- Email: [email protected]
Severe hypertension in an adolescent girl
Volume 101 Number 3
rectal wall distention and anoxia. Although constipated, our patient was only significantly distended at 2 days and 2 months of age, making it difficult to account for the loss of ganglion ceils on this basis. In fact, constipation probably was the result of an initial absence (or early disappearance) of ganglion cells from the sigmoid. Although paucity of ganglion cells in the rectal wall may cause a clinical picture similar to that of Hirschsprung disease, ganglion cells in our patient were readily apparent on acetylcholinesterase staining of the initial rectal biopsy. A viral etiology is possible, although there were no suggestive inflammatory changes noted on the initial biopsy. There was also no history of exposure to neurotoxic agents capable of causing ganglion cell degeneration. After consideration of several possible mechanisms, we believe that acquired distal aganglionosis in this case may have resulted from an inapparent hypoxic event.
Clinical and laboratory observations
409
REFERENCES I. Touloukian R J, and Duncan R: Acquired aganglionic megacolon in a premature infant: Report of a case, Pediatrics 56:459, 1975. 2. Towne BH, Stocker JT, Thompson HE, and Chang JT: Acquired aganglionosis, J Pediatr Surg 14:688, 1979. 3. Dimler M: "Acquired" Hirschsprung's disease, J Pediatr Surg 16:844, 1981. 4. Okamoto E, Iwasaki T, Kakutani T, and Veda T: Selective destruction of the myenteric plexus: It's relation to Hirschsprung's disease, achalasia of the esophagus and hypertrophic pyloric stenosis, J Pediatr Surg 2:444, 1967. 5. Kosloske AM, Burstein J, and Bartow SA: Intestinal obstruction due to colonic structure following neonatal necrotizing enterocolitis, Ann Surg 192:202, 1980. 6. Chow CW, Chan WC, and Yue PK: Histochemical criteria for the diagnosis of Hirschsprung's disease in rectal suction biopsies by acetylcholinesterase activity, J Pediatr Surg 12:675, 1977.
Severe hypertension in an adolescent girl Julia A. Elrod, M.D., Bradley A. Warady, M.D., Eugene C. Beatty, Jr., M.D., EUeen Duggan, M.D., Fayzeh Mansour, M.D., Thomas H. Smith, M.D., and Stanley Hellerstein, M.D.,* Kansas City, Kan.
A GIRL with severe hypertension had a juxtaglomerular cell tumor detected by C A T scan, although renin activity was similar in blood from the right and left renal veins and an initial renal arteriogram did not demonstrate the tumor. CASE REPORT This 14-year-old Caucasian glrl was admitted to The Children's Mercy Hospital on February 20, 1980, because of persistent hypertension. The blood pressure was 160/110 during a physical examination for basketball in September, 1979, and was similarly elevated on repeated examinations during the ensuing five months. She had progressively severe frontal headaches. Past history was pertinent only in that her blood pressure was 90/70 at 8 years of age. There was a strong family history of hypertension. The maternal grandmother had a stroke at age 56 and the paternal grandmother died of a myocardial infarction at 44 years of age. The patient was asymptomatic at the time of admission. The blood pressure was 172/130 in the right arm when in the sitting position. The femoral pulses were normal. The height and weight were at the fiftieth percentile for age. Pertinent initial laboratory studies included: serum sodium concentration 142 mEq/L, potas-
From the University o f Missouri-Kansas City School o f Medicine. *Reprint address." The Children's Mercy Hospital, 24th at Gillham Road. Kansas City, MO 64108.
0022-3476/82/090409+03500.30/0 @ 1982 The C. V. Mosby Co.
slum 3.0 mEq/L, chloride 102 mEq/L, total CO2 25 mM/L, and creatinine 0.75 mg/dl. Several urinalyses were normal. Peripheral plasma renin activity was 11.6 ng/ml/hour. The blood specimen for renin activity was obtained with other initial laboratory studies, with the patient in an upright position. Dietary history, which seemed reliable, indicated a sodium intake of approximately 2 gm/24 hours. Abbreviation used CAT: computerized axial tomography Results of an intravenous pyelogram was considered normal. Plasma renin activity, measured on blood samples obtained during vena caval catheterization, ranged from 6,1 to 6.8 ng/ml/hour in specimens obtained below entry of the renal veins, in the right and left renal veins, and above the renal veins. The patient had received no propranolol for approximately 24 hours prior to these studies. A midstream aortogram and selective right and left renal angiograms were interpreted as normal (Fig. 1, A). The patient was discharged with a presumptive diagnosis of essential hypertension. Initially, treatment consisted of 500 mg chlorothiazide, twice a day, 40 mg propranolol, three times a day, and salt restriction. The addition of hydralazine improved blood pressure control so that it ranged from a high of 145/110 to usual readings of 110 to 120/80 to 90 mm Hg. After about six months the blood pressure was again in the range of 120-170/85-120. The parents brought the patient back for further evaluation in September of 1980 because of an article in the August, 1980, issue of
4 10
Clinical and laboratory observations
The Journal of Pediatrics September 1982
Fig. 1. Right renal arteriogram. A, First study, in which only one right renal artery was identified and injected. B, Second study, in which two right renal arteries were identified. Injection of contrast material into the artery supplying the lower pole demonstrated a filling defect just above the midplane.
Fig. 2. A film through the kidneys taken during the enhanced computerized tomography study. There is a 2.5 cm mass in the posterior portion of the upper P01e of the right kidney.
Good Housekeeping Magazine. The article was entitled, "The Search that Saved Tracie's Life." The parents requested that we do a CAT scan with the hope that we might find a pheochromocytoma. Physical examination was essentially unchanged from that of the previous admission. The blood pressure was 160/120 in the right arm in the sitting position. The peripheral plasma renin activity was 7.5 ng/ml/hour in a morning blood specimen obtained with the patient in the recumbent position and without propranolol therapy for 48 hours. The patient was receiving a diet" with 1,000 mg sodium, and chlorothiazide, 500 mg twice a day. A computerized tomographic study showed a 2.5 cm solid mass in the posterior portion of the superior pole of the right kidney (Fig. 2). The lesion was seen in the study with contrast, but not in that without contrast enhancement. Renal ultrasound did not demonstrate an abnormality in the right kidney. Separate renal
arteries to the upper and lower poles of the right kidney were identified on the midstream aortogram done at this time. Injection of contrast material into the lower pole artery revealed a smooth, round, 3 cm in diameter filling defect just above the midplane (Fig. 1, B). Technical problems prevented selective catheterization of veins draining the right kidney. With the patient off propranolol therapy for more than 48 hours, plasma renin activities were 11.7, 12.5, and 11.7 ng/ml/hour, respectively, in vena caval blood obtained below, at the level of, and above the renal veins. A right nephrectomy was done on October 23, 1980. The operation and the postoperative course were uneventful. All medications were discontinued and the blood pressure remained normal. Five days after surgery the peripheral plasma renin activity was 1.1 ng/ml/hour. The pathologic diagnosis was juxtaglomerular cell tumor. Electron micrographs showed dense granules which were morphologically consistent with renin crystals, and assay of a sample of tumor tissue showed an enormously high-renin concentration. During a nine-month follow-up period the patient has been symptom-free and the blood pressure normal. Two measurements of peripheral plasma renin activity have been 0.5 ng/ml/hour. DISCUSSION H a d the two arteries supplying blood to the right kidney been identified on the first m i d s t r e a m a o r t o g r a m , selective right renal arteriography would almost certainly have shown the t u m o r during the initial study. However, of the 16 reported cases of j u x t a g l o m e r u l a r cell tumor, the first renal a r t e r i o g r a m was n o r m a l in eight, a n d t h e a o r t o g r a m was normal in another two. ~-~~This experience reinforces t h e concept t h a t it ~s necessary to re-evaluate periodically pediatric patients who have persistent, unexplained hypert e n s i o n - i n c l u d i n g those with a strong family history of hypertension.
Volume 101 Number 3
Clinical and laboratory observations
The absence of increased renin activity in blood from the right renal vein compared with that from the left renal vein and the vena cava below the renal veins is difficult to explain. At the time of both vena caval catheterization studies the patient had not been taking propranolol, a drug which suppresses renin secretion. Two possible explanations come to mind. There may have been an accessory vein draining the superior pole of the right kidney, or, at the time of these studies, the tumor was not delivering renin to the venous system. Bonnin et al 1 noted that elevated renin levels may be found in blood from a segmental renal vein when main renal vein or peripheral plasma renin activities are not significantly elevated. We consider it reasonable to suggest C A T scan of the kidneys in a pediatric patient with severe, unexplained hypertension in whom renal arteriography is normal. The tendency for renin-secreting tumors to be small in size and peripheral in location contributes to the difficulty in demonstrating them using other radiologic procedures. 2 We acknowledge the help given by Robert Erlandson, Ph.D., Sloan-Kettering Memorial Center, New York City, and Alan Poisner, M.D., Department of Pharmacology, College of Health Sciences and Hospital, Kansas City, Kansas, for their help in completing the study of the juxtaglomerular cell tumor. REFERENCES
2.
3.
4.
5.
6.
7.
8.
9.
10.
1. Bonnin JM, Cain MD, Jose JS, Mukherjee TM, Perrett LV, Scroop GC, and Seymour AE: Hypertension due to a renin-
411
secreting tumor localized by segmental renal vein sampling, Aust NZ J Med 7:630, 1977. Warshaw, BL, Sudhir AK, Olson DL, Grushkin CM, Heuser ET, and Lieberman E: Hypertension secondary to a reninproducing juxtaglomerular cell tumor, J PEDIATR 94:247, 1979. Robertson PW, Klidjian A, Harding LK, Waiters G, Lee MR, and Robb-Smith AHT: Hypertension due to a reninsecreting renal tumor, Am J Med 43:963, 1967. Corm JW, Cohen EL, McDonald W J, Blough WM, Lucas CP, Mayor GH, Eveland WC, Bookstein J J, and Lapides J: The syndrome of hypertension, hyperreninemia and secondary aldosteronism associated with renal juxtaglomerular cell tumor (primary reninism), J Urol 109:349, 1973. Schambelan M, Howes EL, Stockigt JR, Noakes CA, and Biglier, EG: Role of renin and aldosterone in hypertension due to a renin-secreting tumor, Am J Med 55:86, 1973. Brown J J, Lever AF, Robertson JIS, Fraser R, Morton J J, Tree M, Bell PRF, Davidson JK, and Ruthven IS: Hypertension and secondary hyperaldosteronism associated with a renin-secreting renal juxtaglomerular-cell tumor, Lancet 2:1228, 1973. Gherardi G J, Arya S, and Hickler RB: Juxtaglomerular body tumor: A rare occult but curable Cause of lethal hypertension, Human Pathol 5:236, 1974. Hirose M, Arakawa K, Kikuchi M, Kawasaki T, Omoto T, Kato H, and Nagayama T: Primary reninism with renal hamartomatous alteration, JAMA 230:1288, 1974. ~rjavik US, Aas P, Fauchald P, Hovig T, ~ystese B, Brodwall EK, and Flatmark A: Renin-secreting renal tumour with severe hypertension, Acta Med Scand 197:329, 1975. Connor G, Bennett CM, Lindstrom RR, Brosman SA, Barajas L, and Edelbaum D: Juxtaglomerular cell tumor, Nephron 21:325, 1978.
Late development of chronic renal failure in steroid-responsive nephrotic syndrome Martin A. Nash, M.D.,* Meena A. Bakare, M.D.,** Vivette D'Agati, M.D., and Conrad L. Pirani, M.D., New York, N. Y.
CHILDREN with the idiopathic nephrotic syndrome who respond to prednisone with disappearance of proteinuria have an excellent long-term prognosis for maintenance of
normal glomerular filtration rate and eventual resolution of the syndrome, even in the face of multiple relapses over many years. The response to prednisone is such an accurate Abbreviation used GFR: glomerular filtration rate
From the sections of pediatric nephrology and renal pathology, College o f Physicians and Surgeons o f Columbia University. Supported by grant ROl-AM-25624 from the National Institutes of Health. *Reprint address: Room 701, Babies Hospital, 3975 Broadway, New York. NY 10032. **Supported in part by the New York State Kidney Disease Institute.
0022-3476/82/090411+04500.40/0 9
C. V. MosbyCo.
predictor of underlying minimal lesion disease ~ that in most centers renal biopsies are not routinely performed on these children. On the other hand, the majority of patients with the nephrotic syndrome and renal histological patterns known to be associated with progressive disease do not respond to treatment with prednisone during the initial episode. Although as many as 20 to 30% of patients with
rectal wall distention and anoxia. Although constipated, our patient was only significantly distended at 2 days and 2 months of age, making it difficult to account for the loss of ganglion ceils on this basis. In fact, constipation probably was the result of an initial absence (or early disappearance) of ganglion cells from the sigmoid. Although paucity of ganglion cells in the rectal wall may cause a clinical picture similar to that of Hirschsprung disease, ganglion cells in our patient were readily apparent on acetylcholinesterase staining of the initial rectal biopsy. A viral etiology is possible, although there were no suggestive inflammatory changes noted on the initial biopsy. There was also no history of exposure to neurotoxic agents capable of causing ganglion cell degeneration. After consideration of several possible mechanisms, we believe that acquired distal aganglionosis in this case may have resulted from an inapparent hypoxic event.
Clinical and laboratory observations
409
REFERENCES I. Touloukian R J, and Duncan R: Acquired aganglionic megacolon in a premature infant: Report of a case, Pediatrics 56:459, 1975. 2. Towne BH, Stocker JT, Thompson HE, and Chang JT: Acquired aganglionosis, J Pediatr Surg 14:688, 1979. 3. Dimler M: "Acquired" Hirschsprung's disease, J Pediatr Surg 16:844, 1981. 4. Okamoto E, Iwasaki T, Kakutani T, and Veda T: Selective destruction of the myenteric plexus: It's relation to Hirschsprung's disease, achalasia of the esophagus and hypertrophic pyloric stenosis, J Pediatr Surg 2:444, 1967. 5. Kosloske AM, Burstein J, and Bartow SA: Intestinal obstruction due to colonic structure following neonatal necrotizing enterocolitis, Ann Surg 192:202, 1980. 6. Chow CW, Chan WC, and Yue PK: Histochemical criteria for the diagnosis of Hirschsprung's disease in rectal suction biopsies by acetylcholinesterase activity, J Pediatr Surg 12:675, 1977.
Severe hypertension in an adolescent girl Julia A. Elrod, M.D., Bradley A. Warady, M.D., Eugene C. Beatty, Jr., M.D., EUeen Duggan, M.D., Fayzeh Mansour, M.D., Thomas H. Smith, M.D., and Stanley Hellerstein, M.D.,* Kansas City, Kan.
A GIRL with severe hypertension had a juxtaglomerular cell tumor detected by C A T scan, although renin activity was similar in blood from the right and left renal veins and an initial renal arteriogram did not demonstrate the tumor. CASE REPORT This 14-year-old Caucasian glrl was admitted to The Children's Mercy Hospital on February 20, 1980, because of persistent hypertension. The blood pressure was 160/110 during a physical examination for basketball in September, 1979, and was similarly elevated on repeated examinations during the ensuing five months. She had progressively severe frontal headaches. Past history was pertinent only in that her blood pressure was 90/70 at 8 years of age. There was a strong family history of hypertension. The maternal grandmother had a stroke at age 56 and the paternal grandmother died of a myocardial infarction at 44 years of age. The patient was asymptomatic at the time of admission. The blood pressure was 172/130 in the right arm when in the sitting position. The femoral pulses were normal. The height and weight were at the fiftieth percentile for age. Pertinent initial laboratory studies included: serum sodium concentration 142 mEq/L, potas-
From the University o f Missouri-Kansas City School o f Medicine. *Reprint address." The Children's Mercy Hospital, 24th at Gillham Road. Kansas City, MO 64108.
0022-3476/82/090409+03500.30/0 @ 1982 The C. V. Mosby Co.
slum 3.0 mEq/L, chloride 102 mEq/L, total CO2 25 mM/L, and creatinine 0.75 mg/dl. Several urinalyses were normal. Peripheral plasma renin activity was 11.6 ng/ml/hour. The blood specimen for renin activity was obtained with other initial laboratory studies, with the patient in an upright position. Dietary history, which seemed reliable, indicated a sodium intake of approximately 2 gm/24 hours. Abbreviation used CAT: computerized axial tomography Results of an intravenous pyelogram was considered normal. Plasma renin activity, measured on blood samples obtained during vena caval catheterization, ranged from 6,1 to 6.8 ng/ml/hour in specimens obtained below entry of the renal veins, in the right and left renal veins, and above the renal veins. The patient had received no propranolol for approximately 24 hours prior to these studies. A midstream aortogram and selective right and left renal angiograms were interpreted as normal (Fig. 1, A). The patient was discharged with a presumptive diagnosis of essential hypertension. Initially, treatment consisted of 500 mg chlorothiazide, twice a day, 40 mg propranolol, three times a day, and salt restriction. The addition of hydralazine improved blood pressure control so that it ranged from a high of 145/110 to usual readings of 110 to 120/80 to 90 mm Hg. After about six months the blood pressure was again in the range of 120-170/85-120. The parents brought the patient back for further evaluation in September of 1980 because of an article in the August, 1980, issue of
4 10
Clinical and laboratory observations
The Journal of Pediatrics September 1982
Fig. 1. Right renal arteriogram. A, First study, in which only one right renal artery was identified and injected. B, Second study, in which two right renal arteries were identified. Injection of contrast material into the artery supplying the lower pole demonstrated a filling defect just above the midplane.
Fig. 2. A film through the kidneys taken during the enhanced computerized tomography study. There is a 2.5 cm mass in the posterior portion of the upper P01e of the right kidney.
Good Housekeeping Magazine. The article was entitled, "The Search that Saved Tracie's Life." The parents requested that we do a CAT scan with the hope that we might find a pheochromocytoma. Physical examination was essentially unchanged from that of the previous admission. The blood pressure was 160/120 in the right arm in the sitting position. The peripheral plasma renin activity was 7.5 ng/ml/hour in a morning blood specimen obtained with the patient in the recumbent position and without propranolol therapy for 48 hours. The patient was receiving a diet" with 1,000 mg sodium, and chlorothiazide, 500 mg twice a day. A computerized tomographic study showed a 2.5 cm solid mass in the posterior portion of the superior pole of the right kidney (Fig. 2). The lesion was seen in the study with contrast, but not in that without contrast enhancement. Renal ultrasound did not demonstrate an abnormality in the right kidney. Separate renal
arteries to the upper and lower poles of the right kidney were identified on the midstream aortogram done at this time. Injection of contrast material into the lower pole artery revealed a smooth, round, 3 cm in diameter filling defect just above the midplane (Fig. 1, B). Technical problems prevented selective catheterization of veins draining the right kidney. With the patient off propranolol therapy for more than 48 hours, plasma renin activities were 11.7, 12.5, and 11.7 ng/ml/hour, respectively, in vena caval blood obtained below, at the level of, and above the renal veins. A right nephrectomy was done on October 23, 1980. The operation and the postoperative course were uneventful. All medications were discontinued and the blood pressure remained normal. Five days after surgery the peripheral plasma renin activity was 1.1 ng/ml/hour. The pathologic diagnosis was juxtaglomerular cell tumor. Electron micrographs showed dense granules which were morphologically consistent with renin crystals, and assay of a sample of tumor tissue showed an enormously high-renin concentration. During a nine-month follow-up period the patient has been symptom-free and the blood pressure normal. Two measurements of peripheral plasma renin activity have been 0.5 ng/ml/hour. DISCUSSION H a d the two arteries supplying blood to the right kidney been identified on the first m i d s t r e a m a o r t o g r a m , selective right renal arteriography would almost certainly have shown the t u m o r during the initial study. However, of the 16 reported cases of j u x t a g l o m e r u l a r cell tumor, the first renal a r t e r i o g r a m was n o r m a l in eight, a n d t h e a o r t o g r a m was normal in another two. ~-~~This experience reinforces t h e concept t h a t it ~s necessary to re-evaluate periodically pediatric patients who have persistent, unexplained hypert e n s i o n - i n c l u d i n g those with a strong family history of hypertension.
Volume 101 Number 3
Clinical and laboratory observations
The absence of increased renin activity in blood from the right renal vein compared with that from the left renal vein and the vena cava below the renal veins is difficult to explain. At the time of both vena caval catheterization studies the patient had not been taking propranolol, a drug which suppresses renin secretion. Two possible explanations come to mind. There may have been an accessory vein draining the superior pole of the right kidney, or, at the time of these studies, the tumor was not delivering renin to the venous system. Bonnin et al 1 noted that elevated renin levels may be found in blood from a segmental renal vein when main renal vein or peripheral plasma renin activities are not significantly elevated. We consider it reasonable to suggest C A T scan of the kidneys in a pediatric patient with severe, unexplained hypertension in whom renal arteriography is normal. The tendency for renin-secreting tumors to be small in size and peripheral in location contributes to the difficulty in demonstrating them using other radiologic procedures. 2 We acknowledge the help given by Robert Erlandson, Ph.D., Sloan-Kettering Memorial Center, New York City, and Alan Poisner, M.D., Department of Pharmacology, College of Health Sciences and Hospital, Kansas City, Kansas, for their help in completing the study of the juxtaglomerular cell tumor. REFERENCES
2.
3.
4.
5.
6.
7.
8.
9.
10.
1. Bonnin JM, Cain MD, Jose JS, Mukherjee TM, Perrett LV, Scroop GC, and Seymour AE: Hypertension due to a renin-
411
secreting tumor localized by segmental renal vein sampling, Aust NZ J Med 7:630, 1977. Warshaw, BL, Sudhir AK, Olson DL, Grushkin CM, Heuser ET, and Lieberman E: Hypertension secondary to a reninproducing juxtaglomerular cell tumor, J PEDIATR 94:247, 1979. Robertson PW, Klidjian A, Harding LK, Waiters G, Lee MR, and Robb-Smith AHT: Hypertension due to a reninsecreting renal tumor, Am J Med 43:963, 1967. Corm JW, Cohen EL, McDonald W J, Blough WM, Lucas CP, Mayor GH, Eveland WC, Bookstein J J, and Lapides J: The syndrome of hypertension, hyperreninemia and secondary aldosteronism associated with renal juxtaglomerular cell tumor (primary reninism), J Urol 109:349, 1973. Schambelan M, Howes EL, Stockigt JR, Noakes CA, and Biglier, EG: Role of renin and aldosterone in hypertension due to a renin-secreting tumor, Am J Med 55:86, 1973. Brown J J, Lever AF, Robertson JIS, Fraser R, Morton J J, Tree M, Bell PRF, Davidson JK, and Ruthven IS: Hypertension and secondary hyperaldosteronism associated with a renin-secreting renal juxtaglomerular-cell tumor, Lancet 2:1228, 1973. Gherardi G J, Arya S, and Hickler RB: Juxtaglomerular body tumor: A rare occult but curable Cause of lethal hypertension, Human Pathol 5:236, 1974. Hirose M, Arakawa K, Kikuchi M, Kawasaki T, Omoto T, Kato H, and Nagayama T: Primary reninism with renal hamartomatous alteration, JAMA 230:1288, 1974. ~rjavik US, Aas P, Fauchald P, Hovig T, ~ystese B, Brodwall EK, and Flatmark A: Renin-secreting renal tumour with severe hypertension, Acta Med Scand 197:329, 1975. Connor G, Bennett CM, Lindstrom RR, Brosman SA, Barajas L, and Edelbaum D: Juxtaglomerular cell tumor, Nephron 21:325, 1978.
Late development of chronic renal failure in steroid-responsive nephrotic syndrome Martin A. Nash, M.D.,* Meena A. Bakare, M.D.,** Vivette D'Agati, M.D., and Conrad L. Pirani, M.D., New York, N. Y.
CHILDREN with the idiopathic nephrotic syndrome who respond to prednisone with disappearance of proteinuria have an excellent long-term prognosis for maintenance of
normal glomerular filtration rate and eventual resolution of the syndrome, even in the face of multiple relapses over many years. The response to prednisone is such an accurate Abbreviation used GFR: glomerular filtration rate
From the sections of pediatric nephrology and renal pathology, College o f Physicians and Surgeons o f Columbia University. Supported by grant ROl-AM-25624 from the National Institutes of Health. *Reprint address: Room 701, Babies Hospital, 3975 Broadway, New York. NY 10032. **Supported in part by the New York State Kidney Disease Institute.
0022-3476/82/090411+04500.40/0 9
C. V. MosbyCo.
predictor of underlying minimal lesion disease ~ that in most centers renal biopsies are not routinely performed on these children. On the other hand, the majority of patients with the nephrotic syndrome and renal histological patterns known to be associated with progressive disease do not respond to treatment with prednisone during the initial episode. Although as many as 20 to 30% of patients with