Antidiuretic Hormone Secretion in an Infant With Severe Pneumonia
Inappropriate
J.
Mor; E. Ben-Galim; A. Abrahamov
A 6-week-old boy with severe pneumonia developed hyponatremia as a result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Cerebral edema
and seizures occurred after administration of fluids and diuretics. Fluid restriction and resolution of the pneumonia corrected the severe electrolyte imbalance. The possibility of SIADH should be considered in cases of severe and resistant pneumonia in infancy.
Acute il
an
hypoelectrolytemia infrequent finding in
is not severe
infections.13 In 1929, Darrow and Hartmann were among the first to describe this condition in children.4 Children with acute pneumonia were found to have lower total plasma ion concentrations. Hyponatremia could be explained by an increase in plasma volume because of water retention. The syndrome of inappropriate anti¬ diuretic hormone secretion (SIADH)3 explains these findings. It was subse¬ quently described in a number of Received for publication May 23, 1973: accepted June 17, 1974. From the Department of Pediatrics B., Bikur Cholim General Hospital, Jerusalem. Reprint requests to Department of Pediatrics B., Bikur Cholim General Hospital, PO Box 492, Jerusalem, Israel (Dr. Abrahamov).
cases of severe pneumonia,68 but has not been well documented in the
pediatrie literature. We recently
ob¬ served an infant with severe pneu¬ monia who developed acute symp¬ tomatic hyponatremia and all the cardinal features of SIADH. REPORT OF A CASE A 6-week-old boy was hospitalized be¬ of severe respiratory distress. The child had been delivered by cesarean sec¬ tion, after an unremarkable pregnancy. His birth weight was 2,530 gm (5 lb 5 oz); the Apgar score was 9. Except for slow weight gain, his past medical and family history were unremarkable. His present illness began four days prior to admission with mild cough and gradually increasing respiratory difficulties that had not re¬ sponded to treatment. On admission he was severely ill. Normal skin turgor and moist mucous membranes were found. His temperature was 35.5 C (95.9 F), his pulse rate, 140 beats per minute, and his respira¬ tion rate was 75 per minute. He became cyanotic outside the oxygen tent. Respira¬ tions were labored with intercostal and subcostal retractions and flaring of his nostrils. Chest examination revealed bilat¬ eral pneumonia. A chest x-ray disclosed consolidation of both lung fields with areas of cystic lucency. The child was treated cause
penicillin G sodium, 300,000 mg given intravenously six times daily together with electrolyte solutions (5% glucose+ 0.18% Na Cl) 150 ml/kg/24 hr. Digitalis and di¬ uretics were given because of signs of im¬ pending heart failure. Generalized tonoclonic seizures occurred on the third day. They lasted about two minutes and termi¬ nated spontaneously. Blood glucose level with
120 mg/100 ml; calcium, 9.0 mg/100 ml; potassium, 4.2 mEq/liter; and bicar¬
was
bonate 22.3 millimols/liter. The serum so¬ dium level was 107 mEq/liter; chloride, 77 mEq/liter. Efforts to correct the hypona¬ tremia with 3% hypertonic saline and desoxycorticosterone acetate failed. Sodium concentration in the urine at that time was 120 mEq/liter and urinary osmolality 620 mOsm/kg. Fluid restriction and improve¬ ment of the pneumonia succeeded in cor¬ recting the severe electrolyte imbalance (Fig 1). Normal renal function was sug¬ gested by blood urea levels not exceeding 20 mg/100 ml and a blood creatinine level of 0.5 mg/100 ml. The 17-hydroxysteroid excretion was 0.08 mg/24 hr; 17-ketoste¬ roid excretion was 0.13 mg/24 hr.
COMMENT Since the clear delineation of the
syndrome of inappropriate antihormone secretion by Schwartz and as¬ sociates in 1957,3 the syndrome has been more frequently recognized.
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/10/2015
Bronchogenic carcinoma, a variety of nervous system (CNS) dis¬ eases, myxedema, acute porphyria, pulmonary and CNS tuberculosis, certain drugs, and pneumonia may
Desoxycorticosterone
Acetate
central
be associated with SIADH. In most instances the mechanism is only partially understood.91" The cardinal features of the syndrome were delineated by Bartter and Schwartz": (1) hyponatremia with corresponding hypoosmolality of the serum and ex¬ tracellular fluid; (2) urine that is hy¬ pertonic to plasma; (3) continued uri¬ nary excretion of sodium despite
hyponatremia (a finding sary for the diagnosis of SIADH if the intake of sodium is low); (4) nor¬ mal renal and adrenal function; (5) not
neces¬
absence of clinical evidence of fluid volume depletion (ie, normal skin tur¬ gor and blood pressure); (6) absence of clinical edema; (7) improvement of renal loss of sodium and hypona¬ tremia by fluid deprivation. The administration of isotonic saline solu¬ tions, hypertonic saline solutions, and mineralocorticoids in most instances is not effective in correcting the hypo¬ natremia. Hypertonic saline adminis¬ tration is indicated in symptomatic hyponatremia (manifest as convul¬ sions or coma because of cerebral swelling) in an attempt to rapidly correct the osmolality of extracellular fluid. In most instances a new steady state is reached in which sodium ex¬ cretion reflects sodium intake without any influence on free water clear¬ ance."
Pneumonia is
one
of the least ap¬
preciated causes of SIADH. Nonethe¬ less acute hyponatremia is encoun¬ tered not infrequently in adults with pneumonia."8 Descriptions of the same condition in the pediatrie litera¬ ture
are scarce.
Antidiuretic hormone is released from the posterior pituitary gland as a result of osmotic and nonosmotic stimuli.11 One of the most effective nonosmotic stimuli is a decrease in tension in the left atrium and pulmo¬ nary veins with reduced intrathoracic blood volume.11 Acute hypoxia in pa¬ tients with severe pneumonia could produce pulmonary vasoconstriction and reduced venous return to the left side of the heart. Perfusion studies in
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Serum Na
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Urine Na -
_L 2
3
4
5
6
Hospitalization, Days Fig 1.—Clinical
patients
with
course.
pneumonia
demon¬
strate avascular segments of lung corresponding to the pneumonia.
findings suggest volume and pressure changes in the pulmonary These
vasculature and the left side of the heart.1- It is also possible that an ADH-like substance is elaborated by the infected lung tissue, as has been demonstrated in pulmonary tubercu¬ losis.13 It is hypothesized that severe pneumonias produce a decrease of pulmonary blood flow, causing reduc¬ tion of tension in the capacitance ves¬ sels of the lung and in the left atrium. This stimulates inappropriate ADH secretion by interference with vagai inflow. The increased amount of ADH
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/10/2015
would lead to fluid
retention, and an expanded plasma volume stimulates
release of "third factor" and inhibits secretion of aldosterone.4·" The com¬ bined effect of both hormones would be natriuresis in spite of hypona¬ tremia (Fig 2). In our patient, hyponatremia could be caused by the proposed mecha¬ nism. The hyponatremia revealed it¬ self at the peak of the pulmonary dis¬ ease. It was aggravated by the fluid and diuretic administration. Were it not for the symptoms of brain edema, the hyponatremia could have passed undetected. The onset and resolution of SIADH are particularly acute when associ-
Intrathoracic Blood Volume Severe Pneumonia
Tension in Left Atrial Wall and
-
Pulmonary Veins
\ Vagai Inflow to Hypothalamus Renal Water
Water
Reabsorption
/
ADH Secretion
Ingestion
Aldosterone
^L.
Third Factor Plasma Dilution
'
Fig 2.—Pathogenesis
Hyponatremia
of SIADH and
hyponatremia
ated with pneumonia.8 As the pneu¬ monia resolves and lung perfusion increases, there is an increase in intrathoracic blood volume. This per se inhibits the release of ADH, en-
in
pneumonia.
abling free water diuresis and correc¬ tion of expanded blood volume. Because pneumonia in childhood is very sensitive to treatment, transient hyponatremia could remain unde-
tected. This may be the reason for the scarcity of reports in the pediatrie lit¬ erature. However, the possibility of SIADH has to be considered in cases of severe and resistant pneumonia.
References 1. Soule HC, Buckmann TE, Darrow DC: Blood volume in fever. J Clin Invest 5:229\x=req-\ 242, 1928. 2. Nyhan WL, Cooke RE: Symptomatic hyponatremia in acute infections of the central nervous system. Pediatrics 18:604\x=req-\ 613, 1956. 3. Gonzalez CF, Finberg L, Bluestein DD: Electrolyte concentrations during acute infections: Observations in infants and children. Am J Dis Child 107:476-482, 1964. 4. Darrow DC, Hartmann HF: Chemical changes occurring in the body as a result of certain diseases: IV. Primary Pneumonia in children. Am J Dis Child 37:323\x=req-\ 334, 1929. 5. Schwartz WB, Bennett W, Curelop S,
syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic horet al: A
Am J Med 23:529-542, 1957. 6. Stormont JM, Waterhouse C: Severe hyponatremia associated with pneumonia. Metabolism 11:1181-1186, 1962. 7. Overholt EL: Water intoxication: Its diagnosis and management. Milit Med 133:607-613, 1968. 8. Rosenow III EC, Segar WE, Zehr JE: antidiuretic hormone secreInappropriate tion in pneumonia. Mayo Clin Proc 47:169\x=req-\ 174, 1972. 9. Bartter EC, Schwartz WB: The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 42:790-806, 1967. mone.
10. Bartter EC: The syndrome of inappropriate secretion of antidiuretic hormone. J R Coll Physicians Lond 4:264-272,
1970. 11. Kleeman CR, Fichman MP: The clinical physiology of water metabolism. N Engl J Med 277:1300-1307, 1967. 12. Sieniewicz DJ, Rosenthal L, Herba MJ, et al: Correlative assessment of the macroalbumin lung scan with the clinical and roentgenographic chest findings. Am J Roentgenol Radium Ther Nucl Med 100:822-834, 1967. 13. Vorherr H, Massry SG, Fallet R, et al: Antidiuretic principle in tuberculous lung tissue of a patient with pulmonary tuberculosis and hyponatremia. Ann Intern Med 72:383-387, 1970.
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/10/2015
Inappropriate
J.
Mor; E. Ben-Galim; A. Abrahamov
A 6-week-old boy with severe pneumonia developed hyponatremia as a result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Cerebral edema
and seizures occurred after administration of fluids and diuretics. Fluid restriction and resolution of the pneumonia corrected the severe electrolyte imbalance. The possibility of SIADH should be considered in cases of severe and resistant pneumonia in infancy.
Acute il
an
hypoelectrolytemia infrequent finding in
is not severe
infections.13 In 1929, Darrow and Hartmann were among the first to describe this condition in children.4 Children with acute pneumonia were found to have lower total plasma ion concentrations. Hyponatremia could be explained by an increase in plasma volume because of water retention. The syndrome of inappropriate anti¬ diuretic hormone secretion (SIADH)3 explains these findings. It was subse¬ quently described in a number of Received for publication May 23, 1973: accepted June 17, 1974. From the Department of Pediatrics B., Bikur Cholim General Hospital, Jerusalem. Reprint requests to Department of Pediatrics B., Bikur Cholim General Hospital, PO Box 492, Jerusalem, Israel (Dr. Abrahamov).
cases of severe pneumonia,68 but has not been well documented in the
pediatrie literature. We recently
ob¬ served an infant with severe pneu¬ monia who developed acute symp¬ tomatic hyponatremia and all the cardinal features of SIADH. REPORT OF A CASE A 6-week-old boy was hospitalized be¬ of severe respiratory distress. The child had been delivered by cesarean sec¬ tion, after an unremarkable pregnancy. His birth weight was 2,530 gm (5 lb 5 oz); the Apgar score was 9. Except for slow weight gain, his past medical and family history were unremarkable. His present illness began four days prior to admission with mild cough and gradually increasing respiratory difficulties that had not re¬ sponded to treatment. On admission he was severely ill. Normal skin turgor and moist mucous membranes were found. His temperature was 35.5 C (95.9 F), his pulse rate, 140 beats per minute, and his respira¬ tion rate was 75 per minute. He became cyanotic outside the oxygen tent. Respira¬ tions were labored with intercostal and subcostal retractions and flaring of his nostrils. Chest examination revealed bilat¬ eral pneumonia. A chest x-ray disclosed consolidation of both lung fields with areas of cystic lucency. The child was treated cause
penicillin G sodium, 300,000 mg given intravenously six times daily together with electrolyte solutions (5% glucose+ 0.18% Na Cl) 150 ml/kg/24 hr. Digitalis and di¬ uretics were given because of signs of im¬ pending heart failure. Generalized tonoclonic seizures occurred on the third day. They lasted about two minutes and termi¬ nated spontaneously. Blood glucose level with
120 mg/100 ml; calcium, 9.0 mg/100 ml; potassium, 4.2 mEq/liter; and bicar¬
was
bonate 22.3 millimols/liter. The serum so¬ dium level was 107 mEq/liter; chloride, 77 mEq/liter. Efforts to correct the hypona¬ tremia with 3% hypertonic saline and desoxycorticosterone acetate failed. Sodium concentration in the urine at that time was 120 mEq/liter and urinary osmolality 620 mOsm/kg. Fluid restriction and improve¬ ment of the pneumonia succeeded in cor¬ recting the severe electrolyte imbalance (Fig 1). Normal renal function was sug¬ gested by blood urea levels not exceeding 20 mg/100 ml and a blood creatinine level of 0.5 mg/100 ml. The 17-hydroxysteroid excretion was 0.08 mg/24 hr; 17-ketoste¬ roid excretion was 0.13 mg/24 hr.
COMMENT Since the clear delineation of the
syndrome of inappropriate antihormone secretion by Schwartz and as¬ sociates in 1957,3 the syndrome has been more frequently recognized.
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/10/2015
Bronchogenic carcinoma, a variety of nervous system (CNS) dis¬ eases, myxedema, acute porphyria, pulmonary and CNS tuberculosis, certain drugs, and pneumonia may
Desoxycorticosterone
Acetate
central
be associated with SIADH. In most instances the mechanism is only partially understood.91" The cardinal features of the syndrome were delineated by Bartter and Schwartz": (1) hyponatremia with corresponding hypoosmolality of the serum and ex¬ tracellular fluid; (2) urine that is hy¬ pertonic to plasma; (3) continued uri¬ nary excretion of sodium despite
hyponatremia (a finding sary for the diagnosis of SIADH if the intake of sodium is low); (4) nor¬ mal renal and adrenal function; (5) not
neces¬
absence of clinical evidence of fluid volume depletion (ie, normal skin tur¬ gor and blood pressure); (6) absence of clinical edema; (7) improvement of renal loss of sodium and hypona¬ tremia by fluid deprivation. The administration of isotonic saline solu¬ tions, hypertonic saline solutions, and mineralocorticoids in most instances is not effective in correcting the hypo¬ natremia. Hypertonic saline adminis¬ tration is indicated in symptomatic hyponatremia (manifest as convul¬ sions or coma because of cerebral swelling) in an attempt to rapidly correct the osmolality of extracellular fluid. In most instances a new steady state is reached in which sodium ex¬ cretion reflects sodium intake without any influence on free water clear¬ ance."
Pneumonia is
one
of the least ap¬
preciated causes of SIADH. Nonethe¬ less acute hyponatremia is encoun¬ tered not infrequently in adults with pneumonia."8 Descriptions of the same condition in the pediatrie litera¬ ture
are scarce.
Antidiuretic hormone is released from the posterior pituitary gland as a result of osmotic and nonosmotic stimuli.11 One of the most effective nonosmotic stimuli is a decrease in tension in the left atrium and pulmo¬ nary veins with reduced intrathoracic blood volume.11 Acute hypoxia in pa¬ tients with severe pneumonia could produce pulmonary vasoconstriction and reduced venous return to the left side of the heart. Perfusion studies in
Furosemide 5 mg
4
4
i
44
i
I
600
150
ai
E
100
—
-3-
400
EX
200
5
€ •D
50
O
150
•j= LU
E
-
.·
140
>-
130
(0
2
120
E
I
11°
100
LU
E co
o^
50
/
100
150
Serum Na
«
Urine Na -
_L 2
3
4
5
6
Hospitalization, Days Fig 1.—Clinical
patients
with
course.
pneumonia
demon¬
strate avascular segments of lung corresponding to the pneumonia.
findings suggest volume and pressure changes in the pulmonary These
vasculature and the left side of the heart.1- It is also possible that an ADH-like substance is elaborated by the infected lung tissue, as has been demonstrated in pulmonary tubercu¬ losis.13 It is hypothesized that severe pneumonias produce a decrease of pulmonary blood flow, causing reduc¬ tion of tension in the capacitance ves¬ sels of the lung and in the left atrium. This stimulates inappropriate ADH secretion by interference with vagai inflow. The increased amount of ADH
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/10/2015
would lead to fluid
retention, and an expanded plasma volume stimulates
release of "third factor" and inhibits secretion of aldosterone.4·" The com¬ bined effect of both hormones would be natriuresis in spite of hypona¬ tremia (Fig 2). In our patient, hyponatremia could be caused by the proposed mecha¬ nism. The hyponatremia revealed it¬ self at the peak of the pulmonary dis¬ ease. It was aggravated by the fluid and diuretic administration. Were it not for the symptoms of brain edema, the hyponatremia could have passed undetected. The onset and resolution of SIADH are particularly acute when associ-
Intrathoracic Blood Volume Severe Pneumonia
Tension in Left Atrial Wall and
-
Pulmonary Veins
\ Vagai Inflow to Hypothalamus Renal Water
Water
Reabsorption
/
ADH Secretion
Ingestion
Aldosterone
^L.
Third Factor Plasma Dilution
'
Fig 2.—Pathogenesis
Hyponatremia
of SIADH and
hyponatremia
ated with pneumonia.8 As the pneu¬ monia resolves and lung perfusion increases, there is an increase in intrathoracic blood volume. This per se inhibits the release of ADH, en-
in
pneumonia.
abling free water diuresis and correc¬ tion of expanded blood volume. Because pneumonia in childhood is very sensitive to treatment, transient hyponatremia could remain unde-
tected. This may be the reason for the scarcity of reports in the pediatrie lit¬ erature. However, the possibility of SIADH has to be considered in cases of severe and resistant pneumonia.
References 1. Soule HC, Buckmann TE, Darrow DC: Blood volume in fever. J Clin Invest 5:229\x=req-\ 242, 1928. 2. Nyhan WL, Cooke RE: Symptomatic hyponatremia in acute infections of the central nervous system. Pediatrics 18:604\x=req-\ 613, 1956. 3. Gonzalez CF, Finberg L, Bluestein DD: Electrolyte concentrations during acute infections: Observations in infants and children. Am J Dis Child 107:476-482, 1964. 4. Darrow DC, Hartmann HF: Chemical changes occurring in the body as a result of certain diseases: IV. Primary Pneumonia in children. Am J Dis Child 37:323\x=req-\ 334, 1929. 5. Schwartz WB, Bennett W, Curelop S,
syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic horet al: A
Am J Med 23:529-542, 1957. 6. Stormont JM, Waterhouse C: Severe hyponatremia associated with pneumonia. Metabolism 11:1181-1186, 1962. 7. Overholt EL: Water intoxication: Its diagnosis and management. Milit Med 133:607-613, 1968. 8. Rosenow III EC, Segar WE, Zehr JE: antidiuretic hormone secreInappropriate tion in pneumonia. Mayo Clin Proc 47:169\x=req-\ 174, 1972. 9. Bartter EC, Schwartz WB: The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 42:790-806, 1967. mone.
10. Bartter EC: The syndrome of inappropriate secretion of antidiuretic hormone. J R Coll Physicians Lond 4:264-272,
1970. 11. Kleeman CR, Fichman MP: The clinical physiology of water metabolism. N Engl J Med 277:1300-1307, 1967. 12. Sieniewicz DJ, Rosenthal L, Herba MJ, et al: Correlative assessment of the macroalbumin lung scan with the clinical and roentgenographic chest findings. Am J Roentgenol Radium Ther Nucl Med 100:822-834, 1967. 13. Vorherr H, Massry SG, Fallet R, et al: Antidiuretic principle in tuberculous lung tissue of a patient with pulmonary tuberculosis and hyponatremia. Ann Intern Med 72:383-387, 1970.
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/10/2015
