Analysis of IGF(CA)19 and IGFBP3-202A/C gene polymorphisms in patients with acromegaly: association with clinical presentation and response to treatments (original) (raw)
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Metabolism, 1997
To evaluate the utility of measuring the serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) level and the IGF-I/IGFBP-3 ratio in the management of acromegalic patients, we comparatively studied the basal concentration of the aforementioned parameters with determination of plasma IGF-I levels and an index of clinical activity of acromegaly in 16 newly diagnosed acromegalic patients (aged 34 to 64 years) before and after hypophysectomy. After adenomectomy, 10 patients remained with "active" disease and six were "cured." Twenty-nine healthy sex-and age-matched volunteers were also studied. Comparison of individual values between untreated acromegalic patients and control subjects showed that none of the patients had overlapping values for IGF-I, whereas five of 16 and three of 16 patients had overlapping values for serum IGFBP-3 and IGF-I/IGFBP-3 ratio, respectively. When we compared the study parameters between the patients who remained with active disease after adenomectomy and the controls, two of 10 had overlapping values for IGF-I, but six of 10 and five of 10 had overlapping values for serum IGFBP-3 and IGF-I/IGFBP-3 ratio, respectively. Moreover, comparison of these parameters between cured and active patients after hypophysectomy showed that none had overlapping values for IGF-I, whereas three of six and one of six had overlapping values for serum IGFBP-3 and IGF-I/IGFBP-3 ratio, respectively. All biochemical variables studied showed significant relationships with an index of clinical activity of disease. In conclusion, our results seem to indicate that among determinations of plasma IGF-I, serum IGFBP-3, and the ratio IGF-I/IGFBP-3 in the evaluation of acromegalic patients, measurement of the plasma IGF-I level has the most discriminative value in the management of these patients.
D3 GH receptor polymorphism is not associated with IGF1 levels in untreated acromegaly
European Journal of Endocrinology, 2009
ContextA discrepancy between serum GH and IGF1 concentrations is frequent in patients with acromegaly. Here, we examined whether the exon 3-deleted (d3) GH receptor (GHR) variant, which has been linked to increased responsiveness to GH treatment in short children, influences the GH/IGF1 relationship in patients with acromegaly.ObjectiveTo study the possible influence of the GHR genotype on the GH/IGF1 relationship in untreated acromegalic patients.DesignGHR genotype analysis with retrospective clinical and biochemical data collection performed in a single third-reference medical center.Patients and methodsClinical data were obtained from the medical records of 105 acromegalic patients who had GH and IGF1 assays in the same laboratory and who were genotyped for the full-length (fl) or d3-GHR alleles.ResultsThe distribution of GHR genotypes was 51% fl/fl, 30% fl/d3, and 19% d3/d3. Patients with d3/d3 genotype were younger than the patients in the other two groups (P<0.05). Baseline...
Growth Hormone & IGF Research, 2001
The aim was to evaluate, markers of disease activity in acromegaly in relation to perceived disease activity. Thirty-seven consecutively treated, acromegalic patients, classified by clinical symptoms as inactive (n = 16), slightly active (n = 10) and active (n = 11), entered the study. When evaluating the inactive and the active groups, we found that positive and negative predictive values (PV pos , PV neg ) for clinical disease activity of total and free insulin-like growth factor-I (IGF-I) were 0.59, 0.90 and 1.00, 0.82 respectively. Acid-labile subunit (ALS) showed diagnostic merit similar to insulin-like growth factor binding protein-3 (IGFBP-3) with PV pos of 0.69 and 0.71 and PV neg of 0.91 and 0.92 respectively. We conclude that free IGF-I is more closely related than total IGF-I to perceived disease activity and is as such useful when evaluating previously treated acromegaly for disease activity. Total IGF-I, IGFBP-3 and ALS possess a higher PV neg for the clinical disease activity. None of the parameters can at present be claimed to be superior to the others and thus all the measured parameters are recommended to be part of the evaluation of acromegalic patients.
Filter paper collection of plasma for IGF-I test in patients with acromegaly
Annals of clinical and laboratory science, 2002
The concentration of insulin-like growth factor I (IGF-I) was determined in paired specimens of liquid plasma and of plasma that had been applied to a filter paper disk, dried, and eluted; the measurements were performed by an immunochemiluminometric assay (ICMA). The 129 paired assays showed good correlation: y = 1.04x + 4.99; R2 = 0.934, where y is the result on dried samples and x is that on liquid samples. In 18 patients with acromegaly who lived on an island off the West Pacific Rim, plasma specimens were collected, applied to filter paper, dried, and mailed to a laboratory in the Upper Midwest of the United States. IGF-I was eluted from the filter paper disks and measured by ICMA. IGF-I concentrations ranged from 101 to 254 ng/ml in 11 patients with newly diagnosed but untreated acromegaly, 138 to 503 ng/ml in 4 patients with recurrent acromegaly, and 27 to 88 ng/ml in 3 patients with surgically cured acromegaly. These data demonstrate that plasma specimens of patients with ac...
Biochemical markers of acromegaly: GH vs. IGF-I
Growth Hormone & IGF Research, 2004
The development of sensitive and specific growth hormone (GH) and insulin-like growth factor I (IGF-I) assays opened a new page in the diagnosis and surveillance of acromegaly. Currently, it is possible to make an accurate pre-operative diagnosis even in patients with virtually no typical clinical signs of the disease and to monitor the efficacy of therapeutic intervention with a high degree of precision. This review briefly discusses the performance parameters of GH and IGF-I as diagnostic and surveillance tools in patients with acromegaly. In brief, whereas GH-based parameters may offer the advantage of disclosing dysregulation of GH secretion, a single plasma IGF-I measurement provides the most comprehensive assessment of both the overall GH output as well as the pattern of GH presentation to the peripheral tissues. Judicious use of both biochemical markers allows accurate and early diagnosis, precise assessment of the efficacy of therapeutic interventions, permits adjustment in the dose of medication and allows for unequivocal demonstration of a final cure.
The Journal of the Association of Physicians of India, 2014
Diagnosis of acromegaly in presence of uncontrolled diabetes mellitus is not well validated. The study included 10 patients of active acromegaly with uncontrolled blood glucose, 10 patients of type 2 diabetes mellitus with poor glycemic control and 10 healthy subjects. The growth hormone level following oral glucose tolerance test and insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) were done at baseline in all the 3 groups and it was repeated after short term glycemic control in type 2 diabetics and acromegalics with diabetics In the acromegalic group the basal GH value was very high (36.5 + 1.6) ng/ml and it was non-suppressible (32.5 + 1.43) ng/ml after OGTT. The mean IGF-1 and IGFBP-3 values were also high at baseline (208.38 + 38.51) ng/ml, and 7322 + 370 ng/ml respectively. In the non-acromegalic diabetic patients, the basal growth hormone value was marginally elevated (2.3 + 0.02) ng/ml. However, it was suppressible to 0.2 + 0.04...
Clinical Endocrinology, 2008
Background IGF-I is a useful tool in GH disorders diagnosis, however, the use of commercially available kits needs to be validated. Objective To validate the use of serum IGF-I concentrations measured by four immunoassays in the diagnosis of adult GH deficiency and acromegaly. Design Cross-sectional study. Patients Fifty GH-deficient (GHD) patients, 41 acromegaly patients and 405 controls. Measurements Serum IGF-I concentrations were measured by four commercial immunoassays: (1) RIA-NICHOLS; (2) ICMA-IMMULITE; (3) IRMA-IMMUNOTECH; and (4) non-extraction-IRMA-DSL. Reference values were established from the control population in six age groups. Individual results were transformed to standard deviation score (SD score) from the age-related reference population and reference data provided by each assay manufacturer. Diagnostic sensitivity for GH deficiency was calculated. Results IGF-I measured by the four assays differed significantly. In controls, assay 2 yielded the lowest results, followed by assays 1, 3 and 4 ( P < 0·0001 for all comparisons). IGF-I declined with age, but no sex-related differences were observed. When IGF-I was standardized with respect to reference data obtained from the manufacturers, it showed better sensitivity in assays 1 and 2, than with our controls (65% vs. 77·5% and 58% vs. 70%, respectively) for GHD diagnosis. With assays 3 and 4, higher sensitivity was obtained when standardized with our controls (62% vs. 52% and 56% vs. 36%, respectively). In acromegaly, IGF-I was > 2 SD score with all assays.
Clinical Endocrinology, 1991
Acromegaly is characterized by a hypersecretion of GH, which in turn results in an excess of IGF-I, an important mediator of its actions. IGF-I itself is intimately related to insulin both in structure and function. IGF-I circulates associated with specific binding proteins which appear to have important effects on its actlvity. We have examined the interrelations between GH, prolactin, Insulin, IGF-I and one of the binding proteins, IGFBP-1, in 62 patients with acromegaly of varying activity. Serum IGF-I levels were closely related to the logarithm of mean GH levels (f = 0.76; n = 62; P < 0.001) but multiple regression analysis suggested that, after accounting for the variation due to GH, Insulin accounted for some of the additional variation of IGF-I. IGF-l concentrations were Independent of prolactin. Fasting insulin levels were high and unrelated to mean GH levels but correlated with those of IGF-I (r=0.542; n = 57; P < 0.001). This correlation coefficient was further improved by also accounting for variations in IGFBP-1 (f = 0.684; n = SI; P < 0.001). Even in subjects whose acromegaly was well controlled or cured, as indicated by GH levels of < 1 mull or IGF-i levels of < 2 Ulml, fasting insulin levels remained significantly elevated in some individuals. The reason for this persistent abnormality Is not clear. Fasting IGFBP-1 levels were low and unrelated to mean GH but were lnveraely related to fasting insulin levels (r =-0.593; n = 57; P < 0.001). We propose that a cascade of evenis occurs in acromegaly. GH hypersecretion causes chronic elevation of IGF-i levels which In turn could lead to increased pancreatic Insulin production. This raised Insulin could then have additional effects, raising IGF-i levels further and lowering IGFBP-1; the latter could then result in accentuated IGF-activity.