Twinkle:Tokyo Womens Medical University - 東京女子医科大学

Title
Author(s)
Journal
URL
低身長者における血中ソマトメディンA値：特に成
長ホルモン欠損症の診断，成長ホルモン治療時の血中ソ
マトメディンA値測定の有用性について
肥塚, 直美
東京女子医科大学雑誌, 48(9):800-809, 1978
http://hdl.handle.net/10470/3655
Twinkle:Tokyo Women's Medical University - Information & Knowledge Database.
http://ir.twmu.ac.jp/dspace/
14
(4tiT,o,k,yo,gY,oNM,,1ij[eg,,C,O,iS)
Semm Somatomedin A in Patients with Short Stature
Usefulness of Serum Somatomedin A Measurement in Diagnosing GH Deficiency
and Evaluating tlie Effects of GH Treatment
Naoni HIZUKA, M.D.
Department of Internal Medicine (Director: Pro￡ Kazuo SHIZUME) Tokyo Women's Medical College
Received June 24, accepted July 6
Abstract
for evaluation of GH treatment in patients
The levels of serum somatomedin A were
with GH deficiency.
determined in I07 patients with short stature
introduction
I4 1957 Salmon and Daughaday (1) demon-
by a radioreceptor assay. Low levels were fbund
in 10 children with growth hormone (GH)
strated that growth hormone (GH) had no
deficiency and 7 children with relative GH
direct effect on sulfate uptake in cartilage, but
deficiency, with means of O.26±O.03 and
O.48±e.04Ulml, respectively. Serum soma-
called somatomedins (2). Four peptides have
acted through secondary plasma factors, the so-
tomedin A levels in 42 growth-retarded children
been purified from human plasma; somatomedin
with norma] GH secretion, 28 patients with
A designates a factor which stimulates the in-
Turner's syndrome and 8 patients with achon-
corporation of sulfate into chick cartilage (3,
droplasia were within normal range. No correla-
4); somatomedin C designates a factor which
tion was observed between the severity of short
stimu!ates the incroporation of both sulfate and
stature and serum somatomedin A levels.
thymidine into rat cartilage (5) ;, and the insu]in-
Significant increases in somatomedin A were
like growth factors I and II (IGF-I, IGF-II)
found after hGH administration in children with
stimulate glucose oxidation in epididymal adipose
GH deficiency, but not in children with normal
tissue (6, 7). These fbur peptides have similar
GH secretion. There was a dose dependency
effects in their biological activity (8). Different
between the logarithmic doses of hG}I and
methods have been developed for their determina-
somatomedin A.
tion such as bioassay, radioreceptor assay and
In children with GH deficiency, linear growth
radioimmunoassay (5, 6, 9-13).
was accelerated and serum somatomedin A in-
It has been reported that the serum soma-
creased after hGH treatment, and there was a
tomedin activity in patients with GH deficiency
positive correlation between serum levels of soma-
is low and increases after GH administration (14-
tomedin A and growth rate.
20). Furthermore, it has been observed that
These results show that determination of soma-
serum somatornedin correlates with the growth
rate during hGH treatment (16, 18-19).
tomedin A in serum correlates well witli the state
In this study, we determined serum soma-
of GH secretion, and is of importance both for
selection of patients for treatment with hGH and
tomedin A levels in children with GH deficiency as
-seo-
15
well as children with other types of growth
tion and during Iong term ticeatment of hGH
retardation such as constitutional short stature,
in children with GH deficiency were studied and
delayed adolescence, Turner's syndrome and
the correlation between serum somatomdein A
achondroplasia. Thecorrelationsbetweenserum
levels and the growth rate was determined.
Materials and Methods
somatomedin A levels on the one hand and the
This study was composed of 107 patients Who
degree of growth hormone secretion, the severity
of short stature and bone maturation on the other
were refered to the Endocrine Clinic of the
were investigated. Furthermore, serum soma-
Tokyo Women's Medical College for evalua-
tomedin A levels after a single hGH administra-
tion and treatment ofshort stature. Height, bone
Tablel Clinicalan
d laboratory data in patients with short stature
Chron-
ological Bone
Age (CA) Age (BA)
No.
Group I
SD SD
Normal
12 13･3±2rl I3･5±2･8
Subjects
Group II
(yrs) (yrs)
Mean± Mean±
GH
Height
Age (HA)
Somato-･
(yrs)
BA/CA
HAICA
BA/HA
Mean±
Mean±
Mean±
Mean±
SEM
SD
SEM
medin A
(UYml)
Mean±
SEM
SEM
12.5±1.4 1. Ol±O.04
O.94±O.02 1.07±O.04
O.95±O,09
10 13.4±2.5
7.8±3.3
7.3±2.9
O.58±O.06
O.53±O.04 1.08±O.04
O.26±O.03
7 11.6±2.3
9.2±1.9
8,8±1.8
O.76±O.04
O.76±O.02 1.00±O.03
O.48±O.04
Group IV Normal
42 l3.0±2.3 11.3±3.2
9.8±1.9
O.85±O.03
O.75±O.02 1.13±OD4
O.83±O.05
Group V Turner's
28 16.2±3,9 12.2±2.2
9.5±1.7
O.77±O.02
ol6b±o.o2 1.3o±O.03
O.77±O.O'5
O.52±O.05
O.81±O.09
deficiency
Group III Relative GH
deficiency
GH
syndrome
Group VI Achondro-
6.8±3.3
8 13.7±6.9
plasia
Tabie 2 C!inical and la boratory data in patients with GH d
Subject
1
2
3
Sex
M
M
M
Age
Bone Age
(yrs)
Height
(cm)
Body Weight
(yrs)
3
94.0
l4.0
2.4
10
2112
6
107.0
19.0
2.1'
11
8f12
5
105.5
19.5
2.0
6112
6
lll.5
20
1.6
2.7
F
5
F
12 10112
8
9
10
M
M
M
M
M
GH Max*
6112
12
7
'. (kg) '
9
4
6
eficiency
9
1209
25.5
14
12,5
132.5
43.0
1.5
15
5
105.4
17.5
1.7
2.4
15
7/12
10
129.6
34'
15
9/12
9
130.7
40
<O.6
12
145.1
40
1.7
17
*Maximal response of plasma growth hormone
glycemic test or propranolol-glucagon test.
-801-
level after either insulin hypo-
16
age, serum somatomedin A, growth hormone
or their maximum GH levels after insulin-induc-
(GH), thyroxine (T,), triiodothyronine (T,),
ed hypoglycemia were above 5 ng!ml. Growth
follicle stimulating hormone (FSH) and IUteiniz-
hormone reserve was normal in all members of this
ing hormone (LH) were measured. The levels of
group. Most of the patients in this group were
T4 and T3 in these subjects were within the
considered to have constitutional short stature
normal ranges. Patients were divided into 6
and delayed adolescence.
Turner's syndrome (Group V): This group
groups as described in Table 1.
Normal subjects (Group I): This group con-
consisted of 28 girls, aged 6-25 years. They had
sisted of 8 boys and 2 girls, aged 10-17 years,
heights of more than 2 SD below the mean for
Although they visited our clinic for evaluation of
their age. Twenty of these patients had the
short stature, they were within 1 SD of mean
characteristic somatic stigmata of Turner's syn-
height for age as reported by the Japanese
drome: webbed neck, cubitus valgus and me-
Ministry of Health and Welfare. From this
tacarpal signs. These patients had high basal
reason, we chose thi.s.group as tl}g normal control.
plasma FSH and LH levels with a mean of
'
Children
with GH deficiency (Group II):
' consisted of 8 boys and 2 girls aged
This group
respectively, and delayed hyperresponse of LH and
9-17 years. The diagnosis of GH deficiency was
FSH to LH-RH tests which supported the di--
116.7±7.4 (mean±SEM) and 52.5±5.2mlUfml,
established by failure of piasma GH to respond
agnosis of ovarian dysgenesis. Nineteen of these
to both insulin-induced hypoglycemia and pro-
patients were subjected to chromosomal analysis.
pranolol-glucagon tests. They had heights of
The chromosomal constitution of two of them was
more than 3 SD below the mean for their age and
45XO and the others showed various forms of
greatly delayed bone ages. The clinical and
-mosalclsm.
laboratory data for each subjects is shown in
Achondropiasia (Group VI): This group consisted of 4 boys and 4 girls aged 5-26 years.
Table 2.
Children with relative GH deficiency (Group
They had heights of more than 2 SD below the
III); This group consisted of 4 boys and 3
mean for their age with the characteristic somatic
girls aged 8-14 years whose maximum GH levels
stigmata of short limbs, prominent skull vault and
after insulin-induced hypoglycemia were below
saddle nose.
5 nglml but those after propranolol-glucagon tests
Eight children with GH ddiciency (Group II)
which are reported as a strong GH provocation
and two children in Group IV received in-
tests (21), were above 5ng/ml. They had re-
tramuscular iajections of hGH in doses of 100 pg
tarded bone ages and heights of more than 2
per kg of body weight. Five children in Group
SD below thp mean for their age. A relative
II received GH in doses ranging from O.5 mg to
GH deficiency was suggested.
8 mg. Venous blood samples were drawn both
Growth retarded children with normal GH
'
secretion (Group IV): This group consisted of
before and 8-24 hours afte' r hGH iniection for
determination of somatomedin A,
31 boys and 11 girls, aged 8-17 years. They
Eight children with GH deficiency (No. 1, 2,
had heights more than 1 SD below the mean
3,4,7,8,9,10) were treated With O.20-O.55 U/kglw
for their age. Their GH levels determined
hGH for 1-2 years. During each patients' visit
to our clinic one day after the last hGH iajec-
when they visited our clinic were above 5 ng!ml
- 802 -
17
tion, height and serum somatomedin A were de
Student's t-test was used for statistical analysis.
termined. Growth rates were calculated from
Results
height measurements taken at intervals of three
Serum somatomedin A Ievels in normal subjects
months or more. Serum was stored at -200C
(Group I) varied between O.56 and 1.33 Ulml
until used for somatomedin A determination.
Serum somatomedin A was determined by the
with a mean of O.95±O.09 U/ml (mean±SEM).
In children with GH deficiency (Group II),
radioreceptor assay described by Takano et al.
relative GH deficiency (Group III) and normal
(22, 23).The somatomedin A used for labelling
GH (Group IV), serum somatomedin A levels
was purified by Dr. L. Fryklund at Recip Poly-
ranged from O.12 to O.37 with a mean of O.26±
peptide Laboratory, AB Kabi, Stoqkholm. In all
O.03 Ulml, from O.39 to O.69 with a mean of
instances, a symmetrical 4-point design was used
with two diflerent ' volumes of the local reference
O.48±O.04 Ulml and from O.45 to 1.64 with a
mean of O.83 l O.05 Ufml, respectivey (Fig. 1).
serum and of the unknown serum. Pooled serum
frgm two healthy males and two healthy females
1.8
between 20 and 25 years of age was used as an
l.6
arbitrary reference. One unit (U) of somatomedin A is defined here as somatomedin content
E･･ 1,4
in one ml of this pooled serum. The data present-
( I.2
ed are given relative to this local arbitrary unit.
)
.
.
.
:
g
This radioreceptor assay fbr somatomedin A
not on]y measures the polypeptide somatomedin
E e.6
8
'
.--
.
.
el
-IiE-
.
:
i
O,4
..
t
e
.
.
.
.
.
t
..
.
a
somatomedin C (24) and IGF-I and II with
.
e
'
.
.
.
.
･i
.
.
.
.
.
.
.
2 1,o
es
.
:
s
.
i O,8
A but also biologically related polypeptides as
}ISD
.
G
.:
-iE- MEAN
.
.
.
.
l.
･
.
IE-.'
O,2
similar potency (Hall, personal communication).
o
Plasma GH measured by a radioimmunoassay technique using hGH Wilhelmi 51523D as
GROUP
NORMAL
GROUP
!I
GROUP
IIf
GROUP
RELATIVEGH
DEFICiENCY DEFICIENCY
GROUP
TURNER'S
GH
GH
GROUPM
ACHONDROPLASIA
a standard and separating bound and unbound
Fig. 1. Serum somatomedin A levels in normal
labelled GH with dextran-coated charcQal. Com-
subjects (Group I) and growth retarded patients
with GH deficiency (Group II), relative GH de-
mercial radioimmunoassay kits were used to
ficiency (Group III), normal GH (Group IV),
determine serum T4, T,, FSH and LH. The
Turner's syndrome (Group V) and achondroplasia
(Group VI).
GH preparation used for intramuscular administration was highly purified hGH, Crescormon [R],
from AB KabilRecip, Stockholm, Sweden. This
A significant diffbrence in serum somatomedinA
preparation contained 2IU per mg, and was
leve}s was found among the three groups (p<
essentially free from ACTH, FSH, LH, TSH,
O.O05). However, no significant diflk}rence was
vasopression, oxytocin and polymers of GH.
found between the values obtained from Group
Bone age was estimated according to standards
I and IV. Therefore, serqm somatomdein A
of Greulich & Pyle [25]. Correlation coeracients
levels in Group I and IV were plotted according
between serum somatomedin A and other observa-
to chronological age as shown in Fig. 2. There
tions were calculated by the Ieast squares method.
was a slight increase of somatomedin A between
- 803 -
18
N,S.
o
1,6
rr N.S･-
1,4
.
E
) 12
e
(
D
g
fi O.4
.
nlI
.6
e
--
e
r.
.4
et
･
.
e 1-t
s
-t-- .
.e.
.
-o
.
--
.
.
.
e
e
<' 12
.
2
(=
.o
ts
o
a
"
.
.
.
.
.
.
.
.8
i
O.2
.
.
l
.
.
.
.
-
.
ca
o
r N･S･ 7
.
.
! 1,O
2
oE o,g
?
E
8 o.6
.
,
.
.
.
.6
...
..
p4
8 9 10 11 12 13 14 15 l6 17 18
.
.
.
..
..
.
E
.
.
.
.
.
.2
M±ISD
AGE, YEARS
Fig. 2 Relationship between serum somatomedin
A and chronological age in normal subjects (N;
male, M; female) and growth retarded children
with normal GH secretion(e ; male, O ; female).
o
-ISD2-
>-2SD -2SD 2u >-3SD
-3SD
2rm
us Fig.
3 Serum somatomedin A levels in growth
retarded children with normal GH secretion
(Group IV). They divided in3groupsaccor-
the ages of 12 and 15 years, but there was no age
ding to their heights as indicated in the figure.
dependency of somatomedin A tevels in children
NS; not significant.
with normal GH secretion aged between 8 and 17
ranged from O.45 to 1.41, with a mean of O.88±
years.
In Group IV, some children were more than 3
O.09 Ufml. In 18 children whose heights were
SD below the mean heights for their age, but
serum somatomedin A levels were not low and
medin A levels ranged from O.45 to 1.39 with
below -2 SD and above -3 SD, serum somato-
their bone ages were not retarded. The relation-
a mean of O.75±O.07UlmL In 12 children
ship between serum somatomedin A and the
whose heights were below -3 SD, serum somato-
degree of short stature was studied in children
medin A levels ranged from O.55 to 1.64, with a
with normal GH (Group I and IV). The
mean of O.91±O.10 (Fig. 3). There was no
children in Group IV were divided according to
significant diflbrence between serum somato-
their height. Serum somatomedin A in 12 chil-
medin A levels and severity of short stature.
dren, whose heights were below -1 SD and
above -2 SD of the Japanese standard mean,
The relationship between somatomedin A levels
and other parameters was studied in Group IV
Table 3 Correlation coeMcients between serum Somatornedin A (SMA) and
ether parameters in Group IV
SMA
SMA
SMA
SMA
SMA
vs Bone Age
vs Height Age
vs Bone Age/Chronological Age
vs Height Age/Chronological Age
vs Bone Age/Height Age
*P<O.05, **P<O.Ol
n==number
r r== correlation coeMcient
- 804 -
n
r
35
42
O.422*
O.185
O.462**
-O.O164
O.432*
35
42
35
19
(Table 3). A positive correlation was fbund be-
slight increase of somatomedin A was observed.
tween- serum somatomedin A and bone age, the
Maximum somatomedin A values were observed
ratio of bone age to chronological age and the
between 8 and 24 hours, Mean levels of somato-
ratio of bone age to height age. However,
medin A obtained before and maximum values
there was no correlation between serum somato-
after hGH administration in these children were
medin A and height age or the ratio of height
O.39±O.03 Ulml and O.70±O.06 U/ml, respectively. Therewasasignificantdiflbrencebetween
age to chronological age.
The levels of somatomedin A in patients with
these two values (p<O.O05). One child in Group
Turner's syndrome (Group V) and achondro-
IV showed a slight increase (27.9%) in somato-
plasia (Group VI) varied between O.48 and 1.44,
medin A at 16 hours after hGH administration;
with a mean of O.77±O.05 U/ml, and between
however, no increase was observed in the other.
O.49 and 1.20, with a mean of O.81±O.09 U/ml,
Five children in Group II rcceived intramus-
respectively (Fig. 1). These values did not sig-
cular iajection of hGH in doses between O.5
nificantly difler from those found in Goups I
and 8mg (14.7-200 yglKg body weight). In
and IV. In patients with Turner's syndroinc,
each $ubject, serum sQmatornedin A !evels increas-
the retardation of height age was more than that
ed after hGH administration at these doses.
of bone age (Table 1).
The relationship between the dosage of hGH
Human GH (100 @glkg) was administered to
and the maximum level of serum somatomedin
8 children with GH deficiency (Group II) and
A is shown in Fig. 5. In three cases (No. 8,
two children in Group IV (Fig. 4). Increases in
1.2
1.2
-E
X-s -s
aut
E
o
t
g
<" X't.
't
"-- ----"' " 3
si
I O.8 ..･t'" 'Ss. ,9,
O,6
-"--- 16
8 O,4
go.6 ,
2s o,2
4
ulct]
O.4
co
E
=
or
;t l,o ,i,O
:- O.8
lll 1.0 --'-----------.---+----------k 8
o
7
OIO 50 100 500
log Dose of hGH, "glkg
O.2
LLI
co
o
Fig. 5 Relationship between doses of hGE[ and
maximum values of serum somatomedin A after
O 12 24
TIME, HOURS
intramuscular ibjection of hGH in five patients
Fig. 4 Serum somatomedin A levels afte; intramuscular iajection of hGH (100yglkg) in growth
retarded children with normal GH secretion
(e･･･e) and GH deficiency (O-o). Numbers
in the figure are the same as in Table 2.
with hGH deficiency. Numbers in the figure
are the same as in Table 2.
9, 10), a linear dose dependency was noted be-
tween the Iogarithmic doses of hGH and the
serum somatomedin A were found in the 8
maximum levels of serum somatomedin A. It
children with GH deficiency. In 6 out of 8
required about 25-50 yg of hGH per Kg body
patients, the levels of somatomedin A increased
weight to reach a normal level of serum somato-
at 8 hours after hGH administration and increased
medin A.
further afterwards. In one patient (No. 7), a
- 805 -
Eight children in Group II were treated with
20
14
hGH 5mg/W
HEIGHTH
cm
?
l i,o
E O,8 140
Yp
ls-L
.13s ...."JAsv""'R:u.gtAxb.I-a...tiii
!
a O.4
m
E
otr O.2
13e /'
oco
i
E
o
tli-
.
.
.. .
.
. -.-- --.
.
----i
2o 4
b
"- tt
o
.
oe
2
---
.
.
.
y=],lx+2.J
[ =. O,37
o
ee
P<O.Ol
e
o O.1 O.2 O,3 O.4 O.5 O.6 O.7 O,8 O,9 1.0
sOMNOMEDIN A, Ufm[
if
BodyWeighKkg)40 44.S aB 52 55
l5 16 17 18
.
Fig. 8 Correlation between serum somatomedin
Alevels and growth rates in eight patients with
CHRONOLOGICAL AGE, YEARS
Fig.
.
.
g
.- 8
?
or
;=6
b
rf O,6
.
--
;' 10
LN, M
145
.
12
6 The heights and serum somatomedin A
GH deficiency prior to ( O) and during (e)
treatment with hGH in 55 samples.
levels before and during hGH treatment in one
patient with GH deficiency (No. 9).
During hGH treatment, linear growth was ac-
hGH for 1-2 years. The heights and serum
celerated and serum somatomedin A levels in-
somatomedin A levels in one patient (No. 9)
creased. When somatomedin A levels in 55
before and during hGH treatment are shown in
serum samples and growth rate were compared,
Fig. 6. The serum levels of somatomedin A and
a slightly significant correlation (r=O.367, p<
growth rates were plotted fbr each subject (Fig. 7).
O.Ol) was observed (Fig. 8).
CASE3 CAst4
i
CASEI CASE2
t2
t2
le
lo8
8 .;. .,
6i64
4g"
2o 2
lo t2
'2. IZ
Ie l']
6 8.
vi 86 S.
4s 4
1
:
2
-4
GE` e i2 o.4 o.6 D.s i.o D 'o.2 o.4 o.6 o.s i.e
O.2O.4 O.6
O.8 1.0
:-
:
:
CASE7 CASE8
-1
.
O,2 O.4
O.6 C.81,O
O.2 O.4 O.6 O.8 1.0
CASE 9
R; 12
lo.3'
4.12Io :
466
4elst
2･ 2
oo
o
oo
o,2 o.4 o.6 o,s 1.o
12
i
10
i
.8
CASE ID
12
10
e
8
3--5
6
4-
4
6
5
--6
ISI
4
:
e
2
2
e
o
o.2 o.4 e.6 e.s 1.o
o
i
02 OA O.6 O.8 1.0
SERUM SOMIYTOMEDIN A, Ulml
Flg. 7 Relationship between serum somatomedin A levels and growth
patients with GH deficiency prior to (O) and during (o) treatment
in the figure are the same as in Table 2.
-806-
rates in eight individual
with hGH. Case numbers
21
Discussion
cant age-dependency in our subjects between the
Serum somatomedin A levels in children with
age of 8 and 17 years.
short stature.were determined by a radioreceptor
In patients with Turner's syndrome, serum
assayforsomatomedinA. SignificantlyIowIevels
somatomedin A levels were within the normal
of somatomedin A were tbund in children with
range. This findings confirm previous reports
GH deficiency as compared to children with
(14, 23, 27, 32, 33). In patients with achon-
normal GH sccretion. Serum somatomedin A
droplasia, serum somatomedin A levels were also
levels in normal subjects and growth retarded
withinthenormalrange. Thisresultsupportsthe
children with normal GH secretion, Turner's
findings of Horton et al. (34). In children with
syndrome and achondroplasia were within
both Turner's syndrome and achondroplasia,, the
the range for normal adults (N==131) (26).
levels of somatomedin were within the normal
In children with a relative GH deficiency, serum
range. These results suggest that the causes
somatomedin A leve]s were intermediate be-
of short stature may depend on impairment of
tween those in children with GH deficiency and
receptor sites in such cases.
those in children with normai GH secretion.
In patients with GH deficiengy, an increase in
These findings indicate that serum somatomedin
serum somatomedin A was observed at 8-24
is GH dependent and confirm previous reports
hours after intramuscular ibj'ection of hGH.
However, no obvious increase in serum
(19, 23, 27).
In growth-retarded children with normal GH
somatomedin A was found in children with normal
secretion (Group IV), serum somatomedin A
GH secretion. The greater responsiveness in
correlated with the bone age and the ratio of bone
children with GH deficiency than in the others
age to chronological age. These results indicate
may be attributed to lower baseline GH stimu-
that serum somatomedin is related to bone
lation. A linear dose responsiveness was ob-
maturation, and support the findings of Schwalbe
served between the doses of GH iajected and the
et al. (28). Van den Brande (29) reported that
somatomedin A increases in children with GH
serum somatomedin values in short children were
deficiency. A high dosage of hGE[ may be rte-
slightly but significantly lower than those Of
quired to induce a somatomedin A increase in
normal children. However, we did not observe
children with normal GH secretion. In one
that serum somatomdein A values correlated with
patient (No. 7), a slight increase of somatomedin
the severity of short stature as long as GH
A level was fbund. This patient was 15 years
secretion was normal. These findings indicate
old; however his bone age was 5 years and
that a decreased sensitivity of target cells to
body weight was 17.5 kg. Other factors such as
somatomedin may play some role in the causes
nutrition andlor ability of the liver to produce
of short stature. Further study on receptor
somatomedin might be the cause of the low
sites in growth-retarded children with normal GH
response somatomedin to hGH.
secretion is required. It has been reported that
Eight children with GH deficiency were treat-t
serum somatomedin is low at birth and increases
ed for 1 to 2 years with hGH. During treatment
with age until puberty (17, 19, 30, 31). Al-
a Iinear growth was accelerated and serum somato-
though slight increases in somatomedin A were
medin A levels increased. There was a slight
observed at puberty, we did not find any signifi-
but significant correlation between serum soniato-
- 807 -
22
medin A levels and growth rate. This result
confirms the findings reported by Hall and Olin
(16) and D'Ercole et al. (19).
A single determination of plasrna GH at the
3) Hall, K.: Acta Endocrinol (Kbh) Suppl. 163
1-52 (1972)
4).Uthne, K.: Acta Endocrinol (Kbh) Suppl. 175
l-35 (1973) ' ･
5) Van Wyk, J.J,, L.E. Underwood, R,L. Hintz,
S.J. Voina and R.P. Weaver: Recent Prog
basal Ievel in normal children usually is below
Horm Res 30 259-318 (1974)
the sensitivity of the assay of hGH. Therefbre,
6) Jakob, A., C. Hauri and E.R. Frdesch: J
CIin Invest a7 2678-2688 (l968)
they can not be diflerentiated with confidence
from those with GH deficiency by a single GH
determination. For this reason, GH determina- '
7) Rinderknecht, E. and R.E. Humbel: Proc
Natl Acad Sci USA 73 2365-2369 (1976)
8) Chochinov, R.H. and W.H. Daughaday: Diabetes (New York) 25 994-1007 (1976)
tions have been carried out after a provocative
challenge such as the insulin hypogjycemic test,
glucagon-propranolol test or arginine test. In
9) Hall, K.: Acta Endocrinol (Kbh) 63 338-350
(l970)
10) Marghall, R.N., L.E. Underwood, S.J. Veina,
D.B. Foushee and J.J. Van Wyk: J CIin
this study, we observed tb at there were significant-
ly low levels of somatomedin A in children with
Endocrinol Metab 39 283-292 (1974)
11) Ha", K., K. Takano and L. Fryklund: J
GH deficiency and intermediate values in
children with relative G}I deficiency. It has
been reported that there is no obvious diurnal
variation of serum somatomedin (14, 17, 20).
CIin Endocrinol Metab 39 973-976 (1974)
12) Megye,si, K., R. Kahn, J. Roth and P. Gerdern :
J CIin Endocrinol Metab 38 931-934 (l974)
13) Furlanetto, R.W., L.E. Underwood, J.J.Van
Wyk and A. J. D'Ereole: J CIin Invest 60
648-657 (1977)
Other factors such as liver function, nutrition
and other hormone levels are reported as being
14) Daughaday, W.H., W.D. Salmon and F.
Alexander: J CIin EndocrinQl Metab 19 743-
important in the generation of somatomedin (26,
758 (1959)
35-42). Excluding these situations, a single de-
15) Daughaday, W.H. and M.L. Parker: J CIia
useful fbr evaluating the state of GH secretion,
Endocrinol Metab 23 638-650 (1963)
16) Hall, K. and P. Olin: Acta Endocrinol (Kbh)
69 417-433 (1972)
diagnosing GH deficiency and evaluating the
17) Van den Brande, J.L. and M.V.L. Du Cdju:
termination of serum somatomedin A is very
DHEW publication No. (NIH) 71612 98-115
effbct of GH treatment on patients with GH
(1974)
18) Schimpeq R.M. Donnadieu M. Goumelen
deficiency.
Acknewledgementg
I would like to express my sincere gratitude to
Professor Kazuo Shizume ' and Dr. Kazue Takano
for their guidance in this study. I also wouid like to
and F. Girard: Horm Metab Res 6 494--498
(1974)
19) D'Ercole,A.J., L.E.Underwood and J.J. Van
Wyk: J Pediatr 90 375-381 (1977)
20) Ihkano,, K., N. Hizuka, K. Shizume and K.
Hall: Endocrinol Jpn 24 359-365 (1977)
thank my co!leagues at the Tokyo Women's Medical
College fbr their help.
This report was supported by a Research Grant
from the Intractable Diseases Division, Public Health
Bureau, Ministry of Health and Welfare, Japan.
2i) Parks, J.S., J.A. Armhein, V. Vaidya, T.
Moshang, Jr. and A.M. Bongievannft J CIin
Endocrinol Metab 37 85-92 (1973)
22) Takano, K., K. Hall,,L. Fryklund, A.
Holrngren, H. Sievertsson and K. Uthne:
References
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Acta Endocrinol (Kbh) 80 1-18 (t975)
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and H. Sievertsson: Acta Endocrinol (Kbh)
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2) Daughaday, W.H., K. Hall, M.S, Raben, W.D.
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標章長者における血中ソマトメディンA値一特に成長ホルモン欠損症の診断，
成長ホルモン治療時の血中ソマトメディンA値測定の有用性について
東京女子医科大学内科学教室（主任鎮目和夫教授）
大学院学生肥塚直美
ヒ
ヅカ
ナ才
ミ
107名の低身長者の血中ソマトメディンA（SMA）値
命長者においては有意なる増加を認めなかった．この
をradiQreceptor assayにて測定した，10名の成長ホル
際G且欠損症においては，GH投与量と上昇した血中
モン（GH）欠損症及び7名の相対的GH欠損症におい
SMA値の間に用量反応関係を認めた．
’
てSMA値は低く，おのおのの平均は0．26±0．03（平均
更にGH欠損症患者をhGHで治療すると身長は増
±標準誤差），0．48±0・04U／mlであった．42名のGH
加し血中SMAも上昇した．この血中SMA値と成長：率
分泌正常を呈する低身長者，28名のTurner症候群，8
名め軟骨異栄養症においては，血中SMA値は正常範囲
との間に正の相関関係を認めた．
にあった．低身長の程度と血中SMA値との間には有意
く反映しており，hGH治療の対象となる早老の選択に
の相関を認めなかった．
右用であり，またGH治療を評価する上で有用である
ヒトGH（hGH）投与により，GH欠損症の患者では
以上の結果は血中SMAの測定がGH分泌状態をよ
ことを示した．
血中SMA値は有意に増加したが， GH分泌が正常の朝
一809一

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