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Congenital Ureteral Dilatation with Renal Hyperparathyroidism
THE JOURNAL OF UROLOGY
Vol. 65, No. 6, June 1951 Printed in U.S.A.
CONGENITAL URETERAL DILATATION WITH RENAL HYPERPARATHYROIDISM ROBERT BRENDZE
AND
R. WILLIAM PROVENZANO
From the Pediatric Service of the Cambridge City Hospital, Cambridge, Mass.
Despite intensive investigation,1- 12 the etiology of congenital ureteral dilatation remains obscure. The lack of information regarding the neuro-anatomy and neurophysiology of the ureter is a major cause for the confusion. Lapides 4 conducted an extensive series of experiments and believes that neither the sympathetic nor parasympathetic nervous systems have any effect on the ureter, and concludes that the ureter is an autonomous organ not affected by the central nervous system. Summerfeldt and Brown 5 reported a case in 1934 of persistent pyuria accompanied by dilated ureter in a 13 month old infant which they believed was due to neurogenic dysfunction of the ureter. A presacral sympathectomy was performed, and post-mortem findings on this patient were reported 15 years later when death occurred. 6 These investigators and others7 have since concluded that sympathectomy is valueless. Should the work of Lapides be confirmed, the reason for the failure of that type of surgery will be readily understandable. Vermooten 9 believes that the great majority of congenitally dilated ureters in children is due to a persistent Chwalla's 1 membrane just at or above the ureterovesical junction. He believes that the continued pressure of urine on this membrane causes sufficient ischemia to the ureter to result in fibrosis and stricture at the ureterovesical junction. The nomenclature pertaining to ureteral dilatation is also unsettled, largely 1 Chwalla, R.: The process of formation of cystic dilations of the vesical end of the ureter and of diverticula at the ureteral ostium. Urol. & Cutan. Rev., 31: 499, 1927. 2 Vermooten, V.: The elongation of the ureter. J. Urol., 23: 427, 1930. 3 Vermooten, V.: A new etiology for certain types of the dilated ureters in children. J. Urol., 41: 455, 1939. 4 Lapides, J.: The pathology of the intact human ureter. J. Urol., 59: 501, 1948. 5 Summerfeldt, P. and Brown, A.: Chronic pyuria-presacral sympathectomy. J. Pediat., 5: 735, 1934. 6 Lehman, E. and Hardyment, A. F.: Chronic pyuria-presacral sympathectomy (final report). J. Pediat., 34: 640, 1949. 7 Wayman, T. B.: Surgery of megalo-ureter. J. Urol., 61: 883, 1949. 8 Campbell, E.W.: Megalo-ureter. J. Urol., 60: 31, 1948. 9 Vermooten, V.: Personal communication, 1949. 10 Lucas, R. C.: On a form of late rickets associated with albuminuria, rickets of adolescents. Lancet, 1: 993, 1883. 11 Von Recklinghausen, F.: Die Fibrose oder deformirende Ostitis, die Osteomalacie, und die osteoplastische Carcinose in ihren gegenseitigen Beziehungen. Separatabdruck aus der Rud. Virchow zum 13 October 1891 gewidmeten Festschrift der Assistenten, Berlin, 1891. 12 Park, E. A. and Eliot, M. M.: Brennemann's Practice of Pediatrics III, chapter 29.
989
990
ROBERT BRENDZE AND R. WILLIAM PROVENZANO
because of the varied theories for etiology. This is particularly true as regards the differentiation between megalo-ureter and hydro-ureter, but the most prevalent general opinion is that megalo-ureter applies to a nonobstructive ureteral dilatation, while hydro-ureter is the result of obstruction. 8 Whatever the specific cause of ureteral dilatation, in the absence of more conclusive information, the question of etiology of this abnormality must remain obscure, and etiological theories may be considered in three groups: 1) obstruction, 2) congenital malformation, and 3) neurogenic dysfunction. It is the purpose of this paper to report a case of hyperparathyroidism and associated skeletal lesions secondary to renal insufficiency arising from bilateral ureteral dilatation. This case is noteworthy in that it demonstrates the insidious onset and slmv progression of the disease, as well as the remarkable compensatory reaction of the body to slowly developing but severe derangements of the blood chemistry. CASE REPORT
C. C. H. ::\'.o. 11777. A 14 year old white boy entered the hospital with the chief complaint of progressively increasing polydipsia, polyuria, and persistent albuminuria of approximately 8 years' duration. From birth the child had had frequent attacks of severe upper respiratory infection, but he had no history of scarlet fever, specific renal infection or symptoms referable to the genito-urinary system. The past and family history ,cvas not otherwise revealing. Physical examination revealed a pale, poorly developed child who weighed 69 pounds, and appeared about 10 years of age. His face was puffy and mild peri-orbital edema was present. No other abnormality of the head, neck, heart or lungs were found. Palpation of the abdomen revealed a mass in the left upper quadrant of the abdomen. The blood pressure was 110/65. There were no other positive physical findings. The urine was acid, specific gravity 1.014, sugar negative, albumin 2 plus; microscopic examination revealed 2-4 leukocytes per high power field, and an occasional erythrocyte. ~ o casts were found. Urine culture revealed no grmvth. At no time during the hospital stay was the patient able to concentrate urine above 1.015, even on rigid fluid restriction. Hemoglobin determinations averaged 59 per cent (14.7 gm. equal 100 per cent), with 3.0 million erythrocytes, 11,400 leukocytes, and a normal differential. The sedimentation rate averaged 55 mm. (Wintrobe). Blood serum protein level was 8.1 gm., with albumin equal to 5.5 gm. and globulin 2.6 gm. The nonprotein nitrogen averaged 191 mg. per cent with a maximum of 243 mg. per cent and a minimum of 122 mg. per cent. The CO 2 combining power was 15 mg. per cent, serum chlorides 617 mg. per cent, serum calcium 11.0 mg. per cent, serum phosphorus 6.25 mg. per cent. Alkaline phosphatase was 10.8 Bodansky units. Blood creatinine was equal to 8.0 mg. per cent. Total blood cholesterol was 461 mg. per cent. Despite these grossly distorted blood chemistry values, the patient was in no apparent distress, complaining only of intermittent weakness. When the
CONGENITAL URETERAL DILATATION
991
acidosis was corrected, and the CO2 combining power raised to 45 volumes per cent, the serum calcium fell to 6.4 mg. per cent, despite the administration of calcium chloride. Tetany was observed on only one occasion during the hospital stay, and was treated by intravenous injection of 10 per cent calcium gluconate. The kidneys were indistinctly outlined on a flat film, but appeared to be enlarged. An excretory urogram revealed no dye in the kidneys, ureters, or
FIG. 1. A, bilateral pyelogram revealing tremendous dilatation and tortuosity of both ureters. Note irregularity of epiphyses. B, cystogram of dilated bladder.
FIG. 2. A, showing grossly irregular, widened epiphyses of femurs and tibiae. B, showing large cystic area in skull.
bladder. Retrograde pyelography was then performed. A cystoscope passed easily into the bladder, which was found to be completely free of abnormality. The mucosa was pink-white, there was no exaggeration of the blood vessels and no evidence of tumor, calculus, or infection. The bladder wall showed no evidence of trabeculation. The urethra was observed, and there was no evidence of any obstructive process in the nature of congenital valves. The ureteral orificetl were in normal position, slit-like, refluxing normally, and free of obstruction or narrowing. No. 4 ureteral catheters were easily passed a distance of 20 cm. on both sides and there was no evidence of ureteral obstruction. The ureteral drip was steady,
992
ROBERT BRENDZE AND R. WILLIAM PROVENZANO
rapid and productive of clear, water-like urine. Phenolsulfonphthalein was injected intravenously; no excretion of the dye occurred 1 hour later. Bilateral pyelography revealed enormous dilatation, tortuosity, and kinking of both ureters (fig. 1, A). No narrowing of either ureter was seen. Both ureters filled well, but no dye entered the kidney pelves or calyces. The bladder appeared to be greatly dilated on x-ray examination (fig. 1, B). Cultures of urine from both kidneys and ureters, and from the bladder were negative. X-ray films of the long bones revealed gross irregularity of the epiphyses of the femurs, the humerus, and in the lower end of the tibia, with widening of the epiphyseal lines. There was a diffuse osteoporosis of all the shafts (fig. 2, A). Lateral films of the skull revealed many irregular, rounded, cystic areas, none larger than 1 cm. in size (fig. 2, B). The pituitary fossa was normal in size, outline, and position. This patient is being observed at regular intervals in the outpatient clinic. The patient's symptoms have persisted but are not greatly increased in severity. The derangement of the blood chemistry findings has, however, become more marked. During the most recent outpatient visit, these values were as follows: the blood serum calcium was 12.2 mg. per cent, the alkaline phosphatase 56.3 Bodansky units, with a nonprotein nitrogen of 134 mg. per cent and a CO 2 combining power of 30. DISCUSSION
Despite the fact that many aspects of this syndrome, in particular those relating to the metabolism of calcium, are not clear, most investigators agree that the primary lesion is renal, and that the skeletal changes are a consequence of the secondary involvement of the parathyroid glands. The renal lesions may vary widely; most commonly the kidneys present a combination of defective development and infection. Among reported renal lesions are congenital urethral valves at the vesical outlet, cystic kidneys, solitary atrophic kidneys, chronic nephritis, and obstructive uropathy. The ultimate consequence of any of these lesions may be renal insufficiency. The presence of extreme renal insufficiency of long duration is all that is necessary for development of this syndrome. One of the early consequences of renal insufficiency is increased retention of nitrogenous products, which is almost always accompanied by parallel retention of phosphorus due to inability of the kidney to excrete endogenous waste phosphates. Mitchell13 believes that the retained phosphorus is readily capable of precipitating calcium in the intestinal tract as the insoluble calcium phosphate, which is excreted by the bowel. The result is failure of calcium absorption, and calcium starvation occurs. The exact sequence of events by which renal insufficiency results in increased parathyroid activity is not clear, but Albright and his co-workers 14 have suggested that low blood calcium provides the stimulus for hypertrophy of the parathyroid 13 Mitchell, A.G.: Nephrosclerosis in childhood. Am. J. Dis. Child., 40: 101,345, 1930. "Albright, F., Drake, T. G., and Sulkowitch, H. W.: Renal osteitis fibrosa cystica. Bull. Johns Hopkins Hosp., 60: 377, 1937.
CONGENITAL URETERAL DILATATION
993
glands, and Pappenheimer15 states that the parathyroid glands react to the loss of renal tissue by an increase in volume ,vhich is roughly proportional to the severity of the renal disease. ·whatever the immediate stimulus to parathyroid hypertrophy, the excessive secretion of parathyroid hormone results finally in increased osteoclastic activity and the skeletal lesions described as osteitis fibrosa cystica. There may be wide variation in the character of the skeletal lesions, 12 and osteoporosis, delay and irregularity in ossification, epiphyseal irregularity and separation, and bony translucency have all been described. Albright et al.1 6 state that skeletal involvement is an index of the duration and not the severity of the disease, and believes that the age of onset of the disease is the final determinant of the type of bony lesion which occurs; thus, the younger the age of onset, the greater will be the damage to the epiphyses. The case reported here is marked by regular elevation of serum phosphorus levels in the presence of depressed serum calcium levels, severe acidosis, anemia, and retarded grmvth, and illustrates many of the principles already discussed. The differential diagnosis in cases of renal hyperparathyroidism lies between chronic nephritis, hyperparathyroidism (adenoma), cystic renal disease, obstructive uropathy, and diabetes insipidus. In primary hyperparathyroidism, the serum calcium may be normal or elevated, while in secondary hyperparathyroidism, such as may occur from renal disease, the serum calcium may be normal or depressed. Parathyroid hyperactivity is not able to compete successfully with renal insufficiency. 15 The similarity to diabetes insipidus does not extend much beyond the symptoms of polydipsia and polyuria. The presence of tetany is not frequent in this syndrome, largely because renal insufficiency results in chronic acidosis, which increase the ionization of calcium and, therefore, the availability of calcium.17 This observation was confirmed in the case reported here. SUMMARY
A case of renal hyperparathyroidism with osteitis fibrosa cystica secondary to congenital bilateral ureteral dilatation is presented. The pathogenesis and certain aspects of the pathologic physiology involved in this syndrome are discussed. 520 Commonwealth
Boston 15, .J.l/[ass.
Pappenheimer, A. M.: Effect of experimental reduction of kidney substance upon parathyroid glands and skeletal tissue. Jour. Exp. Med., 64: 965, 1936. '6 Albright, F., Baird, P. C., Cope, 0., and Bloomberg, E.: Studies on the physiology of the parathyroid glands. IV Renal Complications of Hyperparathyroidism. Am. J. Med. Sci., 187: 49, 1934. 1, Pincus, J.B., Peterson, I-L .A., and Kramer, B.: A study by means of ultrafiltration of the condition of several inorganic constituents of blood serum in disease. J. BioL Chem., 68: 601, 1926. 15
Vol. 65, No. 6, June 1951 Printed in U.S.A.
CONGENITAL URETERAL DILATATION WITH RENAL HYPERPARATHYROIDISM ROBERT BRENDZE
AND
R. WILLIAM PROVENZANO
From the Pediatric Service of the Cambridge City Hospital, Cambridge, Mass.
Despite intensive investigation,1- 12 the etiology of congenital ureteral dilatation remains obscure. The lack of information regarding the neuro-anatomy and neurophysiology of the ureter is a major cause for the confusion. Lapides 4 conducted an extensive series of experiments and believes that neither the sympathetic nor parasympathetic nervous systems have any effect on the ureter, and concludes that the ureter is an autonomous organ not affected by the central nervous system. Summerfeldt and Brown 5 reported a case in 1934 of persistent pyuria accompanied by dilated ureter in a 13 month old infant which they believed was due to neurogenic dysfunction of the ureter. A presacral sympathectomy was performed, and post-mortem findings on this patient were reported 15 years later when death occurred. 6 These investigators and others7 have since concluded that sympathectomy is valueless. Should the work of Lapides be confirmed, the reason for the failure of that type of surgery will be readily understandable. Vermooten 9 believes that the great majority of congenitally dilated ureters in children is due to a persistent Chwalla's 1 membrane just at or above the ureterovesical junction. He believes that the continued pressure of urine on this membrane causes sufficient ischemia to the ureter to result in fibrosis and stricture at the ureterovesical junction. The nomenclature pertaining to ureteral dilatation is also unsettled, largely 1 Chwalla, R.: The process of formation of cystic dilations of the vesical end of the ureter and of diverticula at the ureteral ostium. Urol. & Cutan. Rev., 31: 499, 1927. 2 Vermooten, V.: The elongation of the ureter. J. Urol., 23: 427, 1930. 3 Vermooten, V.: A new etiology for certain types of the dilated ureters in children. J. Urol., 41: 455, 1939. 4 Lapides, J.: The pathology of the intact human ureter. J. Urol., 59: 501, 1948. 5 Summerfeldt, P. and Brown, A.: Chronic pyuria-presacral sympathectomy. J. Pediat., 5: 735, 1934. 6 Lehman, E. and Hardyment, A. F.: Chronic pyuria-presacral sympathectomy (final report). J. Pediat., 34: 640, 1949. 7 Wayman, T. B.: Surgery of megalo-ureter. J. Urol., 61: 883, 1949. 8 Campbell, E.W.: Megalo-ureter. J. Urol., 60: 31, 1948. 9 Vermooten, V.: Personal communication, 1949. 10 Lucas, R. C.: On a form of late rickets associated with albuminuria, rickets of adolescents. Lancet, 1: 993, 1883. 11 Von Recklinghausen, F.: Die Fibrose oder deformirende Ostitis, die Osteomalacie, und die osteoplastische Carcinose in ihren gegenseitigen Beziehungen. Separatabdruck aus der Rud. Virchow zum 13 October 1891 gewidmeten Festschrift der Assistenten, Berlin, 1891. 12 Park, E. A. and Eliot, M. M.: Brennemann's Practice of Pediatrics III, chapter 29.
989
990
ROBERT BRENDZE AND R. WILLIAM PROVENZANO
because of the varied theories for etiology. This is particularly true as regards the differentiation between megalo-ureter and hydro-ureter, but the most prevalent general opinion is that megalo-ureter applies to a nonobstructive ureteral dilatation, while hydro-ureter is the result of obstruction. 8 Whatever the specific cause of ureteral dilatation, in the absence of more conclusive information, the question of etiology of this abnormality must remain obscure, and etiological theories may be considered in three groups: 1) obstruction, 2) congenital malformation, and 3) neurogenic dysfunction. It is the purpose of this paper to report a case of hyperparathyroidism and associated skeletal lesions secondary to renal insufficiency arising from bilateral ureteral dilatation. This case is noteworthy in that it demonstrates the insidious onset and slmv progression of the disease, as well as the remarkable compensatory reaction of the body to slowly developing but severe derangements of the blood chemistry. CASE REPORT
C. C. H. ::\'.o. 11777. A 14 year old white boy entered the hospital with the chief complaint of progressively increasing polydipsia, polyuria, and persistent albuminuria of approximately 8 years' duration. From birth the child had had frequent attacks of severe upper respiratory infection, but he had no history of scarlet fever, specific renal infection or symptoms referable to the genito-urinary system. The past and family history ,cvas not otherwise revealing. Physical examination revealed a pale, poorly developed child who weighed 69 pounds, and appeared about 10 years of age. His face was puffy and mild peri-orbital edema was present. No other abnormality of the head, neck, heart or lungs were found. Palpation of the abdomen revealed a mass in the left upper quadrant of the abdomen. The blood pressure was 110/65. There were no other positive physical findings. The urine was acid, specific gravity 1.014, sugar negative, albumin 2 plus; microscopic examination revealed 2-4 leukocytes per high power field, and an occasional erythrocyte. ~ o casts were found. Urine culture revealed no grmvth. At no time during the hospital stay was the patient able to concentrate urine above 1.015, even on rigid fluid restriction. Hemoglobin determinations averaged 59 per cent (14.7 gm. equal 100 per cent), with 3.0 million erythrocytes, 11,400 leukocytes, and a normal differential. The sedimentation rate averaged 55 mm. (Wintrobe). Blood serum protein level was 8.1 gm., with albumin equal to 5.5 gm. and globulin 2.6 gm. The nonprotein nitrogen averaged 191 mg. per cent with a maximum of 243 mg. per cent and a minimum of 122 mg. per cent. The CO 2 combining power was 15 mg. per cent, serum chlorides 617 mg. per cent, serum calcium 11.0 mg. per cent, serum phosphorus 6.25 mg. per cent. Alkaline phosphatase was 10.8 Bodansky units. Blood creatinine was equal to 8.0 mg. per cent. Total blood cholesterol was 461 mg. per cent. Despite these grossly distorted blood chemistry values, the patient was in no apparent distress, complaining only of intermittent weakness. When the
CONGENITAL URETERAL DILATATION
991
acidosis was corrected, and the CO2 combining power raised to 45 volumes per cent, the serum calcium fell to 6.4 mg. per cent, despite the administration of calcium chloride. Tetany was observed on only one occasion during the hospital stay, and was treated by intravenous injection of 10 per cent calcium gluconate. The kidneys were indistinctly outlined on a flat film, but appeared to be enlarged. An excretory urogram revealed no dye in the kidneys, ureters, or
FIG. 1. A, bilateral pyelogram revealing tremendous dilatation and tortuosity of both ureters. Note irregularity of epiphyses. B, cystogram of dilated bladder.
FIG. 2. A, showing grossly irregular, widened epiphyses of femurs and tibiae. B, showing large cystic area in skull.
bladder. Retrograde pyelography was then performed. A cystoscope passed easily into the bladder, which was found to be completely free of abnormality. The mucosa was pink-white, there was no exaggeration of the blood vessels and no evidence of tumor, calculus, or infection. The bladder wall showed no evidence of trabeculation. The urethra was observed, and there was no evidence of any obstructive process in the nature of congenital valves. The ureteral orificetl were in normal position, slit-like, refluxing normally, and free of obstruction or narrowing. No. 4 ureteral catheters were easily passed a distance of 20 cm. on both sides and there was no evidence of ureteral obstruction. The ureteral drip was steady,
992
ROBERT BRENDZE AND R. WILLIAM PROVENZANO
rapid and productive of clear, water-like urine. Phenolsulfonphthalein was injected intravenously; no excretion of the dye occurred 1 hour later. Bilateral pyelography revealed enormous dilatation, tortuosity, and kinking of both ureters (fig. 1, A). No narrowing of either ureter was seen. Both ureters filled well, but no dye entered the kidney pelves or calyces. The bladder appeared to be greatly dilated on x-ray examination (fig. 1, B). Cultures of urine from both kidneys and ureters, and from the bladder were negative. X-ray films of the long bones revealed gross irregularity of the epiphyses of the femurs, the humerus, and in the lower end of the tibia, with widening of the epiphyseal lines. There was a diffuse osteoporosis of all the shafts (fig. 2, A). Lateral films of the skull revealed many irregular, rounded, cystic areas, none larger than 1 cm. in size (fig. 2, B). The pituitary fossa was normal in size, outline, and position. This patient is being observed at regular intervals in the outpatient clinic. The patient's symptoms have persisted but are not greatly increased in severity. The derangement of the blood chemistry findings has, however, become more marked. During the most recent outpatient visit, these values were as follows: the blood serum calcium was 12.2 mg. per cent, the alkaline phosphatase 56.3 Bodansky units, with a nonprotein nitrogen of 134 mg. per cent and a CO 2 combining power of 30. DISCUSSION
Despite the fact that many aspects of this syndrome, in particular those relating to the metabolism of calcium, are not clear, most investigators agree that the primary lesion is renal, and that the skeletal changes are a consequence of the secondary involvement of the parathyroid glands. The renal lesions may vary widely; most commonly the kidneys present a combination of defective development and infection. Among reported renal lesions are congenital urethral valves at the vesical outlet, cystic kidneys, solitary atrophic kidneys, chronic nephritis, and obstructive uropathy. The ultimate consequence of any of these lesions may be renal insufficiency. The presence of extreme renal insufficiency of long duration is all that is necessary for development of this syndrome. One of the early consequences of renal insufficiency is increased retention of nitrogenous products, which is almost always accompanied by parallel retention of phosphorus due to inability of the kidney to excrete endogenous waste phosphates. Mitchell13 believes that the retained phosphorus is readily capable of precipitating calcium in the intestinal tract as the insoluble calcium phosphate, which is excreted by the bowel. The result is failure of calcium absorption, and calcium starvation occurs. The exact sequence of events by which renal insufficiency results in increased parathyroid activity is not clear, but Albright and his co-workers 14 have suggested that low blood calcium provides the stimulus for hypertrophy of the parathyroid 13 Mitchell, A.G.: Nephrosclerosis in childhood. Am. J. Dis. Child., 40: 101,345, 1930. "Albright, F., Drake, T. G., and Sulkowitch, H. W.: Renal osteitis fibrosa cystica. Bull. Johns Hopkins Hosp., 60: 377, 1937.
CONGENITAL URETERAL DILATATION
993
glands, and Pappenheimer15 states that the parathyroid glands react to the loss of renal tissue by an increase in volume ,vhich is roughly proportional to the severity of the renal disease. ·whatever the immediate stimulus to parathyroid hypertrophy, the excessive secretion of parathyroid hormone results finally in increased osteoclastic activity and the skeletal lesions described as osteitis fibrosa cystica. There may be wide variation in the character of the skeletal lesions, 12 and osteoporosis, delay and irregularity in ossification, epiphyseal irregularity and separation, and bony translucency have all been described. Albright et al.1 6 state that skeletal involvement is an index of the duration and not the severity of the disease, and believes that the age of onset of the disease is the final determinant of the type of bony lesion which occurs; thus, the younger the age of onset, the greater will be the damage to the epiphyses. The case reported here is marked by regular elevation of serum phosphorus levels in the presence of depressed serum calcium levels, severe acidosis, anemia, and retarded grmvth, and illustrates many of the principles already discussed. The differential diagnosis in cases of renal hyperparathyroidism lies between chronic nephritis, hyperparathyroidism (adenoma), cystic renal disease, obstructive uropathy, and diabetes insipidus. In primary hyperparathyroidism, the serum calcium may be normal or elevated, while in secondary hyperparathyroidism, such as may occur from renal disease, the serum calcium may be normal or depressed. Parathyroid hyperactivity is not able to compete successfully with renal insufficiency. 15 The similarity to diabetes insipidus does not extend much beyond the symptoms of polydipsia and polyuria. The presence of tetany is not frequent in this syndrome, largely because renal insufficiency results in chronic acidosis, which increase the ionization of calcium and, therefore, the availability of calcium.17 This observation was confirmed in the case reported here. SUMMARY
A case of renal hyperparathyroidism with osteitis fibrosa cystica secondary to congenital bilateral ureteral dilatation is presented. The pathogenesis and certain aspects of the pathologic physiology involved in this syndrome are discussed. 520 Commonwealth
Boston 15, .J.l/[ass.
Pappenheimer, A. M.: Effect of experimental reduction of kidney substance upon parathyroid glands and skeletal tissue. Jour. Exp. Med., 64: 965, 1936. '6 Albright, F., Baird, P. C., Cope, 0., and Bloomberg, E.: Studies on the physiology of the parathyroid glands. IV Renal Complications of Hyperparathyroidism. Am. J. Med. Sci., 187: 49, 1934. 1, Pincus, J.B., Peterson, I-L .A., and Kramer, B.: A study by means of ultrafiltration of the condition of several inorganic constituents of blood serum in disease. J. BioL Chem., 68: 601, 1926. 15