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Growth Hormone Deficiency (growth + hormone_deficiency)

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Medical Sciences	96%

Selected Abstracts

Growth hormone (GH) replacement in hypopituitary adults with GH deficiency evaluated by a utility-weighted quality of life index: a precursor to cost,utility analysis

CLINICAL ENDOCRINOLOGY, Issue 1 2008
Maria Ko, towska-Häggström
Summary Objectives To examine quality of life (QoL) measured by a utility-weighted index in GH-deficient adults on GH replacement and analyse the impact of demographic and clinical characteristics on changes in utilities during treatment. Design Utilities for items in the QoL-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDAutility) were estimated based on data obtained from the general population in England and Wales (E&W). These estimates were used to calculate QoL changes in GH-treated patients and compare these with normative population values. Patients A total of 894 KIMS patients (53% women) from E&W were followed for 1 to 6 years. Measurements QoL-AGHDAutility at baseline and at the last reported visit, total QoL-AGHDAutility gain and QoL-AGHDAutility gain per year of follow-up. Results QoL-AGHDAutility in patients before GH treatment differed from the expected population values [0·67 (SD 0·174) vs. 0·85 (SD 0·038), P < 0·0001], constituting a mean deficit of ,0·19 (SD 0·168). There was a difference in the mean QoL-AGHDAutility deficit for men [,0·16 (SD 0·170)] and women [,0·21 (SD 0·162)] (P < 0·001). The main improvement occurred during the first year of treatment [reduction of a deficit to ,0·07 (SD 0·163) (P < 0·001) in the total cohort]; however, patients' utilities remained lower than those recorded for the general population during subsequent follow-up (P < 0·001). Despite an observed impact of age, primary aetiology, disease onset and comorbidities on QoL-AGHDAutility, all patients showed a similar beneficial response to treatment. Conclusions QoL-AGHDAutility efficiently monitors treatment effects in patients with GHD. The study confirmed the QoL-AGHDAutility deficit before treatment and a similar QoL-AGHDAutility gain observed after commencement of GH replacement in all patients. [source]

Autoimmune polyglandular syndrome Type 3 and growth hormone deficiency

PEDIATRIC DIABETES, Issue 6 2010
JB Quintos
Quintos JB, Grover M, Boney CM, Salas M. Autoimmune polyglandular syndrome type 3 and growth hormone deficiency. The simultaneous occurrence of prepubertal Graves' disease, type 1 Diabetes Mellitus (DM), and Growth hormone deficiency (GHD) is uncommon. GHD has been reported in Autoimmune Polyglandular Syndrome (APS) Type 1 and Type 2 but not in APS Type 3. We report a 3-yr-old boy who presented simultaneously with type 1 DM and Graves' disease. After he developed urticarial rash to Propylthiouracil and Methimazole with persistent thyrotoxicosis, he received 8 millicuries of 131I at 5 yr of age. We diagnosed GHD at age 8 yr 8 months because of growth deceleration (from 95 to 25%) and abnormal growth rate (3 cm/yr) despite euthyroidism, fair glycemic control, and normal weight gain. Both insulin-like growth factor (IGF) 1 (90 ng/mL; normal 113,261 ng/mL) and IGFBP3 (1.3 mcg/mL; normal 2.1,4.2 mcg/mL) levels were low and peak growth hormone level measured by RIA was 5.2 ng/mL after L-Dopa and insulin tolerance test. The rest of his pituitary functions and magnetic resonance imaging of the pituitary gland were normal. Growth hormone treatment (0.3 mg/kg/wk) was administered at 8 yr 9 months until near final adult height (FAH). Near FAH (172 cm) was close to midparental target height of 180 cm. GHD may be a component of all APS even though it is rare. Growth in treated children with Graves' disease should be followed closely as catch down growth below genetic height potential may be a harbinger of underlying GHD. [source]

Growth hormone deficiency and combined pituitary hormone deficiency: does the genotype matter?

CLINICAL ENDOCRINOLOGY, Issue 2 2005
Mehul T. Dattani
Summary The past 12 years have witnessed an explosion in our understanding of the development of the anterior pituitary gland, and of mechanisms that underlie the diagnosis of growth hormone deficiency (GHD) and combined pituitary hormone deficiency (CPHD). The anterior pituitary is the end-product of a carefully orchestrated pattern of expression of signalling molecules and transcription factors that leads to the development of this complex organ secreting six hormones from five different cell types. Naturally occurring and transgenic murine models have demonstrated a role for many of these molecules in the aetiology of GHD/CPHD. These include the transcription factors HESX1, PROP1, POU1F1, LHX3, LHX4, GLI2 and SOX3. Depending upon the expression patterns of these molecules, the phenotype may consist of isolated hypopituitarism, or more complex disorders such as septo-optic dysplasia (SOD) and holoprosencephaly. The phenotype and the mode of inheritance can be highly variable. Novel mutations within the GH-1 and GHRHR genes have also shed light on the phenotype and pathogenesis of isolated GHD (IGHD). To date, genetic mutations have been identified in a modest proportion of patients with IGHD/CPHD and associated syndromes such as SOD. It is, however, clear that many genes remain to be identified, and characterization of these will further elucidate the pathogenesis of these complex conditions. [source]

The effects of 12 months of growth hormone replacement therapy on cardiac autonomic tone in adults with growth hormone deficiency

CLINICAL ENDOCRINOLOGY, Issue 6 2005
F. Tanriverdi
Summary Objectives, Growth hormone deficiency (GHD) in adults is associated with a cluster of cardiovascular risk factors. Some abnormalities of cardiac structure and function have been reported in adult patients with GHD, but there are few data related to cardiac autonomic tone. Non-invasive assessment of cardiac autonomic status can be achieved by heart rate variability (HRV), which can be measured by using time-domain or frequency-domain variables. To our knowledge, short-term (6 months) effects of GH replacement therapy (GHRT) on HRV in a limited number of patients have been evaluated prospectively in only two previous studies. The present study was therefore designed to investigate the effects of GHD and 12 months of GHRT on cardiac autonomic tone in a larger number of adult patients with severe GHD. Patients and methods, HRV measurement, by using time-domain variables, was performed in 22 patients with GHD (eight men, 14 women; mean age 45·4 ± 2·4 years) and 22 healthy controls (nine men, 13 women; mean age 40·8 ± 1·8 years) at baseline. The time-domain variables (sympathetically influenced parameters SDNN and SDANN and parasympathetically influenced parameters RMSSD and PNN50) were derived from 24-h electrocardiogram (ECG) recordings. In the patient group, cardiac autonomic tone was re-evaluated after 6 and 12 months of GHRT. Results, Mean baseline values of SDNN and SDANN were significantly higher (higher values mean lower sympathetic activity) in GHD patients than in healthy controls (P < 0·05), but mean baseline values of RMSSD and PNN50 did not differ significantly in healthy controls and patients. After 6 and 12 months of GHRT, mean SDNN and SDANN were decreased significantly when compared with the baseline values before GHRT (P < 0·05). However, mean RMSSD and PNN50 did not differ significantly from baseline. When SDNN and SDANN measurements were evaluated individually for each patient, after 12 months of GHRT both of the sympathetically influenced parameters decreased in 90% of the patients. Conclusions, These data indicate that sympathetic tone is decreased in adult patients with severe GHD. Additionally, an increment in sympathetic activity and normalization of sympathovagal balance have been demonstrated after 6 and 12 months of GHRT. This result suggests that, at least at the doses used in this study, GHRT improves sympathetic tone, without an obvious arrhythmogenic effect. [source]

Growth hormone deficiency and vascular risk

CLINICAL ENDOCRINOLOGY, Issue 1 2002
Roland W. McCallum
Summary The importance of growth hormone deficiency (GHD) in adult life has become more apparent over the last decade. As well as a distinct clinical syndrome there is a significant excess risk of cardiovascular disease. Although it is difficult to ascertain what part is played by the original pituitary disorder and the concomitant replacement hormonal therapies, there is clear evidence that GHD is associated with known cardiovascular risk factors such as body shape, lipid profile, insulin resistance, blood pressure, vessel wall morphology and haemostatic factors. Novel means of assessing vascular risk such as pulse wave velocity and flow-mediated dilatation can also estimate the risk without invasive procedures. The role of possible mediators of endothelial function such as nitric oxide and free radicals is being investigated further. Replacement of GH in GH-deficient patients leads to many effects on the above indices, some but not all of which are associated with reduced vascular risk. Long-term follow-up studies of morbidity and mortality are required for an accurate assessment of the beneficial effects of therapy. [source]

Lipid profiles in untreated severe congenital isolated growth hormone deficiency through the lifespan

CLINICAL ENDOCRINOLOGY, Issue 1 2002
Helena K. Gleeson
Summary objective Growth hormone deficiency (GHD) is associated with adverse changes in lipid profile. However, changes in lipids through life in a homogeneous group of GHD subjects have not been defined. patients and measurements We examined lipid levels in a group of untreated severely GHD patients with a mutation in the GHRH receptor gene from a rural community in North-east Brazil. Lipid profiles in 15 GHD subjects [eight children and adolescents (one male), age (median [range]) 13·2 (5·4,19·9) years; seven adults (one male), age 47 (33,66) years] were compared with those in 29 indigenous controls from the same extended kindred [17 children and adolescents (six male), age 10·2 (5·3,18·4) years; 12 adults (eight male), age 54·5 (33,80) years]. All GHD subjects had a peak GH response of < 0·5 ng/ml in response to an insulin tolerance test and extremely reduced IGF-1 levels (median 5·5 ng/ml). Data were compared between cohorts and with an age- and sex-matched white American reference population. results Abnormalities were confined to plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. More GHD children had levels of plasma TC and LDL-C above the 95th percentile for our reference population (3/8 and 4/7, respectively) compared to controls (0/17 and 1/15, respectively) (P < 0·05). In the adults, median TC and LDL-C levels were higher in the GHD than controls (P < 0·05) (6·3 vs. 4·1 mmol/l; 4·4 vs. 2·7 mmol/l, respectively). Median Z -scores, calculated using values from the reference population, were not different between GHD children and adults for both TC (+0·8 vs.+0·4) and LDL-C (+1·4 vs.+0·7). conclusions The lipid profile in children as well as in adults with very severe GHD is adversely modified. There would appear to be no significant worsening of the lipid abnormality with duration of GHD or achievement of adulthood. [source]

Growth hormone and changes in energy balance in growth hormone deficient adults

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2008
D. Deepak
ABSTRACT Background, Adults with growth hormone deficiency (AGHD) have an adverse body composition with an increased prevalence of obesity. It is not known whether growth hormone replacement (GHR) results in alterations in energy intake (EI) and/or energy expenditure (EE). The aim of the study was to investigate the effects of GHR on EI and EE. Materials and methods, Nineteen hypopituitary adults (14 males, 5 females, mean age 46·2 years) with severe GHD (peak GH response to glucagon , 9 mU L,1) were studied. All patients self-injected recombinant human GH starting with 0·3 mg s.c. daily. The following were measured before and following 6 months of stable maintenance of GHR: food intake during a test meal, appetite ratings, resting EE (indirect calorimetry) and voluntary physical activity (accelerometry). Results, GHR nearly doubled voluntary physical activity (mean activity units 3319 vs. 1881, P = 0·007) and improved quality of life score (mean score 9·1 vs. 16·5, P < 0·0001). Subjects reported higher fasting hunger ratings (mean 64·8 vs. 49·6, P = 0·02) but ad libitum energy intake remained unchanged. Eating behavioural traits were favourably altered with lower disinhibition (mean 6·0 vs. 7·2, P = 0·02) and lower susceptibility to hunger ratings (4·6 vs. 6·8, P = 0·001) after GHR. Additionally, GHR did not result in significant changes in resting EE, body weight and body mass index. Conclusions, GHR in AGHD significantly improves voluntary physical activity and quality of life. Following GHR, subjects experience greater ,state' (physiological) hunger, reductions in eating disinhibition and hunger susceptibility, but no effects on calorie intake or macronutrient choice were detected. [source]

Chronic cognitive sequelae after traumatic brain injury are not related to growth hormone deficiency in adults

EUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2010
D. Pavlovic
Objective:, The objective of the study was to asses the possible influence of hypothalamo,pituitary deficiencies, and growth hormone (GH) deficiency in particular, on cognition in adult patients with traumatic brain injury (TBI). TBI is a recently identified risk factor for cognitive deficits and hypopituitarism. Even the patients with favorable outcome after TBI may present with persistent bodily, psychosocial, and cognitive impairments, resembling patients with untreated partial or complete pituitary insufficiency. Design:, We performed retrospective and cross-sectional study of endocrine and cognitive function in TBI in 61 patients (aged 37.7 ± 1.7 years) of both sexes (44 m,17 f), at least 1 year after TBI (3.9 ± 0.6 years). Serum insulin-like growth factor 1 (IGF-I), thyroxin, thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (in men), prolactin, and cortisol were measured, and GH secretion was assessed by growth hormone releasing hormone (GHRH) + growth hormone releasing peptide-6 (GHRP-6) test. Cognitive function was assessed by using a standard neuropsychological battery. Results:, GH deficiency (GHD) and GH insufficiency (GHI) were found in 20 patients (32.8%). After adjustment for confounders [age, body mass index (BMI), education level, time elapsed from TBI], there were no significant differences in results of neuropsychological tests between patients with TBI with GHD, GHI, and normal GH secretion. There were no correlations of neuropsychological variables with stimulated peak GH secretion or IGF-I level. Conclusions:, GHD persists long after the TBI, independently of trauma severity and age at traumatic event. GH secretion is more sensitive to TBI than other pituitary hormones. No evidence is found for an association of cognitive function impairment and somatotropic axis impairment in adult patients tested more than 1 year after the TBI. [source]

Craniofacial morphology, dental occlusion, tooth eruption, and dental maturity in boys of short stature with or without growth hormone deficiency

EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 5 2000
Heidrun Kjellberg
The aim of this project was to study the craniofacial morphology, dental occlusion, dental maturation and tooth eruption in short-statured boys with growth hormone secretion ranging from low to high. The measurements from lateral and postero-anterior cephalograms, orthopantomograms and plaster models were used. Almost all linear measurements of the facial structures were significantly smaller. A disproportionate growth in the cranial base structures as well as in the jaws resulted in facial retrognathia, a proportionately smaller posterior than anterior facial height, and a steep vertical inclination of the mandible. Dental crowding was more common and the overbite was small. Dental maturity and tooth eruption were delayed 1.2 and 1.3 yr, respectively. No significant differences between the idiopathic short-statured and the growth hormone-deficient group in any of the above-mentioned variables were found. It can be concluded that although most of the cephalometric variables measured differed significantly from the average, the facial appearance of the boys is not conspicuous and is of minor clinical importance. However, the short-statured boys might be in greater need of orthodontic treatment due to the higher percentage of dental crowding. [source]

Growth Hormone Administration and Exercise Effects on Muscle Fiber Type and Diameter in Moderately Frail Older People

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2001
James V. Hennessey MD
OBJECTIVE: Reduced muscle mass and strength are characteristic findings of growth hormone deficiency (GHD) and aging. We evaluated measures of muscle strength, muscle fiber type, and cross sectional area in response to treatment with recombinant human growth hormone (rhGH) with or without a structured resistance exercise program in frail older subjects. DESIGN: Placebo-controlled, randomized, double blind trial. SETTING: Outpatient clinical research center at an urban university-affiliated teaching hospital. PARTICIPANTS: Thirty-one consenting older subjects (mean age 71.3 ± 4.5 years) recruited as a subset of a larger project evaluating rhGH and exercise in older people, who underwent 62 quadricep-muscle biopsies. INTERVENTION: Random assignment to a 6-month course of one of four protocols: rhGH administered subcutaneously daily at bedtime, rhGH and a structured resistance exercise program, structured resistance exercise with placebo injections, or placebo injections only. MEASUREMENTS: Muscle biopsy specimens were obtained from the vastus lateralis muscle. Isokinetic dynamometry strength tests were used to monitor individual progress and to adjust the weights used in the exercise program. Serum insulin-like growth factor-I (IGF-I) was measured and body composition was measured using a Hologic QDR 1000W dual X-ray densitometer. RESULTS: The administration of rhGH resulted in significant increase in circulating IGF-I levels in the individuals receiving rhGH treatment. Muscle strength increased significantly in both the rhGH/exercise (+55.6%, P = .0004) as well as the exercise alone (+47.8%, P = .0005) groups. There was a significant increase in the proportion of type 2 fibers between baseline and six months in the combined rhGH treated subjects versus those not receiving rhGH (P = .027). CONCLUSIONS: Our results are encouraging in that they suggest an effect of growth hormone on a specific aging-correlated deficit. IGF-I was increased by administrating rhGH and muscle strength was increased by exercise. The administration of rhGH to frail older individuals in this study resulted in significant changes in the proportions of fiber types. Whether changes in fiber cross-sectional area or absolute number occur with long-term growth hormone administration requires further study. [source]

Increased melatonin concentrations in children with growth hormone deficiency

JOURNAL OF PINEAL RESEARCH, Issue 2 2007
Michal Karasek
Abstract:, A relationship between melatonin and growth hormone (GH) is poorly understood. We compare circadian melatonin rhythms in short children with normal and decreased GH secretion. The analysis included 22 children (20 boys and 2 girls) aged 11.1,16.9 yr (mean ± S.E.M. = 14.1 ± 0.3 yr) with short stature (height SDS below ,2.0). Based on the GH peak in stimulation tests patients were divided into two groups: idiopathic short stature (ISS, n = 11; GH peak , 10 ng/mL) and GH deficiency (GHD, n = 11; GH peak < 10 ng/mL). In all patients the circadian melatonin rhythm was assessed on the basis of nine blood samples, collected in 4-hr intervals during the daytime and 2-hr intervals at night, with dark period lasting from 22:00 to 06:00 hr. Magnetic resonance imaging examination excluded organic abnormalities in central nervous system in all patients. Melatonin concentration at 24:00, 02:00 and 04:00 hr as well as the area under curve of melatonin concentrations (AUC) were significantly higher in the patients with GHD than in individuals with ISS. Significant correlations between GH secretion and melatonin concentrations at 24:00, 02:00 and 04:00 hr, and AUC were also observed. On the basis of these data it seems that the assessment of nocturnal melatonin secretion might be a valuable diagnostic tool used for the improvement of the difficult diagnosis of short stature in children. [source]

Obesity and metabolic changes are common in young childhood brain tumor survivors

PEDIATRIC BLOOD & CANCER, Issue 7 2009
Sari Pietilä MD
Abstract Background A population based cross-sectional study was used to examine the prevalence of metabolic syndrome and its components in childhood brain tumor survivors. Procedure Fifty-two survivors were examined at a mean age of 14.4 years (range 3.8,28.7). Lipid and glucose metabolism, thyroid function, and plasma uric acid were evaluated. Fat mass and fat percentage were assessed by dual-energy X-ray absorptiometry (DXA). Metabolic syndrome was defined on International Diabetes Federation criteria. Results Ten (19%) patients were overweight and four (8%) were obese. According to DXA, 16/46 (35%) patients were obese. Central obesity was found in 11 (21%) patients. Cranial irradiation, hypothalamic/hypophyseal damage, growth hormone (GH) deficiency and impaired mobility were associated with overweight/obesity and central obesity. Thirteen (25%) subjects had hypercholesterolemia, 14 (27%) had raised low-density lipoprotein cholesterol (LDL-C), 12 (23%) had raised blood pressure, four (8%) had metabolic syndrome, two (4%) had hyperinsulinemia and five (10%) had hyperuricemia. Cranial irradiation was associated with hypercholesterolemia (P,=,0.019), raised LDL-C (P,=,0.028), raised blood pressure (P,=,0.040), and metabolic syndrome (P,=,0.018). Impaired mobility was associated with hypercholesterolemia (P,=,0.034). Hypothalamic/hypophyseal damage was associated with metabolic syndrome (P,=,0.003) and hyperuricemia (P,=,0.011) as was GH deficiency (P,=,0.034 and P,=,0.008). GH supplementation alleviated adverse metabolic outcomes among brain tumor survivors with GH deficiency. Conclusions Obesity/overweight, dyslipidemia, hypertension, metabolic syndrome, and hyperuricemia were common in young childhood brain tumor survivors. Cranial irradiation, hypothalamic/hypophyseal damage, growth hormone deficiency, and/or impaired mobility were associated with higher risk for obesity and metabolic changes among these patients. Pediatr Blood Cancer 2009;52:853,859. © 2009 Wiley-Liss, Inc. [source]

A case of moyamoya syndrome and hemoglobin E/beta-thalassemia

PEDIATRIC BLOOD & CANCER, Issue 3 2009
Torrey M. Parker BSc
Abstract Moyamoya syndrome is a rare diagnosis that has been linked to a small number of hemoglobinopathies. Children with Moyamoya syndrome tend to present with transient ischemic attacks, mental deficiency, and/or neurological deficits. We describe a case of a 15-year-old Cambodian male with HbE/,-thalassemia who was found to have left Moyamoya syndrome as part of an evaluation for growth hormone deficiency. The link between Moyamoya syndrome and HbE/,-thalassemia may be multifactorial, but Moyamoya syndrome is an important consequence to consider in children with HbE/,-thalassemia. Pediatr Blood Cancer 2009;52:422,424. © 2008 Wiley-Liss, Inc. [source]

Autoimmune polyglandular syndrome Type 3 and growth hormone deficiency

Central corneal thickness in children with growth hormone deficiency

ACTA OPHTHALMOLOGICA, Issue 6 2010
Fulvio Parentin
Acta Ophthalmol. 2010: 88: 692,694 Abstract. Purpose:, To evaluate central corneal thickness (CCT), intraocular pressure (IOP) and eye refraction in patients with congenital growth hormone (GH) deficiency. Methods:, Retrospective case series. Forty-five patients with growth defect treated with recombinant GH and 45 healthy children underwent ophthalmological examination, including CCT measurements, applanation tonometry and cycloplaegic refraction. Results:, The average CCT in the GH deficiency group was 570.6 ,m [standard deviation (SD) 37.4]. In the control group, it was 546.0 (SD 24.9). The average IOP in the GH deficiency group was 18.2 mmHg (SD 3.4). In the control group, it was 14.6 (SD 2.0). The mean refractive error (spherical equivalent) in the GH deficiency group was 0.59 D (SD 1.9). In the control group, it was 0.11 (SD 2.1). Conclusion:, GH and insulin-like growth factor 1 are involved in ocular growth by influencing the synthesis of the extracellular matrix of the sclera. Children with congenital GH deficiency or insensitivity have a mean hyperopic defect related to a shorter axial length. A number of studies have demonstrated that CCT in newborns is significantly greater than in adults; a decrease in CCT is closely correlated with an increase in corneal diameter. This finding suggests that the growth of the eye, with possible remodelling and stretching of collagen fibres, may play an important role in the reduction of corneal thickness in the first years of life. Therefore, we conclude that a greater CCT can represent a sign of a delayed growth of the eye in patients with GH deficiency. Finally, our study confirms the influence of corneal thickness on IOP measures, and the prevalence of hyperopia among children with growth defect. [source]

Non-conventional use of growth hormone therapy

ACTA PAEDIATRICA, Issue 2006
Marco Cappa
Abstract Human growth hormone therapy is allowed in certain clinical conditions according to national healthcare criteria. Growth hormone, however, produces a wide spectrum of effects. Linear growth is only one of the many expected results, and there are interesting possibilities to explore which could provide additional means of improving the quality of life for the ever-increasing numbers of chronic paediatric patients. Conclusion: In this review, we discuss the rationale for and possibility of using growth hormone therapy in some conditions not strictly related to growth hormone deficiency. [source]

Partial growth hormone deficiency in adults; should we be looking for it?

CLINICAL ENDOCRINOLOGY, Issue 4 2010
Stephen M. Shalet
Summary Quantitatively, GH secretion exists as a continuum in states ranging from good health through to hypopituitarism. Currently, GH replacement is considered only for adults designated as being severely GH deficient (GHD). In clinical practice the gold standard, on which the biochemical diagnosis of severe GHD is based, centres on the presence of two or more additional anterior pituitary hormone deficits. Cohorts of adults with partial GHD (Growth Hormone Insufficiency [GHI]) have been reported with adverse body composition changes, dyslipidaemia, insulin resistance, altered cardiac performance and increased carotid intima-media thickness. The diagnosis of GHI in an individual patient, however, is extremely difficult because such patients rarely exhibit additional anterior pituitary hormone deficits, and the levels of GH-dependent proteins, including IGF-I, are normal in the majority. Currently, GH replacement therapy should only be considered in a patient characterized as GHI by dynamic GH testing in whom there is a plausible cause for hypopituitarism and in whom the IGF-I level is pathologically low. [source]

Lower ability to oxidize lipids in adult patients with growth hormone (GH) deficiency: reversal under GH treatment

CLINICAL ENDOCRINOLOGY, Issue 4 2006
F. Brandou
Summary Background, The aim of the study was to characterize lipid oxidation at exercise in adults with growth hormone deficiency (GHD) and to evaluate the effect of 6 and 12 months of GH replacement therapy on substrate carbohydrate (CHO) and lipid utilization at exercise. Patients and measurements, Twenty-five patients with GHD and 40 matched controls participated in the study. Ten of the 25 GH-deficient patients were treated with recombinant GH for 12 months. Anthropometric measurements and exercise calorimetry were performed before and after treatment. Maximal fat oxidation and the crossover point [that is the percentage of the theoretical maximal power (Wmax th) where CHO become the predominant fuel used for oxidation] were determined. Results and conclusion, The GH-deficient patients exhibited a highly significant shift in the balance of substrate oxidation during exercise, towards a decrease in fat oxidation, and a shift towards lower intensities of the crossover (52 ± 5·5%vs. 72·6 ± 6·6% of Wmax th, P < 0·03) and maximal fat oxidation (131·04 ± 14 vs. 234·4 ± 30·1 mg/min, P < 0·03) in the GHD and control groups, respectively. However, GH treatment at 6 and 12 months partially reversed this defect, resulting in an increase (+83%, P < 0·001) in the maximal ability to oxidize fat during exercise. These findings are consistent with the hypothesis that a lack of GH reduces the ability to oxidize lipids during exercise and that GH treatment restores this muscular metabolic property. [source]

Growth hormone deficiency and combined pituitary hormone deficiency: does the genotype matter?

Mutations within the transcription factor PROP1 are rare in a cohort of patients with sporadic combined pituitary hormone deficiency (CPHD)

CLINICAL ENDOCRINOLOGY, Issue 1 2005
James P. G. Turton
Summary Objective, Mutations within the pituitary-specific paired-like homeobox gene PROP1 have been described in 50,100% of patients with familial combined pituitary hormone deficiency (CPHD). We screened a cohort of sporadic (n = 189) and familial (n = 44) patients with hypopituitarism (153 CPHD and 80 isolated hormone deficiencies) for mutations within the coding sequence of PROP1. Design and patients, Patients with congenital hypopituitarism were recruited from the London Centre for Paediatric Endocrinology as well as several national and international centres. The pituitary phenotype ranged from isolated growth hormone deficiency (IGHD) to panhypopituitarism. Clinical data, including endocrine and neuro-radiological studies were obtained from patient records, and DNA was collected and screened for mutations within PROP1 using PCR and single-stranded conformation polymorphism (SSCP) analysis. Positive results on SSCP were sequenced directly. Results, The prevalence of PROP1 mutations in unselected sporadic cases of hypopituitarism was lower (1·1%) than in familial cases (29·5%). PROP1 mutations can be associated with a highly variable phenotype, and both pituitary hypoplasia and pituitary hyperplasia. We describe the waxing and waning of a pituitary mass over 20 months in association with a PROP1 mutation that is predicted to lead to complete loss of function. Additionally, we have identified a possible founder mutation in CPHD patients from the Indian subcontinent. Conclusions,PROP1 mutations are rare in sporadic cases of CPHD, although the prevalence rises if there is a positive family history or if the patients are carefully selected with respect to the endocrine and neuroradiological phenotype. There is considerable phenotypic variability in families with the same mutation, indicating the role of other genetic or environmental factors on phenotypic expression. Finally, the pituitary enlargement that is observed in patients with PROP1 mutations can wax and wane in size before eventual involution. [source]

The effects of 12 months of growth hormone replacement therapy on cardiac autonomic tone in adults with growth hormone deficiency

The impact of idiopathic childhood-onset growth hormone deficiency (GHD) on bone mass in subjects without adult GHD

CLINICAL ENDOCRINOLOGY, Issue 1 2005
Martin Lange
Summary objective, Despite seemingly adequate growth hormone (GH) treatment during childhood, children with GH deficiency (GHD) have reduced bone mineral density (BMD) at final height. The aim was to evaluate BMD and bone mineral content (BMC) in adults treated for idiopathic childhood-onset (CO) GHD, 18 years after stopping GH treatment. subjects and methods, Twenty-six (11 females) patients with idiopathic CO GHD participated. All patients but two had been treated for isolated GHD in childhood. The childhood diagnosis was established by an insulin tolerance test (ITT) and reassessed in adulthood by an ITT (N = 21) or arginine test (n = 5), revealing that 10 patients had GHD according to adult criteria. Accordingly, the patient group was divided into (1) patients who did not have persistent GHD in adulthood and (2) patients who did have persistent adult GHD. Twenty-six healthy subjects acted as age-, gender- and body mass index (BMI)-matched controls. results, The patients who did not have persistent GHD had significantly lower IGF-I values and whole-body, femoral neck and lumbar spine BMD compared to controls [0·994 ± 0·10 vs. 1·114 ± 0·11 g/cm2 (P = 0·003), 0·842 ± 0·12 vs. 0·962 ± 0·11 g/cm2 (P = 0·006) and 1·026 ± 0·14 vs. 1·127 ± 0·13 g/cm2 (P = 0·004), respectively]. Femoral neck BMD was significantly reduced in the patients who had persistent GHD, compared to controls (0·842 ± 0·09 vs. 0·938 ± 0·11, P = 0·04). Significant correlations were observed between all bone variables and IGF-I in all subjects, whereas no correlations were observed between bone variables and GH peak levels in the 26 patients. conclusion, In conclusion, we found that (1) patients with idiopathic CO GHD, who at retest in adulthood did not have GHD according to adult criteria, had reduced serum IGF-I and BMD/BMC compared to controls. (2) This observation was also made in the patients who did have persistent GHD in adulthood. The findings may reflect the fact that the present diagnostic criteria for adult GHD (i.e. response to the ITT) do not reflect the clinical consequences of disordered GH,IGF axis in CO GHD young adults who were treated with GH in childhood. Alternatively, despite seemingly adequate GH treatment in childhood an optimal peak bone mass in adolescence may never have been reached in either of the groups. (3) IGF-I levels correlated with clinical signs of the adult GHD syndrome. We believe that further studies on the indications and diagnostic procedures for GH treatment after cessation of linear growth are necessary. [source]

Serum homocysteine concentrations in children with growth hormone (GH) deficiency before and after 12 months GH replacement

CLINICAL ENDOCRINOLOGY, Issue 5 2004
Valentina Esposito
Summary objective, This open, prospective study was designed to evaluate the effect of growth hormone deficiency (GHD) and GH replacement therapy on serum homocysteine (Hcy) concentration in children with GHD. subjects, Seventeen prepubertal children with GHD (11 boys and six girls) aged 8·6 ± 1·9 years were studied before and after 12 months of GH replacement therapy at a dose of GH of 30 µg/kg/day. Seventeen healthy children acted as controls and were matched for age, sex and body mass index (BMI). methods, At study entry, height, weight, blood pressure, serum Hcy, serum IGF-I, total-low density lipoprotein (LDL)- and high density lipoprotein (HDL) cholesterol, triglycerides, free T4, free T3, vitamin B12, folate, glucose and creatinine were measured in all subjects. The atherogenic index (AI) was also calculated as the ratio of total cholesterol/HDL cholesterol (T/HDL). In GHD children these parameters were also revaluated after 12 months of GH therapy. results, At study entry height and serum IGF-I were significantly lower, as expected, in GHD patients than in controls (P < 0·0001 and P < 0·007, respectively). Serum Hcy levels were significantly higher in GHD patients than in healthy children (8·4 ± 2·9 vs. 6·0 ± 2·9 µmol/l; P < 0·03), although the absolute values were within the normal values for age and sex. There were no significant differences at baseline with respect to blood pressure, serum vitamin B12, folate, fT3, fT4, lipid profile, creatinine and glucose levels. After 12 months of GH replacement therapy height and serum IGF-I increased significantly compared to pretreatment values (P < 0·0001); serum Hcy levels decreased significantly (6·0 ± 3·3 µmol/l; P < 0·002) compared to baseline values, becoming similar to control values. Total cholesterol (3·5 ± 0·6 mmol/l) and the AI (2·5 ± 0·8) decreased significantly with respect to both pretreatment (4·2 ± 1·0 mmol/l; P < 0·0002 and 3·4 ± 0·8; < 0·002, respectively) and control values (4·2 ± 0·4 mmol/l; P < 0·0005 and 3·3 ± 1·1; P = 0·02, respectively). conclusions GHD in children is associated with higher serum levels of Hcy compared to controls, without significantly affecting the lipid profile. GH replacement for 12 months significantly decreased the Hcy levels and improved the lipid profile with a decrease of total cholesterol and the total/HDL cholesterol ratio, compared to pretreatment values. Given the small number of patients, further larger studies are needed to clarify whether these results may have significant effects in the prevention of cardiovascular disease in adulthood. [source]

Assessment of quality of life in adults receiving long-term growth hormone replacement compared to control subjects

CLINICAL ENDOCRINOLOGY, Issue 1 2003
I. A. Malik
Summary objective There are few studies of quality of life (QOL) in adults with growth hormone deficiency (GHD) compared to matched control populations without GHD. These have shown impairments in a variety of QOL measures, which improve but do not normalize after short-term replacement with GH. There is little information on QOL in long-term treated GHD patients compared with controls without GHD. patients and methods A total of 120 adults with GHD who had received GH replacement for at least 1 year were identified from the neuroendocrine clinic. Patients were asked to complete eight QOL questionnaires and an Energy Visual Analogue Scale (VAS). Results were compared with 83 control subjects without GHD from the local population who agreed to complete seven of the QOL questionnaires (excluding Disease Impact scale) and the energy VAS. The eight questionnaires were a combination of generic and disease-specific questionnaires used to assess health related QOL, namely: Short Form-36 (SF-36), Nottingham Health Profile (NHP), Disease Impact, Life Fulfilment and Satisfaction scales, Mental Fatigue Questionnaire (MFQ) and Self Esteem scale, Hospital Anxiety Depression (HAD) scale and QOL-AGHDA (assessment of GHD in adults). results Eighty-nine patients returned questionnaires and 85 (71%) had complete data for analysis. The mean (SD) duration of GH replacement was 36·0 ± 26·4 (range 13,159) months. Mean age was 43·9 ± 15·8 years (37 males) in treated GHD patients compared to a mean age 41·7 ± 10·5 years (32 males) in the controls. Mean IGF-1 levels were 22·5 ± 13·6 nmol/l in the GHD patients and the mean dose of GH replacement was 1·2 ± 0·4 IU daily. Analysis of the QOL questionnaires from the GH treated patients revealed highly significant impairments in all measures (most P , 0·0001, except life fulfilment-material, P = 0·33) compared to the control population. conclusions This large population with treated GH deficiency have significant impairments in multiple aspects of QOL despite replacement with GH and other pituitary hormones for at least 1 year (mean 3 years). It is likely therefore that other factors in addition to GH deficiency must influence QOL in these patients. Further strategies to improve QOL in these individuals should therefore be considered, e.g. psychological support and treatments and physical treatments (such as exercise programmes). [source]

Re-assessment of growth hormone secretion in young adult patients with childhood-onset growth hormone deficiency

CLINICAL ENDOCRINOLOGY, Issue 4 2003
Juliane Donaubauer
Summary objective Patients with childhood-onset GH deficiency (coGHD) need retesting in late adolescence or young adulthood to verify whether they need to continue GH treatment. For this purpose the Growth Hormone Research Society (GRS) recommends the insulin tolerance test (ITT), or as an alternative the arginine + growth hormone releasing hormone test (ARG + GHRH test) as a diagnostic tool in adolescents and adults. However, there are no standardized cut-off levels based on normal GH secretion for determining GHD vs. GH sufficiency in young adults for the ITT, the ARG + GHRH test or the pyridostigmine + GHRH (PD + GHRH) test, a further new GH stimulation test. patients and measurements We studied 43 patients (28 with organic coGHD, 15 with idiopathic coGHD; 30 males, 13 females; aged 20·4 years, range 16·2,25·4; body mass index 23·5, range 16·3,35·8) using the ARG [0·5 g/kg intravenously (i.v.)] + GHRH (1 µg/kg i.v.) test, the PD (120 mg orally) + GHRH (1 µg/kg i.v.) test and the ITT (0·1 IU/kg i.v.) and compared these data with the results of 40 healthy age- and weight-matched volunteers. results The GH response in patients was significantly lower than in healthy controls: ARG + GHRH test, 0·8 µg/l (interquartile range 0·3,2·6) vs. 51·8 µg/l (32·6,71·2) in controls (P < 0·0001); PD + GHRH test, 0·9 µg/l (0·3,1·9) vs. 40·4 µg/l (27·1,54·4) in controls (P < 0·0001); ITT, 0.1 µg/l (0·0,0·8) vs. 20·3 µg/l (14·7,31·7) in controls (P < 0·0001). In the ARG + GHRH test we found a diagnostic sensitivity of 100% and a specificity of 97·5% for a cut-off range from 15·1 to 20·3 µg/l, in the PD + GHRH test a sensitivity of 100% and a specificity of 97% (cut-off range 9·1,13·1 µg/l) and in the ITT a sensitivity and specificity of 100% each within a cut-off range from 2·7 to 8·8 µg/l. conclusion There were no marked differences in sensitivity and specificity in young adults among ARG + GHRH test, PD + GHRH test and the ITT in assessing GH secretion. Because of the lack of side-effects, the ARG + GHRH test is the recommended method for re-evaluation of coGHD in young adults when pituitary GHD is suspected. Furthermore, in adult patient groups where organic pituitary coGHD is common, the ITT may be completely replaced by the ARG + GHRH test. Because of the predominance of hypothalamic GHD in childhood, the ITT is commonly performed for the re-evaluation of patients with childhood-onset GHD because of its mechanism of GH stimulation. The present results confirm the high discriminatory capability of the ITT in young adults. [source]

Testing for growth hormone deficiency in adults , how to respond?

CLINICAL ENDOCRINOLOGY, Issue 1 2003
J. O. L. Jørgensen
No abstract is available for this article. [source]

Growth hormone deficiency and vascular risk

Lipid profiles in untreated severe congenital isolated growth hormone deficiency through the lifespan

Endocrine responses to ghrelin in adult patients with isolated childhood-onset growth hormone deficiency

CLINICAL ENDOCRINOLOGY, Issue 6 2002
Gianluca Aimaretti
Summary objective Ghrelin, a 28 amino acid acylated peptide, is a natural ligand of the GH secretagogues (GHS) receptor (GHS-R), which is specific for synthetic GHS. Similar to synthetic GHS, ghrelin strongly stimulates GH secretion but also displays significant stimulatory effects on lactotroph and corticotroph secretion. It has been hypothesized that isolated GH deficiency (GHD) could reflect hypothalamic impairment that would theoretically involve defect in ghrelin activity. patients In the present study, we verified the effects of ghrelin (1 µg/kg i.v.) on GH, PRL, ACTH and cortisol levels in adult patients with isolated severe GHD [five males and one female, age (mean ± SEM) 24·7 ± 2·6 years, BMI 25·7 ± 2·7 kg/m2]. In all patients, the GH response to insulin-induced hypoglycaemia (ITT, 0·1 IU regular insulin i.v.) and GH releasing hormone (GHRH) (1 µg/kg i.v.) + arginine (ARG, 0·5 g/kg i.v.) was also studied. The hormonal responses in GHD were compared with those in age-matched normal subjects (NS, seven males, age 28·6 ± 2·9 years, BMI 22·1 ± 0·8 kg/m2). results IGF-I levels in GHD were markedly lower than in NS (69·8 ± 11·3 vs. 167·9 ± 19·2 µg/l, P < 0·003). Ghrelin administration induced significant increase in GH, PRL, ACTH and cortisol levels in all GHD. In GHD, the GH response to ghrelin was higher (P < 0·05) than that to GHRH + ARG, which, in turn, was higher (P < 0·05) than that to ITT (9·2 ± 4·1 vs. 5·3 ± 1·7 vs. 1·4 ± 0·4 µg/l). These GH (1 µg/l = 2 mU/l) responses in GHD were markedly lower (P < 0·0001) than those in NS (ghrelin vs. GHRH + ARG vs. ITT 92·1 ± 16·7 vs. 65·3 ± 8·9 vs. 17·7 ± 3·5 µg/l). In GHD, the highest individual peak GH response to ghrelin was markedly lower than the lowest peak GH response in NS (28·5 vs. 42·9 µg/l). GHD and NS showed overlapping PRL (1 µg/l = 32 mU/l) (10·0 ± 1·4 vs. 14·9 ± 2·2 µg/l), ACTH (22·3 ± 5·3 vs. 18·7 ± 4·6 pmol/l) and cortisol responses (598·1 ± 52·4 vs. 486·9 ± 38·9 nmol/l). conclusions This study shows that ghrelin is one of the most powerful provocative stimuli of GH secretion, even in those patients with isolated severe GHD. In this condition, however, the somatotroph response is markedly reduced while the lactotroph and corticotroph responsiveness to ghrelin is fully preserved, indicating that this endocrine activity is fully independent of mechanisms underlying the GH-releasing effect. These results do not support the hypothesis that ghrelin deficiency is a major cause of isolated GH deficiency but suggest that ghrelin might represent a reliable provocative test to evaluate the maximal GH secretory capacity provided that appropriate cut-off limits are assumed. [source]

Confirmation of severe GH deficiency after final height in patients diagnosed as GH deficient during childhood

CLINICAL ENDOCRINOLOGY, Issue 4 2002
Andrea F. Attanasio
Summary objective Human GH treatment of patients with childhood-onset (CO) growth hormone deficiency (GHD) ceases when they reach final height; this provides an opportunity to retest GH status in all patients before determining whether GH therapy will be required in adult life. At present, the diagnostic approach to these patients is not fully standardized. This study aimed to characterize a large group of previously GH-treated CO GHD patients and establish their GH status. patients and methods The multinational study included 167 patients diagnosed as GH deficient and treated with hGH to final height during childhood. Mean age was 19·2 years and mean height standard deviation score (SDS) was ,1·08. Peak serum GH concentrations were determined in standard GH stimulation tests. IGF-I and IGFBP-3 concentrations were determined at a central laboratory and converted to SDS values by reference to a normal population. results Using only a peak GH value of less than 3 µg/l (1 mg = 3 U) in stimulation tests as the cut-off, 133 (79·6%) patients would be classed as GH deficient. Using only an IGF-I value less than ,2 SDS as the cut-off, 134 (80·2%) patients would be classed as GH deficient. However, by using both criteria there were 120 (71·9%) patients who were definitely severely GH deficient (group 1) and 20 (12·0%) who were not GH deficient (group 2), leaving 14 (8·4%) classed as GH deficient from IGF-I SDS only (group 3) and 13 (7·8%) classed as GH deficient from stimulation test only (group 4). There was no difference between the groups in height SDS or body mass index (BMI), but the GH-deficient patients tended to have been diagnosed at a younger age (group 1, 8·2 ± 3·9; group 2, 10·0 ± 4·0; P = 0·052). For patients classed as GH deficient compared with those not GH deficient, the percentage of males was lower (group 1, 64·2%; group 2, 90·0%; P = 0·022) and the percentage with multiple pituitary hormone deficiencies was higher (group 1, 81·7%; group 2, 20·0%; P < 0·001), with the other two groups being intermediate in each case. Only the group classed as GH deficient by both criteria had a mean IGFBP-3 less than ,2 SDS and both IGF-I SDS and IGFBP-3 SDS increased steadily across the four groups. conclusions A high percentage (71·9%) of these childhood-onset GH-deficient patients were still GH deficient in adult life and are likely to require further hGH treatment. While 12·0% could be classed as definitely no longer GH deficient, there are some patients who are intermediate (16·2%) and may be classed as GH deficient by one criterion but not the other. When GH stimulation test results and IGF-I concentration are discordant, the IGFBP-3 level does not establish diagnosis and the hGH treatment requirement of such patients remains a dilemma. [source]