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ABSTRACT: A method based on two serum biomarkers - insulin-like growth factor-I (IGF-I) and pro-collagen type III N-terminal propeptide (P-III-NP) - has been devised to detect growth hormone (GH) misuse. The aims of this study were to determine the stability of IGF-I and P-III-NP concentrations in serum stored at -20°C and to establish the effects of one freeze-thaw cycle. Blood was collected from 20 healthy volunteers. Serum aliquots were analyzed after storage for one day at 4°C and one day, one week, five weeks, and three months at -20°C. IGF-I and P-III-NP results were combined to calculate a GH-2000 discriminant function score for each volunteer. Inter-assay precision was determined by analysing one quality control sample at each time-point. A single freeze-thaw cycle, storage of serum at 4°C for one day and at -20°C for up to three months had no significant effect on IGF-I or P-III-NP concentration. Intra-sample variability for IGF-I was 6.8% (Immunotech assay) and 12.9% (DSL assay). Intra-sample variability for P-III-NP was 10.9% (Cisbio assay) and 13.7% (Orion assay). When IGF-I and P-III-NP results were combined, intra-sample variability of the GH-2000 score expressed as a standard deviation varied between 0.31 and 0.50 depending on the assay combination used. Variability in IGF-I and P--III-NP results of stored samples is largely determined by the characteristics of the assays. A single freeze-thaw cycle, storage of serum at 4°C for one day or at -20°C for up to 3 months does not result in a significant change in GH-2000 score. Copyright © 2012 John Wiley & Sons, Ltd.
Drug Testing and Analysis 04/2012; 4(6):455-9. · 2.54 Impact Factor
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ABSTRACT: The GH-2000 project developed a method for detecting GH misuse based on the measurement of insulin-like growth factor-I (IGF-I) and the amino-terminal pro-peptide of type III collagen (P-III-NP). The objective of this study was to develop decision limits for the GH-2000 score to detect GH misuse in elite athletes using two currently available commercial assays for each analyte.
Subjects: 404 male (mean age 23.9 yrs, range 12-37 yrs) and 94 female elite athletes (mean age 24.5 yrs, range 18-34 yrs) participated. Blood samples were collected according to World Anti-Doping Agency (WADA) guidelines at various sporting events including 238 samples collected as part of the UK Anti-Doping Testing Programme. Laboratory analysis: IGF-I was measured by Siemens Immulite IGF-I assay and Immunotech A15729 IGF-I IRMA. P-III-NP was measured by RIA-gnost P-III-P and the UniQ™ PIIINP RIA. Statistical analysis: The GH-2000 score decision limits were developed through the analysis of the elite athlete samples.
For males and females separately, the distributions of GH-2000 scores were consistent with Normal distributions. Using a specificity of 99.99% new decision limits were determined which included an allowance for uncertainty associated with calculations based on a finite sample size. One outlier was identified with results incompatible with normal physiology and tested positive with the current isoform GH test.
We have developed decision limits using currently available commercial assays to measure IGF-I and P-III-NP in elite athletes. This should allow the introduction of a test for GH misuse based on the measurement of these GH sensitive biomarkers.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 02/2012; 22(2):53-8. · 2.35 Impact Factor
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ABSTRACT: The GH-2000 team proposed a method based on IGF1 and type III pro-collagen (P-III-P) to detect exogenously administered GH. As previous studies involved predominantly white European athletes, it is important to assess whether the response of these markers to recombinant human GH (rhGH) differs with ethnicity.
To examine the response of serum IGF1 and P-III-P and GH-2000 score to rhGH in non-Caucasian amateur athletes.
Double-blind placebo-controlled rhGH administration study.
Wellcome Trust Clinical Research Facility, Southampton General Hospital.
The study included 31 male and 14 female amateur athletes of different ethnicities. Intervention The subjects were assigned to treatment with placebo or 0.1 IU/kg per day (low dose) or 0.2 IU/kg per day (high dose) rhGH for 28 days. Blood was collected weekly during treatment and on days 35, 42 and 84 during the washout period. Serum IGF1 and P-III-P were measured, and GH-2000 score was calculated.
IGF1, P-III-P and GH-2000 score rose in response to both low- and high-dose GH in both men and women. When compared with the Caucasian volunteers of the previous GH-2000 study, mean baseline and placebo-treated P-III-P and GH-2000 score were lower in GH-2004 men and women. Post-GH, however, peak IGF1 or P-III-P did not differ between studies but the peak GH-2000 score was lower in GH-2004 men. There was no difference between studies in the maximal change in IGF1, P-III-P and GH-2000 score in response to GH in either gender.
These data do not support a significant ethnic effect on the peak or maximal response to rhGH.
European Journal of Endocrinology 07/2010; 163(1):45-54. · 3.42 Impact Factor
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Nishan Guha,
Ioulietta Erotokritou-Mulligan,
Caroline Burford,
Gail Strobridge,
Joanna Brigg,
Tamsin Drake,
E Eryl Bassett,
David Cowan,
Christiaan Bartlett, Peter H Sönksen,
Richard I G Holt
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ABSTRACT: A method based on two GH-dependent markers, IGF-I and pro-collagen type III N-terminal peptide (P-III-P), has been devised to detect exogenously administered GH. Because previous studies on the detection of GH abuse involved predominantly adult athletes, the method must be validated in adolescent athletes.
The aim of the study was to examine serum IGF-I and P-III-P concentrations in elite adolescent athletes and to determine whether the method developed in adults is appropriate to detect GH abuse in this population.
We conducted a cross-sectional observational study at national sporting organization training events.
A total of 157 (85 males, 72 females) elite athletes between 12 and 20 yr of age participated in the study.
Serum IGF-I and P-III-P were each measured by two commercially available immunoassays. GH-2000 discriminant function scores were calculated.
Both IGF-I and P-III-P rose to a peak during adolescence, which was earlier in girls than in boys. All GH-2000 scores lay below the proposed cutoff limit of 3.7 (although some scores were close to this value), indicating that none of these athletes would be accused of GH doping if the GH-2000 discriminant formulae were used. The results between the two immunoassays for IGF-I and P-III-P were closely aligned.
The GH-2000 score rises in early adolescence, reaches a peak in athletes aged 13-16 yr, and then falls. We have found no evidence that the proposed GH-2000 score developed in adults would lead to an unacceptable rate of false-positive results in adolescent athletes, but caution may be required around the time of peak growth velocity.
The Journal of clinical endocrinology and metabolism 06/2010; 95(6):2969-76. · 6.50 Impact Factor
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Clinical Endocrinology 03/2010; · 3.17 Impact Factor
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ABSTRACT: It is widely believed that growth hormone (GH) is abused by athletes for its anabolic and lipolytic effects. Many of the physiological effects of GH are mediated by the production of insulin-like growth factor-I (IGF-I). Both GH and IGF-I appear on the World Anti-Doping Agency list of prohibited substances. Little is known, however, about the prevalence of abuse with exogenous IGF-I. IGF-I has effects on carbohydrate, lipid and protein metabolism and some of these actions could prove beneficial to competitive athletes. No studies have demonstrated a positive effect of IGF-I on physical performance in healthy individuals but this has not yet been studied in appropriately designed trials. Two pharmaceutical preparations of IGF-I have recently become available for the treatment of growth disorders in children. This availability is likely to increase the prevalence of IGF-I abuse. Combining IGF-I with its binding protein IGFBP-3 in one preparation has the potential to reduce the side-effect profile but the adverse effects of long term IGF-I abuse are currently unknown. Detection of abuse with IGF-I is a major challenge for anti-doping authorities. It is extremely difficult to distinguish the exogenous recombinant form of the hormone from endogenously-produced IGF-I. One approach currently being investigated is based on measuring markers of GH and IGF-I action. This has already proved successful in the fight against GH abuse and, it is hoped, will subsequently lead to a similar test for detection of IGF-I abuse.
Current Drug Abuse Reviews 09/2009; 2(3):263-72.
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ABSTRACT: Growth Hormone is abused by athletes for its lipolytic and anabolic properties. Its use is prohibited by the World Anti-Doping Agency. The GH-2000 project developed a methodology to detect its abuse using the concentrations of two GH-dependent biomarkers, IGF-I and type 3 procollagen (P-III-P). The sensitivity of this method may be improved by considering intra-individual variability.
The aim of this study was to examine the intra-individual variability of IGF-I, P-III-P and the GH-2000 score.
IGF-I, P-III-P and GH-2000 score were evaluated in four longitudinal studies involving 303 elite and 78 amateur athletes. Samples were collected over a period of up to 12 months from a total of 238 men and 143 women aged between 17 and 53 years (mean 24.2).
The four studies showed good agreement with no apparent difference in within-individual variation between amateur and elite athletes. The intra-individual variability for IGF-I ranged between 14-16% while the variability for P-III-P was 7-18%. No athlete tested positive for growth hormone during any of the studies. The overall mean intra-individual variability of the GH-2000 score was less than 0.6 units in all studies.
The high stability of marker levels suggests that concentrations are largely genetically determined. Adopting a test based on the concept of an athlete's 'passport' or 'profiling' would take advantage of this and most likely increase the sensitivity of the test. These data also provide strong evidence that a positive test result for GH abuse would not occur as a result of chance variability.
Clinical Endocrinology 08/2009; 72(4):520-6. · 3.17 Impact Factor
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ABSTRACT: The growth hormone (GH)/ insulin-like growth factor-I (IGF-I) axis exerts short-and long-term metabolic effects that are potentially important during exercise. Exercise is a potent stimulus to GH release and there is some evidence that the acute increase in GH is important in regulating substrate metabolism post-exercise. Regular exercise also increases 24-hour GH secretion rates, which potentially contributes to the physiologic changes induced by training. The effects of GH replacement in GH-deficient adults provide a useful model with which to study the effects of the more long-term effects of the GH/ IGF-I axis. There is convincing evidence that GH replacement increases exercise capacity. Measures of exercise performance including maximal oxygen uptake (VO2max) and ventilatory threshold (VeT) are impaired in GH deficiency and improved by GH replacement, probably through some combination of increased oxygen delivery to exercising muscle, increased fatty acid availability with glycogen sparing, increased muscle strength, improved body composition and improved thermoregulation. Administration of supraphysiologic doses of GH to athletes increases fatty acid availability and reduces oxidative protein loss particularly during exercise, and increases lean body mass. It is not known whether these effects translate to improved athletic performance, although recombinant human GH is known to be widely abused in sport. The model of acromegaly provides evidence that long-term GH excess does not result in improved performance but it is possible that a "window" exists in which the protein anabolic effects of supraphysiologic GH might be advantageous.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 07/2009; 19(4):308-19. · 2.35 Impact Factor
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ABSTRACT: The earliest records of doping in sport come from the Ancient Olympics games when athletes are reported to have taken figs to improve their performance. With the advent of modern pharmacology in the 19th century, many athletes began to experiment with cocktails of drugs to improve strength and overcome fatigue. As this practice was not illegal, there are good records of the lengths athletes would go to in order to win. Alongside the benefits, came the dangers and following several fatalities, a code to ban performance enhancing drugs was gradually developed. Growth hormone was first isolated from the human pituitary gland in the 1950s. Its anabolic effects were soon recognised and athletes had begun to abuse it by the early 1980s, at least a decade before it was used therapeutically by adult endocrinologists. A number of high profile athletes have admitted using growth hormone. Detection of its abuse has been challenging and the lack of an effective test has undoubtedly encouraged its abuse. Only now are methodologies being developed that should stem this tide.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 06/2009; 19(4):320-6. · 2.35 Impact Factor
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ABSTRACT: Growth hormone is abused by athletes for its anabolic and lipolytic properties. The detection of GH abuse is challenging because it is an endogenous hormone whose concentration varies widely in any one day. The GH-2000 project proposed a test based on the measurement of IGF-I and type III pro-collagen (P-III-P). When the results of the GH-2000 project were presented to an expert workshop, the method was supported but it was felt that several issues needed to be resolved before the method could be adopted. The first was a potential effect of ethnicity as most subjects in the GH-2000 were white Europeans and the second was a possible effect of injury as P-III-P is a marker of soft tissue turnover. The GH-2004 project was conceived to address these concerns. The GH-2004 project has shown that while there are minor differences in IGF-I and P-III-P between ethnicities, these are small and do not affect the performance of the test. Injury leads to a small rise in P-III-P but again this is not of sufficient magnitude to affect the performance of the test. The GH-2004 project has provided further support for the marker approach as a means of detecting GH abuse in athletes. As WADA have not developed their own immunoassays, however, further work is needed to validate newer commercial assays measuring IGF-I and P-III-P to establish reliable conversion factors to the original GH-2000 units to allow the published formulae to be used.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 06/2009; 19(4):346-51. · 2.35 Impact Factor
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ABSTRACT: As the tests for detecting growth hormone (GH) abuse develop further, it is likely that athletes will turn to doping with insulin-like growth factor-I (IGF-I). IGF-I mediates many of the anabolic actions of growth hormone. It stimulates muscle protein synthesis, promotes glycogen storage and enhances lipolysis, all of which make IGF-I attractive as a potential performance-enhancing agent. Pharmaceutical companies have developed commercial preparations of recombinant human IGF-I (rhIGF-I) for use in disorders of growth. The increased availability of rhIGF-I increases the opportunity for athletes to acquire supplies of the drug on the black market. The long-term effects of IGF-I administration are currently unknown but it is likely that these will be similar to the adverse effects of chronic GH abuse. The detection of IGF-I abuse is a challenge for anti-doping organisations. Research has commenced into the development of a test for IGF-I abuse based on the measurement of markers of GH action. Simultaneously, the effects of rhIGF-I on physical fitness, body composition and substrate utilisation in healthy volunteers are being investigated.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 06/2009; 19(4):408-11. · 2.35 Impact Factor
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Ioulietta Erotokritou-Mulligan,
E Eryl Bassett,
Christiaan Bartlett,
David Cowan,
Cathy McHugh,
Rick Seah,
Benjamin Curtis,
Victoria Wells,
Kate Harrison, Peter H Sönksen,
Richard I G Holt
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ABSTRACT: A method to detect exogenously administered growth hormone (GH) based on the measurement of two GH-dependent markers, IGF-I and type 3 procollagen (P-III-P) has been proposed. Skeletal or soft tissue injury may alter these markers. Elevations in either of these proteins after injury might lead to a false accusation of doping with GH.
The objective of the study was to assess the effect of musculoskeletal or soft tissue injury on IGF-I and P-III-P concentrations in amateur and elite athletes and assess the effect of injury on the proposed GH detection method.
This was a longitudinal observational study after sporting injury.
The study was conducted at Southampton General Hospital and British Olympic Medical Centre.
Subjects included elite and amateur athletes after an injury.
Interventions included measurement of IGF-I and P-III-P and application of the GH-2000 discriminant function score up to 84 d after an injury as well as classification of injury by type and severity.
IGF-I and P-III-P concentration and ability to detect GH abuse in athletes without the risk of false accusation because of an injury were measured.
There was no change in IGF-I concentration after an injury. By contrast, P-III-P concentrations rose by 41.1 +/- 16.6%, reaching a peak around 14 d after an injury. The rise in P-III-P varied according to injury type and severity. This rise had a trivial effect on the GH-2000 discriminant function score, and no subject reached the threshold needed for a doping offense.
Although there was a rise in P-III-P after injury, this was insufficient to invalidate the GH-2000 detection method based on IGF-I and P-III-P concentrations.
Journal of Clinical Endocrinology & Metabolism 08/2008; 93(7):2760-3. · 6.50 Impact Factor
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ABSTRACT: IGF-I and type III procollagen (P-III-P) have been proposed as markers to detect GH abuse. This study aims to determine whether the pre-analytical storage temperature or delayed centrifugation affect the measured IGF-I and P-III-P concentrations.
Observational study.
Wellcome Trust Clinical Research Facility, Southampton.
Nineteen healthy volunteers.
Blood was collected into bottles containing a clotting agent, lithium heparin or EDTA. One sample from each group was centrifuged and stored at -80 degrees C (control sample). The remaining samples from each group were stored as either serum or whole blood at 4 degrees C or room temperature for up to five days prior to storage at -80 degrees C.
IGF-I and P-III-P.
The storage temperature or timing of centrifugation did not appear to affect IGF-I concentration. In contrast, the measured P-III-P concentration rose by 6.5-7% per day in clotted and lithium heparin samples when stored as whole blood (p<0.006) or serum (6.2-6.5% per day) at room temperature (p<0.001). P-III-P did not change when the samples were stored at 4 degrees C. Although collection into EDTA inhibited the rise in P-III-P, the baseline measured values were significantly higher than in other media and spiking experiments demonstrated that EDTA exerted a significant matrix effect on the assay.
While the optimum collection method is immediate centrifugation and storage at -80 degrees C, it would seem acceptable to store serum or clotted blood samples at 4 degrees C, but not ambient temperature, for up to five days. It is incumbent on the anti-doping authorities to provide facilities to allow this.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 07/2008; 19(1):43-50. · 2.35 Impact Factor
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ABSTRACT: A method based on the two GH dependent markers, IGF-I and procollagen III peptide (P-III-P) has been proposed to detect exogenously administered GH. As previous studies involved predominantly white European elite athletes, it is necessary to validate the method in other ethnic groups.
To examine serum IGF-I and P-III-P in elite athletes of different ethnicities within 2 h of competing at national or international events.
Cross-sectional observational study.
National and International sporting events.
1085 elite athletes of different ethnicities.
Serum IGF-I and P-III-P were measured and GH-2000 discriminant function score was calculated. Effect of ethnicity was assessed.
In men, IGF-I was 21.7 +/- 2.6% lower in Afro-Caribbeans than white Europeans (P < 0.0001) but there were no differences between other ethnic groups. In women, IGF-I was 14.2 +/- 5.1% lower in Afro-Caribbeans (P = 0.005) and 15.6 +/- 7.0% higher in Orientals (P = 0.02) compared with white Europeans. P-III-P was 15.2 +/- 3.5%, 26.6 +/- 6.6% and 19.3 +/- 5.8% lower in Afro-Caribbean (P < 0.0001), Indo-Asian (P < 0.0001) and Oriental men (P = 0.001), respectively, compared with white European men. In women, P-III-P was 15.7 +/- 4.7% lower in Afro-Caribbeans compared to white Europeans (P =0.0009) but there were no differences between other ethnicities. Despite these differences, most observations were below the upper 99% prediction limits derived from white European athletes. All GH-2000 scores lay below the cut-off limit proposed for doping.
The GH-2000 detection method based on IGF-I and P-III-P would be valid in all ethnic groups.
Clinical Endocrinology 06/2008; 70(1):161-8. · 3.17 Impact Factor
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ABSTRACT: The syndrome of adult GH deficiency and the effects of GH replacement therapy provide a useful model with which to study the effects of the GH/IGF-I axis on exercise physiology. Measures of exercise performance including maximal oxygen uptake and ventilatory threshold are impaired in adult GH deficiency and improved by GH replacement, probably through some combination of increased oxygen delivery to exercising muscle, increased fatty acid availability with glycogen sparing, increased muscle strength, improved body composition, and improved thermoregulation. In normal subjects, in addition to the long-term effects of GH/IGF-I status, there is evidence that the acute GH response to exercise is important in regulating substrate metabolism after exercise. Administration of supraphysiological doses of GH to athletes increases fatty acid availability and reduces oxidative protein loss, particularly during exercise, and increases lean body mass. Despite a lack of evidence that these metabolic effects translate to improved performance, GH abuse by athletes is widespread. Tests to detect GH abuse have been developed based on measurement in serum of 1) indirect markers of GH action, and 2) the relative proportions of the two major naturally occurring isoforms (20 and 22kDa) of GH. There is evidence that exercise performance and strength are improved by administration of GH and testosterone in combination to elderly subjects. The potential benefits of GH in these situations must be weighed against potential adverse effects.
Endocrine Reviews 11/2007; 28(6):603-24. · 19.93 Impact Factor
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ABSTRACT: The detection of exogenously administered growth hormone (GH) poses a formidable challenge but a detection method based on the measurement of two GH-dependent markers, IGF-I and type 3 pro-collagen (P-III-P) has been proposed. The measurement of multiple markers in conjunction with discriminant functions can improve the sensitivity and specificity of detection compared with single marker analysis.
To provide further validation of the GH-dependent marker approach.
Analysis of discriminant function scores for GH detection on independent datasets.
Two independent (GH-2000 and Kreischa) double blind, placebo controlled, hGH administration studies.
Healthy active male volunteers.
GH-2000 proposed a discriminant function involving IGF-I and P-III- P while the Kreischa function involved IGF-I, P-III-P and IGFBP-3. After adjustment for assay differences the formulae were applied to the other dataset.
Ability to detect GH use in independent datasets using a predefined specificity of approximately 1 in 10000.
The GH-2000 formula was able to detect 90% of those receiving GH in the Kreischa study at one or more time points during the study period. This sensitivity was similar to that obtained on the original GH-2000 dataset. The Kreischa formula correctly identified 41% of individuals receiving GH in the GH-2000 study.
The study provides further validation that the test proposed by GH-2000 based on IGF-I and P-III-P concentrations can be used to detect subjects receiving exogenous GH.
Growth Hormone & IGF Research 11/2007; 17(5):416-23. · 2.16 Impact Factor
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ABSTRACT: The objectives were (1) to report the preliminary development of the Hormone Deficiency-dependent Quality of Life (HDQoL) questionnaire, a new individualized questionnaire in which respondents rate personally applicable domains for importance and impact of hormonal deficiency and its treatment; (2) to evaluate the HDQoL's psychometric properties for adults with hypopituitarism including growth hormone deficiency (GHD).
Internal consistency reliability, aspects of validity, and sensitivity to change of the HDQoL were investigated in: (1) a cross-sectional survey of 157 adults with treated or untreated GHD; (2) a randomized, placebo-controlled study of 3 months' growth hormone (GH) withdrawal from 12 of 21 GH-treated adults.
Thirteen of the original 18 HDQoL domains were relevant and important for GH-deficient adults. The shorter 13-item HDQoL had excellent internal reliability (Cronbach's alpha coefficient = 0.914, n = 109), and was sensitive to sex differences (cross-sectional study): women perceived worse present QoL than men [t(149.8) = 2.33, P = 0.021]. The HDQoL was sensitive to change (GH-withdrawal study) with a significant between-group difference in change in domain scores for things I can do physically[t(16) = 2.47, P = 0.025, 2-tailed], patients withdrawn from GH reporting greater negative impact of hormone deficiency on this domain at end-point. Qualitative work resulted in the addition of seven new HDQoL domains, including energy and bodily pain.
The HDQoL, although at an early stage of development, proved useful in identifying expected changes following GH withdrawal. The extended 20-item version is recommended for further evaluation in assessing the impact of hypopituitarism on QoL.
Journal of Evaluation in Clinical Practice 11/2006; 12(5):501-14. · 1.23 Impact Factor
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ABSTRACT: Ambient temperature alters exercise induced GH secretion. It is unknown whether temperature affects GH secretion at exercise intensities above the anaerobic threshold when other factors may override the relationship seen at lower intensities.
Cross-over study of ambient temperature on exercise induced GH in swimmers and rowers.
St Thomas Hospital, London.
Ten healthy men (age 21.7+/-0.8 yrs). Five swimmers and five rowers.
Forty-minute exercise test at 105% of anaerobic threshold at room temperature (RT) and at 4 degrees C.
Cutaneous and core body temperature. Serum GH concentration.
Cutaneous body temperature increased during exercise at RT but decreased in the cold. Although core temperature rose in both settings, the rise was greater at RT (p=0.021). GH increased at both temperatures but the onset was delayed by the cold. Peak GH tended to be higher at RT (17.4+/-3.6 microg/L vs. 9.5+/-1.5 microg/L, p=0.07). Total GH secretion was greater at RT (353.3+/-99.1 microg min/L) than 4 degrees C (128.3+/-21.0 microg min/L), p=0.038. Change in core temperature correlated with log peak GH (r=0.66, p=0.039) and log incremental GH (r=0.67, p=0.032) when exercising at 4 degrees C. There was no difference between swimmers and rowers.
Exercise at 4 degrees C reduces GH secretion during exercise at intensities above the anaerobic threshold. A change in core body temperature may be one mechanism by which exercise induces GH secretion. The difference in GH between swimmers and rowers during their respective events relates to the conditions under which they compete.
Growth Hormone & IGF Research 05/2006; 16(2):125-31. · 2.16 Impact Factor
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ABSTRACT: Epidemiological studies suggest that hypopituitary patients have an increased risk for cardiovascular mortality. The dyslipidaemia associated with this condition is often characterised by an increase in total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol (LDL-C) and may contribute to these findings. The underlying mechanisms are not fully elucidated.
LDL apolipoprotein B (apoB) production rate and metabolic clearance rate were measured in seven patients with hypopituitarism (including GH deficiency) under stable conventional replacement therapy (three males and four females; age 40-16.1 years; body mass index 29.0-6.1 kg/m(2) (means +/- s.d.)) and seven age-, gender- and body mass index-matched control subjects with an infusion of 1-(13)C-leucine. Fasting lipid profile and lipid composition of LDL were also measured.
Fasting TC, triglycerides (TG), high-density lipoprotein-C, LDL-C and free fatty acid concentrations were not different between hypopituitary patients and control subjects. LDL-TG (P < 0.006) and LDL-TG/LDL apoB ratio (P < 0.02) were significantly increased in hypopituitary patients. LDL apoB pool size was not statistically different between patients and control subjects. In the hypopituitary patients, LDL apoB metabolic clearance rate (P < 0.05) and LDL apoB production rate (P < 0.02) were lower than in the control subjects.
The present results suggest that LDL apoB turnover and LDL composition is altered in hypopituitary patients. Whether these findings explain the increased risk for cardiovascular disease in hypopituitary patients remains to be established.
European Journal of Endocrinology 04/2006; 154(3):459-66. · 3.42 Impact Factor
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ABSTRACT: Psychometric properties of two measures of psychological well-being were evaluated for adults with growth hormone deficiency (GHD): the General Well-being Index, (GWBI)--British version of the Psychological General Well-being Index, and the 12-item Well-being Questionnaire (W-BQ12).
Reliability, structure and other aspects of validity were investigated in a cross-sectional study of 157 adults with treated or untreated GHD, and sensitivity to change in a randomised placebo-controlled study of three months' growth hormone (GH) withdrawal from 12 of 21 GH-treated adults.
Very high completion rates were evidence that both questionnaires were acceptable to respondents. Factor analyses did not indicate the existence of useful GWBI subscales, but confirmed the validity of calculating a GWBI Total score. However, very high internal consistency reliability (Cronbach's alpha = 0.96, N = 152), probably indicated some item redundancy in the 22-item GWBI. On the other hand, factor analyses confirmed the validity of the three W-BQ12 subscales of Negative Well-being, Energy, and Positive Well-being, each having excellent internal reliability (alphas of 0.86, 0.86 and 0.88, respectively, N from 152 to 154). There was no sign of item redundancy in the highly acceptable Cronbach's alpha of 0.93 (N = 148) for the whole W-BQ12 scale. Whilst neither questionnaire found significant differences between GH-treated and non-GH-treated patients, there were correlations (for GH-treated patients) with duration of GH treatment for GWBI Total (r = -0.36, p = 0.001, N = 85), W-BQ12 Total (r = 0.35, p = 0.001, N = 88) and for all W-BQ12 subscales: thus the longer the duration of GH treatment (ranging from 0.5 to 10 years), the better the well-being. Both questionnaires found that men had significantly better overall well-being than women. The W-BQ12 was more sensitive to change than the GWBI in the GH-Withdrawal study. A significant between-group difference in change in W-BQ12 Energy scores was found [t(18) = 3.25, p = 0.004, 2-tailed]: patients withdrawn from GH had reduced energy at end-point. The GWBI found no significant change.
The W-BQ12 is recommended in preference to the GWBI to measure well-being in adult GHD: it is considerably shorter, has three useful subscales, and has greater sensitivity to change.
Health and Quality of Life Outcomes 02/2006; 4:16. · 2.11 Impact Factor
