Cardiomyopathy
Echocardiographic dimensions and function in adults with primary growth hormone resistance (Laron Syndrome)

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Abstract

Patients with primary growth hormone (GH) resistance—Laron Syndrome (LS)—have no GH signal transmission, and thus, no generation of circulating insulin-like growth factor-I (IGF-I), and should serve as a unique model to explore the controversies concerning the long-term effect of GH/IGF-I deficiency on cardiac dimension and function. We assessed 8 patients with LS (4 men, 4 women) with a mean ( ± SD) age of 38 ± 7 years (range 22 to 45), and 8 aged-matched controls (4 men, 4 women) with a mean age of 38 ± 9 years (range 18 to 47) by echocardiography at rest, following exercise, and during dobutamine administration. Left ventricular (LV) septum, posterior wall, and end-diastolic diameter were significantly reduced in untreated patients with LS compared with the control group (p <0.05 for all). Systolic Doppler-derived parameters, including LV stroke volume, stroke index, cardiac output, and cardiac index, were significantly lower (p <0.05 for all) than in the control subjects, whereas LV diastolic Doppler parameters, including mitral valve waves E, A, E/A ratio, and E deceleration time, were similar in both groups. LV ejection fraction at rest as well as the stress-induced increment of the LV ejection fraction were similar in both groups. Our results show that untreated patients with long-term IGF-I deficiency have reduced cardiac dimensions and output but normal LV ejection fraction at rest and LV contractile reserve following stress.

Section snippets

Methods

The study was approved by the hospital ethical committee, and each patient signed an inform consent before testing.

Cardiac dimensions

The values of LV dimensions are displayed in Table I. Mean estimated LV mass in patients with LS was 85 ± 16 g; normalized to body surface area (BSA), LV mass was 70 ± 17 g/m2 and to height it was 66 ± 13 g/m. It is apparent that LV wall thickness, cardiac dimensions, LV volume, and mass are significantly smaller compared with the control group.

Doppler variables

Doppler measurements are displayed in Table I. LV outflow tract diameter as well as estimated LV stroke volume and cardiac output were significantly

Discussion

This is the first study of cardiac dimensions and functions in adult patients with primary GH resistance (LS), who due to molecular defects of the GH receptor or postreceptor pathways, have no GH signal transmission and no generation of the circulating IGF-I but high levels of GH.7, 8, 9 Because of this syndrome, we were able to evaluate the long-term role of these hormones on cardiac structure and function. In the present study, LV dimensions, Doppler-derived outflow parameters, and estimated

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      Measurements of organ weights in GHR-KO pigs revealed that growth of liver, kidneys, and heart is particularly dependent on GHR/GH action, as their relative weights were significantly decreased in comparison to control pigs. Reduced relative liver and kidney weights have also been observed in Ghr KO mice [55], and interestingly LS patients have disproportionately reduced cardiac dimensions [59]. The important role of the GH/IGF1 system in the growth of these organs is supported by their disproportionate overgrowth in conditions of GH/IGF1 excess, as in GH-overexpressing transgenic mice [60,61] and in patients with acromegaly [62].

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