| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Neuroendocrine Unit (M.M., K.K.M., K.R., A.A., C.A., A.K.), and Eating Disorders Unit (D.B.H.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Pediatric Endocrine Unit (M.M.), Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts 02114; Core Laboratory (G.N.), General Clinical Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114; and Core Laboratory (J.B.), General Clinical Research Center, Massachusetts Institute of Technology, Boston, Massachusetts 02142
Address all correspondence and requests for reprints to: Anne Klibanski, M.D., BUL 457B, Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114. E-mail: aklibanski{at}partners.org.
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
At 0 min (0') of the oral glucose tolerance test, girls with AN had significantly lower levels of glucose (P = 0.009) and higher levels of GH (P = 0.04) than controls. Nadir GH values were higher in AN than in controls (2.0 ± 1.8 vs. 0.5 ± 0.5 ng/ml, P = 0.001). Only 31.6% of girls with AN suppressed their GH values to 1 ng/ml or less vs. 85.0% of healthy adolescents (P = 0.0005). All healthy controls had nadir postglucose GH values of 2 ng/ml or less. Nadir GH concentrations during the oral glucose tolerance test correlated directly with all measures of GH secretion [basal (r = 0.37, P = 0.02), pulsatile (r = 0.56, P = 0.0002), and total (r = 0.57, P = 0.0002)]. Adolescent girls who did not suppress their GH values to 1 ng/ml or less had significantly higher levels of ghrelin at 0', 30', and 60' (P = 0.02, 0.004, and 0.008), significantly higher GH at 0' (P = 0.001), and higher nocturnal basal (P = 0.002), pulsatile (P = 0.05), and total GH secretion (P = 0.03) than those who did suppress below this level. Ghrelin values were higher in AN than in controls at each time point (P = 0.02, 0.0002, and 0.01 at 0', 30', and 60') but did not predict GH values at these time points.
Adolescent girls with AN fail to adequately suppress their GH values after a 100-g oral glucose load. This lack of suppression may be related to the higher GH secretion seen in adolescents with this disorder. In contrast, all healthy adolescents suppress their GH values to 2 ng/ml or less but not 1 ng/ml or less after a glucose load. Although ghrelin values are higher in AN than in controls, we could not demonstrate a relationship between ghrelin and GH values. The inability of healthy girls to uniformly suppress GH levels to 1 ng/ml or less, a normal level defined for adults, may be related to higher GH secretion in the pubertal years, compared with adult life. Further studies are needed to define GH suppression in an adolescent population.
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
In this pilot study, we examined the suppression of GH values with a 100-g oral glucose load in girls with AN and in healthy controls of similar bone age and chronological age. We also examined levels of ghrelin, a GH secretagogue, in our patients to investigate glucose regulation of ghrelin and relationship to GH secretion. Previous studies demonstrated elevated levels of ghrelin in adult women with AN, compared with healthy controls, and higher ghrelin values during an OGTT in an adult group with AN (17, 18, 19, 20, 21, 22, 23). Whereas we have shown that low IGF-I levels predict high GH levels in adolescents with AN (1), it is uncertain whether high ghrelin values also contribute to the high GH levels seen in this disorder. In addition, to our knowledge, ghrelin values in adolescent girls with AN and effects of an oral glucose load on ghrelin values in this younger population have not been reported.
We hypothesized that girls with AN would not suppress their GH values adequately with this oral glucose load, as opposed to healthy adolescents, who would demonstrate adequate suppression. We also hypothesized that ghrelin values would be higher in AN than in healthy adolescents and would predict higher GH levels at different time points after oral glucose administration. In addition, to determine factors that regulate suppression after oral glucose, we examined clinical, anthropometric and hormonal characteristics of adolescents who do suppress with oral glucose vs. those who do not.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
We enrolled 19 adolescent girls with AN diagnosed by DSM-IV criteria and 20 healthy controls of comparable age in the study. Demographic and baseline hormonal data on the 19 girls with AN and 19 controls have been reported previously (1). Subjects were Caucasian and ranged in age from 12.2 to 18.8 yr. The duration since diagnosis of AN ranged from 1 to 36 months. Girls with AN had a body mass index (BMI) ranging from 14.6 to 20.5 kg/m2, whereas in healthy adolescent girls the BMI ranged from 16.8 to 28.0 kg/m2, between the 14th and 95th percentiles for age (24). Only two of the 19 girls with AN had a BMI greater than 18 kg/m2 and were included in the study because of evidence of marked ongoing weight loss from a previously robust weight, amenorrhea of more than 3 months duration, and the body image issues associated with AN. Girls with AN were primarily of the restrictive subtype. Only two AN subjects had history of very occasional bulimic behavior. None of the healthy controls had any history of eating disorders or significant dieting behavior, which was an exclusion criterion for the study. Four girls with AN had not attained menarche, and 15 had secondary amenorrhea. Four controls were premenarchal. We recruited girls with AN through referrals from primary care providers, nutritionists, psychiatrists, and therapists and also from in-patient and day-treatment eating disorder programs in Massachusetts, New Hampshire, and Maine. For recruitment of healthy controls, we used mass mailings to primary care providers and advertisements in community newspapers and also within hospitals in the Partners HealthCare network. All subjects with AN were enrolled in integrated eating disorder programs at study initiation. The Institutional Review Board of the Partners Health Care system approved the study, and informed assent and consent were obtained from all subjects and their parents.
Experimental protocol
Subjects underwent a screening visit at the General Clinical Research Center (GCRC) of Massachusetts General Hospital, which included a history, physical examination, and screening laboratory tests (TSH, FSH, LH, prolactin, hematocrit, potassium and glucose). TSH, FSH, LH, and prolactin within the normal range, a hematocrit greater than 30%, potassium greater than 3 mmol/liter, and glucose greater than 50 mg/dl were necessary for study participation.
Eligible subjects were admitted overnight to the GCRC. A bone age was obtained on the day of admission. Subjects were served dinner before 1930 h. Frequent sampling for GH and cortisol was carried out every 30 min from 2000 h on the night of admission until 0800 h the next morning. After frequent sampling, a fasting blood sample was obtained for glucose, GH, ghrelin, IGF-I, and leptin. Subjects then drank a solution containing 100 g glucose over 10 min. Blood samples for glucose and GH were drawn at 30 and 60 min after the oral glucose load. A 24-h urine sample was collected for urinary free cortisol and creatinine.
Methods
Anthropometric measurements. Subjects were weighed wearing a hospital gown on an electronic scale. We used a single stadiometer at the GCRC to measure heights of subjects using an average of triplicate measurements. One investigator assessed bone age using the methods of Greulich and Pyle (25). Tanner stage was determined for all patients by the same investigator, a pediatric endocrinologist.
Biochemical assessment. Glucose and urine creatinine were measured by the hospital laboratory using published methods (26). Glucose levels may be converted to SI units (millimoles per liter) by dividing by 18. We measured GH levels using an IRMA (Nichols Institute Diagnostics, San Juan Capistrano, CA; detection limit of 0.05 ng/ml and an intraassay coefficient of variation of 2.4–9.4%). An IRMA (Nichols Institute Diagnostics) was used to measure serum IGF-I (detection limit of 30 µg/liter and coefficient of variation 3.1–4.6%). Urinary free cortisol was measured by the GammaCoat I125 RIA (Diasorin Inc., Stillwater, MN, detection limit of 1 µg/dl, coefficient of variation of 7.0%) using the extraction method. We used a RIA to measure serum cortisol values (Diagnostic Products Corp., Los Angeles, CA, limit of sensitivity 1.0 µg/dl, coefficient of variation 2.5–4.1%), serum leptin (Linco Diagnostics, St. Louis, MO, sensitivity of 0.5 µg/liter, coefficient of variation of 3.4–8.3%), and ghrelin (Phoenix Pharmaceuticals, Belmont, CA, sensitivity 2 pg/ml, coefficient of variation 10.0%). Levels of GH, IGF-I, and leptin can be converted to SI units (micrograms per liter) by multiplying by 1, whereas cortisol values can be converted to SI units (nanomoles per liter) by dividing by 0.0363. Samples were stored at –80 C until analysis, and all samples were run in duplicate.
Analysis of GH secretion
Deconvolutional analysis. The multiple parameter deconvolutional analysis described by Veldhuis et al. (27) and Veldhuis and Johnson (28) was employed to uncover individual secretory bursts during the 12 h of nocturnal sampling. Basal GH secretion rate, total basal GH secretion (basal GH secretion rate x duration of sampling), GH half-life, frequency of secretion bursts, area under secretion bursts (burst mass), secretory burst amplitude, total pulsatile production (mean burst mass x number of secretory bursts), and total GH secretion (sum of basal and pulsatile secretion) were determined using this analysis. Results of nocturnal basal, pulsatile and total GH secretion, and the number of nocturnal secretory bursts are reported here. Details of data obtained from deconvolutional analysis have been reported earlier by our group (1).
Approximate entropy (ApEn). The orderliness of GH secretion was determined using ApEn. This score increases in magnitude as the secretory pattern becomes more disorderly (2).
Body composition
Measurements of fat mass and lean body mass were obtained from whole-body dual-energy x-ray absorptiometry, which has been validated for body composition measurements (29, 30). The precision error (SD) of dual-energy x-ray absorptiometry is reported to be 425 g for whole-body fat and fat-free mass (29), with a correlation of 0.99 with a four compartment model body composition method for measuring fat-free mass, and 0.93–0.97 with multislice computed tomography for measuring regional fat-free mass (30).
Statistical methods
Data are described as mean ± SD. Version 4 of the JMP program (SAS Institute, Cary, NC) was used for statistical analysis. We used the Student t test to calculate differences between means. For data that did not have a normal distribution, we used the Wilcoxon’s rank sum test to determine significant differences. Correlational and multiple regression analyses were used to determine predictors of GH and ghrelin concentrations during the OGTT. A 
2 test was used to determine significant differences between proportions.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Clinical characteristics for girls with AN and healthy adolescents are summarized in Table 1
. The groups did not differ in chronological, bone age, or Tanner stage. Mean duration since diagnosis of AN was 7.0 ± 8.2 months and mean duration of amenorrhea was 4.2 ± 3.5 months. Girls with AN had significantly lower weight, BMI, and fat mass, compared with controls, whereas lean body mass was comparable in the two groups. Girls with AN had higher mean nocturnal serum cortisol values than healthy adolescent girls, and urine free cortisol values standardized for creatinine trended higher in AN. Levels of leptin and IGF-I were markedly lower in girls with AN, compared with controls. Mean GH values over 12 h of nocturnal sampling were higher in AN than in healthy subjects. Girls with AN had higher basal, pulsatile, and total GH secretion, with a larger number of secretory bursts over the 12-h sampling period (data previously reported) (1).
|
Glucose.
In the 1-h OGTT (Table 2 and Fig. 1), baseline values of glucose were significantly lower in girls with AN than in healthy adolescents [79.2 ± 9.1 vs. 85.8 ± 5.3 mg/dl (4.4 ± 0.5 vs. 4.8 ± 0.3 mmol/liter), P = 0.009]. Mean glucose values were highest at 30' in healthy controls [140.5 ± 25.6 mg/dl (7.8 ± 1.4 mmol/liter)] and did not differ from mean glucose values in AN [140.2 ± 22.4 mg/dl (7.8 ± 1.2 mmol/liter)] at this time point. At 60', glucose levels decreased in controls [123.5 ± 43.2 g/dl (6.9 ± 2.4 mmol/liter)] but remained about the same as at 30' of the OGTT in AN [141.6 ± 45.0 g/dl (7.9 ± 2.5 mmol/liter)].
|
|
). The upper limit for nadir GH concentration during the OGTT in healthy adolescents was 1.5 ng/ml, lower than the mean nadir GH concentration in AN. The mean change in glucose values over the 1-h OGTT was 63 ± 47 mg/dl (3.5 ± 2.6 mmol/liter) in AN vs. 38 ± 41 mg/dl (2.1 ± 2.3 mmol/liter) in controls (P = 0.09). Despite the greater increase in glucose levels in AN, the change in GH levels was not different between the groups (–2.1 ± 6.1 ng/ml in AN vs. –2.0 ± 4.3 ng/ml in controls, P = NS).
|
). Both girls with AN with BMIs above 18 kg/m2 failed to suppress their GH values to less than 1 ng/ml. The BMIs of the healthy controls who failed to suppress less than 1 ng/ml were 19.1, 23.7, and 28 kg/m2.
|
GH levels below the limit of assay sensitivity were noted in one control at 30' and in another control at 60' of the OGTT. A value of 0.05 ng/ml (limit of sensitivity of IRMA used in this study) was assigned to these two GH levels. All other subjects had GH levels above the limit of assay sensitivity.
Ghrelin.
Ghrelin values were significantly higher in girls with AN than in healthy controls at 0' (763 ± 210 vs. 599 ± 208 pg/ml, P = 0.02) and remained significantly higher at 30' (729 ± 267 vs. 447 ± 145 pg/ml, P = 0.0002) and 60' (637 ± 208 vs. 476 ± 181 pg/ml, P = 0.01) (Table 2
and Fig. 1). The 30' ghrelin value was higher than the 0' value in two of 20 controls, and seven of 19 AN. The 60' ghrelin value was higher than the 0' value in six of 19 controls and four of 19 AN. Ghrelin levels in controls suppressed significantly with oral glucose (nadir ghrelin values 411 ± 150 vs. 0' ghrelin values of 599 ± 208 pg/ml, P = 0.002). In girls with AN, similarly, nadir ghrelin values were significantly lower than 0' values (580 ± 166 vs. 763 ± 210 pg/ml, P = 0.005). However, the mean nadir ghrelin value was significantly higher in AN than in controls (580 ± 166 vs. 411 ± 150 pg/ml, P = 0.002) (Fig. 2).
The mean + 2 SD value of nadir ghrelin during the OGTT was 711 pg/ml for controls. Six of the 19 girls with AN had nadir ghrelin values that were greater than 711 pg/ml. The extent of ghrelin suppression with oral glucose (baseline ghrelin-nadir ghrelin), however, did not differ between the two groups (183 ± 135 pg/ml in AN vs. 188 ± 176 pg/ml in controls, P = NS), nor did the percent decrease in ghrelin levels (–22.8 ± 14.3% in AN vs. –27.2 ± 22.6% in controls, P = NS). The nadir ghrelin value correlated strongly with 0' ghrelin levels (r = 0.72, P < 0.0001).
Factors contributing to lack of GH suppression after oral glucose
To investigate the factors contributing to a lack of GH suppression with oral glucose, we compared AN subjects and controls whose nadir GH values during the OGTT were below the adult limit signifying adequate suppression (
1 ng/ml) (suppressed group: n = 23) with those whose GH values did not suppress below this level (nonsuppressed group: n = 16) (Table 3).
|
). Table 3 also shows hormone levels in the two groups. Serum cortisol levels were significantly higher in the nonsuppressed group, although 24-h urinary free cortisol values did not differ between the groups. No correlation was observed between serum or urinary cortisol levels and nadir GH after the glucose load. Levels of IGF-I trended lower in the nonsuppressed group, whereas leptin levels were significantly lower and ghrelin levels significantly higher in this group, compared with the suppressed group. The nonsuppressed group had lower glucose levels and higher GH levels at 0' than the group that suppressed adequately with oral glucose. The nonsuppressed group also had higher nocturnal basal, pulsatile, and total GH secretion and a larger number of secretory bursts than the suppressed group. ApEn was higher in the group that did not suppress its GH values less than 1 ng/ml on the OGTT. The three healthy adolescent girls who did not suppress their GH values to 1 ng/ml or less all had 0' GH values that were above 4.5 ng/ml (19.4, 5.3, and 4.7 ng/ml). In contrast, only one healthy adolescent who suppressed to 1 ng/ml or less had a 0' GH value greater than 4.5 ng/ml (9.5 ng/ml). Other GH concentration and secretion characteristics did not differ in the healthy girls who did not suppress less than 1 ng/ml vs. those who did.
Relationship between nadir and 0' GH concentration during the OGTT and body composition and hormonal parameters (AN and controls)
Nadir GH concentrations during the OGTT correlated weakly and inversely with BMI (r = –0.29, P = 0.08) and percent body fat (r = –0.30, P = 0.07). Strong inverse correlations were observed between nadir GH concentrations during the OGTT and 0' glucose levels, (r = –0.57, P = 0.0001), whereas positive correlations were observed with all measures of GH including 0' GH levels (r = 0.52, P = 0.0006), mean nocturnal GH concentration (r = 0.54, P = 0.0004), nocturnal basal GH secretion (r = 0.37, P = 0.02), nocturnal pulsatile GH secretion (r = 0.56, P = 0.0002), total nocturnal GH secretion (r = 0.57, P = 0.0002), and number of nocturnal secretory bursts (r = 0.51, P = 0.001). Nadir GH correlated inversely with IGF-I (r = –0.33, P = 0.04) and leptin levels (r = –0.39, P = 0.01). No correlation was noted between nadir GH concentration and values of ghrelin. Subjects with higher GH secretion and concentration thus had a higher nadir level during the OGTT.
On stepwise regression analysis including 0'GH value, basal, pulsatile, and total GH secretion, total GH secretion accounted for 32.5% of the variability of nadir GH concentration, and the 0' GH value accounted for an additional 11.3% of the variability. When total secretion was excluded from the analysis, pulsatile secretion accounted for 30.8% of the variability and 0'GH for 11.4% of the variability. On stepwise regression analysis including BMI, fat mass, nocturnal GH basal, and pulsatile secretion and 0' GH values, BMI and fat mass were no longer significant predictors of nadir GH concentration.
GH values at 0' of the OGTT correlated inversely with glucose levels (r = –0.31, P = 0.05) and positively with mean nocturnal GH concentration (r = 0.29, P = 0.08), pulsatile GH secretion (r = 0.38, P = 0.02), and total nocturnal GH secretion (r = –0.38, P = 0.02). No relationship was observed between the 0' GH value and measures of body composition (BMI, fat mass, lean body mass, or percent fat mass) or with leptin, ghrelin, IGF-I, or cortisol. Conversely, measures of nocturnal GH secretion and mean nocturnal GH concentration correlated inversely with BMI, fat mass, percent fat mass, and leptin. Basal GH secretion correlated weakly with IGF-I (data not reported).
Relationship between ghrelin values during the OGTT and body composition and hormonal parameters (AN and controls)
Ghrelin correlated inversely with fasting leptin at 0' (r = –0.28, P = 0.08), 30' (r = –0.40, P = 0.0007), and 60' (r = –0.31, P = 0.05). No correlation was noted between corresponding values of ghrelin and GH, or ghrelin and glucose, during the OGTT. The 30' ghrelin value correlated inversely with IGF-I levels (r = –0.36, P = 0.03) and positively with mean GH concentration (r = 0.40, P = 0.01), nocturnal basal GH secretion (r = 0.35, P = 0.03), and number of secretory bursts (r = 0.30, P = 0.06). In addition, the 30' ghrelin value correlated positively with chronological age (r = 0.35, P = 0.03) and inversely with BMI (r = –0.38, P = 0.02), fat mass (r = –0.39, 0.02), and percent fat mass (r = –0.39, P = 0.02). These correlations were not observed with the 0' (fasting) ghrelin value. The 60' ghrelin value correlated inversely with mean GH concentration (r = 0.60, P = 0.0001) but not with other hormonal parameters. Nadir ghrelin levels correlated inversely with IGF-I levels (r = –0.36, P = 0.02) and also correlated weakly with BMI (r = –0.30, P = 0.07).
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
High ghrelin levels have been reported in adult women with AN (17, 18, 19, 20, 21, 22, 23), and similar to the adult studies, we found elevated ghrelin levels in adolescent girls with AN, compared with healthy controls. Nakai et al. (17) reported significant decreases in ghrelin values after a 75-g oral glucose load in adult women with AN. In our study, ghrelin values did decrease in AN after glucose administration but remained significantly higher than in controls at each time point, and nadir ghrelin values were higher in AN than in controls, suggesting inadequate suppression of ghrelin secretion with oral glucose in AN. However, nadir ghrelin concentrations were significantly lower than baseline ghrelin values in both groups; the extent of ghrelin suppression (baseline-nadir ghrelin values) with oral glucose did not differ between the groups, and nadir ghrelin concentration correlated strongly with baseline ghrelin values. This suggests that higher nadir ghrelin levels in AN were a consequence of higher baseline ghrelin values in this group.
Although ghrelin has been demonstrated to be a GH secretagogue (31), we did not find any relationship between ghrelin and GH values at corresponding time points (0', 30', or 60'). Whereas fasting ghrelin values did not correlate with mean nocturnal GH concentration, the 30' and 60' ghrelin values did, suggesting that possibly fed state ghrelin levels rather than fasting ghrelin levels reflect GH secretory capacity of ghrelin. However, further studies such as frequent nocturnal sampling for ghrelin levels need to be performed to more conclusively determine whether elevated ghrelin levels in AN drive the higher GH values noted during frequent sampling in this population (1). It is also interesting that the 30' ghrelin value correlated with BMI and fat mass, but the 0' ghrelin level did not. Similar to data reported by Tolle et al. (23) in adults, inverse correlations were noted between ghrelin and leptin. Of note, we measured total ghrelin in our subjects, and the significance of total vs. bioactive ghrelin in this population is unknown.
Girls with AN have increased GH secretion and behave like subjects with acromegaly in that their GH concentrations do not suppress adequately with oral glucose (10, 32). Higher 24-h basal GH concentrations with increased number of secretory bursts have been demonstrated in acromegaly (33, 34, 35). Recently Dimaraki et al. (32) demonstrated higher nadir and 24-h trough GH concentrations in adults with acromegaly by cluster analysis. In their study, nadir GH concentrations after the glucose load correlated with the 24-h trough GH levels. Our data likewise show a direct relationship between the postglucose GH nadir and the basal 12-h nocturnal GH secretion on deconvolutional analysis, suggesting that higher levels of GH secretion are associated with less complete suppression after oral glucose. The difference from acromegaly lies in IGF-I levels. Whereas IGF-I levels are elevated in acromegaly, they are very low in AN. In contrast to AN, GH secretion in obesity is suppressed and concentrations of GH are low (36). Suppression of GH levels to values below those observed in healthy adults would be expected given this suppression in GH secretion. However, studies have reported a lack of suppression of GH with oral glucose in obesity (37, 38).
It would have been useful to compare girls with AN whose GH values suppress adequately with an oral glucose load with healthy adolescents to determine whether these groups differ in their clinical characteristics. Because only six of our AN subjects suppressed their GH values adequately after oral glucose administration, our study was not sufficiently powered for such a comparison. A larger study is necessary to address this question.
Tamai et al. (39) performed an iv glucose tolerance test in adults with AN and controls and reported no difference in glucose levels at baseline. A paradoxical increase in GH levels after oral glucose was also reported. Our data differ in that our patients had lower glucose concentrations at the onset of the glucose tolerance test, with higher GH levels than in controls. No paradoxical increase in mean GH values at 30' was observed in girls with AN (as a group) after the oral glucose load. Only two controls and four girls with AN had 30' GH values that were higher than at baseline.
Given that this was a pilot study lasting only an hour, it is uncertain whether a longer period of testing would have resulted in lower mean nadir GH concentrations in the two groups. However, because glucose levels had declined at 60' in controls, compared with the 30' time point, and leveled off in girls with AN, it would be expected that near maximal GH suppression had been achieved even at 60'. This can be confirmed, however, only with a longer OGTT. In the study by Chapman et al. (40), women achieved nadir GH concentrations during an OGTT at a mean of 65 min after glucose administration, suggesting that values obtained over 60' may be adequate in women. In addition, in a study of tall, healthy children, eight of the 10 reported subjects achieved nadir or near nadir GH concentrations at 60' of an OGTT (41). These data suggest that, at least in healthy adolescents, near maximal GH suppression is achieved by 60 min.
In healthy controls, the lack of adequate GH suppression in 15% of the girls is consistent with higher GH levels seen in adolescents, compared with adults (12, 13). However, contrary to a recent review (15), the cut-off for GH suppression after the oral glucose load was lower in this study than the reported gold standard in children of 5 ng/ml. The upper limit for nadir GH concentrations in healthy adolescents was 1.5 ng/ml, and all controls suppressed to 2 ng/ml or less. This level of GH suppression was greater than that reported in normal tall children by Holl et al. (16), despite a longer period of testing on the OGTT in the latter study. Greater suppression in this study may be consequent to improved assay sensitivity of currently used IRMAs, compared with older RIAs, and a higher administered glucose load (100 g vs. 75 g) and possibly higher GH values in tall children. Moreover, the 100-g glucose load is the standard for assessing GH suppression vs. the 75-g glucose load, which is the standard for determining glucose tolerance. Postulated mechanisms whereby oral glucose suppresses GH secretion include a decrease in response of pituitary somatotropes to GHRH release or an increase in somatostatin secretion.
Adolescent girls with AN have higher basal, pulsatile, total GH secretion, and higher ghrelin levels than healthy adolescents, and also fail to suppress adequately after an oral glucose load. GH suppressibility with glucose varies directly with basal GH values and GH secretion indices. Healthy adolescents suppress their GH values less than adults, possibly because of higher GH secretion in adolescence. However, healthy pubertal girls suppress their GH values to 1.5 ng/ml or less with 100-g oral glucose. A longer period of testing will be useful in confirming these findings. In addition, overnight frequent sampling for ghrelin and GH simultaneously will be useful in determining the contribution of elevated ghrelin levels to the high GH secretion observed in AN.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Results from this work were presented in part at the 85th Annual Meeting of The Endocrine Society, Philadelphia, Pennsylvania, June 2003.
Abbreviations: AN, Anorexia nervosa; ApEn, approximate entropy; BMI, body mass index; IRMA, immunoradiometric assay; OGTT, oral glucose tolerance test.
Received October 27, 2003.
Accepted January 8, 2004.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  A. C Prince, S. J Brooks, D. Stahl, and J. Treasure Systematic review and meta-analysis of the baseline concentrations and physiologic responses of gut hormones to food in eating disorders Am. J. Clinical Nutrition, March 1, 2009; 89(3): 755 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Misra, J. Cord, R. Prabhakaran, K. K. Miller, and A. Klibanski Growth Hormone Suppression after an Oral Glucose Load in Children J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4623 - 4629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Misra, P. Tsai, E. J Anderson, J. L Hubbard, K. Gallagher, L. A Soyka, K. K Miller, D. B Herzog, and A. Klibanski Nutrient intake in community-dwelling adolescent girls with anorexia nervosa and in healthy adolescents. Am. J. Clinical Nutrition, October 1, 2006; 84(4): 698 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Tritos and E. G. Kokkotou The Physiology and Potential Clinical Applications of Ghrelin, a Novel Peptide Hormone Mayo Clin. Proc., May 1, 2006; 81(5): 653 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Misra, K. K. Miller, P. Tsai, K. Gallagher, A. Lin, N. Lee, D. B. Herzog, and A. Klibanski Elevated Peptide YY Levels in Adolescent Girls with Anorexia Nervosa J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1027 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Misra, K. K. Miller, V. Stewart, E. Hunter, K. Kuo, D. B. Herzog, and A. Klibanski Ghrelin and Bone Metabolism in Adolescent Girls with Anorexia Nervosa and Healthy Adolescents J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5082 - 5087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Misra, K. K. Miller, K. Kuo, K. Griffin, V. Stewart, E. Hunter, D. B. Herzog, and A. Klibanski Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents Am J Physiol Endocrinol Metab, August 1, 2005; 289(2): E347 - E356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Jaakkola, T. Kuusela, T. Jartti, U. Pesonen, M. Koulu, T. Vahlberg, and J. Kallio The Leu7Pro Polymorphism of PreproNPY Is Associated with Decreased Insulin Secretion, Delayed Ghrelin Suppression, and Increased Cardiovascular Responsiveness to Norepinephrine during Oral Glucose Tolerance Test J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3646 - 3652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Stock, P. Leichner, A. C. K. Wong, M. A. Ghatei, T. J. Kieffer, S. R. Bloom, and J.-P. Chanoine Ghrelin, Peptide YY, Glucose-Dependent Insulinotropic Polypeptide, and Hunger Responses to a Mixed Meal in Anorexic, Obese, and Control Female Adolescents J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2161 - 2168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Meier and A. M. Gressner Endocrine Regulation of Energy Metabolism: Review of Pathobiochemical and Clinical Chemical Aspects of Leptin, Ghrelin, Adiponectin, and Resistin Clin. Chem., September 1, 2004; 50(9): 1511 - 1525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Misra, K. K. Miller, C. Almazan, K. Ramaswamy, A. Aggarwal, D. B. Herzog, G. Neubauer, J. Breu, and A. Klibanski Hormonal and Body Composition Predictors of Soluble Leptin Receptor, Leptin, and Free Leptin Index in Adolescent Girls with Anorexia Nervosa and Controls and Relation to Insulin Sensitivity J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3486 - 3495. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
