bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of radiation‐induced growth hormone deficiency with growth hormone‐releasing hormone
Authors: Ogilvy‐Stuart A. L. , Stirling H. F. , Kelnar C. J. H. , Savage M. O. , Dunger D. B. , Buckler J. M. H. , Shalet S. M. 
Published: November 2003

In children with hypothalamic causes for GH deficiency there are theoretical reasons why a GHRH analogue might be better than conventional GH therapy in promoting growth.OBJECTIVEWe have aimed to determine the efficacy and safety of growth hormone‐releasing hormone (GHRH) (1–29)‐NH2 given as a twice daily subcutaneous injection in the treatment of growth failure in children with radiation‐induced GH deficiency.DESIGNA multicentre study comparing growth before and after 1 year of treatment with GHRH (1–29)‐NH2, 15 μg/kg twice daily, by subcutaneous injection in children with radiation‐induced GH deficiency. On completion of the study year all children were treated with GH (05 U/kg/week) and growth parameters were documented over the next year.PATIENTSNine children (six boys) with radiation‐induced GH deficiency following cranial (n = 4) or craniospinal (n = 5) irradiation for a brain tumour distant from the hypothalamic–pituitary axis (n = 8) or prophylaxis against central nervous system leukaemia (n = 1) were studied. All were prepubertal when the study commenced, which was at least 2 years from radiotherapy.MEASUREMENTSAnthropometry and pubertal staging were carried out at 3‐monthly intervals and bone age estimations at 6‐monthly intervals (TW2 method). Pretreatment standing height velocities were compared with values during the year of GHRH treatment and then after the first year of GH therapy. In those that had received craniospinal irradiation, a change in leg‐length Standard deviation score (SDS) was noted before and after GHRH therapy. Changes in skin‐fold thickness and bone age during the GHRH study year were documented. Adverse events and 3‐monthly measurements of clinical chemistry, haematology, lipid profile and thyroid function were recorded.RESULTSThere was a significant increase in height velocity from 33 (SD 11) cm/year before treatment, to 60 (SDS 15) cm/year after 1 year of GHRH treatment (P = 0004). GHRH maintained or improved the leg length SDS in children who had received craniospinal irradiation. Bone age increased by a mean of 11 years/chronological year during treatment with GHRH. Subsequent height velocity during 1 year of GH therapy was 75 (SD 15) cm/year. No adverse changes in biochemical or hormonal analyses were noted or adverse events that could be attributed to GHRH therapy. One child went into puberty during the GHRH study year and three were pubertal during the first year of GH therapy.CONCLUSIONIn cranially irradiated children, GHRH was effective in increasing growth velocity but this was less than that seen in response to GH therapy, although it matched that in children with isolated idiopathic GH deficiency treated with the same dose and schedule of GHRH administration.
Thyroid dysfunction in patients with amyloid goitre
Authors: Kimura Hironori , Yamashita Shunichi , Ashizawa Kiyoto , Yokoyama Naokata , Nagataki Shigenobu 
Published: November 2003

OBJECTIVESWidespread amyloid deposition in the thyroid gland causes diffuse, clinically apparent enlargement of the thyroid (amyloid goitre: AG). The aim of this study was to clarify the abnormalities of thyroid function in patients with AG.DESIGNThirty patients with secondary amyloidosis were retrospectively analysed. Their thyroid status was evaluated using the results of routine thyroid function tests and measurement of thyroid autoantibodies. Thyroid needle biopsy was carried out to identify amyloid deposition in the thyroid gland.RESULTSThyroid enlargement was observed in 19 (63%) of 30 patients with amyloidosis. Eleven of these 19 patients had a thyroid biopsy and/or autopsy and amyloid deposition was histologically revealed in 10 (defined as AG) of these 11 patients. Nine of 10 patients (90%) with AG had abnormalities of thyroid function, including five patients with hypothyroidism, one with hyperthyroidism, one with transient hypothyroidism, and two with low T3 syndrome. Five had thyroid autoantibodies. The patient with hyperthyroidism had positive thyroid stimulating antibody (TSAb) and high 131I thyroidal uptake, suggesting the coexistence of Graves’ disease. Another patient suffered from thyroidal pain and showed transient hypothyroidism, high level of serum thyroglobulin and low thyroidal uptake of 123I, the clinical course being compatible with subacute thyroiditis.CONCLUSIONSThe incidence of thyroid abnormalities accompanied by AG, although asymptomatic, is unexpectedly high. Thyroid function should therefore be regularly assessed during follow‐up of patients with systemic amyloidosis.
Insulin‐like growth factor‐I in growth hormone‐deficient adults: relationship to population‐based normal values, body composition and insulin tolerance test
Authors: Svensson Johan , Johannsson Gudmundur , Bengtsson Bengt‐Åke 
Published: November 2003

BACKGROUNDAlthough an insulin tolerance test (ITT) is the most commonly used method for detecting growth hormone (GH) deficiency (GHD) in adults, measurements of serum insulin‐like growth factor‐I (IGF‐I) may also be of value.OBJECTIVETo validate the use of serum IGF‐I concentration in the diagnosis of GHD in adults.DESIGNA cross‐sectional study.PATIENTSOne hundred and four patients, 60 men and 44 women, with known pituitary disease and verified GHD based on ITT.MEASUREMENTSSerum IGF‐I was determined by radioimmunoassay after acid–ethanol extraction. Body composition was estimated with total body potassium combined with total body water assessments.RESULTSAccording to age‐ and sex‐adjusted population‐based reference values, 51 patients had serum IGF‐I concentrations below −2 SD of the predicted values and 53 had concentrations within 2 SD. Fifty‐seven per cent of the patients aged 41 years (25th percentile) or below and 39% of the patients aged 57 years (75th percentile) or above had serum IGF‐I concentrations below −2 SD. Women had lower mean IGF‐I SD scores than men (P < 0.01). Serum IGF‐I was correlated with peak GH response during ITT (r = 0.40; P < 0.001), age (r = −0.27; P < 0.01), duration of hypopituitarism (r = −0.52; P < 0.001), number of pituitary hormonal deficiencies (r = −0.35; P < 0.001), body cell mass (r = 0.30; P < 0.01) and serum insulin (r = 0.21; P < 0.05). The peak GH response during ITT correlated with spontaneous GH secretion, duration (P = −0.48; P < 0.001) and number of deficiencies (r = −0.50; P  0.001).CONCLUSIONThe measurement of serum IGF‐I concentrations is not suitable as a single diagnostic test for growth hormone deficiency in adults. Even as a screening test, its use appears to be limited, especially in elderly subjects. The serum level of IGF‐I was influenced by several factors in addition to GH, such as age, gender, anthropodometry and serum insulin level. The peak GH response during the insulin tolerance test appears to be influenced to a lesser degree by these factors.
Acromegaly, colonic polyps and carcinoma
Authors: Jenkins Paul J. , Fairclough Peter D. , Richards Toby , Lowe David G. , Monson John , Grossman Ashley , Wass John A. H. , Besser Michael 
Published: November 2003

OBJECTIVEIt has been suggested that patients with acromegaly may be at risk of developing colorectal carcinoma. In order to clarify this issue, we have evaluated the prevalence of carcinoma, premalignant tubulovillous adenomas and hyperplastic colonic polyps in a large cohort of patients with acromegaly.DESIGNProspective colonoscopic examination by a single operator.PATIENTSOne hundred and twenty‐nine patients with biochemically proven acromegaly.RESULTSAt least one lesion was visualized in 63 patients. Adenocarcinoma was present in six patients (5%), but only two had symptoms; all lesions were endoscopically obvious. Compared with a normal group, the odds ratio of colorectal cancer is increased at 13.5 (95% confidence intervals (c.i.) 3.1–75). One or more tubulovillous adenoma was found in 34 patients (26%) and this prevalence was age‐dependent, occurring in 39% of patients aged 70 years or over. Comparing the prevalence of left‐sided colonic adenomas with that in a normal group, there is a higher prevalence among patients over 49 years with an odds ratio of 4.2 (95% c.i. 2.5–6.8). Patients with acromegaly who had an adenoma were significantly older than unaffected patients (61.9 vs 54.1 years; P < 0.001) but had similar GH and IGF‐1 levels and duration of disease.CONCLUSIONSPatients with acromegaly have an increased risk of developing colorectal cancer and a significantly higher prevalence of tubulovillous adenomas compared with normal subjects. Routine surveillance colonoscopy is indicated in this group of patients.
Altered bioavailability due to changes in the formulation of a commercial preparation of levothyroxine in patients with differentiated thyroid carcinoma
Authors: Olveira G. , Almaraz M. C. , Soriguer F. , Garriga M. J. , Gonzalez‐Romero S. , Tinahones F. , Ruiz de Adana M. S. 
Published: November 2003

OBJECTIVESIn July 1995 we began noticing an unusually high rate of elevated TSH levels in patients with differentiated thyroid cancer treated with levothyroxine — specifically the brand Levothroid®— becoming more obvious from September 1995. Faced with the possibility that these findings had some relationship to the drug taken, we carried out a prospective study, changing this brand of levothyroxine for another.DESIGN AND PATIENTSWe studied 58 patients with differentiated thyroid carcinoma (50 women and eight men; aged 22–75 years) who were being treated with levothyroxine and who had previously had adequate TSH suppression. Their Levothroid® tablets were changed to the same dose of Dexnon® tablets, and their clinical and analytical response was evaluated 2 months later. The patients were divided into two groups according to their TSH level at the start of the study: group 1, 42 patients with TSH > 0.2 mU/l (not suppressed) and group 2, 16 patients with TSH ≤ 0.2 mU/l (suppressed).RESULTSAfter 2 months with Dexnon® the TSH levels in group 1 fell significantly (P < 0.0001) also decreasing in group (P < 0.09). The free T4 and free T3 rose significantly in both groups. After the change to Dexnon®, 17 patients (40%) in group 1 had suppressed TSH and 26 (62%) had free T4 levels above the upper limit of normal vs none at baseline (P < 0.001). The group 2 patients maintained their inhibited TSH values after treatment with Dexnon®, and the free T4 was above the upper limit of normal in 15 (94%) vs 3 (19%) at baseline (P < 0.001). The Levothroid® tablets collected from the patients in both groups formed part of those which the manufacturer later withdrew from the market. These batches possessed the correct dosage, but they had been made from ‘non‐micronized’ raw materials from another supplier.CONCLUSIONSThe most probable cause of the inadequate TSH suppression in our patients was the reduction in bioavailability in certain batches of Levothroid®, although we are unable to rule out the possibility that the results obtained after the changeover to Dexnon® were due to its greater bioavailability. Simple changes in the manufacture of levothyroxine tablets may produce important variations in their bioavailability, having an adverse effect on the clinical control of the patients, and causing extra expense by the need for repeated patient visits and thyroid function tests.
Different effects of growth hormone releasing peptide (GHRP‐6) and GH‐releasing hormone on GH release in endogenous and exogenous hypercortisolism
Authors: Borges Maria‐Helena S. , DiNinno Fernanda B. , Lengyel Ana‐Maria J. 
Published: November 2003

OBJECTIVEChronic hypercortisolism is associated with decreased GH responsiveness to GHRH. GHRP‐6 is a synthetic hexapeptide that releases GH in several species, including man. As GHRH and GHRP‐6 apparently stimulate GH release by different mechanisms, we evaluated the GH responses to these peptides in patients with endogenous and exogenous glucocorticoid excess and also in control subjects.DESIGNSix patients with endogenous hypercortisolism, nine with exogenous glucocorticoid excess and 10 normal controls were submitted to three tests, in random order, with GHRH (100 μg), GHRP‐6 (1 μg/kg) or GHRP+GHRP‐6, in the same doses, i.v., on separate days.MEASUREMENTSGH was measured by immunofluorometric assay. IGF‐I was determined by radioimmunoassay. Plasma glucose was measured by the glucose‐oxidase technique.RESULTSPeak GH values (mean ± SE; μg/l) after GHRH were significantly blunted in endogenous (2.0 ± 0.7) and exogenous (3.6 ± 1.2) hypercortisolaemic patients compared to controls (24.9 ± 5.1). The endogenous group had lower peak GH values after GHRP‐6 alone (7.7 ± 1.9) or together with GHRH (18.8 ± 5.8) than those observed in controls (GHRP‐6: 22.1 ± 3.6; GHRH+GHRP‐6: 77.4 ± 15.0) and in exogenous hypercortisolism (27.4 ± 6.2 and 78.1 ± 19.9). There were no differences in the GH responses to GHRP‐6 alone or in combination with GHRH when controls were compared to the exogenous group. No changes in plasma IGF‐I and glucose levels were observed.CONCLUSIONSOur results suggest that hypercortisolism had a different effect on the GH‐releasing mechanisms stimulated by GHRH and GHRP‐6. Moreover, in endogenous hypercortisolism both GHRH and GHRP‐6 pathways are affected, while in the exogenous group GHRP‐6 releasing mechanisms are apparently preserved.
Serum leptin through childhood and adolescence
Authors: Clayton Peter E. , Gill Matthew S. , Hall Catherine M. , Tillmann Vallo , Whatmore Andrew J. , Price David A. 
Published: November 2003

OBJECTIVELeptin is the protein product of the recently cloned ob gene, that has been implicated in the control of body weight and thermogenesis, but also independently stimulates the reproductive axis. As major changes in body composition and gonadal function occur during human adolescence, we have assessed serum leptin concentration through childhood.SUBJECTS AND MEASUREMENTSSerum leptin was measured in a radioimmunoassay in samples from 235 healthy children from 5 to 18 years of age. Its relationship to body mass index (BMI) (expressed as standard deviation score (SDS)) and the changes in concentration both within and between sexes over the stages of puberty were analysed.RESULTSSerum leptin was present at similar concentrations in both sexes over the prepubertal years and increased in parallel into early puberty (breast stage (B) 2, genital stage (G) 2). Thereafter serum leptin in the boys declined to a nadir in G5. In contrast in girls, leptin remained constant in mid‐puberty rising to a peak at B5. Factors influencing leptin (BMI SDS, age and testicular volume) were assessed therefore in the pre‐ and peripubertal stages (B1–2, G1–2) compared to the later pubertal stages (B3–5, G3–5). In all groups, leptin was positively correlated to BMI SDS (r2=38–41% in girls, r2=31–35% in boys). However in B1–2 and G1–2, leptin was also positively related to age, which contributed a further 27% and 20% respectively to the variability. In B3–5, age only accounted for an additional 5% in leptin variability. In contrast in G3–5, leptin was related positively to BMI SDS (r2=35%) and negatively to testicular volume (r2=24%).CONCLUSIONSThe influence of BMI on leptin is a significant factor throughout the prepubertal and pubertal years of both sexes. The additional negative effect of testicular volume in the boys contributes to the sexual dichotomy in leptin concentration at the completion of puberty. The similar rise in leptin over the prepubertal years into early puberty in both sexes, related not only to BMI SDS but also independently to age, would suggest that leptin may have a facilitatory role in human pubertal development.
Methionine potentiates both basal and GHRH‐induced GH secretion in children
Authors: Bellone J. , Farello G. , Bartolotta E. , Aimaretti G. , Bellone S. , Mucci M. , De Matteis F. , Ghigo E. 
Published: November 2003

OBJECTIVEIt is widely accepted that arginine is a potent GH secretagogue in man, probably acting via inhibition of hypothalamic somatostatin release. Although many other amino acids are known to stimulate GH secretion, their effects and mechanisms of action have not been extensively studied in humans. The aim of the present study was to clarify the effect, if any, of methionine (MET) on GH secretion in children with normal short stature (normal height velocity and IGF‐1 >100 μg/l).DESIGNWe studied the effect of MET (0.2 g/kg intravenously (i.v.) over 30 min) on both basal and GHRH (1 μg/kg i.v. at 0 min)‐induced GH secretion (group A) comparing its effect with that of arginine (ARG) at low and classical doses 0.2 and 0.5 g/kg i.v. over 30 min) (groups B and C). The effect of the combined administration of MET and ARG (0.5 g/kg i.v. over 30 min) (group D) on GH secretion was also studied.PATIENTSThirty‐four children (20 male and 14 female, age 12.8–14.0 years), divided into four groups.MEASUREMENTSSerum GH was measured in duplicate by immunoradiometric assay.RESULTSIn group A, MET increased basal GH levels (peak, mean ± SEM 14.6 ± 2.6 vs 2.6 ± 0.6 mU/l; P < 0.01) and potentiated the GH response to 1 μg/kg i.v. GHRH (78.0 ± 17.6 vs 41.6 ± 9.8 mU/l; P < 0.02). In group B, ARG (0.2 g/kg) increased basal GH levels (16.2 ± 5.2 vs 2.4 ± 0.6 mU/l; P < 0.03) and potentiated the GH response to GHRH (119.6 ± 20.4 vs 48.8 ± 14.2 mU/l; P < 0.01). In group C, ARG (0.5 g/kg) induced a clear GH rise (28.0 ± 3.8 vs 2.0 ± 0.6 mU/l; P < 0.001) and potentiated the GH response to GHRH (93.4 ± 10.0 vs 34.2 ± 4.6 mU/l; P < 0.001). The GH responses to MET and ARG alone in groups A and B were similar and lower than that to ARG in group C. The GH responses to MET or ARG combined with GHRH in groups A, B and C were similar. In group D MET failed to modify the GH response to 0.5 g/kg i.v. ARG (10.8 ± 6.4 vs 9.6 ± 6.0 mU/l).CONCLUSIONMethionine potentiates both basal and GHRH‐induced GH secretion in children as effectively as arginine. As methionine has no interaction with arginine, our data suggest that these amino acids act via a common mechanism.
A novel mutation causing complete deficiency of thyroxine binding globulin
Authors: Ueta Yoshihiko , Mitani Yasuo , Yoshida Akio , Taniguchi Shinichi , Mori Atsumi , Hattori Kimihiko , Hisatome Ichiro , Manabe Ichiro , Takeda Kyoko , Sato Ryoichi , Ahmmed Gias U. , Tsuboi Mariko , Ohtahara Akira , Hiroe Koh , Tanaka Yasushi , Shigemasa Chiaki 
Published: November 2003

OBJECTIVEThyroxine binding globulin (TBG) is a serum protein that transports thyroxine. Three naturally occurring mutations have been reported to produce complete deficiency of TBG (TBG‐CD). The first to be reported was TBG‐CD5 in caucasian families of French‐Canadian origin and consists of substitutions in exons 2 and 3. TBG‐CD of English ethnic origin (TBG‐CD6) is characterized by a thymine deletion in codon 165 (exon 1). In Japanese families with TBG‐CD (TBG‐CDJ), a variant has been characterized with a deletion of the first base of the codon for amino acid 352 (exon 4) in the common type TBG. In this communication we report a new type of TBG‐CD in a family of japanese ethnic origin that is characterized by a single nucleotide substitution in place of two nucleotides in exon 1. This is an uncommon mutation which we have been unable to find in other genes.DESIGNExons of the TBG gene amplified by the polymerase chain reaction (PCR) were subcloned and sequenced. To examine for the presence of the same mutation in potentially affected individuals, we performed PCR using primer‐directed mutagenesis or allele‐specific amplification.PATIENTSThe index case was of Japanese ethnic origin, and was diagnosed as having TBG deficiency on the basis of undetectable serum TBG. The patient consented to this evaluation and the protocol was in accordance with IRB standards.MEASUREMENTSSerum thyroid hormones, thyrotrophin binding inhibitory immunoglobulin and TBG concentrations were measured by conventional radioimmunoassay. Genomic DNA was extracted from white blood cells.RESULTSIn the index case exons 2, 3 and 4 were normal, but nucleotides 144 (cytosine) and 145 (thymine) in exon 1 were substituted with a single base (adenine) which induced a frame shift in the reading frame, resulting in an early stop codon at codon 51. The patient and his daughters were confirmed as having this mutation using primer‐directed mutagenesis or allele‐specific amplification.CONCLUSIONSWe have described a novel mutation in the TBG gene in a Japanese family. This results in a frame shift and premature stop codon, and was associated with undetectable serum TBG in the index case.
Glucoregulatory disorders in school refusal students
Authors: Iwatani Noritaka , Miike Teruhisa , Kai Yumiko , Kodama Mihoko , Mabe Hiroyo , Tomoda Akemi , Fukuda Keiko , Jyodoi Takako 
Published: November 2003

OBJECTIVESOur previous studies demonstrated autonomic nervous system disorders and cerebral blood hypoperfusion in school refusal students with underlying emotional distress due to fear or anxiety associated with school attendance. Because severe stress is known to affect glucoregulatory metabolism, this study used the oral glucose tolerance test (OGTT) to measure glucose metabolism in school refusal students.DESIGNA three‐hour OGTT was performed. In preparation for the test, students fasted overnight. After a fasting blood sample was drawn, students were given solutions containing a predetermined amount of glucose based on their body weight (1.75 g/kg to a maximum 75 g). After glucose ingestion, blood samples were drawn at 30, 60, 90, 120, 150, and 180 min to measure blood glucose (BG), immunoreactive insulin (IRI), pancreatic glucagon (IRG) and growth hormone (GH) levels. BG levels, IRI response, cumulative BG (ΣBG), cumulative IRI (ΣIRI), insulin/glucose ratio (ΔIRI/ΔBG), and insulinogenic index (ΣIRI/ΣBG) were then compared to previously reported normal control data. As an index of emotional difficulties, the self‐rating depressive scale (SDS) was carried out.PATIENTSEighty‐one school refusal students (40 males and 41 females), 11–19 years of age (14.8 ± 2.1), were studied. Their school refusal periods ranged from one month to eight years. All students were within – 15 to + 20 %(‐0.04 ± 8.6) of ideal body weight.MEASUREMENTSBG levels were determined using a glucose oxidase reaction method. Serum hormones were measured by radioimmunoassay.RESULTSBG levels at all OGTT time intervals and ΣBG were significantly higher in school refusal students than the normal control data (ΣBG: 39.5 ± 4.4 vs 33.3 ± 3.4 mmol/l, P < 0.001). Although the insulin response was abnormally low relative to the prevailing hyperglycaemia (ΣIRI/ΣBG: subjects vs control = 232 ± 129 vs 375 ± 271, P < 0.01), normal beta cell secretory ability was speculated (ΣIRI: subjects vs controls = 2805 ± 1274 vs 2523 ± 1219 pmol/l). This suggests a relative suppression of insulin secretion. A paradoxical increase of GH was observed in 19 students after glucose ingestion.CONCLUSIONSGlucoregulatory disorders observed in school refusal students may be caused by emotional distress. Multiple factors including autonomic nervous system disorders, derangement of neuropeptides in the hypothalamus, and hormonal imbalances may also affect glucoregulatory metabolism, predisposing these students to hyperglycaemia. We speculate that the glucoregulatory system compensates for decreased blood flow to the brain by increasing blood glucose concentrations, thereby providing sufficient glucose as the primary energy source used during normal brain metabolism.