CLINICAL CONFERENCE
Unforgettable patients David Cornfeld, MD
The following three cases represent variations on a theme-elevation of blood pressure in three unusual (and, for me, instructive) circumstances. PATIENT
1
It was July 1, 1950, day 1 of my pediatric internship. A 5-year-old boy was admitted to the hospital in the early evening with a chief complaint of grand real seizures. On the afternoon of admission he had his first seizure, which lasted approximately 5 minutes. When seen in the emergency department, he had another grand mal episode, which was controlled with parenteral administration of phenobarbital and phenytoin. Except for mild anorexia and vague abdominal discomfort, he had no other acute symptoms. His medical history was unremarkable, as was the family history. On initial examination the patient's temperature was 38.0 ~ C, blood pressure was 130/90 mrn Hg, and pulse was 60 beats/rain. He was sleepy but responded to questioning. Results of the general physical examination, including funduscopic evaluation, were otherwise entirely normal. Initial laboratory studies included a normal complete blood cell count and a urinalysis, which showed a specific gravity of 1.028, a trace of protein, and a rare erythrocyte per high-power field. Serum chemistry studies showed normal blood urea nitrogen, calcium, and sugar levels. A lumbar puncture was performed; the initial pressure was 180 m m / H g with no cells, and spinal fluid protein values were normal. The diagnostic impression was that this child's seizure was probably the first manifestation of an idiopathic seizure disorder and that the mild elevation of blood pressure was a result of seizure activity. The child was maintained with anticonvulsant therapy. On the morning after admission he voided grossly abnormal, smoky urine. Myriads of erythrocytes and erythrocyte casts were seen on examination of the sediment. The blood pressure at this time was 145/100 mm Hg. The laboratory subsequently re-
Dr. Cornfeld is Professor and Vice Chairman of the Department of Pediatrics, University of PennsylvaniaSchool of Medicine, and Deputy Physician-in-Chief, Children's Hospital of Philadelphia. From 1979 to 1989 he was Editor of Clinical Pediatrics and currently serves as the Editor of The Pediatric Video Digest. 9/32/35224
494
ported that the child had an elevated antistreptolysin O titer and that group A/3-hemolytic streptococci were isolated from a culture of oropharyngeal secretions. It was now obvious that the child's seizures were caused by a hypertensive encephalopathy complicating an acute poststreptococeal glomerulonephritis. There may be no demonstrable abnormalities on funduscopic evaluation in the patient with acute hypertensive encephalopathy associated with nephritis. A benign urinary picture is occasionally seen in this syndrome.l, 2 (Incidentally, initial routine laboratory studies including complete blood cell counts and urinalyses were done by the admitting intern in that era.) PATIENT
2
The patient, an 11-year-old girl, had had intermittent headaches for a year. The headaches had been a persistent and recurring problem, interfering with school attendance and recreation. Most occurred early in the morning and were occasionally associated with vomiting. The child had noted that the headaches were particularly prominent when she urinated. Blood pressure was said to have been normal when recorded at a routine examination 6 months previously. Six weeks before admission to the hospital, the headaches became more severe and were associated with transient sweating episodes. The headaches were not exacerbated by defecation, but they were now even more clearly associated with urination. When the patient was seen by her physician, her b!opd pressure was 250/200 mm Hg, and early papilledema was noted on funduscopic examination. Evaluation at a community hospital demonstrated markedly elevated urinary metanephrine, vanillylmandelicacid, and total catecholamine values. The patient was transferred to Children's Hospital of Philadelphia. At this time her blood pressure was 175/115 mm Hg, and physical examination findings were as previously noted. She was given phenoxybenzamine and then c~-methyltyrosine, which adequately controlled her blood pressure. However, she still had headaches on voiding. She was therefore taken to surgery for abdominal exploration. In the operating room, palpation suprapubically did not produce any elevation of the blood pressure. The surgeon therefore elected to explore the upper portion of the abdomen and the paraganglionic area initially. No tumor was located. However, further explora-
Volume 121 Number 3
Unforgettable patients
tion revealed a mass deep in the pelvis, pressing on the bladder under the symphysis pubis. After its removal the child's blood pressure returned to normal. Pathologic study confirmed the presence of a chromaffin paraganglioma of the bladder wall. Comment. The value of a complete history is demonstrated by this case--that of a child seen in the era before imaging techniques such as magnetic resonance imaging, computed tomographic scan, and ultrasonography were available. The history of headache on urinating was instrumental in defining the probable location of this tumor. PATIENT
3
A female infant had been seen at age 5 months (1 month before the current hospital admission) for evaluation of persistent proteinuria and intermittent hyponatremia. She had previously been hospitalized at age 2 months and again at 4 months with fever associated with proteinuria and hematuria. Initially she had been treated for presumed pyelonephritis, but on the second admission the urine had been consistently sterile. At the 5-month evaluation the blood pressure was 85 mm Hg by palpation, the urine had only trace amounts of protein and occasional erythrocytes, the culture was again sterile, and a voiding cystourethrogram demonstrated no abnormalities. At age 6 months the infant was admitted to Children's Hospital of Philadelphia with fever, proteinuria, dehydration, and irritability, as well as weight loss of 0.8 kg during the previous 3 weeks. Aside from moderate dehydration, the physical examination findings were unremarkable. The blood pressure was 70/52 mm Hg. The initial evaluation demonstrated a serum sodium concentration of 124 mEq/L, normal blood urea nitrogen and creatinine values, and evidence of renal sodium wasting (urine sodium concentration 58 mEq/L). On urinalysis, proteinuria (4+), a trace amount of glucose, 10 to 20 erythrocytes, and occasional leukocytes were noted. Several urine cultures were sterile. The serum sodium concentration remained low despite administration of twice the calculated amount of maintenance sodium replacement therapy; 840 mg of protein was found in a 24-hour urine collection. Renal ultrasonography demonstrated asymmetry of the kidneys, with the right kidney measuring 4.8 cm and the left 6.3 cm in vertical diameter; increased echogenicity was also noted in the right kidney. An open renal biopsy was recommended to clarify the diagnosis. During induction of aries-
495
thesia a hypertensive crisis ensued, with systolic blood pressures as high as 240 mm Hg recorded, requiring emergency therapy with nitroprusside and subsequently with captopril and minoxidil. Subsequent study demonstrated significant hyperreninemia and a severe stenosis of the distal portion of the right renal artery, with poststenotic dilation on arteriography. After a right nephrectomy was performed, the blood pressure, electrolyte values, and plasma renin levels normalized, and the proteinuria completely resolved. Three years after surgery the child continues to have normal blood pressure, serum electrolyte values, and growth pattern. Comment. Both hyponatremia and nephrotic levels of proteinuria have been reported with renal vascular disease, but not occurring concurrently. Under experimental conditions, renal salt loss, even in the face of secondary hyperaldosteronism and hyperreninemia, may occur with malignant hypertension, presumably resulting from high pressure diuresis. 3 In the experimental animal, infusion of renin can also result in significant proteinuria. This has been noted in human subjects as well. 4, 5 It is likely that the nephrotic level of proteinuria in our patients was a result of the hyperreninemia, because it decreased with angiotensin converting enzyme inhibitor therapy and was cured by unilateralnephrectomy. COMMENT The lessons that I have learned from these cases include the importance of measuring blood pressure and interpreting it correctly, carefully obtaining the history, and understanding the potential unusual pathophysiologic consequences of renal artery stenosis. REFERENCES
1. CohenJA, Levitt MF. Acute glomerulonephritiswith few urinary abnormalities. N Engl J Med 1963;268:749-53. 2. Albert MS, Leeming JM, Scaglione PR. Acute glomerulonephritis without abnormalities of the urine. J PEDIATa 1966;68:525-9. 3. Blanc F, Bensman A, Baudon JJ. Renovascular hypertension:a rare cause of neonatal salt loss. Pediatr Nephrol 1991;5: 304-6. 4. Montoliu J, Bodey A, Torras A, Darnell A, Revert L. Renininducedmassiveproteinuria in man. Clin Nephrol 1979;11:26771. 5. Eiser AR, Katz SM, Swartz C. Reversible nephrotic range proteinuria with renal artery stenosis: a clinical diagnosis of renin--associated proteinuria. Nephron. 1982;30:374-7.
Unforgettable patients David Cornfeld, MD
The following three cases represent variations on a theme-elevation of blood pressure in three unusual (and, for me, instructive) circumstances. PATIENT
1
It was July 1, 1950, day 1 of my pediatric internship. A 5-year-old boy was admitted to the hospital in the early evening with a chief complaint of grand real seizures. On the afternoon of admission he had his first seizure, which lasted approximately 5 minutes. When seen in the emergency department, he had another grand mal episode, which was controlled with parenteral administration of phenobarbital and phenytoin. Except for mild anorexia and vague abdominal discomfort, he had no other acute symptoms. His medical history was unremarkable, as was the family history. On initial examination the patient's temperature was 38.0 ~ C, blood pressure was 130/90 mrn Hg, and pulse was 60 beats/rain. He was sleepy but responded to questioning. Results of the general physical examination, including funduscopic evaluation, were otherwise entirely normal. Initial laboratory studies included a normal complete blood cell count and a urinalysis, which showed a specific gravity of 1.028, a trace of protein, and a rare erythrocyte per high-power field. Serum chemistry studies showed normal blood urea nitrogen, calcium, and sugar levels. A lumbar puncture was performed; the initial pressure was 180 m m / H g with no cells, and spinal fluid protein values were normal. The diagnostic impression was that this child's seizure was probably the first manifestation of an idiopathic seizure disorder and that the mild elevation of blood pressure was a result of seizure activity. The child was maintained with anticonvulsant therapy. On the morning after admission he voided grossly abnormal, smoky urine. Myriads of erythrocytes and erythrocyte casts were seen on examination of the sediment. The blood pressure at this time was 145/100 mm Hg. The laboratory subsequently re-
Dr. Cornfeld is Professor and Vice Chairman of the Department of Pediatrics, University of PennsylvaniaSchool of Medicine, and Deputy Physician-in-Chief, Children's Hospital of Philadelphia. From 1979 to 1989 he was Editor of Clinical Pediatrics and currently serves as the Editor of The Pediatric Video Digest. 9/32/35224
494
ported that the child had an elevated antistreptolysin O titer and that group A/3-hemolytic streptococci were isolated from a culture of oropharyngeal secretions. It was now obvious that the child's seizures were caused by a hypertensive encephalopathy complicating an acute poststreptococeal glomerulonephritis. There may be no demonstrable abnormalities on funduscopic evaluation in the patient with acute hypertensive encephalopathy associated with nephritis. A benign urinary picture is occasionally seen in this syndrome.l, 2 (Incidentally, initial routine laboratory studies including complete blood cell counts and urinalyses were done by the admitting intern in that era.) PATIENT
2
The patient, an 11-year-old girl, had had intermittent headaches for a year. The headaches had been a persistent and recurring problem, interfering with school attendance and recreation. Most occurred early in the morning and were occasionally associated with vomiting. The child had noted that the headaches were particularly prominent when she urinated. Blood pressure was said to have been normal when recorded at a routine examination 6 months previously. Six weeks before admission to the hospital, the headaches became more severe and were associated with transient sweating episodes. The headaches were not exacerbated by defecation, but they were now even more clearly associated with urination. When the patient was seen by her physician, her b!opd pressure was 250/200 mm Hg, and early papilledema was noted on funduscopic examination. Evaluation at a community hospital demonstrated markedly elevated urinary metanephrine, vanillylmandelicacid, and total catecholamine values. The patient was transferred to Children's Hospital of Philadelphia. At this time her blood pressure was 175/115 mm Hg, and physical examination findings were as previously noted. She was given phenoxybenzamine and then c~-methyltyrosine, which adequately controlled her blood pressure. However, she still had headaches on voiding. She was therefore taken to surgery for abdominal exploration. In the operating room, palpation suprapubically did not produce any elevation of the blood pressure. The surgeon therefore elected to explore the upper portion of the abdomen and the paraganglionic area initially. No tumor was located. However, further explora-
Volume 121 Number 3
Unforgettable patients
tion revealed a mass deep in the pelvis, pressing on the bladder under the symphysis pubis. After its removal the child's blood pressure returned to normal. Pathologic study confirmed the presence of a chromaffin paraganglioma of the bladder wall. Comment. The value of a complete history is demonstrated by this case--that of a child seen in the era before imaging techniques such as magnetic resonance imaging, computed tomographic scan, and ultrasonography were available. The history of headache on urinating was instrumental in defining the probable location of this tumor. PATIENT
3
A female infant had been seen at age 5 months (1 month before the current hospital admission) for evaluation of persistent proteinuria and intermittent hyponatremia. She had previously been hospitalized at age 2 months and again at 4 months with fever associated with proteinuria and hematuria. Initially she had been treated for presumed pyelonephritis, but on the second admission the urine had been consistently sterile. At the 5-month evaluation the blood pressure was 85 mm Hg by palpation, the urine had only trace amounts of protein and occasional erythrocytes, the culture was again sterile, and a voiding cystourethrogram demonstrated no abnormalities. At age 6 months the infant was admitted to Children's Hospital of Philadelphia with fever, proteinuria, dehydration, and irritability, as well as weight loss of 0.8 kg during the previous 3 weeks. Aside from moderate dehydration, the physical examination findings were unremarkable. The blood pressure was 70/52 mm Hg. The initial evaluation demonstrated a serum sodium concentration of 124 mEq/L, normal blood urea nitrogen and creatinine values, and evidence of renal sodium wasting (urine sodium concentration 58 mEq/L). On urinalysis, proteinuria (4+), a trace amount of glucose, 10 to 20 erythrocytes, and occasional leukocytes were noted. Several urine cultures were sterile. The serum sodium concentration remained low despite administration of twice the calculated amount of maintenance sodium replacement therapy; 840 mg of protein was found in a 24-hour urine collection. Renal ultrasonography demonstrated asymmetry of the kidneys, with the right kidney measuring 4.8 cm and the left 6.3 cm in vertical diameter; increased echogenicity was also noted in the right kidney. An open renal biopsy was recommended to clarify the diagnosis. During induction of aries-
495
thesia a hypertensive crisis ensued, with systolic blood pressures as high as 240 mm Hg recorded, requiring emergency therapy with nitroprusside and subsequently with captopril and minoxidil. Subsequent study demonstrated significant hyperreninemia and a severe stenosis of the distal portion of the right renal artery, with poststenotic dilation on arteriography. After a right nephrectomy was performed, the blood pressure, electrolyte values, and plasma renin levels normalized, and the proteinuria completely resolved. Three years after surgery the child continues to have normal blood pressure, serum electrolyte values, and growth pattern. Comment. Both hyponatremia and nephrotic levels of proteinuria have been reported with renal vascular disease, but not occurring concurrently. Under experimental conditions, renal salt loss, even in the face of secondary hyperaldosteronism and hyperreninemia, may occur with malignant hypertension, presumably resulting from high pressure diuresis. 3 In the experimental animal, infusion of renin can also result in significant proteinuria. This has been noted in human subjects as well. 4, 5 It is likely that the nephrotic level of proteinuria in our patients was a result of the hyperreninemia, because it decreased with angiotensin converting enzyme inhibitor therapy and was cured by unilateralnephrectomy. COMMENT The lessons that I have learned from these cases include the importance of measuring blood pressure and interpreting it correctly, carefully obtaining the history, and understanding the potential unusual pathophysiologic consequences of renal artery stenosis. REFERENCES
1. CohenJA, Levitt MF. Acute glomerulonephritiswith few urinary abnormalities. N Engl J Med 1963;268:749-53. 2. Albert MS, Leeming JM, Scaglione PR. Acute glomerulonephritis without abnormalities of the urine. J PEDIATa 1966;68:525-9. 3. Blanc F, Bensman A, Baudon JJ. Renovascular hypertension:a rare cause of neonatal salt loss. Pediatr Nephrol 1991;5: 304-6. 4. Montoliu J, Bodey A, Torras A, Darnell A, Revert L. Renininducedmassiveproteinuria in man. Clin Nephrol 1979;11:26771. 5. Eiser AR, Katz SM, Swartz C. Reversible nephrotic range proteinuria with renal artery stenosis: a clinical diagnosis of renin--associated proteinuria. Nephron. 1982;30:374-7.
