Insulin-like Growth factor-I Standard Deviation Score Research Articles

IGF-I measurements in the diagnosis of adult growth hormone deficiency

Although serum insulin-like growth factor I (IGF-I) concentrations have utility as a screening test for growth hormone (GH) deficiency in children and young adults, they are less accurate for screening in adults over 40 years of age. There are two main limitations in the clinical use of IGF-I levels as a marker of GH secretion. First, IGF-I synthesis is not only regulated by GH but also by nutrient supply and by other hormones; second, low IGF-I levels in the presence of normal or increased GH secretion may reflect a peripheral resistance to GH action. Although serum IGF-I cannot be used as a stand-alone test for the diagnosis of adult GH deficiency, very low IGF-I levels in the context of documented hypothalamic or pituitary disease may be helpful in identifying patients with a high probability of GH deficiency. In the presence of two or more additional pituitary hormone deficiencies, an IGF-I level <84 microg/l (assayed by Esoterix Endocrinology, Inc. Calabasas Hills, CA, USA) indicates a 99% probability of GH deficiency. As this cut-off value has not been validated for other IGF-I assays, an IGF-I standard deviation score (SDS) of <-3 may be considered in adults over age 28; an even lower IGF-I SDS is needed for diagnosis in younger adults. In clinical practice, other causes of low serum IGF-I such as malnutrition, diabetes, hypothyroidism, liver disease, etc., should be excluded before applying these diagnostic criteria.

Opposite associations of age-dependent insulin-like growth factor-I standard deviation scores with nutritional state in normal weight and obese subjects

Insulin-like growth factor-I (IGF-I) has been suggested to be a prognostic marker for the development of cancer and, more recently, cardiovascular disease. These diseases are closely linked to obesity, but reports of the association of IGF-I with measures of obesity are divergent. In this study, we assessed the association of age-dependent IGF-I standard deviation scores with body mass index (BMI) and intra-abdominal fat accumulation in a large population. A cross-sectional, epidemiological study. IGF-I levels were measured with an automated chemiluminescence assay system in 6282 patients from the DETECT study. Weight, height, and waist and hip circumference were measured according to the written instructions. Standard deviation scores (SDS), correcting IGF-I levels for age, were calculated and were used for further analyses. An inverse U-shaped association of IGF-I SDS with BMI, waist circumference, and the ratio of waist circumference to height was found. BMI was positively associated with IGF-I SDS in normal weight subjects, and negatively associated in obese subjects. The highest mean IGF-I SDS were seen at a BMI of 22.5-25 kg/m2 in men (+0.08), and at a BMI of 27.5-30 kg/m2 in women (+0.21). Multiple linear regression models, controlling for different diseases, medications and risk conditions, revealed a significant negative association of BMI with IGF-I SDS. BMI contributed most to the additional explained variance to the other health conditions. IGF-I standard deviation scores are decreased in obesity and underweight subjects. These interactions should be taken into account when analyzing the association of IGF-I with diseases and risk conditions.

Efficacy of needle‐free administration of recombinant human growth hormone in adults with growth hormone deficiency

Needle-free administration of recombinant human growth hormone (rhGH) is effective in the treatment of growth hormone deficiency (GHD) in children, but has not been studied in adult patients. Therefore, we evaluated the efficacy of needle-free administration of rhGH in adults with GHD. Insulin-like growth factor-I (IGF-I) concentrations were compared in newly diagnosed patients with GHD (n = 21) and in patients previously treated by subcutaneous injection of rhGH (switchers, n = 34), at baseline, 12 months and 24 months. In the new patients, IGF-I standard deviation scores (SDS) increased from - 1.82 +/- 0.46 to + 0.75 +/- 0.33 at 12 months and to + 0.65 +/- 0.41 at 24 months (P < or = 0.001 vs. baseline). In switchers, IGF-I SDS remained unchanged with values of + 0.98 +/- 0.32 at baseline, + 0.87 +/- 0.23 at 12 months and + 0.73 +/- 0.29 at 24 months (P = 0.696 vs. baseline). In new patients, the rhGH dose was 0.46 +/- 0.03 mg day(-1) at 12 months and 0.47 +/- 0.03 mg day(-1) at 24 months. In switchers, the rhGH dose was 0.53 +/- 0.04 mg day(-1) at baseline (s.c. injection), 0.52 +/- 0.03 mg day(-1) at 12 months and 0.48 +/- 0.03 mg day(-1) at 24 months (NS between the different time points). There was no difference in the dose of rhGH at 12 and 24 months between the two groups. Side-effects were generally minor and consisted of local tissue reactions. Administration of rhGH by needle-free, transdermal injection is effective in maintaining IGF-I concentrations in the normal range for age in adults with GHD, and is as effective as traditional subcutaneous injection of rhGH.

Endocrine function in thai children infected with human immunodeficiency virus.

Most children infected by HIV show manifestations which mimic the clinical features of endocrine dysfunction, such as failure to thrive and hyperpigmentation. Our cross-sectional study was designed to assess the endocrine function of Thai children infected with HIV and to determine any relationship between disease severity, height and endocrine function. Thirty-six prepubertal children infected by HIV, 12 boys and 24 girls, aged 4-12 years (mean +/- SD 7 +/- 2 years), were tested for thyroid function (serum T4, T3, TSH and free T4), morning serum cortisol level, serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3). Disease severity was assessed using CD4+ T-lymphocyte percentage. Ten (28%) patients showed abnormal thyroid function. Five patients had euthyroid sick syndrome. Thyroid function tests indicated another five patients had a condition compatible with compensated hypothyroidism. Most patients had normal morning serum cortisol levels. Two-thirds and one-third of the patients showed low IGF-I and IGFBP-3 standard deviation scores (SDS), respectively. Twenty-six (72%) patients had CD4+ T-lymphocyte <15%, thus were classified as severely immune suppressed. A weak linear relationship was indicated between disease severity and endocrine function (r = -0.03 to 0.41). Statistical significance was found between CD4+ percentage and IGF-I SDS, IGFBP-3 SDS, serum T3 and free T4 (p-value = 0.03, 0.02, 0.02 and 0.01, respectively. Nearly half (44%) the patients were below the third percentile for height of Thai children. There was also a weak correlation between height SDS and endocrine function (r = -0.03 to 0.41). Statistical significance was observed between height SDS and IGF-I SDS, serum T3 and TSH (p-value = 0.02 and 0.01, respectively). We conclude that HIV-infected children with demonstrated growth failure and greater disease severity tend to have abnormal endocrine function, particularly disordered IGF-I levels.

The hypothalamus–pituitary function after pituitary stereotactic radiosurgery: evaluation of growth hormone deficiency

Radiation therapy to the pituitary gland means a considerable risk of developing hypopituitarism. The aim of the study was to investigate the growth hormone releasing hormone (GHRH)-growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis after treatment with stereotactic radiosurgery to the pituitary because of Cushing's disease. Inpatient ward in university clinic. Eleven adult patients (eight women, three men), 20-65 years of age were studied 2.5-11.3 years after stereotactic radiosurgery (isocentre dose 50-100 Gy lesion-1) and compared with healthy controls. Spontaneous GH secretion was evaluated as 12-h night GH profiles. Stimulated GH responses were evaluated in seven of 11 patients using arginine-insulin and GHRH tests. Serum IGF-I levels were measured in fasting serum morning samples. All patients except one displayed blunted nocturnal GH profiles. After arginine-insulin challenge, six of seven patients displayed low GH release. GH response was higher after GHRH injection compared with both the response to arginine-insulin and to the maximum GH levels in the nocturnal profiles. Seven patients had an IGF-I standard deviation score (SDS) within the normal range for age. Serum IGF-I values were correlated to mean GH values in the 12-h night profile (r = 0.67, P < 0.05) and both these variables were negatively correlated to time elapse since last radiation treatment (r = -0.64, P < 0.05 and r = -0.78, P < 0.05, respectively). Our patients with Cushing's disease evaluated several years after stereotactic radiosurgery as the primary and only treatment, demonstrated severely blunted spontaneous GH secretion and GH response to arginine-insulin. A disturbed regulation at the hypothalamic level was suggested as mechanism for this. Noteworthy is that serum IGF-I values correlated to the mean values of the 12-h GH profile.

Low Serum Concentrations of Insulin-like Growth Factor-I in Children with Active Crohn Disease: Effect of Enteral Nutritional Support and Glutamine Supplementation

Background: Impaired growth is a frequent problem in childhood Crohn disease. Low serum concentrations of insulin-like growth factor-I (IGF-I), an important marker of nutritional status and linear growth, have been described in children with Crohn disease. This study tested the hypotheses that enteral nutritional support and glutamine supplementation would be associated with improvements in serum IGF-I levels in children with Crohn disease. Methods: In a double-blind randomized controlled study, 15 children with active Crohn disease (8 boys, 7 girls; mean age 11.3 years, range 6.8-15.7) were assigned to receive a 4-week course of either a standard low glutamine polymeric diet (4% of amino acid content) (Group S, n = 8) or an isocaloric, isonitrogenous, glutamine-enriched polymeric diet (42% of amino acid content) (Group G, n = 7). Serum IGF-I was measured by a radioimmunoassay method at 0 and 4 weeks and converted to standard deviation scores (SDS). Weight SDS, height SDS, weight-for-height, height-for-age, mid-arm circumference (MAC), serum albumin, platelet count, orosomucoid and the paediatric Crohn disease activity index (PCDAI) were also measured at 0 and 4 weeks. Results: IGF-I SDS were significantly depressed in all the children at the start of the study (below-2 SDS) and remained so after 4 weeks of enteral nutritional support. Within each group, there was no significant change in IGF-I SDS ( P = 0.306 for Group S and P = 0.903 for Group G). Nor was there any significant difference between the two groups when changes in IGF-I SDS over the 4-week period were compared ( P = 0.568), although the proportion of patients experiencing an increase in IGF-I levels was greater in Group S (7 of 8 (87%) versus 2 of 7 (28%); P = 0.040). Weight SDS ( P = 0.002), weight-for-height ( P = 0.001) and mid-arm circumference ( P = 0.001) increased significantly in Group S but the increases in Group G were not statistically significant. No significant correlation was found between changes in IGF-I SDS and changes in the following parameters: weight SDS ( r = 0.170; P = 0.545), height SDS ( r = -0.240; P = 0.389), weight-for-height ( r = 0.261; P = 0.348), PCDAI ( r = -0.156; P = 0.579) or orosomucoid ( r = 0.173; P = 0.537). There was a significant negative correlation between changes in PCDAI and changes in weight SDS ( r = -0.79; P < 0.001), and serum albumin ( r = -0.76; P = 0.001) and a positive correlation between changes in PCDAI and changes in platelet count ( r = 0.69; P = 0.004). Conclusions: Serum IGF-I SD scores were greatly diminished in children with active Crohn disease and showed no significant improvements after 4 weeks of nutritional support. Glutamine supplementation was not associated with any significant alterations in serum IGF-I.

Interleukin-6 Release by Cultured Peripheral Blood Mononuclear Cells Inversely Correlates with Height Velocity, Bone Age, Insulin-like Growth Factor-I, and Insulin-like Growth Factor Binding Protein-3 Serum Levels in Children with Perinatal HIV-1 Infection

Spontaneous and phytohemagglutinin (PHA)-stimulated interleukin (IL)-6 release by cultured peripheral blood mononuclear cells was related to height velocity, bone age, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) serum level standard deviation scores (SDS) of 32 children [aged 91 (median; range 13–151) months] with human immunodeficiency virus-type 1 (HIV-1) perinatal infection and severe disease. Spontaneous and PHA-stimulated IL-6 release inversely correlated with height velocity, bone age, IGF-I, and IGFBP-3 SDS. Ten children with height velocity SDS ≤ −2, compared to 22 children with height velocity SDS > −2, showed higher spontaneous and PHA-stimulated IL-6 release and lower IGF-I and IGFBP-3 SDS (irrespective of CD4-positive T-lymphocyte counts, viral load, liver disease, or nutrition status). IL-6 overproduction may be a mechanism of IGF-I and IGFBP-3 down-regulation and impaired linear growth in children with perinatal HIV-1 infection. Growth-promoting strategies, including targeted anticytokine treatments, could be devised for such children.

Failure of IGF-I and IGFBP-3 to diagnose growth hormone insufficiency.

Growth hormone insufficiency (GHI) is diagnosed conventionally by short stature and slow growth, and is confirmed by diminished peak GH response to a provocation test. Insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) have previously been considered individually To test the hypothesis that the combined analysis of IGF-I and IGFBP-3 could act as a surrogate marker for the diagnosis of GHI. Reference ranges for IGF-I and IGFBP-3 were calculated using 521 normal individuals. A retrospective analysis was performed on 318 children referred for investigation of short stature. No significant difference was found between either the IGF-I or IGFBP-3 standard deviation scores (SDSs) in children with and without GHI. If the requirement were for both tests to be positive (< -2 SDS) for a diagnosis of GHI, then 99% of children without GHI would be correctly identified; however, the sensitivity of the test was only 15%. Neither IGF-I nor IGFBP-3 alone is a marker for GHI. In addition, they cannot be used as an effective screening test in combination.

Insulin-like growth factor I, IGF binding protein 3, and IGFBP protease activity: relation to anthropometric indices in solid tumours or leukaemia.

To measure the serum concentrations of insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3), and the level of IGFBP-3 protease activity in 38 children presenting with malignancies, and to assess their relation with auxological parameters and nutritional status. Height, weight, skinfold thickness, and mid-upper arm circumference (MUAC) were recorded using standard techniques. IGF-I and IGFBP-3 were measured using specific radioimmunoassays. Serum IGFBPs were also visualised on western ligand blot. IGFBP-3 protease activity was assessed by the extent of fragmentation of recombinant [125I]-IGFBP-3, compared with that induced by pregnancy serum. Anthropometric and radioimmunoassay data were expressed as standard deviation scores (SDS). The median (range) IGF-I SDS was significantly reduced in all patients (-1.1 (-5.1 to 1.2)) and lower in children who were malnourished (-2.5 (-3.9 to 0.1)). IGFBP-3 SDS was within the normal range for 31 of 38 patients but IGFBP-3 protease activity was raised in all patients. Neither IGFBP-3 concentration nor protease activity was affected by nutritional status. IGF-I correlated with MUAC (r = 0.41) and subscapular skinfold thickness SDS (r = 0.38), but not with weight, height, weight for height, or triceps skinfold thickness. IGF-I is low in children with malignancies, and even lower in those who are malnourished. IGFBP-3 concentrations were normal in most patients but interpretation is complicated by the presence of raised IGFBP-3 protease activity, which could lead to overestimating concentrations of intact peptide. IGF-I appears to relate to arm anthropometry as an index of nutritional status but not height, weight, or weight for height, as would be expected in normal children.

National Cooperative Growth Study substudy VI: The clinical utility of growth-hormone–binding protein, insulin-like growth factor I, and insulin-like growth factor–binding protein 3 measurements

Objective: To assess the clinical utility of growth-hormone–binding protein (GHBP), along with growth hormone (GH), insulin-like growth factor I (IGF-I), and insulin-like growth factor–binding protein 3 (IGFBP-3), levels in the evaluation of short stature. Study design: Prospective substudy of the National Cooperative Growth Study, a multicenter observational study. Results: A total of 6447 assessable subjects undergoing workup for short stature were enrolled at 197 sites. At baseline the cause of short stature was undefined in 77% of subjects. Mean GHBP levels were lowest in subjects with renal disease and highest in those with Turner syndrome. No cases of complete GH insensitivity syndrome (Laron syndrome) were identified. Subjects with low GHBP levels were among those tested for GH receptor mutations. IGF-I standard deviation scores (SDS) and IGFBP-3 SDS were positively correlated; both increased during GH therapy. There was a weak positive correlation between log peak GH levels and both IGF-I SDS and IGFBP-3 SDS and a weak negative correlation between log peak GH levels and GHBP SDS. Mean changes in GHBP SDS in subjects treated with GH and untreated subjects were not significant. Change in height SDS in subjects treated with GH was negatively correlated with age and IGF-I level but not correlated with baseline GHBP SDS. Conclusion: GHBP levels are GH independent and not predictive of responses to GH therapy, although low GHBP levels may indicate GH receptor abnormalities and partial GH insensitivity. (J Pediatr 1997;131:S56-60)

Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion.

The relationship between 24-h GH secretion, insulin-like growth factor (IGF) I serum levels, IGF-binding protein 3 (IGFBP-3) levels and height was studied in 114 healthy children and adolescents (147 tests). A significant correlation was found between the spontaneous GH secretion expressed as the area under the curve above baseline (AUCb) or the calculated 24-h GH secretion rate (GHb) and IGF-I (n = 147, r = 0.65, or 0.78, respectively, P < 0.001) or IGFBP-3 levels (r = 0.48 or 0.62, P < 0.001). Correlations were also significant within the various subgroups [females (n = 51), males (n = 96), prepubertal children (n = 75), pubertal children (n = 72)]. The slopes of the regression lines of IGF-I levels vs. AUCb or GHb were clearly steeper in pubertal children than in prepubertal ones; this was not as evident with IGFBP-3. In prepubertal children, a significant correlation was found between height (compared to Swedish reference values) standard deviation scores (SDS) and IGF-I SDS (n = 75, r = 0.66, P < 0.001) or IGFBP-3 SDS (r = 0.61, P < 0.001). The reproducibility during repeated testing (19 individuals, 6 prepubertal) was best with IGFBP-3 as compared to AUCb, GHb, or IGF-I which showed considerable variability. The data suggest: 1) that IGF-I and IGFBP-3 serum levels reflect spontaneous GH secretion in healthy individuals; 2) IGF-I levels are more sensitive to GH regulation than IGFBP-3; 3) in puberty, there may be increased sensitivity of IGF-I regulation by GH as compared to the prepubertal stage; 4) short children have low IGF-I and IGFBP-3 levels, whereas tall children have high levels, a fact which is likely to contribute to the understanding of height variability in a healthy population; 5) the good reproducibility of IGFBP-3 on repeated testing makes it an interesting parameter for the evaluation of the GH-IGF-axis. IGFBP-3 measurements may substitute for GH profiles in many cases, when the goal is an estimation of the GH secretion rate.