(Accepted March 17, 1959; submitted November 6, 1958.)
This work was made possible by a research grant from the Division of Research Grants and
Fellow-ships of the National Institutes of Health, United States Public Health Service.
Dr. Blizzard was a Fellow of the National Foundation for Infantile Paralysis.
ADDRESS: (D.W.S.) Department of Pediatrics, University of Wisconsin Medical School, Madison 6,
Wisconsin.
258
PEmATiucs, August 1959
tively few reports have appeared in the United States; Deutch and Sentunia’8 and
Daeschnen and Daeschnenl9 described mdi-vidual cases, and Bongiovanni et 20
re-ported three cases with a review of the literature. With few exceptions most infants
with unexplained hypercalcemia have been receiving preparations of cow’s milk with a goodly intake of vitamin D, usually more than 1,500 units/day. Many infants in the United Kingdom receive such dosage.
Creeny and Neill2’ reviewed tile vitamin D intake of 1,087 normal infants in Belfast, Ireland, and found that 51 received
be-tween 1,000 and 2,000 units/day. Therefore, it is readily evident that the incidence of
the disease among infants taking 1,000 to 2,000 units/day is quite low. The basic
etiology of the disease has remained
ob-scure, although the predominant feeling is
tilat the condition is secondary to an exag-gerated response to a moderate dosage of vitamin D.9’ ‘ 22, 23
The purpose of this paper is to report a
case of prolonged hypercalcemia in which
assays of vitamin D in the serum were
pen-formed.
METHODS
The initial assay for content of vitamin D in
the serum was performed by Dr. Bernard Spur
urine were as follows: concentration of cal-cium ill serum was determined by the method of Harrison and Harrison;2’ concentration of phosphorus in the serum by the method of
Fiske and Subbarow;26 and that of citrate b the method of Natelson et al.27 Concentration
of calcium in the urine was determined by the method of Clark and Collip.2
History
CASE REPORT
S.H. was admitted to the Harriet Lane Home
at 5 ‘ears of age (September 15, 1954) with the chief complaints of unilateral facial weakness, intermittent abdominal pain, and poor weight gain.
The patient was born on July 25, 1949, of a
full-term pregnancy during which the mother received supplemental calcium. The birth weight was 2,610 gm. Formula consisted of evaporated milk (400 units of vitamin D per 13 oz can). At 15 months of age homogenized milk (400 units of vitamin D per quart) was substituted for evaporated milk. The intake was about one quart daily after 23 ‘ears of age.
Supplemental water-soluble vitamin D was taken in the following dosages: 1,000 units/day
until 18 months of age, 1,500 units/day from
18 months uiitil 5 years of age, and 4,400
umts/day during the month before admission.
Developmentally, she sat at 7 months of age
ARTICLES 259
of age. From birth she had frequent vomiting, slow weight gain, anorexia, relative
constipa-tion, and frequent upper respiratory illnesses.
At 10 months of age she was first admitted to
Harriet Lane Home weighing 6.65 kg. She was a slim, undernourished infant with fretful dis-position and tendency to vomit.
Concentrations of calcium in the serum ranged from 12.2 to 16.2 mg/100 ml; phos-phorus, 4.0 to 5.8 mg/100 ml; alkaline
phos-phatase, 9 to 15 Bodanski units/100 ml. The concentration of nonprotein nitrogen in the serum was 32-49 mg/100 ml and the content of
carbon dioxide 23.3 mmole/l. Urinary exere-tion of phenolsulfonphthalein after intravenous
injection was 60% in 2 hours.
An intravenous pyelogram was 1101-ma! with
no evidence of nephrocalcinosis.
Roentgeno-grams of the long bones disclosed slight
osteo-porosis with relative increase in density of the
epiphvseal plate.
During a 4-month period of hospitalization, while receiving milk and 1,000 units of vita-mm D per day, she continued to vomit and was discharged weighing the same as at the time of admission.
Between 14 and 26 months of age vomiting
ceased and she gained to 8.86 kg. The
con-centration of calcium in the serum during this
period ranged from 137#{149}to 16.4 mg/100 ml. She was not seen at the Harriet Lane Home from 26 months of age until 5 years of age.
At 3 years of age anorexia except for milk
was a problem, and there was gradual onset of
polyuria, polvdipsia and occasional headaches. Three months before the second admission she became listless and intermittently complained
of abdominal pain and vague pains in the
cx-tremities. Two months before admission an episode of severe abdominal pain occurred
with fever and leukocvtosis (30,000/mm).
Because of these findings and a rigid abdomen, explorato:-y laparotomv was performed at an other hospital. White plaques were noted over the peritoneal surfaces, which on biopsy proved to contain calcium. She remained listless and suffered from generalized pruritus. A right facial palsy developed which resolved partially be-fore admission.
Physical Findings
At the time of admission to the Harriet Lane
Home at 5 ears of age the weight was 11.5 kg, height-age of 33 years. She was slim and
undernourished with an apathetic appearance. She preferred to lie down, whimpering when disturbed. The blood pressure was 120/90 mm Hg. The skin over the abdomen and lateral aspects of the trunk showed a faint caf#{233}an lait
discoloration. There was redness of the left
con-junctivae. Slit-lamp examination revealed fine crystalline deposits beneath the conjunctival basement membrane. There was brownish
dis-coloration at the base of the teeth. Abdominal
palpation disclosed variable tenderness with muscular guarding, most marked in the left upper quadrant. No mass was palpable. Pressure exerted over the wrists and knees
caused pain, though no redness or swelling was
discernible. There was slight facial weakness on the right.
Laboratory Findings
In tile serum the concentration of calcium
was 17.1 mg/100 ml; that of phosphorus, 4.8 mg/100 ml; alkaline phosphatase, 15.4 Bodan-sky units; nonprotein nitrogen, 60 mg/100 ml; and total protein, 7.9 gm/100 ml. The content of carbon dioxide was 23.3 mmole/l and the concentration of citrate was 5.3 mg/100 ml (normal 2.5 mg/100 ml). The concentration of hemoglobin was 11.0 gm/100 ml with a leuko-cyte count of lO,700/mm’. Urinalysis showed a trace of albumin, no cellular elements, maxi-mal specific gravity of 1.014, and a 4+ Sulko-witch test for calcium. Urinary excretion of phenolsulfonphthalein was 40% in 2 hours.
Roentgenographic Findings
Roentgenograms of the abdomen disclosed nephrocalcinosis in addition to mottled density
in the perirenal areas. The intravenous
pyelo-gram showed poor concentration with delayed
clearance. Roentgenograms of the skull
re-vealed calcification in the falx cerebri,
tento-ium cerebri, petroclinoid ligaments and
in-ternal carotid arteries (Fig. 1). The base of the skull did not appear abnormally dense.
Roent-genograms of the long bones showed relative
osteOporosis (Fig. 2) with prominent trabeeu-Ian pattern, peniosteal elevations along the shafts
and a band of radiolucency in the
subepi-phvseal portion of the long bones. Tile
epi-phvseal plates appeared relatively dense.
Initial Assay of Vitamin D
FIG. 1A. Anteroposterior projection showing calcification in the falx cerebri
and the carotid arteries (arrow).
Dr. Bernard Spur, Director of the Milk Re-search Laboratory of the Children’s Hospital of
Philadelphia, and showed a concentration of
23 units of vitamin D per milliliter of plasma,
as compared to a normal value of 0.66-1.65
units/mi noted by Warkany and Mahon.29 Be-cause of an insufficient amount of serum, this
test was performed on only four rachitic rats instead of the usual 8 or 10 animals. The result
must therefore be taken with some reservation.
Course (Fig. 3)
EXCRETION OF CALCIUM IN URINE : During
the
hospitalization of 2 months the patient wasweak, listless and complained of occasional pain
in the abdomen and extremities. Initially, while
receiving a milk diet, the 24-hour excretion of calcium in the urine was 135 mg. After 2 weeks
of receiving a milk-free diet, the 24-hour
un-nary excretion of calcium on two occasions was
less than 40 mg.
HYPERCALCEMIC “CRISIS”: On September 23,
after 24 hours of poor fluid intake, she corn-plained of severe abdominal pain; the abdomen was noted to be rigid, the leukocyte count was 30,000/rnm and the blood pressure rose from
con-FIG. lB. Lateral projection showing calcification of petroclinoid ligament. The
base of the skull does not appear sclerotic.
ARTICLES
261vulsion, and lapsed into coma. The concentra-tion of calcium in the serum was 16.0 mg/100 ml, and that of phosphorus was 6.8 mg/100
ml. Sodium EDTA* (sodium Versenate#{174}) was given intravenously, 200 rng over the first hour and 800 rng over the next 16 hours.
Within 30 minutes she regained consciousness
and 6 hours thereafter was able to retain fluids
orally. After 8 hours of therapy the oxalate-precipitable calcium in the serum was 12.8 mg/100 ml, with a total ashed calcium of 15.7 mg/lOOml.
Subsequently, the blood pressure remained elevated between 130/90 and 210/160 mm
0 Sodium ethylenediaminetetraacetate. Lamb soup “recipe” :#{176}
1j cups strained lamb (prepared baby food)
2% tbs. sugar
, tsp. salt
2 tsp. olive oil 2% tbs. rice flour
32
oz. waterHg, being usually 160/110. There was no sponse to administration of Raudixin#{174} or intra-muscular administration of magnesium sulfate. The concentration of non-protein nitrogen re-mained elevated between 35 and 60 mg/100 ml.
In order to exclude the possibility of
para-thyroid adenoma, an exploration of the neck and anterior portion of the mediastinum was performed and no adenoma was found.
On October 1, the patient had a second
“crisis,” though symptomatically not as severe as the first. On this occasion the concentration
of calcium in the serum was 18.2 mg/100 ml.
She was again given sodium Versenate#{174} intra-venously with improvement.
CORTISONE THERAPY: On October 2, oral ad-ministration of cortisone, 100 mg/day, was
be-gun with a gratifying fall in the concentration of calcium. Before cortisone therapy, the
con-centration of calcium was 14.7 to 18.2 mg/100
12.0 to 17.3 Bodanskv units; the concentration of citrate in the serum was 5.3 mg/100 ml. While receiving cortisone therapy the concen-tration of calcium in the serum was 1 1 .8 to 13.7 mg/100 ml and the alkaline phosphatase activity was 3.2 to 11.1 Bodansky units. The
concentration of citrate dropped to levels of 1.8 and 2.8 mg/100 ml. She continued to
re-fuse most foods other than milk, which she was allowed to take. While on this regimen the
24-hour urinary excretion of calcium was less than
40 mg/24 hours on two occasions.
On November 3, 1954, multiple petechiae
were noted over the lower extremities but these disappeared in 3 days; the platetlet count was 388,000/mm3.
The dosage of cortisone was gradually de-creased and, finally, administration was discon-tinued. On November 11, she was discharged from the hospital with a mandatory fluid intake of 1,000 ml/dav, with milk as desired. No vita-mm D was given after admission or
subse-quently.
Five days after administration of cortisone was discontinued, the concentration of calcium
in the serum had risen to 14.6 mg/100 ml, and after 23 weeks it was 16.4 mg/100 ml. On
No-vember 30, the oral administration of 25 mg of cortisone daily was again begun and the con-centration of calcium in the serum fell to 13.4 mg/100 ml. In January 1955, the dosage of cortisone was reduced to 12.5 mg/day, and 3 months later the concentration of calcium had risen to 15.6 mg/100 ml. Henceforth, 18.5 mg of cortisone was given per day until November 1955. The dosage of cortisone was then gradu-ally reduced and administration was discon-tinued without a subsequent rise in concentra-tion of calcium in the serum.
At the time of discharge from the hospital a
firm abdominal mass was palpable in the left upper quadrant. This enlarged further during the subsequent week and was associated with moderate pain. Roentgenograms of the abdo-men disclosed a mottled radio-opaque mass in the left upper quadrant. One month later the
mass was no longer palpable, nor was it
de-monstrable by roentgenograms. This was
pre-sumed to be spleen which became infarcted and receded, with probable atrophy.
Low
CALCIUM DIETS: In February 1955,elimi-FIG. 2C. Roentgenogram at 5%2 years (March 1955) discloses increase in the width of the
sub-epiphyseal rarefaction with minute trabecular
frac-tures noted at the ends of the long bones. The
relative density of the epiphyses is again noted.
----. --. --- D
‘-1956) discloses re-mineralization of the radiolucent
areas with healing of the minute trabecular
frac-tures, calcification in the periosteal elevations, and decrease in the relative density of the epiphyses.
ARTICLES 263
0 See recipe in footnote on page 261.
nation of foods of high-calcium content and substitution of a “lamb soup”#{176}for milk. In spite
of the unpleasant taste of the lamb soup, she
took 600 ml/day, which contained 27 mg of
calcium. The total daily diet was analyzed on two occasions and contained 58 mg/day and
80 mg/day of calcium, respectively.
From the time the diet low in calcium was
introduced there was gradual and remarkable improvement in personality and activity. From a listless, fretful child she became active and
pleasant.
CONCENTRATION OF VITAMIN D IN SERUM:
Six months after admission and discontinuation of administration of vitamin D, a vitamin D
assay of serum revealed a level of 5 units/mI,
which is above the normal of 1 0.5 units/ml. A vitamin D assay performed in June 1956 re-vealed a vitamm D level in the serum of 2.0
units/mi. This was after 21 months of a regi-men without added vitamin D.
CITRATE THERAPY: The concentration of cal-cium in the serum continued to be at the upper limits of normal in spite of the low intake of calcium, and the urinary excretion of calcium
was high (108 to 208 mg/24 hr). In September 1955, in an effort to reduce the hypercalciunia, she was given Poly Citra#{174} (molar sodium and
potassium citrate), #{176}45 mi/day. After 6 weeks,
the dosage was reduced to 20 ml/day because of alkalosis. With this therapy the urinary cx-cretion of calcium fell from 108 to 37.5 mg/24
hours. Balance studies revealed a negative
cal-cium balance of -94 mg/day just before
cit-rate therapy and -23 mg/day after 6 weeks of citrate therapy. The concentration of cal-cium in the serum was 11.4 mg/100 ml at the onset of citrate therapy and 11.1 mg/100 ml after 6 weeks. During citrate therapy the con-centration of citrate in the serum was high, ranging from 6.2 to 8.3 mg/100 ml.
In February 1956 the concentration of cal-cium in the serum was 12.0 mg/100 ml and an
additional 100 mg of calcium was given in the diet in the form of calcium lactate, 700 mg/ day. After February 1956, the concentration
of calcium in the serum remained between 10.9 and 12.0 mg/100 ml and the intake of calcium
0 Supplied by the Willen Drug Co., Baltimore,
Maryland. This preparation supplies 1 meq each
a
0
L)
.‘ 1)10
co. ‘4
ci
- Q
C
e a
C) bI
‘4
0
5 6 7
CHRONOLOGICAL
AGE
FIG. 4. Developmental curve illustrating advance-ment in height, weight and bone age during the period of treatment. (Height and weight standards from Wilkins, L. : The Diagnosis and Treatment of
Endocrine Disorders in Childhood and Adoles-cence, 1st Ed. Springfield, Thomas, 1950.)
ARTICLES
265was gradually increased to 550 mg of calcium/ day in April 1956. The urinary output of cal-cium remained low. A balance study done in
J
une 1956 disclosed a positive calcium balance of 152 mg/24 hours. Roentgenograms of theabdomen and skull made in July 1956 revealed no evident change in soft tissue calcification.
In July 1956, the citrate therapy was discon-tinued with no rise in concentration of calcium
in the serum, but a rise in the urinary excretion of calcium did occur from 47 mg/24 hours to 121 mg/24 hours 1 month later. The concen-tration of citrate in the serum fell from 8.0 to 2.8 mg/100 ml.
Between July 1956 and December 1957 the
concentration of calcium in the serum varied
between 10.5 and 11.5 mg/100 ml. Urinary excretion of calcium in November 1956 was 65
mg/24 hours and in May 1957, 80 mg/24 hours. During this period the concentration of phosphorus in the serum gradually fell from 5.2 mg/100 ml in September 1956 to 3.2 mg/ 100 ml in January 1957, and in May 1957 was 5.0 mg/100 ml. The alkaline phosphatase ac-tivity remained constant between 15 and 20 Bodansky units. The dietary intake of calcium was gradually increased until in May 1957 she was taking 480 ml of milk daily, and either cheese or ice cream daily.
ROENTGENOGRAMS OF LONG BONES: In March 1955, while the patient was receiving a diet low in calcium and 12.5 mg/day of corti-sone orally, roentgenograms of the long bones showed a further progression of the pathologic findings. The bands of subepiphyseal
rarefac-tion had become widen with minute trabecular
fractures noted at the ends of several of the
long bones (Fig. 2C). This picture was prac-tically the same in July 1955. In September 1955, when the patient was in negative cal-cium balance, roentgenograms disclosed
re-mineralization of the subepiphyseal areas of
radiolucency at the ends of the long bones with healing of the minute trabecular fractures. Further evidence of improvement was noted in roentgenograms made in February 1956 (Fig.
2D). Osteoporosis of the shaft had become less in degree while the relative density of the
epiph-yses had become less marked. Roentgeno-grams made in July 1956 disclosed normal bone structure.
HYPERTENSION AND RENAL FUNCTION: The blood pressure had been persistently elevated to 160/100 mm Hg or higher until January
1956 when it began to fall and in March 1956
the blood pressure was 106/70 mm Hg.
Study of renal function disclosed that the concentration of nonprotein nitrogen in the
serum remained elevated between 40 and 48 mg/100 ml. In January 1956, the urea
clear-ance was 28% of normal, excretion of phenol-sulfonphthalein was 37.5% in 2 hours, and the maximal specific gravity was 1.014. Urinalysis was normal. Urea clearance in January 1957 was 43% and excretion of
phenolsulfonphthal-em was 48% in 2 hours, suggesting some im-provement of renal function. Specific gravity, however, remained fixed at 1.010.
GROWTH: Until December 1955 growth in height had been relatively slow; however, dun-ing the next 3 months she grew 4.5 cm and during the next year, 1 1 cm (Fig. 4).
NEUROLOGIC CHANGES: During the study the
patient displayed evidence of nervous system
damage. The partial right facial palsy which was present at the time of admission resolved in 2 weeks time. On October 25, 1954, a
intermit-Fe-
FP2FP
2FP
I0
2T
4T4
- F 8time constant 0.03 sec.
Fic. 5. Electroencephalogram made in June 1956 showing three independent foci or spikes associated
with slow waves in left occiput (01), right occiput (02), and right pre-frontal (Fp2). Electrode labeling
is International Standard. J.H.H. EEG # 10705.
tent twitching of the right eyebrow and right hand for 3 days. She continued to have
sei-zures characterized by aphonia and gradual
loss of contact to the point of coma. These
oc-curred at intervals of from 3 days to 1 month until December 1955. Five such episodes were observed during which the concentration of calcium in the serum was not elevated above the nonseizure levels. In August 1956, admin-istration of diphenlhvdantoin (Dilantin#{174}) was begun and since then no seizures have occurred. An electroencephalogram in June 1956 was grossly abnormal with independent foci of spikes with slow waves (Fig. 5).
At times there was apparent hearing impair-ment. Evaluation disclosed normal reception but inability to perceive sound accurately,
in-dicating a central inability to interpret sound.
In April 1956, a Wechsler Intelligence Test
disclosed a verbal intelligence quotient (I.Q.)
of 67, and a nonverbal I.Q. of 74; full I.Q. , 67. It was again noted that she had difficulty
de-ciphering the spoken word.
DISCUSSION
The patient manifested a clinical
pie-ture of unexplained mild idiopathic
hypen-calcemia of infancy at 10 months of age.
No therapeutic measures were taken at this
time to connect the hypencalcemia, and when
hospitalized at 5 years of age symptoms of
severe idiopathic hypercalcemia were
cvi-dent. However, this patient differs in
cer-tam
respects from other patients withse-vene idiopathic hypencalcemia. She does not
show either the elfin facies or the osteo-sclerosis described by Schlesinger et al.13 in a review of 10 cases.
The daily supplementation of vitamin D
which the patient received would not nor-mally be considered a toxic dosage, but the initial concentration of vitamin D in the
serum was elevated (23 units/mI of serum) and only gradually fell to within normal
limits 21 months after administration of
vitamin D was discontinued, at the time
when the concentration of calcium in the serum became normal.
ranefac-ARTICLES 267
tion, peniosteal elevations, and relative
rare-faction of the shafts of the long bones as compared to the epiphyses. These changes
are similar to tilose described by Ross3’ and Debre32 in cases of vitamin D intoxication
in children. However, roentgenograms in
this case did not show the marked increased density at the epiphyseal plate which is
usually noted in both vitamin D intoxication
and idiopathic hypercalcemia. Certain
cx-penimental findings are of interest in an at-tempt to understand the bone picture
dis-played by this patient. Harris and Innes33
found that high doses of irradiated ergos-terol given to rats initially resulted in in-creased deposition of calcium in the bone, particularly at the epiphyseal line. With
prolonged therapy, demineralization
oc-curned with resorption of the subepiphyseal
spongiosa. With time they noted that the
renal excretion of calcium increased,
re-sulting in negative calcium balance. The
demineralization is probably a direct effect of vitamin D on the bone tissue and it is
possible that the demineralization of the bone in the patient studied by us was due
to a prolonged cumulative effect of vitamin
D. As hypencalcemia improved, remineral-ization took place, even in the face of
nega-tive calcium balance. The source of calcium for nemineralization was therefore endogen-ous, either from soft tissue deposits or from redistribution in the bone itself. The latter
possibility seems more likely since there was no evident decrease in
roentgeno-graphic evidence of soft tissue calcification
at the time of reminenalization. It is felt that the unusual duration of the disease fostered the changes of demineralization.
Hypercalciunia may have acted as a safety
valve to allow the disease to persist so long before severe symptoms of hypercalcemia were present.
In addition it should be emphasized that
the patient has now been followed for 2 years since the concentration of calcium in
the serum returned to normal (3% years in
all). During this period she has received a
full diet with 480 ml of milk and no added vitamin D, and on this regimen has been
normocalcemic with a normal rate of
growth. Though not conclusive, this follow-up does not implicate any other factor as a
cause for hypencalcemia in the absence of supplemental vitamin D.
The fall in the concentration of
phos-phonus in the serum noted in this patient
during convalescence is of interest. Howard and Meyer4 reported a low concentration
of phosphorus in the serum during the con-valescent period in adults with vitamin D
intoxication.
The concentration of citrate in the serum
was initially elevated, a finding which
Han-nison35 observed in hypervitammnosis D. He
noted that elevated citrate levels have been
found in a variety of conditions in which deminenalization of the skeleton and hyper-calcemia occur. Winberg and ZetterstrOm36 reported a low concentration of citrate in
the serum in hypervitammnosis D, and Fonfar and associates12 noted a low concentration in idiopathic hypercalcemia, but too few
determinations have been made in such
patients to permit any conclusions concern-ing the significance of citrate levels in
hy-percalcemic states. The subsequent citrate
levels disclosed low to normal values during
cortisone therapy, high values during
ci-trate therapy, and normal values after ad-ministration of citrate was discontinued and
osseous healing had occurred.
The fundamental reason why idiopathic
hypencalcemia should occur in infants re-ceiving moderate dosage of vitamin D is not settled. There could be a physiologic
differ-ence in the response to vitamin D. Follis
et
al.7 have stated that there is a wide van-ability in the vitamin D requirements in infancy. A second possibility is a metabolic
defect in the degradation mechanism of
vitamin D such that excessive accumulation of the vitamin could occur. In this regard
Fyfe38 demonstrated high concentrations of
vitamin A in the serum with a greater than
normal rise after oral administration of vita-mine A to patients with idiopathic hypercal-cemia of infancy. He suggested that there
might be a concomitant defect in the
infants. The assays of vitamin D in the
serum of the patient studied by us also sug-gest failure of normal metabolism of vitamin
D. On the other
hand,
Morgan
and
co-work-ens4#{176}have recently obtained vitamin D
as-says in the serum of two patients with
idio-pathic hypercalcemia in infancy. The re-suits, performed by the same laboratory as the latter two determinations in the patient studied by us, were within normal limits. The paucity of determinations of concentra-tions of vitamin D in the serum of infants
with hypercalcemia and the discrepant re-sults reported prevent any conclusions from being made concerning the fundamental metabolic disturbance.
Whether the role of vitamin D is primary
or secondary, it appears to have been con-tributory as a cause of the hypercalcemia in this particular case. Since a daily intake of
400
units of vitamin D has been shown to be adequate for normal growth and preventionof rickets in infancy,41 it would seem ad-visable to limit the prophylactic vitamin D doses to this level rather than incur the danger of hypercalcemia on higher dosage,
rare though it may be.
Clinically, several points are worthy of
note. The retardation in growth rate per-sisted throughout the period of
hypercal-cemia. When the concentration of calcium in the serum returned to normal and the osseous abnormalities improved, an aced-crated growth spurt occurred, followed by a
normal rate of growth (Fig. 4). The hyper-tension gradually resolved, with normal blood pressure being obtained when the
concentration of calcium in the serum
re-turned
to
normal. Other effects of hyper-calcemia left permanent residua. RenalAfter discontinuation of supplemental vita mm D ar J a diet low in calcium the con-centrations of calcium and vitamin D in the serum gradually returned to normal over a period of 18 months. Roentgenograms of te
bones showed evidence of demineralization rather than increased density as reported in other cases of “idiopathic” hypercaicemia. During a subsequent 2-year follow-up the
patient has maintained a normal serum cal-cium. The etiology is discussed with
par-ticular refere’ce to the role of vitamin D in this case
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