| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Molecular and Clinical Endocrinology and Oncology (A.Co., C.D.S., M.F., F.R., S.S., G.L.), and Biomorphological and Functional Sciences and Nuclear Medicine Centre of the National Council of Research (A.Cu., W.A., M.S.), "Federico II" University of Naples, 80131 Naples, Italy
Address all correspondence and requests for reprints to: Annamaria Colao, M.D., Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University, via S. Pansini 5, 80131 Napoli, Italy. E-mail: colao{at}unina.it.
 |
Abstract |
|---|
 Top Abstract IntroductionPatients and MethodsResultsDiscussionReferences |
|---|
Compared with controls, decreased left ventricular ejection fraction at rest was found only in severe GHD patients (55.0 ± 8.8 vs. 63.4 ± 4.5%, P < 0.001); decreased left ventricular ejection fraction response on effort in severe (–4.6 ± 17.4 vs. 15.2 ± 9.1%, P < 0.001) and partial GHD patients (3.6 ± 6.6 vs. 14.6 ± 8.3%, P < 0.001); decreased diastolic filling at rest in severe (2.53 ± 0.68 vs. 3.01 ± 0.48 end-diastolic volume per second, P < 0.001) and partial GHD (2.61 ± 0.45 vs. 2.89 ± 0.54 end-diastolic volume per second, P = 0.004) patients; and decreased exercise duration and capacity in all the patient groups. A normal systolic performance on effort was found in 21.4% of severe GHD, 55.6% of partial GHD, all non-GHD, and 93.7% of controls. A normal diastolic filling at rest was found in 57.1% of severe GHD, 74.1% of partial GHD, 76.5% of non-GHD, and 90% of controls.
In conclusion, cardiac performance is correlated with the GH status because significant impairment was found in patients with severe and partial GHD but not in non-GHD hypopituitary patients.
|
Introduction |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
By echocardiography, in GHD patients with childhood-onset disease, reduced cardiac mass with an impaired systolic function was found in some but not all studies (6). By equilibrium radionuclide angiography, which enables a more accurate estimation of cardiac performance on effort, we found an impaired left ventricular (LV) ejection fraction (LVEF), considered a main parameter of systolic function in the vast majority of GHD adults (10). Interestingly, reduced cardiac size was a more common finding in young patients with childhood-onset GHD (11, 12) and in children (13, 14) than in the adults, whereas impaired cardiac performance was not correlated with patients’ age and was found in young (10), middle-aged (10), and elderly (15) patients. To further confirm a direct role of GHD in determining cardiac dysfunction, GH replacement was shown by us (14, 16, 17, 18, 19) and others (11, 13, 20, 21, 22, 23) to improve LVEF. Of note, adult GHD patients not receiving GH replacement were reported to have a further impairment of cardiac performance (18) and increased intima-media thickness at common carotid arteries (22). Furthermore, in severe GHD adolescents, withdrawal from GH replacement was followed by decreased cardiac size and reduced cardiac performance that were promptly reversed by GH treatment reinstitution (19).
We did previously show that the severity of GHD, measured as peak GH after the combined GHRH plus arginine (ARG) test, was correlated with the degree of abnormality of lipid profile (24) and bone loss (25). Of particular interest was the finding that patients with a GH peak after GHRH+ARG test between the first and the third percentile of normal according to Aimaretti et al. (26) and so diagnosed as having partial GHD showed abnormalities in lipid profile (24), body composition (24), and bone density (25) in between the patients with severe GHD and those without GHD. Our previous findings have been recently confirmed by Murray et al. (27) using the insulin tolerance test: these authors showed that adults with partial GHD (GH peak after insulin tolerance test between 3–7 µg/liter) have abnormal body composition similar to GHD and that the degree of this abnormality lied between that of healthy subjects and GHD adults and correlated with the IGF-I level.
To investigate whether the severity of GHD is also correlated with the degree of cardiac impairment and whether patients with partial GHD or even with some degree of pituitary dysfunction without GHD have alterations of cardiac performance, we designed this observational, case-control study. Cardiac performance, at rest and at peak exercise, was evaluated by equilibrium radionuclide angiography in 100 hypopituitary patients, each of them matched for gender and age with a healthy control. We considered as primary end point systolic performance, measured as LVEF at rest and at peak exercise and as secondary end points diastolic filling, measured as peak filling rate (PFR); hemodynamics, measured as heart rate; systolic (SBP) and diastolic blood pressure (DBP); and exercise performance, measured as duration and capacity of maximal physical exercise at cycloergometer. To avoid interference by obesity in this analysis, patients with body mass index (BMI) above 30 kg/m2 were excluded.
|
Patients and Methods |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
One hundred nonobese hypopituitary patients (44 men, 56 women, aged 18–75 yr) diagnosed at the Department of Molecular and Clinical Endocrinology and Oncology of the University "Federico II" of Naples were included in this study. Exclusion criteria were: 1) present or previous concomitant diseases affecting cardiac function, such as chronically uncontrolled diabetes mellitus, coronary artery diseases, long-standing hypertension, or hyperthyroidism (n = 22); 2) abnormal renal and/or hepatic function (n = 1); and 3) BMI above 30 kg/m2 (n = 19). All patients had been previously operated on by transsphenoidal and/or transcranic route for nonfunctioning pituitary adenoma, meningioma, or craniopharyngioma. Sixteen patients had also been irradiated 3–7 yr before receiving testing for GHD. Before entering the study, the patients had undergone replacement therapy with L-thyroxine (50–100 µg orally daily), cortisone acetate (25–37.5 mg/d), intranasal desmopressin (5–20 µg/d), testosterone-enanthate (250 mg im monthly) in men, and oral and/or transdermal estrogens associated with progesterone in premenopausal females, as appropriate. Adequacy of hormone replacement therapy was periodically assessed by measuring serum free thyroid hormones, testosterone, urinary free cortisol and blood pressure, and serum Na+ and K+ measurements. At study entry, these hormonal parameters were in the normal range for age in all patients. None of the patients had ever received GH treatment. Sixty-eight patients were nonsmokers, whereas the remaining were mild smokers (less than 15 cigarettes/day).
Controls
Eighty nonobese (BMI < 30 kg/m2) healthy subjects were recruited among the medical and paramedical personnel of our department and their relatives and agreed to serve as controls: they were matched with the patients for age (±1 yr) and gender. Twenty healthy subjects served as case-control for two patients. The protocol of the study was approved by the Ethical Committee of the "Federico II" University of Naples, and all subjects gave their informed consent to the study. Fifty-five controls were nonsmokers (68.7%), whereas the remaining were mild smokers (less than 15 cigarettes/day). Patients’ and controls’ profile, according to the diagnosis of GHD, at study entry is shown in Table 1
.
|
At study entry, in all cases we measured IGF-I levels and performed the GHRH+ARG test. ARG (arginine hydrochloride, Salf, Bergamo, Italy) was given at the dose of 0.5 g/kg, up to a maximal dose of 30 g, slowly infused from time 0 to 30 min, whereas GHRH (1–29, Geref, Serono, Rome, Italy) was given at the dose of 1 µg/kg as iv bolus at time 0. Blood samples were taken every 15 min from –15 up to 90 min. Accordingly with previous findings in normal nonobese population (26), the GH response after ARG+GHRH was classified as follows: severe GHD when GH peak was less than 9 µg/liter, partial GHD when GH peak was 9.1–16.5 µg/liter, and normal GH response when GH peak was 16.5 µg/liter or more. According to these criteria, 56 patients had severe GHD, 27 patients had partial GHD, and 17 patients with normal GH response were classified as non-GHD. All controls had a normal GH response to the test. Within 7–15 d from GH testing, all subjects were evaluated for cardiac performance by equilibrium radionuclide angiography. Heart rate and SBP and DBP were measured during the procedure by expert nuclear medicine physicians (W.A., A.Cu.), unaware whether studying a hypopituitary or a control subject.
Equilibrium radionuclide angiography
In vivo labeling of red blood cells was performed with 555 MBq (15 mCi) 99mTc. Radionuclide angiography was performed at rest and during dynamic physical exercise as previously described (15, 16, 17, 18). A small field of view 
-camera (Starcam 300 A/M, General Electric, Milwaukee, WI) equipped with a low-energy, all-purpose collimator was used. Exercise studies were performed using a bicycle ergometer with a restraining harness to minimize patient motion under the camera. In all 180 subjects, exercise loads were increased by 25 W every 2 min until angina, limiting dyspnea, or fatigue developed. Heart rate, SBP, and DBP were monitored during exercise at each stage. None of the controls or hypopituitary patients developed high-grade ventricular arrhythmias necessitating termination of exercise; eight patients (8%) could not perform exercise due to very early muscular exhaustion. Radionuclide angiography studies were analyzed using a standard commercial software system (General Electric). LV regions of interest were automatically drawn for each frame, and a background region of interest was also computer delineated on the end systolic frame. After background correction, a LV time-activity curve was generated. Indexes of LV were derived by computer analysis of the background-corrected time-activity curve. LVEF was computed on the basis of relative on end-diastolic and end-systolic counts. Peak LV ejection and filling rates were also calculated after a Fourier expansion with four harmonics. PFR was computed as the maximum positive peak after end systole on the first derivative of LV time-activity curve and was computed in LV counts per second, normalized for number of counts at end diastole and expressed as end-diastolic volume (EDV) per second. Normal ranges were: PFR 2.5 or more EDV/sec; LVEF at rest 50% or more; exercise-induced changes of LVEF (
LVEF) an increase of 5% or more of LVEF at peak exercise, compared with resting values.
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 (CVs) 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 20–40, 41–60, and over 60-yr-old subjects was 110–494, 100–300, and 78–260 µg/liter, respectively. The intraassay CVs were 3.4, 3.0, and 1.5% for low, medium, and high point on the standard curve, respectively. The interassay CVs were 8.2, 1.5, and 3.7% for low, medium, and high point on the standard curve.
Statistical analysis
The statistical analysis was performed by the SPSS package (SPSS Inc., Chicago, IL). Data are reported as mean ± SD unless otherwise specified. Comparison between patients and controls was performed by the Mann-Whitney U test. Comparison among severe, partial, and non-GHD groups was performed by the Wilcoxon followed by the Dunn test. Significance was set at 5%. Categorical variables were compared using the Pearson’s 
2 test. Correlation coefficients were calculated by measuring the Pearson coefficient. The stepwise multiple linear regression was performed to evaluate the relative importance of age, BMI, peak GH after GHRH+ARG, IGF-I levels, and z-score of IGF-I on primary (LVEF at rest and at peak exercise) and secondary end points (PFR at rest and at peak exercise, SBP and DBP at rest and at peak exercise, heart rate at rest and at peak exercise, exercise duration and performance). In this analysis, we entered only those variables that had a P < 0.01 in the univariate analysis.
|
Results |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
). Serum IGF-I levels were lower than in controls in not only severe GHD but also partial GHD and non-GHD patients (Table 1). In both patients and controls, the GH peak to GHRH+ARG was correlated with age (r = –0.28, P = 0.005; r = –0.28, P = 0.004), BMI (r = –0.31, P = 0.001; r = –0.20, P = 0.041), and IGF-I levels (r = 0.84, P < 0.0001; r = 0.29, P = 0.003). Primary end point: GH peak after GHRH+ARG test vs. systolic performance
In both patients and controls, the GH peak to GHRH+ARG was correlated with LVEF at rest (r = 0.28, P = 0.004; r = 0 .35, P = 0.0004) and at peak exercise (r = 0.57, P < 0.0001; r = 0.45, P < 0.0001) as well as with LVEF (Fig. 1). Patients with severe GHD (55.0 ± 8.8 vs. 63.4 ± 4.5%, P < 0.001) and partial GHD (57.7 ± 3.7 vs. 61.9 ± 4.4%, P = 0.01), but not non-GHD, had significantly lower LVEF at rest than controls (Fig. 2, top). Normal LVEF at rest was found in 44 severe GHD patients (78.6%) and all partial GHD and non-GHD patients and controls. LVEF response at peak exercise was significantly lower in severe (53.2 ± 9.4 vs. 72.4 ± 7.4%, P < 0.001) and partial GHD patients (59.6 ± 2.0 vs. 71.1 ± 7.4, P < 0.001) than in controls and non-GHD (Fig. 2, middle). Non-GHD patients had a LVEF response at peak exercise similar to controls (70.9 ± 5.2 vs. 73.5 ± 5.9, P = 0.18). Eight patients with severe GHD could not perform the exercise test due to muscular exhaustion. A normal LVEF response at peak exercise was found in 12 severe GHD (21.4%), 15 partial GHD (55.6%), all non-GHD (100%), and 75 controls (93.7%, P = < 0.01). So LVEF was significantly lower in severe (–4.6 ± 17.4 vs. 15.2 ± 9.1%, P < 0.001) and partial GHD (3.6 ± 6.6 vs. 14.6 ± 8.3%, P < 0.001) but not in non-GHD patients (16.4 ± 6.8 vs. 17.0 ± 10.8%, P = 0.53) than in controls. LVEF in severe and partial GHD patients was significantly lower than in non-GHD patients (P < 0.001; Fig. 2, bottom).
|
|
Diastolic filling. In both the patients and controls, the GH peak to GHRH+ARG was correlated with PFR at rest (r = 0.36, P = 0.0002 and r = 0.21, P = 0.031) and at peak exercise (r = 0.39, P = 0.0001 and r = 0.47, P < 0.0001). Normal PFR at rest was found in 32 severe GHD (57.1%), 20 partial GHD (74.1%), and 13 non-GHD patients (76.5%) and 72 controls (90%, P < 0.0001). PFR at rest and at peak exercise was significantly lower in severe GHD patients than in controls and non-GHD patients (Table 2). Individual values of PFR in different groups are reported in Fig. 3.
|
|
).
Exercise performance. In both the patients and controls, the GH peak to GHRH+ARG was correlated with exercise duration (r = 0.46, P < 0.0001 and r = 0.52, P < 0.0001) and capacity (r = 0.41, P < 0.0001 and r = 0.20, P = 0.043). Exercise duration was significantly lower in all the patient groups than controls and was significantly lower in severe and partial GHD than in non-GHD (Table 2, P < 0.01). Exercise capacity was significantly lower in all patient groups than their controls and was significantly lower in severe GHD than in non-GHD (Table 2, P < 0.001).
Results of the stepwise multiple linear regression (Table 3)
The GH peak after GHRH+ARG and/or IGF-I levels were the best predictors of LVEF at rest, LVEF, and exercise duration and capacity in both groups. In only the patients, IGF-I was the best predictor of PFR, whereas in the controls best predictor of PFR was BMI.
|
|
Discussion |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
Several studies showed that patients with GHD have impaired cardiac performance (5, 6) both in resting conditions and on effort. We had previously demonstrated that adult patients with GHD have impaired systolic and diastolic performance (10, 15), partially reversed by 1-yr GH replacement at low doses (17) and further aggravated by 1 yr of GH deprivation (18). Slight but significant impairment of systolic and diastolic functions was also found in adolescent patients with severe GHD undergoing withdrawal of GH replacement at the achievement of final stature (19). However, although GH replacement improves cardiac performance (11, 14, 16, 17, 18, 19, 20, 21, 22, 23), its final beneficial effect on cardiovascular and cerebrovascular mortality in GHD patients is still to be proven. In fact, despite the wide number of experimental evidences linking GHD to cardiac derangement (5, 6), the increased mortality of hypopituitary patients is considered to be due more likely to other negative factors, such as previous radiotherapy, glucocorticoid and thyroid hormone overreplacement, or gonadal steroid underreplacement (1, 2, 3, 4). In particular, radiotherapy can have also direct effects in inducing cerebrovascular mortality, as suggested by a recent study in the cohort of patients with acromegaly (28). Radiotherapy had been performed several years before entering the study in 16 of the 100 patients: 14 of the 16 were classified as severe GHD and two as partial GHD. Gleeson et al. (29) recently reported that cranial irradiation during childhood for cancer does not inevitably cause severe GHD in adulthood and that these patients require retesting. Our patients were all diagnosed after the age of 16 yr, after their final height had been achieved, and were tested 3–7 yr after radiotherapy so that the diagnosis is likely to be appropriate. Of the two irradiated patients with partial GHD, one was a 20-yr-old woman who received radiotherapy 3.5 yr before entering the study, with a peak GH after GHRH+ARG of 10.5 µg/liter and an IGF-I z-score of –1.2, and the other was a 33-yr-old man who received radiotherapy 4 yr before entering the study, with a peak GH after GHRH+ARG of 13.5 µg/liter and an IGF-I z-score of –0.75. It should be mentioned, however, that the most recent study focusing on the mortality of hypopituitary patients (4) could not demonstrate any effect of GHD on mortality, probably due to the limited number of cases undergoing diagnostic testing for GHD. This is not surprising considering that the GHD syndrome in adult subjects has been described only in the past 15 yr.
The GHD syndrome is characterized by a cluster of detrimental factors for the cardiovascular system, i.e. high cholesterol levels, low high-density lipoprotein-cholesterol levels, high body fat mass, low muscle mass and performance, endothelial dysfunction, and precocious atherosclerosis (5, 6, 7, 8, 9). To diagnose GHD in adult patients, the insulin tolerance test (ITT) and GHRH+ARG test are considered gold standards (30). In particular, it is relevant to note that the first percentile of normal response to ITT gives a threshold value of 3 µg/liter, whereas the identical threshold of the GHRH+ARG test is 9 µg/liter (26). This broader range to establish GHD by the more potent GHRH+ARG test enables a more accurate estimation of the severity of GHD. In fact, by using the GHRH+ARG test, we demonstrated that the GH response correlated with the severity of lipid abnormalities (24), alterations of body composition (24), and bone loss (25). BMI has recently been shown to affect the GH response to the GHRH+ARG test. In fact, Biller et al. (31) compared five different GH stimulation tests for diagnosing adult GHD in patients with pituitary diseases and healthy controls matched with the patients for age, sex, BMI, and estrogen use. They reported a GH peak cut-off to discriminate GHD patients and controls of 4.1 µg/liter, so it was lower than that reported by Aimaretti et al. (26) of 9 µg/liter. However, in the U.S. series, both patients and controls had a higher BMI than the patients we studied in the past (24, 25) as well as those included in the present study. To keep our old diagnostic criteria (24, 25), also considering the results of the U.S. series (31), in the current study, we excluded the patients with a BMI 30 kg/m2 or more: this should have ruled out any effect of obesity in determining the alterations of cardiac and exercise performance. In line with Biller et al. (31), in our series the GH peak after GHRH+ARG was significantly correlated with BMI in both the patients and controls, although in these latter, the correlation was faint.
In this study, we show that GHD has clear-cut negative effects on systolic performance, diastolic filling, and ability to perform physical exercise. The severity of GHD, measured as GH peak to GHRH+ARG test, was correlated with the severity of systolic impairment, measured as LVEF on effort, and diastolic performance, measured as PFR. Besides, the GH peak to GHRH+ARG was also correlated with LVEF in our controls: this result was likely due to the fact that there is an important effect of age in determining a higher GH response and a higher LVEF in the young than middle-aged and elderly subjects. However, because the results were analyzed in an age-matched, case-control study, the effect of age was irrelevant in the observed difference between the patients and controls. Interestingly, the patients having other pituitary deficiencies but GH, thus classified as non-GHD, and receiving appropriate hormone replacement according to current clinical practice had a normal cardiac performance and an impaired exercise performance. These data, even if collected in a still small series of patients, indicate that the current replacement therapies with gonadal steroids, glucocorticoids, and thyroid hormones do not negatively affect cardiac performance. It is relevant to note that the patients with a GH peak to GHRH+ARG between 9 and 16.5 µg/liter, the first and third percentile of normalcy according to Aimaretti et al. (26), had impaired systolic, diastolic, and exercise performance, compared with healthy controls, like the patients with severe GHD, but impairment was less relevant than these latter. Recently Murray et al. (27), using the ITT, have also shown that adults with partial GHD, by a GH peak after ITT between 3 and 7 µg/liter, have abnormal body composition similar to the patients with severe GHD. These findings, which agree with our previous results (24, 25), suggest that patients with partial GHD should be carefully followed up and eventually retested to further investigate the clinical implications of reduced GH secretion.
In conclusion, GHD is characterized by an impairment of cardiac performance demonstrated by an abnormal response of the LVEF and an inadequate diastolic filling. The prevalence of systolic and diastolic derangement is higher in patients with severe GHD than in those with partial GHD. Patients with a normal GH response to the GHRH+ARG test have a normal cardiac performance. These results further substantiate the detrimental effect of GHD on the heart and indicate that the GHRH+ARG test is a reliable method to investigate the GH deficiency in adults because its results correlate with clinical end points, such as cardiac and exercise performance.
|
Footnotes |
|---|
Abbreviations: ARG, Arginine; BMI, body mass index; CV, coefficient of variation; DBP, diastolic blood pressure; EDV, end-diastolic volume; GHD, GH deficiency; IRMA, immunoradiometric assay; ITT, insulin tolerance test; LV, left ventricular; LVEF, LV ejection fraction; LVEF, change of LVEF; PFR, peak filling rate; SBP, systolic blood pressure.
Received June 2, 2004.
Accepted September 21, 2004.
|
References |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  J. Gibney, M.-L. Healy, and P. H. Sonksen The Growth Hormone/Insulin-Like Growth Factor-I Axis in Exercise and Sport Endocr. Rev., October 1, 2007; 28(6): 603 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. di Iorgi, A. Secco, F. Napoli, C. Tinelli, A. Calcagno, N. Fratangeli, L. Ambrosini, A. Rossi, R. Lorini, and M. Maghnie Deterioration of Growth Hormone (GH) Response and Anterior Pituitary Function in Young Adults with Childhood-Onset GH Deficiency and Ectopic Posterior Pituitary: A Two-Year Prospective Follow-Up Study J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 3875 - 3884. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Devin, L. S. Blevins Jr., D. K. Verity, Q. Chen, J. R. Bloodworth Jr., J. Covington, and D. E. Vaughan Markedly Impaired Fibrinolytic Balance Contributes to Cardiovascular Risk in Adults with Growth Hormone Deficiency J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3633 - 3639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Brabant, A. Krogh Rasmussen, B. M. K. Biller, M. Buchfelder, U. Feldt-Rasmussen, K. Forssmann, B. Jonsson, M. Koltowska-Haggstrom, D. Maiter, B. Saller, et al. Clinical Implications of Residual Growth Hormone (GH) Response to Provocative Testing in Adults with Severe GH Deficiency J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2604 - 2609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Murray, M. Bidlingmaier, C. J. Strasburger, and S. M. Shalet The Diagnosis of Partial Growth Hormone Deficiency in Adults with a Putative Insult to the Hypothalamo-Pituitary Axis J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1705 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Marzullo, C. Marcassa, R. Campini, E. Eleuteri, A. Minocci, L. Priano, P. Temporelli, A. Sartorio, R. Vettor, A. Liuzzi, et al. The Impact of Growth Hormone/Insulin-Like Growth Factor-I Axis and Nocturnal Breathing Disorders on Cardiovascular Features of Adult Patients with Prader-Willi Syndrome J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5639 - 5646. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
), the 27 patients with partial GHD (
) and their controls (
), and the 17 non-GHD patients (
) and their controls (
). The interrupted lines indicate the normal threshold of 50% for LVEF at rest and 5% of 