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Clinical Studies |
Department of Endocrinology and Diabetology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden; and Kolling Institute of Medical Research (R.C.B.), Sydney, Australia
Address all correspondence and requests for reprints to: Dr. Marja Thorén, Department of Endocrinology and Diabetology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Serum levels of IGF-I, ALS, and IGFBP-3 above the normal range were reached in seven, five, and three subjects, respectively, after 12 months of GH therapy. IGF-I and ALS levels, but not IGFBP-3 levels, correlated with the total daily GH dose (r = 0.676; P = 0.001 and r = 0.631; P = 0.003). The mean increase in lean body mass (LBM) measured by dual energy x-ray absorptiometry was 3.0 ± 0.5 kg (P < 0.001). At 12 months, the LBM values were significantly correlated to the IGF-I levels (r = 0.718; P < 0.001), but not to ALS or IGFBP-3 levels. No correlation was found before therapy, and the increase in LBM at 12 months correlated with the IGF-I increase (r = 0.514; P = 0.029) only after exclusion of two nonresponders. Both before and during therapy, LBM was inversely related to IGFBP-1 (r = -0.715; P < 0.004 at 12 months). None of the GH-induced proteins could be used as indicators of body fat changes.
In conclusion, both IGF-I and ALS can be used as indicators to avoid GH excess during replacement therapy, but only IGF-I relates to changes in LBM.
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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GHD during adult life is associated with abnormalities in body composition, i.e. increased fat mass, decreased lean body mass (LBM), and decreased bone mineral density, and these variables improve during GH therapy (8, 9, 10). The individual response to treatment in terms of effects on body composition is to some extent dependent on gender, body mass index (BMI), and age (11). However, even when these variables are taken into account, the interindividual response varies considerably. At present, no GH-dependent serum marker, such as IGF-I, ALS, or IGFBP-3, has been shown to predict long term effects on body composition in adults. The choice of serum markers during GH therapy is dependent on whether the therapeutic goal is the anabolic or lipolytic effects of GH in adults. In children (12, 13), the total IGF-I concentration has been shown to reflect the growth-promoting effect of GH, and the normal age-dependent pattern has been well established using reliable techniques (14). Other GH-dependent factors, such as IGFBP-3 and ALS, have also been suggested as markers (5, 15).
The aims of the present work were to evaluate the effect of GH therapy in GH-deficient (GHD) adults on serum levels of ALS and IGFBP-3 and to reveal whether any of the long term effects on body composition are related to these serum markers. In addition, we studied the effects of GH therapy on insulin-regulated IGFBP-1 and its relation to body composition.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Twenty patients with GHD of various etiologies participated.
Eighteen had panhypopituitarism (Table 1
). All had serum
GH levels below 2 µg/L in a glucagon stimulation test. The two
patients with partial pituitary deficiency as well as all patients with
childhood-onset disease had undergone insulin hypoglycemia with lack of
GH response at the time of diagnosis. In addition, no patient had a GH
value above 0.7 µg/L in samples collected over 24 h at 20-min
intervals using the continuous withdrawal technique, and serum IGF-I
levels were below -2 SD for age in all.
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The first 6-month period of the study was randomized and double blind, with somatotropin vs. placebo. After this initial double blind period, the study was continued as an open study for another 6 or 12 months, ensuring all patients a total GH treatment period of 12 months. Baseline values are those immediately before GH therapy. Serum IGF-I and body composition data in this patient group have been reported previously as part of a larger patient study (11, 16).
Treatment
The recombinant GH used was somatotropin (Genotropin, Pharmacia, Sweden; biopotency, 1 mg = 3 IU). During the first 4 weeks of the first two 6-month periods, the patients injected a volume corresponding to a target dose of 0.125 IU/kg·week divided into seven daily sc injections. The mean actual dose was 0.128 ± 0.003 IU/kg·week. Thereafter, the target dose was 0.25 IU/kg·week for 11 months. However, due to side-effects mainly attributed to water retention, the dose was reduced in seven patients. The mean dose between 2–12 months was 0.23 ± 0.01 IU/kg·week, which resulted in a variation in the total dose/day from 0.7–4.3 IU. The patients injected themselves with an injection pen (Kabipen, Pharmacia) before going to bed at night.
Study protocol
The patients were studied as ambulatory patients. Blood samples were drawn in the morning (0730–0830 am) after an overnight fast. Blood samples for the determination of serum IGF-I and IGFBP-3 were taken before therapy; after 1, 2, 3, 6, 7, 8, and 9 months; and every third month thereafter. Serum insulin and IGFBP-1 were analyzed in samples drawn before and every third month during the study. Serum ALS was assessed in baseline samples and after 1, 3, and 12 months of active treatment.
Assessment of body fat (BF) and LBM was performed before the study and at 6-month intervals during the treatment period.
Assessment of body composition
BF and LBM were determined by dual energy x-ray absorptiometry and performed using a whole body scanner (Lunar DPX-L, Lunar Corp., Madison, WI) according to a standard procedure described previously (17). The coefficient of variation (CV) was 4% for BF and 1.6% for LBM (17).
Total body water (TBW) was measured by bioelectric impedance analysis using BIA 101/S equipment (Akern-RJL, Florence, Italy). A two-compartment model provided by the manufacturer was used for calculation of TBW.
RIAs
IGF-I was determined in serum by RIA after separation of IGFs from IGFBPs by acid-ethanol extraction and cryoprecipitation and with des(1, 2, 3)-IGF-I as radioligand (18) to minimize interference of remaining IGFBPs in the extract. The intra- and interassay CVs were 4% and 11%, respectively. The IGF-I values were age dependent, declining with age. Normal values, based on 247 healthy subjects, aged 20–83 years, showed a geometrical mean concentration of 269 µg/L, with a range of 167–434 µg/L (±2 SD) at 20 yr of age and a mean of 151 µg/L with a range of 94–244 µg/L at 60 yr of age (7). The values for males and females were similar in this normal material. IGF-I values were also expressed as SD scores calculated from the regression line of the values in these 247 healthy adult subjects (7): IGF-I SD score = (10logYobs - 10logYpred)/0.104, where Yobs is the observed value and 10logYpred = 2.555–0.00625 x age.
Serum IGFBP-3 was measured by RIA using a commercially available RIA kit with slight modification (DSL 6700, Diagnostic Systems Laboratories, Webster, TX). The intra- and interassay variations were 4.9% and 7.2%, respectively. Cross-reactivity with IGFBP-1, IGFBP-2, and IGFBP-4 was less than 0.3%. The mean and normal range were 3.6 and 2.1–5.0 mg/L in men and 3.8 and 2.3–5.3 mg/L in women.
ALS was measured in serum using a RIA described by Baxter (19). The between-assay CV was 10.5% at 5.3 mg/L, 5.4% at 24 mg/L, and 6.5% at 57.5 mg/L. The within-assay CV was 3.4% at 5.1 mg/L, 3.3% at 20.8 mg/L and 3.4% at 42.7 mg/L. The normal range of ALS in healthy subjects was 15–34 mg/L.
IGFBP-1 concentrations in serum were determined according to the method of Póvoa et al. (20). The sensitivity of the RIA was 3 µg/L, and the intra- and interassay CVs were 3% and 10%, respectively. The geometrical mean and range of IGFBP-1 were 34 and 12–91 µg/L in healthy subjects, aged 20–66 yr (21).
Insulin was measured using guinea pig antiserum and charcoal addition to separate bound and free insulin (22). The intraassay CV was 5%, and the interassay CV was 10%. The detection limit was 56 pmol/L, and in healthy subjects, fasting values are below 136 pmol/L. The equation for the linear regression line comparing our insulin assay and a commercially available RIA kit (Pharmacia) is: y = 1.16x + 39.9, where x is the commercial RIA, and y is the laboratory RIA (r = 0.98).
Data analysis
Results are presented as the mean ± SEM. Data were analyzed by one-way repeated measures ANOVA followed by Dunnett’s test to determine treatment effects compared to baseline and Student-Newman-Keuls test for pairwise comparison. Correlations between variables were assessed using least square linear regression analysis. Variables with nonnormal distribution, IGFBP-1 and insulin, were log transformed before analysis, because the transformed data more closely approximated a Gaussian distribution. The value of acceptance for statistical significance was set at P < 0.05. For the purpose of calculation, undetectable insulin levels were assigned a value of 56 pmol/L.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Mean IGF-I SD score increased from -7.25 ± 0.60
before treatment to -1.43 ± 0.59, 0.20 ± 0.51, 0.30
± 0.55, and 1.07 ± 0.45 at 1, 3, 6, and 12 months in 20 patients
with GHD given a mean daily GH dose after the first month of 33 mIU/kg
BW, whereas IGF-I levels were unchanged during 6 months of placebo
therapy in 10 of the subjects (37 ± 7 to 36 ± 6.7 µg/L).
Concomitant with the rise in IGF-I, mean IGFBP-3 and ALS levels
increased from low basal values into the normal range (Fig. 1). The mean IGF-I, IGFBP-3, and ALS at 12 months were
significantly higher than those at 3 months (P < 0.05)
despite unchanged or reduced GH dose. The mean percent IGF-I increase
was significantly higher than the percent increase in IGFBP-3 and ALS.
As a consequence, the ratios between the IGF-I and ALS concentrations
or IGF-I and IGFBP-3 concentrations increased 2- to 3-fold during GH
treatment, whereas the ALS and IGFBP-3 ratio did not change
significantly.
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A strong positive correlation was observed between IGF-I and ALS serum
levels both before and during GH therapy, whereas the positive relation
between IGF-I and IGFBP-3 as well as that between ALS and IGFBP-3 found
at baseline were lost during therapy (Fig. 2). IGF-I and
ALS levels after 12 months of GH replacement correlated to the mean
daily GH dose IU/day during 2–12 months of therapy (r = 0.676;
P = 0.001 and r = 0.631; P =
0.003, respectively), but not with the mean daily GH dose per kg BW, as
the target was a constant dose per kg. The correlation coefficient
between the increase in IGF-I and the daily GH dose (r = 0.653;
P = 0.002) did not improve when the GH dose was
corrected for body area (r = 0.665; P = 0.001)
There was no correlation between IGFBP-3 and the GH dose.
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). The inverse correlation between IGFBP-1 and insulin found at
baseline (r = -0.584; P = 0.007) and after 3
months of therapy (r = -0.492; P = 0.028) was no
longer significant at 12 months. In contrast, serum IGFBP-1 and IGF-I,
which were not correlated at baseline, displayed a significant inverse
correlation during treatment (r = -0.716; P <
0.001 and r = -0.872; P < 0.001 at 3 and 12
months, respectively). Similarly, IGFBP-1 and ALS displayed negative
correlations only during treatment (r = -0.690; P
< 0.001 and r = -0.649; P = 0.002 at 3 and 12
months), whereas no relationship was found between IGFBP-1 and IGFBP-3.
During treatment, a moderate positive correlation between IGF-I and
insulin (r = 0.480; P = 0.032) and between ALS and
insulin (r = 0.444; P = 0.050) was found at 3
months. Body composition variables (LBM, BF, and TBW) and their correlations to serum concentrations of IGF-I, ALS, IGFBP-3, IGFBP-1, and insulin
Before therapy, individual LBM, TBW, BF, and BMI, or LBM, BF, and
TBW as a percentage of total body weight, were not correlated to
baseline serum concentrations of IGF-I, ALS, IGFBP-3, or insulin. The
mean reduction of BF was 2.9 ± 0.7 and 2.8 ± 0.7 kg
(P < 0.001) at 6 and 12 months of GH therapy, but the
mean BMI did not change during treatment. The mean increases in TBW
were 2.5 ± 0.5 and 1.8 ± 0.4 kg at 6 and 12 months
(P < 0.001). The concomitant mean increases in LBM
were 2.1 ± 0.4 and 3.0 ± 0.5 kg (P <
0.001). LBM, however, was unchanged in two patients with BMI 36 and 25
kg/m2, who reduced their caloric intake during GH therapy
and lost 4.6 and 9.6 kg, respectively, although all patients were asked
to continue with their usual diet. Despite their caloric reduction, GH
induced a rise in IGF-I, IGFBP-3, and ALS. When these two patients were
excluded, the individual increase in total LBM or LBM related to height
(kilograms per m2) correlated to the increase in IGF-I at
12 months (n = 18; r = 0.514; P = 0.029 and
r = 0.546; P = 0.019, respectively), but not to
changes in ALS or IGFBP-3 levels or in the IGF-I/IGFBP-3 ratio. In
addition, LBM after 12 months of therapy was highly significantly
correlated to the IGF-I level (r = 0.718; P <
0.001; Fig. 3), but not to ALS or IGFBP-3 levels. TBW at
12 months was correlated to IGF-I (r = 0.709; P <
0.001) and ALS (r = 0.448; P = 0.047), but not to
IGFBP-3. The changes in BF did not display any correlations to the
concentrations of or increase in IGF-I, ALS, and IGFBP-3 or the ratio
of IGF-I/IGFBP-3. There was no correlation between the LBM or TBW
increases and the mean daily doses of GH despite the correlation
between IGF-I level and GH dose.
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), and that for LBM related
to body height (kilograms per m2) was -0.778
(P < 0.001), but it was nonsignificant when LBM was
calculated as a percentage of the total body weight. The corresponding
correlation between LBM and insulin at 12 months was 0.620
(P = 0.004), but no correlation was observed under
basal conditions. Similarly, at 12 months TBW correlated to IGFBP-1 (r = -0.745; P < 0.001). Before therapy the correlation coefficient between TBW and IGFBP-1 (r = -0.624; P = 0.003) was opposite that between total body resistance and IGFBP-1 (r = 0.664; P = 0.001). A low inverse correlation was found between BMI and IGFBP-1 both before and during therapy (r = -0.515; P = 0.020, r = -0.530; P = 0.016, and r = -0.560; P = 0.010 at 0, 3, and 12 months, respectively), which could be secondary to the positive correlation between BMI and insulin at 3 and 12 months of therapy (r = 0.825; P < 0.001 and r = 0.618; P = 0.004), although no relation was found at baseline.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Both before and during GH therapy there was a close correlation between serum levels of IGF-I and ALS, which both correlated to the total GH dose. In contrast, IGFBP-3 levels were not correlated with IGF-I, ALS, or GH dose during GH therapy, most likely due to differences in their sources of production and their regulation (23). In the liver, IGF-I and ALS expression in hepatocytes is directly stimulated by GH in vivo, whereas hepatic IGFBP-3 expression in Kupffer cells is secondary to GH-dependent factors derived from hepatocytes (24). It has also been shown that GH administration causes higher expression of IGF-I messenger ribonucleic acid than IGFBP-3 messenger ribonucleic acid in rat liver and kidney (25). Indeed, much of the apparent GH dependency of serum IGFBP-3 might be secondary to its stabilization by ALS, as IGFBP-3 disappears rapidly from the circulation unless it becomes part of a high mol wt complex (26).
As an IGF-I level above +2 SD for age is a useful criterion in the diagnosis of acromegaly, the same criterion has been used to indicate GH excess during replacement therapy in adult GHD patients. The increase in IGF-I and ALS levels, but not in IGFBP-3 levels, correlated to the daily total GH dose. In patients who reached IGF-I levels within ±2 SD of the normal range for age, the mean and range of the daily GH total replacement dose were 2.3 and 0,7- 3.2 IU. After correction for body area, the average daily GH dose of 1.2 IU did not differ from the average GH dose of 1.4 IU reported by de Boer et al. (5) in the young GHD men who reached IGF-I levels within ±2 SD after 6 months of therapy. In our seven patients, who reached IGF-I levels above the normal range, the daily GH doses ranged from 2.0–4.3 IU and overlapped the doses required for normalization of IGF-I. During long term GH therapy, IGF-I seems to be a more sensitive serum marker of GH excess than ALS and IGFBP-3, which is in accordance with the results of de Boer et al. (5).
In the present study the changes in body composition with increases in LBM and TBW and a decrease in BF did not differ from results obtained in previous studies with similar GH doses (10). Quantitative measurement of LBM was used to determine the effects of GH on anabolism and cellular growth. The increase in serum IGF-I during GH therapy has been found to predict the long term growth rate in growth-retarded children, children with GHD, and girls with Turner’s syndrome (12, 13). Of the three GH-induced serum markers evaluated in the present study, only IGF-I correlated to LBM. After 12 months of GH therapy, about 50% of the variation in LBM was explained by the serum IGF-I concentration, although no relation was found before therapy. However, only 30% of the variation in LBM increases was explained by the serum IGF-I increase, and this finding was only observed when the two nonresponders, who reduced their caloric intake drastically, were excluded. This finding may explain why no correlation was found between LBM increase and IGF-I in the multicenter study with 8 nonresponders among 68 GHD patients (11). Therefore, the increase in total IGF-I has limited value as a predictor of anabolic GH effects and can only be used as a serum marker in patients who do not reduce their caloric intake.
The majority of IGF in the circulation is bound in a ternary complex with IGFBP-3 and ALS, and in this form IGF-I cannot leave the circulation. An increased IGF-I/IGFBP-3 or IGF-I/ALS ratio has been supposed to increase the bioavailability of IGF (27, 28, 29). However, this would only be true if the total IGF-I plus IGF-II concentration increases to exceed the IGFBP-3-binding capacity, and this has not been explicitly demonstrated after GH therapy. An inverse correlation has recently been found between free IGF-I and serum IGFBP-1 concentrations, when free IGF-I was determined after ultrafiltration (30, 31). Caloric restriction, which causes a rapid elevation of IGFBP-1 levels, is supposed to further reduce free IGF-I concentration. In this context, the highly significant inverse correlation between individual LBM and IGFBP-1 levels both before and during GH therapy was the most interesting finding in the present study. After 12 months of GH therapy, about 50–60% of the variation in LBM (or in LBM in relation to body height) could be explained by IGFBP-1 levels. Although the causal relation between LBM and IGFBP-1 is not proven in the present study, it seems unlikely that IGFBP-1 is the dependent variable considering the present knowledge about the regulation of hepatic IGFBP-1 expression (32, 33). Furthermore, the increase in LBM during GH therapy did not cause any change in IGFBP-1 levels. The most likely explanation is that IGFBP-1 reduces the bioavailability of IGF-1 and thereby attenuates the anabolic action of IGF-I. The recent findings of an inverse relation between free IGF-I and IGFBP-1 (31) led us to assume that free IGF-I, although not determined in the present study, decreased with increasing IGFBP-1. Further studies are required to confirm and clarify the inverse relation between LBM and IGFBP-1. A larger group of patients is required in multiple regression analyses with several serum markers to explain the wide variation in LBM in GHD adults.
Although TBW after 12 months of therapy was positively related to IGF-I and negatively to IGFBP-1, the basal TBW was only inversely related to IGFBP-1. This lack of correlation between total body resistance and IGF-I under basal conditions is in contrast to the finding by de Boer et al. (34), who showed an inverse correlation between total body resistance and IGF-I levels. This difference in results may be explained by our patients being older and displaying a wider variation in BMI, probably resulting in a larger variation in IGFBP-1. The BF independence of IGF-I or IGFBP-1 during GH therapy was expected, as differentiated adipocytes are lacking IGF-I receptors, and the lipolytic effect of GH is direct and not mediated by IGF-I. In the previous multicenter study, about 10% of the variation in BF decrease could be explained by a decrease in GH-binding protein (11). Therefore, serum markers for the lipolytic effect of GH are still required.
The lack of correlation between the increases in LBM and the daily GH dose is surprising considering that these two variables displayed significant correlations to an increase in IGF-I, which was dependent on GH dose. Only studies with larger number of GHD adults can reveal variables that may predict the effects of GH. The individual response to daily GH injection in GHD adults and the lack of simple and inexpensive measurements of body composition make it necessary to use serum markers to guide the choice of GH dose for normalization of body composition. The total IGF-I level is hitherto the only GH-induced serum marker that correlates to LBM. However, both IGF-I and ALS levels are valuable tools to avoid treatment with GH in excess. The advantage of IGF-I determination is that the age-dependent levels are well established with simple methods, which are not influenced by IGFBPs. As long as only IGF-I or ALS levels are used as serum markers of the effects of GH, the daily GH replacement dose is not related to body weight in adults.
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Acknowledgments |
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Footnotes |
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Received May 22, 1996.
Revised August 29, 1996.
Accepted September 13, 1996.
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References |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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) subunit of the high molecular
weight insulin-like growth factor binding protein complex. J Clin
Endocrinol Metab. 70:1347–1353.This article has been cited by other articles:
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  T. Munzer, C. J. Rosen, S.M. Harman, K. M. Pabst, C. St. Clair, J. D. Sorkin, and M. R. Blackman Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E1006 - E1013. [Abstract] [Full Text] [PDF]
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 A. Mukherjee, J. E Adams, L. Smethurst, and S. M Shalet Interdependence of lean body mass and total body water, but not quality of life measures, during low dose GH replacement in GH-deficient adults Eur. J. Endocrinol., November 1, 2005; 153(5): 661 - 668. [Abstract] [Full Text] [PDF]
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 W. M. Drake, S. J. Howell, J. P. Monson, and S. M. Shalet Optimizing GH Therapy in Adults and Children Endocr. Rev., August 1, 2001; 22(4): 425 - 450. [Abstract] [Full Text] [PDF]
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 P. Marzullo, C. Di Somma, K. L. Pratt, J. Khosravi, A. Diamandis, G. Lombardi, A. Colao, and R. G. Rosenfeld Usefulness of Different Biochemical Markers of the Insulin-Like Growth Factor (IGF) Family in Diagnosing Growth Hormone Excess and Deficiency in Adults J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3001 - 3008. [Abstract] [Full Text] [PDF]
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 B. C. Nindl, W. J. Kraemer, J. O. Marx, P. J. Arciero, K. Dohi, M. D. Kellogg, and G. A. Loomis Overnight responses of the circulating IGF-I system after acute, heavy-resistance exercise J Appl Physiol, April 1, 2001; 90(4): 1319 - 1326. [Abstract] [Full Text] [PDF]
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M. Arosio, S. Garrone, P. Bruzzi, G. Faglia, F. Minuto, and A. Barreca Diagnostic Value of the Acid-Labile Subunit in Acromegaly: Evaluation in Comparison with Insulin-Like Growth Factor (IGF) I, and IGF-Binding Protein-1, -2, and -3 J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1091 - 1098. [Abstract] [Full Text]
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J. Khosravi, A. Diamandi, J. Mistry, and R. G. Krishna The High Molecular Weight Insulin-Like Growth Factor-Binding Protein Complex: Epitope Mapping, Immunoassay, and Preliminary Clinical Evaluation J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2826 - 2833. [Abstract] [Full Text]
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A. Hilding, K. Hall, I.-L. Wivall-Helleryd, M. Sääf, A.-L. Melin, and M. Thorén Serum Levels of Insulin-Like Growth Factor I in 152 Patients with Growth Hormone Deficiency, Aged 19-82 Years, in Relation to Those in Healthy Subjects J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2013 - 2019. [Abstract] [Full Text]
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|
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H. Olivecrona, A. Hilding, C. Ekström, H. Barle, B. Nyberg, C. Möller, P. J. Delhanty, R. C. Baxter, B. Angelin, T. J. Ekström, et al. Acute and Short-Term Effects of Growth Hormone on Insulin-Like Growth Factors and Their Binding Proteins: Serum Levels and Hepatic Messenger Ribonucleic Acid Responses in Humans J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 553 - 560. [Abstract] [Full Text]
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A. Juul, S. Møller, E. Mosfeldt-Laursen, M. H. Rasmussen, T. Scheike, S. A. Pedersen, K. W. Kastrup, H. Yu, J. Mistry, S. Rasmussen, et al. The Acid-Labile Subunit of Human Ternary Insulin-Like Growth Factor Binding Protein Complex in Serum: Hepatosplanchnic Release, Diurnal Variation, Circulating Concentrations in Healthy Subjects, and Diagnostic Use in Patients with Growth Hormone Deficiency J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4408 - 4415. [Abstract] [Full Text]
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 J. Frystyk, H. Gronbak, C. Skjarbak, A. Flyvbjerg, H. Orskov, and R. C. Baxter Developmental Changes in Serum Levels of Free and Total Insulin-Like Growth Factor I (IGF-I), IGF-Binding Protein-1 and -3, and the Acid-Labile Subunit in Rats Endocrinology, October 1, 1998; 139(10): 4286 - 4292. [Abstract] [Full Text] [PDF]
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R. C. Baxter The Binding Protein's Binding Protein-- Clinical Applications of Acid-Labile Subunit (ALS) Measurement J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 3941 - 3943. [Full Text] [PDF]
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