Acromegaly Subjects Research Articles

THU417 Associations Between Glucose Metabolism And Trabecular Bone Score In Subjects With Acromegaly

Abstract Disclosure: M. Kuzma: None. J. Payer: None. P. Vanuga: None. I. Sagova: None. D. Pavai: None. P. Jackuliak: None. Z. Killinger: None. Introduction: Previously, it was thought that increased risk of vertebral fractures (VF) in acromegaly is associated with impaired trabecular bone. More recently, cortical bone was proposed as one of the fracture risk determinant. However, trabecular compartment is still decreased. Glucose intolerance is a frequent complication of acromegaly and is directly attributable to the excess circulating growth hormone and IGF-1 concentrations and thus possibly lead to trabecular bone detoriation.Objectives: To assess effect of glucose metabolism on DXA-derived bone parameters, such as bone mineral density (BMD), trabecular bone score (TBS), cortical and trabecular vBMD, surface BMD and cortical thickness of proximal femur among patients with acromegaly. Patients and methods: In total, 70 consecutive patients (24 males/56 female, mean age = 55.6 years) with acromegaly based on current ADA guidelines were divided in two subgroups according to glucose metabolism(GM): abnormal GM (n=35; 14 males/21 females; 15 with active disease) and normal GM (n=35;10 Males /25 Females; 11 with active disease). Subjects were prospectively followed up for two years. At baseline and year 2; all subjects had pituitary hormonal measures, fasting plasma glucose (FPG), HBA1c, C-peptide, insulin resistance index (IRI) and DXA measurement performed. From DXA, BMD, TBS and 3D-Shaper parameters were derived. Results: At baseline; subjects with abnormal GM had lower TBS (1.166±0.15) in comparison to normal GM subjects (1.232±0.12; p<0.05). Insulin like growth factor 1 (IGF-1), FPG, HBA1c, C-peptide, IRI and bone parameters was correlated in simple regression model. FPG, HBA1c, C-peptide and IRI was negatively associated with TBS. No correlation between GM parameters and other bone measures was observed. Multiple regression model of all GM parameters weighted by IGF-1 revealed HBA1c as a significant predictor of TBS value (Estimate =-0,054; p=0.04). At year 2; FPG and HBA1c was negatively associated with TBS. In multiple regression IGF-1-weighted model, no significant predictor of TBS was observed. Conclusion: Acromegaly subjects with abnormal GM have lower TBS in comparison to those with normal GM. The best GM parameter to predict TBS in acromegaly was HBA1c. This study showed that trabecular bone microstructure, as indirectly assessed by TBS, is likely resulting of impaired glucose metabolism. Presentation: Thursday, June 15, 2023

Erectile function and androgen and estrogen beta receptor gene polymorphisms in acromegalic men

PurposeSexual dysfunctions are often experienced by male patients with acromegaly, due to a combination of hypogonadism and other comorbidities, but are a scarcely investigated complication. Erectile dysfunction is also closely related to cardiovascular diseases through endothelial dysfunction. Therefore, this project aimed to assess the prevalence of erectile dysfunction in a population of acromegalic men and evaluate its association with cardio-metabolic disorders, also exploring associations with androgen and estrogen receptor gene polymorphisms.MethodsSexually active men aged 18–65 with previous diagnosis of acromegaly were recruited. Clinical and laboratory data were retrospectively collected. Each patient also provided a blood sample for AR and ERβ gene polymorphisms analyses and filled out the IIEF-15 questionnaire.ResultsTwenty men with previous diagnosis of acromegaly (mean age 48.4 ± 10.0 years) were recruited. 13/20 subjects (65%) had erectile dysfunction, but only four had a concurrent biochemical hypogonadism, with no significant correlation with IIEF-15 scores. Total testosterone negatively correlated with sexual intercourse satisfaction domain (ρ = − 0.595; p = 0.019) and general satisfaction domain (ρ = − 0.651; p = 0.009). IGF-1 levels negatively correlated with biochemical hypogonadism (ρ = − 0.585; p = 0.028). The number of CAG and CA repeats in AR and ERβ receptors genes was not significantly associated with IIEF-15 scores or with GH/IGF-1 levels, but a negative correlation between CA repeats and the presence of cardiomyopathy (ρ = − 0.846; p = 0.002) was present.ConclusionsMen with acromegaly have a high prevalence of erectile dysfunction, but it does not appear to be correlated with treatments, testosterone levels and AR/ER-beta signaling. Nonetheless, a shorter CA polymorphic trait (ERbeta) is associated with the presence of cardiomyopathy. If confirmed, these data may suggest an association between an incorrect hormonal balance and increased cardiovascular risk in acromegaly subjects.

Low serm Fibroblast Growth Factor-21 levels is not associated with Carotid intima-media thickness in acromegaly patients.

Elevated fibroblast growth factor-21 (FGF-21) levels are related to carotid intima-media thickness (CIMT), a well-established marker of atherosclerosis. Acromegaly has also been linked to increased CIMT. There has been no data considering the association between FGF-21 levels and atherosclerosis in acromegaly patients. This study aimed to evaluate FGF-21 levels and CIMT in acromegalic patients in relation to atherosclerotic complications. Case-control study. The study group included 70 acromegaly patients and 72 healthy volunteers from the Department of Endocrinology and Metabolism Disease, Marmara University Medical School. FGF-21, growth hormone, insulin-like growth factor I, lipids, glucose, insulin levels were assessed. CIMT was measured from the common carotid artery wall on B-mode ultrasound. Median FGF-21 levels were significantly lower in the acromegaly group than in the control group. CIMT was higher in acromegaly patients compared to controls. Although there was no correlation between FGF-21 levels and CIMT in patients with acromegaly, a positive correlation was found between high-density lipoprotein-cholesterol and FGF-21 levels. Glucose metabolic markers were the determining factors of the FGF-21 levels in acromegaly patients. Our study is the first to examine the relationship between serum FGF-21 levels and atherosclerosis in acromegaly patients. The lower serum FGF-21 levels in acromegaly subjects might be associated with the improving effects of growth hormone on liver fat. Acromegaly was linked to higher CIMT, but there was no correlation between FGF-21 levels and CIMT. The role of FGF-21 in acromegaly as a marker of atherosclerosis requires additional research.

Trabecular bone score and bone mineral density in acromegalic osteopathy assessment: a cross-sectional study.

The evaluation of acromegalic osteopathy is a subject of current interest as there is a lack of evidence concerning proper evaluation techniques and clear diagnostic criteria. The aim of this study was to evaluate lumbar spine trabecular bone score (TBS) and bone mineral density (BMD) in acromegaly patients compared to healthy controls. We conducted a cross-sectional study on 43 acromegaly patients recruited between 2018 and 2020 and a healthy control group matched 1:1 for age, gender, and body mass index (BMI). All subjects underwent DXA, lumbar spine TBS, and bone turnover markers measurement. Acromegaly patients showed significantly decreased lumbar spine TBS (1.244 ± 0.117 vs. 1.343 ± 0.124, p < 0.001) and no difference regarding BMD compared to control patients. In the subgroup analysis, TBS was significantly lower in both males and females (1.282 ± 0.075 vs. 1.366 ± 0.113, p = 0.01 and 1.222 ± 0.132 vs. 1.329 ± 0.130, p = 0.005) and, also, inhypogonadal and eugonadal acromegaly subjects compared to their healthy controls (1.231 ± 0.130 vs. 1.306 ± 0.125, p = 0.04 and 1.280 ± 0.065 vs. 1.381 ± 0.113, p = 0.008). Femoral neck BMD was higher in acromegalic hypogonadal patients [1.027 (IQR: 0.939-1.135) vs. 0.876 (IQR: 0.737-1.014), p = 0.004]. Our study indicates that TBS, but not BMD, is significantly decreased in acromegaly patients, regardless of gender and gonadal status. This data suggests that TBS could be a valuable tool in the assessment of acromegalic osteopathy.

FRI0499 ACROMEGALY ARTROPATHY: IS THERE SOMETHING MORE BEHIND THE PAIN? A CROSS-SECTIONAL STUDY TO EVALUATE RHEUMATIC DISEASE IN GROWTH HORMONE SECRETING TUMOR PATIENTS

Background:Acromegaly is a rare disease with a remarkable impact on patients, both in terms of life expectancy and quality of life. Osteo-articular complications are one of the most frequently reported bothers. The “acromegaly artropathy” characterizes more than 70% of patients at diagnosis. Artropathy affects both spine and peripheral joints. A recent prospective study documented progression of acromegalic arthropathy identified as a worsening of osteophytes and joint space narrowing in 72–74% of patients despite long-term biochemical control. In addiction the Literature has occasionally reported cases of simultaneous presence of rheumatic diseases (rheumatoid arthritis, polymyalgia rheumatica, undifferentiated connective tissue diseases) and acromegaly and in all these cases the treatment has been delayed, because of wrong symptoms attribution to acromegaly artropathy.Objectives:The primary goal of the study is to better characterize joint pain in acromegaly patients and to evaluate the prevalence of rheumatic disease in growth hormone (GH) secreting pituitary tumor patients.Methods:We enrolled 20 acromegaly subjects (AS) and 20 control subjects (CS). In each subject immunological pattern (rheumatoid factor – RF; antinuclear antibodies - ANA, ENA; anti-citrullinated protein antibodies - ACPA; erythrocyte sedimentation rate – ESR) has been evaluated; they, also, underwent bilateral joint ultrasound of hands and wrists and nail capillaroscopy. The Chi square test and the Fisher’s exact test were used to evaluate the association between binary variables, while the Spearman’s test to evaluate the correlation of continuous ones. A multiple or logistic regression model was calculated in order to define the association between the capillaroscopic alterations and other detected variables.Results:Articular pain emerged as significantly more frequent in AS (p = 0.0269). No statistically significant differences are detected regarding immunological pattern. ANA and ENA screening resulted positive in 10% in AS and in 5% in CS. No IgA ACPA were detected in AS or CS, while IgG ACPA were positive only in one AS subject. No significant differences were detected between IgM and IgG RFin the two groups (AS 5% and CS 0%). Three fold higher IgG FR in AS compared to CS were detected. ESR levels were significantly higher than CS (p = 0.0405), as well as increased power doppler (PWD) articular uptake (AS 30% vs CS 5% p 0.081). The capillaroscopic evaluation showed a significant difference in almost each parameter that has been evaluated (logistic regression: number of enlargement p 0.004, hemorragies p 0.01 and capillaries p 0.001), showing a moderate-severe microangiopathy in AS. Interestingly, analyzing only the acromegaly cohort, we noticed higher GH levels at the enrollment in patients which developed capillary enlargements (GH: 0.95 ng/ml IQ 0,6-1,6) compared to other ones (GH: 0.55 ng/ml IQ 0.4-0.7; p = 0.08) and a significant lower number of hemorrhages (p = 0.02) in patients treated with GH antagonist pegvisomant.Conclusion:Our results demonstrated that joint damage in acromegaly does not seem to have an autoimmune etiology. Therefore, articular damage is mechanical and increased ESR and PWD alterations seems to confirm the presence of an inflammatory component. In addition, acromegaly is characterized by a microvascular pattern of moderate-severe microangiopathy, without correlation to IGF-I, but GH levels. Although requiring further confirmatory studies, our preliminary results seem to indicate how the capillaroscopic examination could be useful to detect earlier microangiopathy and to identify patients with a greater risk of macroangiopathy development..

Acromegaly and joint pain: is there something more? A cross-sectional study to evaluate rheumatic disorders in growth hormone secreting tumor patients.

The aim of the present study was to evaluate the rheumatic profile in acromegalic patients to better characterize joint pain. The immunological pattern (rheumatoid factor; antinuclear antibodies-ANA, extractable nuclear antigens-ENA-Ab; anti-citrullinated protein antibodies; erythrocyte sedimentation rate) was evaluated in 20 acromegaly subjects (AS) and 20 control subjects (CS). Bilateral joint ultrasound of hands/wrists and nail capillaroscopy were also performed. Articular pain was more frequent in AS than in CS (p = 0.027). No difference was detected in immunological parameters. ANA and ENA-Ab were positive in only 10% of AS and in 5% of CS, while no difference was found in anti-citrullinated protein antibodies. No difference was detected between rheumatoid factor positivity, but threefold higher IgG were detected in AS compared to CS. The erythrocyte sedimentation rate was significantly higher in AS than CS (p = 0.040), while in AS, there was a trend in increased Power Doppler (PWD) articular uptake. The capillaroscopic evaluation showed a significant difference in almost each parameter (presence and number of tortuous capillaries, capillary enlargements, and hemorrhages), showing a moderate-to-severe microangiopathy in AS. The results of our study suggest that joint damage in acromegaly has not an autoimmune etiology. Increased erythrocyte sedimentation rate levels and PWD alteration in acromegalic population reflect a possible inflammatory nature, while the capillaroscopic findings suggest a moderate-to-severe microangiopathy that could help to identify patients with a greater macroangiopathic risk.

SAT-438 Visceral and Marrow Adiposity in Patients with Acromegaly; Relationships to Disease Activity, Markers of Bone Turnover, Bone Mineral Density, and Peripheral Bone Microarchitecture

Adipose tissue (AT) mass, especially visceral (VAT), is reduced in active acromegaly and rises with treatment. Although the effect of acromegaly and its therapy on marrow AT(MAT) is unknown, data in other populations and in vitro, suggest a reciprocal relationship between GH and marrow adiposity. In other groups, VAT and MAT are associated with reduced bone quality and increased vertebral fracture (VF) risk. Therefore, since acromegaly patients have an increased VF incidence, we examined the relationships of VAT and MAT to bone quality in acromegaly. We studied 65 acromegaly subjects (40 men, 25 women, range 18.7-74 yr.) before (n=20) or before and after (n=45) acromegaly therapy by total body multi-slice MRI(n=159)(measurement of VAT, subcutaneous (SAT) and total (TAT) adipose tissue mass), DXA (BMD (n=120) and body composition (n=145)) and HRpQCT (n=35) (microarchitecture of the tibia and radius). Marrow lipid spectra of the tibial diaphysis were acquired by 1H MRS (PRESS technique)(1.5T MR scanner, Philips) and percentages of bone marrow lipids were quantified (n=53). GH and IGF-1 (n=159) and bone turnover markers (BTM)(n=49) were measured. We examined the relationship between MAT or VAT and GH, IGF-1, age, weight, mass of other MRI measured AT depots, and selected DXA and HRpQCT parameters previously shown to differ in acromegaly compared to healthy subjects and to be associated in other groups with fracture. Data were analyzed by Pearson correlation and the generalized estimating equation (GEE). MAT directly correlated with VAT (r=.249, p=.023) and by HRpQCT (n=13) with bone size (radius: total area (r=.678, p=.01), tibia: total area (r=.535, p=.05)) and trabecular number (r=.543, p=.055). VAT was inversely associated with GH (β= -.017, p<.001), IGF-1 level (expressed as % upper normal limit) (β= -0.004, p=.049) and BTMs (N-Mid Osteocalcin (β= -.0223, p<0.001); CTX (β= -.7283, p=.0134)). VAT was positively associated with age (β=.034, p=.053), weight (β=.072, p <.0001) and with HRpQCT measured bone size (radius: total area (β=.0073, p=.0098); tibia: total area (β= .0049, p <.0001)) and trabecular number (tibia: β=1.9321, p=.0096), and inversely associated with cortical thickness (radius: β= -2.8477, p= .074; tibia: β= -2.3341, p=.0497), trabecular thickness (tibia: β= -92, p<.0001) and total body density (radius β= -.0102, p=.0353; tibia: β= -.0149, p=.003). In summary, VAT is inversely related to acromegaly disease activity, consistent with its known rise as acromegaly is treated. We found that greater VAT is associated with larger bone size and lower bone turnover, but also with some less favorable aspects of bone microarchitecture. MAT correlated with VAT and, in a small number of subjects, with bone size. Whether rising adiposity and reductions in bone turnover with acromegaly therapy are relevant to the skeletal fragility reported in treated acromegaly warrants further study.

Is elevated urotensin II level a predictor for increased cardiovascular risk in subjects with acromegaly?

Acromegaly is a rare disorder existed in the result of overproduction of growth hormone (GH). The disorder is associated with increased cardiovascular risk factors and metabolic abnormalities. Urotensin II (UII), a secreted vasoactive peptide hormone, belonging somatostatin superfamily, plays an essential role in atherosclerosis and glucose metabolism. The aim of this study was to ascertain whether circulating UII levels are altered in subjects with acromegaly, and to describe the relationship between UII and hormonal or cardiometabolic parameters. This cross-sectional study included 41 subjects with active acromegaly, 28 subjects with controlled acromegaly, and 37 age- and BMI-matched controls without acromegaly. Hormonal and metabolic features of the subjects as well as carotid intima media thickness (cIMT) and epicardial fat thickness (EFT) were defined. Circulation of UII levels was determined via ELISA. Both active and controlled acromegalic subjects showed a significant elevation of circulating levels of UII with respect to controls. There was no remarkable difference in circulating levels of UII between active and controlled acromegalic groups. Both cIMT and EFT were remarkably increased in acromegaly subjects comparing to controls. UII positively correlated with cIMT, EFT, BMI, and HOMA-IR. There was no correlation between UII and GH, insulin-like growth factor-1. According to the results obtained from regression models, UII levels independently predicted cIMT and EFT. Elevated UII levels are associated with severity of cardiovascular risk factors including cIMT and EFT in acromegalic subjects.

Is elevated urotensin II level a predictor for increased cardiovascular risk in subjects with acromegaly?

Acromegaly is a rare disorder existed in the result of overproduction of growth hormone (GH). The disorder is associated with increased cardiovascular risk factors and metabolic abnormalities. Urotensin II (UII), a secreted vasoactive peptide hormone, belonging somatostatin superfamily, plays an essential role in atherosclerosis and glucose metabolism. The aim of this study was to ascertain whether circulating UII levels are altered in subjects with acromegaly, and to describe the relationship between UII and hormonal or cardiometabolic parameters. This cross-sectional study included 41 subjects with active acromegaly, 28 subjects with controlled acromegaly, and 37 age- and BMI-matched controls without acromegaly. Hormonal and metabolic features of the subjects as well as carotid intima media thickness (cIMT) and epicardial fat thickness (EFT) were defined. Circulation of UII levels was determined via ELISA. Both active and controlled acromegalic subjects showed a significant elevation of circulating levels of UII with respect to controls. There was no remarkable difference in circulating levels of UII between active and controlled acromegalic groups. Both cIMT and EFT were remarkably increased in acromegaly subjects comparing to controls. UII positively correlated with cIMT, EFT, BMI, and HOMA-IR. There was no correlation between UII and GH, insulin-like growth factor-1. According to the results obtained from regression models, UII levels independently predicted cIMT and EFT. Elevated UII levels are associated with severity of cardiovascular risk factors including cIMT and EFT in acromegalic subjects.

Balance Control and Peripheral Muscle Function in Aging: A Comparison Between Individuals with Acromegaly and Healthy Subjects.

Advances in the knowledge of acromegaly are leading to an increase in the survival rate of acromegalic subjects. This study was conducted to evaluate balance control, risk of falls, and peripheral muscle function in acromegalic older adults. Seventeen older subjects with acromegaly (67 [63-73] years) and 20 paired control subjects were evaluated with balance scales, force platform, and knee isokinetic dynamometry tests. There were significant differences between the groups on several balance and gait scales, with a worse performance and greater risk of falls in the acromegalic older adults. Acromegalic older adults had lower values for peak torque, maximum repetition of the total work, and total work during extension at 240°/s. The acromegalic older adults had higher values in the medial-lateral range. Acromegaly subjects had lateral instability that compromises their body balance and increases the risk of falls. Moreover, there was a propensity for muscle fatigue in these individuals.

Does Apolipoprotein E genotype affect cardiovascular risk in subjects with acromegaly?

Acromegaly is a syndrome that results when the pituitary gland produces excess growth hormone after epiphyseal closure at puberty. Usually, subjects with acromegaly exhibit a 2- to 3-fold higher mortality rate from diseases that are associated with cardiovascular complications when compared to the normal population. In this study, we therefore aimed to evaluate whether a well-established cardiovascular risk factor, the Apolipoprotein E (Apo E) genotype, contributes to increased risk of cardiovascular complications in subjects with acromegaly. A total of 102 unrelated acromegaly subjects were prospectively included into this case-control association study and constituted our study group. The study group was comparable by age and gender with 200 unrelated healthy subjects constituting our control group. Genomic DNA was isolated from the peripheral blood leukocytes of all subjects and Apo E genotype (codon 112/158) was assessed by melting temperature analyses after using a real-time PCR protocol. The Apolipoprotein E4 allele was found at a significantly higher frequency in the study group when compared with the control group (P=0.032). Subjects with the E2 allele, on the other hand, had significantly increased values in body mass index (P=0.004), waist circumference (P=0.001), C-reactive protein (CRP) (P<0.001), and left-side carotid intima media thickness (P=0.025). The Apolipoprotein E2 genotype might contribute to increased risk of cardiovascular complications in subjects with acromegaly since it is concurrently present with other cardiovascular risk factors such as the left-side carotid intima media thickness and CRP.

Increased plasma endothelin level as an endothelial marker of cardiovascular risk in patients with active acromegaly: A comparison with plasma homocysteine

The aim of the present study was to evaluate the plasma endothelin-1 (ET-1) and total homocysteine (tHcy) levels as biochemical markers of endothelial dysfunction and atherosclerosis in patients with active and cured acromegaly in order to assess the relationship between the secretory status of growth hormone (GH)/insulin-like growth factor I (IGF-I) and ET-1/tHcy levels. The patients were divided in two subgroups: 1) patients with active disease (n = 30); and 2) patients with nonactive cured acromegaly (n = 21). Plasma ET-1 levels were directly determined by a highly sensitive enzyme immunoassay and plasma tHcy concentrations were measured by a fluorescence polarization immunoassay. In active acromegaly subjects, plasma ET-1 levels were 1.24 +/- 0.2 pmol/L, significantly higher than in both nonactive acromegalics (0.39 +/- 0.1 pmol/L) and age-matched healthy controls (0.49 +/- 0.2 pmol/L) (P < 0.001). Plasma tHcy concentrations, however, did not differ significantly in all studied groups: nonactive acromegalics: 9.54 +/- 4.42 micromol/L; active acromegalics: 9.0 +/- 3.14 micromol/L; and control subjects: 9.96 +/- 2.95 micromol/L (P > 0.05). In conclusion, our study demonstrated that elevated ET-1 levels probably contributed to premature atherosclerosis and cardiovascular disease and represent a new risk factor for endothelial dysfunction and early vascular complications in acromegaly. We propose that GH and IGF-I secretory status are important determinants of plasma ET-1 but not tHcy levels.

Lower Visceral and Subcutaneous but Higher Intermuscular Adipose Tissue Depots in Patients with Growth Hormone and Insulin-Like Growth Factor I Excess Due to Acromegaly

GH and IGF-I are important regulators of metabolism and body composition. In acromegaly, a state of GH and IGF-I excess, the lipolytic and insulin antagonistic effects of GH may alter adipose tissue (AT) distribution. Our objective was to test the hypothesis that in acromegaly whole-body AT mass is less and to examine for the first time the relationship between GH/IGF-I excess and intermuscular AT (IMAT), an AT depot associated with insulin resistance in other populations. We conducted a cross-sectional study in 24 adults with active acromegaly compared with predicted models developed in 315 healthy non-acromegaly subjects. Mass of AT in the visceral AT (VAT), sc AT (SAT), and IMAT compartments from whole-body magnetic resonance imaging and serum levels of GH, IGF-I, insulin, and glucose were measured. VAT and SAT were less in active acromegaly (P < 0.0001); these were 68.2 +/- 27% and 79.5 +/- 15% of predicted values, respectively. By contrast, IMAT was greater (P = 0.0052) by 185.6 +/- 84% of predicted. VAT/trunk AT ratios were inversely related to IGF-I levels (r = 0.544; P = 0.0054). Acromegaly subjects were insulin resistant. VAT and SAT, most markedly VAT, are less in acromegaly. The proportion of trunk AT that is VAT is less with greater disease activity. IMAT is greater in acromegaly, a novel finding, which suggests that increased AT in muscle could be associated with GH-induced insulin resistance. These findings have implications for understanding the role of GH in body composition and metabolic risk in acromegaly and other clinical settings of GH use.

Growth Hormone, Body Composition and Somatomedin C after Treatment of Acromegaly

Acromegaly is associated with abnormal indices of body composition (as determined by exchangeable sodium, exchangeable potassium and total body water estimations) which may be corrected by treatment. We related these indices of body composition to the attained growth hormone levels (mean of five daytime values) in 42 treated acromegalics. Somatomedin C was measured in 30 subjects. The mean duration of treatment was 7.7 years (range 1-26). Exchangeable sodium, potassium and total body water were significantly lowered by treatment. After treatment of acromegaly subjects whose growth hormone level was below 5 mU/l achieved normal body composition more often than those with higher levels. Growth hormone concentration of below 5 mU/l after treatment should be regarded as more appropriate index of control of acromegaly than the higher levels previously recommended.