Basal Growth Hormone Levels Research Articles

Basal growth hormone concentrations in blood and the risk for prostate cancer: A case-control study

To assess the relationship between basal serum growth hormone (GH) levels and prostate cancer risk. We conducted a population-based case-control study; cases included 68 men, aged 45-85 years, diagnosed with incident, primary, histologically confirmed, and clinically apparent (stage B and higher) prostate cancer. Controls included 240 men, frequency matched on age and residential area. Age, race, BMI, waist circumference, history of enlarged prostate, education, and current smoking status, were all considered as possible confounders. We found a statistically significant trend of decreasing prostate cancer risk across increasing GH quintiles, in both crude (OR: 0.31, 95% CI: 0.12-0.83, P for trend 0.01) and adjusted models (OR: 0.35, 95% CI: 0.12-1.05, P for trend 0.03), in the highest compared to the lowest quintile, respectively. Lower basal levels of GH in serum are associated with increased prostate cancer risk. The inverse association may be explained by the negative feedback loop generated by IGF-1 produced by the tumor on GH secretion.

A case of excess growth hormone levels

Patients with anorexia nervosa are known to have elevated basal growth hormone levels, which fail to suppress normally during glucose tolerance testing. We describe a case of probable anorexia nervosa initially diagnosed as acromegaly despite a low insulin-like growth factor-1 level and treated with transsphenoidal surgery based on a pituitary microadenoma on magnetic resonance imaging and a lack of suppression of growth hormone levels during glucose tolerance testing. This case highlights, firstly, that pituitary magnetic resonance imaging will suggest a pituitary adenoma in up to 10% of normal individuals. Secondly, that a diagnosis of acromegaly should be made on clinical features as well as growth hormone measurements.

Usefulness of the Thyrotropin-Releasing Hormone Test in Pre-Clinical Acromegaly

Acromegaly is caused primarily by pituitary growth hormone (GH)-secreting tumors. It is usually recognized because of characteristic manifestations, and diagnosed clinically. However, there exists a mild stage of acromegaly, which poses a diagnostic problem due to the absence of typical clinical manifestations. Here we present four patients with pre-clinical acromegaly, who showed minimal acromegaloid features with elevated levels of insulin-like growth factor-I. Basal GH levels were within normal levels in 3 of 4 cases, while insulin-like growth factor-I levels were elevated above normal in all cases. Plasma GH levels were elevated in response to thyrotropin-releasing hormone (TRH) in all cases, indicating a diagnostic value of the TRH stimulation test. In contrast, an oral glucose tolerance test was not useful for the diagnosis, because of the low GH levels (less than 1 ng/ml) and/or secondary to diabetes mellitus. In response to a dopamine agonist, GH levels were increased in the two cases, whereas GH levels were decreased or remained unchanged in the other two cases. We therefore suggest that the TRH stimulation test would be helpful to examine the presence of pre-clinical acromegaly. Diagnosis of the early stages of acromegaly is important to prevent progression to overt acromegaly.

Difference between diabetic and nondiabetic smokers in the pituitary response to physical exercise

The growth hormone (GH), cortisol, and arginine vasopressin (AVP) responses to bicycle ergometry (with increasing workload until exhaustion) were measured in 20 patients affected by insulin-dependent diabetes mellitus (IDDM) (10 habitual smokers and 10 nonsmokers) and 20 nondiabetic subjects (normal controls) (10 habitual smokers and 10 nonsmokers). Cardiorespiratory parameters such as heart rate, blood pressure, ventilation, frequency of breathing, tidal volume, oxygen consumption (V o 2), carbondioxide production (V co 2), and respiratory exchange ratio (R) were monitored before and during exercise tests. No significant differences between groups were observed; furthermore, there were no differences in circulating somatomedin-C (SM-C) and free fatty acids (FFA) levels between groups. Blood glucose levels were similar before exercise and followed a similar pattern during tests in diabetic smokers and nonsmokers. Basal GH, cortisol, and AVP levels were similar in diabetic smokers, diabetic nonsmokers, normal smokers, and normal nonsmokers. In all groups, exercise induced a significant increase in the serum concentrations of all examined hormones. Increments were significantly higher in diabetic than in nondiabetic groups. No significant differences were observed between diabetic smokers and nonsmokers for all examined hormones. AVP responses during tests were similar in normal smokers and nonsmokers. In contrast, exercise-induced GH and cortisol increments were significantly lower in normal smokers than in normal nonsmokers.These data support the hypothesis that in normal subjects habitual nicotine consumption may attenuate both GH and cortisol responses to a releasing stimulation, such as physical exercise. This phenomenon may represent an expression of adaptation of nicotinic neurotransmission to chronic stimulation. Furthermore, the data show that the effect induced by habitual smoking is absent in diabetics, probably because of diabetes-induced neuroendocrine alterations in the central nervous system.

Impaired cholecystokinin secretion and disturbed appetite regulation in women with polycystic ovary syndrome

Increased amount of abdominal fat and obesity are common in polycystic ovary syndrome (PCOS). A higher prevalence of bulimia nervosa and greater cravings for sweets have also been reported in these patients. The present study aimed to compare meal-related appetite and secretion of the ‘satiety peptide’ cholecystokinin (CCK) and glucose regulatory hormones in PCOS women and controls. Sixteen pairs of women with PCOS and controls matched for age and body mass index participated in the study. After an overnight fast, blood samples were collected during ingestion of a standardized meal. We determined basal and postprandial blood levels of CCK, insulin, C-peptide, glucagon, cortisol, growth hormone and glucose. Self-ratings of appetite were assessed by a visual analog scale. PCOS women had a significantly lower meal-related CCK response (p < 0.05) with no association with satiety, as in the controls (r = 0.64). There was a tendency to higher ratings of craving for sweets in PCOS women (p = 0.07) but no correlation with insulin, as in the controls (r = 0.50). Within the PCOS group, ratings of craving for sweets were inversely related to testosterone (r = −0.60) and the CCK response was positively correlated with levels of free testosterone (r = 0.50). We conclude that women with PCOS have reduced postprandial CCK secretion and deranged appetite regulation associated with increased levels of testosterone. Impaired CCK secretion may play a role in the greater frequency of binge eating and overweight in women with PCOS.

Serum growth hormone and insulin but not insulin-like growth factor-1 levels are elevated in patients with fibromyalgia syndrome

Standard radioimmunoassay (RIA) was employed to quantify basal serum growth hormone (GH), insulin-like growth factor-I (IGF-1), and insulin levels in 32 normoglycemic patients with clinically active fibromyalgia and in 29 normoglycemic control subjects. The GH concentration was significantly higher (P < 0.001) in female fibromyalgia patients than age-matched, normal female subjects. In contrast, basal serum IGF-1 concentrations did not differ between these groups. A scatter plot generated from two-stage, least-squares analysis showed that serum GH lacked correlation with the serum IGF-1 concentrations of normal female subjects (P = 0.73) and female fibromyalgia patients (P = 0.19). In addition to the results from serum GH and IGF-1 RIA, we also found significantly higher fasting serum insulin levels (P = 0.03) in male fibromyalgia patients and a trend toward elevated fasting serum insulin levels in the female fibromyalgia population ( P = 0.07), with the mean fasting level in the male fibromyalgia group (35.7 microU/ml(-1)) exceeding the upper limit of normal serum insulin levels (i.e., 27 microU/ml(-1)). Based on these results, basal serum GH and fasting serum insulin levels appear to be valuable surrogate markers in clinically active, normoglycemic fibromyalgia patients.

Réponses de GH, IGF-1 et IGF-BP3 à un exercice submaximal : différences entre sujets entraînés et sédentaires

Aim. – We explored growth hormone (GH), insulin-like growth factor 1 (IGF-1) and IGF-BP3 (IGFs binding protein 3) responses during a submaximal exercise and its recovery in trained and sedentary young subjects. Subjects and methods. – The study investigates 18 year old sportsmen ( N = 20) and sedentary boys of the same age as control group ( N = 19). A 20 min exercise is performed on an ergocycle to reach by steps 90% of the theoretical maximal heart rate which is maintained during the last 7 min. Blood samples were drawn before the test, at the end of exercise and at 10th, 20th and 45th minutes in the recovery period. Results. – Basal GH levels are higher in sportsmen than in controls (4 ± 5 vs. 2 ± 1 mUI/ml; P < 0.05) and during recovery ( P < 0.005). Basal IGF-1 level is lower in sportsmen than in controls (705 ± 232 vs. 357 ± 83 ng/ml; P < 0.0001), at all times during exercise. Basal IGF-BP3 levels are 4.5 ± 1.1 μg/ml in sportsmen and 4.4 ± 1.2 in controls. IGF-PB3 is not modified by exercise and does not depend on the training level. The W170 (power capacity at 170 pulses/min), and the maximal oxygen uptake differ between the two groups ( P < 0.0001). Glycaemic variations during the test did not differ significantly between the two groups. Conclusion. – Response of GH to exercise is more significant in sportsmen than in sedentary men; IGF-1 and IGF-BP3 levels do not vary significantly during exercise.

Basal and stimulated levels of growth hormone, insulin-like growth factor-I (IGF-I), IGF-I binding and IGF-binding proteins in beta-thalassemia major.

A significant percentage of children with beta-thalassemia major shows retardation in longitudinal growth as they progress towards puberty due to skeletal dysplasia, endocrine gland hypofunction or trace element deficiencies. The aim of this study was to evaluate GH/IGF-I secretion and action in prepubertal patients with beta-thalas-semia major. Eight prepubertal patients with short stature (group A) and seven prepubertal patients with normal stature (group B) were studied. Basal and stimulated (after administration of the hexapeptide Hexarelin) GH levels were measured with IRMA (Nichols); IGF-I and IGFBP-3 levels were measured with RIA (Nichols). IGF-I binding proteins (IGFBPs) were analyzed qualitatively with Western ligand blot. IGF-I binding to B-lymphocytes of the patients was also measured with competitive binding studies using human recombinant IGF-I and 125I-IGF-I (Amersham). Basal GH levels did not differ statistically between the groups. Peak GH levels after Hexarelin stimulation test were higher in group A (A: 27.9 +/- 15.6 ng/ml vs B: 9.1 +/- 4.7 ng/ml) (Wilcoxon test, p < 0.05). IGF-I levels in the two groups were low-normal and comparable (A: 168.0 +/- 81.6 ng/ml vs B: 126.6 +/- 25.5 ng/ml). IGFBP-3 levels were low in both groups (A: 1.21 +/- 0.27 microg/ml vs B: 1.08 +/- 0.20 microg/ml). Western ligand blot did not reveal any discernible difference in IGFBPs. However, IGF-I binding on B-lymphocytes was at least 20% lower in group A compared to group B (t-test, p < 0.01). IGF-I binding inversely correlated with peak GH levels (r = -0.54, p < 0.05). Patients in group A were older and chronological age correlated with IGF-I levels (r = 0.53, p < 0.05) whereas it inversely correlated with IGF-I binding (r = -0.63, p < 0.05). Moreover, patients in group A had higher ferritin levels. No correlation was found between ferritin levels, desferrioxamine dose/compliance or liver enzyme levels and the parameters of the GH axis studied. However, desferrioxamine dose x years correlated with IGFBP-3 (r = 0.56, p < 0.05) and correlated inversely with IGF-I binding (r = -0.74, p < 0.01). In conclusion, we have shown adequate GH secretion, higher secretive capacity after the administration of Hexarelin and lower IGF-I binding in prepubertal beta-thalassemic patients with short stature. Whatever the cause, reduced IGF-I action has to be considered when treating beta-thalassemic patients with short stature.

Familial Acromegaly: A Familial Report and Review of the Literature

Familial acromegaly without features of multiple endocrine neoplasie type 1 (MEN 1) is an exceptional clinical entity. We report in this article three cases of acromegaly due to pituitary macroadenomas without any other endocrinopathy in a family. A 31‐year‐old woman (subject A) and her 34‐year‐old sister (subject B) with elevated basal rolactin (PRL) levels, elevated growth hormone (GH) levels during the oral glucose tolerance test (OGTT) and a pituitary adenoma in Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) were diagnosed as acromegaly. Subject A was treated only with radiotherapy and Lysuride. Subject B underwent transsphenoidal microsurgical extirpation 15 years ago. 11 years later her 24‐year‐old son (subject C) also presented with typical signs of acromegaly, elevated basal PRL level and elevated GH levels during OGTT. A pituitary macroadenoma was identified by MRI and he also underwent transsphenoidal adenomectomy. Pathology reports confirmed the diagnosis of GH‐secreting pituitary adenoma in subject B and C. Immunocytochemistry revealed that tumours of subject B (> 20% of tumour cells) and C (> 50% of tumour cells) were positive for GH. Tumours of subject B (> 10% of tumour cells) and C (> 50% of tumour cells) also exhibited immunoreactivity for PRL. On investigation of histocompatibility antigens, it was observed that the subject A, B, and C shared the same haplotypes [HLA A24(9), HLA B13(6), HLA B35, HLA DQ7(3), HLA DR13(6)] and so it is very possible that investigation of HLA antigens in patients with pituitary tumour, contributes to better identification of its familial nature and frequency. Here we describe an acromegaly family and the distributions of HLA antigens.

Constitutionally Tall Stature with Morphological Abnormality of the Pituitary Gland

We describe two male pubertal cases of constitutionally tall stature (CTS) with an enlarged pituitary gland or pituitary microadenoma. Both patients' basal serum growth hormone (GH) levels were normal. Neither had oversecretion of any other pituitary hormones. However, their serum GH levels were paradoxically increased in response to an intravenous administration of thyrotropin-releasing hormone (TRH). A later GH response to an intravenous administration of luteinizing hormone-releasing hormone (LHRH) was also found in one patient. In addition, oral glucose loading (OGL) caused a late increase in serum GH at 180 min in both patients. Our present findings suggest that endocrinological and morphological abnormalities of the pituitary gland are found in some subjects with CTS during puberty. It is speculated that these paradoxical GH responses are associated with dysregulation of GH secretion. Finally, it is important to investigate whether tall children with morphological abnormalities of the pituitary gland such as our patients are preacromegalic, in which case, given that overproduction of GH secretion may occur in the future, further observation is necessary.

Body Composition Modulates the Effects of Hormone Replacement Therapy on Growth Hormone and Insulin-Like Growth Factor-I Levels in Postmenopausal Women

Objective: To examine the relationships of body composition with basal serum estrone, estradiol, androstenedione, cortisol, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in 73 postmenopausal women. Design: Cross-sectional study of hormone levels and body composition determined by dual-energy X-ray absorptiometry and anthropometry in women who were not taking oral hormone replacement therapy (HRT) and women taking HRT. Because high adiposity may modify hormone levels, subjects were grouped by fatness into obese (BMI >25 kg/m² and waist circumference >80 cm) and lean groups, as well as by HRT use. Results: Total levels of estrone, estradiol, GH and cortisol were significantly higher and IGF-1 was lower in HRT users. In HRT users, estradiol levels were higher and GH levels were lower in obese than lean women. IGF-1 levels were lower in obese HRT users than lean nonusers. Total cortisol levels were significantly higher in lean HRT users than lean nonusers and obese users. GH and IGF-1 were significantly inversely correlated with trunk fat and percent body fat. Multiple regression revealed that only trunk fat was a significant (negative) determinant of GH and IGF-1 levels, whereas HRT use positively and negatively predicted GH and IGF-1, respectively. Percent body fat significantly predicted estradiol levels. Body composition did not differ by HRT use. Conclusions: Our results suggest that trunk fat attenuates the HRT-induced increase on GH levels. In addition, trunk fat is a significant determinant of low IGF-1 levels in postmenopausal women, and IGF-1 levels decline more with HRT use.

Growth Hormone Releasing Hormone Test for Infertile Men With Spermatogenetic Maturation Arrest

Growth hormone has an important role in the function of the male reproductive system. We investigated infertile men with impaired growth hormone secretion. Growth hormone status was studied in 8 fertile men and 9 infertile men with azoospermia due to spermatogenetic maturation arrest. Growth hormone releasing hormone, the specific stimulatory neurohormone, was used in the growth hormone stimulation test. A dose of 100 microg. of growth hormone releasing hormone was infused intravenously and serum growth hormone concentrations were measured at 0, 15, 30, 60, 90 and 120 minutes. Serum follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone and estradiol were also measured before the test. Serum follicle-stimulating hormone concentrations were significantly increased in the azoospermic group and basal levels of growth hormone were similar to those in the control group. Serum growth hormone concentrations increased after injection of growth hormone releasing hormone and the levels of growth hormone peaked after 30 minutes in both groups. At time 30 minutes growth hormone levels had decreased significantly more in the azoospermic group than in the controls. Men with azoospermia due to spermatogenetic maturation arrest had a low response to the growth hormone releasing hormone test. Relative growth hormone insufficiency, which may be caused by reduced reactivity to growth hormone releasing hormone in pituitary growth hormone secretory cells, is strongly related to spermatogenic dysfunction.

Pulsatile secretion pattern of growth hormone in dogs with pituitary-dependent hyperadrenocorticism

The amplitude and frequency of growth hormone (GH) secretory pulses are influenced by a variety of hormonal signals, among which glucocorticoids play an important role. The aim of this study was to investigate the pulsatile secretion pattern of GH in dogs in which the endogenous secretion of glucocorticoids is persistently elevated, i.e. in dogs with pituitary-dependent hyperadrenocorticism (PDH). Blood samples for the determination of the pulsatile secretion pattern of GH were collected at 10-min interval between 08:00 and 14:00 h in 16 dogs with PDH and in 6 healthy control dogs of comparable age. The pulsatile secretion patterns of GH were analyzed using the Pulsar program. GH was secreted in a pulsatile fashion in both dogs with PDH and control dogs. There was no statistical difference between the mean (±S.E.M.) basal GH level in dogs with PDH (0.7±0.1 μg/l) and the control dogs (0.6±0.1 μg/l). The mean area under the curve (AUC) for GH above the zero-level in dogs with PDH (4.6±0.6 μg/l per 6 h) was significantly lower than that in the control dogs (7.3±1.0 μg/l per 6 h). Likewise, the mean AUC for GH above the base-level in dogs with PDH (0.6±0.1 μg/l per 6 h) was significantly lower than that in the control dogs (3.7±1.0 μg/l per 6 h). The median GH pulse frequency in the dogs with PDH (2 pulses/6 h, range 0–7 pulses/6 h) was significantly lower ( P=0.04) than that (5 pulses/6 h, range 3–9 pulses/6 h) in the control group. The results of this study demonstrate that PDH in dogs is associated with less GH secreted in pulses than in control dogs, whereas the basal plasma GH concentrations were similarly low in both groups. It is discussed that the impaired pulsatile GH secretion in dogs with PDH is the result of alterations in function of pituitary somatotrophs and changes in supra-pituitary regulation.

Different neuroendocrine profiles of remitted and nonremitted schizophrenic patients

Background: Thyrotropin-releasing hormone (TRH) test and Dexamethasone Suppression Test (DST) are two neuroendocrine tests that have been extensively used in an attempt to predict treatment response and outcome in schizophrenia. The objectives of this study were to investigate (1) the relationship between TRH test and DST and various psychiatric symptoms and (2) the potential value of these tests in prediction of short-term outcome in schizophrenic patients. Methods: TRH test and DST were administered to 58 patients with schizophrenia. All patients were evaluated with a battery of rating scales before neuroendocrine test procedures and at regular intervals for 1 year. Patients were divided into two groups as remitted (RP; n=30) and nonremitted patients (NRP; n=28). Baseline results of these two groups were compared with each other and 30 healthy controls. Results: Basal levels of total T 3 (T 3T) and free T 3 (T 3F) were higher in RP group than controls. Basal prolactin (PRL) level was higher in RP group, but not in NRP, compared to controls. Basal growth hormone (GH) and thyroid-stimulating hormone (TSH) levels of NRP were significantly higher than those of RP. DST nonsuppression was observed at a significantly higher rate in RP than NRP and control group. Blunted TSH response rate in RP group was higher significantly compared to other two groups. Conclusions: The data implicate that higher basal TSH and GH levels may be associated with a poorer treatment response, whereas higher total and free T 3 levels, a blunted TSH response to TRH and nonsuppression on the DST may indicate a better response in schizophrenics.

The genetics of signal transduction and the outcome of diagnostic tests in growth retardation.

The effects of 'normal' genetic variability of signal transduction on endocrine function may be more evident during stimulation tests than is observed in basal states, thereby contributing to a greater understanding of the possible role of signal transduction genetics in the pathogenesis of endocrine disorders. In the present study, we have studied the outcome of growth hormone (GH) stimulation testing by insulin in growth-retarded children in relation to the genotype of ACP1 (acid phosphatase locus 1; also referred to as cLMWPTP, cytosolic low molecular weight phosphotyrosine phosphatase). ACP1 is an enzyme, expressed as two distinct isoforms designated F and S, that down-regulates insulin receptor signal transduction and which shows a genetic polymorphism with strong quantitative enzymatic differences among genotypes. In this study, we examined 116 growth-retarded children of which 101 were genotyped for ACP1. We found that the basal level of GH is higher in ACP1 genotypes with low concentrations of the S isoform than in genotypes with high S isoform concentrations (P<0.02). Additionally, during GH stimulation with insulin, the genotypes with low S isoform concentrations were found to perform better (P<0.005) and to react more promptly than the genotypes with high S isoform concentrations (P<0.05). These findings suggest that high S isoform ACP1 activity slows down the effect of insulin, resulting in a retardation of its metabolic effect.

Hormonal Responses to Exercise Stress Test in Patients with Fibromyalgia Syndrome

Twenty patients with fibromyalgia syndrome (FMS) and 20 matched healthy controls were subjected to an exercise stress test above their anaerobic threshold. Serum samples for the measurement of growth hormone (GH), insulin-like growth factor-1 (IGF-1), prolactin (PRL), adrenocorticotrophic hormone (ACTH) and cortisol were taken prior to and after the test at 30-min intervals. Compared to the controls, the patients with FMS displayed significantly lower basal GH levels and slightly, though significantly, higher prolactin levels. Following the exercise test there was a significant increase in the mean GH level in the patient group (P = 0.0474) and a significant decrease in the control group (P = 0.0286) 1 hour after the exercise. A slight decrease in ACTH levels in the control group was observed (P = 0.0002), but there was no significant change in FMS patients. Cortisol levels were significantly lower in both groups after the exercise (P = 0.0001). These results suggest the possibility of a perturbation in hormonal response to exercise in patients with FMS.

Effects of Long-Term Erythropoietin Therapy on the Hypothalamo–Pituitary–Testicular Axis in Male Capd Patients

Gonadal dysfunction has been recognized for a long time in uremic male patients. The present study assesses the hypothalamo-pituitary-testicular axis and growth hormone status in male continuous ambulatory peritoneal dialysis (CAPD) patients, before and after recombinant human erythropoietin (rHuEPO) therapy. Single-center prospective study. Ten anemic male patients with chronic renal insufficiency, and 11 healthy volunteers with normal renal function, matched for age, were included in the study. All patients were on CAPD therapy and none had received rHuEPO treatment previously. Blood samples were collected between 0800 and 0900 hr from all patients for the determination of basal follicle stimulating hormone (FSH), luteinizing hormone (LH), and growth hormone (GH) levels. A luteinizing hormone-releasing hormone (LH-RH) stimulation test was carried out using LH-RH 100 microg intravenous as a bolus injection. Blood for FSH, LH, and GH determinations was drawn every 30 minutes during the 3-hour test period. Human chorionic gonadotropin (hCG) test was performed after 48 hours. After estimations of basal serum total and free testosterone levels, 2000 IU hCG was administered intramuscularly and repeated 48 hours later. Total and free testosterone levels were measured in blood samples collected before and 48 hours after two injections of hCG. After improvement in anemia with exogenous rHuEPO, LH-RH and hCG tests were repeated. Baseline FSH concentrations before and after rHuEPO treatment were slightly higher in CAPD patients than in healthy volunteers (p = 0.85 and p = 0.70, respectively). Areas-under-the-curve (AUCs) for FSH secretion before and after rHuEPO treatment were also slightly higher in patients than in healthy volunteers (p = 1.00 and p = 0.75, respectively). The pretreatment basal LH levels in patients were significantly higher than in controls (p < 0.001). After the improvement in anemia with rHuEPO, serum LH levels declined significantly (p < 0.05). The AUCs for LH secretion before and after rHuEPO treatment were significantly higher in patients than in controls (p < 0.05). All patients had elevated basal levels of GH with paradoxical response to LH-RH. Baseline GH levels in patients were significantly higher than those in healthy subjects (p < 0.001) before rHuEPO treatment. After treatment with rHuEPO, basal GH levels declined but did not normalize, and baseline levels of free testosterone increased significantly (p < 0.05). Anemic uremic male patients on CAPD have normal levels of testosterone with normal response to hCG administration, elevated basal levels of GH, and elevated basal levels of LH, with exaggerated response to LH-RH administration. Improvement in anemia with rHuEPO reduced the basal levels of LH and GH, but exaggerated the LH response; paradoxical GH response to LH-RH administration persisted. These results indicate a defect at the level of the hypothalamus and pituitary gland in uremic male patients undergoing CAPD, and that the improvement in anemia with rHuEPO partially restores some of these endocrine abnormalities.

Terapia de reposição hormonal contínua na pós-menopausa: ênfase no hormônio do crescimento, insulina, fator de crescimento semelhante à insulina I (IGF-I) e proteína ligadora 3 do IGF (IGFBP-3)

A importância da terapia de reposição hormonal da menopausa (TRHM) na qualidade de vida na pós-menopausa é inquestionável. Entretanto, nem todos os efeitos determinados pelo seu emprego estão bem estabelecidos. Este estudo tem como objetivo avaliar a influência da TRHM sobre os níveis séricos do hormônio do crescimento (GH), fator de crescimento semelhante à insulina I (IGF-I), proteína ligadora 3 do IGF (IGFBP-3), glicose e insulina. Realizamos um ensaio clínico controlado, prospectivo, longitudinal e comparativo, no qual 53 mulheres na pós-menopausa, natural ou cirúrgica, foram submetidas ou não a TRHM contínua, durante um período de 6 meses, com estrogênios conjugados (EC-0,625mg/d) associados ou não ao acetato de medroxiprogesterona (AMP-2,5mg/d), pela via oral. As participantes foram subdivididas em 3 grupos: Grupo EC + AMP &gt; 20 mulheres com útero, que utilizaram EC e AMP; Grupo EC &gt; 20 mulheres histerectomizadas, que usaram EC; Grupo C &gt; 13 mulheres, sem TRHM. Ao início e ao final do estudo foram realizadas as dosagens basais do GH; IGF-I e IGFBP-3. Também realizamos o teste oral de tolerância à glicose (TOTG) de 2 horas, com determinação dos níveis de glicose e insulina; a área abaixo da curva (AAC) de glicose e de insulina e o índice de resistência à insulina (IRI). O emprego da TRHM reduziu os níveis do IGF-I no EC + AMP (p= 0,01) e EC (p= 0,0007), sem alteração nos níveis do IGFBP-3. Os níveis do GH se elevaram mediante a TRHM, (EC + AMP: p= 0,004 e EC: p= 0,0003), entretanto, as concentrações séricas do IGF-I e do IGFBP-3 não parecem ser bons marcadores da secreção circadiana do GH. Aos 6 meses observou-se uma correlação negativa do IGF-I com a AAC de glicose nos três grupos (EC + AMP: r= -0,42, p= 0,06; EC: r= -0,58, p= 0,007 e C: r= -0,64, p= 0,01). O IGFBP-3 e a AAC de glicose apresentaram correlação negativa no grupo EC (r= -0,45, p= 0,04) e tendência no EC + AMP (r= -0,42, p= 0,06). A associação do AMP determinou o aparecimento de ITG em 30% das pacientes do grupo EC + AMP (n= 6). Nossos dados sugerem uma interação entre o metabolismo dos carboidratos com o IGF-I e o IGFBP-3. Os efeitos gerados pelo emprego prolongado da TRHM contínua na regulação do GH, IGF-I e IGFBP-3 ainda necessitam elucidação.

Increased glucose-dependent insulinotropic polypeptide (GIP) secretion in acromegaly.

Acromegaly is often associated with fasting and postprandial hyperinsulinemia, and the mechanisms involved are only partly understood. Hypersecretion of incretins such as glucose-dependent insulinotropic polypeptide (GIP) could play a role in determining hyperinsulinemia in acromegaly, but the available data are inconsistent. The aim of this study was to characterize the fasting and postprandial pattern of plasma GIP and insulin in a group of acromegalic patients. Eleven non-diabetic patients with newly diagnosed acromegaly and 11 sex- and age-matched healthy subjects were studied. Blood samples were taken at regular intervals in fasting conditions and for 3 h after a standard solid-liquid meal for growth hormone (GH), GIP and insulin measurements. Not only insulin, but also fasting and postprandial GIP levels were significantly higher in the patients with acromegaly than the healthy subjects (P<0.01). In the former group fasting GIP levels and the integrated GIP response to the meal correlated significantly with GH basal levels (r=0.83, P<0.01 and r=0.65, P<0.05, respectively). Moreover, multivariate linear regression analysis showed that the presence of acromegalic status was associated with higher fasting and postprandial GIP levels independently of sex, age, fasting and postprandial plasma glucose and insulin levels, and the occurrence of normal or impaired glucose tolerance. This study provides evidence that in patients with acromegaly fasting and postprandial GIP levels are abnormally high. GIP hypersecretion in turn might play a role in the pathogenesis of hyperinsulinemia that characterizes acromegaly.

Somatotropic axis dysfunction in critically ill patients: altered response to growth hormone-releasing hormone

The aim of this study was to investigate the pituitary‘s capacity to release growth hormone (GH) in critically ill patients by stimulation with GH-releasing hormone (GHRH). Thirty-two patients with severe sepsis and 20 critically ill, nonseptic patients after major surgery were studied in the setting of a surgical intensive care unit. Nine healthy individuals without clinical signs of disturbance of the somatotropic hypothalamic-pituitary axis were included for comparison. The pituitary‘s capacity to release GH was tested with an intravenous bolus injection of 1μg per kg body weight GHRH (Ferring, Kiel, Germany). The median basal plasma GH level was comparable in all groups studied. In contrast, the median peak plasma GH level was significantly lower in critically ill, nonseptic patients after major surgery (5.1, range 1.3–131.0ng/ml, n=20) compared to healthy individuals (23.2, range 12.8–35.2 ng/ml, n=9) (p ;0.01). However, the median peak plasma GH level in patients with severe sepsis (15.3, range 1.6–111.5ng/ml, n=32) was not significantly different compared to healthy individuals (23.2, range 12.8–35.2ng/ml, n=9) (p>>;0.05). The median plasma insulin-like growth factor-I (IGF-I) level was significantly decreased in patients with severe sepsis (32.0, range 32.0–150.0ng/ml, n=32) and in critically, ill, nonseptic patients after major surgery (50.0, range 32.0–144.0ng/ml, n=20) compared to healthy individuals (229.0, range 129.0–503.0ng/ml, n=9) (p ;0.001). No significant difference was found between patients after major surgery and patients with severe sepsis. In conclusion, a low level of circulating IGF-I was associated with the pituitary‘s low capacity to release GH in critically ill, nonseptic patients after major surgery, whereas patients with severe sepsis had a widespread range of pituitary capacity to release GH associated with low IGF-I levels. The pathophysiological basis for not secreting stored GH during critical illness is at present unclear. The treatment with high doses of human GH has been shown to attenuate the catabolic response to injury, surgery and sepsis, whereas in patients with severe sepsis GH administration bypasses its pituitary storage and may trigger a hyperinflammatory response. However, critically ill nonseptic patients after major surgery may profit from GH treatment since they possess a low pituitary capacity to release GH. Thus, performing a GHRH test might facilitate the decision for treatment with human GH.