|
1
|
|
|
2
|
Qian K, Wan Z, Hao LS, Zhang MM, Zhou Y, Wu XT. Effects of short-term application of low-dose growth hormone on trace element metabolism and blood glucose in surgical patients. World J Gastroenterol 2007; 13:6259-63. [PMID: 18069770 PMCID: PMC4171240 DOI: 10.3748/wjg.v13.i46.6259] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of short-term application of low-dose growth hormone on trace element metabolism and blood glucose in surgical patients
METHODS: A total of 48 consecutive patients undergoing abdominal operations were randomized to receive either subcutaneous rhGH (0.15 IU/kg) or placebo (menstruum) injections daily for 7 d after surgery. The two groups had similar nutrition intake. Blood, feces, urine and drain samples were collected to measure zincum, cuprum and ferrum as well as glucose levels. Accumulative intake, excretion and balance of zincum, cuprum and ferrum, apparent absorption (AA) and apparent utilization (AU) of zincum, cuprum and ferrum, blood glucose levels and adverse events were estimated.
RESULTS: There were no differences in accumulative intake and drain excretion between the two groups. The feces excretion and accumulative excretion of cuprum were lower in the rhGH group (P < 0.05). The urinary excretion of zincum, cuprum and ferrum was all significantly decreased in the rhGH group (P < 0.05) and the accumulative balance of zincum, cuprum and ferrum was improved compared with the placebo group (P < 0.05). AA of cuprum in the rhGH group was almost twice as much as the placebo group (P < 0.05), and AU of zincum, cuprum and ferrum was all improved in the rhGH group (P < 0.05). The mean blood glucose level was significantly higher in the rhGH group than in the placebo group from d 3 to d 6 after operation (P < 0.05).
CONCLUSION: Postoperative low-dose rhGH treatment improves the retention of zincum, cuprum and ferrum and decreases the excretion of zincum, cuprum and ferrum, improves the balance of zincum, cuprum and ferrum, and promotes the AA and AU of zincum, cuprum and ferrum. rhGH can be well tolerated without significant adverse effects and the blood glucose level can be well controlled.
Collapse
|
|
3
|
Zhang MM, Wu XT, Zhou Y, Qian K, Zheng YM. Short-term application of low-dose growth hormone in surgical patients: Effects on nitrogen balance and blood glucose. World J Gastroenterol 2007; 13:452-6. [PMID: 17230618 PMCID: PMC4065904 DOI: 10.3748/wjg.v13.i3.452] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effectiveness and safety of recombinant human growth hormone (rhGH) in postoperative patients.
METHODS: A total of 48 consecutive patients undergoing abdominal operations were randomized to receive either subcutaneous rhGH (0.15 IU/kg) or placebo (menstruum) injections daily for 7 d after surgery. The two groups had similar nutritional intake. Blood samples for serum fibronectin, albumin, prealbumin, transferrin and the total lymphocyte count, as well as glucose levels were collected to study the rhGH effect. Basal laboratory evaluation, and nutritional status were estimated on d 1 before as baseline and d 3 and 10 after operation using standard laboratory techniques. Nitrogen balance was measured from d 3 to 9 after operation.
RESULTS: The cumulative nitrogen balance was significantly improved in rhGH group compared with the placebo group (11.37 ± 16.82 vs -9.11 ± 17.52, P = 0.0003). Serum fibronectin was also significantly higher in the rhGH group than in the placebo group (104.77 ± 19.94 vs 93.03 ± 16.03, P < 0.05), whereas changes in serum albumin, prealbumin, transferrin and total lymphocyte counts were not statistically significant. Mean blood glucose levels were significantly higher in the rhGH group from d 3 to 6 after operation.
CONCLUSION: If blood glucose can be controlled, low-dose growth hormone together with hypocaloric nutrition is effective on improving positive nitrogen balance and protein conservation and safe is in postoperative patients.
Collapse
Affiliation(s)
- Ming-Ming Zhang
- Department of General Surgery, West China Hospital, Sichuan University, 37 Guo Xue Rd., Chengdu 610041, Sichuan Province, China
| | | | | | | | | |
Collapse
|
|
4
|
Abstract
Trauma, sepsis, and surgery are associated with global hypercatabolism and a negative nitrogen balance. When critical illness is prolonged the relentless loss of lean tissue becomes functionally important. Protein catabolism in the critically ill patient is associated with complex changes in the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. Many small clinical studies indicate that treatment with recombinant human (rh) GH would be a safe and effective means of limiting the deleterious effects of the catabolic response. Unexpectedly, however, two large prospective randomized controlled trials (PRCTs) demonstrated that administration of rhGH to long-stay critically ill adults increases morbidity and mortality. Some progress has been made in understanding the mechanisms underlying this observation.
Collapse
Affiliation(s)
- Teng Teng Chung
- Department of Endocrinology, 5th Floor, King George V Building, St. Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
| | | |
Collapse
|
|
5
|
Uronen-Hansson H, Allen ML, Lichtarowicz-Krynska E, Aynsley-Green A, Cole TJ, Höidén-Guthenberg I, Fryklund L, Klein N. Growth hormone enhances proinflammatory cytokine production by monocytes in whole blood. Growth Horm IGF Res 2003; 13:282-286. [PMID: 12932750 DOI: 10.1016/s1096-6374(03)00034-0] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Growth hormone (GH) has been used as anabolic therapy to treat catabolic patients. In a recent study, however, administration of high doses of GH to critically ill adults was associated with an increase in morbidity and mortality. Preponderance of septic shock and uncontrolled infections as causes of death in these patients suggests an immuno-modulatory effect of GH. Our hypothesis was that GH treatment may modulate the production of proinflammatory cytokines, which are implicated in sepsis. In our study, human monocytes in whole blood were activated with lipopolysaccaharide (LPS) (1-100 ng/ml) purified from a clinical isolate of group B Neisseria meningitidis in the presence of a high dose of GH (100 ng/ml). The subsequent proinflammatory cytokine response was analysed by intracellular cytokine staining and flow cytometry. Our results show that GH enhances IL1-alpha, IL-6 and TNF-alpha production by LPS activated monocytes in whole blood. The modulation of cytokines by GH may be responsible for the adverse consequences of GH in critically ill patients.
Collapse
Affiliation(s)
- H Uronen-Hansson
- Institute of Child Health, Immunobiology, 30 Guilford Street, London WC1N 1EH, UK.
| | | | | | | | | | | | | | | |
Collapse
|
|
6
|
Gu Y, Wu ZH. The anabolic effects of recombinant human growth hormone and glutamine on parenterally fed, short bowel rats. World J Gastroenterol 2002; 8:752-7. [PMID: 12174391 PMCID: PMC4656333 DOI: 10.3748/wjg.v8.i4.752] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the metabolic effects associated with administration of rhGH and/or Gln in parenterally fed, short-bowel rats.
METHODS: Forty SD rats subjected to 75% intestinal resection and maintained with parenteral nutrition were randomly divided into 4 groups as follows: -rhGH, -Gln; -rhGH, +Gln; +rhGH, -Gln; +rhGH, +Gln. Body weight and nitrogen balance were evaluated daily. After 6 d of PN, rats were killed, various organs were dissected and weighted, the carcasses were used for analysis of body composition. Serum GH and IGF-1 were determined by RIA method.
RESULTS: Weight loss in rats with rhGH (17.4 ± 12.8 g) and rhGH+Gln (23.8 ± 3.5 g) was significantly less than rats with PN alone (29.6 ± 6.9 g) and rats with Gln-supplemented PN (31.85 ± 12.8 g), P < 0.05. The accumulated NB in rats with rhGH (1252.9 ± 294.3 mg N/d) and rhGH+Gln (1261.7 ± 85.5 mg N/d) was significantly greater than those with PN alone (704.8 ± 379.0 mg N/d) and with Gln-supplemented PN (856.7 ± 284.4 mg N/d), P < 0.05. The absolute weight of gastrocnemius muscle in rats with rhGH (2683.9 ± 341.6 mg) and rhGH+Gln (2579.1 ± 359.5 mg) was greater than those with PN alone (2176.3 ± 167.1 mg) and with Gln-supplemented PN (2141.9 ± 353.6 mg). Although the absolute weight of remnant small intestine itself was not significantly different in 4 experimental groups, the weight/length of the segments was greater in rats with rhGH and/or Gln (48.7 ± 5.5, 52.7 ± 4.1 and 67.4 ± 5.3 respectively) than those with PN alone (47.8 ± 5.0), there were synergistic effects between rhGH and Gln in improvement of the weight/length of remnant small intestine, P < 0.05. Analyses of body carcass composition showed that a higher percentage of carcass weight as protein and a lower percentage of carcass weight as fat were occurred in rats with rhGH (20.8 ± 4.0, 6.0 ± 2.6) and rhGH+Gln (21.3 ± 2.4, 4.4 ± 1.5) than those with PN alone (16.4 ± 2.4, 9.2 ± 3.7) and with Gln-supplemented PN (17.8 ± 3.0, 6.3 ± 2.0), rhGH had significant effects on alteration of body composition, P < 0.05. Serum GH and IGF-1 concentration in rats with rhGH (5.221 ± 0.8 and 425.1 ± 19.2 ng/mL respectively) and rhGH+Gln (5.507 ± 1.0 and 461.1 ± 49.9 ng/mL respectively) were greater than those with PN alone (3.327 ± 1.7 and 325.8 ± 29.6 ng/mL respectively) and with Gln-supplemented PN (3.433 ± 0.1 and 347.7 ± 55.7 ng/mL respectively), P < 0.01.
CONCLUSION: rhGH significantly improves the anabolism in parenterally fed. Short bowel rats, anabolic effect with Gln is less dramatic, there is no synergistic effect between rhGH and Gln in improvement of whole body anabolism. IGF-1 plays an important part in growth-promoting effects of rhGH.
Collapse
Affiliation(s)
- Yan Gu
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Second Medical University, Shanghai 200011, China.
| | | |
Collapse
|
|
7
|
Abstract
Providing nutrition and metabolic support to the CCI patient is based on the rational application of scientifically derived data and clinical experience with this unique population. Much of the data presented has been extrapolated from the critically ill ICU patients and the chronically ill hospitalized or nursing home patient, as there are limited data solely based on an experience with the CCI [table: see text] patient population. The key principles are: (1) primacy of protein provision and avoidance of overfeeding energy, (2) use of combined modality (enteral, parenteral, and oral) nutrition to meet needs as required, (3) use of adjunctive agents to promote nitrogen retention when needed, and (4) recognition of and adjustment for altered nutrient requirements (Table 3).
Collapse
Affiliation(s)
- Jeffrey I Mechanick
- Division of Endocrinology, Diabetes, and Bone Disease, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
| | | |
Collapse
|
|
8
|
Abstract
Prolonged length of stay is the major challenge for modern intensive care because of the associated morbidity and the impact on resource utilization. Severe trauma or infection is associated with a catabolic response, which is characterized by increased protein turnover and negative nitrogen balance. Severe catabolism leads to end-organ dysfunction and muscular weakness, prolonging the need for mechanical ventilation. Catabolism cannot be prevented with standard parenteral or enteral nutritional formulas. In order to prevent the complications of catabolism in intensive care patients, recombinant growth hormone has been applied as an experimental therapy for two decades in patients requiring parenteral nutrition and in patients with respiratory failure. Administration of recombinant growth hormone has resulted in positive nitrogen balance, and studies in mechanically ventilated patients suggest that it may shorten the need for ventilatory support. In contrast to the results of these relatively small studies, a recent multinational randomized controlled trial revealed that the administration of recombinant growth hormone (with doses 10-20 times higher than used for replacement therapy) increases mortality of critically ill patients. The excessive mortality in patients treated with recombinant growth hormone was related to infections and development of multiple organ failure, leading to the conclusion that administration of high doses of recombinant growth hormone cannot be recommended for critically ill patients. This review reinforces that conclusion.
Collapse
Affiliation(s)
- Esko Ruokonen
- Critical Care Research Program, Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland
| | | |
Collapse
|
|
9
|
Pittoni G, Gallioi G, Zanello M, Gianotti L, Boghen MF, Colombo S, Broglio F, Santoro C, Davià G, Papini MG, Destefanis S, Minuto F, Miola C, Ghigo E. Activity of GH/IGF-I axis in trauma and septic patients during artificial nutrition: different behavior patterns? J Endocrinol Invest 2002; 25:214-23. [PMID: 11936462 DOI: 10.1007/bf03343993] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The aim of this study was to compare several parameters of GH/IGF-I axis activity in septic and trauma patients during Intensive Care Unit (ICU) stay. To this goal, 13 patients with sepsis (SEP) and 16 with trauma (TRA) were studied. Thirty-three adult subjects (AS) were studied as controls. Serum IGF-I and -II, IGFBP-1, -2 and -3, GH and GHBP levels were studied on day 1, 3, 5 and 7 after ICU admission, during comparable artificial nutrition in SEP and TRA and basally in AS. In 5 patients with SEP and 6 with TRA, the GH response to GHRH was evaluated on day 3. On ICU day 1, IGF-I and -II and IGFBP-3 in SEP were lower (p<0.05) than in TRA which, in turn, were lower (p<0.01) than in AS. IGF-I increased (p<0.05) both in SEP and TRA, but, on ICU day 7, those in SEP persisted lower than in TRA, which became similar to those in AS. IGF-II levels increased (p<0.05) in SEP only, persisting lower (p<0.05) than in TRA. On ICU day 1, GH in SEP and TRA were similar and did not vary until day 7, overlapping those in AS. The GH response to GHRH in SEP and TRA was similar and lower (p<0.01) than in AS. These findings indicate that IGF-I activity is impaired more in septic than in trauma patients. Reduced IGF-I activity probably reflects peripheral GH resistance though basal and GHRH-induced GH levels were not increased in these conditions.
Collapse
Affiliation(s)
- G Pittoni
- Institute of Anesthesiology and Intensive Care, University of Padova, Italy
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
10
|
Gianotti L, Stella M, Bollero D, Broglio F, Lanfranco F, Aimaretti G, Destefanis S, Casati M, Magliacani G, Ghigo E. Activity of GH/IGF-1 axis in burn patients: comparison with normal subjects and patients with GH deficiency. J Endocrinol Invest 2002; 25:116-24. [PMID: 11929081 DOI: 10.1007/bf03343974] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The aim of this study was to clarify the activity of GH/IGF-1 axis as well as the variations of nutritional parameters following a thermal injury in man. To this goal, in 22 patients with burn [BURN, age (mean+/-SE): 46.5+/-3.4 yr, BMI: 25.0+/-0.8 kg/m2, % burn surface area: 26.0+/-3.0%, ROI score: 0.22+/-0.1] we evaluated IGF-1, IGF binding protein (IGFBP-3), GH, GH binding protein (GHBP), pre-albumin (pre-A), albumin (A) and transferrin (TRA) levels on days 1, 3, 7, 14 and 28 after intensive care unit (ICU) admission. IGF-1, IGFBP-3, GH and GHBP levels were also assayed basally in 29 normal subjects (Ns) (Ns, age: 47.5+/-2.8 yr, BMI: 22.0+/-1.4 kg/m2) and in 34 panhypopituitary patients with severe GH deficiency (GHD, age: 42.7+/-2.5 yr, BMI: 25.6+/-0.8 kg/m2). On ICU day 1, IGF-1 and IGFBP-3 in BURN were higher than those in GHD (p<0.05 for both, respectively) and lower than those in Ns (p<0.05) while GH levels in BURN did not differ from those in Ns and higher than GHD (p<0.01). In BURN, IGF-I and IGFBP-3 levels showed a progressive decline (p<0.05) with nadir on day 14, when they overlapped those in GHD, and then an increase on day 28, though persisting lower than in Ns, while GH levels did not vary during ICU stay. IGF-I levels were associated neither to burn extension nor to ROI score. On ICU day 1 pre-A, A and TRA levels were similar to those in Ns, but underwent a progressive decrease with nadir on day 7 (p<0.001) for pre-A and TRA, and later, on day 14 (p<0.05) for A; pre-A and TRA but not A showed a rebound increase (p<0.01) on day 14, though persistingly lower than in Ns. In conclusion, our present data firstly show the time course variation of IGF-I levels in burn patients as function of nutritional and hormonal variables. It has to be emphasized that in the most critical phase after burn injuries, IGF-1 levels are as low as in hypopituitary patients with severe GHD. The physiological basis which leads to the impairment of this endogenous anabolic drive in this phase is, however, not clear yet.
Collapse
Affiliation(s)
- L Gianotti
- Department of Internal Medicine, University of Turin, Italy
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
11
|
Justová V, Lacinová Z, Melenovský V, Marek J, Holly JM, Hass T. The changes of IGF binding proteins after rhGH administration to patients totally dependent on parenteral nutrition. Growth Horm IGF Res 2001; 11:407-415. [PMID: 11914029 DOI: 10.1054/ghir.2001.0257] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
The objective was to study the effect of recombinant human growth hormone (rhGH) administration to patients with chronic malnutrition maintained on total parenteral nutrition (TPN) on the levels of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) during a double-blind trial. After 1 week of TPN the patients were randomized into group I (placebo) or group II (rhGH). Samples were collected on the first day (start of the TPN) to measure basal values, the seventh day to study the effect of TPN and the 10th, 14th and 21st days to evaluate the rhGH effect. Basal laboratory evaluation, nutritional status and glucose tolerance were assessed using standard laboratory techniques. Radioimmunoassays were used to analyse IGF-I, free IGF-I (fIGF-I) and IGFBP1-3. Electrophoresis with Western ligand blotting and Western immunoblotting was applied to find the pattern of IGFBPs. TPN had no effect on the circulating IGF-I concentration and the pattern of IGFBPs present in the studied groups of patients. The rhGH administration led to significant increases of IGF-I, total IGFBP-3, glycosylated IGFBP-3 (39, 42 kDa) and the 29 kDa fragment of IGFBP-3 and the decrease of IGFBP-2 during the trial (P<0.05). The mean levels of IGFBP-1, fIGF-I and the parameters of nutritional status in group II during the trial were not significantly influenced by rhGH. However, it has been found that IGFBP-1 and fIGF-I levels were correlated with the levels of the weekly nitrogen balance of each patient in group II at the end of the trial. In spite of the significant changes of IGF-I, IGFBP-2, total IGFBP-3 and IGFBP-3 (29 kDa proteolytic fragment) after rhGH administration to patients with malnutrition, maintained on parenteral nutrition, the increase of nitrogen balance was seen only in patients who decreased their IGFBP-1 and increased bioavailable IGF-I as reflected by measurement of fIGF-I. The levels of IGFBP-1 may provide a useful marker of IGF-I bioavailability in monitoring the efficiency of the rhGH therapy in malnourished patients.
Collapse
Affiliation(s)
- V Justová
- Third Medical Department of Charles University, Prague, Czech Republic.
| | | | | | | | | | | |
Collapse
|
|
12
|
Freeman BD, Danner RL, Banks SM, Natanson C. Safeguarding patients in clinical trials with high mortality rates. Am J Respir Crit Care Med 2001; 164:190-2. [PMID: 11463585 DOI: 10.1164/ajrccm.164.2.2011028] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- B D Freeman
- Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
| | | | | | | |
Collapse
|
|
13
|
Raguso CA, Genton L, Kyle U, Pichard C. Management of catabolism in metabolically stressed patients: a literature survey about growth hormone application. Curr Opin Clin Nutr Metab Care 2001; 4:313-20. [PMID: 11458027 DOI: 10.1097/00075197-200107000-00012] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
In the effort to improve the long-term outcome in critically ill patients, the utilization of anabolic agents, such as human recombinant growth hormone, has been proposed in order to reduce catabolism and improve nutritional status. A recent multicentre study regarding the use of human recombinant growth hormone in intensive care unit patients showed an unexpected increase in the mortality rate in human recombinant growth hormone-treated patients. This finding is in contrast with previous literature data reporting either no differences or an even lower mortality rate with the administration of human recombinant growth hormone. This review evaluates the possible reasons for this dramatic difference in outcomes between the multicentre study and the existing literature. Articles dealing with human recombinant growth hormone administration either in intensive care unit patients (n=26) or in postoperative patients (n=16) have been reviewed. Our analysis suggests that the low caloric intake given to patients enrolled in the multicentre study might have been inadequate to compensate for the hypermetabolism of these patients, and could not support the prolonged and delayed administration of high doses of human recombinant growth hormone. Whether the beneficial metabolic effects of human recombinant growth hormone translate into better clinical outcomes deserves further investigation. In addition, the careful selection of patients to be treated, and close monitoring of both the adequacy of caloric support and modality of human recombinant growth hormone administration would favour the safety of human recombinant growth hormone utilization in critical care settings.
Collapse
Affiliation(s)
- C A Raguso
- Clinical Nutrition, Geneva University Hospital, Geneva, Switzerland
| | | | | | | |
Collapse
|
|
14
|
Abstract
The consequences of "pharmacological" growth hormone administration have been studied in a number of conditions, including those characterized by high rates of catabolism. The majority of studies have reported favourable effects on metabolism but recent reports indicate that GH treatment results in increased mortality in critically ill humans. The objective of the study was to assess the safety of large doses of rhGH therapy in human adults. Original trials were identified by searching MEDLINE (1966-March 2000) and the Cochrane database (2000). References of all identified trials were also inspected for more studies. All relevant trials in which GH had been administered to non-GH-deficient (GHD) adult humans were selected from. Outcomes such as death, clinically significant change in function, change in length of hospital stay or need for treatment, and adverse effects were sought. Studies were selected, quality-assessed and passed suitable for inclusion by two independent reviewers. Those studies that were placebo-controlled with satisfactory randomization were considered for inclusion. Twenty-one reports were included in the review. A wide range of patient groups were studied by a variety of investigators, employing a range of doses and duration of GH treatment. The study protocols differed markedly. The majority of studies were small and were designed and/or powered to enable identification of specific effects on nutritional status, protein metabolism, level of function or quality of life. Only two studies were designed to assess safety issues and mortality. In these, GH treatment was associated with a marked increase in mortality in critically ill ICU patients, with a range of diagnoses. Multi-organ failure and the effects of sepsis/infection accounted for most of the excess mortality. In addition morbidity, in terms of length of ICU stay, was increased by GH administration. Other less marked effects were increased fluid retention and hyperglycaemia as a consequence of GH administration. Functional improvement following GH therapy was documented in some studies. There have been few studies assessing the safety aspects of "pharmacological" GH treatment in adult humans. Two well-designed reports indicate that GH administration results in increased morbidity and mortality in a wide variety of critically ill subjects across a spectrum of age ranges. The mechanism(s) of the GH-associated mortality remain poorly understood. Based on current trial evidence, pharmacological GH treatment cannot be recommended for widespread use in critically ill subjects. Well-conducted and reported randomized trials are still needed to inform practice as to whether GH administration will be safe in specific illness categories.
Collapse
Affiliation(s)
- P V Carroll
- Department of Endocrinology, St. Bartholomew's Hospital, London EC1A 7BE, UK.
| | | |
Collapse
|
|
15
|
Abstract
The marked endocrine changes that occur in anorexia nervosa have aroused a great deal of interest, and over the last decade much research has been conducted in this field. The endocrine disturbances are not specific to this disorder, as they also occur in starvation states secondary to other causes, and they return to normal upon weight restoration. However, emaciation may have profound effects on psychological processes, establishing an intricate circular interaction whereby somatic and psychological manifestations of starvation may continue to act. The purpose of this paper is to provide an overview of the large body of literature concerning endocrine aspects of anorexia nervosa with the main focus on the latest results, which provide leads for potential etiological theories.
Collapse
Affiliation(s)
- R K Støving
- Department of Endocrinology, Odense University Hospital, Denmark.
| | | | | |
Collapse
|
|
16
|
Abstract
The increased availability of growth hormone (GH) in the mid-1980s, as a result of advances in recombinant DNA techniques, has allowed research into the use of this hormone at physiological dosage, as replacement therapy for adults with GH deficiency (GHD) and at pharmacological dosages as a possible therapeutic agent, for a number of disease states. GHD adults have increased body fat and reduced muscle mass and consequently, reduced strength and exercise tolerance. In addition, they are osteopenic, have unfavourable cardiac risk factors and impaired quality of life. In these individuals, replacing GH reverses these anomalies, although it may not alter the reduced insulin-sensitivity. A proportion of adults with GHD perceive a dramatic improvement in their well-being, energy levels and mood following replacement. GH has protein and osteoanabolic, lipolytic and antinatriuretic properties. GH has been considered for the therapeutic treatment of frailty associated with ageing, osteoporosis, morbid obesity, cardiac failure, major thermal injury and various acute and chronic catabolic conditions. Initial small, uncontrolled studies for many of these clinical problems suggested a beneficial effect of GH, although, later placebo-controlled studies have not observed such dramatic effects. Furthermore, with a recent publication demonstrating an approximate 2-fold increase in mortality in critically ill patients receiving large doses of GH, the use of GH should remain in the realms of replacement therapy and research, until there are significant advances in our understanding.
Collapse
Affiliation(s)
- R D Murray
- Department of Endocrinology, Christie Hospital, NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK
| | | |
Collapse
|
|
17
|
Abstract
Prolonged stay of patients is the major challenge for modern intensive care because of its effects on morbidity and resource utilization. Severe trauma or infection are associated with the catabolic response, characterized by increased protein turnover and negative nitrogen balance. Severe catabolism leads to end-organ dysfunction and muscular weakness prolonging the need for mechanical ventilation. Catabolism cannot be prevented with standard parenteral or enteral nutritional formulas. In order to prevent the complications of catabolism in intensive care patients, recombinant growth hormone (rhGH) has been applied during two decades as an experimental therapy for patients requiring parenteral nutrition and for those with respiratory failure. Administration of rhGH has resulted in positive nitrogen balance, and studies in mechanically ventilated patients suggest that it may shorten the need for ventilatory support. In contrast to the results of these relatively small studies, a recent multinational randomized controlled trial revealed that the administration of rhGH (with doses 10-20 times higher than those used for replacement therapy) increases the mortality of critically ill patients. This excessive mortality in patients treated with rhGH was related to infections and development of multiple organ failure. Administration of high doses of rhGH to critically ill patients cannot thus be recommended.
Collapse
Affiliation(s)
- E Ruokonen
- Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Finland
| | | |
Collapse
|
|
18
|
Abstract
The recent increase in the elderly population, current health trends, and awareness of age-related changes in the male endocrine system have led to discussions about the endocrine system being a "pacemaker" of male aging. Better prevention and treatment of "non-beneficial states of health" in aging men, such as generally decreased well-being and virility, increased visceral fat, osteopenia, atherosclerosis, and impaired cognitive function, is based on improved understanding of aging, particularly the significance of age-associated hormonal changes. Although not as dramatic as in women, men also show declining hormone serum concentrations with aging (Vermeulen and Kaufman, 1995). Because aging is associated with deleterious effects resembling the clinical signs of hypogonadism or states of subnormal hormone concentrations, the potential role of hormone supplementation in aging men paralleling hormone replacement therapy in postmenopausal women is the topic of discussion. The goal of hormone replacement would be to improve body composition and increase muscle strength and quality of life in men, thereby reducing mortality and morbidity. The findings so far support the need for long-term studies of hormonal supplementation in older males showing decreased hormone serum levels. Nevertheless, to date, such a use outside the context of a clinical trial is not justified.
Collapse
Affiliation(s)
- M Hermann
- Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck
| | | |
Collapse
|
|
19
|
Takala J, Ruokonen E, Webster NR, Nielsen MS, Zandstra DF, Vundelinckx G, Hinds CJ. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 1999; 341:785-92. [PMID: 10477776 DOI: 10.1056/nejm199909093411102] [Citation(s) in RCA: 668] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND The administration of growth hormone can attenuate the catabolic response to injury, surgery, and sepsis. However, the effect of high doses of growth hormone on the length of stay in intensive care and in the hospital, the duration of mechanical ventilation, and the outcome in critically ill adults who are hospitalized for long periods is not known. METHODS We carried out two prospective, multicenter, double-blind, randomized, placebo-controlled trials in parallel involving 247 Finnish patients and 285 patients in other European countries who had been in an intensive care unit for 5 to 7 days and who were expected to require intensive care for at least 10 days. The patients had had cardiac surgery, abdominal surgery, multiple trauma, or acute respiratory failure. The patients received either growth hormone (mean [+/-SD] daily dose, 0.10 +/- 0.02 mg per kilogram of body weight) or placebo until discharge from intensive care or for a maximum of 21 days. RESULTS The in-hospital mortality rate was higher in the patients who received growth hormone than in those who did not (P<0.001 for both studies). In the Finnish study, the mortality rate was 39 percent in the growth hormone group, as compared with 20 percent in the placebo group. The respective rates in the multinational study were 44 percent and 18 percent. The relative risk of death for patients receiving growth hormone was 1.9 (95 percent confidence interval, 1.3 to 2.9) in the Finnish study and 2.4 (95 percent confidence interval, 1.6 to 3.5) in the multinational study. Among the survivors, the length of stay in intensive care and in the hospital and the duration of mechanical ventilation were prolonged in the growth hormone group. CONCLUSIONS In patients with prolonged critical illness, high doses of growth hormone are associated with increased morbidity and mortality.
Collapse
Affiliation(s)
- J Takala
- Critical Care Research Program, Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Finland
| | | | | | | | | | | | | |
Collapse
|
|
20
|
Affiliation(s)
- C Corcoran
- Neuroendocrine Unit, Massachusetts General Hospital, and Harvard Medical School, Boston 02114, USA
| | | |
Collapse
|
|
21
|
Ward WE, Atkinson SA. Growth hormone and insulin-like growth factor-I therapy promote protein deposition and growth in dexamethasone-treated piglets. J Pediatr Gastroenterol Nutr 1999; 28:404-10. [PMID: 10204505 DOI: 10.1097/00005176-199904000-00011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Dexamethasone treatment facilitates the weaning of premature infants from mechanical ventilation but impairs protein homeostasis, lean tissue deposition, and growth. The current study was conducted to investigate whether dexamethasone mediates these effects by reducing protein synthesis or elevating protein breakdown, and whether adjuvant growth hormone+/-insulin-like growth factor-I therapy can attenuate such effects. METHODS Piglets (n = 24) were randomized to placebo, a tapered course of dexamethasone (0.5, 0.3, 0.2 mg/kg per day for 5, 5 and 4 days each, respectively), dexamethasone + growth hormone 0.1 mg/kg per day, or dexamethasone + growth hormone + insulin-like growth factor-I 0.1 mg/kg per day for 14 days. On day 13, 15N-glycine was administered as a single oral dose, and urine was collected at timed intervals during the subsequent 48 hours. RESULTS Total urinary N and cumulative 15N excretion were higher in all dexamethasone groups than in control subjects. Protein synthesis was suppressed, whereas protein breakdown was unaltered by dexamethasone. Adjunctive growth hormone+/-insulin-like growth factor-I therapy enhanced protein synthesis, but only combined therapy improved net protein gain compared with dexamethasone alone. Higher circulating insulin-like growth factor-I may have mediated the greater net protein gain. Blood urea nitrogen was elevated in all dexamethasone-treated groups at days 6 and 11 but was normalized by day 15 with adjunctive growth hormone+/-insulin-like growth factor-I. From a functional perspective, both adjunctive growth hormone and growth hormone+/-insulin-like growth factor-I partially attenuated the dexamethasone-induced reduction in weight and length gain but not in whole body lean and fat mass. CONCLUSION Adjunctive growth hormone+/-insulin-like growth factor-I therapy partially reverses the dexamethasone-induced reduction in protein synthesis, resulting in improved growth when given concurrently with a low tapering dose of dexamethasone.
Collapse
Affiliation(s)
- W E Ward
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
| | | |
Collapse
|
|
22
|
Abstract
Anorexia nervosa is a syndrome of unknown etiology. It is associated with multiple endocrine abnormalities. Hypothalamic monoamines (especially serotonin), neuropeptides (especially neuropeptide Y and cholecystokinin) and leptin are involved in the regulation of human appetite, and in several ways they are changed in anorexia nervosa. However, it remains to be clarified whether the altered appetite regulation is secondary or etiologic. Increased secretion of corticotropin-releasing hormone and proopiomelanocortin seems to be secondary to starvation, however, there is evidence that it may maintain and intensify anorexia, excessive physical activity and amenorrhea. Hypothalamic amenorrhea, which is a diagnostic criterion in anorexia nervosa, is not solely related to the low body weight and exercise. Growth hormone resistance with low production of insulin-like growth factor I and high growth hormone secretion reflect the nutritional deprivation. The nutritional therapy of patients with anorexia nervosa might be improved by administering an anabolic agent such as growth hormone or insulin-like growth factor I. So far none of the endocrine abnormalities have proved to be primary, however, there is increasing evidence that some of these might participate in a vicious circle.
Collapse
Affiliation(s)
- R K Støving
- Department of Endocrinology and Centre for Eating Disorders, Odense University Hospital, Odense C, Denmark
| | | | | | | |
Collapse
|
|
23
|
Jenkins RC, Ross RJ. Acquired growth hormone resistance in adults. BAILLIERE'S CLINICAL ENDOCRINOLOGY AND METABOLISM 1998; 12:315-29. [PMID: 10083899 DOI: 10.1016/s0950-351x(98)80025-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Acquired growth hormone resistance (AGHR) may be defined as the combination of a raised serum growth hormone (GH) concentration, low serum insulin-like growth factor-1 (IGF-1) concentration and a reduced anabolic response to exogenous GH. A wide range of conditions exhibit the syndrome to a variable degree, including sepsis, trauma, burns, AIDS, cancer, and renal or liver failure. The primary defect seems to be a reduction in IGF-1 concentration which then leads to increased GH concentration by a loss of negative feedback. It is not clear whether IGF-1 concentration falls because of decreased production or increased clearance from the circulation, or both. Treatment to reverse the biochemical defect by restoring IGF-1 levels, either by the administration of GH or IGF-1, has resulted in improvements in a wide range of metabolic parameters and, more recently, to definite clinical benefit in well-defined groups, such as patients with AIDS. These results cannot be extrapolated to other groups with AGHR as a recent unpublished report suggested increased mortality in critically ill patients treated with GH. Research needs to focus on the molecular basis of AGHR if we are to develop therapies for catabolism.
Collapse
Affiliation(s)
- R C Jenkins
- Department of Medicine, University of Sheffield, UK
| | | |
Collapse
|
|
24
|
Gianotti L, Broglio F, Aimaretti G, Arvat E, Colombo S, Di Summa M, Gallioli G, Pittoni G, Sardo E, Stella M, Zanello M, Miola C, Ghigo E. Low IGF-I levels are often uncoupled with elevated GH levels in catabolic conditions. J Endocrinol Invest 1998; 21:115-21. [PMID: 9585386 DOI: 10.1007/bf03350325] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Increased GH together with decreased IGF-I levels pointing to peripheral GH insensitivity in critically ill patients have been reported by some but not by other authors. To clarify whether elevated GH levels are coupled with low IGF-I levels in all catabolic conditions, basal GH and IGF-I levels were evaluated in patients with sepsis (SEP, no.=13; age [mean+/-SE]=59.2+/-1.2 yr), trauma (TRA, no.=16; age=42.3+/-3.4 yr), major burn (BUR, no.=26; age=52.8+/-4.2 yr) and post-surgical patients (SUR, no.=11; age=55.0+/-4.7 yr) 72 hours after ICU admission or after cardiac surgery. GH and IGF-I levels were also evaluated in normal subjects (NS, no.=75; age=44.0+/-1.5 yr), in adult hypopituitaric patients with severe GH deficiency (GHD, no.=54; age=44.8+/-2.3 yr), in patients with liver cirrhosis (LC, no.=12; age=50.4+/-2.8 yr) and in patients with anorexia nervosa (AN, no.=19; age=18.7+/-0.8 yr). Basal IGF-I and GH levels in GHD were lower than in NS (68.6+/-6.4 vs 200.9+/-8.7 microg/l and 0.3+/-0.1 vs 1.4+/-0.2 microg/l; p<0.01). On the other hand, AN and LC showed IGF-I levels (70.4+/-9.1 and 52.4+/-10.5 microg/l) similar to those in GHD while GH levels (10.0+/-2.8 and 7.9+/-2.1 microg/l) were higher than those in NS (p<0.01). IGF-I levels in SEP (84.5+/-8.8 microg/l) were similar to those in GHD, AN and LC and lower than those in NS (p<0.01). IGF-I levels in BUR (105.2+/-10.9 microg/l) were lower than in NS (p<0.01) but higher than those in GHD, AN, LC and SEP (p<0.01). On the other hand, in TRA (162.8+/-17.4 microg/l) and SUR (135.0+/-20.7 microg/l) IGF-I levels were lower but not significantly different from those in NS and clearly higher than those in GHD, AN, LC, SEP and BUR. Basal GH levels in SEP (0.6+/-0.2 microg/l), TRA (1.8+/-0.5 microg/l), SUR (2.2+/-0.5 microg/l) and BUR (2.2+/-0.5 microg/l) were similar to those in NS, higher (p<0.05) than those in GHD and lower (p<0.01) than those in AN and LC. In conclusion, our data demonstrate that low IGF-I levels are not always coupled with elevated GH levels in all catabolic conditions. Differently from cirrhotic and anorectic patients, in burned and septic patients GH levels are not elevated in spite of very low IGF-I levels similar to those in panhypopituitaric GHD patients. These findings suggest that in some catabolic conditions peripheral GH insensitivity and somatotrope insufficiency could be concomitantly present.
Collapse
Affiliation(s)
- L Gianotti
- Dipartimento di Medicina Interna, Università di Torino, Italy
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
|
|
26
|
Cresci GA, Martindale RG. Metabolic and nutritional management of a patient with multiple enterocutaneous fistulas. Nutrition 1997; 13:446-8; discussion 448-9. [PMID: 9225338 DOI: 10.1016/s0899-9007(97)00094-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- G A Cresci
- Department of Surgery, Medical College of Georgia, Augusta 30912-4004, USA
| | | |
Collapse
|
|
27
|
Plauth M, Merli M, Kondrup J, Weimann A, Ferenci P, Müller MJ. ESPEN guidelines for nutrition in liver disease and transplantation. Clin Nutr 1997; 16:43-55. [PMID: 16844569 DOI: 10.1016/s0261-5614(97)80022-2] [Citation(s) in RCA: 212] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- M Plauth
- IV. Medizinische Klinik, Klinikum Charitéder Humboldt Universität, D-10098 Berlin, Germany
| | | | | | | | | | | |
Collapse
|
|
28
|
Affiliation(s)
- W W Souba
- Division of Surgical Oncology, Massachusetts General Hospital, Boston 02114, USA
| |
Collapse
|
|
29
|
Ellegård L, Bosaeus I, Nordgren S, Bengtsson BA. Low-dose recombinant human growth hormone increases body weight and lean body mass in patients with short bowel syndrome. Ann Surg 1997; 225:88-96. [PMID: 8998124 PMCID: PMC1190610 DOI: 10.1097/00000658-199701000-00010] [Citation(s) in RCA: 107] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The authors investigate the effects of low dose recombinant human growth hormone (rhGH) on body composition and absorptive capacity in patients with short bowel syndrome from Crohn's disease. SUMMARY BACKGROUND DATA Patients with short bowel syndrome usually are malnourished because of malabsorption. The anabolic effects of high doses of rhGH have been tested in different clinical catabolic conditions, recently including patients with short bowel syndrome. The authors have investigated the effects of low-dose rhGH in short bowel syndrome in a placebo-controlled crossover clinical trial. METHODS Ten patients were treated with daily subcutaneous doses of rhGH/placebo (0.5 international units/kg-1 per week-1 = 0.024 mg/kg-1 per day-1) for 8 weeks in a randomized, double-blind, placebo-controlled crossover clinical trial with a minimum of 12 weeks wash-out. Absorptive capacity and biochemical parameters were investigated in a metabolic ward before treatment and during first and last week of treatment. Body composition was determined by DEXA-Scan (Lunar DPX, Scanexport Medical, Helsingborg, Sweden), impedance analysis, and whole body potassium counting. RESULTS Low-dose rhGH doubled serum levels of insulin-like growth factor-1 (IGF-1) and increased body weight, lean body mass, and total body potassium by 5% (p < 0.05). Fat-free mass and total body water increased by 6% (p = 0.008). Increases in IGF-1 levels correlated with increases in fat-free mass (r = 0.77, p < 0.02). No significant changes in absorptive capacity of water, energy, or protein were detected. CONCLUSION Eight weeks of low-dose rhGH treatment leads to increases in body weight, lean body mass, and fat-free mass in patients with short bowel syndrome, correlated to increases in IGF-1 levels.
Collapse
Affiliation(s)
- L Ellegård
- Department of Clinical Nutrition, Sahlgrenska University Hospital, Gothenburg, Sweden
| | | | | | | |
Collapse
|
|
30
|
Jeevanandam M, Holaday NJ, Petersen SR. Integrated nutritional, hormonal, and metabolic effects of recombinant human growth hormone (rhGH) supplementation in trauma patients. Nutrition 1996; 12:777-87. [PMID: 8974104 DOI: 10.1016/s0899-9007(96)00220-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
An anabolic stimulus is needed in addition to conventional nutritional support in the catabolic "flow" phase of severe trauma. One promising therapy appears to be rhGH infusion which has direct as well as hormonal mediated substrate effects. We investigated on a whole-body level, the basic metabolic effects of trauma within 48-60 h after injury in 20 severely injured (injury severity score [ISS] = 31 +/- 2), highly catabolic (N loss = 19 +/- 2 g/d), hypermetabolic (resting energy expenditure [REE] = 141 +/- 5% basal energy expenditure [BEE]), adult (age 46 +/- 5 y) multiple-trauma victims, before starting nutrition therapy and its modification after 1 wk of rhGH supplementation with TPN (1.1 x REE calories, 250 mg N.kg-1.d-1). Group H (n = 10) randomly received at 8:00 a.m. on a daily basis rhGH (0.15 mg.kg-1.d-1) and Group C (n = 10) received the vehicle of infusion. Protein metabolism (turnover, synthesis and breakdown rates, and N balance); glucose kinetics (production, oxidation, and recycling); lipid metabolism, (lipolysis and fat oxidation rates), daily metabolic and fuel substrate oxidation rate (indirect calorimetry); and plasma levels of hormones, substrates, and amino acids were quantified. In group H compared to group C: N balance is less negative (-41 +/- 18 vs -121 +/- 19 mg N.kg-1.d-1, P = 0.001); whole body protein synthesis rate is 28 +/- 2% (P = 0.05) higher; protein synthesis efficiency is higher (62 +/- 2% vs 48 +/- 3%, P = 0.010); plasma glucose level is significantly elevated (256 +/- 25 vs 202 +/- 17 mg/dL, P = 0.05) without affecting hepatic glucose output (1.51 +/- 0.20 vs 1.56 +/- 0.6 mg N.kg-1.min-1), glucose oxidation and recycling rates; significantly enhanced rate of lipolysis (P = 0.006) and free fatty acid reesterification (P = 0.05); significantly elevated plasma levels of anabolic GH, IGF-1, IGFBP-3, and insulin; trauma induced counter-regulatory hormone (cortisol, glucagon, catecholamines) levels are not altered; trauma induced hypoaminoacidemia is normalized (P < 0.05) and 3-methylhistidine excretion is significantly low (P < 0.001). Improved plasma IGF-1 levels in Group H compared with Group C account for protein anabolic effects of adjuvant rhGH and may be helpful in promoting tissue repair and early recovery. Skeletal muscle protein is spared by rhGH resulting in the stimulation of visceral protein breakdown. The hyperglycemic, hyperinsulinemia observed during rhGH supplementation may be due to defective nonoxidative glucose disposal, as well as inhibition of glucose transport activity into tissue cells. The simultaneous operation of increased lipolytic and reesterification processes may allow the adipocyte to respond rapidly to changes in peripheral metabolic fuel requirements during injury. This integral approach helps us to better understand the mechanism of the metabolic effects of rhGH.
Collapse
Affiliation(s)
- M Jeevanandam
- Trauma Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA
| | | | | |
Collapse
|
|
31
|
Jeevanandam M, Holaday NJ, Petersen SR. Adjuvant recombinant human growth hormone does not augment endogenous glucose production in total parenteral nutrition-fed multiple trauma patients. Metabolism 1996; 45:450-6. [PMID: 8609830 DOI: 10.1016/s0026-0495(96)90218-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hyperglycemia and insulin resistance are well-known, consistent responses to severe injury. The purpose of this study was to investigate the mechanism for the further exaggerated hyperglycemia due to adjuvant recombinant human growth hormone (rhGH) treatment in multiple trauma patients. We have measured in 20 adult severely injured, highly catabolic, hypermetabolic multiple trauma patients, the glucose kinetics (appearance, clearance, oxidation, and recycling) once in the basal state (study I), 48 to 60 hours after injury but before starting nutritional therapy, and again (study II) after 7 days of intravenous nutrition (1.1 times resting energy expenditure, 250 mg nitrogen [N]/kg/d) with or without adjuvant rhGH. Group H (n = 10) randomly received daily (8 AM) rhGH (0.15 mg/kg/d) and group C (n = 10) received the vehicle of infusion. Adjuvant rhGH treatment in intravenously fed trauma patients (1) increases plasma insulin-like growth factor-1 (IGF-1) and insulin concentrations, (2) improves N balance, and (3) exaggerates the hyperglycemic response without affecting endogenous glucose output, glucose oxidation, or recycling. The mechanism for the hyperglycemic hyperinsulinemia in trauma may be due to a defective nonoxidative glucose disposal, as well as inhibition of glucose transport activity into tissue cells.
Collapse
Affiliation(s)
- M Jeevanandam
- Trauma Center, St Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA
| | | | | |
Collapse
|
|
32
|
|
|
33
|
Boggio Bertinet D, Costantino A, Finocchiaro C, Galletti R, Rovera G, Balzola F. Special issues in home parenteral nutrition: non-essential nutrients. Clin Nutr 1995; 14 Suppl 1:75-8. [PMID: 16843980 DOI: 10.1016/s0261-5614(95)80289-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- D Boggio Bertinet
- Department of Gastroenterology and Clinical Nutrition, Molinette Hospital, C. So Bramante, 88-10126 Turin, Italy
| | | | | | | | | | | |
Collapse
|
|
34
|
Voerman BJ, Strack van Schijndel RJ, Groeneveld AB, de Boer H, Nauta JP, Thijs LG. Effects of human growth hormone in critically ill nonseptic patients: results from a prospective, randomized, placebo-controlled trial. Crit Care Med 1995; 23:665-73. [PMID: 7712756 DOI: 10.1097/00003246-199504000-00014] [Citation(s) in RCA: 60] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
OBJECTIVES To study the effects of growth hormone administration on insulin-like growth factor I concentration, nitrogen balance, and fuel utilization, and to study its safety in critically ill nonseptic patients. DESIGN Prospective, randomized, placebo-controlled trial. SETTING Medical intensive care unit of a university hospital. PATIENTS Eighteen critically ill nonseptic patients were studied for 8 days after admission. INTERVENTIONS Growth hormone (0.1 mg/kg/day) or placebo was administered as a continuous intravenous infusion on the second, third, and fourth days after admission. The study period was 8 days. MEASUREMENTS AND MAIN RESULTS Plasma hormone concentrations were measured every 6 hrs and average daily values were calculated. The 24-hr urinary nitrogen and 3-methylhistidine excretion were measured. Indirect calorimetry was used to calculate fuel utilization. Insulin-like growth factor I concentrations increased in the treatment group from subnormal to normal values and remained increased despite discontinuation of growth hormone treatment (p = .02). Nitrogen balance differed between the groups upon admission: growth hormone group (3.9 +/- 4.1 g/day) vs. controls (13.8 +/- 5.4 g/day), but improved with growth hormone. This finding appeared independent of the imbalance between the groups. The 3-methylhistidine excretion was not different between the groups and did not change during growth hormone administration. Free fatty acids and glycerol concentrations increased during growth hormone treatment, but calculated fuel utilization did not change. During growth hormone treatment, insulin concentrations increased, due to the increased administration of insulin necessary for glycemic control. Side effects other than hyperglycemia were not observed. CONCLUSIONS Growth hormone administration in a heterogeneous group of critically ill nonseptic patients resulted in normalization of insulin-like growth factor I levels, even after cessation of growth hormone treatment. Nitrogen balance improved, but this change was transient. Hence, growth hormone affects nitrogen balance, probably partly independent of insulin-like growth factor I.
Collapse
Affiliation(s)
- B J Voerman
- Medical Intensive Care Unit, Free University Hospital, Amsterdam, The Netherlands
| | | | | | | | | | | |
Collapse
|
|
35
|
Voerman BJ, Strack van Schijndel RJ, de Boer H, Groeneveld AB, Nauta JP, van der Veen EA, Thijs LG. Effects of human growth hormone on fuel utilization and mineral balance in critically ill patients on full intravenous nutritional support. J Crit Care 1994; 9:143-50. [PMID: 7981777 DOI: 10.1016/0883-9441(94)90010-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
PURPOSE The effects of recombinant human growth hormone (GH) on fuel utilization, mineral and fluid balance in critically ill patients were studied. METHODS Twenty patients requiring mechanical ventilation and receiving standard parenteral nutrition were studied. GH 0.1 mg/kg/day (n = 10) or placebo (n = 10) was administered as continuous intravenous infusion for 3 days. Plasma mineral levels, urinary nitrogen, and mineral excretion were measured. Indirect calorimetry was used to calculate energy production rate and fuel utilization. RESULTS Insulin-like growth factor I concentrations increased: day 4 GH, 18.9 +/- 7.0 ng/mL; controls 11.6 +/- 3.2 ng/mL (P < .05). During GH administration, the nitrogen balance became zero, whereas it remained negative in controls (P = .03). Fuel utilization did not differ between the groups. Neither did oxygen consumption, carbon dioxide production, or the respiratory quotient (RQ). Nonprotein RQ showed a tendency to decrease in the GH group, whereas an increase was present in controls. Mineral balance improved in both groups. Phosphate balance improved by 250% in the GH group (P = .054). CONCLUSIONS GH administration in critically ill patients reduces nitrogen loss and improves phosphate retention but does not have an important effect on fuel utilization.
Collapse
Affiliation(s)
- B J Voerman
- Department of Endocrinology, Free University Hospital, Amsterdam, The Netherlands
| | | | | | | | | | | | | |
Collapse
|
|
36
|
Ziegler TR, Gatzen C, Wilmore DW. Strategies for attenuating protein-catabolic responses in the critically ill. Annu Rev Med 1994; 45:459-80. [PMID: 8198396 DOI: 10.1146/annurev.med.45.1.459] [Citation(s) in RCA: 75] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Specialized enteral and parenteral nutrition are now a standard components of care in critically ill patients. This adjunctive therapy corrects and prevents nutrient deficiencies, attenuates the loss of body protein, and improves clinical outcomes in malnourished patients. Several novel strategies designed to improve the metabolic and clinical effects of specialized nutrition are under vigorous clinical investigation. These new approaches include increased emphasis on enteral feeding to maintain intestinal absorptive, immune, and barrier function; administration of conditionally essential amino acids (glutamine, arginine); use of specialized lipid products and antioxidants; and administration of growth factors such as human growth hormone. Randomized, controlled clinical trials will define the clinical and metabolic efficacy and cost-effectiveness of these therapies in specialized nutrition support.
Collapse
Affiliation(s)
- T R Ziegler
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | | | | |
Collapse
|
|
37
|
|