Hyponatremia During ACTH Infusions LESLIE R. SHEELER, M.D.; and O. PETER SCHUMACHER, M.D., Ph.D. The Cleveland Clinic Foundation and The Cleveland Clinic Educational Foundation; Cleveland, Ohio
A L T H O U G H we have found the 48-h A C T H test of Rose and associates (1) to be an excellent diagnostic tool, in three cases, the infusion of A C T H in 5 % dextrose in water produced severe hyponatremia despite dexamethasone therapy. Rose and associates had identified this problem and advised care in doing the test. However, standard textbooks either do not mention the intravenous fluid to be used or recommend dextrose in water (2, 3); some pharmaceutical literature recommends 5 % dex798
May 1979 • Annals of Internal Medicine • Volume 90 • Number 5
Downloaded from https://annals.org by University of Otago user on 01/20/2019
Table 1 . Laboratory Values
Patient
17-Hydroxycorticoid
Serum Electrolytes Before Infusion Sodium
Potassium
After Infusion Chloride
Sodium
Potassium
Chloride
4.6 5.2 3.9
80 70 85
>
/f.
1 2 3
144 134 144
4.4 4.2 4.0
meg/litre 98 102 105
After 24 h
109 101 116
t r o s e in w a t e r ( 4 , 5). F o r t y u n i t s of A C T H ( a c t h a r ) a d d e d t o 5 0 0 m L o f 5 % d e x t r o s e in w a t e r w a s u s e d a s t h e infusing s o l u t i o n in e a c h of t h r e e p a t i e n t s . T h e infusion w a s for 12 h a n d r e p e a t e d a s l o n g a s a t o t a l of 48 h o r t o t h e t e r m i n a t i o n of t h e test. Brief c a s e d e s c r i p t i o n s a n d t h e clinical r e s u l t s of t h e A C T H infusions follow; k e y l a b o r a t o r y v a l u e s a r e in T a b l e 1. Patient 1: A 46-year-old white housewife had a 1-year history of fatigue, 27-kg weight loss, anorexia, nausea, vomiting, postural dizziness, and hyperpigmentation. H e r blood pressures were 84/60 m m H g sitting and 60/40 m m Hg standing. T h e thyroid gland was firm and enlarged. Laboratory data at admission were normal except for a thyroid-stimulating hormone level of 44.0 jLiu/mL and a thyroxine level of 2.5 n g / d L (normal, 4.0 to 9.0 n g / d L ) . She was given dexamethasone, 0.5 mg twice daily, and a 48-h A C T H infusion was begun. At the end of the test (after 2000 m L of 5 % dextrose in water had been infused), the patient became confused and then rapidly obtunded, with myoclonic jerks and bilateral extensor plantar responses, but no focal neurologic signs. Serum electrolyte levels were abnormal (see Table 1). She improved rapidly with treatment with normal saline, intravenous hydrocortisone, and intramuscular cortisone acetate; serum electrolyte levels were normal 24 h later. Patient 2: A 31-year-old white woman with moderate azotemia and active pulmonary tuberculosis in 1969 was examined in December 1974; she had been receiving steroids in various doses since 1966 for membranoproliferative glomerulonephritis. She had three episodes of apparent adrenal insufficiency with intercurrent infections while taking maintenance doses of prednisone, 5.0 mg twice daily. Efforts on these occasions to discontinue steroid therapy had produced nausea, vomiting, anorexia, weight loss, and hyperpigmentation. She had cushingoid features, and initial laboratory data included a serum creatinine level of 2.4 m g / d L and a creatinine clearance of 10.0 m L / m i n . A n A C T H test was done to exclude primary adrenal failure. She was given dexamethasone, 0.5 mg twice daily, and an infusion of A C T H in 5 % dextrose in water was begun. After infusion of about 1500 mL, the patient became nauseated and confused and vomited twice. Serum electrolyte levels were abnormal, but reversed to admission values through 2 d of treatment with normal saline, oral and intramuscular dexamethasone, and fluorocortisone acetate. Patient 3: A 35-year-old white housewife was examined because of a diagnosis of Addison's disease made 5 years earlier from urinary assays and symptoms of fatigue, a 9.1-kg weight loss through 2 years, and anorexia. She had been taking cortisone acetate, 12.5 mg three times daily, for 5 years. She had not felt well on this regimen and had symptoms of fatigue, lethargy, depression, and anxiety. Physical findings were normal. She was given 0.75 mg dexamethasone in the morning and 0.375 mg in the afternoon, and the A C T H infusion was begun. A chill, with a coarse hard tremor and vomiting, developed after infusion of about 1600 mL; serum electrolyte levels were abnormal. They were corrected with normal saline, intramuscular cortisone acetate, and intravenous hydrocortisone; within 1
Highest Plasma Cortisol
After 48 h mg
0.8 0.7 10.8
ng/dL 2.3 4.0 40
3.2 0 23
d, electrolyte values were normal. T h e test was later repeated with normal saline as the infusate. Tests of pituitary reserve with Metopirone® (metyrapone) and insulin hypoglycemia showed good responses. She was advised to taper and discontinue steroid therapy. I n e a c h p a t i e n t , severe h y p o n a t r e m i a w a s i n d u c e d w i t h t h e A C T H , 5 % d e x t r o s e in w a t e r s o l u t i o n . N o p e r m a nent neurologic complications developed, although a l a r m i n g signs a n d s y m p t o m s o c c u r r e d in e a c h p a t i e n t . D e x a m e t h a s o n e , a b o u t 1 m g / d in d i v i d e d d o s e s , d i d n o t p r e v e n t h y p o n a t r e m i a . T h e c a u s e for t h i s c o m p l i c a t i o n is n o t clear. P a t i e n t s w i t h A d d i s o n ' s disease h a v e l o n g b e e n k n o w n t o h a v e d i m i n i s h e d ability t o e x c r e t e a w a t e r l o a d . A n a l t e r n a t i v e e x p l a n a t i o n is t h a t t h e A C T H is c o n t a m i n a t e d b y a n t i d i u r e t i c h o r m o n e ( A D H ) , a n d a s t a t e of inappropriate A D H secretion might be induced during t h e infusion. W e r e c o m m e n d t h a t 5 % d e x t r o s e in w a t e r b e a b a n d o n e d a s t h e infusing s o l u t i o n , a l t h o u g h t h e d a n g e r of c o n g e s t i v e h e a r t failure exists, t h e o r e t i c a l l y , w i t h t h e u s e of n o r m a l saline. Careful a t t e n t i o n t o t h e p a t i e n t ' s s t a t u s is n e e d e d d u r i n g t h i s test. REFERENCES 1. R O S E LI, W I L L I A M S G H , JAGGER PI, L A U L E R DP: The 48-hour adreno-
corticotrophin infusion test for adrenocortical insufficiency. Ann Intern Med 73:49-54, 1970 2. L I D D L E GW, M E L M O N KL: The adrenals, in Textbook
of
Endocrinolo-
gy, edited by WILLIAMS RH. Philadelphia, W.B. Saunders Co., 1974, p. 251 3. W I L L I A M S G H , D L U H Y RG, T H O R N GW: Diseases of the adrenal cortex,
in Harrison's Principles of Internal Medicine, edited by W I N T R O B E MW, T H O R N GW, A D A M S R D , B E N N E T T IL J R , B R A U N W A L D E, ISSELBACH-
ER KJ, PETERSDORF RG. New York, McGraw Hill Book Company, 1974, p. 497 4. K I N G JC: Guide to Parenteral Admixtures. St. Louis, Cutter Laboratories, 1976 5. M E R R E L L - N A T I O N A L LABORATORIES: ACTH Solution Product Information. Cincinnati, Merrella National Laboratories, 1972 © 1 9 7 9 American College of Physicians
Brief Reports
Downloaded from https://annals.org by University of Otago user on 01/20/2019
799
A L T H O U G H we have found the 48-h A C T H test of Rose and associates (1) to be an excellent diagnostic tool, in three cases, the infusion of A C T H in 5 % dextrose in water produced severe hyponatremia despite dexamethasone therapy. Rose and associates had identified this problem and advised care in doing the test. However, standard textbooks either do not mention the intravenous fluid to be used or recommend dextrose in water (2, 3); some pharmaceutical literature recommends 5 % dex798
May 1979 • Annals of Internal Medicine • Volume 90 • Number 5
Downloaded from https://annals.org by University of Otago user on 01/20/2019
Table 1 . Laboratory Values
Patient
17-Hydroxycorticoid
Serum Electrolytes Before Infusion Sodium
Potassium
After Infusion Chloride
Sodium
Potassium
Chloride
4.6 5.2 3.9
80 70 85
>
/f.
1 2 3
144 134 144
4.4 4.2 4.0
meg/litre 98 102 105
After 24 h
109 101 116
t r o s e in w a t e r ( 4 , 5). F o r t y u n i t s of A C T H ( a c t h a r ) a d d e d t o 5 0 0 m L o f 5 % d e x t r o s e in w a t e r w a s u s e d a s t h e infusing s o l u t i o n in e a c h of t h r e e p a t i e n t s . T h e infusion w a s for 12 h a n d r e p e a t e d a s l o n g a s a t o t a l of 48 h o r t o t h e t e r m i n a t i o n of t h e test. Brief c a s e d e s c r i p t i o n s a n d t h e clinical r e s u l t s of t h e A C T H infusions follow; k e y l a b o r a t o r y v a l u e s a r e in T a b l e 1. Patient 1: A 46-year-old white housewife had a 1-year history of fatigue, 27-kg weight loss, anorexia, nausea, vomiting, postural dizziness, and hyperpigmentation. H e r blood pressures were 84/60 m m H g sitting and 60/40 m m Hg standing. T h e thyroid gland was firm and enlarged. Laboratory data at admission were normal except for a thyroid-stimulating hormone level of 44.0 jLiu/mL and a thyroxine level of 2.5 n g / d L (normal, 4.0 to 9.0 n g / d L ) . She was given dexamethasone, 0.5 mg twice daily, and a 48-h A C T H infusion was begun. At the end of the test (after 2000 m L of 5 % dextrose in water had been infused), the patient became confused and then rapidly obtunded, with myoclonic jerks and bilateral extensor plantar responses, but no focal neurologic signs. Serum electrolyte levels were abnormal (see Table 1). She improved rapidly with treatment with normal saline, intravenous hydrocortisone, and intramuscular cortisone acetate; serum electrolyte levels were normal 24 h later. Patient 2: A 31-year-old white woman with moderate azotemia and active pulmonary tuberculosis in 1969 was examined in December 1974; she had been receiving steroids in various doses since 1966 for membranoproliferative glomerulonephritis. She had three episodes of apparent adrenal insufficiency with intercurrent infections while taking maintenance doses of prednisone, 5.0 mg twice daily. Efforts on these occasions to discontinue steroid therapy had produced nausea, vomiting, anorexia, weight loss, and hyperpigmentation. She had cushingoid features, and initial laboratory data included a serum creatinine level of 2.4 m g / d L and a creatinine clearance of 10.0 m L / m i n . A n A C T H test was done to exclude primary adrenal failure. She was given dexamethasone, 0.5 mg twice daily, and an infusion of A C T H in 5 % dextrose in water was begun. After infusion of about 1500 mL, the patient became nauseated and confused and vomited twice. Serum electrolyte levels were abnormal, but reversed to admission values through 2 d of treatment with normal saline, oral and intramuscular dexamethasone, and fluorocortisone acetate. Patient 3: A 35-year-old white housewife was examined because of a diagnosis of Addison's disease made 5 years earlier from urinary assays and symptoms of fatigue, a 9.1-kg weight loss through 2 years, and anorexia. She had been taking cortisone acetate, 12.5 mg three times daily, for 5 years. She had not felt well on this regimen and had symptoms of fatigue, lethargy, depression, and anxiety. Physical findings were normal. She was given 0.75 mg dexamethasone in the morning and 0.375 mg in the afternoon, and the A C T H infusion was begun. A chill, with a coarse hard tremor and vomiting, developed after infusion of about 1600 mL; serum electrolyte levels were abnormal. They were corrected with normal saline, intramuscular cortisone acetate, and intravenous hydrocortisone; within 1
Highest Plasma Cortisol
After 48 h mg
0.8 0.7 10.8
ng/dL 2.3 4.0 40
3.2 0 23
d, electrolyte values were normal. T h e test was later repeated with normal saline as the infusate. Tests of pituitary reserve with Metopirone® (metyrapone) and insulin hypoglycemia showed good responses. She was advised to taper and discontinue steroid therapy. I n e a c h p a t i e n t , severe h y p o n a t r e m i a w a s i n d u c e d w i t h t h e A C T H , 5 % d e x t r o s e in w a t e r s o l u t i o n . N o p e r m a nent neurologic complications developed, although a l a r m i n g signs a n d s y m p t o m s o c c u r r e d in e a c h p a t i e n t . D e x a m e t h a s o n e , a b o u t 1 m g / d in d i v i d e d d o s e s , d i d n o t p r e v e n t h y p o n a t r e m i a . T h e c a u s e for t h i s c o m p l i c a t i o n is n o t clear. P a t i e n t s w i t h A d d i s o n ' s disease h a v e l o n g b e e n k n o w n t o h a v e d i m i n i s h e d ability t o e x c r e t e a w a t e r l o a d . A n a l t e r n a t i v e e x p l a n a t i o n is t h a t t h e A C T H is c o n t a m i n a t e d b y a n t i d i u r e t i c h o r m o n e ( A D H ) , a n d a s t a t e of inappropriate A D H secretion might be induced during t h e infusion. W e r e c o m m e n d t h a t 5 % d e x t r o s e in w a t e r b e a b a n d o n e d a s t h e infusing s o l u t i o n , a l t h o u g h t h e d a n g e r of c o n g e s t i v e h e a r t failure exists, t h e o r e t i c a l l y , w i t h t h e u s e of n o r m a l saline. Careful a t t e n t i o n t o t h e p a t i e n t ' s s t a t u s is n e e d e d d u r i n g t h i s test. REFERENCES 1. R O S E LI, W I L L I A M S G H , JAGGER PI, L A U L E R DP: The 48-hour adreno-
corticotrophin infusion test for adrenocortical insufficiency. Ann Intern Med 73:49-54, 1970 2. L I D D L E GW, M E L M O N KL: The adrenals, in Textbook
of
Endocrinolo-
gy, edited by WILLIAMS RH. Philadelphia, W.B. Saunders Co., 1974, p. 251 3. W I L L I A M S G H , D L U H Y RG, T H O R N GW: Diseases of the adrenal cortex,
in Harrison's Principles of Internal Medicine, edited by W I N T R O B E MW, T H O R N GW, A D A M S R D , B E N N E T T IL J R , B R A U N W A L D E, ISSELBACH-
ER KJ, PETERSDORF RG. New York, McGraw Hill Book Company, 1974, p. 497 4. K I N G JC: Guide to Parenteral Admixtures. St. Louis, Cutter Laboratories, 1976 5. M E R R E L L - N A T I O N A L LABORATORIES: ACTH Solution Product Information. Cincinnati, Merrella National Laboratories, 1972 © 1 9 7 9 American College of Physicians
Brief Reports
Downloaded from https://annals.org by University of Otago user on 01/20/2019
799
