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Biomedical subjects

C Camacho-Hübner

Publications and source records attributed to C Camacho-Hübner.

46 records · Page 3Linked to original sources
PubMed1996

Normal growth hormone secretion in growth hormone insufficient children retested after completion of linear growth.

OBJECTIVE: The recognition of the syndrome of adult GH deficiency suggests that young GH deficient adults, deprived of GH replacement at completion of linear growth, may suffer effects of GH deficiency. We assessed GH reserve in young adults previously diagnosed as having idiopathic GH insufficiency, who were treated with hGH replacement (14 IU/m2/week) in childhood. DESIGN: Eight patients (7 males, 1 female) diagnosed as having GH insufficiency by insulin tolerance test (ITT) in childhood (ages 8.5-15.6 years) were retested by ITT at completion of linear growth (ages 15.1-19.6 years), 3 months after discontinuation of hGH therapy. MEASUREMENTS: GH reserve was measured during ITT at diagnosis and at retesting. Height velocity (HV) and HV SDS were calculated before and during GH therapy. RESULTS: At diagnosis, the mean peak GH response to ITT was 10.5 +/- 2.0 mU/l (range 7.7-13.6). At retesting, mean GH was 52.4 +/- 33.2 mU/l (range 10.4-100), 7/8 subjects having peak GH levels greater than 15 mU/l. During hGH therapy mean HV increased from 4.0 +/- 1.5 cm/year at diagnosis to 7.3 +/- 1.9 cm/year during the 1st year (P = 0.004) and 6.9 +/- 2.3 cm/year during the 2nd year (P = 0.02). Mean HVSDS increased from -1.6 +/- 2.1 at diagnosis to 3.1 +/- 2.9 during the 1st year (P = 0.004) and 2.2 +/- 4.2 during the 2nd year (P = 0.05, NS) of treatment. CONCLUSIONS: Seven out of 8 children diagnosed as having idiopathic GH insufficiency had normal GH secretion at completion of linear growth. Children with GH insufficiency cannot be assumed to become GH deficient adults and should not continue on GH therapy into adult life without reinvestigation. All who were GH insufficient children should be retested at completion of linear growth to identify those who are truly GH insufficient adults and may benefit from replacement therapy.

Adolescent↗
PubMed1996

The differential regulation of the circulating levels of the insulin-like growth factors and their binding proteins (IGFBP) 1, 2 and 3 after elective abdominal surgery.

OBJECTIVES: Patients undergoing abdominal surgery often suffer from morbidity associated with increased protein catabolism. Therapeutic recombinant human insulin-like growth factor (rhIGF)-I has been proposed as a means of reversing this process. As IGFBPs modulate the bioavailability of the IGFs, we have studied the changes in the circulating levels of these peptides during surgery. DESIGN: Patients undergoing elective intestinal surgery were recruited prospectively. Blood samples were taken before, during and after surgery. Standard anaesthetic techniques were used. METHODS: Twelve adults (aged 30-70 years; 9 female, 3 male) undergoing surgery were studied. Serum was taken before premedication (preop), end of surgery (end surg), 2 h, 6 h post surgery, on days 1-4, 7, 10 and 14, and on recovery at 6 weeks. MEASUREMENTS: Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, insulin and C-peptide were measured by radioimmunoassay. IGFBP profiles were also assessed by Western ligand blot (WLB). Samples taken preop and at 2 days were separated by fast-phase liquid chromatography (FPLC) using a Superose 12 column under neutral conditions (pH 7.4), and the fractions were analysed subsequently by WLB and immunoblot using a specific IGFBP-3 antiserum. RESULTS: IGF-I fell rapidly during surgery from 170 +/- 21 (preop) to 133 +/- 14 micrograms/l (end surg) (P < 0.05). The magnitude of this fall could not be explained by haemodilution. IGF-I levels then fell further to a nadir of 103 +/- 10 micrograms/l at day 4 (P < 0.05). IGF-II fell from 580 +/- 46 (preop) to 397 +/- 38 micrograms/l (day 2). Both IGF-I and IGF-II recovered to preop levels at 6 weeks (205 +/- 14 micrograms/l and 623 +/- 30 micrograms/l respectively). IGFBP-3 levels fell similarly from 4.46 +/- 0.45 to 3.2 +/- 0.3 mg/l (end surg) and to a nadir of 2.66 +/- 0.19 mg/l at day 2. There was a close correlation between IGFBP-3 levels and the sum of IGF-I and IGF-II levels before surgery (r = 0.9, P < 0.01) and this was maintained throughout the post-operative period (mean correlation coefficient of 0.86 +/- 0.02, P < 0.05). On days 2 and 3 there was a small but significant increase in the ratio between serum IGF-I and IGFBP-3 levels compared with the preop ratio (P < 0.05 and < 0.005, respectively). WLB demonstrated almost complete absence of IGFBP-3 by day 2. This discrepancy between RIA and WLB analysis of IGFBP-3 suggested the presence of IGFBP-3 protease activity between days 1 and 4. This was confirmed by WLB and immunoblot analyses of samples taken 2 days after surgery. The decrease in IGFBP-3 on WLB was shown to be associated with an increase in the proteolytically cleaved fragments of IGFBP-3. These fragments following FPLC were detected in the high molecular weight fractions, suggesting that the fragments were still able to form the high molecular weight IGFBP-3/ALS complex which is thought to form only when IGF is bound by IGFBP-3. IGFBP-1 levels rose during surgery (mean duration of surgery was 125 minute) from 18 +/- 3 (preop) to 51 +/- 12 micrograms/l (end surg) (P < 0.05). This rise in IGFBP-1 paralleled increases in insulin from 7.3 +/- 1.0 to 20.8 +/- 7.5 mU/l and glucose from 4.6 +/- 0.3 to 8.7 +/- 1.2 mmol/l. IGFBP-1 levels then fell to basal values by 6 hours. IGFBP-2, in contrast, fell slightly during surgery from 636 +/- 14 to 599 +/- 96 mg/l and then returned to basal levels by 6 hours. CONCLUSION: After major surgery there are complex and diverse changes in the IGFs and IGFBPs. The effect of these changes on IGF bioavailability may significantly affect the therapeutic potential of IGF-I in this setting.

Abdomen↗
PubMed1996

The short-term effects of growth hormone therapy on height velocity and cardiac ventricular wall thickness in children with Noonan's syndrome.

Noonan's syndrome (NS) is associated with short stature and cardiac defects. Small studies reported linear growth increases with recombinant human GH (rhGH) therapy, but also raised concerns related to the anabolic effects of rhGH and the possible progression of ventricular hypertrophy. We report a multicenter study examining the efficacy and safety of rhGH (4 IU/m2.day, sc) in children with NS. Entry criteria were: NS confirmed by single observer, height SD score less than -2(UK Height Standards 1990), prepubertal, and normal maximal left ventricular (LV) wall thickness less than 1 cm by 2-dimensional echocardiography. Thirty subjects were recruited (19 males and 11 females), aged 8.9 +/- 0.5 yr (range, 4.8-13.7 yr). Growth was monitored for 12 months before and at 3-month intervals during therapy. Measurements of maximal LV wall thickness were taken at 0 and 12 months. Serum insulin-like growth factor I(IGF-I), IGF-II, and IGF-binding protein-3 levels were determined at 0, 3, 6, 9, and 12 months. Ten subjects with NS (4 females and 6 males), aged 8.8 +/- 0.7 yr (range, 6.3-11.8 yr), were monitored over the same period as a comparison group. In the treatment group, 27 subjects completed 12 months of therapy. Height SD score increased from -3.01 +/- 0.10 to -2.36 +/- 0.10 (P < 0.0001) after 12 months; height velocity (HV) increased from 4.9 +/- 0.2 to 8.9 +/- 0.3 cm/yr at 6 months and 8.1 +/- 0.4 cm/yr (P < 0.0001) from 6-12 months. The HV SD score increased from -0.7 +/- 0.15 to +2.42 +/- 0.32 over 12 months (P < 0.0001). The increase in HV was more than 2 cm/yr in 24 patients. IGF-I increased from 121 +/- 13 to 240 +/- 22 micrograms/L at 12 months (P < 0.0001), and IGF-binding protein-3 increased from 2.65 +/- 0.20 to 4.01 +/- 0.42 mg/L at 12 months (P = 0.0009). In the comparison group, there was no change in height SD score (-2.03 +/- 0.19), HV (4.4 +/- 0.24 CM/yr), or HV SD score (- 1.08 +/- 0.21). There was no increase in mean maximal LV wall thickness during the study in either the treatment group (12 month values were 0.63 +/- 0.02 cm at the mitral valve level and 0.66 +/- 0.02 cm at the papillary muscle level) or in the comparison group (0.63 +/- 0.04 cm at the mitral valve level and 0.61 +/- 0.03 cm at the papillary muscle level). In conclusion, rhGH was effective in 24 of the treated patients; these subjects achieved a significant increase in height SD score and HV over 1 yr. Abnormal anabolic effects of rhGH on myocardial thickness were not confirmed, and no patient developed features of hypertrophic cardiomyopathy.

Adolescent↗
PubMed1996

Insulin-like growth factor-I and- II in combination inhibit the release of growth hormone-releasing hormone from the rat hypothalamus in vitro.

This study was designed to investigate the feedback loop between insulin-like growth factor-I (IGF-I) and IGF-II and the hypothalamic hormones growth hormone-releasing hormone (GHRH) and somatostatin (SS) using an in vitro rat hypothalamic model. IGF-I and, to lesser extent, IGF-II, both activate type 1 IGF receptors, while type 2 receptors are activated by IGF-II alone. IGF-I, IGF-II, their various specific analogues (Des[1-3]IGF-I, [Arg54/Arg55]IGF-II and [Leu27]IGF-II), insulin and the type 2 receptor antagonist beta-galactosidase were used on their own or in combination to study their effect on GHRH and SS release. Our results suggest that the simultaneous activation of type 1 and type 2 IGF receptors is needed for the negative feedback effect of IGFs on GHRH release in this in vitro system, in agreement with earlier findings in vivo. Somatostatin was not altered by any combination of peptides.

Animals↗
PubMed1995

The 'dawn phenomenon' in adolescents with insulin dependent diabetes mellitus: possible contribution of insulin-like growth factor binding protein-1.

OBJECTIVE: Insulin resistance increases during adolescence, and is exaggerated in patients with insulin dependent diabetes mellitus (IDDM). A relative deficiency of insulin-like growth factor-I (IGF-I) may contribute to this increased insulin requirement. Two mechanisms have been proposed: (a) increased GH secretion, caused by failure of IGF feedback control, leading to increased insulin resistance and (b) lack of insulin-like action of the IGFs which is reinforced by high plasma levels of IGFBP-1, an inhibitor of IGF action. The contribution of these two mechanisms to the 'dawn phenomenon' is assessed. DESIGN: The two possible mechanisms were studied during the dawn rise of glucose in pubertal adolescent patients with IDDM. Two overnight studies were performed in each subject. Patients remained on the same insulin regimen throughout. SUBJECTS: Twenty-two diabetic adolescent subjects, aged (mean +/- SEM) 14.0 +/- 0.4 years, duration of IDDM 7.9 +/- 0.8 years, were recruited. Pubertal status was: group 1 (breast stage 1-2; testicular volume < 4-8 ml) 3 male and 4 female, group 2 (breast stage 3; testicular volume 10-12 ml) 0 male 4 female, group 3 (breast stage 4-5; testicular volume 15-25 ml) 4 male and 7 female. Height standard deviation score (mean +/- SD) (-0.02 +/- 0.99) and daily insulin dose (50.4 +/- 3.1 U/day) did not change between studies. There were no differences in HbA1 (study A 11.26 +/- 0.45%, study B 11.09 +/- 0.42%). METHODS: The subjects were admitted for the two studies 0.3 +/- 0.03 years apart. Blood samples were taken via an indwelling cannula every 20 minutes between 1900 and 0700 h. MEASUREMENTS: GH was assayed every 20 minutes, IGFBP-1, glucose and free insulin every hour and IGF-I at 0700 h. GH, IGFBP-1, IGF-I and free insulin were measured by radioimmunoassay. IGFBPs were also analysed by Western ligand blotting techniques. GH profiles were analysed by Pulsar and results compared by paired Student's t-test. The relations between the dawn rise in glucose and the changes in IGFBP-1, GH and free insulin were examined by multiple linear regression analysis. RESULTS: Serum IGFBP-1 levels rose overnight in the two studies (study A, from 9 +/- 1 at 2200 to 59 +/- 9 micrograms/l at 0700 h; study B, from 10 +/- 1 at 2100 to 64 +/- 14 micrograms/l at 0700 h) whilst insulin levels fell from 47 +/- 5 at 2200 to 16 +/- 2 mU/l at 0700 h (study A) and from 45 +/- 5 at 2000 to 14 +/- 2 mU/l at 0700 h (study B). Glucose levels fell from 16.0 +/- 1.0 to 9.3 +/- 0.9 mmol/l at 0400 h, and then rose to 11.9 +/- 1.1 mmol/l at 0700 h during study A, and from 13.4 +/- 1.3 to 10.1 +/- 1.1 mmol/l at 0400 h and then rose to 13.5 +/- 1.0 mmol/l at 0700 h during study B. There were no differences in GH secretion between studies (mean GH levels (mean +/- SD) (study A, 15.7 +/- 6.6 mU/l; study B, 16.2 +/- 7.1 mU/l; correlation within subjects between studies r = 0.77, P < 0.001), sum of GH peaks (study A, 189.9 +/- 90.3 mU/l; study B, 185.8 +/- 100.2 mU/l; r = 0.57, P = 0.006)). Mean GH levels varied with pubertal stage (group 1, 12.1 +/- 1.5 mU/l; group 2, 23.3 +/- 2.1 mU/l; group 3, 15.3 +/- 1.2 mU/l). Serum IGF-I levels were not different (study A, 203 +/- 12 micrograms/l; study B, 218 +/- 13 micrograms/l). REGRESSION ANALYSIS: The change in plasma glucose between 0200 and 0700 h in both studies related to free insulin, IGFBP-1 and the sum of the GH levels over the preceding hour (log glucose = 7.87 + 5.32 log IGFBP-1 (P = 0.0001) - 5.05 log free insulin (P = 0.0001) - 1.44 log GH (P = 0.004); R2 = 72%). Mean overnight GH levels did not predict the morning rise in plasma glucose. CONCLUSION: The morning rise of IGFBP-1 and plasma glucose appear to be related in this group of subjects with IDDM and this was a consistent finding in the two studies. This relation was additive to the effect of insulin deficiency.

Adolescent↗
PubMed1995

Low circulating IGF-I levels in hyperthyroidism are associated with decreased GH response to GH-releasing hormone.

OBJECTIVE: Several abnormalities in the GH response to pharmacological stimuli have been described in hyperthyroidism. Both normal and high serum IGF-I levels have been reported, as well as a decrease in IGF-I bioactivity. We have evaluated the GH response to GH-releasing hormone (GHRH) in hyperthyroid patients and the effects of hyperthyroidism on serum IGF-I levels. The possible relations between nutritional status, thyroid hormones and IGF-I levels were also investigated. We also studied the influence of long-term beta-adrenoceptor blockade on the GH response to GHRH in these patients. DESIGN: In 18 hyperthyroid patients and in 12 control subjects, GHRH (100 micrograms) was administered as an i.v. bolus injection. Eight hyperthyroid patients and 8 control subjects received 50 micrograms GHRH i.v. Seven hyperthyroid patients were reevaluated after beta-adrenoceptor blockade. IGF-I and albumin levels were measured initially in all hyperthyroid patients and control subjects. Body composition was determined in 11 hyperthyroid patients and in a group of 33 matched normal controls. PATIENTS: Hyperthyroid patients were compared to control subjects. MEASUREMENTS: GH, TSH and free T4 were measured by immunofluorometric assay. IGF-I, total T3 and total T4 were measured by radioimmunoassay. Body composition was determined using a dual-energy X-ray absorptiometer. RESULTS: The GH response to 100 micrograms GHRH in hyperthyroid patients was blunted compared to control subjects. The mean peak GH levels and the area under the curve were significantly lower in hyperthyroid patients compared to control subjects (11 +/- 1 vs 27 +/- 5 micrograms/l and 820 +/- 113 vs 1879 +/- 355 micrograms/l 120 min, respectively; P < 0.01). IGF-I levels were significantly reduced in hyperthyroid patients compared to controls (131 +/- 10 vs 201 +/- 16 micrograms/l, respectively; P < 0.01). Ideal body weight, serum albumin levels and the lean body mass were also reduced in hyperthyroid patients. After beta-adrenoceptor blockade there were no changes in the blunted GH response to GHRH in hyperthyroid patients. CONCLUSION: Our data suggest that the blunted GH response to GHRH in hyperthyroidism is apparently not related to circulating IGF-I levels. It is possible that nutritional factors could play a role in the reduced circulating IGF-I levels found in these patients.

Adolescent↗
PubMed1994

The insulin-like growth factor I generation test in the investigation of short stature.

Genotypic and phenotypic heterogeneity in patients with growth hormone (GH) insensitivity syndrome suggests that partial defects exist in the GH receptor. The insulin-like growth factor I (IGF-I) generation test was assessed as a means of identifying partial GH receptor defects in a heterogeneous group of 22 prepubertal children with short stature. In a subgroup of nine patients with peak GH levels of 63.7 +/- 3.7 mU/l during a glucagon tolerance test, the response to the IGF-I generation test was no different from that for the group as a whole (peak GH, 43.3 +/- 4.5 mU/l), despite the fact that this subgroup exhibited a negative relationship between height SDS and peak GH and a positive relationship between height SDS and IGF binding protein-3. This preliminary study therefore suggests that the IGF-I generation test in its present form will not be useful as a primary screening test for partial GH insensitivity. Despite this, the IGF-I generation test has been extremely useful in the confirmation of the diagnosis of GHIS and may therefore also prove useful in the confirmation of partial defects in the GH receptor. A subgroup of short children with peak GH levels above 40 mU/l had some characteristics of partial GH receptor deficiency. These children, to whom GH therapy would not normally be given, may respond better to recombinant human IGF-I.

Body Height↗
PubMed1993

The effect of recombinant human insulin-like growth factor-I treatment on growth hormone secretion in two subjects with growth hormone insensitivity (Laron syndrome).

OBJECTIVE: Growth hormone (GH) secretion is increased in conditions of GH insensitivity such as Laron syndrome, with elevation of both basal and peak levels. We have studied the effect of recombinant IGF-I therapy on the pattern of GH secretion in two subjects with GH insensitivity. SUBJECTS: Two pubertal subjects with GH insensitivity (female, 16.4 years, breast stage 3; male 13.6 years, genital stage 2) were investigated after 6 months of IGF-I therapy (120 micrograms/kg twice daily s.c. at 0800 and 1900 h). GH profiles taken before the start of IGF-I therapy, when both subjects were prepubertal (aged 14.0 and 11.5 years respectively), were used for comparison. METHODS: GH profiles were performed with blood samples taken every 20 minutes between 2000 and 0800 h from an indwelling cannula. MEASUREMENTS: Serum samples were assayed for GH by immunoradiometric assay and IGF-I, IGFBP-1 and insulin by radioimmunoassay. RESULTS: Before IGF-I therapy, GH profile studies demonstrated pulsatile GH secretion. Basal GH was elevated with no value falling below the limit of detection of the assay and an increase in peak levels (maximum 203 and 206 mU/l at 0000 h and 0020 h respectively). After 6 months IGF-I therapy, the GH profiles were significantly different. With the onset of puberty a further increase in GH secretion would have been expected; nevertheless, following administration of IGF-I at 1900 h, GH secretion decreased with a reduction in mean overnight GH levels from 65 to 33 mU/l and 53 to 11 mU/l respectively. GH pulsatility was also suppressed in the two subjects, for the first 3.5 and 6 hours overnight respectively. Pulsatile GH secretion then returned with peak levels reaching 130 and 63 mU/l respectively. Prior to therapy IGF-I levels were at the lower limit of assay detection. On IGF-I therapy serum IGF-I levels reached a peak within 3 hours (298 and 438 micrograms/l) coinciding with the suppression of GH secretion. IGF-I levels fell rapidly overnight to 92 and 101 micrograms/l at 0800 h prior to the next injection. The fall in serum IGF-I coincided with the return of GH secretion. IGFBP-1 levels increased overnight both before and during IGF-I therapy, rising from 24 to 83 and 22 to 110 micrograms/l before therapy and 13 to 60 and 13 to 71 micrograms/l during therapy. This rise in IGFBP-1 appeared to be inversely related to the fall in serum insulin levels overnight and appeared not to be affected by IGF-I therapy. CONCLUSION: GH secretion is suppressed by exogenous IGF-I therapy in GH insensitive subjects. The failure to maintain high serum IGF-I levels overnight, presumably due to a persisting defect in serum IGFBP-3 levels, was associated with an early return of GH secretion. These findings may have implications for the dose and regimen of IGF-I therapy in subjects with growth hormone insensitivity.

Adolescent↗
PubMed1989

Identification of the types of insulin-like growth factor-binding proteins that are secreted by muscle cells in vitro.

We have previously shown that muscle cells secrete insulin-like growth factor-binding proteins. In the present study, BC3H-1 cells were shown to secrete one binding protein of Mr 32,000, whereas L6 cells secreted two binding proteins of Mr 31,000 and 24,000, as determined by ligand blotting. Subconfluent proliferating L6 cells secrete more of the Mr 24,000 binding protein, relative to the Mr 31,000 form. In contrast, differentiated L6 myotubes secreted similar quantities of the two forms. Insulin-like growth factor I preferentially stimulated secretion of the Mr 31,000 versus the Mr 24,000 binding protein from L6 cells and caused an increase in the secretion of the Mr 32,000 binding protein from BC3H-1 cells. The Mr 31,000 binding protein from L6 cells had a greater affinity for insulin-like growth factor II compared with insulin-like growth factor I, as did the Mr 32,000 binding protein of BC3H-1 cells. In contrast, the Mr 24,000 binding protein of L6 cells preferred insulin-like growth factor I. Neither porcine insulin nor relaxin competed for 125I-IGF-I binding. In conclusion, these muscle cell lines secrete only one or two forms of insulin-like growth factor-binding proteins. L6 cell differentiation is associated with a relative increase in the secretion of the Mr 31,000 binding protein compared with the Mr 24,000 form. Insulin-like growth factor I stimulates the secretion of its own binding proteins from muscle cells, and this may be an important mechanism for modulating cellular responsiveness to this growth factor.

Animals↗