The effects of recombinant human insulin-like growth factor-1/insulin-like growth factor binding protein-3 administration on lipid and carbohydrate metabolism in recreational athletes.

OBJECTIVE: Previous studies suggested that recombinant human IGF-1 (rhIGF-1) administration affects carbohydrate and lipid metabolism in healthy people and in people with diabetes. This study aimed to determine the effects of rhIGF-1/rhIGF binding protein-3 (rhIGFBP-3) administration on glucose homeostasis and lipid metabolism in healthy recreational athletes. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled rhIGF-1/rhIGFBP-3 administration study at Southampton General Hospital, UK. PARTICIPANTS: 56 recreational athletes (30 men, 26 women). METHODS: Participants were randomly assigned to receive placebo, low-dose rhIGF-1/rhIGFBP-3 (30 mg/day) or high-dose rhIGF-1/rhIGFBP-3 (60 mg/day) for 28 days. The following variables were measured before and immediately after the treatment period: fasting lipids, glucose, insulin, C-peptide and glycated haemoglobin. The homeostatic model assessment (HOMA-IR) was used to estimate insulin sensitivity and indirect calorimetry to assess substrate oxidation rates. The general linear model approach was used to compare treatment group changes with the placebo group. RESULTS: Compared with the placebo group, there was a significant reduction in fasting triglycerides in participants treated with high-dose rhIGF-1/rhIGFBP-3 (p = .030), but not in the low-dose group (p = .390). In women, but not in men, there were significant increases in total cholesterol (p = .003), HDL cholesterol (p = .001) and LDL cholesterol (p = .008). These lipid changes were associated with reduced fasting insulin (p = .010), C-peptide (p = .001) and HOMA-IR (p = .018) in women and reduced C-peptide (p = .046) in men. CONCLUSIONS: rhIGF-1/rhIGFBP-3 administration for 28 days reduced insulin concentration, improved insulin sensitivity and had significant effects on lipid profile including decreased fasting triglycerides.

Comparison of normal distribution-based and nonparametric decision limits on the GH-2000 score for detecting growth hormone misuse (doping) in sport.

This paper is motivated by the GH-2000 biomarker test, though the discussion is applicable to other diagnostic tests. The GH-2000 biomarker test has been developed as a powerful technique to detect growth hormone misuse by athletes, based on the GH-2000 score. Decision limits on the GH-2000 score have been developed and incorporated into the guidelines of the World Anti-Doping Agency (WADA). These decision limits are constructed, however, under the assumption that the GH-2000 score follows a normal distribution. As it is difficult to affirm the normality of a distribution based on a finite sample, nonparametric decision limits, readily available in the statistical literature, are viable alternatives. In this paper, we compare the normal distribution-based and nonparametric decision limits. We show that the decision limit based on the normal distribution may deviate significantly from the nominal confidence level 1-α or nominal FPR γ when the distribution of the GH-2000 score departs only slightly from the normal distribution. While a nonparametric decision limit does not assume any specific distribution of the GH-2000 score and always guarantees the nominal confidence level and FPR, it requires a much larger sample size than the normal distribution-based decision limit. Due to the stringent FPR of the GH-2000 biomarker test used by WADA, the sample sizes currently available are much too small, and it will take many years of testing to have the minimum sample size required, in order to use the nonparametric decision limits. Large sample theory about the normal distribution-based and nonparametric decision limits is also developed in this paper to help understanding their behaviours when the sample size is large.

Determination and regulation of body composition in elite athletes.

In 2011, the International Association of Athletics Federations (IAAF) and IOC introduced a 'hyperandrogenism' rule that excluded women with a serum testosterone >10 nmol/L from participating in elite sport. This rule was based on the false premise that the greater lean body mass in men was a consequence of their higher serum testosterone. This rule did not have scientific backing and the Court of Arbitration for Sport subsequently rescinded the rule following an appeal from an Indian athlete barred from the Commonwealth Games. This review covers the scientific knowledge about the development and regulation of body composition in humans but also considers the lessons learnt from evolution and breeding in animals. The importance of heredity has been documented in family and twin studies. The roles of growth hormone and sex steroids are reviewed. The Androgen Insensitivity Syndrome (AIS) is considered as a model of the role of testosterone in development of body composition and also as evidence of the importance of other factors carried on the Y-chromosome that are of prime importance but have been systematically ignored. Finally the key factors determining body composition are considered and placed in a suggested order of importance.

Statistical methodology for age-adjustment of the GH-2000 score detecting growth hormone misuse.

BACKGROUND: The GH-2000 score has been developed as a powerful and unique technique for the detection of growth hormone misuse by sportsmen and women. The score depends upon the measurement of two growth hormone (GH) sensitive markers, insulin-like growth factor-I (IGF-I) and the amino-terminal pro-peptide of type III collagen (P-III-NP). With the collection and establishment of an increasingly large database it has become apparent that the score shows a positive age effect in the male athlete population, which could potentially place older male athletes at a disadvantage. METHODS: We have used results from residual analysis of the general linear model to show that the residual of the GH-2000 score when regressed on the mean-age centred age is an appropriate way to proceed to correct this bias. As six GH-2000 scores are possible depending on the assays used for determining IGF-I and P-III-NP, methodology had to be explored for including six different age effects into a unique residual. Meta-analytic techniques have been utilized to find a summary age effect. RESULTS: The age-adjusted GH-2000 score, a form of residual, has similar mean and variance as the original GH-2000 score and, hence, the developed decision limits show negligible change when compared to the decision limits based on the original score. We also show that any further scale-transformation will not change the adjusted score. Hence the suggested adjustment is optimal for the given data. The summary age effect is homogeneous across the six scores, and so the generic adjustment of the GH-2000 score formula is justified. CONCLUSIONS: A final revised GH-2000 score formula is provided which is independent of the age of the athlete under consideration.

Insulin-like growth factor-I (IGF-I) misuse in athletes and potential methods for detection.

To athletes, insulin-like growth factor-I (IGF-I) is an attractive performance-enhancing drug, particularly as an alternative to growth hormone (GH) because IGF-I mediates many of the anabolic actions of GH. IGF-I has beneficial effects on muscle protein synthesis and glycogen storage that could enhance performance in several sporting disciplines. Recombinant human IGF-I (rhIGF-I) is used in clinical practice, but a variety of IGF-I compounds and IGF-I analogues are also advertised on the internet and many have been available on the black market for several years. Although methods for detecting GH misuse are now well established and there have been several cases in which athletes have tested positive for GH, no test is yet in place for detecting IGF-I misuse. The GH-2004 research group has been investigating methods for detection of IGF-I misuse and a test is being developed on the basis of the principles of the successful GH-2000 marker method, in which markers from the IGF axis and markers of collagen and bone turnover are used to detect GH misuse. Commercial immunoassays for these markers have been validated for anti-doping purposes but new methods, including IGF-I measurement by use of mass spectrometry, should improve the performance of the tests and help in the detection of athletes who are doping with these peptide hormones.

The growth hormone/insulin-like growth factor-I axis in exercise and sport.

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.

The use of growth hormone (GH)-dependent markers in the detection of GH abuse in sport: Physiological intra-individual variation of IGF-I, type 3 pro-collagen (P-III-P) and the GH-2000 detection score.

BACKGROUND: 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. AIM: The aim of this study was to examine the intra-individual variability of IGF-I, P-III-P and the GH-2000 score. SUBJECTS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Influence of ethnicity on IGF-I and procollagen III peptide (P-III-P) in elite athletes and its effect on the ability to detect GH abuse.

CONTEXT: 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. OBJECTIVE: 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. DESIGN: Cross-sectional observational study. SETTING: National and International sporting events. SUBJECTS: 1085 elite athletes of different ethnicities. INTERVENTION: Serum IGF-I and P-III-P were measured and GH-2000 discriminant function score was calculated. Effect of ethnicity was assessed. RESULTS: 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. CONCLUSIONS: The GH-2000 detection method based on IGF-I and P-III-P would be valid in all ethnic groups.

Exact statistical calculation of the uncertainty term in the decision limits of the GH-2000 score for growth hormone misuse (doping) detection.

The GH-2000 score has been developed as a powerful and unique technique for the detection of growth hormone misuse by sportsmen and women. The score depends upon the measurement of two growth hormone sensitive markers, insulin-like growth factor-I and the amino-terminal pro-peptide of type III collagen. It also includes a term to adjust for the age of the athlete. Decision limits for the GH-2000 score have been developed and are incorporated into the guidelines of the World Anti-Doping Agency. These decision limits are derived by setting a 1 in 10,000 false-positive rate rule. As these decision limits are estimated from samples of GH-2000 scores, they carry uncertainty. In previous work, this uncertainty has been addressed by establishing an upper 95% confidence interval for the true decision limits based on a normal approximation which has been shown to be appropriate if sample sizes are large (such as 1000 and above). Here, we show that these approximations, whether reasonable or not, can be entirely avoided by developing an upper 95% confidence interval for the true decision limits using an approach based upon the t-distribution. While there are considerable differences for smaller sample sizes, these become negligible when the sample size is large such as 1000 and above.

The effects of growth hormone and/or testosterone on whole body protein kinetics and skeletal muscle gene expression in healthy elderly men: a randomized controlled trial.

CONTEXT: Alterations of protein turnover may contribute to the progressive decline of muscle mass with aging. OBJECTIVE: Our objective was to examine the effects of near-physiological recombinant human GH and/or testosterone (T) administration to older men on whole body protein kinetics and muscle gene expression. DESIGN, SETTINGS, AND PARTICIPANTS: A 6-month randomized, double-blind, placebo-controlled trial in 21 healthy elderly men aged 65-75 yr, was performed. Participants were randomized to receive placebo GH and placebo T, rhGH and placebo T (GH), T and placebo GH (T), or rhGH and T (GHT). INTERVENTIONS: The leucine rate of appearance (index of proteolysis), nonoxidative leucine disposal rate (an index of protein synthesis), and leucine oxidation rate were measured with an infusion of l-[1-(13)C] leucine. Muscle biopsies for the measurement of gene expression were performed. Body composition and aerobic capacity (maximal oxygen capacity) were measured. RESULTS: Serum IGF-I levels increased significantly with GH and GHT (P < 0.001) compared with placebo. T increased significantly only in the T group (P = 0.028). Leucine rate of appearance and nonoxidative leucine disposal rate increased with GH (P = 0.015, P = 0.019) and GHT (P = 0.017, P = 0.02), but leucine oxidation did not change significantly in any treatment group. Midthigh muscle mass and maximal oxygen capacity increased (P < 0.04) with GHT only. Expression of muscle function genes did not change significantly, but the within-group comparisons revealed a significant increase of androgen receptor expression in the GHT group (P = 0.001). CONCLUSION: This study showed that 6-month treatment with low-dose GH alone or with T in healthy elderly men produces comparable increments in whole body protein turnover and protein synthesis.

The effect of sports injury on insulin-like growth factor-I and type 3 procollagen: implications for detection of growth hormone abuse in athletes.

CONTEXT: 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. OBJECTIVE: 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. DESIGN: This was a longitudinal observational study after sporting injury. SETTING: The study was conducted at Southampton General Hospital and British Olympic Medical Centre. SUBJECTS: Subjects included elite and amateur athletes after an injury. INTERVENTION: 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. OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

A correction to the age-adjustment of the GH-2000 score used in the detection of growth hormone misuse.

OBJECTIVE: The GH-2000 biomarker test has been introduced by the World Anti-Doping Agency as a method of detecting growth hormone misuse in professional sport. The test involves the measurement insulin-like growth factor-I and the amino-terminal pro-peptide of type III collagen (P-III-NP) which increase in a dose-dependent manner in response to GH. These measurements are combined in sex specific formulae that include an age adjustment. The original age adjustment overcorrects the effect of age in male athletes and could potentially place older men at a disadvantage. The purpose of this note is to investigate the performance of a previously suggested correction term in two new and larger data sets. RESULTS: The GH-2000 score was calculated for 7307 samples obtained from 15 accredited WADA laboratories in 2017 and 3916 samples measured at Drug Control Centre, King's College London, UK between 2013 and 2017. The GH-2000 scores were investigated for positive age effects using standard regression modelling. As previously, all analyses confirmed a positive age effect. Applying the earlier suggested correction term of 0.032 × age showed a significant over-correction leading to a negative association of the GH-2000 score with age. We now suggest a smaller age correction of 0.020 × age, which corresponds to the smallest effect found in the earlier studies.

Why do endocrine profiles in elite athletes differ between sports?

BACKGROUND: Endocrine profiles have been measured on blood samples obtained immediately post-competition from 693 elite athletes from 15 Olympic Sports competing at National or International level; four were subsequently excluded leaving 689 for the current analysis. METHODS: Body composition was measured by bioimpedance in a sub-set of 234 (146 men and 88 women) and from these data a regression model was constructed that enabled 'estimated' lean body mass and fat mass to be calculated on all athletes. One way ANOVA was used to assess the differences in body composition and endocrine profiles between the sports and binary logistical regression to ascertain the characteristic of a given sport compared to the others. RESULTS: The results confirmed many suppositions such as basketball players being tall, weightlifters short and cross-country skiers light. The hormone profiles were more surprising with remarkably low testosterone and free T3 (tri-iodothyronine) in male powerlifters and high oestradiol, SHBG (sex hormone binding globulin) and prolactin in male track and field athletes. Low testosterone concentrations were seen 25.4% of male elite competitors in 12 of the 15 sports and high testosterone concentrations in 4.8% of female elite athletes in 3 of the 8 sports tested. Interpretation of the results is more difficult; some of the differences between sports are at least partially due to differences in age of the athletes but the apparent differences between sports remain significant after adjusting for age. The prevalence of 'hyperandrogenism' (as defined by the IAAF (International Association of Athletics Federations) and IOC (International Olympic Committee)) amongst this cohort of 231 elite female athletes was the highest so far recorded and the very high prevalence of 'hypoandrogenism' in elite male athletes a new finding. CONCLUSIONS: It is unclear whether the differences in hormone profiles between sports is a reason why they become elite athletes in that sport or is a consequence of the arduous processes involved. For components of body composition we know that most have a major genetic component and this may well be true for endocrine profiles.

Validation of the growth hormone (GH)-dependent marker method of detecting GH abuse in sport through the use of independent data sets.

CONTEXT: 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. OBJECTIVE: To provide further validation of the GH-dependent marker approach. DESIGN: Analysis of discriminant function scores for GH detection on independent datasets. SETTING: Two independent (GH-2000 and Kreischa) double blind, placebo controlled, hGH administration studies. SUBJECTS: Healthy active male volunteers. INTERVENTION: 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. OUTCOME MEASURES: Ability to detect GH use in independent datasets using a predefined specificity of approximately 1 in 10000. RESULTS: 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. CONCLUSIONS: 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.

Novel markers to detect recombinant human insulin-like growth factor-I (rhIGF-I)/rhIGF binding protein-3 (rhIGFBP-3) misuse in athletes.

Insulin-like growth factor-I (IGF-I) is abused by elite athletes for its metabolic and anabolic effects. We have previously shown that it is possible to detect IGF-I misuse by measuring serum IGF-I and procollagen type III amino-terminal propeptide (P-III-NP) but a pilot study suggested measuring IGF-II, IGF binding protein-2 (IGFBP-2) and acid-labile subunit (ALS) may improve the detection of IGF-I administration. The aim of the study was to assess this in a randomized controlled trial. Twenty-six female and 30 male recreational athletes were randomized to 28 days' treatment with placebo or recombinant human (rh)IGF-I/rhIGF binding protein-3 (IGFBP-3) complex (30 mg/day or 60 mg/day), followed by 56 days' washout. IGF-II, IGFBP-2 and ALS (women only) were measured using commercial immunoassays. IGFBP-2 increased and IGF-II decreased in response to both low and high dose rhIGF-I/rhIGFBP-3 in both women and men while ALS decreased in women in response to high dose rhIGF-I/rhIGFBP-3. Two days after discontinuing treatment, significant differences remained between the three treatment groups in IGFBP-2 and IGF-II, but not ALS. Thereafter there were no significant differences between the three treatment groups in any of the markers. Combining IGF-I with IGF-II and/or IGFBP-2 improved the performance of the test to detect rhIGF-I/rhIGFBP-3 administration in both women and men. Copyright © 2016 John Wiley & Sons, Ltd.

The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial.

CONTEXT: Declines in GH and testosterone (Te) secretion may contribute to the detrimental aging changes of elderly men. OBJECTIVE: To assess the effects of near-physiological GH with/without Te administration on lean body mass, total body fat, midthigh muscle cross-section area, muscle strength, aerobic capacity, condition-specific quality of life (Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire), and generic health status (36-Item Short-Form Health Survey) of older men. DESIGN, SETTINGS, AND PARTICIPANTS: A 6-month, randomized, double-blind, placebo-controlled trial was performed on 80 healthy, community-dwelling, older men (age, 65-80 yr). INTERVENTIONS: Participants were randomized to receive 1) placebo GH or placebo Te, 2) recombinant human GH (rhGH) and placebo Te (GH), 3) Te and placebo rhGH (Te), or 4) rhGH and Te (GHTe). GH doses were titrated over 8 wk to produce IGF-I levels in the upper half of the age-specific reference range. A fixed dose of Te (5 mg) was given by transdermal patches. RESULTS: Lean body mass increased with GHTe (P = 0.008) and GH (P = 0.004), compared with placebo. Total body fat decreased with GHTe only (P = 0.02). Midthigh muscle (P = 0.006) and aerobic capacity (P < 0.001) increased only after GHTe. Muscle strength changes were variable; one of six measures significantly increased with GHTe. Significant treatment group by time interactions indicated an improved Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire score (P = 0.007) in the GH and GHTe groups. Bodily pain increased with GH alone, as determined by the Short-Form Health Survey (P = 0.003). There were no major adverse effects. CONCLUSION: Coadministration of low dose GH with Te resulted in beneficial changes being observed more often than with either GH or Te alone.

Low-density lipoprotein apolipoprotein B100 turnover in hypopituitary patients with GH deficiency: a stable isotope study.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.