å¡ CASE REPORT å¡ Amyotrophic Lateral Sclerosis Associated with the Syndrome of Inappropriate Secretion of Antidiuretic Hormone Yoshiharu Motoo, Hideki Ohta, Takashi Okai and Norio Sawabu A 71-year-old female with amyotrophic lateral sclerosis (ALS) developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) during respiratory failure due to atrophy of the respiratory muscles. Serum sodium concentration fell to 116 mEq/1 and then returned to the normal range after water restriction and respiratory care. This is considered to be the first case report of ALS31: associated with1992) SIADH. (Internal Medicine 1023-1025, Key words: muscular atrophy, hyponatremia, respiratory failure
Introduction The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is characterized by dilutional hyponatremia due to excessive secretion of ADH. Since Schwartz et al first reported an association with this condi tion in two patients with lung cancer (1), SIADH has been recognized in various diseases. However, there has been no report on the association of SIADH and amyotrophic lateral sclerosis (ALS). We report a patient with ALS who developed SIADH during respiratory failure. Respiratory failure due to atrophy of the respiratory muscles played a Consciousness is usually alert inofALS, even thecase. terminal major role in the development SIADH in at this stage. However, the association of SIADH might cause severe consciousness disturbance and it may greatly affect the clinical course of the patient. This is the first case report on the clinical characteristics of ALS associated with SIADH. Case Report
were limited bilaterally. Her tongue was atrophic and fasciculation was recognized. As for the motor system, marked atrophy of systemic muscles and fasciculation were noted. Muscle strength was decreased to 4/5-2/5. No sensory disturbance was noticed. Deep tendon reflexes were slightly decreased, and there no pathologic Electromyogram (EMG) was were obtained at the rightreflexes. biceps brachii, abductor digiti minimi and rectus femoris. Neuromuscular units showed high voltage, long duration and a polyphasic pattern, and a decrease in recruitment was seen. These EMG findings were compatible with neurogenic disorders, in particular ALS. Nerve conduction velocity was normal. Laboratory data showed mild anemia; erythrocytes 330 xbiochemical lOVmm3, hemoglobin 10.7creatine g/dl, hematocrit 34.0%. Other data including phosphokinase
were normal. Chest X-ray film on admission showed mild pulmonary emphysema. She could not complete the program of spiro graphy because she was unable to respirate deeply (%VC 39.13%, FEV % 88.57%). Arterial blood gas analysis showed an elevated level of PCO2 (pH 7.37, PCO2 68 mmHg,PO282mmHg, HCO^ 39 mmol/1, BE ll A 71-year-old woman was hospitalized for evaluation of mmol/1, O2Sat 95%). On admission, she performed weight loss. Despite a good appetite she had lost 20 kg activities of daily living normally but gradually developed within the previous two-year period. Physical findings general malaise and dyspnea during walking. During this included generalized muscular atrophy (height: 142 cm, respiratory failure, probably due to weakness of the weight: 32 kg). Neurological examination disclosed bulbar respiratory muscles, serum levels of sodium decreased from palsy and lower motor neuron disorder. She was alert, but the normal range (138 mEq/1) to 116 mEq/1 within about mild dysarthria was noted. There was no meningeal stimula one month. The patient showed a sleeping tendency, but tion or visual disorder. Her countenance was poor due to no severe consciousness disturbance. She had no edema, and atrophy the facial muscles. Movements soft palate From theofDepartment of Internal Medicine,of Cancer Research Institute, Kanazawa Kanazawa there was no signUniversity, of dehydration. Despite hyponatremia and Received for publication January 27, 1992; Accepted for publication April 21, 1992 Reprint requests should be addressed to Dr. Yoshiharu Motoo, the Department of Internal Medicine, Cancer Research Institute, Kanazawa 4-86 Yoneizumi, Kanazawa 921, Japan Internal
Medicine
Vol.
31, No. 8 (August
1992)
1023
Motoo et al nitrogen was 8.6 mg/dl, serum creatine was 0.4 mg/dl and serum uric acid was 2.3 mg/dl (Table 1). Serum ADH level was high (8.8 pg/ml: normal 0.3-3.5). Plasma renin activity was normal. Pituitary and adrenal functions were Table 1. Laboratory Data at the Time of Diagnosis of SIADH also normal (Table 2). From these data the diagnosis of W BC 5 ,000/m m 3 C PK 140 IU /1 SIADH was made. Water restriction and infusion of con RBC 35O x lO4/m m 3 s -A m y1 126 som ogyiU H b ll.3 g/d l T -cho 1 20 5 m g/d l centrated NaCl elevated the serum level of sodium to 140 P its 15.9 x lO4/m m 3 TG 64 m g/d l mEq/1. But the serum sodium level gradually decreased E SR 12m m /h BU N 8 .6 m g/d l again, and the respiratory movement of the patient became u rin alysis n .p . Cr 0 .4 m g/d l TP 6.8 g/ dl UA 2 .3 m g/d l weaker. On the 60th hospital day, respiratory arrest G OT 32 U N a l16 m E q /1 suddenly occurred. Emergent cardiopulmonary resuscita G PT 20 U 3.7 m E q /1 A LP 4 .6 U C1 75 m E q /1 tion was performed. The next day she gained very weak r -G T P 8 U C cr 69 .1 m l/m in spontaneous respiration, but mechanical ventilation was C RP (- ) p lasm a O sm 235 m O sm /kg CEA 1.8 ng/m l u rin ary N a 120 m E q /day needed afterward. After starting the mechanical ventilation, C A 19 -9 5 U /m l u rin ary K 24 m E q /day there has been no recurrence of SIADH and serum ADH u rin ary C 1 103 m E q /day level was normalized (2.2 pg/ml) despite the lack of water Discussion restriction or concentrated NaCl infusion (Fig. 1).
plasma hypoosmolarity (235 mOsm/kg), urinary secretion of sodium was high (120 mEq/day) whereas blood urea
Table 2. Endocrinological Data at the Time of Diagnosis of SIADH (n o rm a l ra n g e) A D H
8 .8 p g / m l (0 .3- 3 .5 )
fre e T , fre e T 4 T SH
3 .6 p g / m l (3 .0 - 5 .8 ) 1 .5 4 n g / m l (0 .7 8- 2 .l l) 1 .5 9 a IU / m l (0 .3 6 - 3 .2 5 )
G H
0 .8 n g / m l ｫ
c o rtiso 1 PR A
1 2 .0 /fg / d l (3 .7 - 13 .0 ) 2 .7 n g / m l/ h r (0 .2 - 2 .7 )
PA C
5 n g / m l)
16 0 p g / m l (5 7 - 1 6 1)
u - 17 K S
3 .2 m g / d a y (2 .4 - l l .0 )
u -1 7 O H C S
4 .1 m g / d a y (2 .2 - 7 .3 )
serum Na
To our knowledge, an association between ALS and SIADH has not yet been reported. Hata et al (2) reported a 3-year-old girl with infantile spinal muscular atrophy, Werdnig-Hoffmann's disease, who developed pneumonia and SIADH. In this disease, the respiratory muscles become atrophic, and this leads to deterioration of pneumonia, hypoxia and hypercapnia, and changes in intrathoracic circulation. All of these can stimulate the secretion of ADH as follows. Hypoxia causes contraction of the pulmonary Hypoxia alsodecreases stimulatesvenous the hypothalamus secrete ADH vessels, and return to thetoleft atrium (3). directly (4), or indirectly via carotid baroreceptors (5). Hypercapnia stimulates ADH secretion via the baro-
admission I
mechanical rventilation respiratory arrest
(mEq/L) 150 140 130 120 110 100 4/21 5/1 16 22266/14 8 12 18 7/1 Fig. 1. Clinical course of the patient. 1024
Internal
Medicine
Vol. 31,
No. 8 (August
1992)
SIADH in Amyotrophic
Lateral Sclerosis
receptors (5) or by inducing acidosis (5). Changes in intra thoracic circulation include decreases in venous return, pulmonary blood flow and left atrial pressure. In the present case of ALS, subclinical respiratory dysfunction was present on admission, which was suggested hypercapnia. Hypoxia was not detected before the by respiratory arrest. The
by certain changes in the intrathoracic or systemic circula tion. Therefore, hypercapnia and intrathoracic circulatory changes might have induced SIADH in the present case.
serum sodium concentration gradually decreased during the progressive respiratory failure. Long et al reported 8 patients with botulism associated with SIADH in 1985 (6). These patients suffered from rapidly progressive respiratory failure and required ventilatory support. Although Long et al corre lated SIADH with mechanical ventilation, respiratory failure itself respiratory may cause failure SIADHwas by the mechanism described above. After treated by mechanical ventila tion, the serum sodium concentration and serum ADH level were normalized without the need for water restriction or concentrated NaCl infusion as reported here. There was no sign of pneumonia in the present case. However, mild pulmonary emphysema might be a factor in the pathogenesis of SIADH. Although a hemodynamic study could not be completed, the abrupt onset of respiratory arrest suggests that subclinical chronic respiratory failure was exacerbated
1) Schwartz WB, Bennett W, Curelop S, Bartter FC. A syndrome of renal sodium loss and hyponatremia probably resulting from in appropriate secretion of antidiuretic hormone. Am J Med 23: 529, 1957. 2) Hata D, YoshidaA, Ohkubo H, Mochizuki Y, Mizutani A. A case of Werdnig-Hoffmann disease associated with pneumonia and SIADH. Jpn J Pediatr 40: 3398, 1987 (in Japanese). 3) Mor J, Ben-Galim E, Abrahamov A. Inappropriate antidiuretic hormone secretion in an infant with severe pneumonia. Am J Dis Child 129: 133, 1975. 4) Alexander DP, Forsling ML, Martin MJ, et al. The effect of maternal hypoxia on fetal pituitary hormone release in the sheep. Biol Neonate 21: 219, 1972. 5) Rose CE Jr, Anderson RJ, Carey RM. Antidiuresis and vasopressin release with hypoxemia and hypercapnia in conscious dogs. Am J Physiol 247: R127, 1984. 6) Long SS, Gajewski JL, Brown LW, Gilligan PH. Clinical, laboratory, and environmental features of infant botulism in southeastern Pennsylvania. Pediatrics 75: 935, 1985.
Internal
Medicine
Vol. 31, No. 8 (August
1992)
References
1025
Introduction The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is characterized by dilutional hyponatremia due to excessive secretion of ADH. Since Schwartz et al first reported an association with this condi tion in two patients with lung cancer (1), SIADH has been recognized in various diseases. However, there has been no report on the association of SIADH and amyotrophic lateral sclerosis (ALS). We report a patient with ALS who developed SIADH during respiratory failure. Respiratory failure due to atrophy of the respiratory muscles played a Consciousness is usually alert inofALS, even thecase. terminal major role in the development SIADH in at this stage. However, the association of SIADH might cause severe consciousness disturbance and it may greatly affect the clinical course of the patient. This is the first case report on the clinical characteristics of ALS associated with SIADH. Case Report
were limited bilaterally. Her tongue was atrophic and fasciculation was recognized. As for the motor system, marked atrophy of systemic muscles and fasciculation were noted. Muscle strength was decreased to 4/5-2/5. No sensory disturbance was noticed. Deep tendon reflexes were slightly decreased, and there no pathologic Electromyogram (EMG) was were obtained at the rightreflexes. biceps brachii, abductor digiti minimi and rectus femoris. Neuromuscular units showed high voltage, long duration and a polyphasic pattern, and a decrease in recruitment was seen. These EMG findings were compatible with neurogenic disorders, in particular ALS. Nerve conduction velocity was normal. Laboratory data showed mild anemia; erythrocytes 330 xbiochemical lOVmm3, hemoglobin 10.7creatine g/dl, hematocrit 34.0%. Other data including phosphokinase
were normal. Chest X-ray film on admission showed mild pulmonary emphysema. She could not complete the program of spiro graphy because she was unable to respirate deeply (%VC 39.13%, FEV % 88.57%). Arterial blood gas analysis showed an elevated level of PCO2 (pH 7.37, PCO2 68 mmHg,PO282mmHg, HCO^ 39 mmol/1, BE ll A 71-year-old woman was hospitalized for evaluation of mmol/1, O2Sat 95%). On admission, she performed weight loss. Despite a good appetite she had lost 20 kg activities of daily living normally but gradually developed within the previous two-year period. Physical findings general malaise and dyspnea during walking. During this included generalized muscular atrophy (height: 142 cm, respiratory failure, probably due to weakness of the weight: 32 kg). Neurological examination disclosed bulbar respiratory muscles, serum levels of sodium decreased from palsy and lower motor neuron disorder. She was alert, but the normal range (138 mEq/1) to 116 mEq/1 within about mild dysarthria was noted. There was no meningeal stimula one month. The patient showed a sleeping tendency, but tion or visual disorder. Her countenance was poor due to no severe consciousness disturbance. She had no edema, and atrophy the facial muscles. Movements soft palate From theofDepartment of Internal Medicine,of Cancer Research Institute, Kanazawa Kanazawa there was no signUniversity, of dehydration. Despite hyponatremia and Received for publication January 27, 1992; Accepted for publication April 21, 1992 Reprint requests should be addressed to Dr. Yoshiharu Motoo, the Department of Internal Medicine, Cancer Research Institute, Kanazawa 4-86 Yoneizumi, Kanazawa 921, Japan Internal
Medicine
Vol.
31, No. 8 (August
1992)
1023
Motoo et al nitrogen was 8.6 mg/dl, serum creatine was 0.4 mg/dl and serum uric acid was 2.3 mg/dl (Table 1). Serum ADH level was high (8.8 pg/ml: normal 0.3-3.5). Plasma renin activity was normal. Pituitary and adrenal functions were Table 1. Laboratory Data at the Time of Diagnosis of SIADH also normal (Table 2). From these data the diagnosis of W BC 5 ,000/m m 3 C PK 140 IU /1 SIADH was made. Water restriction and infusion of con RBC 35O x lO4/m m 3 s -A m y1 126 som ogyiU H b ll.3 g/d l T -cho 1 20 5 m g/d l centrated NaCl elevated the serum level of sodium to 140 P its 15.9 x lO4/m m 3 TG 64 m g/d l mEq/1. But the serum sodium level gradually decreased E SR 12m m /h BU N 8 .6 m g/d l again, and the respiratory movement of the patient became u rin alysis n .p . Cr 0 .4 m g/d l TP 6.8 g/ dl UA 2 .3 m g/d l weaker. On the 60th hospital day, respiratory arrest G OT 32 U N a l16 m E q /1 suddenly occurred. Emergent cardiopulmonary resuscita G PT 20 U 3.7 m E q /1 A LP 4 .6 U C1 75 m E q /1 tion was performed. The next day she gained very weak r -G T P 8 U C cr 69 .1 m l/m in spontaneous respiration, but mechanical ventilation was C RP (- ) p lasm a O sm 235 m O sm /kg CEA 1.8 ng/m l u rin ary N a 120 m E q /day needed afterward. After starting the mechanical ventilation, C A 19 -9 5 U /m l u rin ary K 24 m E q /day there has been no recurrence of SIADH and serum ADH u rin ary C 1 103 m E q /day level was normalized (2.2 pg/ml) despite the lack of water Discussion restriction or concentrated NaCl infusion (Fig. 1).
plasma hypoosmolarity (235 mOsm/kg), urinary secretion of sodium was high (120 mEq/day) whereas blood urea
Table 2. Endocrinological Data at the Time of Diagnosis of SIADH (n o rm a l ra n g e) A D H
8 .8 p g / m l (0 .3- 3 .5 )
fre e T , fre e T 4 T SH
3 .6 p g / m l (3 .0 - 5 .8 ) 1 .5 4 n g / m l (0 .7 8- 2 .l l) 1 .5 9 a IU / m l (0 .3 6 - 3 .2 5 )
G H
0 .8 n g / m l ｫ
c o rtiso 1 PR A
1 2 .0 /fg / d l (3 .7 - 13 .0 ) 2 .7 n g / m l/ h r (0 .2 - 2 .7 )
PA C
5 n g / m l)
16 0 p g / m l (5 7 - 1 6 1)
u - 17 K S
3 .2 m g / d a y (2 .4 - l l .0 )
u -1 7 O H C S
4 .1 m g / d a y (2 .2 - 7 .3 )
serum Na
To our knowledge, an association between ALS and SIADH has not yet been reported. Hata et al (2) reported a 3-year-old girl with infantile spinal muscular atrophy, Werdnig-Hoffmann's disease, who developed pneumonia and SIADH. In this disease, the respiratory muscles become atrophic, and this leads to deterioration of pneumonia, hypoxia and hypercapnia, and changes in intrathoracic circulation. All of these can stimulate the secretion of ADH as follows. Hypoxia causes contraction of the pulmonary Hypoxia alsodecreases stimulatesvenous the hypothalamus secrete ADH vessels, and return to thetoleft atrium (3). directly (4), or indirectly via carotid baroreceptors (5). Hypercapnia stimulates ADH secretion via the baro-
admission I
mechanical rventilation respiratory arrest
(mEq/L) 150 140 130 120 110 100 4/21 5/1 16 22266/14 8 12 18 7/1 Fig. 1. Clinical course of the patient. 1024
Internal
Medicine
Vol. 31,
No. 8 (August
1992)
SIADH in Amyotrophic
Lateral Sclerosis
receptors (5) or by inducing acidosis (5). Changes in intra thoracic circulation include decreases in venous return, pulmonary blood flow and left atrial pressure. In the present case of ALS, subclinical respiratory dysfunction was present on admission, which was suggested hypercapnia. Hypoxia was not detected before the by respiratory arrest. The
by certain changes in the intrathoracic or systemic circula tion. Therefore, hypercapnia and intrathoracic circulatory changes might have induced SIADH in the present case.
serum sodium concentration gradually decreased during the progressive respiratory failure. Long et al reported 8 patients with botulism associated with SIADH in 1985 (6). These patients suffered from rapidly progressive respiratory failure and required ventilatory support. Although Long et al corre lated SIADH with mechanical ventilation, respiratory failure itself respiratory may cause failure SIADHwas by the mechanism described above. After treated by mechanical ventila tion, the serum sodium concentration and serum ADH level were normalized without the need for water restriction or concentrated NaCl infusion as reported here. There was no sign of pneumonia in the present case. However, mild pulmonary emphysema might be a factor in the pathogenesis of SIADH. Although a hemodynamic study could not be completed, the abrupt onset of respiratory arrest suggests that subclinical chronic respiratory failure was exacerbated
1) Schwartz WB, Bennett W, Curelop S, Bartter FC. A syndrome of renal sodium loss and hyponatremia probably resulting from in appropriate secretion of antidiuretic hormone. Am J Med 23: 529, 1957. 2) Hata D, YoshidaA, Ohkubo H, Mochizuki Y, Mizutani A. A case of Werdnig-Hoffmann disease associated with pneumonia and SIADH. Jpn J Pediatr 40: 3398, 1987 (in Japanese). 3) Mor J, Ben-Galim E, Abrahamov A. Inappropriate antidiuretic hormone secretion in an infant with severe pneumonia. Am J Dis Child 129: 133, 1975. 4) Alexander DP, Forsling ML, Martin MJ, et al. The effect of maternal hypoxia on fetal pituitary hormone release in the sheep. Biol Neonate 21: 219, 1972. 5) Rose CE Jr, Anderson RJ, Carey RM. Antidiuresis and vasopressin release with hypoxemia and hypercapnia in conscious dogs. Am J Physiol 247: R127, 1984. 6) Long SS, Gajewski JL, Brown LW, Gilligan PH. Clinical, laboratory, and environmental features of infant botulism in southeastern Pennsylvania. Pediatrics 75: 935, 1985.
Internal
Medicine
Vol. 31, No. 8 (August
1992)
References
1025
