Biomedical subjects

R Brauner

Publications and source records attributed to R Brauner.

At least 55 records · Page 3Linked to original sources

PubMed1999

Idiopathic growth hormone deficiency: presentation, diagnostic and treatment during childhood.

The clinical and biological presentation of idiopathic growth hormone (GH) deficiency (GHD) varies greatly, demonstrating the variety of its pathogenic features and explaining why it is difficult to diagnose. We examined 48 patients (26 males) with certain idiopathic GHD diagnosed at 4.8 +/- 0.7 yr. The symptoms that led to the diagnosis of GHD were low growth rate (33 cases), hypoglycemia (12 cases), microphallus (1 case) and in 2 cases the GHD was diagnosed from magnetic resonance imaging (MRI) performed for delayed mental development (1 case), or congenital blindness (1 case). The 2 other cases were diagnosed from routine GH evaluation performed at birth because of idiopathic GHD in siblings. Thirteen had congenital malformation. Twenty three cases (48%) had features suggesting that the GHD was of antenatal origin. Six of them were born by breech delivery. Twenty one cases (44%) had features suggesting a hypothalamic origin. The decrease in growth rate occurred before 0.5 year in 21 (55%), before 1 year in 27 (71%) and before 2 years in 30 (79%): 8 patients (21%) maintained a normal growth rate after this age. Among these 8 patients, 5 had signs suggesting an antenatal origin and 4 had severe episodes of hypoglycemia from birth. The mean GH peak after the pharmacological stimulation test was 3.6 +/- 0.5 micrograms/l. The mean plasma insulin-like growth factor 1 (IGFI) was 0.1 +/- 0.02 U/ml. The GH deficiency was associated with deficiencies of thyrotropin in 26 (54%) and of adrenocorticotrophic hormone in 17 (35%) patients. Among the 15 patients of pubertal age, 9 (60%) had gonadotrophin deficiency. No patient had diabetes insipidus. The MRI showed pituitary stalk interruption syndrome in 39 patients and normal pituitary anatomy in 6 patients. GH treatment reduced the difference between target and actual heights from 3.5 SD (before) to I SD (after 3 years) in the 39 more recently seen patients given 0.5-0.6 U/kg/w GH in 6 or 7 weekly injections. Height gain during the first year and cumulative height gain over 3 years (SD) was correlated negatively with height (SD) at the start of treatment (p < 0.01). We conclude that most of the patients with GHD have features suggesting an antenatal origin. Despite this early origin, the decreased growth rate may occur after 2 years.

Body Height↗

PubMed1998

Growth hormone secretion, puberty and adult height after cranial irradiation with 18 Gy for leukaemia.

UNLABELLED: The dose of prophylactic cranial irradiation given to patients for acute lymphoblastic leukaemia has been decreased from 24 to 18 Gy, but the beneficial effect of this decrease on growth is controversial. This study compares the growth hormone (GH) secretion and growth of 35 patients (20 boys) given 18 Gy at 3.7+/-0.3 (SE) years, and routinely evaluated 5.4+/-0.4 years after irradiation to define the indications for GH treatment in these patients. Of these, 63% had a low GH peak (< 10 microg/l) after one (22 cases) or two (17 cases) stimulation tests. The plasma concentrations of insulin-like growth factor I and its GH-dependent binding protein were normal for age in all but two cases. The height changes between irradiation and evaluation were correlated with the GH peaks (P < 0.03) and were concordant, except in patients with early puberty. This occurred in 16 patients including all 12 girls irradiated before 4 years of age. A significant (P < 0.03) reduction in height (SD) between irradiation and adult height occurred in untreated GH-deficient patients (-1+/-0.3, n=6), but not in GH-deficient patients given GH (-0.6+/-0.3, n=8) or in those with normal GH peak (-0.4+/-0.3, n=7). CONCLUSION: In children irradiated for acute lymphoblastic leukaemia, GH deficiency is frequent after 18 Gy but its impact on adult height is smaller than after higher doses. We suggest that the indications for gonadotropin releasing hormone analogue therapy should be broad in patients with early or rapidly progressing puberty and those for GH therapy in those patients with a below average constitutional height before irradiation.

Adolescent↗

PubMed1998

Ovarian function after bone marrow transplantation during childhood.

Ovarian failure is often brought about by the conditioning protocol used for bone marrow transplantation (BMT). We monitored ovarian function in 31 girls conditioned for BMT at 10.3 +/- 0.6 (s.e., 3.2-17.5) years by chemotherapy alone (group 1, n = 8) or chemotherapy plus body irradiation (12 Gy, fractionated in group 2, n = 9, or 10 Gy single total body in group 3, n = 7, and 5 or 6 Gy single thoraco-abdominal in group 4, n = 7, irradiation) at 13.4 +/- 0.4 (11.7-18.6) years. Breast development was normal (n = 11), did not occur (n = 14), or did not progress spontaneously (n = 2) after BMT. The other four girls who menstruated before BMT had permanent amenorrhea. Basal plasma gonadotropin concentrations were measured in 29; follicle-stimulating hormone was increased in them all and luteinizing hormone in 23. At the last clinical evaluation at 16.3 +/- 0.4 (12.1-21.6) years, 23 girls had complete ovarian failure, two had partial ovarian failure, and six had normal ovarian function. Three of these were the youngest group 1 patients and those who had not received busulfan. We conclude that conditioning for BMT given during childhood frequently prevents normal estrogen secretion at puberty. Adequate substitutive treatment may be necessary to induce growth acceleration and sexual development.

Adolescent↗

PubMed1998

Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation.

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r-hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067 mg/kg) s.c., during 3 y and the children in Group 2 started the study with a 1-y observation period followed by a 3-y treatment period. At birth, their mean weight standard deviation score (SDS) was -2.5 and their mean length SDS -3.5. At baseline, the patients were prepubertal, non-GH deficient, with no known dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was -3.4, height velocity (HV) SDS was -1.6, and body mass index SDS was -1.4. After 1 y of treatment, linear HV in Group 1 increased in comparison with the pre-treatment period (from 5.7 +/- 2.0 to 10.1 +/- 1.7 cm/y; p < 0.001) and with the first year of observation in Group 2 (p < 0.001). Increased HV was sustained during the second and third year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3 y of GH treatment in Group 2. Mean height SDS for chronological age increased by 2.0 +/- 0.7 in the two groups after 3 y of treatment. HV after 1 y of treatment was negatively correlated with growth velocity at baseline. Bone age remained retarded but increased with a mean of almost 4 y after 3 y of treatment in both groups. Even at a dose that is three times the replacement dose treatment with r-hGH was well tolerated. From these results, we conclude that r-hGH treatment over 3 y can induce sustained catch-up growth in young children with severe short stature and a history of IUGR. Long-term studies are needed to assess ultimate effects on final height.

Adolescent↗

PubMed1998

Long-term follow up of 69 patients treated for optic pathway tumours before the chemotherapy era.

AIM: To analyse the long-term results of conservative management with radiotherapy in patients with optic pathway tumours. DESIGN: All 69 patients were symptomatic at diagnosis and most neoplasms involved the optic chiasm and hypothalamus. RESULTS: At 10 years, overall survival and progression free survival were 83% and 65.5%, respectively. After radiotherapy, vision improved in 18 patients and remained stable in 29 other patients. Cerebrovascular complications occurred in nine of 53 patients treated with radiotherapy after a median interval of two and a half years. These complications were five times more frequent in patients with neurofibromatosis type 1 (NF1). Severe intellectual disabilities were present in 18 children, most of whom underwent irradiation at a very young age (median age, 4 years). IMPLICATIONS: Radiotherapy is a valuable treatment in terms of tumour response, visual outcome, and progression free survival. However, in young children and in patients with NF1, major sequelae are encountered and new treatment strategies should be proposed for these patients.

Adolescent↗

PubMed1998

Pituitary apoplexy in an adolescent with prolactin-secreting adenoma.

A 14.8-year-old girl was treated with bromocriptine for a prolactin-secreting adenoma. She suddenly developed headaches, vomiting, fever and meningeal syndrome. This was associated with corticotropin, thyrotropin and gonadotropin deficiencies. Magnetic resonance imaging showed peripheral enhancement and a central hyposignal suggesting intra-adenoma hemorrhage and then disappearance of the adenoma. Hydrocortisone was initiated in emergency to prevent any risk to life.

Adolescent↗

PubMed1998

Androgens and fetal growth.

Boys are heavier than girls at term birth. Children with a 46,XY karyotype and androgen insensitivity syndrome (clinically complete form and/or proven mutations in the androgen receptor gene) were found to have a birth weight comparable to that of girls. These findings support the hypothesis that the difference in birth weight between boys and girls is generated by androgen action.

Androgen-Insensitivity Syndrome↗

PubMed1998

Femoro-femoral bypass for repeat open-heart surgery.

Repeat open-heart operations are becoming more frequent with a patient population at higher risk. Sternal re-entry poses the risk of possible damage to vital structures. These include laceration of the myocardium, especially the right ventricle, tearing of patent grafts and internal mammary grafts in particular, or dislodgement of emboli from patent vein grafts. To minimize the risk associated with sternal re-entry, we adopted the method of establishing femoral artery-femoral vein cardiopulmonary bypass (CPB) in order to achieve cardiac decompression prior to sternotomy. Between June 1994 and October 1997, 94 patients underwent repeat open-heart operations at our institution. Of these, seven were a second time reoperation. Mean age was 62 years (range 31-80 years), and 65 were male. Fifty-nine patients had coronary bypass, 27 had aortic valve replacement, 45 had mitral valve replacement, and nine had other procedures (these numbers include patients having combined procedures). In patients with no known vascular disease, the femoral vessels were exposed, and if found suitable, were cannulated, and the patients connected to CPB. The sternum was opened with an oscillating saw, and on penetration through the posterior table, the heart was drained to allow for decompression. If the femoral vein cannula did not allow full bypass, ventilation was maintained until the right atrium was exposed and cannulated and full bypass was achieved. Femoro-femoral bypass was established in 75 patients. In 19 patients it was not done for the following reasons: eight patients had a diseased femoral artery, in one patient the femoral vein could not be cannulated, nonuse of CPB altogether occurred in three patients, and it was because of surgeon's preference in seven patients. In one patient a high pressure developed in the arterial line, requiring conversion to aortic cannulation during the course of CPB, without any negative consequences. There were no problems associated with sternal re-entry, no patient had limb ischemia or venous thrombosis. Two patients (2.6%) had complications related with femoral cannulation, with one having trauma to an atherosclerotic femoral artery requiring repair with vein interposition, and the other a tear of iliac vein requiring laparotomy. Groin wound infection occurred in five patients (6.6%), and groin hematoma in four patients (5.3%). All complications were treated successfully with no permanent damage. Operative mortality was 9% (seven patients). Causes of death included myocardial infarction (2), infection (3), respiratory (1), and cirrhosis (1). We conclude that femoro-femoral bypass prior to sternotomy is a safe and easy method to reduce the risk of sternal re-entry by allowing early decompression of the heart, and in unstable patients it offers better myocardial protection by earlier connection to CPB. Proper selection of patients is important in order to minimize related comorbidity. We recommend this method in redo patients in whom femoral cannulation is feasible.

Adult↗

PubMed1997

Deletions of distal 9p associated with 46,XY male to female sex reversal: definition of the breakpoints at 9p23.3-p24.1.

Monosomy of distal 9p is associated in rare cases with abnormalities of testicular determination, which can lead to male to female sex reversal in a 46,XY genetic background. We present two 46,XY individuals partially monosomic for 9p who were raised as females. Definition of the breakpoints using somatic cell hybrids containing only the rearranged chromosome 9 indicated that in the first patient the breakpoint was located between markers D9S256 and D9S144 and in the second patient, the breakpoint was distal to the marker D9S144. In both cases this corresponds to the cytogenetic position 9p23.3-p24.1. Analysis of highly polymorphic microsatellite markers demonstrated a paternal origin of the rearranged chromosome 9 in both patients. These studies define the minimum region associated with male to female sex reversal as 9p24.1-pter.

Child, Preschool↗

PubMed1997

Contribution of growth hormone deficiency to the growth failure that follows bone marrow transplantation.

Conditioning for bone marrow transplantation (BMT) by total body irradiation frequently causes growth failure. The contribution of growth hormone (GH) deficiency to this failure was assessed in 38 patients given three types of body irradiation: group 1 (n = 18) was given 12 Gy total body irradiation as six fractions, group 2 (n = 14) 10 Gy (one dose) total body irradiation, and group 3 (n = 6) 6 Gy (one dose) thoracoabdominal irradiation, which did not involve the hypothalamic-pituitary area. At the first evaluation, 2.9 +/- 0.2 (SE) years after BMT, the values for the plasma insulin-like growth factor I (IGF-I) and its GH-dependent binding protein (IGFBP-3) were similar in groups 1 and 2 but significantly greater in group 3 (p < 0.02 for IGF-I and 0.01 for IGFBP-3). These values were similar in those patients in groups 1 and 2 who had low GH peaks after stimulation (12 patients: IGF-I, 0.8 +/- 0.2 U/ml; IGFBP-3, 1.6 +/- 0.2 mg/L) and in those with normal GH peaks (20 patients: 1 +/- 0.1 U/ml and 1.8 +/- 0.1 mg/L). The decrease in height 2 years after BMT was significantly (p < 0.01) greater in group 2 than in groups 1 and 3, but 5 years after BMT it was similar in groups 1 and 2 (0.9 +/- 0.2 and 1.4 +/- 0.3 SD), significantly (p < 0.05) greater in group 2 than in group 3 (0.7 +/- 0.2 SD). The individual height changes between BMT and the last clinical evaluation before GH therapy were not correlated with the age at BMT, GH peak after stimulation, plasma IGF-I concentration, or IGFBP-3 concentration. Seven patients with GH deficiency were given GH therapy; their growth rate became normal for age (-2.1 +/- 0.9 SDS before and -0.2 +/- 0.4 SDS for the first year; not significant) without any catch-up growth. We conclude that plasma IGF-I and IGFBP-3 values are of no diagnostic value for GH deficiency after TBI. Their normal or high levels, despite low GH peaks, suggest that bone irradiation induces lesions causing resistance to IGF-I.

Body Height↗

PubMed1997

Intracoronary adenovirus-mediated transfer of immunosuppressive cytokine genes prolongs allograft survival.

BACKGROUND: Intracoronary transfer and expression of recombinant genes in the intact heart is now feasible. In the transplant setting, local modulation of host immune responses by a genetically modified allograft may offer an attractive alternative to systemic immunosuppression. METHODS: We tested the efficacy and in vivo effect of intracoronary transfer of two immunosuppressive cytokine genes. First-generation E1-deleted adenoviral vectors expressing the Epstein-Barr virus interleukin-10 (AdSvIL10) or human transforming growth factor--beta 1 (AdCMVTGF-beta) were used. Rabbit cardiac allografts were transduced during cold preservation by slow (1 ml/min) intracoronary infusion of 10(10) pfu/gm diluted viral vectors and then implanted heterotopically. Controls included E1-deleted adenovirus (Ad5dI434) and AdCMVLacZ. Beating allografts were collected on day 4 for analysis of gene transfer efficacy and distribution. Additional grafts were used for evaluation of alloreactivity (n = 34). RESULTS: Mean allograft viral uptake was 81% (up to 91%). Polymerase chain reactions and reverse transcription-polymerase chain reactions confirmed the presence and expression of both genes in the grafts. beta-Galactosidase staining in AdCMVLacZ-infected grafts demonstrated efficient gene expression, which was highest (100%) in subepicardial regions. More homogeneous transmyocardial distribution of the transgene (in 25% to 40% of cells) could be achieved by pulsatile slow delivery. Allograft survival was 6.9 +/- 0.9 days in controls (n = 12), 11.1 +/- 1.7 days in AdCMVTGF-beta-infected grafts (n = 11, p < 10(-4)), and 11.2 +/- 3 days in AdSvIL10-infected grafts (n = 11, p < 10(-4)). Histologic scores (blinded) showed significantly (p < 0.005) higher regression coefficients for rejection in controls compared with both cytokine-transduced groups. Perioperative administration of cyclosporine A (INN: ciclosporin) to recipients had no effect on survival of AdCMVTGF-beta-infected grafts but reduced survival of AdSvIL10-infected grafts. CONCLUSIONS: Intracoronary gene transfer of immunosuppressive cytokines to cardiac allografts is efficient and effectively prolongs graft survival. Vectors that would induce long-term expression of such genes may make this approach clinically applicable.

Adenoviridae↗

PubMed1997

Controlled periadventitial administration of verapamil inhibits neointimal smooth muscle cell proliferation and ameliorates vasomotor abnormalities in experimental vein bypass grafts.

OBJECTIVE: Inhibition of early myointimal proliferation may improve longterm patency of vein grafts, but the clinical use of many experimental drugs is limited by systemic toxicity. To determine whether this goal can be achieved by low-dose targeted drug administration, we constructed a polymeric system delivering verapamil and evaluated the effects on local and downstream vein graft morphology, neointimal smooth muscle cell proliferation, and vasomotor function. METHODS: Ethylene-vinyl acetate polymeric delivery systems were constructed, containing 2% verapamil by weight. These are flexible, biocompatible, and nonbiodegradable matrices, delivering the drug at a rate of 10 micrograms/day. The autologous external jugular vein was used to create a carotid artery bypass graft in hypercholesterolemic (n = 22) rabbits. Verapamil-containing matrices (n = 12) or plain polymers (control, n = 10) were wrapped around the proximal third of the veins after reperfusion. Graft vasomotor function was evaluated and was also compared with function of an additional group of normocholesterolemic vein grafts (n = 8). RESULTS: Twenty-eight days after grafting, intimal index (intima/media thickness ratio) was 31% lower, neointima/original lumen surface ratio was 26% lower, and residual luminal area was 71% greater (4.00 +/- 1.2 mm2 versus 2.34 +/- 0.9 mm2, all p < 0.01) under verapamil matrices compared with control grafts. Neointimal smooth muscle cell content was reduced from 45.4% to 28.2%, and net neointimal smooth muscle cell thickness was reduced by 47% (30 microns vs 15.8 microns, both p < 0.01). Verapamil-treated segments distal to the matrices also showed significantly lower neointimal smooth muscle cell density and increased lumen size. Sensitivity to serotoin and vasomotor responses to serotonin, norepinephrine, and sodium nitroprusside in distal segments were significantly lower in verapamil-treated grafts than in controls. CONCLUSIONS: Periadventitial controlled administration of verapamil below 1% of the systemic dose effectively inhibits myointimal hyperplasia in vein grafts. Local polymeric drug delivery may be readily applicable to coronary revascularization operations.

Animals↗

PubMed1997

Intracoronary gene transfer of immunosuppressive cytokines to cardiac allografts: method and efficacy of adenovirus-mediated transduction.

OBJECTIVE: Allograft-targeted immunosuppressive gene therapy may inhibit recipient immune activation and provide an alternative to systemic immunosuppression. We studied the optimal technique and efficacy of intracoronary gene transfer of viral interleukin-10 and human transforming growth factor-beta 1 in a rabbit model of heterotopic heart transplantation. METHODS: Replication-defective adenoviral vectors were constructed, expressing viral interleukin-10 (AdSvIL10) or transforming growth factor-beta 1 (AdCMVTGF-beta 1). Intracoronary delivery of vectors was accomplished ex vivo by either bolus injection or slow infusion. The allografts were implanted heterotopically in recipient rabbits and collected 4 days after the operation. Vector dose was 4 x 10(9) to 6 x 10(10) pfu/gm of donor heart. Transfer was confirmed by DNA amplification for both genes. Gene product expression in tissue was quantified by immunoassay and visualized by immunohistochemical staining. RESULTS: Allograft viral uptake was only 9.9% +/- 2.4% with bolus injection, but increased to 80.5% +/- 6.8% at 1 ml/min infusion rate (p = 5 x 10(-14)). Uptake ratio was not affected by vector quantity or slower infusion rates. Transforming growth factor-beta 1 was consistently detected in allografts infected with AdCMVTGF-beta 1, but not with control adenovirus or AdSvIL10. Expression was proportional to infused vector quantity and reached 10 ng/gm of allograft at infused 10(10) pfu/gm. Transforming growth factor-beta 1 was also detected in recipient's serum at less than 1 ng/ml. Viral interleukin-10 was detected in minor amounts only (< 1 ng/gm) in allografts infected with AdvIL10 up to 5 x 10(10) pfu/gm. Nevertheless, it was detected in recipient serum at concentrations up to 0.4 ng/ml. CONCLUSIONS: Intracoronary gene transfer of immunosuppressive cytokines to cardiac allografts during cold preservation is feasible. Slow infusion is superior to bolus injection. In vivo effects on allograft rejection remain to be determined.

Adenoviridae↗

PubMed1997

Benefits of early surgical repair in fixed subaortic stenosis.

OBJECTIVES: We sought to determine whether early resection can improve outcome in fixed subaortic stenosis. BACKGROUND: The diagnosis of subaortic stenosis (SAS) is often made before significant gradients occur. Whereas resection is the accepted treatment, it remains uncertain whether surgical intervention at this early stage can reduce the incidence of recurrence or influence the progression of aortic valve damage. METHODS: Follow-up was available for 75 of 83 consecutive patients operated on for fixed SAS; the average duration of follow-up was 6.7 years. The lesion was discrete in 68 patients (91%) and of a tunnel type in 7, with associated ventricular septal defect in 28 (37%). All underwent transaortic resection. RESULTS: There were no deaths. There were 18 recurrences of SAS in 15 patients (20%). Thirteen patients (17%) underwent 17 reoperations for recurrence or aortic valve disease. The cumulative hazard of recurrence was 8.9%, 16.1% and 29.4% +/- 2.3% (mean +/- SEM), and the hazard of events, including recurrence and reoperation, was 9.2%, 18.4% and 35.1% +/- 3.5% at 2, 5 and 10 years, respectively. Residual end-operative left ventricular outflow tract (LVOT) gradients (> 10 mm Hg, n = 8) and tunnel lesions were univariate predictors of recurrence (p = 0.0006 and p = 0.003, respectively). Multivariate predictors included higher preoperative LVOT gradient (p < 10(-4)) and younger patient age (p = 0.002). Only two recurrences (0.87 per 100 patient-years of follow-up) were noted in patients with a preoperative peak LVOT gradient < or = 40 mm Hg (n = 40), whereas higher gradients (n = 35) were associated with a greater than sevenfold recurrence rate (6.45 events per 100 patient-years, p = 0.002). The aortic valve required concomitant repair in 17 cases in the high gradient group (48.6%) but in only 8 in the low gradient group (20%, p = 0.018). Despite relief of the obstruction, progressive aortic regurgitation was noted at follow-up after 14 procedures in the high gradient group (40%) but after only 5 procedures in the low gradient group (12.5%, p = 0.014). CONCLUSIONS: The data suggest that surgical resection of fixed subaortic stenosis before the development of a significant (> 40 mm Hg) outflow tract gradient may prevent recurrence, reoperation and secondary progressive aortic valve disease.

Aortic Stenosis, Subvalvular↗

PubMed1997

Growth after bone marrow transplantation in young children conditioned with chemotherapy alone.

Short stature is a potential side-effect of BMT, brought about by the conditioning protocol and/or the complications of BMT. This study evaluates the effects of conditioning by chemotherapy, and BMT complications on growth. Thirty children conditioned for BMT by chemotherapy alone (cyclophosphamide and busulfan) were classified according to the occurrence of serious or prolonged complications after BMT: group 1 (n = 12) had no complication, while group 2 (n = 18) did. Fifteen of them were severely growth retarded (< or = -2 s.d.) at BMT, because of their initial disease. At the time of BMT, the two groups had similar ages (1.0 +/- 0.2, s.e.m. year, in group 1 and 1.7 +/- 0.5 year in group 2), height (-1.7 +/- 0.5; -1.8 +/- 0.3 s.d.) and plasma insulin-like growth factor I (IGFI) levels (0.3 +/- 0.1 U/ml in both). Group I grew significantly and their plasma IGFI increased but group 2 did not, as assessed 2 years post-BMT. We conclude that conditioning with chemotherapy alone does not prevent the catch-up growth induced by BMT in young children; the lack of catch-up growth is due to complications occurring after BMT, and the change in plasma IGFI suggests that complications of BMT prevent any increase in plasma IGFI, and thereby catch-up growth.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Adult height in 24 patients treated for growth hormone deficiency and early puberty.

This study evaluates the capacity of treatment with the combination of growth hormone (GH) and gonadotropin releasing hormone (GnRH) analog to preserve the height potential of 24 patients (15 girls, 9 boys) with GH deficiency and early puberty (onset at 7.8 +/- 0.5 SE yr in girls and 9.0 +/- 0.7 yr in boys). All but 4 were given cranial irradiation. They (group 1) were compared with 17 patients of normal pubertal age treated with GH for cranial irradiation-induced GH deficiency (group 2) and with 19 girls treated with GnRH analog for idiopathic central precocious puberty (group 3). The adult heights in groups 1, 2 and 3 were -0.5 +/- 0.2, -1.3 +/- 0.2, and -0.2 +/- 0.2 SD, significantly lower (P < 0.01) in group 2. They were lower than the target heights in groups 1 and 2 (P < 0.001), and similar in group 3. They were similar to the predicted heights at the onset of therapy (combined, GH, or GnRH analog therapy), except in group 3 (adult height > predicted height, P < 0.0001) In group 1, as in group 3, the differences between adult and predicted heights (1.1 +/- 1.3 and 6.5 +/- 1.4 cm respectively) correlated positively with the difference between bone and chronological ages (P < 0.05), negatively with the predicted height (P < 0.002), and positively with the difference between the target and predicted heights (P < 0.001) at the onset of therapy. In conclusion, treatment with the combination of GH and GnRH analog in patients with GH deficiency and early puberty leads to a normal adult height. This height is similar to the predicted height at the onset of therapy but lower than the target height.

Adult↗

PubMed1997

Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of its pathogenesis.

The detection of pituitary stalk interruption syndrome (PSIS) by magnetic resonance imaging is a diagnostic marker of permanent GH deficiency (GHD), but the pathogenesis of PSIS is unknown. Fifty-one patients (27 males) with GHD and PSIS were classified according to whether the GHD was isolated (group 1, 16 cases) or associated with other anterior pituitary abnormalities (group 2, 35 cases). The 2 groups had similar characteristics (frequencies of perinatal abnormalities, ages at occurrence of first signs and at diagnosis, height, GH peak response to stimuli other than GHRH), but associated malformations were less frequent in group 1 (12%) than in group 2 (54%; P < 0.01), hypoglycemia occurred in 25% of group 1 and 70% of group 2 (P < 0.01), and the GH peak response to GHRH was less than 10 micrograms/L in 0% of group 1 (4 cases evaluated) and 57% of group 2 (21 cases; P < 0.05). Thirty-one cases (61%; 25 from group 2) had features suggesting an antenatal origin: familial form (4 cases), microphallus (10 boys), and/or associated malformations (50%; 21 cases). Twenty-seven cases (53%, 22 from group 2) had features suggesting a hypothalamic origin. The three group 1 patients with a GH peak of 1 microgram/L or less had no large GH-N gene deletion. One familial form had no linkage between the GHD phenotype and abnormal GH-N locus, and the only mutation described to date in the GHRH receptor gene was absent. The two patients with low plasma PRL levels had no Pit-1 gene abnormality. Thus, most of the patients with GHD associated with multiple anterior pituitary abnormalities and PSIS have features suggesting an antenatal origin. The GH-N, GHRH receptor, and Pit-1 genes do not seem to be implicated in PSIS.

Adolescent↗

PubMed1996

Adult height after cranial irradiation with 24 Gy: factors and markers of height loss.

The decrease in adult height of children who have been given cranial irradiation (24 Gy) for acute lymphoblastic leukaemia is attributed to chemotherapy, growth hormone (GH) deficiency and early puberty. This study evaluates the factors involved in the height loss between irradiation and adult height and its markers in 43 patients irradiated at 5.8 +/- 0.4 (SEM) years. The mean height loss was 0.9 +/- 0.2 SD in the children with a normal GH peak (n = 11), 1.7 +/- 0.2 SD in those with a low GH peak and untreated (n = 15) and 0.6 +/- 0.2 SD in those treated with GH (n = 17). The adult height was significantly lower than target height in all three groups. The height loss correlated negatively with the GH peak (p < 0.02) and with the age at onset of puberty (p < 0.05) in the first two groups with spontaneous growth, but not with the chemotherapy regimen or its duration, or the plasma insulin-like growth factor I (IGFI) and its GH-dependent binding protein (BP-3). Early puberty (onset at 8-10 years) occurred in 6 girls from the first two groups. At the first evaluation, 5.6 +/- 0.4 years after irradiation, the GH peak values after arginine-insulin stimulation correlated with the age at irradiation (p < 0.03), taking into account the time since irradiation. The plasma IGFI and BP-3 values were correlated with each other, but not with the GH peak. In conclusion, this study demonstrates the impact of GH deficiency and GH replacement therapy on adult height in children given cranial irradiation for leukaemia. They therefore should be evaluated for their GH secretion 1-2 years after the end of chemotherapy. GH therapy is indicated for those with low GH peak and decreased growth rate or no increase in growth rate despite puberty.

Antineoplastic Combined Chemotherapy Protocols↗