Rise In Growth Hormone Levels Research Articles

Elucidating the relationship between blood glucose dynamics and growth hormone responses in glucagon stimulation tests among children with short stature

Introduction: The use of glucagon as a provocative agent for growth hormone (GH) assessment is a cornerstone in pediatric endocrinology. Glucagon's role as a GH secretagogue is integral to growth hormone stimulation tests (GHSTs), which diagnose suspected GH deficiency (GHD) in children. These tests are crucial for assessing the hypothalamic-pituitary-adrenal (HPA) axis's integrity. Despite its prevalent use, the exact mechanisms by which glucagon prompts GH release and the impact of ensuing blood glucose (BG) fluctuations are not fully understood. Objectives: This study aims to explore the relationship between GH and BG levels in children with short stature following glucagon administration. Patients and Methods: A retrospective cohort study involved 42 pediatric patients, aged 6 to 11, with short stature. We analyzed GH and BG levels before and after intramuscular glucagon Simulation test (GST). Blood samples were taken at baseline and multiple intervals post-injection. Results: The results revealed that the mean glucose peaked at 60 minutes and declined to a nadir at 120 minutes, which corresponded with a significant rise in GH levels. GH concentrations peaked at 120 minutes post-injection, with 31% of children showing peak GH levels of less than 7 μg/L. Notably, the study found an inverse correlation between BG and GH at peak glucose times, suggesting a complex interplay between glucose dynamics and GH response. Discussion: Our findings indicate a dynamic interrelation between BG and GH post-glucagon injection, challenging traditional interpretations of GST results. The study reinforces the notion that GHST results should be interpreted with consideration of patient-specific factors such as BMI to ensure accurate evaluation of GH reserve and subsequent clinical decision-making. Conclusion: The study corroborates the dynamic nature of GH and glucose responses following glucagon administration and highlights the need for personalized approaches in interpreting GHSTs. Further investigation is warranted to elucidate the mechanisms influencing this complex relationship, which is crucial for accurate diagnosis and management of GHD in children.

Hormonal response to a non-exercise stress test in athletes with overtraining syndrome: results from the Endocrine and metabolic Responses on Overtraining Syndrome (EROS) — EROS-STRESS

ObjectivesOvertraining syndrome (OTS) leads to worsened sports performance and fatigue. The pathophysiology of OTS has not been entirely elucidated, and there is a lack of accurate markers for its diagnosis. Changes in hormonal responses implicated in OTS were stimulated by exercise, which has limited their interpretation. Hence, we aimed to evaluate growth hormone (GH) and prolactin responses to a gold-standard and exercise-independent stimulation test, the insulin tolerance test (ITT). DesignVolunteers were recruited and divided into OTS-affected athletes (OTS), healthy athletes (ATL), and healthy non-active subjects (NCS) groups, after general and specific inclusion and exclusion criteria. MethodsWe evaluated the responses of growth hormone (GH) and prolactin to the ITT, and compared between groups. ResultsA total of 51 subjects were included (OTS, n=14, ATL, n=25, and NCS, n=12). OTS disclosed significantly lower basal levels of GH (p=0.003) and prolactin (p=0.048), and GH (p=0.001) and prolactin (p<0.001) responses to ITT (p=0.001), compared to ATL, but similar to NCS. OTS showed a later rise in GH levels in response to hypoglycemia, compared to ATL, but not to NCS. We suggest cutoffs for GH and prolactin levels to aid in the diagnosis of OTS. ConclusionsOTS-affected athletes show reduced GH and prolactin basal levels and responses to a non-exercise stress test compared to healthy athletes, but not to sedentary subjects.

The Glycemia-increasing Effect of a 30-second Sprint is Attenuated Following 60 Minutes of Moderate-Intensity Exercise

The glycemia-increasing effect of a short sprint has been proposed as a potential clinical tool to prevent exercise-mediated hypoglycemia in type 1 diabetes. However, prior moderate-intensity exercise may blunt the counterregulatory responses to further exercise. The purpose of this study was to investigate whether prior moderate-intensity exercise attenuates the counterregulatory response and associated glycemia-increasing effect of a 30-second sprint. Eight healthy males (age 21.8 ± 1.8 years; BMI 23.9 ± 2.2 kg•m-2; VO2peak 48.6 ± 6.6 ml•kg-1•min-1) completed two trials during which they either rested for 60 minutes (CON) or performed 60 minutes of moderate-intensity cycling at ∼65% VO2peak (EX). Following EX or CON, each participant rested for 3 hours and 15 minutes before performing a 30-second maximal cycling sprint and recovering in the laboratory for one hour. Blood glucose increased significantly and similarly in response to the sprint in both trials, peaking at 10 minutes of recovery. Blood glucose then declined at a faster rate in EX compared with CON, resulting in lower blood glucose at 45 minutes of recovery (p=0.024). The faster fall in blood glucose in EX was associated with a more consistent rise in glucose rate of disappearance (Rd) above the rate of appearance (Ra) during recovery. This might be explained, at least in part, by the lesser post-exercise rise in growth hormone levels in EX (p<0.05). These results suggest that prior moderate-intensity exercise does not affect the magnitude of the glycemia-increasing response of a 30-second sprint; however, the subsequent decline in blood glucose is more rapid.

Effect of Bromocryptine on hormones and milk secretion in Murrah buffaloes (Bubalus bubalis)

An experiment was carried out on 10 advance pregnant Murrah buffaloes to determine the role of hormones in milk secretion around parturition. Experimental animals were administered with a single injection of bromocryptine, @ 100 μg/kg BW, for 5 days before expected calving, whereas control group buffaloes were injected with placebo injections. Blood samples collected before parturition (−5,−4,−3,−2,−1 days), on day of parturition (day-0) and on day 1, 2, 3, 4, 5, 10 and 15 post partum were analyzed for growth hormone (GH), insulin like growth factor-I (IGF-I) and prolactin (PRL) by radioimmunassay methods. Milk samples were collected daily for 5 days and on day 10 and 15 after parturition. Milk fat, protein, lactose, citric acid, non-esterified fatty acids (NEFAs) and somatic cell counts (SCCs) were determined in milk samples. Bromocryptine treatment significantly (P < 0.01) decreased pre partum PRL and increased GH levels (P < 0.01) on day of parturition in experimental buffaloes without influencing plasma IGF-I level. Milk yield was significantly lower (P < 0.01) in experimental than in control group. Further, effect of bromocryptine on milk yield was only for a week. Milk yield increased (P < 0.01) gradually and was similar to control group on day 15 post partum. Bromocryptine treatment significantly increased milk SCC (P < 0.01) and protein content (P < 0.01) but there was no effect of treatment on fat, lactose, citric acid, glucose, milk and plasma NEFA concentration. It was concluded that prepartum suppression of PRL by bromocryptine impairs milk secretion temporarily in ensuing lactation. The significant rise in GH level before parturition and on day of parturition suggests a role of it in milk secretion of buffaloes.

Diagnosis of Growth Hormone Deficiency and the Treatment of Short Stature-Reply

In Reply. — We tried to summarize the complexity of current controversies about the diagnosis of growth hormone deficiency and the treatment of non-growth hormone—deficient short stature. The points raised by Dr Rotenstein further illustrate this complexity, and we welcome the opportunity to clarify these issues. Dr Rotenstein raises the question of growth hormone response to growth hormone releasing factor in the diagnosis of growth hormone deficiency. However, the classic definition of growth hormone deficiency does not involve assessment of the growth hormone secretory response to growth hormone releasing factor. The rise in growth hormone levels in some growth hormone—deficient children following administration of growth hormone releasing factor is a separate issue and suggests that the etiology of growth hormone deficiency in many children is actually deficiency of growth hormone releasing factor. We agree that the question of growth hormone treatment for very short non—growth hormone—deficient children who have marginal

Effect of clonidine on the secretion of anterior pituitary hormones in heroin addicts and normal volunteers

Neuroendocrine effects of intravenous injections of clonidine, 0.15 mg, were investigated in 13 heroin addicts and 14 normal control subjects. The study was designed to determine whether continuous opiate administration leads to the development of hypersensitive α 2-adrenergic receptors. The peak increments in levels of plasma growth hormone (GH) and β-endorphin induced by clonidine did not differ between heroin addicts and normal control subjects. At no time interval could the clonidine-induced rise in GH levels in addicts be differentiated from that induced by placebo. Clonidine failed to alter plasma prolactin, gonadotropin, or thyrotropin levels in either heroin addicts or controls. Since clonidine's neuroendocrine effects are reportedly due to the activation of postsynaptic α 2-adrenoceptors, it appears that (1) continuous opiate use does not lead to the development of hypersensitive α 2-adrenergic receptors involved in neuroendocrine mechanisms and (2) brain norepinephrine does not play a role in the regulation of tonic prolactin, gonadotropin, and thyrotropin secretion in man.

Growth Hormone Response to Clonidine is Impaired in Patients with Central Sympathetic Degeneration

Serum growth hormone (GH) levels before and after intravenous clonidine (1.5 mcg/Kg) were measured in normal subjects and patients with chronic idiopathic autonomic failure (AF) due to central sympathetic degeneration. Normal subjects showed a rise in plasma GH from 2 +/- 1 mU/l to 27 +/- 12 mU/l. Basal levels were similar but there was no rise in GH levels in the AF patients. There was no difference in sedation in the two groups, indicating similar central nervous system penetration of the drug. Systolic blood pressure fell in both groups. Diastolic blood pressure fell significantly in normals but not in the AF patients. Clonidine-induced growth hormone release may be a potentially useful neuroendocrine marker indicating derangement of certain components of the central alpha-adrenergic system in man.

An in vivo model for testing somatostatin suppression of growth hormone release in sheep.

To investigate the suppressive effect of somatostatin on growth hormone secretion, a consistent, potent stimulus to growth hormone release is required. The antilipolytic compound 3,5-dimethylpyrazole (DMP) gave a rapid rise in plasma immunoreactive growth hormone following iv administration to fasting sheep. The dose response relationship for iv DMP was defined in 12 sheep, and a rise in growth hormone levels from a baseline of 2.1 +/- 0.4 ng/ml (mean +/- SE) to 38.9 +/- 3.9 ng/ml was achieved in 40 min with 0.1 mg/kg bw of DMP given as a bolus. Infusion of graded doses of somatostatin (50, 100 and 200 micrograms) in 4 sheep over a 90 min period resulted in a dose-dependent suppression of the DMP-provoked growth hormone secretion below the responses observed during saline infusion. This experimental model should facilitate further studies of the inhibitory effects of somatostatin, its analogues and other drugs which suppress growth hormone secretion.

Improvement of growth-hormone stimulation with l-dopa/l-carbidopa by simultaneous administration of propranolol (author's transl)

The effect of simultaneous administration of 250 mg L-dopa + 25 mg L-carbidopa (Nacom) and 1 mg propranolol/kg body weight (maximal dose 40 mg propranolol) on growth-hormone secretion was tested in 96 children with growth retardation. The results were compared with those in a group of children that had been receiving only L-dopa and L-carbidopa. The additional administration of propranolol reduced the number of children unresponsive to adequate growth-hormone stimulation from 16% to 9.5%. There was no significant difference in mean maximal growth-hormone level between both groups, but the addition of propranolol caused a more long-lasting rise in serum growth hormone levels. Some of the children who previously had failed to have a satisfactory rise in growth-hormone level after L-dopa and L-carbidopa showed satisfactory stimulation when propranolol was added. Since only three blood samples need be taken (0, 45 and 90 minutes) and no significant side effects were noted, the combined treatment is suitable for out-patient use.

Failure of oral bromocriptine to affect hypergastrinemia in two patients with the Zollinger-Ellison syndrome

Bromocriptine was administered to 2 subjects with gastrin-secreting tumors of the pancreas. The absorption of the drug was confirmed by a rise in growth hormone levels but no change in the elevated serum gastrin levels were observed. Bromocriptine does not appear to affect gastrin hypersecretion in the way that it influences the hypersecretion of pituitary hormones.

Clonidine-induced increase in serum growth hormone: Possible role of epinephrine-mediated synapses

(1) The central “alpha adrenergic” agonist and antagonist clonidine (10 μg/kg) and piperoxane (1.0 and 2.5 mg/kg) were administered to nonhuman primates ( M. arctoides) in doses believed to increase or decrease activity at epinephrine-mediated synapses. (2) Clonidine, but not piperoxane or saline, produced a significant ( p < 0.05) rise in serum growth hormone (GH) levels at 30 min after the infusion. (3) Either pre-clonidine or post-clonidine administration of piperoxane blocked the clonidine-induced rise in GH levels. (4) These data support the hypothesis that the clonidine-induced increase in serum GH is mediated by alpha adrenergic receptors and suggest a role for epinephrine-mediated synapses in the stimulation of GH secretion.

EFFECTS OF SOMATOSTATIN ON PLASMA INSULIN, GROWTH HORMONE AND GLUCAGON LEVELS IN OBESE AND DIABETIC CHILDREN AND ADOLESCENTS

Somatostatin (GHRIH) could be helpful in the treatment of diabetes mellitus when high levels of growth hormone and glucagon interfere with the metabolic control. In obese children the i.v. injection of 3 ug/kg of ideal body weight of GHRIH before i.v. glucose tolerance test lowered significantly the glucose disappearance rate, the plasma insulin levels, and delayed the peak value. In diabetic children the i.v. administration of 3 μg/kg of GHRIH over two min, followed by a 60 min infusion of 7 μg/kg in saline solution induced a significant decrease of blood sugar, growth hormone and glucagon levels; the administration of 3 μg/kg of CHRIH immediately before a standardized physical exertion significantly reduced the rise of growth hormone levels. GHRIH can open new possibilities in the treatment of juvenile diabetes, at least after puberty.

Growth Hormone Response to Insulin–Induced Hypoglycemia in Newborn Infants

In the article by J. R. Humbert and R. W. Gotlin,1 the authors state that previous reports in which hypoglycemia was induced artificially with insulin demonstrated a variable growth hormone response. They then refer to the paper by Cornblath, et al.2 as reporting a failure to obtain a rise in growth hormone levels. This is incorrect as we found that insulin-induced hypoglycemia actually resulted in a very marked rise in growth hormone levels in both the full-term and premature infants tested.

Pituitary function after yttrium implants as measured by plasma growth hormone levels.

SUMMARY Plasma growth hormone (GH) levels during insulin hypoglycaemia were measured in 30 women with implants of 90Y in the pituitary for advanced breast cancer. There was evidence of continued pituitary activity in six patients (20%), the rise in plasma GH level being greater than 4 ng/ml during hypoglycaemia. Thirteen patients (43%) were regarded as having complete ablations because they had no GH response and a fasting level of less than 4 ng/ml. In the remaining 11 patients (37%) there was no rise in the GH level during hypoglycaemia, but there were significant fasting levels. From the post-mortem evidence it was concluded that these patients also had adequate ablations. This test is shown to be of more value in estimating residual pituitary function than routine tests of thyroid or adrenal function.

Metabolic and Hormonal Responses to Glucose and Glucagon in Patients with Infantile Malnutrition

Extract: The interrelations of plasma levels of glucose, free fatty acids (FFA), α-amino nitrogen (α-aaN), insulin, and growth hormone (GH) were studied in 26 malnourished infants shortly after admission to the hospital and again several weeks later when they had recovered. In the sick children (SC) fasting levels of FFA and GH were high, and insulin and α-aaN were low; with recovery FFA, α-aaN and insulin levels became normal, and GH levels fell. No change occurred in glucose levels. Ten infants were given glucose (0.5 g/kg body weight) intravenously on the 1st or 2nd day after admission and again 6–12 weeks later. Glucose tolerance was impaired in the sick group and, although improved, was not normal when the children had recovered from the nutritional insult. Insulin secretion was stimulated by glucose in those that had recovered (RC), but not in the SC. No significant change occurred in either FFA or α-aaN levels in these groups. Nine infants received glucagon (0.1 mg/kg body weight) intravenously on the 2nd to 6th day after admission and again 6–12 weeks later. Glucagon caused a rise in glucose levels that were greater in RC than in SC but did not cause a significant change in insulin levels in either group. Free fatty acid levels were higher in SC throughout the test, but in both groups FFA levels responded similarly to glucagon administration, falling 10 and 60 min after the injection. Changes in GH levels in plasma after glucose or glucagon administration were compared with the changes caused by five venepunctures in RC. Venepunctures and glucose caused similar rises in GH levels, but glucagon caused a greater rise than either. It was concluded that the stress of repeated venepunctures caused a rise in GH levels in plasma in all three tests, but that, independent of this, glucagon stimulated GH secretion. Speculation: Insulin secretion is impaired in infantile malnutrition and does not improve at the same rate as clinical recovery occurs, suggesting that normal β cell function is not essential for rapid growth. The role of growth hormone in malnutrition is not clear, but it appears to be involved more in the metabolic adaptation to malnutrition than in the control of growth.