GH Response In Patients Research Articles

GH Responsiveness Is not Correlated to IGF1 P2 Promoter Methylation in Children With Turner Syndrome, GHD and SGA Short Stature.

BackgroundThe methylation of IGF1 promoter P2 was reported to negatively correlate with serum IGF-1 concentration and rhGH treatment response in children with idiopathic short stature. These findings have not yet been confirmed.ObjectiveThis study aimed to determine IGF1 promoter P2 methylation in short children treated with rhGH and correlate clinical parameters with the methylation status. In addition, long-term stability of methylation during rhGH treatment was studied.DesignThis was a single tertiary center study analyzing clinical GH response and IGF-1 serum concentration changes in patients with GHD (n=40), SGA short stature (n=36), and Turner syndrome (n=16) treated with rhGH. Data were correlated to the methylation of two cytosine residues (-137, +97) of the P2 promoter of IGF1 in blood cells measured by pyrosequencing in 443 patient samples.ResultsBasal and stimulated IGF-1 concentrations, first year increment in height velocity and studentized residuals of a prediction model did not correlate to the methylation of -137 und +97 in IGF1 P2 promoter. The methylation of these two sites was relatively stable during treatment.ConclusionsThis study did not confirm IGF1 P2 promotor being a major epigenetic locus for GH responsiveness in patients treated with a normal dose of rhGH. Additional studies are warranted.

The diagnosis of GH deficiency in obese patients: a reappraisal with GHRH plus arginine testing after pharmacological blockade of lipolysis

The diagnosis of GH deficiency (GHD) in obese patients is complicated by the reduced GH secretion associated with overweight. A GH response to GHRH+arginine lower than 4.2 microg/l is currently considered indicative of GHD in obesity. The aim of the study was to investigate the effect of acute pharmacological blockade of lipolysis on the GH response to GHRH+arginine in obese patients. Two groups of patients were studied: 12 obese patients with proven GHD and 14 patients with essential obesity. On separate occasions, two tests were carried out in each patient: GHRH+arginine and GHRH+arginine preceded by acipimox. The mean GH peak after GHRH+arginine was significantly lower in hypopituitary patients than in subjects with essential obesity. Acipimox significantly increased the mean GH response in patients with essential obesity, but not in hypopituitary subjects. All hypopituitary patients and 7/14 patients with essential obesity displayed GH peaks lower than 4.2 microg/l after GHRH+arginine: the GH response to the test increased after acipimox pretreatment in five of these seven essentially obese subjects. After acipimox administration, free fatty acids (FFAs) significantly fell in both groups with comparable mean absolute decreases. All IGF1 values were normal in both groups of subjects. Our study has demonstrated that the acipimox-induced acute reduction of circulating FFA levels increases mean somatotropin response to GHRH+arginine in patients with essential obesity, whereas it has no effect in hypopituitary subjects. The current criterion for the diagnosis of GHD in obese patients may be misleading. Indeed, subjects affected by third degree obesity, like most of our patients, may be erroneously classified as really GH-deficient and started on an expensive unjustified treatment. It appears therefore that the current criteria for the diagnosis of GHD in obesity should be reconsidered in the light of further studies also taking into account different body mass index groups.

Growth hormone response to physical exercise in growing patients with classic congenital adrenal hyperplasia

Glucocorticoid over-treatment in children with congenital adrenal hyperplasia (CAH) may suppress GH secretion and growth. Aims of our study were: 1) to evaluate post-exercise GH response in patients affected by CAH due to 21-hydroxylase deficiency, in comparison with a group of healthy subjects; 2) to investigate the relationship between the hormonal markers of adequate steroid therapy and GH secretion. We evaluated GH secretion every 6 months in 20 young CAH patients (8 girls, 12 boys). Mean follow-up was 4.6+/-0.9 yr (107 tests performed, 5.35+/-2.05 repeated tests for each patient). Forty-four healthy subjects (25 boys, 19 girls) were selected as a control group. The range of post-exercise GH peak was very wide, but medians were not statistically different in cases and controls (p=0.570). Multivariate analysis showed that post-exercise GH peak was not related to age (p=0.743), gender (p=0.296) or pubertal status (p=0.440) in both groups. GH increase from baseline showed the same behavior (p=0.265, 0.639 and 0.105, respectively). In CAH patients, GH peak and GH increase were both directly related to 17-OH-progesterone levels [GH peak: p=0.032--95% confidence interval (CI): 0.01-0.34--beta=0.18; GH increase: p=0.008--95% CI: 0.06-0.35--beta=0.20]. The negative effect of glucocorticoid therapy on GH secretion seems to be dominant in CAH. The most effective approach to adjust treatment remains monitoring growth. Relying on hormonal markers to adequate steroid therapy may result in over-treatment, GH suppression, and finally poor linear growth.

Effect of corticotrophin-releasing hormone administration on growth hormone levels in acromegaly: in vivo and in vitro studies.

The ability of CRH to cause a paradoxical response of GH in acromegaly is still under debate. In this study, the effect of CRH administration on GH release was evaluated in a large series of patients with active acromegaly, both in vivo, compared to that of TRH and GnRH, and in vitro. The study was organized as follows. In vivo study: 30 acromegalic patients were submitted to TRH, GnRH, and CRH tests on non-consecutive days: blood samples were collected before and 10, 20, 30, 45, 60, 90, and 120 min after bolus. In nine patients the CRH test was repeated after a 3-month therapy with octreotide and at the dose of 300-600 micrograms sc thrice daily. In vitro study: CRH (10 nmol/l, 100 nmol/l, and 1 mumol/l) was tested on pituitary tumor tissue obtained in eight patients during transsphenoidal adenomectomy and immediately placed in sterile Ca2+ and Mg2+ free buffer phosphate. A paradoxical GH response to TRH (evaluated as a GH increase over 50% of basal values) was recorded in 19 patients (63.3%), whereas 7 patients (23.3%) responded to GnRH and 4 others to CRH (13.3%). TRH administration induced a maximal percent GH increase significantly greater than that induced by GnRH and CRH (p < 0.05). Octreotide caused the normalization of GH and insulin-like growth factor-I levels in all the patients, as well as the disappearance of the GH paradoxical response to CRH in 3/4 patients. All four CRH responders and four CRH non-responders, used as controls, were surgically treated and adenomatous tissue was used for the in vitro study.(ABSTRACT TRUNCATED AT 250 WORDS)

GHRH-induced GH response in patients with senile dementia of the Alzheimer type

To clarify the functional state of the somatotropinergic system at the hypothalamo-hypophyseal level in senile dementia of the Alzheimer type, the GHRH test was performed in three groups of subjects: a) healthy elderly subjects; b) early onset senile dementia patients; and c) late onset senile dementia patients. Intravenous administration of GHRH(1-44)NH2 (100 micrograms) elicited a marked plasma GH response with a maximum peak (709.54 +/- 259.0 pmol/l; P less than 0.005) 60 min after injection in patients with early onset senile dementia, but no significant response was detected in the other two groups. Electroencephalographic recording showed that GHRH modifies brain bioelectrical activity, decreasing frequency (0.52 +/- 0.15 Hz) and increasing amplitude (8.25 +/- 4.5 microV) of the electroencephalogram basic rhythm. The evaluation of mental performance and behaviour with a battery of different tests for mental assessment revealed that GHRH induces transient clinical changes in psychomotor behaviour. According to these results, it seems likely that the somatostatin deficiency reported in senile dementia of the Alzheimer type may account for the enhanced GHRH-induced GH response observed in patients with early onset senile dementia. In consequence, the GHRH test might constitute a useful antemortem marker for senile dementia of the Alzheimer type if the present results can be replicated in early stages of the disease.

GROWTH HORMONE HYPERRESPONSIVENESS TO GROWTH HORMONE‐RELEASING HORMONE IN PATIENTS WITH SEVERE LIVER CIRRHOSIS

Patients with severe liver disease often have high baseline plasma GH levels and/or paradoxical GH release in response to several secretagogues, e.g. TRH. In this paper, we have investigated in a group of cirrhotic patients the GH response to GH-releasing hormone (GHRH) and evaluated the effectiveness of GHRH to cause GH release in TRH responder and non-responder patients. Ten patients and seven age- and sex-matched control subjects were given bolus injections of GHRH (0.1 and 1.0 microgram/kg i.v. on separate occasions). GHRH 0.1 microgram/kg failed to cause a GH response in both control and cirrhotic subjects, but 1.0 microgram/kg caused a significantly higher GH response in patients than in controls. Evaluation of the GH response curve after GHRH revealed a similar pattern of secretion in the TRH-responders (four subjects) and non-responders (six subjects). These results suggest that the enhanced GH responsiveness to GHRH in cirrhotic patients may contribute to their high baseline GH levels and/or secretory rate, and the mechanism(s) of the paradoxical GH rise after TRH seems to be separate from that for GH hyperresponsiveness to GHRH.

Sex difference in the paradoxical response of serum GH to thyrotrophin releasing hormone in cancer patients.

It was demonstrated that thyrotropin-releasing hormone (TRH) elicited a paradoxical increase in basal GH levels in cancer patients. Out of 94 cancer patients, 50 were found to be GH responders and this phenomenon was more frequently recognized in female than in male cancer patients. In cancer patients under 59 years of age, the GH response to TRH was significantly greater in females than in males, although there was no sex difference in the GH response in patients above 60 years of age. In female cancer patients, the GH response to TRH was significantly greater in patients under 59 years of age than in patients above 60 years of age, while there was no age difference in the GH response in male cancer patients. It was concluded that paradoxical responses of serum GH to TRH were recognized in 53 per cent of cancer patients and were more frequently observed in female than in male cancer patients.