Cognition in the adult with childhood-onset GH deficiency

The GH/IGF1 axis may play an important role in cognitive function. This theory is supported by the finding that both GH and IGF1 receptors are located in several brain areas such as the hippocampus, a brain area that is known to play an essential role in cognitive processes, especially memory and learning. However, the exact mechanism by which the GH/IGF1 axis influences the cognitive functions is still unknown. Furthermore, little is known about the cognition in adults with both childhood-onset and adult-onset GH deficiency (CO-GHD and AO-GHD). Recent data indicate that cognitive function, particularly attention and memory, in adults with GHD might be impaired. To date, only a limited number of studies have been conducted to study the effects of GH replacement therapy on cognitive function in adults with GHD. In this paper, the results of studies on cognitive functioning in GHD patients, in particular the results of the studies performed in adults with CO-GHD, and the effects of GH replacement therapy in these patients, will be discussed. © 2008 European Society of Endocrinology

The relationship between IGF-I concentration, cognitive function and quality of life in adults with Prader-Willi syndrome.

Mental retardation is one of the clinical characteristics of Prader-Willi syndrome (PWS) and in part of the patients growth hormone deficiency is demonstrable. Cognitive function seems to be influenced by insulin-like growth factor I (IGF-I); however, little is known about cognitive function in relation to IGF-I levels in PWS adults. The aim of the present study was to evaluate cognitive function in adult PWS patients in comparison to healthy siblings and to investigate whether there is a correlation between cognitive function and IGF-I levels. Anthropometric measurements, IGF-I levels, quality of life (QoL), Appetite Assessment Score, IQ (GIT and Raven) and cognitive function (by four subtests of the Cambridge Neuropsychological Automated Testing Battery, CANTAB) were evaluated in PWS patients and their healthy siblings served as control group. PWS patients had significantly lower IGF-I levels, IQ and QoL when compared to controls. Reaction times were longer and performance was worse on CANTAB subtests in PWS adults. IGF-I on one hand and IQ, Appetite Assessment Score and cognitive performance on the other hand seem to be correlated in PWS patients. In conclusion, IGF-I levels, IQ and QoL are significantly lower in PWS subjects when compared to healthy siblings. In PWS adults, temporal as well as prefrontal cognitive functions are impaired. Higher IGF-I levels appear to be related to better intellectual skills and faster temporal memory processing in PWS patients. © 2011 Elsevier Inc

Serum insulin-like growth factor-I and body composition in community dwelling older people

Objectives The decline in the growth hormoneinsulin-like growth factor-I (GHIGF-I) axis during normal aging might be involved in the changes in body composition associated with increasing age. We conducted a study to investigate serum IGF-I levels across different age categories and a possible association between serum IGF-I and measurements of body composition in older people. Design A cross-sectional analysis of community dwelling older people, which participated in a large longitudinal cohort study (Longitudinal Aging Study Amsterdam). Subjects 1319 subjects, 644 men, mean age 75·6 ± 6·6 years and 675 women, mean age 75·4 ± 6·6 years. Main Outcome Measurements IGF-I, body mass index (BMI), waist, waist-hip ratio (WHR), fat mass, lean body mass and total bone mineral density. Results IGF-I levels were significantly lower in the highest age categories. BMI and biceps skinfold measurements were lower in the lowest IGF-I quartile in men aged ≥75·5 years. In men with a low total physical activity score (174 minday), WHR was lower in the lowest IGF-I quartiles. Conclusion In this large cohort of community dwelling older people, we observed lower serum IGF-I levels in the higher age categories. A low serum IGF-I was associated with significantly lower measurements of body composition, such as BMI, skinfolds and WHR. These results do not support previous findings that high IGF-I levels are favourable for a healthy body composition in community dwelling older people. © 2010 Blackwell Publishing Ltd

The Association of Serum Insulin-Like Growth Factor-I with Mortality, Cardiovascular Disease, and Cancer in the Elderly: A Population-Based Study

Context: Numerous studies have investigated the effect of serum IGF-I concentration on aging and different aging-related diseases, e.g. cardiovascular disease (CVD) and cancer. Decreased as well as increased levels have been reported to be associated with reduced life expectancy in humans. Objective: This study investigates the association of serum IGF-I concentration with all-cause and cause-specific mortality of community-dwelling older persons and the development of CVD and cancer. Design, Setting, and Participants: Data were used from the Longitudinal Aging Study Amsterdam (LASA), an ongoing multidisciplinary cohort study in the general Dutch population of older persons (≥65 yr old) where serum IGF-I was measured (n = 1273). The mortality information was ascertained using the International Classification of Diseases, 10th revision, and the presence or absence of CVD and cancer by self-reports with a follow-up of 11.6 yr. Main Outcome Measure: We measured all-cause, CVD, and cancer mortality and nonfatal CVD and cancer. Results: Fully adjusted Cox proportional hazards models demonstrated an increased risk of all-cause mortality for older persons with IGF-I values in the lowest quintile as compared to the middle quintile [hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.01-1.63]. A more than 2-fold increased risk of CVD mortality was revealed for both low-normal (HR, 2.39;95% CI, 1.22-4.66) and high-normal (HR, 2.03; 95% CI, 1.02-4.06) IGF-I values. Significant associations of serum IGF-I with nonfatal CVD and fatal and nonfatal cancer were not observed. Conclusions: Results suggest a U-shaped relationship between IGF-I level and mortality, with fatal CVD as the most critical outcome in community-dwelling older persons. Copyright © 2010 by The Endocrine Society

The GH/IGF-I axis and pituitary function and size in adults with Prader-Willi syndrome

Background: In adults with Prader-Willi syndrome (PWS), limited information is available about pituitary function, more specifically the prevalence of growth hormone deficiency (GHD). The aim of this study was to gain more insight into endocrine function in PWS adults, with emphasis on GH secretion. Methods: 15 randomly selected adult PWS individuals were included and 14 healthy brothers and sisters served as a control group. Main outcome measures were IGF-I, IGFBP-3 and peak GH level after a combined GHRH-arginine test. Other pituitary hormone deficits are diagnosed based on serum levels of the concerning hormones. The size of the pituitary gland was measured on MRI images. Results: In PWS adults, IGF-I levels were low and IGFBP-3 levels normal when compared to healthy controls. GHD was diagnosed in 8-38% of the PWS patients, depending on the criteria used. Hypogonadism was present in 87% of the patients. Hypothyroidism and adrenal insufficiency could also be demonstrated. Anterior pituitary size was lower in PWS individuals when compared to healthy controls. Conclusion: In this study, pituitary hormone deficiencies are demonstrated in a considerable number of adults with PWS, hypogonadism and GHD being most prominent. Furthermore, the anterior pituitary is smaller in comparison with healthy controls. Copyright © 2011 S. Karger AG, Basel

Acute and short term effects of caloric restriction on metabolic profile and brain activation in obese, postmenopausal women.

OBJECTIVE:Early anthropometric and metabolic changes during a caloric-restricted diet in obese postmenopausal women and correlations between these factors with activity in brain areas involved in processing of visual food related stimuli were investigated.SUBJECTS AND METHODS:An 8-week prospective intervention study of 18 healthy postmenopausal women, with a body mass index of 30–35 kg 

Does growth hormone replacement therapy reduce mortality in adults with growth hormone deficiency? Data from the Dutch national registry of growth hormone treatment in adults

Context: Adults with GH deficiency (GHD) have a decreased life expectancy. The effect of GH treatment on mortality remains to be established. Objective: This nationwide cohort study investigates the effect of GH treatment on all-cause and cause-specific mortality and analyzes patient characteristics influencing mortality in GHD adults. Design, Setting, and Patients: Patients in the Dutch National Registry of Growth Hormone Treatment in Adults were retrospectively monitored (1985-2009) and subdivided into treatment (n =2229), primary (untreated, n = 109), and secondary control (partly treated, n = 356) groups. Main Outcome Measures: Standardized mortality ratios (SMR) were calculated for all-cause, malignancy, and cardiovascular disease (CVD) mortality. Expected mortality was obtained from cause, sex, calendar year, and age-specific death rates from national death and population counts. Results: In the treatment group, 95 patients died compared to 74.6 expected [SMR 1.27 (95% confidence interval, 1.04-1.56)]. Mortality was higher in women than in men. After exclusion of high-risk patients, the SMR for CVD mortality remained increased in women. Mortality due to malignancies was not elevated. In the control groups mortality was not different from the background population. Univariate analyses demonstrated sex, GHD onset, age, and underlying diagnosis as influencing factors. Conclusions: GHD men receiving GH treatment have a mortality rate not different from the background population. In women, after exclusion of high-risk patients, mortality was not different from the background population except for CVD. Mortality due to malignancies was not elevated in adults receiving GH treatment. Next to gender, the heterogeneous etiology is of influence on mortality in GHD adults with GH treatment. Copyright © 2011 by The Endocrine Society

Dutch national registry of GH Treatment in adults: patient characteristics and diagnostic test procedures

Objective: The Dutch National Registry of GH Treatment in Adults was established in 1998 as an initiative of the Ministry of Health. The main goals were to gain more insight into long-term efficacy, safety, and costs of GH therapy (GHT) in adult GH-deficient (GHD) patients in The Netherlands. Methods: Baseline patient characteristics and diagnostic test procedures were evaluated. Results: Until January 2009 in roughly 10 years, 2891 patients (1475 men and 1416 women, mean age 43.5±16.5 years) were registered. GHD was of childhood-onset (CO) in over 20% of the patients and of isolated in 11%. The most common causes of GHD were pituitary tumors and/or their treatment, craniopharyngiomas, and idiopathic GHD. In 85% of the patients, a GH stimulation test was performed, in the majority an insulin tolerance test (ITT) (49%) or a combined GHRH-arginine test (25%). In 12% of the patients, IGF1 levels were ≤-2 S.D. combined with two or more additional pituitary hormone deficits, and in 2%, it concerned patients with CO-GHD continuing GHT in adulthood. Over the years, the test of first choice shifted from ITT toward GHRH-arginine test. Conclusion: Nearly, 2900 patients were included in the nationwide surveillance database of the Dutch National Registry of GH Treatment in Adults until January 2009. Baseline patient characteristics are comparable to that reported previously. In 85% of these patients, the diagnosis of GHD was established by provocative testing, particularly an ITT or a combined GHRH-arginine test, with an evident increase in the percentage of GHRH-arginine tests being performed in the last years. © 2011 European Society of Endocrinology