Growth Hormone Disturbances Research Articles

Growth hormone and ghrelin secretion are associated with clinical severity in Huntington’s disease

Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder caused by an increased CAG repeat size in the huntingtin gene. Apart from neurological impairment, the disease is also accompanied by progressive weight loss, abnormalities in glucose homeostasis and a higher prevalence of diabetes mellitus, which may partly be caused by disturbed growth hormone (GH) and ghrelin secretion. Therefore, we aimed to perform a detailed analysis of GH and ghrelin secretion in HD patients in relation to clinical signs and symptoms. In nine early-stage, medication-free HD patients and nine age-, gender- and body mass index-matched controls, we measured serum GH levels every 10 min for 24 h and assessed ghrelin response to food intake. Multi-parameter auto-deconvolution and approximate entropy analysis were applied to quantify basal, pulsatile, and total GH secretion rates as well as the regularity of GH secretion. We found no significant differences in GH and ghrelin secretion characteristics between HD patients and controls (total GH secretion: 137 +/- 36 vs. 181 +/- 43 mU/l/24 h, respectively; P = 0.439). However, in HD patients, both GH secretion and its irregularity as well as the degree of postprandial ghrelin suppression significantly increased with worsening motor and functional impairment (all P < 0.05). Moreover, postprandial ghrelin suppression also increased with decreasing body weight and higher CAG repeat number (both P < 0.05). These findings suggest changes in the regulation of GH and ghrelin secretion dynamics in early stage HD patients that could become more prominent in the later stages of the disease.

The coagulation system in endocrine disorders: A narrative review

Endocrine disorders can influence the haemostatic balance. Abnormal coagulation test results have been observed in patients with abnormal hormone levels. Also unprovoked bleeding or thrombotic events have been associated with endocrine disease. The aim of the present review is to summarise the available evidence on the influence of common endocrine disorders on the coagulation system, and their possible clinical implications. We focus on thyroid dysfunction, hyper- and hypocortisolism and growth hormone disturbances, while other endocrine disorders are only briefly discussed. In the published literature a clear bleeding diathesis has only been associated with overt hypothyroidism, mainly mediated by an acquired von Willebrand syndrome. A clinically relevant hypercoagulable state may be present in patients with hyperthyroidism, hypercortisolism or abnormal growth hormone levels, but adequate prospective clinical studies are lacking. Also effects of pheochromocytoma, hyperprolactinaemia and hyperaldosteronism on the coagulation system have been described. It is apparent that unprovoked bleeding and thrombotic episodes can be secondary to endocrine disorders.

Growth hormone/insulin-like growth factor system in children with chronic renal failure

Disturbances of the somatotropic hormone axis play an important pathogenic role in growth retardation and catabolism in children with chronic renal failure (CRF). The apparent discrepancy between normal or elevated growth hormone (GH) levels and diminished longitudinal growth in CRF has led to the concept of GH insensitivity, which is caused by multiple alterations in the distal components of the somatotropic hormone axis. Serum levels of IGF-I and IGF-II are normal in preterminal CRF, while in end-stage renal disease (ESRD) IGF-I levels are slightly decreased and IGF-II levels slightly increased. In view of the prevailing elevated GH levels in ESRD, these serum IGF-I levels appear inadequately low. Indeed, there is both clinical and experimental evidence for decreased hepatic production of IGF-I in CRF. This hepatic insensitivity to the action of GH may be partly the consequence of reduced GH receptor expression in liver tissue and partly a consequence of disturbed GH receptor signaling. The actions and metabolism of IGFs are modulated by specific high-affinity IGFBPs. CRF serum has an IGF-binding capacity that is increased by seven- to tenfold, leading to decreased IGF bioactivity of CRF serum despite normal total IGF levels. Serum levels of intact IGFBP-1, -2, -4, -6 and low molecular weight fragments of IGFBP-3 are elevated in CRF serum in relation to the degree of renal dysfunction, whereas serum levels of intact IGFBP-3 are normal. Levels of immunoreactive IGFBP-5 are not altered in CRF serum, but the majority of IGFBP-5 is fragmented. Decreased renal filtration and increased hepatic production of IGFBP-1 and -2 both contribute to high levels of serum IGFBP. Experimental and clinical evidence suggests that these excessive high-affinity IGFBPs in CRF serum inhibit IGF action in growth plate chondrocytes by competition with the type 1 IGF receptor for IGF binding. These data indicate that growth failure in CRF is mainly due to functional IGF deficiency. Combined therapy with rhGH and rhIGF-I is therefore a logical approach.

Arm span, serum IGF-1 and IGFBP-3 levels as screening parameters for the diagnosis of growth hormone deficiency in patients with myelomeningocele--preliminary data.

Short stature is a common problem in patients with myelomeningocele (MMC) and hydrocephalus. We evaluated auxological and laboratory parameters to differentiate short stature due to neurological defect from short stature additionally caused by growth hormone deficiency (GHD). In a group of 38 prepubertal patients with MMC and hydrocephalus aged 3.8-11.0 years, auxological parameters, including arm span and bone age, and serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured. Patients with normal supine length (n = 15) had normal arm span. Serum IGF-1 and IGFBP-3 levels were normal (> or = 10th percentile) in 14/15 patients. Twenty-three MMC patients had short stature (height SDS < -2), 11/23 patients had reduced arm span (SDS < -2), and 12/23 had normal arm span. Serum IGF-1 and IGFBP-3 levels were normal in 10/12 of short statured patients with normal arm span, but low (< 10th percentile) in those patients with reduced arm span (IGF-1: 8/11 patients, P < 0.05; IGFBP-3: 9/11 patients, P < 0.005). In 7/11 short statured MMC patients with reduced arm span and low serum IGF-1 and IGFBP-3 levels, growth hormone secretion was investigated. All had a disturbed growth hormone secretion (GHD: n = 4; neurosecretory dysfunction: n = 3). Arm span, serum IGF-1 and IGFBP-3 levels are estimated to be appropriate screening parameters for GHD in patients with MMC. Initiating growth hormone therapy should be considered not only according to endocrine findings but also with respect to neurological and orthopaedic anomalies.

Children Born Small-for-Gestational Age: Postnatal Growth and Hormonal Status

It is generally recognized that children born small-for-gestational age (SGA) have a 5–7 times higher risk of short stature than children born at normal size. It has been suggested that the programming of the endocrine axes occurs during critical phases of fetal development and is affected by intrauterine growth retardation. This study was undertaken to characterize the postnatal growth pattern and the final height of children born SGA, as part of a population- based study (n = 3,650), from birth to final height, and to evaluate the hormonal status in another group of prepubertal children born SGA (n = 134) without postnatal catch-up growth. The majority (88%) of ‘healthy’ full-term singleton SGA infants achieved catch-up growth during the first 2 years of life, and most of the increase in height occurred by 2 months of age. The SGA children who remained short at 2 years of age had a higher risk of short stature later in life. The risk of having a short final height (<–2 SDS) was five times higher for children with a low birth weight and seven times higher for those with a low birth length in comparison with children with a normal birth size. Moreover, about 20% of all children of short stature were born SGA. As a group, children born SGA will have a final height, expressed in SDS, as they had during the prepubertal years. This is in contrast to children, who became short postnatally. During puberty, these short children will have a mean height gain of 0.6 SDS for girls and 0.7 SDS for boys. The mean estimated secretion rate for growth hormone (GH) was lower in the short children born SGA compared with the reference groups born at an appropriate size for gestational age, of either short (p < 0.05) or normal stature (p < 0.001). Moreover, in the youngest children born SGA (2–6 years of age) a different pattern of GH secretion was found, with a high basal GH level, low peak amplitude, and high peak frequency. The majority of the children born SGA had levels of GH-binding protein within the range previously reported for normal children. However, the levels of insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3) and leptin were significantly reduced compared with the reference values (p < 0.001, p < 0.01 and p < 0.001, respectively). In conclusion, the low spontaneous GH secretion rate and a disturbed GH secretion pattern, together with low serum levels of IGF-I, IGFBP-3 and leptin, might contribute to the reduced postnatal growth in some of the subgroup of children born SGA who remained short during childhood.

Review of Neuroendocrine Disturbances in the Chronic Fatigue Syndrome

AbstractThe investigation of the growth hormone (GH)-IGF-J. axis in patients with chronic fatigue syndrome (CFS) may be important for different reasons. Some of the disturbances of the hypothalamic-pituitary-adrenal axis and central serotonincrgic (5-HT) function in CFS will be reviewed, before elaborating on three hypotheses that may explain the role of a disturbed GH axis activity in CFS. Firstly, the disturbed central 5-HT receptor activity may be the cause of GH axis dysfunction. Secondly, CFS may be considered as a “stress-related illness,” in which the disturbed central 5-HT function is a result rather than the cause of impaired neuroendocrine stress responses. Finally, by analogy with fibromyalgia, sleep abnormalities in CFS may impair nocturnal GH secretion. Whether the disturbed GH axis activity is a primary or secondary phenomenon in the pathogenesis of CFS, should be elucidated by future clinical investigations.

Effects of nutrition, growth hormone disturbances, training, altitude and sleep on lung volumes.

Various modulating factors have been shown to affect postnatal lung growth and development in humans and other mammalian species. Therefore, normative pulmonary function data should ideally indicate the environmental conditions of life. This paper will review current knowledge on the effects of nutrition, growth hormone disturbances, training and altitude on lung volumes in children and adults. Furthermore, the impact of sleep states on lung volumes is considered. The present review is a background paper of a consensus document on measurements of lung volumes in humans.

Growth and growth hormone secretion after treatment for childhood non-Hodgkin's lymphoma.

The aim of this study was to evaluate the growth and growth hormone (GH) secretion, as assessed by the rate and pattern of secretion, in patients in remission from non-Hodgkin's lymphoma (NHL) who had been treated with corticosteroids and intense chemotherapy. None of the patients had received cranial irradiation. Twelve children were investigated yearly by taking 24-hour GH profiles starting 1 year from the time of diagnosis. The mean age at onset of the disease was 7.5 years. Another 12 young adults were studied in a cross-sectional manner 4.1-21.3 years (mean, 9.0 years) after diagnosis of NHL. The mean age at onset of the disease was 10.7 years. The median height velocity was significantly decreased during the 1st year following diagnosis (standard deviation scores [SDS] -0.15, P < .001), especially during the first 3 months (SDS -0.75, P < .001) when the most intense treatment was given. During the 2nd year height velocity was still somewhat reduced (SDS -0.13, P < .001). However, there was no reduction in final attained height. Spontaneous GH secretion, in terms of both secretory rate and pulsatile pattern, was evaluated by measuring integrated GH concentrations in 20-minute blood samples collected over a 24-hour period. The plasma GH concentrations were transformed into GH secretion rates by means of a deconvolution technique. Fourier time series analysis was applied to determine possible disturbances of rhythmicity of the GH secretion. The GH secretion rate and the pulsatile pattern of secretion in the NHL patients were similar to those of the reference population of pubertal matched healthy controls. There was no influence of the age at diagnosis or of the time from diagnosis of NHL on the GH secretion rate. Growth impairment in children with a malignant disease treated only with steroids and chemotherapy is therefore probably not caused by disturbed GH secretion, but rather by direct interference with bone growth of the cytotoxic drugs used. There was no significant influence on weight gain during the treatment period so an indirect effect of chemotherapy on bone growth through interference with adequate nutrition seems unlikely. However, GH secretion was not evaluated during the period of growth retardation, and therefore a transient deficiency was not excluded.

Effect of short-term treatment with recombinant human growth hormone on lipids and lipoproteins in women and men without growth hormone disturbances

The effect of recombinant human growth hormone (rHGH) on cholesterol, high- and low-density lipoprotein (HDL and LDL) cholesterol, triglycerides (TG), apolipoprotein (apo) B, apo A-I, and lipoprotein(a) [Lp(a)] was studied in 40 postmenopausal women treated with 0.05, 0.1, or 0.2 IU/kg/d rHGH or placebo for 7 days. Cholesterol, LDL cholesterol, and HDL cholesterol decreased in a dose-dependent manner ( P = .001, P = .001, and P = .003, respectively), whereas apo B decreased insignificantly ( P = .15). Apo A-I decreased significantly only among women treated with rHGH at a dose of 0.1 IU/kg/d ( P = .03). When all rHGH-treated women were grouped together, Lp(a) increased ( P = .001). We also studied 20 young men treated with either 0.2 IU/kg/d rHGH or placebo. As in women, cholesterol and apo B decreased ( P = .005 and P = .02, respectively), whereas Lp(a) increased ( P = .05). There was no detectable effect of rHGH on TG concentrations in men. As in women, there was no significant effect of 0.2 IU/kg/d rHGH on apo A-I concentrations. All lipid and lipoprotein measures reached pretreatment levels during the first week after treatment was stopped, except Lp(a), which remained elevated 2 weeks after rHGH cessation.

Serum insulin-like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin.

There is a clinical need for population based reference values for serum insulin-like growth factor I (IGF-I). We have therefore determined serum IGF-I concentrations in a random population sample from Sweden and have related the levels to age, sex, life style factors, blood pressure, body composition, blood lipids, plasma fibrinogen, parathyroid hormone (PTH) and osteocalcin. Within the framework of the WHO MONICA Project in the city of Göteborg, Sweden, 197 men and 195 women aged 25-64 years were studied. Women aged 25-34 years had higher IGF-I concentration than men (mean 278 vs 227 micrograms/l) but in the interval 55-64 years values were lower in women than in men (158 vs 171 micrograms/l). IGF-I correlated positively with height and inversely with age, body mass index, systolic blood pressure and total cholesterol in both sexes. Negative relations between IGF-I and high density lipoprotein-cholesterol, as well as with amount of tobacco smoked, were found in men, and between IGF-I and diastolic blood pressure, triglycerides and PTH in women. When age was allowed for in multivariate analyses, most of these relations disappeared. However, among men IGF-I was positively associated with fibrinogen and negatively with age and smoking. IGF-I was negatively associated with age and coffee consumption in women. The present data can be used as reference values for IGF-I (at least in Caucasians) for the diagnosis of growth hormone disturbances and as guidelines for growth hormone substitution.

Immunoreactive IGF-II in serum of healthy subjects and patients with growth hormone disturbances and uraemia.

A radioimmunoassay has been developed for IGF-II, using Sepharose-coupled antibodies. Porcine insulin, human insulin and human proinsulin showed no cross-reaction, whereas the cross-reaction for IGF-I was 10%. To minimize the influence of the binding protein(s), all serum samples were extracted with acid ethanol before assay. The mean serum level of immunoreactive IGF-II and 95% confidence limit in 46 healthy adults were 587 ng/ml and 354-974 ng/ml, respectively. In contrast to the declining levels of IGF-I with increasing age, no such age-dependent decrease was found for IGF-II levels between 20 to 70 years. No difference in IGF-II levels was found between patients with acromegaly and healthy adult controls. In cord serum and serum from adult patients with GH deficiency the levels were significantly lower (P less than 0.001) compared to controls. In diabetic patients with uraemia the mean level and 95% confidence limit were 1222 ng/ml and 532-2808 ng/ml, respectively. Thus, significantly increased serum levels of immunoreactive IGF-II have only been found in serum from patients with uraemia. Whether this is due to an increased production of IGF-II, or secondary to other factors such as the binding protein(s), will require further investigation.

Dissociation of growth hormone and prolactin secretion in Parkinson's disease following chronic L-dopa therapy.

ABSTRACT Growth hormone (GH) and prolactin (PRL) secretion during a 24-hr period was evaluated in 10 patients with Parkinson's disease who had ingested 2–5 g of l-dopa per day for 2.5 to 4 yr. None of the patients displayed clinical evidence of acromegaly and their mean ± sem concentration of GH over a 24-hr period, 2.37 ± 0.27 ng/ml, was normal. l-Dopa failed to stimulate GH secretion 79% of the time in these patients. Only one patient consistently demonstrated a GH secretory peak after each dose of l-dopa given during a 24-hr interval. Further evidence of disturbed GH regulation was provided by an unexpected suppression of GH following l-dopa in 3 patients and a paradoxical increase in GH following glucose found in 2 subjects. However, when challenged with insulin hypoglycemia, each of 7 patients tested responded with a normal GH secretory peak. The mean ± sem basal and peak GH response following insulin were 1.3 ± 0.2 and 15.6 ± 2.3 ng/ml, respectively. In all patients, serum PRL was appropriately supp...