Low Insulin-like Growth Factor-1 Levels Research Articles

Growth hormone/insulin-like growth factor 1 axis alterations contribute to disturbed protein metabolism in cirrhosis patients after hepatectomy

Background/Aim: Liver cirrhosis is accompanied by a fall in whole-body protein turnover and alterations of the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. However, the influence of liver cirrhosis on the GH/IGF-1 axis in the perioperative period, and the contribution of the GH/IGF-1 axis alteration in cirrhosis to postoperative nitrogen metabolism are not known. Methods: Plasma GH, IGF-1 and IGF binding protein 3 (IGF-BP3) levels were measured sequentially in patients undergoing hepatectomy with or without cirrhosis. Postoperative nitrogen excretion and wholebody protein turnover rate were also determined. Results: Preoperative plasma IGF-1 level showed a negative correlation with indocyanine green retention rate. Cirrhosis patients undergoing hepatectomy had low IGF-1 and IGF-BP3 levels, despite extremely high GH levels in the perioperative period. Perioperative IGF-1 levels were lower in patients with postoperative complications than in those without complications. Postoperative nitrogen excretion was higher and wholebody protein turnover rate was lower in patients with cirrhosis than in those without cirrhosis. The postoperative IGF-1 level showed a positive correlation with whole-body protein turnover rate. Conclusions: Postoperative hepatic IGF-1 production may be severely disturbed in patients with cirrhosis, and the impaired IGF-1 production contributes to the suppressed postoperative protein metabolism in cirrhosis. It may be appropriate to increase plasma IGF-1 level in patients with cirrhosis to enhance postoperative protein metabolism and improve the postoperative outcome.

Plasma insulin-like growth factor-1, type 1 procollagen, and serum tumor necrosis factor alpha in children recovering from Trichuris dysentery syndrome.

To explore: 1) the relationship between plasma insulin-like growth factor-1 (IGF-1) and other markers of growth; and 2) the effect of serum concentrations of tumor necrosis factor alpha (TNF) on growth variables in children (2-10 years) stunted by Trichuris dysentery syndrome (TDS), recovering cases, and their matched controls. Fourteen patients with TDS were admitted to the Tropical Metabolism Research Unit, treated with albendazole and iron, and then followed with matched controls (n = 28) for 1 year. Anthropometric and biochemical measurements were done on admission and then every 3 months for the year. Plasma IGF-1, the carboxyterminal propeptide of type 1 procollagen, serum TNF, total serum protein, serum albumin, and complete blood count were determined. Low admission plasma levels of IGF-1 in TDS cases were accompanied by high serum levels of TNF, and total serum protein, normal serum albumin, low hemoglobin, reduced collagen synthesis (low plasma carboxyterminal propeptide of type 1 procollagen), and growth failure. These variables improved significantly after treatment. Plasma levels of IGF-1 were significantly related to the Z-scores for height-for-age (r = 0.60, 0.73, 0.68) and weight-for-age (r = 0.69, 0.80, 0.69) of cases and controls, height-for-age (r = 0.51, 0.52, 0.54) and weight-for-age (r = 0.51, 0.52, 0.54) at each measurement throughout the year. Serum levels of TNF were not related to any of the growth variables. These findings may contribute to the understanding of growth failure in children affected by other forms of chronic inflammatory bowel disease.

Arm span, serum IGF-1 and IGFBP-3 levels as screening parameters for the diagnosis of growth hormone deficiency in patients with myelomeningocele--preliminary data.

Short stature is a common problem in patients with myelomeningocele (MMC) and hydrocephalus. We evaluated auxological and laboratory parameters to differentiate short stature due to neurological defect from short stature additionally caused by growth hormone deficiency (GHD). In a group of 38 prepubertal patients with MMC and hydrocephalus aged 3.8-11.0 years, auxological parameters, including arm span and bone age, and serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured. Patients with normal supine length (n = 15) had normal arm span. Serum IGF-1 and IGFBP-3 levels were normal (> or = 10th percentile) in 14/15 patients. Twenty-three MMC patients had short stature (height SDS < -2), 11/23 patients had reduced arm span (SDS < -2), and 12/23 had normal arm span. Serum IGF-1 and IGFBP-3 levels were normal in 10/12 of short statured patients with normal arm span, but low (< 10th percentile) in those patients with reduced arm span (IGF-1: 8/11 patients, P < 0.05; IGFBP-3: 9/11 patients, P < 0.005). In 7/11 short statured MMC patients with reduced arm span and low serum IGF-1 and IGFBP-3 levels, growth hormone secretion was investigated. All had a disturbed growth hormone secretion (GHD: n = 4; neurosecretory dysfunction: n = 3). Arm span, serum IGF-1 and IGFBP-3 levels are estimated to be appropriate screening parameters for GHD in patients with MMC. Initiating growth hormone therapy should be considered not only according to endocrine findings but also with respect to neurological and orthopaedic anomalies.

A Randomized, Double-Blind, Placebo-controlled Study of Growth Hormone in the Treatment of Fibromyalgia

PURPOSE: The cause of fibromyalgia (FM) is not known. Low levels of insulin-like growth factor 1 (IGF-1), a surrogate marker for low growth hormone (GH) secretion, occur in about one third of patients who have many clinical features of growth hormone deficiency, such as diminished energy, dysphoria, impaired cognition, poor general health, reduced exercise capacity, muscle weakness, and cold intolerance. To determine whether suboptimal growth hormone production could be relevant to the symptomatology of fibromyalgia, we assessed the clinical effects of treatment with growth hormone. METHODS: Fifty women with fibromyalgia and low IGF-1 levels were enrolled in a randomized, placebo-controlled, double-blind study of 9 months’ duration. They gave themselves daily subcutaneous injections of growth hormone or placebo. Two outcome measures—the Fibromyalgia Impact Questionnaire and the number of fibromyalgia tender points—were evaluated at 3-monthly intervals by a blinded investigator. An unblinded investigator reviewed the IGF-1 results monthly and adjusted the growth hormone dose to achieve an IGF-1 level of about 250 ng/mL. RESULTS: Daily growth hormone injections resulted in a prompt and sustained increase in IGF-1 levels. The treatment (n = 22) group showed a significant improvement over the placebo group (n = 23) at 9 months in both the Fibromyalgia Impact Questionnaire score ( P <0.04) and the tender point score ( P <0.03). Fifteen subjects in the growth hormone group and 6 subjects in the control group experienced a global improvement ( P <0.02). There was a delayed response to therapy, with most patients experiencing improvement at the 6-month mark. After discontinuing growth hormone, patients experienced a worsening of symptoms. Carpal tunnel symptoms were more prevalent in the growth hormone group (7 versus 1); no other adverse events were more common in this group. CONCLUSIONS: Women with fibromyalgia and low IGF-1 levels experienced an improvement in their overall symptomatology and number of tender points after 9 months of daily growth hormone therapy. This suggests that a secondary growth hormone deficiency may be responsible for some of the symptoms of fibromyalgia.

Determination of insulin-like growth factor 1 in dogs using a commercially available immunoradiometric assay1).

The objective of the present study was to characterize a commercially available immunoradiometric assay (IRMA) intended for the determination of human insulin-like growth factor 1 (IGF-1) when used to determine IGF-1 in canine plasma samples. The assay was evaluated by assessment of the precision, accuracy, and detection limit, and by comparing the IGF-1 values observed in healthy dogs and in dogs with acromegaly and hereditary pituitary dwarfism to values reported in the literature. Since extraction of IGF-1 from its binding proteins is essential for reliable test results, the efficiency of the extraction method used in the assay was also examined. The main conclusions can be summarized as follows: The commercially available IRMA method offers a precise determination of the IGF-1 concentration in canine plasma samples with IGF-1 values directly comparable to those obtained by others. The assay accuracy was confirmed for normal dogs by parallelity between IGF-1 concentrations and plasma dilutions, whereas plasma from acromegalic dogs could not fullful parallelity. The detection limit was below the IGF-1 concentrations observed in dogs with hereditary pituitary dwarfism. In plasma samples with low or normal IGF-1 levels, the assay's extraction efficiency was comparable to that found using other extraction methods. In samples with IGF-1 concentrations above usual physiological levels, the extraction efficiency decreased unexplainably. However, this decrease in extraction efficiency seems to be of only minor importance when the measurements are used in the diagnosis of canine acromegaly.

Prevalence of malaria and its relationship to anemia, blood glucose levels, and serum somatomedin c (IGF-1) levels in the Solomon Islands

As part of establishing effective methods for malaria control, the malaria-associated nutritional status was surveyed on Guadalcanal Island in the Solomon Islands in 1993. A total of 506 residents participated in this study. The slide positive rate for malaria was 54% (275/506) in all ages, with a high of 79% for children aged 4–6 years. Plasmodium falciparum was the most common species (52%), followed by P. vivax (29%). Splenomegaly in children from infants to age 15 was detected at the rate of 30% (104/343) by the palpation method. Body mass index was lower in Solomon Islanders than for the Japanese population up to 15 years old in both genders. Mean values for serum insulin-like growth factor-1 (IGF-1) were also lower in Solomon Islanders in children under 18 years old. The hemoglobin distribution curves were almost identical in the malaria-positive (P(+)) and -negative (P(−)) groups. The percentage of cases with less than 80 mg/dl of blood glucose and those with less than 50 ng/ml of IGF-1 were higher in the P(+) group than for the anti-malaria drug-untreated malaria-negative (P(−)D(−)) group. It is suggested that low blood glucose and low IGF-1 levels may have some relationship with the malaria infection.

Alveolar type II cell-fibroblast interactions, synthesis and secretion of surfactant and type I collagen.

During alveolar development and alveolar repair close contacts are established between fibroblasts and lung epithelial cells through gaps in the basement membrane. Using co-culture systems we have investigated whether these close contacts influence synthesis and secretion of the principal surfactant apoprotein (SP-A) by cultured rat lung alveolar type II cells and the synthesis and secretion of type I collagen by fibroblasts. The alveolar type II cells remained cuboidal and grew in colonies on fibroblast feeder layers and on Matrigel-coated cell culture inserts but were progressively more flattened on fixed fibroblast monolayers and plastic. Alveolar type II cells cultured on plastic released almost all their SP-A into the medium by 4 days. Alveolar type II cells cultured on viable fibroblasts or Matrigel-coated inserts above fibroblasts accumulated SP-A in the medium at a constant rate for the first 4 days, and probably recycle SP-A by endocytosis. The amount of mRNA for SP-A was very low after 4 days of culture of alveolar type II cells on plastic, Matrigel-coated inserts or fixed fibroblast monolayers: relatively, the amount of mRNA for SP-A was increased 4-fold after culture of alveolar type II cells on viable fibroblasts. Co-culture of alveolar type II cells with confluent human dermal fibroblasts stimulated by 2- to 3-fold the secretion of collagen type I into the culture medium, even after the fibroblasts' growth had been arrested with mitomycin C. Collagen secretion, by fibroblasts, also was stimulated 2-fold by conditioned medium from alveolar type II cells cultured on Matrigel. The amount of mRNA for type I collagen increased only modestly when fibroblasts were cultured in this conditioned medium. This stimulation of type I collagen secretion diminished as the conditioned medium was diluted out, but at high dilutions further stimulation occurred, indicating that a factor that inhibited collagen secretion also was being diluted out. The conditioned medium contained low levels of IGF-1 and the stimulation of type I collagen secretion was abolished when the conditioned medium was pre-incubated with antibodies to insulin-like growth factor 1 (IGF-1). There are important reciprocal interactions between alveolar type II cells and fibroblasts in co-culture. Direct contacts between alveolar type II cells and fibroblasts appear to have a trophic effect on cultured alveolar type II cells, increasing the levels of mRNA for SP-A. Rat lung alveolar type II cells appear to release a factor (possibly IGF-1) that stimulates type I collagen secretion by fibroblasts.

Circulating Markers and Growth Factors as Prognosticators in Men with Advanced Tongue Cancer

A retrospective study was performed on 52 advanced tongue cancer patients (stages III + IV) in order to assess the prognostic value of circulating prolactin, tissue polypeptide-specific antigen (TPS), insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF). These markers were correlated with short-term prognosis (2 years). The advanced tongue cancer patients had significantly elevated levels of prolactin (p < 0.02), TPS (p < 0.05) and EGF (p < 0.01) and low levels of IGF-1 when compared to controls. The patients were grouped according to the commonly used cut-off levels of these markers. A significant difference in survival was observed only between two subgroups of prolactin (< 15.0 and > 15.0 ng/ml; p < 0.001). Hence, prolactin may provide an independent predictor of short-term prognosis in patients with advanced tongue cancer.

Evaluation of treated acromegalic patients with normal growth hormone levels during oral glucose load.

Twenty-one treated acromegalics with plasma GH levels less than or equal to 5 ng/ml were evaluated during an oral glucose tolerance test (OGTT). Serum insulin-like growth factor (IGF) levels, measured by a competitive binding assay, were high in 10, normal in 8 and low in 3 patients. Urinary calcium excretion (Ca U), measured over 24 h, was elevated in 9 of the 10 patients whose IGF levels were high, whereas only 1 of the patients with normal or low IGF levels was hypercalciuric. A paradoxical rise in GH following TRH injection was observed in 5 of the 10 patients whose IGF levels were high, whereas all patients with normal or low IGF levels showed no GH response to TRH. GH levels greater than or equal to 10 ng/ml occurred during ornithine (ORN) administration in 6 of the 18 patients with normal or high IGF levels. The remaining 12 patients with no GH rise during ORN included 2 cases in which IGF levels were high and GH rose following TRH, and 2 cases in which IGF levels were normal and GH levels were greater than or equal to 10 ng/ml during insulin-induced hypoglycaemia (IIH), thus excluding a GH deficiency. These results show that acromegaly is not cured in certain treated patients with normal GH levels during OGTT. It seems that IGF and Ca U determinations are valuable indices of activity, in contrast to GH response to ORN. The GH response to TRH is also relatively useful.