Dataset Information

Effects of growth hormone (GH) therapy withdrawal on glucose metabolism in not confirmed GH deficient adolescents at final height.

ABSTRACT:

Context objective

Growth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR).

Design setting

We performed a longitudinal study (1 year) in a tertiary care center.

Methods

23 GHD adolescent were followed in the last year of rhGH treatment (T0), 6 (T6) and 12 (T12) months after rhGH withdrawal with fasting and post-OGTT evaluations. 40 healthy adolescents were used as controls. HOMA-IR, HOMA%?, insulinogenic (INS) and disposition (DI) indexes were calculated. GHR genotypes were determined by multiplex PCR.

Results

In the group as a whole, fasting insulin (p<0.05), HOMA-IR (p<0.05), insulin and glucose levels during OGTT (p<0.01) progressively decreased from T0 to T12 becoming similar to controls. During rhGH, a compensatory insulin secretion with a stable DI was recorded, and, then, HOMA? and INS decreased at T6 and T12 (p<0.05). By evaluating the GHR genotype, nDel GHD showed a decrease from T0 to T12 in HOMA-IR, HOMA?, INS (p<0.05) and DI. Del GHD showed a gradual increase in DI (p<0.05) and INS with a stable HOMA-IR and higher HDL-cholesterol (p<0.01).

Conclusions

In not confirmed GHD adolescents the fasting deterioration in glucose homeostasis during rhGH is efficaciously coupled with a compensatory insulin secretion and activity at OGTT. The presence of at least one d3GHR allele is associated with lower glucose levels and higher HOMA-? and DI after rhGH withdrawal. Screening for the d3GHR in the pediatric age may help physicians to follow and phenotype GHD patients also by a metabolic point of view.

SUBMITTER: Prodam F

PROVIDER: S-EPMC3907518 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Effects of growth hormone (GH) therapy withdrawal on glucose metabolism in not confirmed GH deficient adolescents at final height.

Prodam Flavia F Savastio Silvia S Genoni Giulia G Babu Deepak D Giordano Mara M Ricotti Roberta R Aimaretti Gianluca G Bona Gianni G Bellone Simonetta S

PloS one 20140130 1

<h4>Context objective</h4>Growth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR).<h4>Design setting</h4>We performed a longitu ...[more]

PMID: 24498035

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Project description:The prevalence of idiopathic oligozoospermia has been esteemed as high as 75%. An Italian survey has reported bilateral testicular hypotrophy in 14% of final-year high school students. The search for determinants of testicular growth in childhood is important for the primary prevention of spermatogenic failure. Therefore, this retrospective study aimed to evaluate the testicular growth and pubertal onset in deficient children treated recombinant human growth hormone (rhGH). To accomplish this, the clinical charts of 93 patients with GH deficiency (GHD) were carefully reviewed. Their mean age at the time of diagnosis was 11.2 ± 2.4 years. rhGH was administered for 44.0 ± 22.4 months, and the onset of puberty was recorded after a mean of 25.8 ± 22.4 months from the first rhGH administration. As expected, serum insulin-like growth factor 1 (IGF1) levels increased significantly after treatment. Before rhGH therapy, the Tanner stage was I in 59 out of 70 boys (84.3%), II in 8/70 (11.4%), III in 3/70 (4.3%). No one was on stage IV or V. The mean Tanner stage was 1.19 ± 0.51. At the last visit, the Tanner stage was I in 8/72 boys (11.1%), II in 6/72 (8.3%), III in 6/72 (8.3%), IV in 16/72 (22.2%), and V in 36/72 (50.0%). After a mean of 44.0 ± 22.4 months of rhGH treatment, the mean Tanner stage was 4.05 ± 1.30. Patients treated with rhGH showed a significant testicular volume (TV) growth over time, whereas no growth was observed in age-matched but not yet treated patients, even when the age was compatible with a spontaneous start of puberty. The multivariate regression analysis showed that the duration of treatment and the mean rhGH dose significantly predicted the percentage of TV increase. In contrast, age, serum FSH, and IGF1 levels, and final rhGH dose did not impact TV growth over time. In conclusion, these findings suggest that GH may play a role in testicular growth and pubertal onset, despite the descriptive nature of this study. Further properly designed studies are needed to confirm these findings. This knowledge may be useful to implement the diagnostic-therapeutic algorithm in case of a lack of testicular growth in childhood.

Project description:OBJECTIVE:The liver is a central target organ of growth hormone (GH), which stimulates the synthesis of insulin-like growth factor 1 (IGF1) and affects multiple biochemical pathways. A systematic multi-omics analysis of GH effects in the liver has not been performed. GH receptor (GHR) deficiency is a unique model for studying the consequences of lacking GH action. In this study, we used molecular profiling techniques to capture a broad spectrum of these effects in the liver of a clinically relevant large animal model for Laron syndrome. METHODS:We performed holistic proteome and targeted metabolome analyses of liver samples from 6-month-old GHR-deficient (GHR-KO) pigs and GHR-expressing controls (four males, four females per group). RESULTS:GHR deficiency resulted in an increased abundance of enzymes involved in amino acid degradation, in the urea cycle, and in the tricarboxylic acid cycle. A decreased ratio of long-chain acylcarnitines to free carnitine suggested reduced activity of carnitine palmitoyltransferase 1A and thus reduced mitochondrial import of fatty acids for beta-oxidation. Increased levels of short-chain acylcarnitines in the liver and in the circulation of GHR-KO pigs may result from impaired beta-oxidation of short-chain fatty acids or from increased degradation of specific amino acids. The concentration of mono-unsaturated glycerophosphocholines was significantly increased in the liver of GHR-KO pigs without morphological signs of steatosis, although the abundances of several proteins functionally linked to non-alcoholic fatty liver disease (fetuin B, retinol binding protein 4, several mitochondrial proteins) were increased. Moreover, GHR-deficient liver samples revealed distinct changes in the methionine and glutathione metabolic pathways, in particular, a significantly increased level of glycine N-methyltransferase and increased levels of total and free glutathione. Several proteins revealed a sex-related abundance difference in the control group but not in the GHR-KO group. CONCLUSIONS:Our integrated proteomics/targeted metabolomics study of GHR-deficient and control liver samples from a clinically relevant large animal model identified a spectrum of biological pathways that are significantly altered in the absence of GH action. Moreover, new insights into the role of GH in the sex-related specification of liver functions were provided.

Dataset Information

Effects of growth hormone (GH) therapy withdrawal on glucose metabolism in not confirmed GH deficient adolescents at final height.

Context objective

Design setting

Methods

Results

Conclusions

Publications

Effects of growth hormone (GH) therapy withdrawal on glucose metabolism in not confirmed GH deficient adolescents at final height.

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