Fifty-four consecutive Caucasian patients, 28 women and 26 men, aged 45.9 ± 13.1 (range 19–67), with adult-onset GHD were enrolled from January 2000 to May 2005. The main diagnosis in these patients was pituitary adenomas in 26 (48.2%), empty sella in 15 (27.8%), previous pituitary inflammation in 3 (5.5%), cranio-pharyngioma in 2 (3.7%). The pathogenesis was not identified in 8 patients (14.8%).

Isolated GHD was observed in 16 patients (29.6%). Of the 31 patients with adenomas, inflammation or cranio-pharyngioma, 25 had undergone surgery and 10 also received radiotherapy.

The diagnosis of GHD was based on the decreased GH responsiveness (GH-peak) to pyridostigmine + GH releasing-hormone stimulation (oral administration of pyridostigmine 120 mg, followed, after 60 minutes, by GH-RH 100 ng/mL iv) and circulating IGF-I levels 24.

The GHD patients were divided into 2 groups based on the response to test : GH-peak was < 3 ng/mL in 38 patients (group A, severe GHD), and 3 to 17 ng/mL in 16 (group B, mild GHD).

Circulating IGF-1 was also tested in the GHD population. The normality range had been previously established in our Institution as follows: a) 131–384 ng/mL in patients aged 18 to 35, b) 100–312 ng/mL in those aged 36 to 50, and c) 106–270 ng/mL in over 50s.

Free triiodothyronine (FT3) and thyroxine (FT4) were measured in all the study population.

The onset of GHD (GHD length) was identified on the basis of clinical history (first diagnosis of pituitary disease, prior surgery, and, if any, previous chemical assays).

On admission, each patient underwent clinical evaluation, including measurements of weight, height, body mass index (BMI), sitting blood pressure, heart rate, standard 12-lead electrocardiography and Doppler echocardiography.

Acute coronary syndrome, previous myocardial infarction, congestive heart failure, congenital heart disease, ventricular arrhythmias, asthma, cancer, severe renal and hepatic dysfunction were all considered as exclusion criteria.

The assessment of high blood pressure was carried out in accordance with the current guidelines 25. Patients who showed mild-to-moderate hypertension were included in the study. The final study group was compared to an age- and weight-matched control group of 20 subjects with no history of cardiac disease, from the same geographic region.

Transthoracic Doppler echocardiography was performed with a commercial ultrasound unit equipped with 2.5–3.5 MHz transducers in harmonic imaging. Patients were examined in the left lateral supine decubitus after 15 minutes resting by an experienced physician, and data stored on magneto-optical disks.

Left ventricular end-diastolic/end-systolic diameters, interventricular septum (IVS) and posterior wall (PW) thickness, absolute and indexed LV mass (LVM and LVMi), relative wall thickness (RWT = IVS + PW thickness/LV end-diastolic diameter), endocardial and midwall fractional shortening (EFS and MFS) were measured according to recommendations of the American Society of Echocardiography and other studies 21222627.

Based on the relationship between LVMi and RWT, using the cut-off values of 125 g/m² for LVMi and 0.45 for RWT, both in men and women, the following geometric models were identified: normal geometry, for RWT≤0.45 and LVMi≤ 125 g/m²; concentric remodeling, for RWT>0.45 and LVMi≤125 g/m²; eccentric hypertrophy, for RWT≤0.45 and LVMi>125 g/m²; and concentric hypertrophy, for RWT>0.45 and LVMi>125 g/m² 20212223.

The general distribution of LVM and LVMi in the GHD population was also recognised, and 3 different categories based on 2 median values were identified.

Once no wall motion abnormalities were found, LV ejection fraction was calculated by the single-plane Simpson rule method (LV diastolic volume – LV systolic volume/LV diastolic volume) from the 4-chamber apical view.

Diastolic function was evaluated by Doppler sampling at LV inflow [trans-mitral valve blood flow sampling: early (E) and late (A) peak velocity, E/A ratio, E-wave deceleration time] and the upper right pulmonary vein outflow [systolic (S) and diastolic (D) velocity, S/D ratio, and reverse atrial velocity (Ap)], in accordance with the current European guidelines 28.

Continuous variables are expressed as mean ± SD, except for data expressed in percents (%). Exact Fisher test, analysis of variance with either Scheffé, Kruskal-Wallis, or chi-squared test when appropriate, were used to check the between-group differences.

Subjects' median age identified the age-related differences in LVM and LV systolic/diastolic functional parameters, and the differences were checked out by Student-T test. Linear correlation between LVMi and IGF-I and GH-peak was performed and a multivariate analysis was done in order to establish the main determinants of LVMi in the whole GHD population. The null hypothesis was rejected at 2 tails for p < 0.05 (95% CI).

Demographic and clinical characteristics of the study population are displayed in Table 1. With the exception of GH-peak and circulating IGF-1 (both lower in group A than in B, p < 0.0001 and < 0.05, respectively), there were no significant differences in basal values.

A higher, but not significant, number of females was present in group B (68.7%) than in A (39.5%) and C (55%).

Growth hormone deficiency length was established from 8 to 384 months (mean value 154 ± 115 months).

At entry, some patients were already treated with specific substitutive hormone for hypothyroidism (n = 29, 53.7%), hypogonadism (n = 26, 48.1%), hyposurrenalism (n = 25, 46.3%) and diabetes insipidus (n = 5, 9.2%), alone or in combination. Thus, FT3 and FT4 serum levels were comparable among the 3 groups.

Standard 12-lead ECG showed normal sinus rhythm in each patient, with no evidence of significant arrhythmias (atrial fibrillation, atrial flutter, premature ventricular beats >100/h, non-sustained tachycardia) and/or ST-T wave abnormalities suggestive of coronary artery disease.

Basal echocardiographic findings are displayed in Table 2. The main difference regarded the higher prevalence of extra-pericardial fat deposit in GHD patients than in controls (p < 0.001).

Average values of LVM/LVMi were comparable among the groups. Figure 1 also shows the median-related distribution of LVM and LVMi in 3 categories (LVM <168 g, 168–244 g, >244 g, and LVMi <98 g/m², 98–133 g/m², >133 g/m²) for each study group. More than 70% of patients with severe GHD had LVM < 244 g and LVMi < 133 g/m².

No significant age-related difference in LVMi, RWT, and systolic functional parameters was observed within the GHD group (Figure 2). Only a decrease in mitral E/A ratio was consistent with age, the same as reported in the general population 28.

Analysis of the LV geometric remodeling showed that the majority of GHD patients and controls had "normal geometry". Twelve GHD patients (10 with severe deficiency) showed "eccentric hypertrophy" (22.2% vs 15.0% in controls, NS). One patient from group A had "concentric remodeling" and another from the same group had "concentric hypertrophy" (Figure 3).

Four out of the 12 GHD patients with "eccentric hypertrophy" (33.3%), the patient with "concentric remodeling" and 1/3 of controls with "eccentric hypertrophy" (33.3%) suffered from systemic hypertension (NS).

However, in comparison with the GHD patients with low-normal LVM/LVMi (n = 41), those with high cardiac mass (n = 13) showed greater systolic blood pressure (131.7 ± 16.3 vs 118.2 ± 16.9 mmHg in the former group, respectively; p = 0.02) and diastolic blood pressure (81.3 ± 7.1 vs 74.8 ± 11.0 mmHg, respectively; p = 0.06), measured on admission.

Overall, there was a moderate, but significant, correlation between LVMi and circulating IGF-I in the whole GHD population (r 0.39, p < 0.005), and particularly in group A (r 0.49, p < 0.002) (Figure 4). And IGF-1 was confirmed to be the main determinant for LVMi at multivariate analysis (Table 3).

Colour-flow mapping and Doppler sampling allowed identification of trivial mitral valve regurgitation in 31 patients from group A (81.6%), 13 from group B (92.8%), and 17 from group C (85%) (NS).