Daily Growth Hormone Research Articles

Increased Orderliness of Growth Hormone (GH) Secretion in GH-Deficient Adults with Low Serum Insulin-Like Growth Factor I

Available studies suggest that a proportion of GH-deficient (GHD) adults maintain serum IGF-I concentrations within the age- and sex-matched normal range. The basis for this distinction is not known. In this study 24-h GH profiles (sampling every 30 min) were appraised in five GHD adults with low serum IGF-I concentrations (<2 SD of the age- and sex-matched normal range), five GHD adults with normal serum IGF-I levels (within +/-2 SD), and five healthy subjects. Serial GH concentrations, measured using a chemiluminescence assay, were analyzed by deconvolution and approximate entropy (ApEn; regularity) analyses. The apparent half-duration of GH secretory bursts was longer in both GHD groups than in the healthy controls, as determined by deconvolution analysis (P < 0.05 each). The GH burst frequency was higher, the interburst interval was shorter, and the GH burst amplitude was lower in GHD adults with normal serum IGF-I than in healthy controls (P < 0.05, P < 0.05, and P < 0.01, respectively). The percentage of total daily GH secretion that was pulsatile was also reduced in the GHD adults with normal serum IGF-I compared with the other two groups (P < 0.05 and P < 0.05, respectively). In contrast, ApEn ratios were lower in the GHD adults with low serum IGF-I than in the GHD adults with normal IGF-I and controls (P < 0.01 and P < 0.05, respectively). Serum IGF-I concentrations correlated positively with ApEn ratios in the total study population (n = 15) and in the GHD adults (n = 10). In conclusion, 24-h patterns of GH release differed in GHD adults with low vs. normal serum IGF-I concentrations. GHD adults with low IGF-I levels maintain low ApEn ratios (denoting greater relative orderliness of GH secretion), whereas GHD patients with normal IGF-I values generate a high frequency, low amplitude GH output. The foregoing contrasts point to distinct neuroendocrine features of the GH-deficient state of adults, which can be related to concurrent IGF-I production.

Impact of two or three daily subcutaneous injections of hexarelin, a synthetic growth hormone (GH) secretagogue, on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans

To extend the insights on the action of GH secretagogues (GHS) on pituitary function, we studied the impact of intermittent daily s.c. administration of a peptidyl GHS, hexarelin (HEX), on 24-h GH, PRL, ACTH and cortisol release in healthy volunteers. We investigated the impact of two or three times daily s.c. administration of a short-acting peptidyl GHS, the hexapeptide HEX (1.5 microg/kg) on 24-h GH, PRL, ACTH and cortisol secretion (sampling every 20 min) in six normal young men. To monitor possible down-regulation, the effect of 1 microg/kg i.v. HEX at the end of each 24-h sampling period was studied. Multi-parameter deconvolution analysis was used to quantitate pulsatile GH, PRL, ACTH and cortisol secretion and estimate the corresponding hormone half-lives. Complementary to deconvolution analysis, approximate entropy was used as a scale- and model-independent statistic to quantify the serial orderliness or pattern regularity of hormone measurements. Mean and integrated (24-h) serum GH concentrations were increased from baseline values to the same extent by two and three HEX injections. Both HEX schedules equally increased GH secretory burst mass (but not burst frequency), mean daily GH production rate, GH half-life and irregularity of GH release patterns. No change occurred in the secretion of IGF-I, PRL, ACTH and cortisol. Intravenous HEX at the end of each spontaneous 24-h profile induced a significant rise in GH, PRL, ACTH and cortisol. Prior HEX administration blunted the GH response, abolished that of ACTH and cortisol and did not modify the PRL increase. The study showed that two or three daily s.c. injections of HEX augmented 24-h GH secretion equally, amplifying selectively GH secretory pulse mass without altering lactotroph and corticotroph secretion. IGF-I levels were not modified by these 1-day HEX treatment schedules.

Optimizing Somatostatin Analog Therapy in Acromegaly

Somatostatin peptide analogs have revolutionized the medical treatment of patients with acromegaly. More recent deep intramuscular depot preparations have further improved control, with consistent suppression of growth hormone secretion and optimal lowering of insulin-like growth factor-1. Effective control of growth hormone should, with long-term use, reduce morbidity and mortality from acromegaly and has been shown to result in partial involution of the pituitary adenoma in the majority of treated patients. The currently available depot formulations allow for an injection frequency of 14 days (lanreotide LA 30mg) to 28 days (octreotide LAR 20mg) according to the manufacturers' recommendations. In clinical practice, dose titration by evaluating a growth hormone day profile prior to the next injection can extend the interval between injection (to 6 or even 8 weeks in certain individuals). This is especially true for octreotide LAR, which also has increased flexibility regarding dosage with a 10 and 30mg preparation. The annual 'drug cost' is broadly similar between the two formulations though the additional expenditure on nurse time and clinic visits incurred by an increased injection frequency is a significant consideration. Decreased injection frequency improves acceptability for the patient without a loss in treatment efficacy. A subjective return of typical acromegalic symptoms, such as sweating and headache, also seem to be useful in predicting the timing of the next injection. Other formulations and doses of lanreotide are currently being evaluated, but more interestingly, newer analogs with greater efficacy at the type 5 somatostatin receptor subtype, and pan-receptor analogs, are being developed. These peptides, in conjunction with the likely availability of a growth hormone receptor blocking agent (pegvisomant), will further expand the medical therapy options for patients with acromegaly.

Effects of 6 years of growth hormone (GH) treatment on bone mineral density in GH-deficient adults.

Adults with growth hormone (GH) deficiency are often osteopenic. Short-term GH replacement therapy has been shown to improve bone mineral density (BMD). However, whether the increases in BMD are progressive with time is still unclear. We therefore examined long-term changes in BMD with GH treatment in GH-deficient adults over a period of 6 years. Open prospective GH therapeutic study. Twelve GH-deficient patients (four women, eight men) with a mean age of 42.5 years (range 24-61 years) at the beginning of GH replacement. Eleven patients suffered in addition from LH/FSH insufficiency, eight from TSH insufficiency and eight from ACTH insufficiency. Before the start of GH substitution, the insufficient anterior pituitary axes were fully substituted for an average of 9.8 years (range 2-22 years). Average daily GH dose was 2.4 IU (SD 0.86). BMD and bone area were measured at annual intervals at the lumbar spine and at the proximal femur using dual-X-ray absorptiometry. Under GH substitution, serum insulin-like growth factor I concentrations increased by 140 microg/l compared to pretherapeutic values (P = 0.0003). BMD at the lumbar spine increased by 0.16 g/cm2 (P = 0.0005), corresponding to a mean increase of 15.9% or an increase of the BMD Z-score by 1.53 SD. Increases in BMD were independently observed from years 3 to 6 by a mean of 5.8% (P = 0.0087). This increase was paralleled by an increase in the area of the lumbar vertebrae. Bone area also increased at selected sites of the proximal femur, but there was no consistent increase in BMD at the proximal femur. GH therapy in GH-deficient adults is able to progressively increase BMD and bone area at the lumbar spine over a period of at least 6 years. However, our study has several limitations, making it necessary to confirm these findings in further long-term studies.

Predictors of the Outcome of Surgical Treatment in Acromegaly and the Value of the Mean Growth Hormone Day Curve in Assessing Postoperative Disease Activity

Predictors of the Outcome of Surgical Treatment in Acromegaly and the Value of the Mean Growth Hormone Day Curve in Assessing Postoperative Disease Activity

Predictors of the outcome of surgical treatment in acromegaly and the value of the mean growth hormone day curve in assessing postoperative disease activity.

Acromegaly is associated with increased morbidity and mortality unless serum GH levels are persistently less than 5 mU/L ( approximately 2 ng/mL) after treatment. Transsphenoidal surgical resection is the best available treatment for restoring GH to such "safe" levels; however, criteria for the assessment of the response to treatment are not uniform. To determine the clinically most useful method of assessing disease activity postoperatively and identify predictors of a favorable response to surgical treatment, we have analyzed 67 patients with acromegaly who underwent transsphenoidal surgery between 1993 and 1998. We used three different definitions of a satisfactory or safe response: 1) a postoperative mean GH less than 5 mU/L obtained from averaging five serum GH values obtained throughout one day; 2) a random single GH less than 5 mU/L; or 3) a serum insulin-like growth factor I (IGF-I) level within the normal range. Relying on a single GH measurement alone, 9 of the 23 patients with a single postoperative mean GH level less than 5 mU/L obtained at least one GH value of more than 5 mU/L (false positive rate, 28%) and 8 of the patients with a postoperative mean GH value of more than 5 mU/L obtained a single GH value of less than 5 mU/L (false negative rate, 15%). Postoperatively, a significant increase in the fluctuation of random GH values around the mean was observed in patients who were rendered safe (coefficient of variation, from 26 +/- 2% to 53 +/- 6%; P < 0.001) compared with patients with persistence of inadequately controlled disease. However, 13% (3 of 23) of patients with mean postoperative GH levels of less than 5 mU/L had elevated serum IGF-I levels postoperatively, and 17% (8 of 44) of patients with mean serum GH levels more than 5 mU/L had postoperative IGF-I levels within the normal range. There was no difference in the rate of agreement between mean GH less than 5 mU/L and normalization of IGF-I in relation to the interval since operation when IGF-I levels were measured. Preoperative tumor size and pretreatment mean GH levels were the major determinants of the outcome of surgery, as patients who were rendered safe had significantly lower preoperative mean GH levels than patients who were not cured (median, 31 mU/L vs. 78.5 mU/L, P < 0.01). IGF-I levels were weakly correlated with tumor size and could not be used to predict the patients who would be rendered safe. Preoperative PRL levels were higher in patients who failed to achieve a surgical satisfactory outcome [498 mU/L (187-857) vs. 196 mU/L (136-315), P < 0.01]. In summary, although single random GH values and IGF-I values are both significantly correlated with mean GH levels, they should not be used as an alternative to averaging several GH values to assess disease activity, because of the pulsatile nature of GH secretion and the multiple factors that may influence serum IGF-I. Because significant discrepancies occur, particularly postoperatively, mean GH levels remain the more reliable indicator of surgical outcome and disease activity. As there is considerably more evidence relating long-term prognosis to serum GH levels than to IGF-I and discrepancies occur between GH levels and IGF-I, we suggest that mean serum GH levels and single IGF-I levels, measured early in the postoperative period, are currently the best biochemical guide to the adequacy of surgery and, hence, the need for further treatment.

Continuous 24-Hour Intravenous Infusion of Recombinant Human Growth Hormone (GH)-Releasing Hormone-(1-44)-Amide Augments Pulsatile, Entropic, and Daily Rhythmic GH Secretion in Postmenopausal Women Equally in the Estrogen-Withdrawn and Estrogen-Supplemented States

Continuous 24-Hour Intravenous Infusion of Recombinant Human Growth Hormone (GH)-Releasing Hormone-(1-44)-Amide Augments Pulsatile, Entropic, and Daily Rhythmic GH Secretion in Postmenopausal Women Equally in the Estrogen-Withdrawn and Estrogen-Supplemented States

Effects of Growth Hormone Plus a Hyperproteic Diet on Methotrexate-induced Injury in Rat Intestines

The aim of this study was to determine whether growth hormone treatment reduces injury to the intestinal mucosa induced by methotrexate (MTX). Wistar rats with intestinal injury induced by methotrexate were treated with daily growth hormone, beginning 3 days before MTX treatment until 3 or 4 days after MTX administration. The rats were killed at 3 or 7 days post-MTX administration. The rats were fed with either a normoproteic diet or a hyperproteic diet. Body weight, mortality, bacterial translocation, intestinal morphometry, proliferation and apoptosis and blood somatostatin and IGF-1 were determined. Combined administration of growth hormone and a hyperproteic diet reduces MTX-induced mortality. This effect was accompanied by increased cell proliferation and decreased apoptosis within the crypt. Morphometric data showed complete recovery of the mucosa by day 7 post-MTX administration. These results indicate a synergistic protective action of growth hormone combined with a hyperproteic diet to MTX-induced injury.

Apparently Complete Restoration of Normal Daily Adrenocorticotropin, Cortisol, Growth Hormone, and Prolactin Secretory Dynamics in Adults with Cushing's Disease after Clinically Successful Transsphenoidal Adenomectomy

Apparently Complete Restoration of Normal Daily Adrenocorticotropin, Cortisol, Growth Hormone, and Prolactin Secretory Dynamics in Adults with Cushing's Disease after Clinically Successful Transsphenoidal Adenomectomy

Effect of sleep deprivation on overall 24 h growth-hormone secretion

After sleep deprivation, the blunting of the normal sleep-related growth-hormone (GH) pulse is compensated during the day. Consequently, the amount of GH secreted during a 24 h period is similar whether or not a person has slept during the night. These results argue against the belief that sleep disorders in children can inhibit growth through a daily GH deficit.

Long-term effects of growth hormone treatment on growth and puberty in patients with chronic renal insufficiency.

Several prospective trials have shown that recombinant human growth hormone (GH) accelerates growth significantly during the first years of therapy, but the effects of long-term GH therapy with regard to long-term growth response and safety have not yet been established. Forty-five Dutch prepubertal children [28 boys, 17 girls, mean (SD) age 7.8 (3.4) years] with chronic renal insufficiency (CRI) and severe growth retardation started GH therapy between 1988 and 1991 within one of the randomized Dutch trials. Long-term GH therapy, in this study a maximum of 8 years, resulted in a sustained and significant improvement of height standard deviation score (SDS) compared with baseline values (P<0.001). The mean height SDS reached the lower end (-2 SDS) of the normal growth chart after 3 years of GH therapy. During the following years the mean height SDS gradually increased, thereby approaching the mean target height SDS after 6 years of GH therapy. Three factors were significantly associated with the height SDS after 4 years of GH therapy: height SDS at the start (+) of therapy, age at the start of therapy (-), and the duration of dialysis treatment (-). Bone maturation did not accelerate during long-term GH therapy. Children on a conservative regimen at the start of GH therapy had no accelerated deterioration of renal function during 6 years of GH therapy. The average daily GH dose administered over the years had no significant influence on the glomerular filtration rate after 4 years. GH therapy had no adverse effects or significant effect on parathyroid hormone concentration, nor were there any radiological signs of renal osteodystrophy. Puberty started at a median age, within the normal range, of 12.4 years in boys and 12.0 years in girls, respectively. Long-term GH therapy leads to a sustained improvement in height SDS in children with growth retardation secondary to CRI, resulting in a normalization of height in accordance with their target height SDS, without evidence of deleterious effects on renal function or bone maturation. A GH dosage of 4 IU/m2 per day appears efficient and safe. Our long-term data show that final height will be within the normal target height range when GH therapy is continued for many years.

Control of ovarian follicles activity in the ewe

During the ovine estrous cycles, three waves of follicular growth, closely associated with the FSH secretion pattern, were observed. The parameters of these follicular waves and the ability of follicles to produce steroids in vitro were studied in various conditions. In vivo, the follicular events were similar between the breeding season and the anestrus, except for the lack of ovulation; but at the end of the breeding season and in anestrus, the follicles lose a big part of their aromatization ability. In ewes carrying the Booroola fecundity gene or Cambridge fecundity gene, the reduction in follicular atresia seems to be one of the main follicular features implicated in the control of high ovulation rate. In vitro, the most relevant difference is an early acquisition of estrogen production ability of small follicles in Booroola fecundity gene barring ewes. Fluoro-gestone-acetate (FGA) pessaries reduced the number of growing follicles; despite this effect disappearing after the sponge withdrawal, the ovulation rate is significantly reduced. But an equine chorionic gonadotrophin (eCG) treatment restores the ovulation rate (OR) by reducing the atresia rate of pre-ovulatory follicles. In similar conditions, a pretreatment of the ewes with melatonin again reduced the atresia rate of large follicles and resulted in an increased ovulation rate. In vitro, FGA blocked aromatization ability, and melatonin inhibited both androstenedione and estradiol production, but a further treatment with eCG partly restores the steroid secretion. Immunization against androstenedione leads to a higher OR, owning to a reduced atresia of large follicles. Daily growth hormone injections for a hole cycle resulted in an increased follicular population and ovulation rate, while FSH plasma levels decreased and the follicle sensitivity to gonadotrophins was reduced.

Peritoneal Loss of Growth Hormone in Children on Automated Peritoneal Dialysis

To provide quantitative data regarding the daily dialytic loss of growth hormone (GH) in children on peritoneal dialysis (PD). Prospective study involving 24-hour dialysate collections on 3 consecutive days in patients with and without recombinant human GH (rhGH) treatment. Single-center outpatient PD program. Twenty-six children undergoing automated PD (APD): 6 with and 20 without daily rhGH. Daily peritoneal losses of GH, alpha1-, beta2-microglobulin, transferrin, and albumin. The mean (+/-SEM) daily dialytic GH loss was 2.18+/-0.62 microg/1.73 m2 per day in rhGH-treated patients and 0.42+/-0.28 microg/1.73 m2 per day in untreated patients, (p < 0.05). The intraindividual coefficient of variation of daily GH loss was 65%. The peritoneal loss of GH was positively correlated with that of beta2-microglobulin (r = 0.77, p < 0.001) and alpha1-microglobulin (r = 0.51, p < 0.01). The variability in beta2-microglobulin and alpha1-microglobulin elimination, together with the use of rhGH, explained 66% of the total variability of daily GH excretion. In patients without rhGH therapy, the daily peritoneal GH loss was approximately 0.05% of the estimated daily endogenous production rate based on previous estimates in children with end-stage renal failure. In patients on rhGH therapy, less than 0.1% of the injected rhGH dose was eliminated by dialysis. Peritoneal losses of GH in children on APD account only for a minute fraction of endogenous metabolic clearance, and do not explain the variability of the rhGH treatment response. The assessment of dialytic GH elimination may be used to estimate time-integrated mean plasma GH concentrations, and to monitor rhGH treatment compliance.

Interrelations Between Sleep and the Somatotropic Axis

In the human as in other mammals, growth hormone (GH) is secreted as a series of pulses. In normal young adults, a major secretory episode occurs shortly after sleep onset, in temporal association with the first period of slow-wave (SW) sleep. In men, approximately 70% of the daily GH output occurs during early sleep throughout adulthood. In women, the contribution of sleep-dependent GH release to the daily output is lower and more variable. Studies involving shifts of the sleep-wake cycle have consistently shown that sleep-wake homeostasis is the primary determinant of the temporal organization of human GH release. Effects of circadian rhythmicity may occasionally be detected. During nocturnal sleep, the sleep-onset GH pulse is caused by a surge of hypothalamic GHRH release which coincides with a circadian-dependent period of relative somatostatin disinhibition. Extensive evidence indicates the existence of a consistent relationship between SW sleep and increased GH secretion and, conversely, between awakenings and decreased GH release. There is a linear relationship between amounts of SW sleep--whether measured by visual scoring or by delta activity--and amounts of concomitant GH secretion, although dissociations may occur, most likely because of variable levels of somatostatin inhibition. Pharmacological stimulation of SW sleep results in increased GH release, and compounds which increase SW sleep may therefore represent a novel class of GH secretagogues. During aging, SW sleep and GH secretion decrease with the same chronology, raising the possibility that the peripheral effects of the hyposomatotropism of the elderly may partially reflect age-related alterations in sleep-wake homeostasis. While the association between sleep and GH release has been well documented, there is also evidence indicating that components of the somatotropic axis are involved in regulating sleep. The studies are most consistent in indicating a role for GHRH in promoting NREM and/or SW sleep via central, rather than peripheral, mechanisms. A role for GH in sleep regulation is less well-documented but seems to involve REM, rather than NREM, sleep. It has been proposed that the stimulation of GH release and the promotion of NREM sleep by GHRH are two separate processes which involve GHRH neurons located in two distinct areas of the hypothalamus. Somatostatinergic control of GH release appears to be weaker during sleep than during wake, suggesting that somatostatinergic tone is lower in the hypothalamic area(s) involved in sleep regulation and sleep-related GH release than in the area controlling daytime GH secretion. While the concept of a dual control of daytime and sleep-related GH secretion remains to be directly demonstrated, it allows for the reconciliation of a number of experimental observations.

CHANGES IN SOMATOTROPIC AXIS RESPONSE AND BODY COMPOSITION DURING GROWTH HORMONE ADMINISTRATION IN PROGRESSIVE CACHECTIC PARASITISM

A multistage protozoan parasitic disease was used as a cachexia model to study the effects of daily administration of bovine growth hormone (GH) on endocrine and body composition changes of young calves from the onset of the acute phase response (APR). Male calves averaging 127.5 ± 2.0 kg body weight were assigned to control, ad libitum fed, noninfected (C); ad libitum fed, infected (250,000 oocysts Sarcocystis cruzi, per os, I); noninfected, pair-fed (PF) to matched I-treatment calves and these respective same treatments in calves injected daily with GH (USDA-bGH-B1), 12.5 mg/calf/day, im) designated as C GH, I GH and PF GH. GH injections were initiated on Day 20 postinfection (PI), 3 to 4 d before the onset of clinical signs of APR, and continued to Day 56 PI, at which time animals were euthanized for tissue collections. Abrupt increases in rectal temperature commensurate with up to 70% reduction in voluntary feed intake were observed in I and I GH beginning 23–25 d PI. For the trial period between Days 20 and 56 PI, average daily carcass protein gains were 123, 52, 109, 124, 48, and 67 g/d and average daily carcass fat gains were 85, 11, 43, 71, −23, and 29 g/d for C, I, PF, C GH, I GH, and PF GH, respectively. Effects of GH were significant for fat accretion and plasma urea depression. Rectus femoris was highly refractory to catabolic effects of infection while psoas major was significantly catabolized during infection. Plasma concentrations of insulin-like growth factor-I (IGF-) I increased significantly in all GH-treated calves between Day 20 and 23 PI. Plasma IGF-I declined well below Day 20 values in all infected calves from the onset of the APR through the end of the study. The decrease in plasma IGF-I concentrations in I and I G was highly correlated with the magnitude of the fever response. Hepatic mRNA for GH receptor and IGF-I was decreased in infected calves. Hepatic microsomal membrane binding of 125I-GH did not differ between groups. The data suggest that effects of GH and parasitism on tissue metabolism during disease may vary among different specific tissue pools. The data demonstrate that daily GH administration in young calves does not prevent lean tissue losses and may accelerate fat depletion associated with cachectic parasitism. Furthermore, the onset of APR overrode the capacity for GH to maintain elevated plasma concentrations of IGF-I, an effect not readily explained through changes in GH-receptor binding.

Once versus twice daily injections of growth hormone in children with idiopathic short stature

The aim of this study was to compare the growth response of 22 short pre‐pubertal children without growth hormone deficiency, treated with a single daily growth hormone injection (group A), to the growth response of 27 similar children, treated with the same daily dose divided into 2 subcutaneous injections per day (group B), for 1 y, in a randomized study. GH treatment significantly promoted growth parameters, height standard deviation score and height velocity standard deviation score in both groups. Serum insulin‐like growth factor I was also increased. There were no significant differences in growth response, serum IGF‐I levels, or the advance in bone age between the two study groups after 1 y of GH therapy. We conclude that twice daily s.c. growth hormone injections provide no advantages over once daily injection of the same dose in promoting the linear growth of short children without growth hormone deficiency.

A Randomized, Double-Blind, Placebo-controlled Study of Growth Hormone in the Treatment of Fibromyalgia

PURPOSE: The cause of fibromyalgia (FM) is not known. Low levels of insulin-like growth factor 1 (IGF-1), a surrogate marker for low growth hormone (GH) secretion, occur in about one third of patients who have many clinical features of growth hormone deficiency, such as diminished energy, dysphoria, impaired cognition, poor general health, reduced exercise capacity, muscle weakness, and cold intolerance. To determine whether suboptimal growth hormone production could be relevant to the symptomatology of fibromyalgia, we assessed the clinical effects of treatment with growth hormone. METHODS: Fifty women with fibromyalgia and low IGF-1 levels were enrolled in a randomized, placebo-controlled, double-blind study of 9 months’ duration. They gave themselves daily subcutaneous injections of growth hormone or placebo. Two outcome measures—the Fibromyalgia Impact Questionnaire and the number of fibromyalgia tender points—were evaluated at 3-monthly intervals by a blinded investigator. An unblinded investigator reviewed the IGF-1 results monthly and adjusted the growth hormone dose to achieve an IGF-1 level of about 250 ng/mL. RESULTS: Daily growth hormone injections resulted in a prompt and sustained increase in IGF-1 levels. The treatment (n = 22) group showed a significant improvement over the placebo group (n = 23) at 9 months in both the Fibromyalgia Impact Questionnaire score ( P <0.04) and the tender point score ( P <0.03). Fifteen subjects in the growth hormone group and 6 subjects in the control group experienced a global improvement ( P <0.02). There was a delayed response to therapy, with most patients experiencing improvement at the 6-month mark. After discontinuing growth hormone, patients experienced a worsening of symptoms. Carpal tunnel symptoms were more prevalent in the growth hormone group (7 versus 1); no other adverse events were more common in this group. CONCLUSIONS: Women with fibromyalgia and low IGF-1 levels experienced an improvement in their overall symptomatology and number of tender points after 9 months of daily growth hormone therapy. This suggests that a secondary growth hormone deficiency may be responsible for some of the symptoms of fibromyalgia.

Differential effects of growth hormone and prednisolone on energy metabolism and leptin levels in humans

Short-term growth hormone (GH) exposure has been shown to stimulate energy expenditure (EE) without concomitant changes in body composition. To what extent this is related to thyroid function, sympathetic activity, hyperinsulinemia, or leptin secretion is unknown. It is also unknown whether the calorigenic effect of GH is influenced by glucocorticoids, which are known to antagonise the anabolic actions of GH. To pursue this, eight normal male subjects (aged 22 to 28 years; body mass index, 21.6 to 26.3 kg/m 2) were randomly studied during four 4-day treatment periods with (1) day subcutaneous (SC) placebo injections and placebo tablets, (2) daily SC GH injections (0.1 IU/kg · d) and placebo tables, (3) daily prednisolone administration (25 mg morning and evening) plus placebo injections, and (4) daily GH injections plus prednisolone administration. GH administration decreased plasma epinephrine significantly (mean ± SE, 34.7 ± 5.7 ng/L for control v 24.8 ± 5.8 for GH, P < .05), had no effect on plasma norepinephrine or serum leptin, and increased both free triiodothyronine (FT 3) levels (5.7 ± 0.3 pmol/L for control v 6.7 ± 0.3 for GH, P < .05) and resting EE ([REE] 1,861 ± 61 kcal/24 h for control v 1,996 ± 69 for GH, P < .05). Prednisolone administration did not affect epinephrine and REE, decreased norepinephrine (116 ± 13, P < .05) and FT 3 (4.7 ± 0.2, P < .05), and increased leptin (3.93 ± 0.71, P < .05). Concomitant GH and prednisolone administration increased REE (2.068 ± 85, P ± .05) and leptin (4.82 ± 0.93 P ± .05), had no effect on either epinephrine or norepinephrine, and decreased FT 3 (5.0 ± 85, P ± .05). Resting heart rate (HR) increased only during GH, whereas sympathetic nerve activity was unchanged in all studies. Our data suggest that (1) the calorigenic effect of GH is not mediated by changes in sympathetic activity or leptin secretion, (2) rapid elevations in leptin induced by glucocorticoids do not affect EE in humans, and (3) the acute calorigenic effects of GH are probably related to increased cardiac workload.

Neuroregulatory Pathophysiology of Impoverished Growth Hormone (GH) Secretion in the Aging Human

A central enigma in neuroendocrine pathophysiology is the virtually uniform, but mechanistically incompletely explicable, attenuation of secretory and trophic activity of the growth hormone (GH)—insulin-like growth factor type I (IGF-I) axis in healthy aging in mammalian species, including the primate and human. Indeed, in humans, the calculated daily GH secretion rate falls approximately 50% every 7 years beginning at age 18 to 21, but this diminution in GH secretion is approximately twofold less rapid in premenopausal women. In contrast, the magnitude of relative GH deficiency appears to be similar in individuals of older (e.g., postmenopausal) age of either gender. Interpreting the mechanisms that underlie such marked attenuation of secretory activity of the GH-IGF-I axis is confounded by endocrinemetabolic covariates that accompany healthy aging, such as an accumulation of (visceral) adiposity, a decline in physical fitness, a reduction in sex steroids, disruption of slow-wave sleep, and concurrent il...

Growth hormone prevents prednisolone-induced increase in functional hepatic nitrogen clearance in normal man

Background/Aims: Glucocorticoid treatment increases urea excretion and leads to negative nitrogen balance. This effect is presumed mainly to reflect actions on tissue protein metabolism, but has been shown in rats to involve an hepatic element in the form of upregulation of the kinetics of ureagenesis. Likewise, the anabolic action of growth hormone administration has been shown to involve an hepatic element, just as growth hormone administration has been shown to prevent the protein catabolic side effects of prednisolone. Whether glucocorticoids increase the ability of the liver to convert amino-N to urea-N in man, and whether growth hormone counteracts any possible effect of glucocorticoid has not been studied. Methods: We measured urea nitrogen synthesis rates and blood a-amino-N levels before, during and after a 4-h constant i.v. infusion of alanine (2 mmol · kg BW −1 · h −1. The urea nitrogen synthesis rate was estimated hourly as urinary excretion corrected for gut hydrolysis and accumulation in body water. The slope of the linear relationship between urea nitrogen synthesis rate and amino-N concentration represents the hepatic kinetics of conversion of amino- to urea-N, and is denoted the functional hepatic nitrogen clearance. Eight normal male subjects (aged 22–28 years; BMI 21.6–26.3 kg/m 2) were randomly studied four times: i) after 4 days of s.c. saline injections, ii) after 4 days of s.c. growth hormone injections (0.1 IU · kg −1 · day −1), iii) after 4 days of glucocorticoid administration (50 mg/d) and iv) after 4 days of growth hormone and glucocorticoid administration. All injections were given at 20 00 hours and 25 mg prednisolone was given morning and evening. Results: Growth hormone decreased functional hepatic nitrogen clearance (l/h) by 21% (from 38.8±1.8 l/h (control) to 30.5±2.7 l/h (4 d growth hormone) (mean±SE) (ANOVA; p<0.05)). Glucocorticoid increased functional hepatic nitrogen clearance by 23% (47.7±3.3 l/h, p<0.05), while growth hormone plus glucocorticoid offset any effect on functional hepatic nitrogen clearance (36.2±3.3 l/h, p=0.83). Conclusions: Glucocorticoid administration leads to loss of nitrogen as urea, in part due to a specific hepatic mechanism, as shown by the increased functional hepatic nitrogen clearance. Growth hormone has the opposite effect, and also neutralises the glucocorticoid effect when given together with prednisolone. This adds to the understanding of the development and treatment possibilities of steroid catabolism.