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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2004-1844
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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 5 2659-2665
Copyright © 2005 by The Endocrine Society

Common Carotid Intima-Media Thickness in Growth Hormone (GH)-Deficient Adolescents: A Prospective Study after GH Withdrawal and Restarting GH Replacement

Annamaria Colao, Carolina Di Somma, Francesca Rota, Salvatore Di Maio, Mariacarolina Salerno, Antonella Klain, Stefano Spiezia and Gaetano Lombardi

Department of Molecular and Clinical Endocrinology and Oncology (A.C., C.D.S., F.R., G.L.), Department of Pediatrics (M.S.), "Federico II" University of Naples, 80131 Naples, Italy; Division of Pediatric Endocrinology (S.D.M., A.K.), Santobono Hospital of Naples, 80123 Naples, Italy; and Emergency Unit, "S. Maria degli Incurabili" Hospital of Naples (S.S.), 80131 Naples, Italy

Address all correspondence and requests for reprints to: Annamaria Colao M.D., Ph.D., Department of Molecular and Clinical Endocrinology and Oncology, "Federico II," University of Naples, Via S. Pansini 5, 80131 Naples, Italy. E-mail: colao{at}unina.it.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
We prospectively investigated the risk of early atherosclerosis, by classical cardiovascular risk factors and intima-media thickness (IMT) at the common carotid arteries, in 23 adolescents diagnosed as GH deficient (GHD) during childhood and in 23 healthy sex-, age-, and BMI-matched controls. Measurements were performed in all subjects before stopping GH replacement. Because the diagnosis of GHD had been confirmed in 15 of the 23 adolescents, the protocol changed according to the diagnosis as follows: measurements were repeated after 6 months of GH withdrawal and 6 months of GH reinstitution in the 15 with GHD, and after 6 and 12 months of GH withdrawal, measurements were also taken in the eight non-GHD subjects.

Serum IGF-I levels were in the normal range for age in all patients before GH withdrawal. When compared with controls, before GH withdrawal, GHD adolescents had reduced high-density lipoprotein cholesterol levels and increased total/high-density lipoprotein cholesterol ratio, fibrinogen, low-density lipoprotein cholesterol, and glucose levels; non-GHD adolescents had increased glucose, insulin, and homeostasis model assessment score. IMT at the common carotid arteries was similar in GHD and controls (0.52 ± 0.03 vs. 0.55 ± 0.06 mm; P = 0.23) and was higher in non-GHD than in controls (0.62 ± 0.03 vs. 0.54 ± 0.06 mm; P = 0.01). In GHD adolescents, 6 months of GH treatment withdrawal and 6 months of GH treatment reinstitution modified IGF-I levels, lipid profile, and insulin resistance but not IMT or systolic and diastolic peak velocities at the common carotid arteries. In non-GHD subjects, 12 months of GH treatment withdrawal significantly decreased IGF-I levels, IMT (to 0.54 ± 0.06 mm; P < 0.001 vs. baseline), systolic and diastolic peak velocities, and improved insulin resistance.

In conclusion, the discontinuation of GH in confirmed GHD adolescents is not followed by significant alterations of the common carotid arteries, despite the profound negative alterations of the lipid profile. In adolescents who were not confirmed to have GHD, IMT was increased while on GH therapy and normalized when they were taken off of GH.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
THE MORTALITY FOR cardiovascular and cerebrovascular diseases is increased in hypopituitary patients (1, 2, 3, 4, 5). Increased cardiovascular risk factors such as body fat, peripheral insulin resistance, the frequency of impaired glucose tolerance, and an abnormal cardiac structure and performance are all typical features of adults who are GH deficient (GHD) (6, 7, 8, 9, 10). GHD adults have also been shown to have vascular disease demonstrated by an increased number of atheromatous plaques in the carotid and the femoral arteries, increased intima-media thickness (IMT) and stiffness of the carotid arteries, and impaired flow-mediated endothelium-dependent dilation of the brachial artery (11, 12, 13, 14, 15, 16). Increased IMT is a sign of premature atherosclerosis directly related to mortality from coronary artery disease (17). More recently, low IGF-I levels were shown to be independently related to an increased risk of death for ischemic heart diseases in a healthy elderly population free of cardiovascular events (18, 19). Low IGF-I levels were also associated with increased IMT and prevalence of atherosclerotic plaques at the common carotid arteries in adult GHD patients (20). To reinforce the role of GH on the negative cardiovascular profile of GHD patients, GH replacement has been shown to induce beneficial effects on lipid profile, cardiac performance, and atherosclerosis (6, 7, 8, 9, 13, 14).

The current practice for childhood GHD patients is to stop GH replacement at final height (21). The persistence of GHD is then reevaluated by appropriate GH testing because one third to one half of the patients with GHD during childhood do not have persistent severe GHD later on in adulthood (22, 23). The discontinuation of GH therapy in adolescents with severe GHD for 1 yr causes the accumulation of cardiovascular risk factors such as increase of total body and abdominal fat mass, a decrease of lean body mass, and an increase of total cholesterol, low-density lipoprotein (LDL)-cholesterol, and apolipoprotein B, with a decrease of high-density lipoprotein (HDL)-cholesterol (24). Lipid alterations in these young patients are particularly relevant, because increased total and LDL-cholesterol levels during adolescence have been shown to predict IMT later on in life in non-hypopituitary subjects (25). We had previously shown that GH discontinuation is inappropriate in adolescents with severe GHD because it induces impairment of lipid profile and cardiac morphology and performance (26). In a cross-sectional study by Lanes et al. (27), however, no difference in cardiac mass and function and in the atherosclerotic profile was found in GHD adolescents during GH replacement, in those studied at the diagnosis of GHD (and thus not receiving GH) or in healthy adolescents.

This prospective study was designed to investigate the risk of early atherosclerosis in GHD adolescents during GH replacement and withdrawal. The classical cardiovascular risk factors such as IMT and systolic and diastolic peak velocities at the common carotid arteries, were measured in adolescent GHD patients reaching their final height within 6 months of stopping GH replacement and 6 months after GH treatment was restarted. The results were compared with sex- and age-matched healthy adolescents who served as a control group and to patients who were not confirmed to have GHD at retesting.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
Patients

Twenty-three adolescent patients with GHD during childhood (10 boys and 13 girls, aged 15–20 yr) with adult bone age and completed puberty (Tanner stages IV–V) and a mean height SD score of –0.27 ± 0.31 were studied. GHD had been diagnosed 4.5–12.3 yr before entering the study by two classical stimulation tests [insulin tolerance test, clonidine or arginine with peak GH concentrations < 10 µg/liter and arginine plus GHRH (ARG+GHRH) with peak GH concentrations < 20 µg/liter]. Fourteen patients had idiopathic, isolated GHD, whereas the remaining nine had organic GHD within a context of hypopituitarism (Table 1Go). All of the patients from the latter group had been treated by surgery alone (n = 6) or associated with radiotherapy (n = 3, nos. 15, 21, and 22; Table 1Go), for pituitary lesions. All of the patients had received GH in the past for a period of 8.9 ± 1.9 yr. Hormone replacement therapy with L-T4 (50–100 µg by mouth daily), cortisone acetate (25–37.5 mg/d), and 1-disamino-ß-D-arginine vasopressin (5–20 µg/d) was given where appropriate. Hypogonadism was treated in boys with testosterone enanthate (250 mg im monthly) and in girls with standard oral estrogen/progestin association. An adequacy of hormone replacement therapy was periodically assessed by serum free thyroid hormones and testosterone and urinary free cortisol together with serum and urinary Na+ and K+ measurements.


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  		TABLE 1. Individual patient profiles at study entry and at the end of the 12-month study

 
At study entry, all of the patients had normal blood pressure and pulse as well as normal adrenal and thyroid function tests; circulating levels of gonadal steroids were appropriate for their age. Ten of the 23 patients had been included in a previous study (26). Informed consent was obtained by the patients or their parents (if the patient was under 18 yr of age), and the study was approved by the local Ethical Committee.

Controls

Twenty-three healthy adolescents (10 boys and 13 girls, aged 15–20 yr) comparable for age (±), sex, pubertal status, BMI (±1) participated in the study as controls. Informed consent was obtained by the patients or their parents (if the patient was aged <18 yr). The patients’ and controls’ profile at study entry is shown in Table 2Go.


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  		TABLE 2. Anthropometrical, endocrine, metabolic, and vascular parameters in 15 adolescent patients with confirmed GHD after retesting (peak GH to ARG+GHRH test, 3.1 ± 1.9 µg/liter) and in eight adolescent patients with no confirmed GHD after retesting (peak GH to ARG+GHRH test, 20.5 ± 1.1 µg/liter) and their age- and gender-matched controls at study entry

 
Treatment protocol

At study entry, the patients received GH replacement at a median dose of 35 µg/kg·d, following the recommendations for the pediatric age. At the restart of the treatment, according to the Consensus Conference that was recently reported (28), all GHD patients received recombinant GH at the starting dose of 8–10 µg/kg·d as suggested for the young adult population. After 3 months, the dose was adjusted, aiming at reaching the 50th percentile of normal serum IGF-I concentrations for sex and age, as previously reported (29, 30). At the end of the study, the median GH dose was 10 µg/kg·d in boys and 12 µg/kg·d in girls; the maximal dose was 11 µg/kg·d in boys and 15 µg/kg·d in girls.

Study protocol

At study entry, all 46 subjects underwent electrocardiogram, systolic and diastolic blood pressure and heart rate measurement, assay of serum IGF-I, total, LDL-, and HDL-cholesterol, triglycerides, glucose, and fibrinogen level, and ultrasonography of the common carotid arteries. The conversion factors (mg/dl to mmol/liter) for lipids and glucose were as follows: cholesterol, 0.02586; triglycerides, 0.01129; and glucose, 0.5551. We also calculated the total/HDL-cholesterol ratio, considered as an index of severe cardiovascular risk (31), and the estimate of insulin resistance by the homeostasis model assessment (HOMA) score, by applying the formula of Matthews et al. (32): fasting serum insulin (µU/ml) x fasting plasma glucose (mmol/liter)/22.5. After 1–3 months of GH withdrawal, retesting of the GH secretory status was performed using the ARG+GHRH test as previously reported (26). According to Aimaretti et al. (23) and our previous studies (33, 34), severe GHD was defined on the basis of a GH peak less than or equal to 9 µg/liter. In GHD patients, IGF-I, total, LDL-, and HDL-cholesterol, triglycerides, and fibrinogen levels and ultrasonography of the common carotid arteries were repeated after 6 months of GH withdrawal and 6 months of restarting GH. In non-GHD patients, IGF-I, total, LDL-, and HDL-cholesterol, triglycerides, and fibrinogen levels and common carotid arteries ultrasonography were repeated after 6 and 12 months of GH withdrawal. A magnetic resonance of the sellar region was performed at study entry and then after 12 months at the end of the study in all GHD patients; no change was observed in the pituitary size.

Carotid ultrasonography

Common carotid arteries ultrasound imaging was carried out with Vingmed Sound CMF 725 equipment (Horten, Norway) by means of a 7.5-MHz annular phased array transducer; the details on the technique were reported elsewhere (20). Right and left carotid arteries were scanned longitudinally, 2.5 cm proximal and 1 cm distal to the bifurcation. When satisfactory B-mode imaging of the common carotid artery wall was achieved, M-mode images were taken for several cardiac cycles to obtain the best quality measurements of IMT. Quantitative and semiquantitative indices were evaluated by echo-Doppler ultrasonography placing the sample volume (set at 75% of lumen caliber) in the middle of the vessel lumen. The variability in the IMT measurement for our instrument was 0.03 mm. Our intra-observer variability for repeated measurements of carotid artery diameter is 0.01 ± 0.02 mm. Flow indices of both carotids were investigated by measuring blood systolic and diastolic peak velocities. The epidemiological data currently available indicate that a value of IMT at or above 1 mm at any age is associated with a significantly increased risk of myocardial infarction and/or cerebrovascular disease (35). The presence, location, and size of plaques were also evaluated at the level of the common carotid arteries. A type IV plaque featured by a thickening of the vascular wall and an increased density of all ultrasonography-detectable layers without any hemodynamic alteration was defined as a well-defined plaque (36).

Assays

Serum GH levels were measured by immunoradiometric assay (IRMA) using commercially available kits (HGH-CTK-IRMA Sorin, Saluggia, Italy). The sensitivity of the assay was 0.2 µg/liter. The intra- and interassay coefficients of variation (CV) were 4.5 and 7.9%, respectively. Plasma IGF-I was measured by IRMA after ethanol extraction. The sensitivity of the assay was 0.8 µg/liter. The normal IGF-I range in adolescent subjects (16–20 yr) is 141 (3rd percentile) to 625 (97th percentile) µg/liter. The 50th percentile of IGF-I levels in our laboratory is 350 µg/liter, calculated in samples taken from 60 healthy adolescents. The intraassay CV was 3.4, 3.0, and 1.5% for the low, medium, and high points on the standard curve, respectively. The interassay CV was 8.2, 1.5, and 3.7% for the low, medium, and high points on the standard curve.

Statistical analysis

Results are expressed as mean ± SD unless otherwise specified. The statistical analysis was performed by SPSS Inc. (Cary, NC) package using nonparametric tests. The comparison between patients and controls was performed by the Wilcoxon matched-pairs test; the comparison between GHD and non-GHD controls was performed by the Mann-Whitney test. The significance was set at 5%. The comparison among baseline and 6 and 12 months in the two groups of adolescents was performed by the Kruskal-Wallis test followed by the Dunn’s test for paired data. The significance was set at 1%.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
Before GH withdrawal (Table 2Go)

Patients were classified as GHD (n = 13) or non-GHD (n = 8) based on the ARG+GHRH test performed 1–3 months after stopping GH replacement (Table 1Go). Non-GHD did not restart GH replacement therapy. Before GH withdrawal, serum IGF-I levels were in the normal range for age in all patients (Table 1Go). They were similar in non-GHD and controls (325.6 ± 33.1 µg/liter vs. 301.6 ± 35.5 µg/liter), lower in both isolated GHD and multiple GHD patients than in controls (198.4 ± 15.7 and 189.2 ± 51.3 vs. 291.0 ± 30.7 µg/liter; P < 0.001) but similar in the two GHD groups (P = 0.33). Compared with controls, before GH withdrawal, GHD adolescents had reduced HDL-cholesterol levels, and increased total/HDL-cholesterol ratio, fibrinogen, LDL-cholesterol, and glucose levels, and non-GHD adolescents had increased glucose, insulin, and HOMA. IMT at the common carotid arteries was similar in GHD and controls and was higher in non-GHD than in controls. Systolic and/or diastolic peak velocities at the common carotid arteries were higher in both GHD and non-GHD patients than in controls.

Six months after GH treatment withdrawal (Table 3Go)

Serum IGF-I levels significantly decreased both in GHD (Fig. 1Go) and in non-GHD adolescents (Fig. 2Go). Only in GHD patients did BMI increase, and lipid profile and insulin resistance were significantly impaired. IMT at the common carotid arteries did not change in GHD patients (Figs. 1Go and 3Go) and significantly decreased in non-GHD patients (Fig. 2Go) and became similar to controls (Fig. 3Go). Systolic and diastolic peak velocities at the common carotid arteries slightly increased in GHD patients, whereas they decreased in non-GHD.


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  		TABLE 3. Endocrine, metabolic, and ultrasonographic parameters in 15 GHD adolescents after retesting (peak GH to ARG+GHRH test, 3.1 ± 1.9 µg/liter) at study entry, after 6 months of GH withdrawal, and 6 months after restarting of GH replacement and in eight adolescent patients with no confirmed GHD after retesting (peak GH to ARG+GHRH test, 20.5 ± 1.1 µg/liter) at study entry and after 6 and 12 months of GH withdrawal

 


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  		FIG. 1. Individual values of serum IGF-I levels (top) and measured mean IMT of right and left common carotid arteries, by ultrasonography (bottom), in the 15 GHD adolescents ({circ}) at study entry, after 6 months of GH withdrawal, and after 6 months of reinstitution of GH replacement and their sex-, age-, and BMI-matched controls (•). Patients with isolated GHD are shown as solid lines; patients with multiple GHD are shown as dashed lines.

 


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  		FIG. 2. Individual values of serum IGF-I levels (top) and measured mean IMT of the right and left common carotid arteries by ultrasonography (bottom), in the eight non-GHD adolescents ({square}) at study entry after 6 and 12 months of GH withdrawal and their sex-, age-, and BMI-matched controls ({blacksquare}).

 


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  		FIG. 3. Measured mean IMT of the right and left common carotid arteries by ultrasonography (bottom) in GHD ({circ}) and non-GHD adolescents ({square}) during the study and their sex-, age-, and BMI-matched controls (•, {blacksquare}) shown as mean ± SD. A, P < 0.01 vs. GHD patients; and B, P < 0.01 vs. controls.

 
Six months after restarting GH treatment in GHD or 12 months after GH withdrawal in non-GHD (Table 3Go)

GH replacement was restarted in the 15 patients who were confirmed to have GHD. The final dose of GH replacement was similar in boys and girls (11.4 ± 2.5 vs. 13.5 ± 3.2 µg/kg·d; P = 0.28); in only one girl with hypopituitarism and receiving oral estro-progestin replacement, the maximal dose was 20 µg/kg·d, higher than that used in boys (Table 1Go). Serum IGF-I levels promptly increased after GH was restarted in GHD patients (Fig. 1Go). However, 6 months after GH was restarted, IGF-I levels were still subnormal in one patient with multiple GHD (no.18, Table 2Go). In non-GHD adolescents, IGF-I levels did not significantly change after 6 months off of GH (Fig. 2Go). Lipid profile and glucose tolerance returned to those measured at study entry in GHD patients and remained unmodified in non-GHD adolescents. However, serum IGF-I and HDL-cholesterol remained lower whereas LDL-cholesterol and total/HDL-cholesterol remained higher than in controls. In non-GHD adolescents, IMT (Fig. 3Go) and systolic and diastolic peak velocities at the common carotid arteries decreased significantly when compared with baseline observations during GH treatment and approximated those of control subjects. In the GHD patients, ultrasonographic parameters did not change, except for a mild decrease in systolic peak velocity that returned to baseline values.


   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
The results of the current prospective study show that the discontinuation of GH replacement in confirmed GHD adolescents impaired lipid profile and insulin resistance without any apparent change of morphological parameters at the common carotid arteries. Six months after restarting GH replacement, the lipid profile and insulin resistance improved, and IGF-I levels normalized in the low-normal range; however, the total/HDL-cholesterol ratio, which is a relevant predictive parameter for cardiovascular risk, still remained slightly higher than in controls. Ultrasonographic parameters of vascular morphology at the common carotid arteries remained unchanged. Interestingly, before GH withdrawal in the adolescents that were not confirmed to have GHD, lipid profile and glucose metabolism were normal, but IMT at both common carotid arteries was increased compared with healthy controls. Twelve months of GH withdrawal in this latter group normalized IMT and systolic and diastolic peak velocities. The results of this short-term study indicate that GH replacement therapy should be continued into adulthood only in severe childhood onset of GHD, to prevent an impairment of cardiovascular risk factors and insulin resistance. Furthermore, special attention should be paid to the patients with partial or isolated GHD, who may not be confirmed to have GHD in adulthood because of potential detrimental effects of GH therapy on major vessels.

An unfavorable lipid profile, increased body fat with decrease of lean body mass, increased peripheral insulin resistance, decreased plasma fibrinolytic activity, abnormal cardiac structure with impaired cardiac performance, and premature atherosclerosis with increased arterial IMT are associated with cardiovascular morbidity and mortality in adult GHD patients (6, 7). GH replacement improves left ventricular morphology and function (7), reduces IMT, and improves endothelial dysfunction (6). GH deprivation for 6 months in severe GHD adolescents (26) and 12 months in severe GHD adults further aggravates cardiac performance (30).

During childhood, reduced growth velocity is an evident clinical end-point of GHD and guides GH replacement, even if it is necessary to confirm the diagnosis by using biochemical testing. Because clear-cut clinical endpoints are lacking in adulthood, the current practice is to stop GH replacement at the final height and to reevaluate the diagnosis of GHD by appropriate GH testing: one third to one half of patients with GHD during childhood do not have persistent severe GHD in adulthood (21, 22, 23). However, discontinuation of GH therapy in adolescents with severe GHD for 6–12 months causes the accumulation of cardiovascular risk factors, such as the increase of total body and abdominal fat mass, decrease of lean body mass, increase of total cholesterol, LDL-cholesterol, lipoprotein-a, and apolipoprotein B, and decrease of HDL-cholesterol, (24, 27) and the impairment of cardiac morphology and performance (26). An impairment of the lipid profile is an early and constant finding of GHD and has been suggested as playing the main role on the coronary risk of GHD patients (37).

To give further insight on the risk of early atherosclerosis in GHD adolescents during GH replacement and withdrawal, we analyzed the classical cardiovascular risk factors and some parameters of the vascular structure and dynamics before and after GH withdrawal and after restarting GH in GHD adolescents. We also compared the results with those obtained in non-GHD adolescents undergoing the same protocol and with the results of sex-, age-, and BMI-matched healthy adolescents. Although we confirmed previous data on the worsening of the lipid profile and insulin sensitivity after GH withdrawal and its improvement after GH reinstitution, we also added some new findings in GHD adolescents. In particular, at the common carotid arteries, we found a normal vascular structure and slightly decreased systolic peak velocity after GH reinstitution. The absence of any alteration of IMT at the common carotid arteries is in agreement with previous findings by Lanes et al. (27) in another cohort of adolescents. However, it is worth noting that non-GHD adolescents showed an increased IMT and systolic and diastolic peak velocities at study entry that returned to normal after 12 months of GH withdrawal. Circulating IGF-I levels play a relevant role on endothelial properties possessing high-affinity binding sites on endothelial cells (38) and increasing nitric oxide (NO) production (39, 40). Decreased NO activity is associated with impaired arterial vasodilator capacity, increased platelet aggregability, and intimal thickening (41), linking GH and IGF-I deficiency with atherosclerosis. GHD patients had decreased NO production that improved after GH replacement (42). Excess GH and IGF-I in acromegaly is also accompanied by a slight increase of IMT (43, 44) and endothelial dysfunction (45, 46) but not, interestingly, by increase of atherosclerotic plaques (43, 47). The evidence that IMT at the common carotid arteries is significantly higher in non-GHD adolescents than in healthy sex-, age-, and BMI-matched controls, in the absence of alterations of the lipid profile, could be explained by a direct effect of a constant but slightly higher IGF-I level during GH treatment in this cohort. It should be mentioned, however, that serum IGF-I levels at study entry and during GH replacement were not different in non-GHD adolescents from those measured in controls. However, IGF-I levels decreased significantly after GH withdrawal, suggesting that they were slightly elevated during GH treatment, even in the accepted normal range for age. Whether these findings could be an expression of a future risk of atherosclerosis in the adolescents diagnosed as GHD and treated with GH during childhood, but not confirmed to maintain GHD in adulthood, cannot be ruled out by our present data.

In conclusion, GH discontinuation in severe GHD adolescents is not followed by significant alterations of the structural parameters at the common carotid arteries and by only a slight decrease of systolic peak velocity, despite alterations of the lipid profile and insulin resistance. These results suggest that increased IMT in the adult GHD population begins later in life or after a longer period of GH deprivation. Interestingly, in the adolescents not confirmed to maintain GHD, IMT at the common carotid arteries was increased during GH treatment and reversed to normal 12 months after GH withdrawal. These results strengthen the recommendation that adolescents with idiopathic GHD be retested for GHD after completion of growth as continued GH replacement in non-GHD subjects could negatively affect endothelial properties, even when IGF-I levels are maintained in the accepted normal range for sex and age. More data are required to understand whether the study of IMT at the common carotid arteries could be an additional parameter to monitor during GH replacement in GHD patients, because it seems to reflect IGF-I activity more than the simple biochemical measurement.


   Acknowledgments
 
We thank Dr. Alfonso Gruosso for the editing of the manuscript.


   Footnotes
 
This study was partially supported by a grant from Regione Campania L. R. (41/94, 1999, no.7492) and by a grant of the Italian Minister of Research and University in Rome (no. 2003069821, 2003).

First Published Online February 15, 2005

Abbreviations: ARG+GHRH, Arginine plus GHRH; BMI, body mass index; CV, coefficient of variation; GHD, GH deficient; HDL, high-density lipoprotein; HOMA, homeostasis model assessment; IMT, intima-media thickness; IRMA, immunoradiometric assay; LDL, low-density lipoprotein.

Received September 17, 2004.

Accepted January 28, 2005.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

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