this treatment could be hazardous in this kind of pa- tomy in a patient without MG (14). Compared to the control tient because it might cause aggravation of hypokalemia and of myasthenia gravis, the control of serum potassium is rela- rhabdomyolysis, and possible initial deterioration of MG af- tively straightforward with supplemental potassium and spi- ter initiation of steroid therapy, so it is imperative to evalu- ronolactone. The patient showed slight but definite improve- ate the clinical conditions properly and make a correct diag- ment of muscle power with the improvement of the serum nosis as soon as possible. potassium level. Because of this clinical process, we elected Myasthenic crisis is the most worrisome problem when a to first perform the thymectomy to reduce the possibility of myasthenic patient shows acute aggravation of muscle power myasthenic crisis during and after adrenalectomy. Indeed, or respiratory state. It is crucial to determine the exacerbat- the patient developed myasthenic crisis after the adrenalec- ing factors and immediately start proper treatment against tomy, which we were able to control rather easily. Although them as well as the crisis itself (1, 2). Usually, it is not so starting prednisolone before the operation might prevent my- difficult to detect the factors responsible for causing myas- asthenic crisis especially when the tumor secretes a subclini- thenic crisis such as infections or medications. However, an- cal amount of corticosteroid, the risk of a recurrence of other muscle disease irrelevant to MG may sometimes com- steroid-induced hypokalemia was deemed to be too great, plicate and make the situation complex (8, 9). In the present since his plasma ACTH level was relatively high (80.0 pg/ case, following his transfer to our hospital, we assumed that mL) and its secretion was not suppressed at all. However, it the deterioration of his symptoms at the former hospital had is physiologically meaningful the preclinical Cushing syn- been myasthenic crisis. The result of an edrophonium test drome was deniable (Table 1). and the repetitive nerve-stimulation test corroborated the di- The present case represents an extremely rare combination agnosis of MG (10, 11). Additionally, the presence of mass of diseases, but it illustrates an important point. Distinct lesion in the anterior mediastinum detected by CT scan neuromuscular diseases could complicate MG and exacer- (Fig. 1) and the positive result of acetylcholine receptor- bate the condition dramatically. In addition, when hypoka- binding antibodies were typical findings in MG. At the time lemia is detected, further investigation of the cause of hy- of his presentation to our hospital, the patient’s serum CK pokalemia should be performed, especially for aldostero- was normal and hypokalemia was not reported from his for- nism. This is the first report of the successful sequential sur- mer doctors, so we considered the low potassium on transfer gery for thymoma and primary aldosteronism in a patient a consequence of steroid therapy. with MG. After the diagnosis of MG, we suspected the possibility

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