Decrease In Growth Hormone Levels Research Articles

Diabetes mellitus in acromegaly: prevalence, pathophysiological particulars and treatment strategies

The prevalence of diabetes mellitus in acromegaly is significantly higher than that in the general population. Carbohydrate metabolism abnormalities often precede other phenotypic manifestations of acromegaly. The review presents data on the prevalence of carbohydrate metabolism disorders in acromegaly and describes their pathophysiological characteristics and approaches to treatment.
 Growth hormone (GH) excess is recognized as a key factor of glucose homeostasis abnormalities due to decreased insulin sensitivity (resulting from active lipolysis) and direct stimulation of insulin secretion. Insulin-like growth factor 1 (IGF1) improves insulin sensitivity; however, the GH diabetogenic effects prevail over the insulin-sensitizing impact of IGF1. Surgical and radiation treatment for somatotropinoma may indirectly improve carbohydrate metabolism, because they decrease the GH levels. Treatment with first generation somatostatin analogues can both improve glycemic control due to decreased GH levels and worsen it due to deterioration of postprandial insulin release, especially in patients with already manifest carbohydrate metabolism disorders. The GH receptor antagonist pegvisomant blocks the effects of excess GH on the target tissues without suppressing insulin secretion, which results in better glucose control; treatment with this agent can be preferred in patients with acromegaly and diabetes mellitus. Management of carbohydrate metabolism disorders in acromegaly is done in accordance with general treatment principles for type 2 diabetes mellitus.

The multiple roles of GH in neural ageing and injury.

Advanced age is typically associated with a decrease in cognitive function including impairment in the formation and retention of new memories. The hippocampus is critical for learning and memory, especially spatial learning, and is particularly affected by ageing. With advanced age, multiple neural components can be detrimentally affected including a reduction in the number of neural stem and precursor cells, a decrease in the formation of adult born neurons (neurogenesis), and deficits in neural circuitry, all of which ultimately contribute to impaired cognitive function. Importantly, physical exercise has been shown to ameliorate many of these impairments and is able to improve learning and memory. Relevantly, growth hormone (GH) is an important protein hormone that decreases with ageing and increases following physical exercise. Originally described due to its role in longitudinal growth, GH has now been identified to play several additional key roles, especially in relation to the brain. Indeed, the regular decrease in GH levels following puberty is one of the most well documented components of neuroendocrine ageing. Growth hormone deficiency (GHD) has been described to have adverse effects on brain function, which can be ameliorated via GH replacement therapy. Physical exercise has been shown to increase circulating GH levels. Furthermore, we recently demonstrated the increase in exercise-mediated GH is critical for improved cognitive function in the aged mouse. Here we examine the multiple roles that GH plays, particularly in the aged brain and following trauma, irradiation and stroke, and how increasing GH levels can ameliorate deficits in cognition.

Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly.

Background Somatotroph adenomas (SAs) exhibit a variable responsiveness to somatostatin analogue (SS-a) treatment, a process that is not well understood. We investigated established and novel histological markers as predictors of SS-a responsiveness. Methods We retrospectively investigated pathology samples from 36 acromegalic patients that underwent transsphenoidal surgery. Clinical, hormonal, and imaging data were available in 24/36 patients, before and after SS-a treatment. Specimens were semiquantitatively analyzed with immunocytochemistry for Ki-67, KER, SSTR-2, SSTR-5, ZAC-1, E-cadherin, and AIP. Results Collectively, 18 (50%) adenomas were each classified as densely/sparsely granulated somatotroph adenomas (DGSAs/SGSAs), respectively. Patients that received preoperative SS-a had lower expression of SSTR-2 compared to those that did not (2.0 (1.0, 3.0) vs. 3.0 (3.0, 3.0), p = 0.042). Compared with DGSAs, SGSAs had higher Ki-67 labeling index (LI) (1.0 (0.5, 1.0) vs. 2.0 (1.0, 3.5), p = 0.013), and a higher proportion of high MR T2 signal (1 (6%) vs. 6 (33%), p = 0.035), and tended to express less ZAC-1 (p = 0.061) and E-cadherin (p = 0.067). In linear regression corrected for baseline growth hormone (GH), ZAC-1 immunostaining was significantly associated with a decrease in GH levels after SS-a treatment (beta (95% confidence interval): −1.53 (−2.80, −0.26), p = 0.021). No markers were associated with changes in circulating insulin-like growth factor-I (IGF-I) after treatment with SS-a. Conclusion The novel marker ZAC-1 was associated with GH response to medical treatment with SS-a. The SGSA cases were characterized by higher Ki-67 values and MR T2 signals indicative of an inferior response to SS-a. These findings improve our understanding of the mechanisms underlying SA response to medical treatment.

Early postoperative measurement of growth hormone level for prognosis of surgical outcomes in acromegaly

To investigate the value of 24 hours post-surgery measurement of growth hormone (GH) level for prognosis of surgical outcomes in acromegaly. A prospective cohort study included 45 patients with newly diagnosed acromegaly. The degree of parasellar extension was measured on the preoperative sellar magnetic resonance imaging according to the Knosps classification. All patients underwent a transsphenoid adenomectomy performed by one neurosurgeon. Basal GH level was measured at 24 hours after surgery. The efficacy of transsphenoidal adenomectomy evaluated at 12 months after surgery. Acromegaly remission was achieved in 19 (42%) of 45 patients at 12 months after surgery. Pituitary microadenomas and the absence of paracellular invasion, corresponding to Knosp Grade 02, had low prognostic value for long-term remission due to low sensitivity (31.6%) and low specificity (38.5%), respectively. The highest prognostic value for acromegaly remission was showed for 24 hours post-surgery GH level with cut-off 1.30 ng/ml with sensitivity of 96.2% (95% confidence interval 81.199.8%) and specificity of 84.2% (95% confidence interval 62.494.4%). The study demonstrated the possibility of using GH level at 24 after surgery as a predictor for acromegaly remission. GH level 1.30 ng/ml at 24 hours after surgery showed better predictive value for long-term remission compared with the presence of microadenomas and Knosp Grade 02. The absence of decrease of GH level on the first day after surgery may serve as a reason for more close monitoring of patients in the postoperative period. Further studies in a larger number of observers are required to confirm our findings.

Modern approaches of radiation therapy in somatotropinomas

The purpose of our study is to study the current approaches of radiation therapy at somatotropinomas and to evaluate neuroimaging indices in long term periods of therapy. The object of the study was 50 patients who underwent radiotherapy. The patients were divided into 3 groups: the 1st group a 1 year after the radiation therapy 7 persons, the 2nd group 1-5 years — 19, the 3rd group 5-10 years — 24 patients. The results of determining the average daily levels of growth hormone at various times after the radiation therapy show that at the time of the first examination, all patients had active acromegaly, which was estimated by the level of growth hormone. Evaluation of the condition of patients in all groups after radiation therapy showed a decrease in growth hormone levels (p<0,01). A significant decrease was observed in group III, the average level of growth hormone was 7,8±1,2 mMe/l. The result of the dynamics of neuroimaging studies at various times after radiation therapy showed a significant decrease in the size of pituitary adenomas in all respects. Conclusion. In the long-term period after radiation therapy, 10% of patients had a decrease in the size of the pituitary gland, 54% had normal pituitary sizes, 16% had no effect and in 20% of cases there was an empty turkish saddle. It has been established that radiation therapy, followed by medical treatment with dopamine agonists, both in the immediate and long term periods after it, contributes to the stabilization of the pathological process of acromegaly.

Immediate Serum Growth Hormone Decrease as a Potential Index of Dopamine-Related Response to Electroconvulsive Therapy in Schizophrenic Patients

: The objective of this study was to investigate the immediate response of the dopamine-regulated growth hormone (GH) to electroconvulsive therapy (ECT) in schizophrenic patients and the changes in the serum GH levels throughout the consecutive sessions of the therapeutic ECT course. : Serum GH levels were measured in a sample of 11 men with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, who were administered a course of 8 bilateral ECT treatments. Measurements were performed 5 minutes before ECT, during ECT, 15 minutes after an ECT session, and 30 minutes after an ECT session during the first, fourth, and eighth ECT sessions. : At both the fourth and the eighth ECT sessions, a significant decrease in GH levels 15 and 30 minutes after ECT was observed compared with the baseline values. No change in baseline serum GH levels was observed either during or at the end of the treatment. Clinical improvement was indicated by a significant reduction in the total score, negative subscale score, and positive subscale score of the Positive and Negative Syndrome Scale. : The results are consistent with the potential role of immediate serum GH changes as an index of potential dopamine-mediated response to ECT. It can be assumed that GH reduction may be partially related to an antidopaminergic action of ECT, but further research is still needed to better evaluate the correlation of the dopamine system instability during the course of the illness with the previously mentioned immediate treatment response. Also, the role of other neurotransmitters in the regulation of GH production and ECT response must be taken into account for the purpose of an overall evaluation of the results and of their potential clinical implications.

Serum Osteopontin Growth hormone , and Other Biochemical Parameters in Children with Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is a custom of leukemia, or cancer of the white blood cells categorized by excess lymphoblasts and Chemotherapy is the initial treatment of choice. Most ALL patients will receive a combination of different treatments.Osteopontin (OPN) is a glycoprotein that cooperates with a variety of cell surface receptors, as well as several integrins and CD44. OPN is secreted by numerous human malignancies. We aimed to evaluate serum levels of osteopontin and growth hormone(GH) in patients with Acute lymphoblastic leukemia in childhood. We studied serum levels of OPN ,GH and other biochemical levels of 60 patients that diagnosis as acute lymphoblastic leukemia. The mean levels of OPN were significantly higher in patients (10.00± 1.15 ng/ml) than in control (7.62± 0.60 ng/ml). The mean levels of GH levels were significantly lower in patients (2.98± 0.51ng/dl) than in control (6.02± 1.00 ng/dl. The mean levels of the iron and total protein in ALL patients were (95.78± 10.11 µg/dl), (6.08 ± 1.16 g/dl)respectively. The present study showed a significant negative correlation between GH with osteopontin (OPN) ,while there a positive significant correlate between GH with hemoglobin in patients group compared to control group. The present study Conclude that elevated levels of osteopontin and decreased GH levels at the diagnosis may predict an unfavorable result in ALL childhood .

Temporal Factors Alter Effects of Social Housing Conditions on Responses to Chemotherapy and Hormone Levels in a Shionogi Mammary Tumor Model

To identify possible hormonal factors involved in the differential responses to chemotherapy observed in our tumor model, we investigated if the timing among tumor cell injection, rehousing, and chemotherapy administration differentially affects levels of corticosterone (CORT), growth hormone (GH), and testosterone and tumor and host responses to chemotherapy. Mice were reared either individually (I) or in groups (G). At 2 to 4 months, mice were injected with tumor cells and retained in their original housing conditions or rehoused into different experimental groups (GG, IG, II, GI) either immediately (experiment 1) or 14 days later (experiment 2); chemotherapy was administered when tumors weighed approximately 0.8 g. In experiment 1, IG and GG mice had better responses to chemotherapy than GI mice. Chemotherapy increased CORT levels in II mice and decreased GH levels in GI mice compared with those of their drug vehicle-treated counterparts. Under the temporal conditions of experiment 2, IG and GG mice lost the advantage seen in experiment 1 in terms of tumor and host responses to chemotherapy. Before chemotherapy administration, CORT levels in IG mice and GH levels in GI mice were higher than those in mice in all other housing conditions. At 1 day after chemotherapy, CORT levels were higher for chemotherapy-treated than for drug vehicle-treated IG mice, and at 5 days post chemotherapy, GH levels were higher in GI than in IG mice. Temporal relationships among tumor cell injection, rehousing, and chemotherapy administration critically influence responses to chemotherapy; these effects may be mediated, in part, by alterations in hormone levels.

A motilin agonist, erythromycin, decreases circulating growth hormone levels in normal subjects but not in diabetic subjects

Erythromycin (EM) is a common antibiotic known to be a specific agonist of motilin receptors. We have previously reported that administration of EM improves glycemic control in type 2 diabetes patients. In the present study, we tested the effect of EM on growth hormone (GH) secretion in normal and type 2 diabetic subjects. Erythromycin (300 mg) was administered orally in fasted type 2 diabetic ( n=12) and normal ( n=10) subjects. Blood samples were obtained before and 2 h after the administration. Blood glucose, plasma insulin, somatostatin (SS), and GH levels were determined. The same fasted groups received intravenous erythromycin infusion (10 mg/kg per hour) for 60 min. Blood samples were collected just prior to the infusion and at 15, 30, 45 and 60 min, and plasma GH and somatostatin levels during the infusion were determined. Oral EM administration increased insulin levels and decreased blood glucose levels. GH levels were significantly decreased, while SS levels did not change in normal subjects. In diabetic subjects, there was an increase in insulin levels, but no change in blood glucose, SS, and GH levels. Intravenous EM infusion resulted in a marked decrease in GH levels, while no change in SS levels occurred in normal subjects. There were no changes in SS and GH levels in diabetic subjects during the infusion. When diabetic subjects were divided into two groups with and without autonomic neuropathy, no changes in GH levels were seen in either group. We conclude that EM decreases GH levels in normal subjects while not changing SS levels. This effect was not observed in type 2 diabetic subjects.

Wound site neutrophil transcriptome in response to psychological stress in young men.

Communication between the central nervous and the immune system occurs through chemical messengers secreted by nerve cells, endocrine organs, or immune cells. Psychological stressors can disrupt these networks. We have previously observed that disruption of the neuroendocrine immune system adversely influences a broad range of physiological processes including wound healing. Migration of neutrophils to the wound site is an early event that induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing. In this study, we have sought to identify stress-sensitive transcripts in wound site neutrophils. A skin blister model was used to collect wound fluid and wound site neutrophils from four young men, experiencing or not examination stress. Self-reported stress was recorded using the Beck Depression Inventory. Stress decreased growth hormone levels at the wound site and was related to impaired wound healing in all subjects. High density microarray analyses were performed using RNA from wound site neutrophils. Results show that psychological stress had an overall suppressive effect on the neutrophil transcriptome. Of the 22,283 transcripts screened, 0.5% were downregulated whereas only under 0.3% were induced by stress in all four out of four subjects. Functionally, stress tilted the genomic balance towards genes encoding proteins responsible for cell cycle arrest, death, and inflammation. Further effort to gain a more comprehensive understanding of the functional significance of such behavior-genome interaction is warranted.

Acute effects of nicotine on serum glucose insulin growth hormone and cortisol in healthy smokers

Cigarette smoking impairs glucose tolerance and alters serum levels of hormones involved in glucose metabolism, but the role of nicotine in such hormonal alterations is not well understood. In order to isolate the effects of transdermal nicotine on serum glucose, insulin, growth hormone, and cortisol in smokers, we conducted a randomized double-blind placebo-controlled cross-over study involving 34 healthy volunteer smokers between 18 and 55 years of age. Administration of a 14-mg transdermal nicotine patch resulted in nonsignificantly lowered fasting quantitative insulin-sensitivity index ( P = .11) and a nonsignificant 9.3-mg/dL mean increase in serum glucose levels during a 75-g oral glucose tolerance test (OGTT) at time 60 minutes ( P = .12). There were no substantial differences between groups in the areas under the curve (AUCs) for glucose ( P = .33) or insulin ( P = .79) during the OGTT. Levels of insulin and cortisol also were not significantly altered by nicotine. A secondary finding observed in the overall study group (primarily in females) was that nicotine caused a 29% median decrease in serum growth hormone ( P = .02). We conclude that nicotine patches may lead to mild hyperglycemia and lowered insulin sensitivity. Further research is needed to determine the clinical implications of the unexpected finding that nicotine decreased growth hormone levels in female smokers.

Endocrine Changes in a Rat Model of Chronic Hypoxia Mimicking Cyanotic Heart Disease

Objective. The endocrine system plays an important role in the adaptation to hypoxia. The aim of this study is to assess the effect of chronic hypoxia on endocrine changes in a neonatal animal model mimicking cyanotic heart disease. Methods. Sprague–Dawley rats were placed in a normobaric hypoxic environment at birth and oxygen levels were maintained at 10% in an airtight Plexiglas chamber. Controls remained in room air. Animals were sacrificed at 4 and 8 weeks of life. Hematocrit, Free T4 (FT4), Thyrotropin (TSH), corticosterone, and Growth hormone (GH) were measured. Results. Significant polycythemia developed in the hypoxic rats. Free T4 levels were significantly lower in the hypoxic (H) group compared to the control (C) group at 4 and 8 weeks with FT4 of 2.44 ± 1.11 ng/dL (H) and 4.35 ± 1.62 (C) at 4 weeks with a p value <0.005 and FT4 of 2.01 ± 0.36 (H) and 3.25 ± 0.54 (C) ng/dL at 8 weeks with p < 0.01. At 8 weeks TSH levels were significantly lower in the hypoxic group (1.84 ± 0.9 ng/mL (H) vs. 3.11 ± 1.1 (C)) with p < 0.05. Corticosterone levels were higher in the hypoxic group with values of 126 ± 14.8 ng/mL (H) and 114.1 ± 12.6 (H) at 4 and 8 weeks respectively, when compared to the control group with values of 82.9 ± 18.1 (C) and 92.7 ± 10.3 (C) and 4 and 8 weeks with p < 0.0005 and <0.05 respectively. Growth hormone levels were significantly lower in the hypoxic group at 4 and 8 weeks with p < 0.05 and p < 0.001, respectively. Conclusion. Chronic hypoxia in our neonatal rat model was associated with a decrease in growth hormone levels and an increase in corticosterone levels. Furthermore, hypoxia resulted in thyroid hormone axis suppression. This effect seems to be centrally mediated.

Effects of pulsatile secretion of growth hormone (GH) on fat deposition in human GH transgenic rats

Growth hormone (GH) is an endocrine regulator of glucose and lipid metabolism as well as body growth. GH levels are decreased and a unique pulsatile secretory pattern becomes obvious after puberty particularly in males. Coincidentally with this, males tend to deposit body fat. Experimental and clinical evidence has accumulated that obesity is associated with a decrease in GH levels. A strain of transgenic rats has been generated with severe obesity but normal nose-to-tail length, which has low circulating GH levels without pulsatility (human growth hormone (hGH) transgenic rats). The present review mainly focuses on recent and current work analysing the relationship between the occurrence of obesity and low GH levels and/or the absence of GH pulsatility in this transgenic animal model. This model has elevated blood glucose, non-esterified fatty acid, insulin and leptin levels associated with hyperphagia, suggesting that these rats also carry insulin- and leptin-resistant characteristics. hGH transgenic rats were subjected to a pair-feeding treatment to normalize food intake and chronic GH replacement to normalize GH levels. While the pair-feeding for 8 weeks successfully suppressed body-weight gain, the fat pad : body weight ratio remained very similar to freely-eating control hGH transgenic rats, which indicates the hyperphagia is not the sole contributor to the excess fat accumulation in this model. However, continuous elevation of peripheral hGH levels (approximately 2-fold) for 8 weeks by means of a slow-release vehicle resulted in a significant decrease in the fat mass : body weight ratios by 30 %. This GH treatment altered neither food intake nor body-weight gain. Thus, two characteristic phenotypes observed in the hGH transgenic rats, hyperphagia and obesity, seem to be closely related to GH levels and GH secretory pattern. This relationship might be working in the regulation of changes in seasonal body composition in wild animals.

Effects of the Neuropeptide Substance P on Sleep, Mood, and Neuroendocrine Measures in Healthy Young Men

The neuropeptide substance P (SP) has been supposed to be involved in the etiopathology of affective disorders, mainly because of the finding of increased levels of SP in the cerebrospinal fluid of depressed patients and the preliminary evidence of antidepressant effects of SP-receptor antagonists in depressed patients. We investigated whether SP may induce changes of sleep, mood and neuroendocrine measures that are similar to those in depressed patients. In a double-blind, randomized cross-over design, 12 healthy young men were investigated in two blocks of three consecutive nights, in which SP or NaCl was intravenously infused during the third night. Polysomnographic recordings were obtained during all nights and blood samples were drawn every 30 min during the third night. Infusion of SP caused a significant worsening of the mood of the subjects, led to an increase of REM latency and time awake during the SP-infusion intervals, caused increased stage 1 sleep in the first part of the night, and led to increased cortisol and thyroid stimulating hormone levels and a trend for decreased growth hormone levels. These effects can be interpreted as evidence for a central arousing effect of SP. Further studies should focus on the effects of substance P in patients with depressive or other psychiatric disorders.

3-Cloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a rat thyroid gland carcinogen, does not affect serum levels of TSH and thyroid hormones

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a chlorine disinfection by-product in drinking water, causes follicular adenomas and carcinomas in thyroid glands of Wistar rats with an unknown mechanism. We evaluated effects of MX on blood thyroid stimulating hormone (TSH), thyroxine (T 4), triiodothyronine (T 3), prolactin (PRL) and growth hormone (GH) levels in male and female Wistar rats to assess their role in the tumorigenesis. The levels of TSH, PRL and GH in serum of male rats were not significantly affected by a single dose of 1, 10 or 60 mg/kg of MX administered by gavage 2 h before sampling. In repeated dose experiments MX was administered at dose levels of 1, 10 or 60 mg/kg of MX (40 mg/kg for females) in water by gavage daily for 1 or 3 weeks. Thyroid glands, adrenal glands and the liver were evaluated for morphological changes and cell proliferation activity after staining with proliferating cell nuclear antigen (PCNA). The dose of 60 mg/kg MX was toxic upon repeated administration. Nevertheless, MX did not affect blood TSH and T 4 levels at any time point in either sex. T 3 concentration increased transiently in males (by 37% after week 1) at the highest MX dose but not in females. MX did not change the weights of thyroid glands, their morphology and cell proliferation activity by the end of the week 3. MX did not affect blood PRL levels but decreased GH levels in males at all doses after the first week of MX treatment. The results indicate that MX does not alter blood TSH and thyroid hormone levels in rats, and imply that MX may not cause thyroid follicular cell tumors by TSH-mediated hormonal promotion.

Étude de l'axe somatotrope des nouveau-nés à terme et prématurés pendant le premier mois de vie

Neonatal somatotropic function is characterized by a discrepancy between elevated growth hormone (GH) levels and low IGF I levels. This study aimed at explaining this discrepancy, particularly to examining if it could result from low GH bioactivity. Serum concentrations of bioactive GH (bio GH), GH measured by radioimmunoassay (riGH), GH binding protein (GHBP), IGF I and IGF binding proteins (IGFBP) were determined in 27 premature and term newborns during the first month of life. At day 4, riGH and bio GH concentrations were elevated in both premature and term newborns as compared with normal prepubertal children; GHBP and IGF I levels were low, with a positive correlation with gestational age (P < 0.001). There was a positive correlation between GHBP and IGF I levels. IGFBP-1 and IGFBP-2 levels were elevated and negatively correlated with gestational age (P < 0.005). IGFBP-3 levels were within the range of prepubertal children values and positively correlated with gestational age (P < 0.005). During the first month, riGH and bio GH levels decreased in all infants, while IGFI levels increased in premature infants only, and GHBP levels in term infants only. The elevated levels of bio GH during the first days of life appear to be related to the low levels of IGF I due to a reduced number or function of GH receptors. In premature infants the decrease in GH levels observed afterwards appears to be secondary to the increase in IGF I levels. In term infants, in the absence of increase in IGFI levels other(s) factor(s) seem(s) to be involved.

Oral glucose ingestion increases endurance capacity in normal and diabetic (type I) humans.

The effects of an oral glucose administration (1 g/kg) 30 min before exercise on endurance capacity and metabolic responses were studied in 21 type I diabetic patients [insulin-dependent diabetes mellitus (IDDM)] and 23 normal controls (Con). Cycle ergometer exercise (55-60% of maximal O2 uptake) was performed until exhaustion. Glucose administration significantly increased endurance capacity in Con (112 +/- 7 vs. 125 +/- 6 min, P < 0.05) but only in IDDM patients whose blood glucose decreased during exercise (70.8 +/- 8.2 vs. 82.8 +/- 9.4 min, P < 0.05). Hyperglycemia was normalized at 15 min of exercise in Con (7.4 +/- 0.2 vs. 4.8 +/- 0.2 mM) but not in IDDM patients (12.4 +/- 0.7 vs. 15.6 +/- 0.9 mM). In Con, insulin and C-peptide levels were normalized during exercise. Glucose administration decreased growth hormone levels in both groups. In conclusion, oral glucose ingestion 30 min before exercise increases endurance capacity in Con and in some IDDM patients. In IDDM patients, in contrast with Con, exercise to exhaustion attenuates hyperglycemia but does not bring blood glucose levels to preglucose levels.

Octreotide Long-Acting Release (LAR)

Octreotide is a somatostatin analogue: a long-acting release (LAR) formulation of octreotide is designed for once-monthly intramuscular administration. As with native somatostatin, octreotide LAR exerts potent inhibitory effects on the secretion of growth hormone and on various peptides of the gastroenteropancreatic endocrine system. When patients with acromegaly who show a positive response to treatment with subcutaneous octreotide 300 to 600 micrograms/day are switched to octreotide LAR 20 or 30 mg, the resulting decrease in growth hormone levels is stable and sustained. Reductions in growth hormone levels to < 5 micrograms/L for about 4 weeks are seen in 86 to 100% of patients, to < 2 to 2.5 micrograms/L in 39 to 75% and to < 1 microgram/L in 24 to 40%. Levels of insulin-like growth factor-1 (IGF-1) decrease in parallel and are often normalised with repeated drug treatment. There is no evidence of tachyphylaxis with long term therapy (up to 34 months). Treatment with octreotide LAR improves facial appearance and soft tissue thickening, and eliminates or reduces the incidence of symptoms such as headache, fatigue, arthralgia and excessive perspiration. Tumour shrinkage has been noted in some, but not all, patients receiving octreotide LAR, although this has not been widely evaluated in clinical studies. Overall, octreotide LAR is well tolerated, and the mild to moderate gastrointestinal events experienced by up to 50% of patients are of short duration and often subside with continued drug administration. The incidence of gallbladder abnormalities (sediment, sludge, microlithiasis and gallstones) increases in patients receiving long term therapy with subcutaneous octreotide, although most patients remain asymptomatic. The incidence of gallbladder abnormalities in patients receiving octreotide LAR compares favourably with that during subcutaneous administration. Glycaemic control is not usually altered during octreotide LAR treatment. In summary, octreotide continues to be the principal pharmacological option for most patients with acromegaly. Octreotide LAR offers the convenience of once-monthly administration compared with daily subcutaneous drug administration. In addition, the good efficacy and tolerability profile of octreotide LAR should enhance patient compliance and acceptability of octreotide therapy and contribute to an improvement in patient quality of life.

Surgical outcome after repeated transsphenoidal surgery in acromegaly.

Transsphenoidal selective adenomectomy is the most efficient primary treatment for acromegaly. However, management of persistent or recurrent disease remains controversial. The objective of the present study was to evaluate the early and long-term efficacy and safety of a second transsphenoidal surgery performed in those cases. The results of a retrospective study of 16 patients undergoing reoperation by the senior author (J.H.) between 1970 and 1991 are reported. Reoperation was performed for persistent or progressive acromegaly in 11 patients, visual impairment in four, and disease recurrence in one. Normalization of growth hormone (GH) was defined as a basal GH level of less than 5 micrograms/L and suppression to less than 2 micrograms/L during the oral glucose tolerance test. Long-term follow-up data were available in 15 patients. The second transsphenoidal surgery induced a greater than 50% decrease of GH level in 11 patients. Three (19%) of 16 patients were cured according to the authors' criteria and remained so after 2, 7, and 20 years. Two more patients had a postoperative basal GH level of less than 5 micrograms/L but incomplete suppression during the oral glucose tolerance test. Thus, a total of five patients (31%) achieved a basal GH of less than 5 micrograms/L. One other patient who had no initial improvement after the second transphenoidal surgery had spontaneous normalization of his GH level after 13 years. The following complications of the second surgery occurred in three patients: one subarachnoid hemorrhage, two new visual field defects, one cranial nerve palsy, and one meningitis. Moreover, 10 patients (62.5%) developed one or more new pituitary hormone deficiencies. In conclusion, reoperation for persistent or recurrent acromegaly has low success and high complication rates. According to the authors' experience, this procedure should be reserved for patients unresponsive to other forms of therapy or with progressive visual impairment despite medical therapy.

Hormonal secretion during nighttime sleep indicating stress of daytime exercise

We tested the hypothesis that long-duration exercise (LDE) of moderate intensity, but not LDE of low intensity, during the daytime changes the typical temporal patterns of hormone release during subsequent nocturnal sleep. Ten trained healthy men participated in a balanced crossover study including three conditions: 1) no exercise, 2) LDE of low intensity (biking 40 km; 1800-2030), and 3) LDE of moderate intensity (biking 120-150 km; 1600-2030). During the subsequent night (2300-0700), somnopolygraphic sleep recordings were obtained, and concentrations of cortisol, growth hormone (GH), and testosterone were measured every 15 min. During the no exercise nights, the typical secretory patterns were present with peak concentrations of GH but nadir concentrations of cortisol during the first half of sleep but increased cortisol levels and minimum GH levels during the second part of sleep. Testosterone concentrations increased during the second half of sleep. LDE of moderate intensity reduced rapid-eye-movement sleep [13.9 vs. 16.9% (no exercise); P < 0.01]. Levels of testosterone decreased with increasing intensity of daytime exercise (P < 0.05). Moderate-, but not low-intensity, LDE decreased GH levels in the first half (P < 0.05) and increased GH levels in the second half (P < 0.005) of sleep. Also, LDE of moderate intensity but not LDE of low intensity increased cortisol levels during the first half (P < 0.005) and decreased cortisol secretion during the second half (P < 0.05) of sleep. Results suggest that nocturnal profiles of GH and cortisol concentrations may serve to indicate the disturbance of normal anabolic functions of sleep due to daytime exercise.