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Cecilia Camacho-Hübner

Publications and source records attributed to Cecilia Camacho-Hübner.

16 recordsLinked to original sources
PubMed2006

Final height in patients with idiopathic short stature and high growth hormone responses to stimulation tests.

UNLABELLED: Children with idiopathic short stature (ISS) may have normal or increased growth hormone (GH) responses to provocation tests and achieve a final height (FH) below -2.0 standard deviation score (SDS) if untreated. FH of subjects with high stimulated GH levels has not been studied in detail. AIM: It was the aim of this study to analyse FH in ISS patients with high GH peak responses to the provocation test. PATIENTS AND METHODS: We studied 16 patients (9 pre-pubertal) with ISS and a GH peak >or=40 mU/l to insulin-induced hypoglycaemia. The patients were recalled at age 19.7 +/- 2.5 years for measurement of FH when blood samples were obtained for serum insulin-like growth factor (IGF)-I, IGF binding protein 3, acid-labile subunit and GH binding protein measurements. GH bioactivity was determined using the Nb2 bioassay. RESULTS: FH was -3.1 +/- 1.0 SDS, being significantly lower than target height (TH). At FH, IGF-I levels were within -1.5 and +1.5 SDS for age and sex in 10 patients and higher than +1.5 SDS in 6 patients. IGF binding protein 3, acid-labile subunit, GH binding protein levels and GH bioactivity values were normal. SUMMARY: These data suggest that patients with ISS and high GH levels during a GH stimulation test may have a more compromised FH. The association of severe ISS with a peak GH >40 mU/l might suggest a degree of insensitivity for the GH-IGF-I axis.

Adolescent↗
PubMed2006

Postnatally elevated levels of insulin-like growth factor (IGF)-II fail to rescue the dwarfism of IGF-I-deficient mice except kidney weight.

This study tested whether elevated levels of IGF-II in the postnatal period can rescue the dwarfism in IGF-I-deficient mice. Heterozygous Igf1 mutant mice [I(+/-) II(wt)] were crossed with heterozygous Igf1 mutant, phosphoenolpyruvate carboxykinase promoter IGF-II transgenic mice [I(+/-) II(tg)], and [I(+/+) II(wt)], [I(+/+) II(tg)], [I(-/-) II(wt)], and [I(-/-) II(tg)] offspring were investigated. IGF-II levels were 11- and 6-fold higher in male and female [I(-/-) II(tg)] vs. [I(-/-) II(wt)] animals. Western ligand blot analysis revealed markedly reduced activities of 30- and 32-kDa IGF binding proteins (IGFBPs) (most likely IGFBP-1 and IGFBP-2) and the 39- to 43-kDa IGFBP-3 double band in serum from IGF-I-deficient mice. These binding proteins were partially restored by overexpression of IGF-II. Analysis of weight data from the early postnatal period until d 60 showed that, in the absence of IGF-I, elevated levels of IGF-II have no effect on body weight gain. A detailed analysis of body proportions, bone parameters, and organ weights of 60-d-old mice also failed to show effects of IGF-II with one important exception: in Igf1 mutant and also Igf1 intact male mice, IGF-II overexpression significantly increased absolute (+32.4 and +28.6%; P < 0.01) and relative kidney weights (+29.0 and +22.4%; P < 0.001). These changes in kidney weight were associated with reduced phosphorylation of p38 MAPK. In summary, our genetic model shows that substantial amounts of IGF-II in the circulation do not rescue the postnatal growth deficit of IGF-I-deficient mice but increase absolute and relative kidney weights of normal and IGF-I-deficient male mice, suggesting a gender-specific role of IGF-II for kidney growth.

Animals↗
PubMed2006

Dehydroepiandrosterone improves psychological well-being in male and female hypopituitary patients on maintenance growth hormone replacement.

CONTEXT: Patients with panhypopituitarism have impaired quality of life (QoL) despite GH replacement. They are profoundly androgen deficient, and dehydroepiandrosterone (DHEA) has been shown to have a beneficial effect on well-being and mood in patients with adrenal failure and possibly in hypopituitarism. OBJECTIVE: Our objective was to determine the effect of DHEA administration on mood in hypopituitary adults on established GH replacement with a constant serum IGF-I. DESIGN: A double-blind, placebo-controlled trial was conducted over an initial 6 months followed by an open phase of 6 months of DHEA. SETTING: The study was conducted at a tertiary referral endocrinology unit. PATIENTS: Thirty female and 21 male hypopituitary patients enrolled. Data from 26 females and 18 males were analyzed after patient withdrawal. INTERVENTIONS: DHEA (50 mg) was added to maintenance replacement including GH. MAIN OUTCOME MEASURES: The primary outcome objective was the effect on QoL and libido assessed by QoL assessment in GH deficiency in adults, Short Form 36, General Health Questionnaire, EuroQol, and sexual self-efficacy scale. RESULTS: Patients had impaired QoL at baseline compared with the age-matched British population. Females showed improvement in QoL assessment in GH deficiency in adults score (-2.9 +/- 2.8 DHEA vs.-0.53 +/- 3 placebo; P < 0.05), in Short Form 36 social functioning (14.6 +/- 23.1 DHEA vs.-4.7 +/- 25 placebo; P = 0.047), and general health perception (9.6 +/- 14.2 DHEA vs.-1.2 +/- 11.6 placebo; P = 0.036) after 6 months of DHEA. Men showed improvement in self-esteem (-1.3 +/- 1.7 DHEA vs. 0.5 +/- 1.5 placebo; P = 0.03) and depression (-1.6 +/- 2.2 DHEA vs. 1.2 +/- 2.4 placebo, P = 0.02) domains of the General Health Questionnaire after 6 months of DHEA. CONCLUSIONS: DHEA replacement leads to modest improvement in psychological well-being in female and minor psychological improvement in male hypopituitary patients on GH replacement.

Dehydroepiandrosterone↗
PubMed2006

Pharmacokinetic studies of recombinant human insulin-like growth factor I (rhIGF-I)/rhIGF-binding protein-3 complex administered to patients with growth hormone insensitivity syndrome.

CONTEXT: GH insensitivity syndrome (GHIS), Laron syndrome, is characterized by severe short stature, high serum GH levels, and very low serum IGF-I and IGF-binding protein-3 (IGFBP-3) levels associated with a genetic defect of the GH receptor. Recombinant human (rh) IGF-I treatment at doses of 80-120 microg/kg given sc twice daily is effective in promoting growth in these patients. We have investigated a newly developed drug, rhIGF-I/rhIGFBP-3, a 1:1 molar complex of rhIGF-I and rhIGFBP-3. OBJECTIVES: The objectives of the study were to determine IGF-I pharmacokinetics after the administration of rhIGF-I/rhIGFBP-3 in adolescents with GHIS and to evaluate its safety and tolerability. DESIGN: This was an open-label clinical study. SETTING: The study was conducted in a general pediatric ward of a university teaching hospital. PARTICIPANTS: Four patients (one female and three males; mean age, 14.9 yr; mean height sd score, -4.9) with confirmed molecular diagnosis of GHIS agreed to participate in the study. INTERVENTION: rhIGF-I/rhIGFBP-3 was administered in a single sc injection at 0.5 and 1.0 mg/kg.dose (equivalent to 100 and 200 microg/kg rhIGF-I) after breakfast with a 2-d interval between doses. RESULTS: IGF-I levels reached a maximum between 19 +/- 8.3 and 15 +/- 6.2 h for the low and high doses, respectively. The circulating IGF-I levels obtained with the low and high doses were similar, although a discrete dose-dependent increase in circulating IGF-I levels was observed. The IGF-I half-life in four subjects after a dose of 0.5 mg/kg rhIGF-I/rhIGFBP-3 was estimated to be 21+/- 4 h. There were no acute adverse events reported, and all blood glucose measurements were normal. CONCLUSION: These data demonstrated that the rhIGF-I/rhIGFBP-3 complex was effective in increasing levels of circulating total and free IGF-I into the normal range for a 24-h period after a single sc administration in patients with GHIS, and that administration of rhIGF-I/rhIGFBP-3 was safe and well tolerated.

Adolescent↗
PubMed2006

Endocrine assessment, molecular characterization and treatment of growth hormone insensitivity disorders.

Advances in the diagnosis and treatment of growth hormone insensitivity disorders have occurred in the past 15 years. We discuss the current status of endocrine and molecular evaluation, focusing on the pediatric age range. All the identified mutations of the growth hormone receptor are included. Treatment with recombinant human insulin-like growth factor (rhIGF) 1 in classical cases is summarized and new targets for treatment are discussed, together with therapy using the complex formed between rhIGF1 and rhIGF-binding protein 3.

Endocrine System↗
PubMed2006

Dehydroepiandrosterone (DHEA) replacement reduces growth hormone (GH) dose requirement in female hypopituitary patients on GH replacement.

OBJECTIVE: GH dose requirement is lower in ACTH replete compared with ACTH deficient hypopituitary patients suggesting that adrenal androgens may augment IGF-I generation for a given GH dose. This study aimed to determine the effect of dehydroepiandrosterone (DHEA) administration on GH dose requirements in hypopituitary adults. DESIGN: A double blind placebo controlled trial was conducted adding 50 mg DHEA to the standard replacement of hypopituitary patients, including GH, over an initial 6 months, followed by an open phase study of 6 months DHEA replacement and a final 2 month washout phase after DHEA withdrawal. The dose of GH was adjusted to achieve a constant serum IGF-I. PATIENTS: Thirty female and 21 male hypopituitary patients were enrolled. Data from 26 women and 18 men were analysed after patient withdrawal. MEASUREMENTS: The primary outcome objective was the GH dose required to achieve a stable serum IGF-I. Secondary outcome measures were lipoprotein profiles, insulin, insulin sensitivity, IGFBP-3, waist/hip ratio and indices of bone remodelling. RESULTS: DHEA replacement in female patients lead to a 14.6 +/- 20% reduction in the dose of GH for a constant serum IGF-I (P < 0.05, 95% CI: 1.8, 32.7). This was maintained for 12 months and there was a significant fall in serum IGF-I two months after withdrawal of DHEA. There was no change in the male group. CONCLUSIONS: DHEA replacement may reduce GH dose requirements in female hypopituitary patients.

Adult↗
PubMed2005

A rapid method for analyzing serum pro-insulin-like growth factor-II in patients with non-islet cell tumor hypoglycemia.

CONTEXT: Non-islet cell tumor hypoglycemia (NICTH) results from the hypersecretion of pro-IGF-II by a large, usually mesenchymal tumor. Detection of pro-IGF-II in serum is a potential tumor marker in these patients. OBJECTIVE: The aim of this study was to validate a rapid and reliable method for determining serum pro-IGF-II. PATIENTS: Serum samples from 16 patients with NICTH were studied. MAIN OUTCOME MEASURE: The main outcome measure was serum concentration of pro-IGF-II determined by immunoblot analysis of pro-IGF-II and mature IGF-II after 16.5% tricine-SDS-PAGE, which was compared with pro-IGF-II measured by standard RIA after size-exclusion acid chromatography. RESULTS: The analyses of patients' sera by size-exclusion acid chromatography showed that 68 +/- 19% of IGF-II were present in the pro-IGF-II form, whereas only 18 +/- 4% corresponded to pro-IGF-II in controls. Scanning densitometry of immunoblots showed 67 +/- 16% in the bands corresponding to pro-IGF-II in patients' sera, compared with 27 +/- 9% in controls. The detection sensitivity of tricine-SDS-PAGE method was the same as for size-exclusion chromatography, but the tricine-SDS-PAGE method is quicker and requires smaller amounts of serum. CONCLUSION: Tricine-SDS-PAGE followed by IGF-II immunoblot analysis provides a rapid, reproducible, and sensitive method for the separation of serum pro-IGF-II from mature IGF-II and is a useful laboratory evaluation of patients with a clinical diagnosis of NICTH.

Adult↗
PubMed2005

Diagnostic and therapeutic advances in growth hormone insensitivity.

Diagnostic and therapeutic advances in growth hormone insensitivity (GHI) have occurred principally in two areas: the molecular characterization of patients with GHI and treatment with recombinant human insulin like growth factor-I (IGF-I). This article discusses the current status of molecular diagnosis across the spectrum of the disorder. Treatment with recombinant human IGF-I in classical cases is summarized, and potential new targets for treatment are discussed together with the potential for therapy using the newly developed compound recombinant human IGF-I/IGF binding protein-3.

Drug Therapy, Combination↗
PubMed2005

Novel growth hormone receptor mutation in a Chinese patient with Laron syndrome.

Laron syndrome, growth hormone (GH) insensitivity syndrome, caused by a mutation of the GH receptor (GHR) gene, is extremely rare in the Chinese population. We report a Chinese girl diagnosed with Laron syndrome at age 1.9 years with height -4.9 SDS, basal GH 344 mIU/ml, IGF-I <12 ng/ml, IGFBP-3 <0.2 mg/ml, and undetectable GHBP. A novel mutation of the GHR, not previously described, was identified at the donor splice site of intron 6.

Amino Acid Substitution↗
PubMed2004

Therapeutic applications of the insulin-like growth factors.

The potential therapeutic applications of the insulin-like growth factors (IGFs) are broad. This review focuses on treatment of humans with recombinant human IGF-I (rhIGF-I), and with a rhIGF-I/IGF binding protein-3 (IGFBP-3) complex. Several groups of patients have been treated effectively, including individuals with growth hormone insensitivity syndrome (GHIS) secondary to GH receptor deficiency, to IGF-I gene deletion, or to defects in GH signal transduction pathways, patients with type 1 and type 2 diabetes mellitus, or individuals with severe insulin resistance syndromes. In each of these conditions rhIGF-I therapy has been demonstrated to be of clear clinical benefit. Other conditions, which may potential targets for therapy with rhIGF-I or rhIGF-I/IGFBP-3, include chronic inflammatory or nutritional disorders such as Crohn's disease, juvenile chronic arthritis, or cystic fibrosis. Therapy with IGFs has not been attempted in these disorders yet, in part because of lack of adequate supplies. Recently, the newly developed rhIGF-I/IGFBP-3 complex has been used in early clinical studies. Pharmacokinetic analyses in patients with diabetes mellitus and GHIS have suggested that a more physiological profile of serum IGF-I results. Improved glycaemic control has been reported in type 1 and type 2 diabetes in adults. A therapeutic trial in naïve children with GHIS is currently under way.

Adolescent↗
PubMed2004

Anti-inflammatory and growth-stimulating effects precede nutritional restitution during enteral feeding in Crohn disease.

OBJECTIVES: Exclusive enteral feeding reduces inflammation and improves well being, nutrition and growth in children with active Crohn disease. Whether improved growth and increases in growth-related proteins are a consequence of improved nutrition or a reduced inflammation is not known. This study was undertaken to test the hypothesis that changes in growth-related proteins are related to decreased inflammation, rather than improvement in nutritional status. METHODS: Twelve children with active Crohn disease treated for 6-weeks with exclusive enteral feeding were studied at days 0, 3, 7, 14, 21, 28, and 56. The Paediatric Crohn's Disease Activity Index (PCDAI), weight, triceps skinfold thickness, and midupper arm circumference were recorded. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), insulin-like growth factor (IGF-I), IGF-binding protein (IGFBP-3), and leptin were measured at each visit. Wilcoxon matched-pairs signed-rank test was used to compare day 0 with follow-up data. RESULTS: Significant improvements (P < 0.05) occurred by day 3 in inflammatory parameters (ESR, IL-6) and by day 7 in PCDAI, CRP, and IGF-I. These changes preceded any significant changes in nutritional parameters (weight-for-age Z score and midupper arm circumference day 14, triceps skinfold thickness day 21). CONCLUSIONS: Early increases in IGF-I during treatment of Crohn disease are attributable to the anti-inflammatory effect of the enteral feed rather than nutritional restitution.

Adolescent↗
PubMed2004

Different states of clinical control are associated with changes in IGF-I and IGFBPs in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

OBJECTIVE: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is characterized by high androgen levels, ambiguous genitalia or premature pubarche, increased height velocity and skeletal maturation. Considering the possibility of changes in the IGF system components depending on the state of clinical control, the objective of the present study was to analyse serum IGF-I, IGF-II and IGFBP levels in children with 21-OHD under two states of clinical control. PATIENTS AND DESIGN: We studied 12 prepubertal children with 21-OHD CAH aged 4.0 +/- 0.7 years. They were classified as good (GC) or poor control (PC) based on growth rate, signs of adrenal insufficiency or Cushing syndrome, progression of sexual characteristics and serum androgens levels. Blood samples were obtained from each patient in two different states of clinical control (GC and PC) for biochemical measurements. MEASUREMENTS: IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 were determined by immunoassays. IGFBPs were also analysed by Western ligand blotting (WLB). RESULTS: Levels of IGF-I (P = 0.03) and IGFBP-3 (P = 0.01) were higher in GC than in PC while IGFBP-1 (P = 0.004) concentrations were lower in GC patients. A trend towards higher levels of IGF-II (P = 0.08) and lower levels of IGFBP-2 (P = 0.08) was observed in GC children. Increased IGFBP-4 band intensity was observed in GC children (P = 0.03). CONCLUSION: Higher levels of IGF-I, IGFBP-3 and IGFBP-4, but lower levels of IGFBP-1, were associated with better control in children with 21-OHD CAH. These findings are different from those observed in children with other causes of increasing androgens levels and are likely to be related to the insufficient glucocorticoid status.

Adrenal Hyperplasia, Congenital↗
PubMed2003

Relationships between serum IGF-1, IGFBP-2, interleukin-1beta and interleukin-6 in inflammatory bowel disease.

AIMS: To study the relationships between serum IGF-1, IGFBP-3 and IGFBP-2 and interleukin (IL)-1beta and IL-6 in inflammatory bowel disease (IBD). METHODS: Thirty-seven patients (18 males, 19 females, aged 8.8-26.1 years) with IBD (Crohn's disease, CD, n = 17, and ulcerative colitis, UC, n = 20) were studied. Patients were in relapse or remission according to established criteria. Serum IGF-1, IGFBP-3, IGFBP-2, IL-1beta and IL-6 levels were determined in patients and 15 healthy controls (aged 8.2-19.0 years). RESULTS: IGF-1 levels were lower in patients with CD in relapse compared with controls (p < 0.05). IGFBP-2 levels were higher in CD in relapse compared with other groups (all p < 0.05). In CD and UC patients (n = 37), IGF-1 levels were inversely correlated with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). IGFBP-2 levels correlated positively with ESR and IL-1beta. IL-6 levels correlated positively with ESR and CRP. IL-1beta levels were elevated in CD in relapse compared to controls (p < 0.05) and were higher in UC in relapse than in other groups (all p < 0.05). In combined CD/UC patients in relapse (n = 20), IL-1beta levels were higher (p < 0.05) in patients with recto-sigmoiditis (n = 5) than in other patients. CONCLUSIONS: IGF-1, IGFBP-2 levels were related to IL levels, disease activity and anatomical distribution, consistent with active inflammation modifying the IGF-IGFBP system, possibly relevant to disturbance of growth.

Adolescent↗
PubMedDate not supplied

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 in girls with premature thelarche.

Premature thelarche (PT) is characterised by precocious breast development without any other sign of puberty, normal height velocity (HV) and normal bone maturation, while girls with central precocious puberty (CPP) show increased HV, bone maturation and increased serum IGF-I and IGFBP-3 levels. This prompted us to study serum IGF-I and IGFBP-3 concentrations in girls with PT. Thirty-nine girls with premature breast development were studied and classified as PT or CPP according to clinical and laboratory evaluation. Normal prepubertal and pubertal girls were studied as controls. Serum IGF-I and IGFBP-3 were determined in all girls by IRMA. IGF-I levels in PT (155 +/- 61 microg/l) were lower than in CPP (337 +/- 149 microg/l) or late-pubertal controls (355 +/- 84 microg/l) and similar to those found in prepubertal (113 +/- 72 microg/l) and early-pubertal (222 +/- 81 microg/l) girls. Considering the SDS of IGF-I for chronological age (CA), the values observed in PT were in an intermediate position between CPP and prepubertal controls and statistically similar to those observed in CPP and prepubertal girls. IGFBP-3 levels in PT (2.1 +/- 0.5 mg/l) were similar to those found in CPP (2.5 +/- 0.8 mg/l), but only the latter were higher than in prepubertal girls (1.9 +/- 0.9 mg/l). IGF-I/IGFBP-3 molar ratios in PT were in an intermediate position between CPP and prepubertal controls. In conclusion, IGF-I and IGF-I/IGFBP-3 values in PT are intermediate between those observed in prepubertal children and in CPP, suggesting that PT could be a very early stage of puberty with slight but real changes in the GH-IGF axis.

Adolescent↗