Vestibular function in severe GH deficiency due to an inactivating mutation in the GH-releasing hormone receptor gene.

PURPOSE: Body balance involves the vestibular, visual, and proprioceptive systems. IGF-I is a GH-dependent key factor in the development and postnatal differentiation of the inner ear in mice and men, but its role in the vestibular function in adult humans is unknown. We have previously described a cohort of individuals with severe isolated GH deficiency (IGHD) caused by a mutation in the GHRH receptor (GHRHR) gene. These individuals complain of dizziness, exhibit mild sensorineural loss, but have normal postural balance, without increase in falls risk. The aim of this study was to evaluate their vestibular function. METHODS: We performed physical examination (clinical head impulse and Fukuda dynamic stepping test), oculomotor (saccadic eye movements, spontaneous, semi-spontaneous and opotokinetic nystagmus, and pendular tracking) and caloric stimulation (postcaloric reflex and ocular fixation index) tests, in 15 GH-naïve IGHD (seven males) and 15 controls (five males). RESULTS: IGHD subjects showed lower height and weight, with similar BMI to controls, and higher number of individuals with abnormal clinical head impulse test and abnormal oculomotor tests, namely the saccadic movements and the spontaneous nystagmus. There was a nonsignificant trend in abnormalities in the Fukuda stepping test and postcaloric reflex test. CONCLUSIONS: Adult untreated IGHD individuals have higher prevalence of moderate peripheral vestibular impairment, and of abnormal vestibular-ocular reflex.

Walking and postural balance in adults with severe short stature due to isolated GH deficiency.

OBJECTIVES: Walking and postural balance are extremely important to obtain food and to work. Both are critical for quality of life and ability to survive. While walking reflects musculoskeletal and cardiopulmonary systems, postural balance depends on body size, muscle tone, visual, vestibular and nervous systems. Since GH and IGF-I act on all these systems, we decided to study those parameters in a cohort of individuals with severe short stature due to untreated isolated GH deficiency (IGHD) caused by a mutation in the GHRH receptor gene. These IGHD subjects, despite reduction in muscle mass, are very active and have normal longevity. METHODS: In a cross-sectional study, we assessed walking (by a 6-min walk test), postural balance (by force platform) and fall risk (by the 'Timed Up and Go' test) in 31 IGHD and 40 matched health controls. RESULTS: The percentage of the walked distance measured in relation to the predicted one was similar in groups, but higher in IGHD, when corrected by the leg length. Absolute postural balance data showed similar velocity of unipodal support in the two groups, and better values, with open and closed eyes and unipodal support, in IGHD, but these differences became non-significant when corrected for height and lower-limb length. The time in 'Timed Up and Go' test was higher in IGHD cohort, but still below the cut-off value for fall risk. CONCLUSION: IGHD subjects exhibit satisfactory walking and postural balance, without increase in fall risk.

Adult individuals with congenital, untreated, severe isolated growth hormone deficiency have satisfactory muscular function.

PURPOSE: While growth hormone (GH) and the insulin-like growth factor type I (IGF-I) are known to exert synergistic actions on muscle anabolism, the consequences of prolonged GH deficiency (GHD) on muscle function have not been well defined. We have previously described a large cohort of subjects with isolated GHD (IGHD) caused by a mutation in the GH-releasing hormone receptor gene, with low serum levels of GH and IGF-I. The aim of this study was to assess muscular function in these IGHD subjects. METHODS: A total of 31 GH-naïve IGHD (16 males) and 40 control (20 males) subjects, matched by age and degree of daily physical activity, were enrolled. Fat free mass was measured by bioelectrical impedance; muscle strength by dynamometry of handgrip, trunk extension, and knee extension; myoelectric activity and muscle fatigue by fractal dimension; conduction velocity in vastus medialis, rectus femoris, and vastus lateralis muscles by surface electromyography. RESULTS: The IGHD group showed higher knee extension strength both when corrected for weight and fat free mass, and higher handgrip and trunk extension strength corrected by fat free mass. They also exhibit higher conduction velocity of the muscles vastus medialis, rectus femoris, and vastus lateralis, but lower free fat mass and myoelectric activity of the vastus medialis, rectus femoris and vastus lateralis. There were no differences between the two groups in fractal dimension in all studied muscles. CONCLUSION: Individuals with untreated IGHD have better muscle strength parameters adjusted for weight and fat free mass than controls. They also exhibit greater peripheral resistance to fatigue, demonstrating satisfactory muscle function.