Effect of growth hormone treatment on diastolic function in patients who have developed growth hormone deficiency after definitive treatment of acromegaly

Abstract

Objective: Although growth hormone (GH) replacement is prescribed for patients with hypopituitarism due to many etiologies, it is not routinely prescribed for patients with GH deficiency (GHD) after cure of acromegaly (acroGHD). This study was designed to investigate the effect of GH replacement on cardiac parameters in acroGHD.

Design: We prospectively evaluated for 12months 23 patients with acroGHD: 15 subjects on GH replacement and eight subjects not on GH replacement. Main outcome measures included LV mass corrected for body surface area (LVM/BSA) and measures of diastolic dysfunction (E/A ratio and deceleration time), as assessed by echocardiography.

Results: After 12months of follow-up, there were no differences between the GH-treated group and the untreated group in LVM/BSA (GH: 74.4±22.5g/m(2) vs untreated: 72.9±21.3g/m(2), p=0.89), E/A ratio (GH: 1.21±0.39 vs untreated: 1.08±0.39, p=0.50) or deceleration time (GH: 224.5±60.1ms vs untreated: 260±79.8ms, p=0.32). The overall degree of diastolic function was similar between the groups with 42.9% of untreated subjects and 50% of GH-treated subjects (p=0.76) classified as having normal diastolic function at follow-up.

Conclusions: There were no significant differences in LVM/BSA or parameters of diastolic function in patients with a history of acromegaly treated for GHD as compared to those who were untreated. These data are reassuring with respect to cardiovascular safety with GH use after treatment for acromegaly, although further longer term study is necessary to evaluate the safety and efficacy of GH treatment in this population.

Keywords: Acromegaly; Cardiovascular risk; Diastolic dysfunction; Growth hormone deficiency.

Figure 1. Left ventricular mass corrected for body surface area (LVM/BSA) in women (Panel A) and men (Panel B) at baseline and follow-up

The horizontal lines encompass the normal range for LVM/BSA and the vertical line separates the GH groups from the untreated group. Panel A: At baseline two female subjects (both on GH) had elevated LVM/BSA values and one normalized at follow-up. Two additional female patients had normal LVM/BSA at baseline which dropped to below normal range at follow-up. One of these subjects was on GH and one was untreated. Subjects 1, 2 and 10 were not on GH at the time of the baseline visit. Panel B: At baseline, five of the male patients had an elevated LVM/BSA (two in the GH group and three in the untreated group) and of these one in the GH group and two in the untreated group had normal values at follow-up. One male subject in the GH group with a normal baseline LVM/BSA had an elevated value at follow-up. Subjects 1,2 and 3 were not on GH at the time of the baseline visit.

Figure 2. E/A ratio in the untreated subjects (Panel A) and the GH treated subjects (Panel B) at baseline and after 12 months follow-up

The horizontal lines encompass the normal range for the E/A ratio. A low E/A ratio is suggestive of impaired relaxation and an elevated ratio suggests restrictive filling. Panel A: In the untreated group, six subjects had an abnormal E/A ratio at baseline and one normalized at the time of the follow-up visit. Panel B: In the GH group, seven subjects had an abnormal E/A ratio at baseline and four of these subjects (#1,3,4 and 15) were not on GH at the time of the baseline visit. Two subjects who started GH after the baseline visit had normalization of their E/A ratio at follow-up (# 1 and 3). Two subjects with a normal E/A ratio at baseline had an elevated value – suggestive of restrictive filling -- at follow-up (subjects 5 and 9) and one subject had a normal E/A ratio at baseline and had a low value – suggestive of impaired relaxation -- at follow-up (subject 14); this subject had been on GH for 166 months at the time of the follow-up visit. Subjects 1–5 and 15 were not on GH at the time of the baseline visit.

Figure 3. Deceleration times in the untreated subjects (Panel A) and the GH treated subjects (Panel B) at baseline and after 12 months follow-up

The horizontal lines encompass the normal range for the deceleration time. A low deceleration time is suggestive of restrictive filling and an elevated time suggests impaired relaxation. Panel A: In the untreated group, two subjects had elevated deceleration times at baseline which remained elevated at follow-up and an additional two had baseline normal deceleration times and elevated times at follow-up; 57% of subjects had an abnormal deceleration time at follow-up. Panel B: In the GH group, four subjects had an abnormal deceleration time at baseline and three of these subjects (# 1, 5 and 15) were not on GH at the time of their baseline visit and the fourth subject (#10) had only been on GH for 1.6 months at the time of the baseline visit. Two of these subjects (#1 and 15) had normalization of their deceleration time at follow-up, whereas the other two had elevated times at follow-up. One subject (# 2) had a normal deceleration time at baseline and a low time – suggestive of restrictive filling -- at follow-up and an additional four subjects had normal deceleration times at baseline and elevated times at follow-up; 50% of subjects in the GH group had an abnormal deceleration time at follow-up. Subjects 1–5 and 15 were not on GH at the time of the baseline visit.