Primary Hyperparathyroidism
in Children
Henry Mannix, Jr, MD, Hartford, Connecticut
Since the introduction of the multichannel analyzer, the incidence of hypercalcemia has increased markedly. Not all patients with hypercalcemia have primary hyperparathyroidism, but this condition is being diagnosed with increasing frequency throughout the country. The Mayo Clinic has treated more than 800 patients with primary hyperparathyroidism [1] and reports of more than 100 cases are relatively easy to find [2--51. However, reports on children under sixteen years of age with primary hyperparathyroidism are still uncommon. Until 1970, forty-three cases had been reported in the literature. Since then, additional patients have been treated and reported on. In the last twelve years, I have observed and treated three such patients. Because some manifestations of this disease may be different in children, a review is worthwhile. Review of the Literature Significant hypercalcemia due to overactivity of the parathyroid can occur at any age. The youngest patient operated on was twenty-days old and was classified as having hereditary parathyroid hyperplasia or neonatal familial hyperparathyroidism [6]. In addition, in a later report an infant at the age of six days began to manifest symptoms of hypercalcemia and was found at autopsy to have parathyroid hyperplasia [7]. Until 1972, ten such infants, all but one of them under four months of age [B], had been treated and reported on. In these patients the serum calcium level may be extremely high, even higher than 25 mg/lOO ml, and prompt surgery is mandatory. In the patients with nonFrom the Departments of Surgery, St. Francis Hospital, Hartford, Connecticut, and New York Hospital, New York, New York. Reprint requests should be addressed to Henry Mannix. Jr. MD, Director of Surgery, St. Francis Hospital, 114 Woodland Street, Hartford, Connecticut 06105.
528
familial disease, in whom the pathologic factor is most likely an adenoma, the largest incidence of the disease was reported in the Russian literature in 1973. In this report, Stukkei and Ignatiev [9] described eight patients between seven and sixteen years of age in a total series of one hundred five patients, all eight of whom were found to have benign adenoma. A third cause of hypercalcemia in children was reported by Foley et al [IO] from the Johns Hopkins Hospital. They characterized the conditions of familial benign hypercalcemia and identified eleven cases among four generations of one family. These patients had elevated serum calcium but normal parathormone levels. Surgery was performed in one member of the group and four normal parathyrpid glands were identified. Other diagnoses should be considered in children with evidence of hypercalcemia. These include carcinoma of different organs with or without bone involvement, vitamin D intoxication, cretinism, hypophosphatasia; there is also a significant number of children in whom the condition is apparently idiopathic. The first review of primary parathyroid disease in children was published in 1960 by Nolan, Hayles, and Woolner [II] who found twenty-three cases. Bjernulf et al [12] reviewed the literature in 1970 and found an additional twenty cases, bringing the total to forty-three cases up to that time. This group of forty-three patients included those with familial conditions as well as isolated cases, and the pathologic factors included hyperplasia and adenoma. In a review of the literature since 1971, I have been able to find fourteen additional cases plus the three included in this report, which brings the total to sixty cases. Table I lists the cases reported up to 1973. Presenting Symptoms. In a large collected review of the subject, it is apparent that symptoms
The American Journal of Surgery
related to renal and bone disorders are the most common. Less prominent, but still well documented, are symptoms of peptic ulcer disease, pancreatitis, hypercalcemic crisis, and neonatal tetany. The symptoms in children seem to be somewhat different. The report by Bjernulf et al [12] emphasized general fatigue, anorexia, dizziness, weight loss, and arrhythmia. A case report by Vasquez [ 131 mentioned hypertension and nephrocalcinosis as symptoms. It is clear that children may have the classic symptoms of renal colic, but they may also have more unusual manifestations. In infants with congenital hyperplasia, the symptoms were associated with the extremely high calcium levels and included failure to thrive, loss of appetite, vomiting, and diffuse cyanosis. In some of these patients, the diagnosis was not made until autopsy. Case Reports Case I. The patient (#910985 NYH), an eleven and a half year old female, was admitted to the New York Hospital in May 1962 because of vomiting and weight loss. The patient was a product of a full term pregnancy, and her growth and development were apparently normal until about two years prior to admission. At that time there was a decrease in appetite but an increase in thirst. Headaches became a problem and several months later she began using eye glasses without significant relief. Over the next twelve t,o sixteen months, she underwent a thorough medical evaluation, with laboratory and x-ray studies including gastrointestinal x-ray films. Results of one serum calcium determination were reported as normal. Until May 1962 her problem was considered psychological. At that time a dentist in South America noted a bone cyst in the jaw and she was sent to the New York Hospital for surgery. At this time the serum calcium level was reported to be 18.6 mg/lOO ml. At the time of admission she was pale and appeared to be chronically ill. She was quite small, and menstruation had not begun. There were no palpable neck masses. Additional preoperative serum calcium levels were 18.8 mg/lOO ml and 18.4 mg/lOO ml. The serum alkaline phosphatase level was 9.6 units (King-Armstrong). X-ray films revealed demineralization and slightly retarded bone age. There was no specific sign of hyperparathyroidism on x-ray study. The jaw tumor was removed and found to be a typical brown tumor. Neck exploration was performed by Doctor Frank Glenn on June 18, 1962 and a large adenoma (Figure 1) was removed. The postoperative serum calcium level decreased to 9.3 mg/lOO ml and the serum alkaline phosphatase level increased to 18.6 units. The postoperative course was complicated by the onset of severe head-
aches, which were eventually type.
There
was a family
Volume
129, May 1975
diagnosed
history
as migraine
of migraine.
in
She re-
I
TABLE --.
--
Reported Cases of Primary km in Children
Hyperparathyoid-
Pathology
Author Bjernulf et al [ J2], 1970 Stukkei and lgnatiev [O], 1972 Goldbloom, Gillis, and Prasad Bergman
[S], 1972 and Hagberg
[ 141, 1972 Vasquez [ 7 31, 1973 Lund [ 151, 1973 Bradford, Wilson, and Gaede [?I, 1973 Present report
Number of Cases
__ M
43 8
25 6
18 2
35 80
2
0
2
02
10
F
HYAden- perUnoma plasia known
110
110 110 10 3
Sex
0
7
1 0 0 0
0 0
0
10 10 110
3
30
0
quired oral calcium postoperatively for about ten days because of low grade symptoms of tetany. Verbal followup seven years later indicated that the patient had developed normally in every way. There have been no further symptoms of hyperparathyroidism. Case II. The patient (#965519 NYH), a fourteen year old female, had two episodes of renal calculi with severe colic. The first episode occurred in the summer of 1963 and details of laboratory studies are not available. She passed the stones successfully. In October 1963, she had a second episode of colic and underwent nephrolithotomy to remove the stone on October 7, 1963. Serum calcium values at that time were 11.9 mg/lOO ml, 12.9 mg/lOO ml, and 13.3 mg/lOO ml, with a low normal phosphorus level. The alkaline phosphatase level was normal. She was subsequently studied in the Metabolic Unit at New York Hospital. She demonstrated an elevated urinary excretion of calcium on a restricted diet and a marked increase in serum calcium in response to the calcium load. The serum calcium level continued to be elevated. X-ray examination of the bones revealed no abnormalities. The patient was a tall, well developed female with all the secondary sexual characteristics. There was no evidence of physical retardation. Her menstrual
Figure 7. An adenoma measuring 2.5 cm, was removed during neck exploration in case I. It was located adjacent to the lower pole on the right thyroid.
529
Mannix
Figure 2. The ribs in this frontal chest x-ray film of the patient in case III are significantly demineralized.
periods were normal. Neck exploration revealed a moderate sized adenoma in the right upper pole area. Interestingly, an aberrant vessel from the common carotid led to the discovery of the tumor. The postoperative course was uncomplicated, with serum calcium values returning to low normal. Seven years later, the serum calcium level was normal and twenty-four hour urinary excretion of calcium on an unrestricted diet was low normal. She had no further renal calculi.
Case III. The patient (#78103006 SFH), a fifteen year old female, was first seen by her general practitioner in the summer of 1972. She complained of nausea
Figure 3. Dorsal vertebrae are clearly less mineralized than would be expected In a fifteen year old female.
530
with vomiting, especially after breakfast. Duration of symptoms was two months and she had begun to lose weight. Anorexia nervosa was diagnosed initially and mild tranquilizers were administered without benefit. During a period of four and a half months she lost fifteen pounds. A second physician examined her and noted lethargy as well as evidence of weight loss. Serum calcium was elevated to 14.3 mg/lOO ml. oh repeated testing the serum calcium level was 14.9 mg/lOO ml and she was promptly admitted to the hospital. At the time of admission, the serum calcium level was 16.4 mg/lOO ml. She was treated with large doses of intravenous saline and the serum calcium level decreased to about 13 mg/lOO ml. The diminished phosphorus reabsorption suggested hyperparathyroidism and additional serum calcium levels were consistently elevated with low phosphorus levels. X-ray films demonstrated bony demineralization (Figures 2 and 3) and a cervical esophagogram showed deviation to the left in the right lower neck. Neck exploration revealed a large adenoma, measuring 2.5 cm, adjacent to the right lower pole of the thyroid, which, in retrospect, had been palpable. The postoperative course was uneventful except for mild symptoms of tetany, which were controlled with oral calcium. Serum calcium decreased to 8.5 mg/lOO ml during the immediate postoperative period. She received oral calcium for six weeks postoperatively, and then it was gradually withdrawn. Follow-up study at one year showed that the patient had gained twenty pounds in weight, had excellent appetite, and at present is slightly overweight for her habitus. Comments
In this review it is apparent that primary hyperparathyroidism may present a somewhat different picture in children from that in adults, The incidence of anorexia, weight loss, and personality changes are all more striking in these patients. The more common manifestations in adults, such as renal and bone disease, are present but to a lesser extent. From the cases presented, it is obvious that the diagnosis of primary hyperparathyroidism may not even be considered in many of these children. This is confirmed from a review of the literature. Death can occur in children as a result of hypercalcemia due to parathyroid adenoma. It may be advised that serum calcium determinations be made in children who present with chronic loss of appetite, anorexia, weight loss, or personality changes before a diagnosis of psychosomatic problems is made. Infants with hereditary parathyroid hyperplasia present a most challenging problem. Frequently they are critically ill and the diagnosis can be obscure. Since the disease is hereditary, it may be suspected in certain instances. Surgical manage-
TheAmerican Journalof Surgery
Hyperparathyroidism
ment, once the diagnosis is made, is very difficult because of the size of the patient and the many aberrant locations for parathyroid tissue. These patients must be treated preoperatively to diminish the serum calcium level before anesthesia is induced. Saline infusions may be useful as well as more specific substances, such as edathamil or various chelating agents. Porcine calcitonin is also available. From a review of the literature it is apparent that there are more males than females with nonhereditary disease, whereas among adult patients with this condition females are encountered much more frequently. The symptoms in these patients are related to the levels of serum calcium. Of the three patients reported on herein, two had serum calcium levels higher than 15 mg/lOO ml and in both patients the diagnosis was not considered early in their course. The third patient presented with the typical adult features, that is, recurrent renal calculi and only moderate elevation of the serum calcium level. In addition, the adenoma in this patient was relatively small, as might be exin the patients petted. Incidence of hyperplasia with nonfamilial disease is low; in fact, it is possibly lower than in adults, although the sample is rather small. The tumor in two of the three cases reported was very large and, in fact, was palpable in one patient. The surgical challenge was therefore not great. Preoperative management of the third patient, employing large doses of saline intravenously, reduced the serum calcium level to less than 14 mg/lOO ml and made operation safe. If the saline therapy had not succeeded, calcium phosphate and even possibly calcitonin would have been administered. In children, many of the tumors are large and easily identified. Although this report emphasizes primary hyperparathyroidism as a cause of significant hypercalcemia in children, the other diagnoses mentioned earlier must be considered in the work-up of these patients. As a general rule, the conditions can be excluded without great difficulty, but it is worth emphasizing that they be considered to avoid unnecessary surgery. Utilization of serum parathormone levels in relation to serum calcium levels simplifies the accurate diagnosis of the condition. At present, it is possible to obtain accurate determinations of the parathormone level on a commercial basis within a week to ten days. In some pa-
Volume 129, May 1075
in Children
tients with borderline serum calcium levels a diagnosis may be established by elevated serum parathormone levels. It is probably not necessary to pursue the more complicated angiographic studies in children before the initial exploration. Careful neck exploration will generally result in discovery of the adenoma and its removal. Summary
Three cases of primary hyperparathyroidism in children are presented and the literature reviewed. Symptoms of nausea, weight loss, and personality changes are more common in children than in adults with this disease. Children may have the diagnosis delayed because of failure to consider hyperparathyroidism. Surgery has been demonstrated to be most effective in treating this condition. References 1. Hoehn JG. Beahrs OH, Woolner LB: Unusual surgical lesions of the parathyroid gland. Am J Surg 118: 770, 1969. 2. Cope 0: Story of hyperparathyroidism at the Massachusetts General Hospital. N Engl J Med 274: 1174, 1966. 3. Rienhoff WF Jr, Rienhoff WF III, Brawley RK, Shelley WM: The surgical treatment of hyperparathyroidism. Ann Surg 166: 1061, 1968. 4. Farr HW, Fahey TJ, Nash AG, Farr CM: Primary hyperparathyroidism and cancer. Am J Surg 126: 539, 1973. 5. Friedman EW, Schwartz AE. Spiro RH: Changing patterns in hyperparathyroidism. Surg Gynecol Dbstet 137: 941, 1973. 6. Hillman EA, Striver CR, Pedvis S, Shragovitch I: Neonatal familial primary hyperparathyroidism. N Engl J Med 270: 483, 1964. 7. Bradford WD. Wilson JW, Gaede JT: Primary neonatal hyperparathyroidism-an unusual cause of failure to thrive. Am J C/in Patho/ 59: 267, 1973. 8. Goldbloom RB, Gillis DA, Prasad M: Hereditary parathyroid hyperplasia: a surgical emergency of early infancy. fediat&s 49: 514, 1972. 9. Stukkei AL, lgnatiev AS: Hyperparathyroidism in childhood and youth. /%&atria 51: 29, 1972. 10. Foley TP Jr, Harrison HC, Arnaud CD, Harrison HE: Familial benign hypercalcemia. J Pediatr81: 1060. 1972. 11. Nolan RB, Hayles AB, Woolner LB: Adenomas of the parathvroid aland in children. Am J Dis Child 99: 622. 1960. 12. Bier&If A,‘i-lall K, Sgogren I, Werner I: Primary hyperthyroidism in children. Acfa Paediatr Stand 59: 249, 1970. 13. Vasquez AM: Nephrocalcinosis and hypertension in juvenile primary hyperparathyroidism. Am J Dis Child 125: 104, 1973. 14. Bergman L, Hagberg S: Primary hyperparathyroidism in a child investigated by determination on ultrafiltrable calciurn. Am J Dis Child 123: 174. 1972. 15. Lund HT: Primary hyperparathyroidism in childhood. Acta PaediatrScand62: 317. 1973.
531
in Children
Henry Mannix, Jr, MD, Hartford, Connecticut
Since the introduction of the multichannel analyzer, the incidence of hypercalcemia has increased markedly. Not all patients with hypercalcemia have primary hyperparathyroidism, but this condition is being diagnosed with increasing frequency throughout the country. The Mayo Clinic has treated more than 800 patients with primary hyperparathyroidism [1] and reports of more than 100 cases are relatively easy to find [2--51. However, reports on children under sixteen years of age with primary hyperparathyroidism are still uncommon. Until 1970, forty-three cases had been reported in the literature. Since then, additional patients have been treated and reported on. In the last twelve years, I have observed and treated three such patients. Because some manifestations of this disease may be different in children, a review is worthwhile. Review of the Literature Significant hypercalcemia due to overactivity of the parathyroid can occur at any age. The youngest patient operated on was twenty-days old and was classified as having hereditary parathyroid hyperplasia or neonatal familial hyperparathyroidism [6]. In addition, in a later report an infant at the age of six days began to manifest symptoms of hypercalcemia and was found at autopsy to have parathyroid hyperplasia [7]. Until 1972, ten such infants, all but one of them under four months of age [B], had been treated and reported on. In these patients the serum calcium level may be extremely high, even higher than 25 mg/lOO ml, and prompt surgery is mandatory. In the patients with nonFrom the Departments of Surgery, St. Francis Hospital, Hartford, Connecticut, and New York Hospital, New York, New York. Reprint requests should be addressed to Henry Mannix. Jr. MD, Director of Surgery, St. Francis Hospital, 114 Woodland Street, Hartford, Connecticut 06105.
528
familial disease, in whom the pathologic factor is most likely an adenoma, the largest incidence of the disease was reported in the Russian literature in 1973. In this report, Stukkei and Ignatiev [9] described eight patients between seven and sixteen years of age in a total series of one hundred five patients, all eight of whom were found to have benign adenoma. A third cause of hypercalcemia in children was reported by Foley et al [IO] from the Johns Hopkins Hospital. They characterized the conditions of familial benign hypercalcemia and identified eleven cases among four generations of one family. These patients had elevated serum calcium but normal parathormone levels. Surgery was performed in one member of the group and four normal parathyrpid glands were identified. Other diagnoses should be considered in children with evidence of hypercalcemia. These include carcinoma of different organs with or without bone involvement, vitamin D intoxication, cretinism, hypophosphatasia; there is also a significant number of children in whom the condition is apparently idiopathic. The first review of primary parathyroid disease in children was published in 1960 by Nolan, Hayles, and Woolner [II] who found twenty-three cases. Bjernulf et al [12] reviewed the literature in 1970 and found an additional twenty cases, bringing the total to forty-three cases up to that time. This group of forty-three patients included those with familial conditions as well as isolated cases, and the pathologic factors included hyperplasia and adenoma. In a review of the literature since 1971, I have been able to find fourteen additional cases plus the three included in this report, which brings the total to sixty cases. Table I lists the cases reported up to 1973. Presenting Symptoms. In a large collected review of the subject, it is apparent that symptoms
The American Journal of Surgery
related to renal and bone disorders are the most common. Less prominent, but still well documented, are symptoms of peptic ulcer disease, pancreatitis, hypercalcemic crisis, and neonatal tetany. The symptoms in children seem to be somewhat different. The report by Bjernulf et al [12] emphasized general fatigue, anorexia, dizziness, weight loss, and arrhythmia. A case report by Vasquez [ 131 mentioned hypertension and nephrocalcinosis as symptoms. It is clear that children may have the classic symptoms of renal colic, but they may also have more unusual manifestations. In infants with congenital hyperplasia, the symptoms were associated with the extremely high calcium levels and included failure to thrive, loss of appetite, vomiting, and diffuse cyanosis. In some of these patients, the diagnosis was not made until autopsy. Case Reports Case I. The patient (#910985 NYH), an eleven and a half year old female, was admitted to the New York Hospital in May 1962 because of vomiting and weight loss. The patient was a product of a full term pregnancy, and her growth and development were apparently normal until about two years prior to admission. At that time there was a decrease in appetite but an increase in thirst. Headaches became a problem and several months later she began using eye glasses without significant relief. Over the next twelve t,o sixteen months, she underwent a thorough medical evaluation, with laboratory and x-ray studies including gastrointestinal x-ray films. Results of one serum calcium determination were reported as normal. Until May 1962 her problem was considered psychological. At that time a dentist in South America noted a bone cyst in the jaw and she was sent to the New York Hospital for surgery. At this time the serum calcium level was reported to be 18.6 mg/lOO ml. At the time of admission she was pale and appeared to be chronically ill. She was quite small, and menstruation had not begun. There were no palpable neck masses. Additional preoperative serum calcium levels were 18.8 mg/lOO ml and 18.4 mg/lOO ml. The serum alkaline phosphatase level was 9.6 units (King-Armstrong). X-ray films revealed demineralization and slightly retarded bone age. There was no specific sign of hyperparathyroidism on x-ray study. The jaw tumor was removed and found to be a typical brown tumor. Neck exploration was performed by Doctor Frank Glenn on June 18, 1962 and a large adenoma (Figure 1) was removed. The postoperative serum calcium level decreased to 9.3 mg/lOO ml and the serum alkaline phosphatase level increased to 18.6 units. The postoperative course was complicated by the onset of severe head-
aches, which were eventually type.
There
was a family
Volume
129, May 1975
diagnosed
history
as migraine
of migraine.
in
She re-
I
TABLE --.
--
Reported Cases of Primary km in Children
Hyperparathyoid-
Pathology
Author Bjernulf et al [ J2], 1970 Stukkei and lgnatiev [O], 1972 Goldbloom, Gillis, and Prasad Bergman
[S], 1972 and Hagberg
[ 141, 1972 Vasquez [ 7 31, 1973 Lund [ 151, 1973 Bradford, Wilson, and Gaede [?I, 1973 Present report
Number of Cases
__ M
43 8
25 6
18 2
35 80
2
0
2
02
10
F
HYAden- perUnoma plasia known
110
110 110 10 3
Sex
0
7
1 0 0 0
0 0
0
10 10 110
3
30
0
quired oral calcium postoperatively for about ten days because of low grade symptoms of tetany. Verbal followup seven years later indicated that the patient had developed normally in every way. There have been no further symptoms of hyperparathyroidism. Case II. The patient (#965519 NYH), a fourteen year old female, had two episodes of renal calculi with severe colic. The first episode occurred in the summer of 1963 and details of laboratory studies are not available. She passed the stones successfully. In October 1963, she had a second episode of colic and underwent nephrolithotomy to remove the stone on October 7, 1963. Serum calcium values at that time were 11.9 mg/lOO ml, 12.9 mg/lOO ml, and 13.3 mg/lOO ml, with a low normal phosphorus level. The alkaline phosphatase level was normal. She was subsequently studied in the Metabolic Unit at New York Hospital. She demonstrated an elevated urinary excretion of calcium on a restricted diet and a marked increase in serum calcium in response to the calcium load. The serum calcium level continued to be elevated. X-ray examination of the bones revealed no abnormalities. The patient was a tall, well developed female with all the secondary sexual characteristics. There was no evidence of physical retardation. Her menstrual
Figure 7. An adenoma measuring 2.5 cm, was removed during neck exploration in case I. It was located adjacent to the lower pole on the right thyroid.
529
Mannix
Figure 2. The ribs in this frontal chest x-ray film of the patient in case III are significantly demineralized.
periods were normal. Neck exploration revealed a moderate sized adenoma in the right upper pole area. Interestingly, an aberrant vessel from the common carotid led to the discovery of the tumor. The postoperative course was uncomplicated, with serum calcium values returning to low normal. Seven years later, the serum calcium level was normal and twenty-four hour urinary excretion of calcium on an unrestricted diet was low normal. She had no further renal calculi.
Case III. The patient (#78103006 SFH), a fifteen year old female, was first seen by her general practitioner in the summer of 1972. She complained of nausea
Figure 3. Dorsal vertebrae are clearly less mineralized than would be expected In a fifteen year old female.
530
with vomiting, especially after breakfast. Duration of symptoms was two months and she had begun to lose weight. Anorexia nervosa was diagnosed initially and mild tranquilizers were administered without benefit. During a period of four and a half months she lost fifteen pounds. A second physician examined her and noted lethargy as well as evidence of weight loss. Serum calcium was elevated to 14.3 mg/lOO ml. oh repeated testing the serum calcium level was 14.9 mg/lOO ml and she was promptly admitted to the hospital. At the time of admission, the serum calcium level was 16.4 mg/lOO ml. She was treated with large doses of intravenous saline and the serum calcium level decreased to about 13 mg/lOO ml. The diminished phosphorus reabsorption suggested hyperparathyroidism and additional serum calcium levels were consistently elevated with low phosphorus levels. X-ray films demonstrated bony demineralization (Figures 2 and 3) and a cervical esophagogram showed deviation to the left in the right lower neck. Neck exploration revealed a large adenoma, measuring 2.5 cm, adjacent to the right lower pole of the thyroid, which, in retrospect, had been palpable. The postoperative course was uneventful except for mild symptoms of tetany, which were controlled with oral calcium. Serum calcium decreased to 8.5 mg/lOO ml during the immediate postoperative period. She received oral calcium for six weeks postoperatively, and then it was gradually withdrawn. Follow-up study at one year showed that the patient had gained twenty pounds in weight, had excellent appetite, and at present is slightly overweight for her habitus. Comments
In this review it is apparent that primary hyperparathyroidism may present a somewhat different picture in children from that in adults, The incidence of anorexia, weight loss, and personality changes are all more striking in these patients. The more common manifestations in adults, such as renal and bone disease, are present but to a lesser extent. From the cases presented, it is obvious that the diagnosis of primary hyperparathyroidism may not even be considered in many of these children. This is confirmed from a review of the literature. Death can occur in children as a result of hypercalcemia due to parathyroid adenoma. It may be advised that serum calcium determinations be made in children who present with chronic loss of appetite, anorexia, weight loss, or personality changes before a diagnosis of psychosomatic problems is made. Infants with hereditary parathyroid hyperplasia present a most challenging problem. Frequently they are critically ill and the diagnosis can be obscure. Since the disease is hereditary, it may be suspected in certain instances. Surgical manage-
TheAmerican Journalof Surgery
Hyperparathyroidism
ment, once the diagnosis is made, is very difficult because of the size of the patient and the many aberrant locations for parathyroid tissue. These patients must be treated preoperatively to diminish the serum calcium level before anesthesia is induced. Saline infusions may be useful as well as more specific substances, such as edathamil or various chelating agents. Porcine calcitonin is also available. From a review of the literature it is apparent that there are more males than females with nonhereditary disease, whereas among adult patients with this condition females are encountered much more frequently. The symptoms in these patients are related to the levels of serum calcium. Of the three patients reported on herein, two had serum calcium levels higher than 15 mg/lOO ml and in both patients the diagnosis was not considered early in their course. The third patient presented with the typical adult features, that is, recurrent renal calculi and only moderate elevation of the serum calcium level. In addition, the adenoma in this patient was relatively small, as might be exin the patients petted. Incidence of hyperplasia with nonfamilial disease is low; in fact, it is possibly lower than in adults, although the sample is rather small. The tumor in two of the three cases reported was very large and, in fact, was palpable in one patient. The surgical challenge was therefore not great. Preoperative management of the third patient, employing large doses of saline intravenously, reduced the serum calcium level to less than 14 mg/lOO ml and made operation safe. If the saline therapy had not succeeded, calcium phosphate and even possibly calcitonin would have been administered. In children, many of the tumors are large and easily identified. Although this report emphasizes primary hyperparathyroidism as a cause of significant hypercalcemia in children, the other diagnoses mentioned earlier must be considered in the work-up of these patients. As a general rule, the conditions can be excluded without great difficulty, but it is worth emphasizing that they be considered to avoid unnecessary surgery. Utilization of serum parathormone levels in relation to serum calcium levels simplifies the accurate diagnosis of the condition. At present, it is possible to obtain accurate determinations of the parathormone level on a commercial basis within a week to ten days. In some pa-
Volume 129, May 1075
in Children
tients with borderline serum calcium levels a diagnosis may be established by elevated serum parathormone levels. It is probably not necessary to pursue the more complicated angiographic studies in children before the initial exploration. Careful neck exploration will generally result in discovery of the adenoma and its removal. Summary
Three cases of primary hyperparathyroidism in children are presented and the literature reviewed. Symptoms of nausea, weight loss, and personality changes are more common in children than in adults with this disease. Children may have the diagnosis delayed because of failure to consider hyperparathyroidism. Surgery has been demonstrated to be most effective in treating this condition. References 1. Hoehn JG. Beahrs OH, Woolner LB: Unusual surgical lesions of the parathyroid gland. Am J Surg 118: 770, 1969. 2. Cope 0: Story of hyperparathyroidism at the Massachusetts General Hospital. N Engl J Med 274: 1174, 1966. 3. Rienhoff WF Jr, Rienhoff WF III, Brawley RK, Shelley WM: The surgical treatment of hyperparathyroidism. Ann Surg 166: 1061, 1968. 4. Farr HW, Fahey TJ, Nash AG, Farr CM: Primary hyperparathyroidism and cancer. Am J Surg 126: 539, 1973. 5. Friedman EW, Schwartz AE. Spiro RH: Changing patterns in hyperparathyroidism. Surg Gynecol Dbstet 137: 941, 1973. 6. Hillman EA, Striver CR, Pedvis S, Shragovitch I: Neonatal familial primary hyperparathyroidism. N Engl J Med 270: 483, 1964. 7. Bradford WD. Wilson JW, Gaede JT: Primary neonatal hyperparathyroidism-an unusual cause of failure to thrive. Am J C/in Patho/ 59: 267, 1973. 8. Goldbloom RB, Gillis DA, Prasad M: Hereditary parathyroid hyperplasia: a surgical emergency of early infancy. fediat&s 49: 514, 1972. 9. Stukkei AL, lgnatiev AS: Hyperparathyroidism in childhood and youth. /%&atria 51: 29, 1972. 10. Foley TP Jr, Harrison HC, Arnaud CD, Harrison HE: Familial benign hypercalcemia. J Pediatr81: 1060. 1972. 11. Nolan RB, Hayles AB, Woolner LB: Adenomas of the parathvroid aland in children. Am J Dis Child 99: 622. 1960. 12. Bier&If A,‘i-lall K, Sgogren I, Werner I: Primary hyperthyroidism in children. Acfa Paediatr Stand 59: 249, 1970. 13. Vasquez AM: Nephrocalcinosis and hypertension in juvenile primary hyperparathyroidism. Am J Dis Child 125: 104, 1973. 14. Bergman L, Hagberg S: Primary hyperparathyroidism in a child investigated by determination on ultrafiltrable calciurn. Am J Dis Child 123: 174. 1972. 15. Lund HT: Primary hyperparathyroidism in childhood. Acta PaediatrScand62: 317. 1973.
531
