24-hour Growth Hormone Concentration Research Articles

Incomplete Modified Fast in Obese Early Pubertal Girls Leads to an Increase in 24-Hour Growth Hormone Concentration and a Lessening of the Circadian Pattern in Leptin

We studied nutrition and GH in eight obese girls, aged 6-11 yr. Blood was sampled every 15 min for 24 h. A 48-h diet providing 25% of assumed caloric needs was imposed, with repeat sampling during the last 24 h. Six nonfasting lean girls were also studied, and their mean GH was 3 times that of the obese girls in the fed state (P = 0.024). Dieting increased mean GH by 60% (P = 0.0028). There was no difference in pulse number for either group, but total secretion for lean girls was 3.9 times greater than that in obese girls during the fed state. With dieting, obese girls increased their total GH secretion by 60% (P = 0.010), but maintained lower total secretion, approximately 40% that of lean girls (P = 0.014). Mean leptin in obese girls in the fed state was 6.2 times greater than mean leptin in lean girls (P = 0.0001), with higher concentrations at night (P < 0.05) and lowering of total mean leptin while dieting. We conclude that in early pubertal obese girls, short-term caloric restriction partially reverses the low GH state that is characteristic of obesity. The change is concomitant with a decrease in leptin and a lessening of circadian differences.

Incomplete Modified Fast in Obese Early Pubertal Girls Leads to an Increase in 24-Hour Growth Hormone Concentration and a Lessening of the Circadian Pattern in Leptin

Incomplete Modified Fast in Obese Early Pubertal Girls Leads to an Increase in 24-Hour Growth Hormone Concentration and a Lessening of the Circadian Pattern in Leptin

Growth hormone release during acute and chronic aerobic and resistance exercise: recent findings.

Exercise is a potent physiological stimulus for growth hormone (GH) secretion, and both aerobic and resistance exercise result in significant, acute increases in GH secretion. Contrary to previous suggestions that exercise-induced GH release requires that a "threshold" intensity be attained, recent research from our laboratory has shown that regardless of age or gender, there is a linear relationship between the magnitude of the acute increase in GH release and exercise intensity. The magnitude of GH release is greater in young women than in young men and is reduced by 4-7-fold in older individuals compared with younger individuals. Following the increase in GH secretion associated with a bout of aerobic exercise, GH release transiently decreases. As a result, 24-hour integrated GH concentrations are not usually elevated by a single bout of exercise. However, repeated bouts of aerobic exercise within a 24-hour period result in increased 24-hour integrated GH concentrations. Because the GH response to acute resistance exercise is dependent on the work-rest interval and the load and frequency of the resistance exercise used, the ability to equate intensity across different resistance exercise protocols is desirable. This has proved to be a difficult task. Problems with maintaining patent intravenous catheters have resulted in a lack of studies investigating alterations in acute and 24-hour GH pulsatile secretion in response to resistance exercise. However, research using varied resistance protocols and sampling techniques has reported acute increases in GH release similar to those observed with aerobic exercise. In young women, chronic aerobic training at an intensity greater than the lactate threshold resulted in a 2-fold increase in 24-hour GH release. The time line of adaptation and the mechanism(s) by which this training effect occurs are still elusive. Unfortunately, there are few studies investigating the effects of chronic resistance training on 24-hour GH release. The decrease in GH secretion observed in individuals who are older or have obesity is associated with many deleterious health effects, although a cause and effect relationship has not been established. While exercise interventions may not restore GH secretion to levels observed in young, healthy individuals, exercise is a robust stimulus of GH secretion. The combination of exercise and administration of oral GH secretagogues may result in greater GH secretion than exercise alone in individuals who are older or have obesity. Whether such interventions would result in favourable clinical outcomes remains to be established.

The relationship of growth rate, plasma growth hormone (GH) concentration, and GH-binding protein.

Growth hormone (GH)-binding protein (GHBP) and GH secretion are potential mediators of linear growth in children. To study the relationship between these variables, we measured GHBP activity, peak stimulated GH (PKGH), and 24-hour integrated GH concentration (ICGH) in 76 children referred for evaluation of growth. Linear growth was expressed as an age- and sex-specific growth rate standard deviation score (GRSD), which was calculated from sequential height measurements in the 6-month period immediately before GH testing. Using multiple regression models, we found that the relationship between GHBP and growth (GRSD) depended on height (height standard deviation [HGTSD] expressed as an age- and sex-specific z score) controlling for ICGH or PKGH. In further analysis of this relationship, we divided the subjects by HGTSD in subsequent analyses. In 19 children of normal stature (HGTSD > -2), GRSD increased with GH concentration (measured both as PKGH and ICGH: P <.013,R2 = .56) but decreased with higher levels of GHBP (P < .005,R2 = .62). In contrast, for 57 subjects with severe short stature (HGTSD < or = -2), GRSD could not be predicted from GHBP, GH secretion, HGTSD, or interaction involving these variables. These data suggest the hypothesis that under normal conditions, GHBP and GH level may be important predictors of growth rate in children.

Diagnosis of growth hormone deficiency in adults.

The potential effects of growth hormone (GH) deficiency in adults and the importance of GH secretion in adult life have only been recognized and documented recently. It has been suggested that GH-deficient adults may have premature mortality, abnormalities in body composition and bone density with impaired physical performance and psychological well-being, which are sometimes improved by GH replacement. It is essential, therefore, to establish reliable standards to define GH deficiency in adults. Patients with possible GH deficiency often have primary pituitary or hypothalamic disorders or have undergone surgery or radiotherapy, and thus show evidence of a failure of one of the other pituitary hormones. Several biochemical approaches have been studied to define GH deficiency in the adult and no universal consensus has yet been reached. The most widely established criterion is the peak serum GH concentration achieved during a provocative test, usually the insulin tolerance test (ITT), or following other pharmacological stimuli (e.g. glucagon, arginine, clonidine or GH-releasing factor) but, alternatively, a more physiological stimulus (such as sleep, fasting or exercise) has been used. Spontaneous circulating levels of hormones of the GH axis [24-hour integrated GH concentration, serum insulin-like growth factor I (IGF-I) or IGF-binding protein-3] have been used in the diagnosis of childhood GH deficiency. They have been tested in adults as well but seem to have a more limited role. There are several factors complicating the evaluation of these results. Basal and stimulated GH and IGF-I levels decline with age and with obesity, levels tend to be higher in females and are dependent on nutritional and physical status. The ITT potentially has some risk attached, e.g. in the presence of ischaemic heart disease, but it has proved to be safe in general when used in specialized departments. Other tests are less reliable; releasing hormone tests only assess the readily releasable stores within the pituitary and not the physiological secretory status. The 'cut-off' point for the definition of subnormal responses ideally needs to be set for each provocative test, for each age group, for each degree of obesity and for both sexes. There is considerable variability in GH assays among different laboratories, which makes it difficult to compare hormone levels. The reproducibility of provocative tests can also be variable. An advantage of the hypoglycaemia and glucagon tests is that they allow simultaneous assessment of the adrenocorticotropic hormone reserve.

Defining growth hormone deficiency in adults

The absence of a distinct clinical syndrome calls for a strategy to reliably identify patients with hyposomatotropism. However, there is no consensus as to the most appropriate method of defining growth hormone (GH) deficiency in adults. Since GH secretion falls with senescence and is also reduced by obesity, both of these factors must be controlled for in such an evaluation. We have investigated the relative diagnostic merits of measuring (1) peak GH response to insulin-induced hypoglycemia (ITT), (2) mean 24-hour GH concentration derived from 20-minute sampling (IGHC), (3) serum IGF-I levels, and (4) serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) levels. These tests were undertaken in 23 patients considered GH-deficient from extensive organic pituitary disease and in 35-sex-matched normal subjects of similar age and body mass index. The ITT was the only test capable of distinguishing patients with organic GH deficiency from matched normal subjects. The sensitivity of the GH radioimmunoassay (0.2 ng/mL) limited the utility of IGHC measurements, since many subjects from both groups had undetectable values. Using a GH assay with a 100-fold greater sensitivity, we found a better but still incomplete separation of values between the two groups. There was a significant overlap of IGF-I and IGFBP-3 values, with only a third of GH-deficient subjects having low IGF-I values. The limitation of IGF-I has been confirmed by others, although its sensitivity as a diagnostic test is greater in young adults. We conclude that organic GH deficiency in adults can be reliably diagnosed by the ITT. IGF-I and IGFBP-3 measurements are unreliable, because these levels may be normal in GH deficiency.

Dynamic changes of growth hormone—binding protein concentrations in normal men and patients with acromegaly: Effects of short-term fasting

Plasma concentrations of growth hormone (GH) and GH-binding protein (GHBP) were measured at hourly intervals in five healthy men and five patients with acromegaly during the fed state and after a 5-day fast. GHBP concentrations (both total and complexed with endogenous GH) were analyzed by the ligand-mediated immunofunctional assay (LIFA). Total GHBP was similar in both groups during the fed state (104.4 ± 5.2 and 101.6 ± 10.3 pmol/L), did not exhibit a diurnal rhythm, and was unchanged by fasting (91.9 ± 5.4 and 109.9 ± 10.5 pmol/L, respectively). However, the GHBP GH complex concentration was significantly higher in acromegalics than in controls (41.0 ± 2.8 v 18.0 ± 2.2 pmol/L, respectively; P < .05), closely followed diurnal GH rhythm in normals, and was significantly correlated with mean 24-hour GH concentrations ( r = .86, P < .01). We conclude that plasma concentrations of GHBP are stable throughout the day and are unchanged either by short-term calorie deprivation or by chronic exposure to high levels of endogenous GH. In contrast, GHBP/GH complex concentrations are altered both acutely and chronically by ambient GH.

Pulsatile nature of growth hormone levels in critically ill trauma victims.

Circulating growth hormone (GH) levels in normal persons fluctuate widely because of pulsatile GH secretion. It is not known whether this pulsatile nature and rhythmicity exist in severe injury. These data become necessary to decide the timing of supplementary GH administration for its optimal utilization. The purpose of this study was to investigate the GH circadian variation with respect to that of insulin-like growth factor-1 (IGF-1), insulin, C-peptide, and cortisol in the early flow phase of injury. Plasma GH, IGF-1, insulin, C-peptide, and cortisol levels were measured at 1-hour intervals during 24 hours (8 AM to 8 AM) in 10 severely injured adults with multiple trauma during the early catabolic flow phase 24 to 48 hours after injury, when patients received maintenance fluids without calories or nitrogen. The 24-hour integrated GH concentration is not different from either 12-hour mean diurnal or 12-hour mean nocturnal or mean 8 AM GH concentration. Pulsatile GH bursts persist in injured patients during both day and night. Pulsatile bursts do not exist for IGF-1, insulin, and C-peptide. The plasma levels of cortisol show time-dependent daily maximum and minimum levels. Pulsatile GH bursts persist in injured patients but less frequently than seen in normal persons. The time of bolus administration of GH to augment the anabolic GH action in patients with trauma does not matter; however, for convenience morning administration may be preferable for patients in the intensive care unit.

Estimation of Growth Hormone Secretory Patterns in Children with Use of a Numerical Deconvolution Technique: Experimental Design with Use of Computer Simulation

Growth hormone (GH) secretion rates were estimated from 24-hour plasma GH concentration profiles using a model-based numerical deconvolution method. The basic kinetic parameters describing GH distribution and elimination were obtained from studies using single intravenous injections in GH-deficient children. Computer simulation techniques were used to produce 24-hour GH secretion profiles, which could serve as reference curves for analysis of the impact of certain practical aspects of the estimation of GH secretion, such as the method of blood sampling (discrete or integrated), sampling frequency and analytical errors. The results show that sampling intervals of 20 min are acceptable even in the presence of analytical errors, and that with this sampling interval, discrete blood sampling does not seem to be preferable to continuous withdrawal of blood.

Aging and Growth Hormone

Detailed studies of the ontogeny of growth hormone (GH) secretion have shown unequivocally that GH is produced throughout life but secretion declines progressively to about 20% of that in puberty. These changes are accounted for in part by changes in central neuro-endocrine function, nutritional factors and by changes in sex steroid milieu. Mean 24-hour GH concentrations in the normal elderly are frequently below the limit of assay detectability where values are indistinguishable from matched adults with organic GH deficiency. The notion that diminished GH action may account for the undesirable changes in body composition and function in the elderly is supported by beneficial findings of GH treatment in GH-deficient adults. Preliminary results of GH treatment in the normal elderly suggest beneficial effects on body composition but a high incidence of side-effects. Questions addressing cost, benefit, dosage, safety and tolerance need to be critically addressed before GH can be considered for use in the aging.

Twenty-four-hour serum growth hormone, insulin, C-peptide and blood glucose profiles and serum insulin-like growth factor-I concentrations in women with polycystic ovaries.

Raised insulin levels are now recognized as a characteristic feature of women with polycystic ovaries (PCO), and hyperinsulinism has been shown to stimulate androgen production in such women. We have, however, recently shown that hyperinsulinaemia is present only in the obese subjects with PCO in whom insulin concentrations correlate with those of luteinizing hormone. We therefore studied 24-hour blood profiles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in obese and non-obese women with PCO, for comparison with their levels of insulin, C-peptide and other hormones, such as androgens which are known to be disturbed in PCO. Mean 24-hour GH levels were higher overall in PCO than in control subjects, although the difference was not significant. When, however, a separate analysis was made in obese as compared with non-obese PCO patients, GH concentrations were significantly higher in the non-obese group than in the obese (p = 0.0005). There was a significant negative correlation between body mass index and mean 24-hour GH concentrations (r = -0.641; p = 0.0006). IGF-I concentrations were however similar in the PCO group overall and in controls, as well as in the obese and non-obese PCO patients. The 24-hour blood glucose profile pattern was significantly different in PCO women from controls (p = 0.009), with absence of post-prandial peaks in blood glucose concentrations. These changes were most marked in the non-obese PCO group, who also had significantly lower blood glucose levels than either controls or obese PCO subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Linear Growth Response to Exogenous Growth Hormone in Children With Short Stature

Response to growth hormone (GH) therapy was evaluated in 38 short children (28 males and 10 females; less than 1% in height for chronologic age [CA]) who were clinically categorized into three groups based on their endogenous mean 24-hour GH concentration (mean 24-hour GH) and peak GH response to two or more provocative agents (peak GH). All patients were treated with biosynthetic somatropin (human growth hormone) (0.15 to 0.30 mg/kg per week) injected subcutaneously three to seven times per week for a mean duration of 12.5 months. Group 1 consisted of 17 subjects (CA, 12.5 +/- 2.9 years [mean +/- SD]; bone age, 9.4 +/- 2.9 years; height velocity [HV], 3.4 +/- 1.8 cm/y; peak GH, 5.8 +/- 2.6 micrograms/L; mean 24-hour GH, 1.7 +/- 0.6 micrograms/L; and insulinlike growth factor-I, 0.40 +/- 0.24 U/mL. Group 2 consisted of 10 subjects (CA, 11.7 +/- 2.7 years; bone age, 9.2 +/- 3.0 years; HV, 3.4 +/- 1.6 cm/y; peak GH, 16.4 +/- 5.2 micrograms/L; mean 24-hour GH, 1.7 +/- 0.5 micrograms/L; and insulinlike growth factor-I, 0.49 +/- 0.27 U/mL. Group 3 consisted of 11 subjects (CA, 12.7 +/- 2.2 years; bone age, 10.2 +/- 2.4 years; HV, 3.5 +/- 1.5 cm/y; peak GH, 22.5 +/- 8.6 micrograms/L; mean 24-hour GH, 3.8 +/- 1.1 micrograms/L; and insulinlike growth factor-I, 1.07 +/- 0.69 U/mL. Following administration of somatropin, an increase (delta) in HV of 2.0 cm/y or greater occurred in 94% (16/17) of the group I subjects (delta HV of 5.1 +/- 2.6 cm/y), in 90% (9/10) of the group 2 subjects (delta HV of 4.3 +/- 2.2 cm/y), and in 73% (8/11) of group 3 subjects (delta HV of 3.7 +/- 2.3 cm/y). However, regardless of provoked and/or endogenous GH secretory dynamics, 88% of the children whose pretreatment HV was 2.0 cm/y or less, 94% whose pretreatment HV was between 2.0 and 4.0 cm/y, and 79% whose pretreatment HV was greater than 4.0 cm/y increased their HVs to 2.0 cm/y or greater while they were receiving somatropin. Significant negative correlations were observed between delta HV and pretreatment HV (r = -.67), delta HV and GH concentration expressed as a 24-hour area under the curve (r = -.33), and delta HV and peak GH (r = -.34).(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of Short‐Term Growth Hormone Therapy in Short Children without Growth Hormone Deficiency

Evaluation of 24-hour endogenous growth hormone (GH) secretion was carried out in 62 children, aged 7-16 years, who did not have classic GH deficiency (GHD). The mean 24-hour GH concentration, determined at 20-minute intervals over 24 hours, was variable, ranging from 1.28 to 11.39 micrograms/l with a mean of 4.95 +/- 2.55 micrograms/l (+/- SD). There was a positive correlation between mean 24-hour GH concentration and plasma insulin-like growth factor I (IGF-I) values (r = 0.54; p less than 0.01). Recombinant human GH, 0.1 IU/kg/day was administered to 30 of the 62 children for 6 months followed by 6 months' observation without treatment. Thereafter, GH was administered at the same dose for a further 6 months to 16 children. The mean height velocities before, during, and after the first treatment period were 4.3 +/- 0.9, 7.3 +/- 1.9 and 4.9 +/- 2.0 cm/year (mean +/- SD), respectively. The height velocity during treatment was greater than pre- and post-treatment values (p less than 0.001). The height velocity increased again during the second treatment period to a mean of 8.5 +/- 2.0 cm/year (p less than 0.001). Nine other children were treated continuously in a similar manner for 1 year and their height velocity increased significantly from 4.1 +/- 1.4 to 6.0 +/- 1.9 cm/year (p less than 0.001). According to our criteria, 29 of the 39 children (74.4%) who were treated for 6-12 months showed a GH-dependent height increase during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone secretory dynamics in subjects with normal stature

To evaluate the dynamics of growth hormone (GH) secretion in subjects with normal stature and to determine whether a correlation exists between height and the quantity of GH secreted, we determined the 24-hour GH concentration by measuring GH levels every 30 minutes in 27 boys and 19 girls of normal height, 7 to 18 years of age, of whom 24 were prepubertal and 22 in various stages of puberty. Spontaneous GH secretion had wide variations, with values ranging from less than 1.0 to 67.0 micrograms/L. In prepubertal children the highest GH levels were usually noted during sleep; in pubertal subjects the highest values were distributed almost equally between sleep and wake hours. In all subjects, GH secretion appeared to decrease before meals, followed by an increase after meals. Most indexes of GH secretion and insulin-like growth factor I levels were significantly greater in pubertal than in prepubertal subjects (p less than 0.002), and in both groups the GH concentration was significantly greater during sleep (p less than 0.005). In all groups the 24-hour GH concentration correlated significantly with the area under the GH curve, 24-hour GH pulse amplitude, and GH concentration and peak GH level during sleep and wake hours (P less than 0.0001); 24-hour GH concentrations correlated with insulin-like growth factor I levels only when the entire group of 46 subjects was considered (p less than 0.01). There were no significant correlations between 24-hour GH concentration and the subjects' age, bone age, height (SD score), weight (SD score), or body mass index. We conclude that in subjects with normal stature, mean 24-hour GH concentrations vary considerably and in the low range overlap with values reported in hypopituitarism.

Growth hormone secretory patterns in children with short stature

To assess whether growth-retarded children with a stimulated growth hormone (GH) level greater than 10 ng/mL have an abnormality in spontaneous GH secretion, we measured GH levels every half hour for 24 hours in 50 children 2.7 to 17 years of age. Growth rate was subnormal in all. Mean 24-hour GH concentration ranged from 1.2 to 7.7 ng/mL, and was significantly greater in pubertal than in prepubertal children (P less than 0.01). In both groups, GH concentration during sleep was significantly greater than during wakeful hours (P less than 0.0005); 24-hour GH concentration correlated significantly with sleep-induced GH peak. A decrease in 24-hour GH concentration and sleep-induced GH peak were noted in four pubertal children with stimulated GH less than 15 ng/mL. A progressive and significant increase in somatomedin C (SmC) level was noted with increasing age and sexual development. No correlations were found between 24-hour GH concentration and rate of growth, age, or bone age. Serum SmC values correlated significantly with age and bone age (P less than 0.01), and with 24-hour GH concentration only in prepubertal children (P less than 0.05). A strong correlation between SmC and growth rate was noted only in pubertal children (P less than 0.01). Growth velocity increased significantly during GH therapy regardless of the 24-hour GH concentration. Our results indicate that in children with growth retardation there is a wide variation in 24-hour GH concentration and a significant increase in GH concentration during puberty; the GH concentration during nocturnal sleep, rather than an entire 24-hour GH concentration, can be used for evaluation; during puberty the SmC level reflects sexual development more than GH reserve; and GH therapy appears to increase growth velocity in both non-GH-deficient and partially GH-deficient short children.

Carbohydrate intolerance in gonadal dysgenesis: evidence for insulin resistance and hyperglucagonemia.

To determine the pathogenesis of carbohydrate intolerance associated with gonadal dysgenesis, plasma glucose, insulin, glucagon, and growth hormone responses to oral glucose and intravenous tolbutamide, arginine and insulin were evaluated in 21 nonobese patients, 7-19 years old. Glucose intolerance was present in 9 of 21 nonobese patients (42.8%). Insulin levels, the area under the insulin curve after oral glucose and intravenous tolbutamide and the insulin to glucose ratio were significantly greater in patients than in controls (p less than 0.005). The decrease in plasma glucose following intravenous tolbutamide was significantly less in patients than in controls (p less than 0.05) despite insulin levels which were greater than in controls (p less than 0.05). After intravenous insulin, plasma glucose fell significantly less in patients than in controls (p less than 0.01). Plasma glucagon levels and the area under the glucagon curve after oral glucose and arginine infusion were significantly greater in patients than in controls (p less than 0.005 and p less than 0.01, respectively). The increase in glucagon after insulin-induced hypoglycemia was significantly less in patients than in controls (p less than 0.025). Fasting and stimulated growth hormone levels and the mean 24-hour growth hormone concentration were similar in patients and controls. These results indicate that glucose intolerance occurs frequently in gonadal dysgenesis and is associated with normal or increased insulin secretory responses. These abnormalities are probably due to insulin resistance and hyperglucagonemia. The decrease in insulin action does not appear to result from excessive growth hormone secretion or treatment with anabolic steroids or estrogen-progesterone medications.

Somatomedin and Growth Hormone Studies

Plasma somatomedin (SM) activity and growth hormone (GH) concentration were measured in ten growth-retarded, well-nourished pediatric renal allograft recipients who received daily prednisone therapy. The SM activity ranged from 0.21 to 1.22 micron/mL, and it was subnormal in three patients. A significant correlation was found between SM activity and creatinine clearance. Serial SM levels were determined during a 24-hour period in five patients; SM activity decreased at six and 12 hours and returned to normal values by 24 hours. The 24-hour plasma GH concentrations ranged from 1.5 to 7.6 mg/mL. Peak GH concentrations ranged from 2.1 to 14.2 ng/mL after insulin-induced hypoglycemia and from 1.8 to 24.6 ng/mL after oral glucose loading. Sleeping GH peaks were absent in two patients. These results suggest that growth failure in renal allograft recipients who receive daily prednisone may result from (1) partial GH deficiency, (2) reduced SM levels owing to diminished allograft function, and (3) daily transient decrease in plasma SM levels after prednisone administration.