Growth hormone secretion in primary adrenal Cushing's syndrome is disorderly and inversely correlated with body mass index

To evaluate the impact on the somatotropic axis of endogenous cortisol excess in the absence of primary pituitary disease, we investigated spontaneous 24-h growth hormone (GH) secretion in 12 adult patients with ACTH-independent hypercortisolism. Plasma GH concentration profiles (10-min samples) were analyzed by deconvolution to reconstruct secretion and approximate entropy to quantitate orderliness of the release process. Comparisons were made with a body mass index (BMI)-, age-, and gender-matched control group and an age- and gender-matched lean control group. GH secretion rates did not differ from BMI-matched controls but were twofold lower compared with lean subjects, mainly due to a 2.5-fold attenuation of the mean secretory burst mass (P = 0.001). In hypercortisolemic patients, GH secretion was negatively correlated with BMI (R = -0.55, P = 0.005) but not cortisol secretion. Total serum IGF-I concentrations were similar in the three groups. Approximate entropy (ApEn) was increased in patients with Cushing's syndrome compared with both control groups (vs. BMI-matched, P = 0.04; vs. lean, P = 0.001), denoting more irregular GH secretion patterns. ApEn in patients correlated directly with cortisol secretion (R = 0.77, P = 0.003). Synchrony between cortisol and GH concentration series was analyzed by cross-correlation, cross-ApEn, and copulsatility analyses. Patients showed loss of pattern synchrony compared with BMI-matched controls, but copulsatility was unchanged. We conclude that hyposomatotropism in primary adrenal hypercortisolism is only partly explained (approximately 30%) by increased body weight and that increased GH secretory irregularity and loss of synchrony suggest altered coordinate regulation of GH release.     

Long-term testosterone supplementation augments overnight growth hormone secretion in healthy older men

Circulating testosterone (T) and GH/IGF-I are diminished in healthy aging men. Short-term administration of high doses of T augments GH secretion in older men. However, effects of long-term, low-dose T supplementation on GH secretion are unknown. Our objective was to evaluate effects of long-term, low-dose T administration on nocturnal GH secretory dynamics and AM concentrations of IGF-I and IGFBP-3 in healthy older men (65-88 yr, n = 34) with low-normal T and IGF-I. In a double-masked, placebo-controlled, randomized study we assessed effects of low-dose T supplementation (100 mg im every 2 wk) for 26 wk on nocturnal GH secretory dynamics [8 PM to 8 AM, Q(20) min sampling, analyzed by multiparameter deconvolution and approximate entropy (ApEn) algorithms]. The results were that T administration increased serum total T by 33% (P = 0.004) and E(2) by 31% (P = 0.009) and decreased SHBG by 17% (P = 0.002) vs. placebo. T supplementation increased nocturnal integrated GH concentrations by 60% (P = 0.02) and pulsatile GH secretion by 79% (P = 0.05), primarily due to a twofold increase in GH secretory burst mass (P = 0.02) and a 1.9-fold increase in basal GH secretion rate (P = 0.05) vs. placebo. There were no significant changes in GH burst frequency or orderliness of GH release (ApEn). IGF-I levels increased by 22% (P = 0.02), with no significant change in IGFBP-3 levels after T vs. placebo. We conclude that low-dose T supplementation for 26 wk increases spontaneous nocturnal GH secretion and morning serum IGF-I concentrations in healthy older men.     

Longitudinal changes in growth hormone secretory process irregularity assessed transpubertally in healthy boys

Clarifying the time evolution, and underlying neuroendocrine regulation, of hormone secretion during puberty is of pivotal importance both physiologically and clinically. We sought to determine whether clinical growth and elevated growth hormone (GH) release in pubertal boys are associated with shifts in the irregularity of GH secretory patterns. We studied GH release in 23 healthy boys longitudinally at approximately 4-mo intervals over a 6-yr period throughout puberty, by repetitive blood sampling at 20-min intervals for 24 h on each study date. To quantify serial irregularity in the GH profiles, we utilized approximate entropy (ApEn), a scale- and model-independent quantification of the extent of sequential "randomness." Complementary statistical analyses establish that on a per-subject basis, serum GH concentration-time series show greatest secretory disorderliness (maximal ApEn) in prepuberty and mid-to-late puberty, followed by a steep decline in ApEn to maximal orderliness in postpubertal adolescence (P < 0.0001, ANOVA). Pooling all subject comparisons, we observed a persistent positive correlation between ApEn and growth velocity (GrVel), Pearson r = 0.467 (P < < 10(-10)). Moreover, in general, ApEn(GH) preceded GrVel evolution, with a time frame lead of 4-8 mo providing the most pronounced correlations between ApEn and GrVel. In the setting of low postpubertal growth, per-subject ApEn values fell to approximately one-half of maximal ApEn values and, on average, were in the 13th percentile from minimal (P < < 10(-10)) for fully mature boys. Thus, in a longitudinal transpubertal analysis, greater irregularity in GH secretion corresponds to greater linear growth in boys, which culminates in highly regular GH secretory dynamics after sexual maturity. In addition to clinical utility, there may be added experimental merit in knowing that GH dynamics typically predict accelerated linear growth in 4-8 mo.     

Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents

Ghrelin is an orexigenic peptide and a growth hormone (GH) secretagogue. Secretory dynamics of ghrelin have not been characterized in adolescents with anorexia nervosa (AN). We hypothesized that, compared with healthy adolescents, girls with AN would have increased ghrelin concentrations measured over 12 h of nocturnal sampling from increased basal and pulsatile secretion, and endogenous ghrelin would independently predict GH and cortisol. We examined ghrelin concentration and secretory dynamics in 22 girls with AN and 18 healthy adolescents 12-18 yr old. Associations between ghrelin, various hormones, and measures of insulin resistance were examined. On Cluster analysis, girls with AN had higher ghrelin concentrations than controls, including total area under the curve (AUC) (P = 0.002), nadir (P = 0.0006), and valley levels (P = 0.002). On deconvolution analysis, secretory burst amplitude (P = 0.03) and burst mass (P = 0.04) were higher in AN, resulting in higher pulsatile (P = 0.05) and total ghrelin secretion (P = 0.03). Fasting ghrelin independently predicted GH burst frequency (r = 0.44, P = 0.005). The nutritional markers body mass index and body fat predicted postglucose and valley ghrelin but not fasting levels. Ghrelin parameters were inversely associated with fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, and IGF-I. HOMA-IR was the most significant predictor of most ghrelin parameters. Valley ghrelin independently predicted cortisol burst frequency (52% of variability), and ghrelin parameters independently predicted total triiodothyronine and LH levels. Higher ghrelin concentrations in adolescents with AN are a consequence of increased secretory burst mass and amplitude. The most important predictor of ghrelin concentration is insulin resistance, and ghrelin in turn predicts GH and cortisol burst frequency.     

Regulated recovery of pulsatile growth hormone secretion from negative feedback: a preclinical investigation

Although stimulatory (feedforward) and inhibitory (feedback) dynamics jointly control neurohormone secretion, the factors that supervise feedback restraint are poorly understood. To parse the regulation of growth hormone (GH) escape from negative feedback, 25 healthy men and women were studied eight times each during an experimental GH feedback clamp. The clamp comprised combined bolus infusion of GH or saline and continuous stimulation by saline GH-releasing hormone (GHRH), GHRP-2, or both peptides after randomly ordered supplementation with placebo (both sexes) vs. E(2) (estrogen; women) and T (testosterone; men). Endpoints were GH pulsatility and entropy (a model-free measure of feedback quenching). Gender determined recovery of pulsatile GH secretion from negative feedback in all four secretagog regimens (0.003 ≤ P ≤ 0.017 for women>men). Peptidyl secretagog controlled the mass, number, and duration of feedback-inhibited GH secretory bursts (each, P < 0.001). E(2)/T administration potentiated both pulsatile (P = 0.006) and entropic (P < 0.001) modes of GH recovery. IGF-I positively predicted the escape of GH secretory burst number and mode (P = 0.022), whereas body mass index negatively forecast GH secretory burst number and mass (P = 0.005). The composite of gender, body mass index, E(2), IGF-I, and peptidyl secretagog strongly regulates the escape of pulsatile and entropic GH secretion from autonegative feedback. The ensemble factors identified in this preclinical investigation enlarge the dynamic model of GH control in humans.     

Episodic and TRH induced growth hormone release in primary hypothyroidism of man and rat.

In 27 hypothyroid subjects studied over 20 to 120 minutes, the concentration of serum growth hormone (GH) was variable with the amplitude and frequency of the secretory patterns similar to those reported by others for normal individuals. Serum GH, after the administration of thyrotropin releasing hormone (TRH) did not differ from values observed as spontaneous surges, in contrast to a consistent increase in thyrotropin and prolactin. Episodic secretion of GH persisted in thyroidectomized rats and did not differ significantly from that present in intact controls. It is concluded that episodic GH secretion is not abolished in primary hypothyroidism and that TRH is not a constant GH secretagogue in human subjects with hypothyroidism.     

Pharmacological activation of the GABAergic system does not affect GH and PRL release in acromegaly

An extensive hypothalamic neurotransmitter impairment has been proposed in acromegaly. However, at the moment, the hypothalamic GABAergic system has been little investigated in this disorder. Since GABA has been shown to modulate growth hormone (GH) and prolactin (PRL) secretion in human subjects, it seemed reasonable to investigate hypothalamic GABAergic functioning through the assessment of basal GH and PRL responses to pharmacological activation of this system. 800 mg of sodium valproate (SV), a drug with GABA facilitating properties, were administered orally to 7 acromegalic patients and 9 healthy volunteers. Blood samples were collected before and after the drug administration for the measurement of plasma GH and PRL levels. SV induced a clear-cut rise in basal GH and a decrease in basal PRL in healthy subjects, but it did not induce any change in the basal levels of these hormones in acromegalics. These results suggest that the response of GH and PRL to SV in acromegaly is qualitatively different from normal controls.     

Spontaneous growth hormone secretion in healthy prepubertal children of normal stature.

To evaluate the dynamics of growth hormone (GH) secretion in healthy prepubertal children of normal stature, we determined spontaneous GH secretion by measuring GH every 30 min in 21 Japanese subjects, age: 5.4 +/- 2.3 (1.6-10.6) years; height: -1.4 +/- 1.1 (-1.98-1.77) SD. The 24-h mean GH concentration was 4.8 +/- 1.5 ng/ml. The 24-h mean GH was similar in boys and girls (mean +/- SD: 4.8 +/- 1.7 vs 4.7 +/- 1.1 ng/ml). No correlation was found between chronological age and the 24-h mean GH. The 24-h mean GH was closely correlated with GH pulse amplitude (r = 0.94; P less than 0.001), but not with the number of GH pulses. The 24-h mean GH was also highly correlated with 3-h mean GH after sleep and 3-h peak GH after sleep (r = 0.86; P less than 0.001 and r = 0.72; P less than 0.001, respectively). Our data suggest that in healthy prepubertal children of normal stature, (1) spontaneous GH secretion is independent of sex and age, (2) the amount of spontaneous GH secretion is controlled by pulse amplitude, not by number of pulses. (3) 3-h mean GH and 3-h peak GH after sleep might represent 24-h total spontaneous GH secretion.     

Enhanced growth hormone responses to growth hormone releasing hormone in male type I diabetic patients.

In a previous paper we have demonstrated that growth hormone (GH) responses to growth hormone releasing hormone (GHRH) are higher in premenopausal normal women than in age matched healthy men. As in type I diabetes mellitus various disturbances of GH secretion have been reported, the aim of our study was to assess the effect of sex on basal and GHRH stimulated GH secretion in type I diabetes mellitus. In 21 female and 23 male type I diabetic patients and 28 female and 30 male control subjects GH levels were measured before and after stimulation with GHRH (1 microgram/kg body weight i.v.) by radioimmunoassay. GH responses to GHRH were significantly higher in female than in male control subjects (p less than 0.02), whereas the GH levels following GHRH stimulation were similar in female and male type I diabetic patients. GH responses to GHRH were significantly higher in the male type I diabetic patients than in the male control subjects (p less than 0.001); in the female type I diabetic patients and the female control subjects, however, GH responses to GHRH were not statistically different. The absence of an effect of sex on GHRH stimulated GH responses in type I diabetes mellitus provides further evidence of an abnormal GH secretion in this disorder.     

Cortisol and GH secretory dynamics, and their interrelationships, in healthy aged women and men

We studied 130 healthy aged women (n = 57) and men (n = 73), age 65-88 yr, with age-related reductions in insulin-like growth factor I and gonadal steroid levels to assess the interrelationships between cortisol and growth hormone (GH) secretion and whether these relationships differ by sex. Blood was sampled every 20 min from 8:00 PM to 8:00 AM; cortisol was measured by RIA and GH by immunoradiometric assay, followed by deconvolution analyses of hormone secretory parameters and assessment of approximate entropy (ApEn) and cross-ApEn. Cortisol mass/burst, cortisol production rate, and mean and integrated serum cortisol concentrations (P < 0.0005), and overnight basal GH secretion (P < 0.05), were elevated in women vs. men. Integrated cortisol concentrations were directly related to most measures of GH secretion in women (P < 0.01) and with mean and integrated GH concentrations in men (P < 0.05). Integrated GH concentrations were directly related to mean and integrated cortisol levels in women (P < 0.005) and men (P < 0.05), with no sex differences. There were no sex differences in cortisol or GH ApEn values; however, the cross-ApEn score was greater in women (P < 0.05), indicating reduced GH-cortisol pattern synchrony in aged women vs. men. There were no significant relationships of integrated cortisol secretion with GH ApEn, or vice versa, in either sex. Thus postmenopausal women appear to maintain elevated cortisol production in patterns that are relatively uncoupled from those of GH, whereas mean hormone outputs remain correlated.     

Effects of food restriction and restoration on gonadotropin and growth hormone secretion in immature male rats

This experiment concerned the changing patterns in secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and growth hormone (GH) under conditions of food restriction and subsequent catch-up growth. Weanling male rats were given either restricted (4 g food/day) or unrestricted access to food until 60 days of age. At this age, food-restricted rats weighed only 25% as much as rats fed ad libitum. Food restriction resulted in a dramatic decrease in the frequency of LH and GH pulses, and in the amplitude of GH pulses. It also slightly but significantly decreased mean blood levels of FSH (which was not secreted in a pulsatile manner in 60-day-old controls fed ad libitum). When restricted rats were given unrestricted access to food, frequency of LH and GH pulses and mean levels of FSH increased significantly and simultaneously within 2 days in half of the animals. Only an additional 8-10% of their body weight decrement was recovered at this time. After 10 days of food restoration, when restricted rats still weighed 50% less than controls, their secretory patterns of all three hormones were not significantly different from those of controls. Thus, recovery of gonadotropin and GH secretion was relatively rapid. Except for the quantitatively lesser impact of food restriction on FSH secretion, there was no evidence of any priorities in the secretion of the three hormones. Under conditions of rapid catch-up growth, the secretory patterns of LH, FSH, and GH appeared to develop simultaneously.     

Changes in Endocrine Orcadian Rhythms as Markers of Physiological and Pathological Brain Aging

We studied the circadian rhythm of plasma melatonin, growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), and Cortisol in 52 mentally healthy old subjects, 35 old demented patients, and 22 clinically healthy young controls. When compared to young controls, the circadian profile of plasma melatonin of old subjects, both demented or not, was clearly flattened, particularly during the night. The selective impairment of nocturnal melatonin secretion was significantly related to both the age and the severity of mental impairment (Mini Mental State Examination [MMSE] score). The PRL and GH circadian profiles were similar in the three groups during the day, but a significant lowering of the values recorded during the night occurred with aging. The impairment of the nocturnal secretion was related to the subjects' age and, for the GH secretory pattern only, also to the MMSE score. The ACTH circadian profile was similar in the three groups studied, even when old subjects exhibited higher ACTH levels throughout the 24h cycle, compared to young controls. Significantly higher Cortisol values at evening- and nighttime occurred in elderly subjects and particularly in the demented group. Both the mean levels and the nadir values of plasma Cortisol were positively related to age and negatively to MMSE score. In order to verify the sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to the steroid feedback, the circadian profile of plasma Cortisol was evaluated also after dexamethasone (DXM) administration (1 mg at 23:00h); the sensitivity of the HPA axis was significantly impaired in old subjects and particularly in the demented ones. These findings suggest that the neuroendocrine alterations already present in physiological aging, due to both anatomical damages and unbalanced central neurotransmitters, are enhanced in senile dementia. (Chronobiology International, 14(4), 385–396, 1997)     

A statistical model of diurnal variation in human growth hormone

The diurnal pattern of growth hormone (GH) serum levels depends on the frequency and amplitude of GH secretory events, the kinetics of GH infusion into and clearance from the circulation, and the feedback of GH on its secretion. We present a two-dimensional linear differential equation model based on these physiological principles to describe GH diurnal patterns. The model characterizes the onset times of the secretory events, the secretory event amplitudes, as well as the infusion, clearance, and feedback half-lives of GH. We illustrate the model by using maximum likelihood methods to fit it to GH measurements collected in 12 normal, healthy women during 8 h of scheduled sleep and a 16-h circadian constant-routine protocol. We assess the importance of the model components by using parameter standard error estimates and Akaike's Information Criterion. During sleep, both the median infusion and clearance half-life estimates were 13.8 min, and the median number of secretory events was 2. During the constant routine, the median infusion half-life estimate was 12.6 min, the median clearance half-life estimate was 11.7 min, and the median number of secretory events was 5. The infusion and clearance half-life estimates and the number of secretory events are consistent with current published reports. Our model gave an excellent fit to each GH data series. Our analysis paradigm suggests an approach to decomposing GH diurnal patterns that can be used to characterize the physiological properties of this hormone under normal and pathological conditions.     

Comparative in vivo and in vitro studies on abnormal GH secretion in patients with acromegaly

Eight patients with active acromegaly due to GH-producing pituitary adenoma were studied. GH secretory dynamics in vitro was evaluated by adding GRF, CRF, or a somatostatin analog, SMS 201-995 to the perifusate of dispersed cells from tumors. A comparison was made between the data obtained in preoperative tests for GH secretion and those obtained in experiments in vitro. Before operation, the GRF test (100 micrograms, iv) resulted in no GH response in three of six patients examined. The CRF test (100 micrograms, iv) resulted in a paradoxical GH increase in two of the same six patients. In vitro studies performed on adenoma cells revealed that exposure to GRF (100 ng/ml) elicited an increase in GH in seven of eight patients examined. Exposure to CRF (100 ng/ml) caused an enhanced GH secretion in four of the same eight patients. There were cases in which GH response to these hypothalamic hormones was observed in vitro but not in vivo, whereas there was only one case in which CRF caused an increase in GH in vivo but not in vitro. Thus, GH secretory dynamics was not always the same in vivo and in vitro. The discrepancy could be ascribed to the different secretory status of hypothalamic hormone (e.g., GRF or somatostatin) in vivo in each acromegalic patient.     

Acute exposure to GH during exercise stimulates the turnover of free fatty acids in GH-deficient men.

The secretion of growth hormone (GH) increases acutely during exercise, but whether this is associated with the concomitant alterations in substrate metabolism has not previously been studied. We examined the effects of acute GH administration on palmitate, glucose, and protein metabolism before, during, and after 45 min of moderate-intensity aerobic exercise in eight GH-deficient men (mean age = 40.8 +/- 2.9 yr) on two occasions, with (+GH; 0.4 IU GH) and without GH administered (-GH). A group of healthy controls (n = 8, mean age = 40.4 +/- 4.2 yr) were studied without GH. The GH replacement during exercise on the +GH study mimicked the endogenous GH profile seen in healthy controls. No significant difference in resting free fatty acid (FFA) flux was found between study days, but during exercise a greater FFA flux was found when GH was administered (211 +/- 26 vs. 168 +/- 28 micromol/min, P < 0.05) and remained elevated throughout recovery (P < 0.05). With GH administered, the exercise FFA flux was not significantly different from that observed in control subjects (188 +/- 14 micromol/min), but the recovery flux was greater on the +GH day than in the controls (169 +/- 17 vs. 119 +/- 11 micromol/min, respectively, P < 0.01). A significant time effect (P < 0.01) for glucose rate of appearance from rest to exercise and recovery occurred in the GH-deficient adults and the controls, whereas there were no differences in glucose rate of disappearance. No significant effect across time was found for protein muscle balance. In conclusion, 1) acute exposure to GH during exercise stimulates the FFA release and turnover in GH-deficient adults, 2) GH does not significantly impact glucose or protein metabolism during exercise, and 3) the exercise-induced secretion of GH plays a significant role in the regulation of fatty acid metabolism.     

Effect of growth hormone-releasing hormone and clonidine on growth hormone release in type 1 diabetic patients

We administered growth-hormone releasing hormone (GHRH), clonidine or thyrotropin-releasing hormone (TRH) as intravenous boli each in three different randomized mornings to nine well-controlled Type 1 diabetic men and to six age-matched healthy men who served as controls. GHRH and clonidine evoked a prompt and brisk GH release both in diabetic and in control subjects with no significant difference being evident between the two groups. Only one diabetic subject showed a paradoxical GH release after TRH when he was under long-term poor metabolic control. These results indicate that in insulin-dependent patients with good control of the metabolic disease the response of somatotropes to pituitary- or central nervous system-directed stimuli is normal. These data are supportive of the idea that altered GH secretion in Type 1 diabetes rather than reflecting a primary hypothalamic and/or pituitary alteration may be a state-dependent phenomenon related to the metabolic state of the disease.     

Nocturnal growth hormone secretory dynamics are altered after resistance exercise: deconvolution analysis of 12-hour immunofunctional and immunoreactive isoforms

To characterize the effects of daytime exercise on subsequent overnight growth hormone (GH) secretion and elimination dynamics, serum was sampled, and GH was measured every 10 min for 12 h (1800 to 0600) in a control (CON) condition and after a 50-set resistance exercise protocol (EX) from 1500 to 1700. GH was measured with a conventional immunoreactive (IR) and an immunofunctional (IF) assay, and values were analyzed via a multi-parameter deconvolution analysis. EX resulted in a higher overnight secretory burst frequency [CON: 7.6 (SD 2.4) < EX: 9.4 (2.2) bursts per 12 h, P = 0.005] but lower mean burst mass [CON: 9.2 (4.7) > EX: 6.0 (2.9) microg/l, P = 0.019] and secretory rate [CON: 0.68 (0.29) > EX: 0.48 (0.23) microg/l/min; P = 0.015; ANOVA main effect means presented]. Approximate entropy (ApEn) was greater after EX, indicating a less orderly GH release process than CON. The estimated half-life of IF GH was significantly lower than IR GH [IF: 15.3 (1.1) < IR 19.8 (1.6) min, P < 0.001] but similar between the CON and EX conditions (approximately 17 min). Despite the changes in secretory dynamics, 12-h mean and integrated GH concentrations were similar between conditions. The results suggest that although quantitatively similar total amounts of GH are secreted overnight in CON and EX conditions, resistance exercise alters the dynamics of secretion by attenuating burst mass and amplitude yet increasing burst frequency.     

Effect of sodium oxybate on growth hormone secretion in narcolepsy patients and healthy controls

Hypocretin deficiency causes narcolepsy and may affect neuroendocrine systems and body composition. Additionally, growth hormone (GH) alterations my influence weight in narcolepsy. Symptoms can be treated effectively with sodium oxybate (SXB; γ-hydroxybutyrate) in many patients. This study compared growth hormone secretion in patients and matched controls and established the effect of SXB administration on GH and sleep in both groups. Eight male hypocretin-deficient patients with narcolepsy and cataplexy and eight controls matched for sex, age, BMI, waist-to-hip ratio, and fat percentage were enrolled. Blood was sampled before and on the 5th day of SXB administration. SXB was taken two times 3 g/night for 5 consecutive nights. Both groups underwent 24-h blood sampling at 10-min intervals for measurement of GH concentrations. The GH concentration time series were analyzed with AutoDecon and approximate entropy (ApEn). Basal and pulsatile GH secretion, pulse regularity, and frequency, as well as ApEn values, were similar in patients and controls. Administration of SXB caused a significant increase in total 24-h GH secretion rate in narcolepsy patients, but not in controls. After SXB, slow-wave sleep (SWS) and, importantly, the cross-correlation between GH levels and SWS more than doubled in both groups. In conclusion, SXB leads to a consistent increase in nocturnal GH secretion and strengthens the temporal relation between GH secretion and SWS. These data suggest that SXB may alter somatotropic tone in addition to its consolidating effect on nighttime sleep in narcolepsy. This could explain the suggested nonsleep effects of SXB, including body weight reduction.     

Comparative effect of clonidine and growth hormone (GH)-releasing hormone on GH secretion in adult patients on chronic glucocorticoid therapy.

Glucocorticoids are thought to inhibit growth hormone (GH) secretion through an enhancement of endogenous somatostatin tone. The aim of our study was to evaluate the effects of GH-releasing hormone (GHRH) and clonidine, an alpha-2-adrenergic agonist which increases GH secretion acting at the hypothalamic level with an unknown mechanism, on GH secretion in seven adult patients (3M, 4F) with non endocrine diseases and on daily immunosuppressive glucocorticoid therapy. Eleven normal subjects (7M, 4F) served as controls. Steroid-treated patients showed a blunted GH response to GHRH (GH peak 8.3 +/- 3 micrograms/L) with respect to normal subjects (GH peak 19.3 +/- 2.4 micrograms/L). The GH responses to clonidine were also blunted (p less than 0.05) in steroid-treated patients (GH peak 5.8 +/- 2.8 micrograms/L) with respect to normal subjects (GH peak 17.6 +/- 2.3 micrograms/L). No significant differences between the GH responses to GHRH and clonidine were observed either in steroid-treated or in normal subjects. Clonidine is not able to enhance GH secretion similar to GHRH in patients chronically treated with steroids. It can be hypothesized that clonidine does not elicit GH secretion decreasing hypothalamic somatostatin tone.     

Plasma levels of total and active ghrelin in acromegaly and growth hormone deficiency

Ghrelin is an endogenous growth hormone (GH) secretagogue recently isolated from the stomach. Although it possesses a strong GH releasing activity in vitro and in vivo, its physiological significance in endogenous GH secretion remains unclear. The aim of this study was to characterize plasma ghrelin levels in acromegaly and growth hormone deficiency (GHD). We investigated plasma total and active ghrelin in 21 patients with acromegaly, 9 patients with GHD and 24 age-, sex- and BMI-matched controls. In all subjects, we further assessed the concentrations of leptin, soluble leptin receptor, insulin, IGF-I, free IGF-I and IGFBP-1, 2, 3 and 6. Patients with acromegaly and GHD as well as control subjects showed similar levels of total ghrelin (controls 2.004+/-0.18 ng/ml, acromegalics 1.755+/-0.16 ng/ml, p=0.31, GHD patients 1.704+/-0.17 ng/ml, p=0.35) and active ghrelin (controls 0.057+/-0.01 ng/ml, acromegalics 0.047+/-0.01 ng/ml, p=0.29, GHD patients 0.062+/-0.01 ng/ml, p=0.73). In acromegalic patients plasma total ghrelin values correlated negatively with IGF-I (p<0.05), in GHD patients active ghrelin correlated with IGF-I positively (p<0.05). In the control group, total ghrelin correlated positively with IGFBP-2 (p<0.05) and negatively with active ghrelin (p=0.05), BMI (p<0.05), WHR (p<0.05), insulin (p=0.01) and IGF-I (p=0.05). Plasma active ghrelin correlated positively with IGFBP-3 (p=0.005) but negatively with total ghrelin and free IGF-I (p=0.01). In conclusion, all groups of the tested subjects showed similar plasma levels of total and active ghrelin. In acromegaly and growth hormone deficiency plasma ghrelin does not seem to be significantly affected by changes in GH secretion.