bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carbohydrate metabolism during growth hormone treatment and after discontinuation of growth hormone treatment in girls with Turner syndrome treated with once or twice daily growth hormone injections
Authors: Sas Theo , De Muinck Keizer‐Schrama Sabine , Aanstoot Henk‐Jan , Stijnen Theo , Drop Stenvert ,   the Dutch Advisory Group on Growth Hormone
Published: March 2003

OBJECTIVETo assess possible side‐effects of treatment with supraphysiological GH dosages on carbohydrate (CH) metabolism in girls with Turner syndrome (TS) during GH treatment until adult height is reached as well as after discontinuation of GH treatment.DESIGNIn a prospective, randomized injection frequency‐response study, the effect of GH treatment in combination with low dose ethinyl oestradiol on CH metabolism was evaluated, comparing twice daily (BID) with once daily (OD) injections of a total GH dose of 6 U/m2/day until adult height was reached.PATIENTSNineteen untreated girls with TS, mean (SD) pretreatment age 13.3 (1.7) (range 11.0–17.6) year.MEASUREMENTSGlucose and insulin concentrations during oral glucose tolerance tests (OGTT) were measured before and during GH treatment, as well as at 6 months after discontinuation of GH treatment.RESULTSGH treatment was discontinued after a mean of 43 (range 27–57) months. In one of the 19 girls, a different girl at each time point before, during and after discontinuation of GH treatment, the glucose response to OGTT after 120 minutes was above 7.8 mmol/l but below 11.1 mmol/l, indicating impaired glucose tolerance. None of the girls developed diabetes mellitus. Fasting glucose levels did not significantly change during, or after discontinuation of GH treatment. The 3 h area under the curve for time–concentration adjusted for fasting levels during the OGTT for glucose showed a significant decrease during GH treatment. In contrast to the glucose levels, GH treatment induced considerably higher insulin levels compared to pretreatment values. After discontinuation of GH insulin levels decreased to values comparable with pretreatment levels. None of these observed changes were different between the GH injection frequency groups. The changes in CH variables during and after discontinuation of GH were not related to changes in body mass index.CONCLUSIONSGH treatment with 6 U/m2/day in combination with low dose ethinyl oestradiol in girls with Turner syndrome aged ≥ 11 years did not negatively influence glucose levels, but induced higher levels of insulin indicating relative insulin resistance. These changes in insulin levels were independent of the frequency of the GH injections (once vs. twice daily). After discontinuation of GH treatment, insulin values decreased to baseline levels.
Goitrogenesis during pregnancy and neonatal hypothyroxinaemia in a borderline iodine sufficient area
Authors: Kung A. W. C. , Lao T. T. , Chau M. T. , Tam S. C. F. , Low L. C. K. 
Published: March 2003

Severe iodine deficiency disorders (IDDs) may have been eradicated in many parts of the world, but milder forms still exist and may escape detection. We evaluated the impact of pregnancy on the maternal and fetal thyroid axis in Hong Kong, a coastal city in southern China with borderline iodine intake.A prospective study performed in a maternity hospital.Two hundred and thirty pregnant women were prospectively studied and their neonates assessed at birth.Urine iodine concentration, thyroid function tests and thyroid volume (TV) by ultrasound were determined in the mothers during pregnancy and up to 3 months postpartum and in the neonates.Increased urinary iodine concentration was seen from first trimester onwards and the proportion of women having urine iodine concentration of < 0·4 µmol/l decreased from 11·3% in the first trimester to 4·7% in the third trimester. There was progressive reduction in circulating fT4 and fT3 concentrations and free thyroxine index (FTI) with increasing gestation and the percentage of women having subnormal levels at term were 53·2%, 61·1% and 4·8%, respectively. The serum TSH concentration during pregnancy doubled towards term. In the first trimester, multiparous women had significantly larger TV than the nulliparous women (P < 0·001). By the third trimester, TV had increased by 30% (range 3–230%) so that the goitre incidence was 14·1%, 21·8%, 25·9% during the three trimesters of pregnancy, and 24·3% and 21·9% at 6 weeks and 3 months postpartum (ANOVA, P < 0·05). The change in thyroid volume during pregnancy correlated positively with the change in thyroglobulin (r = 0·225, P < 0·002) and negatively with urinary iodine concentration (r = − 0·149, P < 0·02).Fourteen women with excessive thyroidal stimulation in the second trimester (defined as those with thyroglobulin (Tg) concentrations in the highest tertile and FTI in the lowest tertile) were found to have lower urine iodine concentrations and larger TV (both P < 0·005) throughout pregnancy, and their neonates had higher cord TSH (P < 0·05), Tg (P < 0·05) and slightly larger TV (P = 0·06) as compared to the findings in 216 pregnant women without evidence of thyroid stimulation. Seven neonates (50%) born to these women had subnormal fT4 levels at birth.In a borderline iodine sufficient area, pregnancy posed an important stress resulting in higher rates of maternal goitrogenesis as well as neonatal hypothyroxinaemia and hyperthyro‐ trophinaemia. An adequate iodization program is necessary to eliminate iodine deficiency disorders during pregnancy.
Congenital thyrotoxicosis in premature infants
Authors: Smith Christopher , Thomsett Michael , Choong Catherine , Rodda Christine , McIntyre H. David , Cotterill Andrew M. 
Published: March 2003

Graves' disease (GD) complicates 0·1% to 0·2% of pregnancies, but congenital thyrotoxicosis is rare occurring in one in 70 of these pregnancies independent of maternal disease status. Antenatal prediction of affected infants is imprecise; however, maternal history, coupled with a high maternal serum TSH receptor binding immunoglobulin index (TBII) predict adverse neonatal outcome. Mortality is reported to be as high as 25% in affected infants and would therefore be expected to be higher in premature infants. This study illustrates that in sick, premature, extreme low birth weight (ELBW) or intrauterine growth retarded (IUGR) infants, the diagnosis maybe overlooked especially in the absence of antenatal risk assessment and management of thyrotoxicosis in this setting is complex.The records of premature neonates born at the three main maternity units in Brisbane, between January 1996 and July 1998 diagnosed with congenital thyrotoxicosis were reviewed. Data were recorded on gestational age, birth weight (B Wt), maternal thyroid history and current status, and neonatal course. Thyroid function and TBII status was assessed using standard biochemical assays.Seven neonates from five pregnancies were identified (four female, three male). Mean gestational age was 30 week (25–36 week) and median B Wt was 1·96 kg (0·50–2·62 kg). Only one mother received formal antenatal counselling by a paediatric endocrine service and had a TBII (54%) measured prior to delivery. Three of five mothers had elevated TBII measured after diagnosis in their offspring (57%, 65%, 83%) and in one mother, a TBII was not performed. All mothers were biochemically euthyroid at delivery. Mean age at diagnosis was 9 days (1–16 days) and mean age at commencement of treatment was 12 days (7–26 days). Two infants received propylthiouracil and five received a combination of carbimazole and pro‐pranolol. Four became biochemically hypothyroid, in three this resolved with cessation of the antithyroid drug (ATD), and one required ongoing T4 supple‐mentation. Only one infant required treatment for cardiac failure and there were no deaths in this cohort.This is a large series of extremely small and premature infants with neonatal thyro‐toxicosis. Presentation was nonspecific. The diag‐nosis was delayed because of low birth weight, prematurity, multiple birth and/or an unrecognized maternal history of Graves' disease. The treatment of neonatal thyrotoxicosis was difficult in these extreme low birth weight infants yet no infant died and significant morbidity was confined to high output cardiac failure in one infant. With antenatal recog‐nition of past or active Graves' disease, assessment of maternal TSH receptor binding immunoglobulin index prior to delivery and postnatal monitoring of cord TSH and venous fT4 and TSH on days 4 and 7 rapid treatment of affected infants may have further reduced neonatal morbidity.
The exon 3‐retaining and the exon 3‐deleted forms of the growth hormone‐binding protein (GHBP) in human serum are regulated differently
Authors: Kratzsch J. , Wu Z. , Kiess W. , Dehmel B. , Bosse‐Henck A. , Reuter W. , Pflaum C. D. , Strasburger C. J. 
Published: March 2003

Recently, two isoforms of the growth hormone‐binding protein (GHBP), which is identical with the extracellular domain of the growth hormone receptor (GHR), have been described. One isoform contains the exon 3 (E3(+)GHBP) and one excludes the exon 3 (E3(–)GHBP). The distribution of both isoforms in peripheral blood and their functional relevance is so far unknown.To study the molecular distribution of both species we have analysed sera of 141 subjects with average weight, overweight and obesity by newly developed immunoassays. The relationship between the different molecular forms of GHBP and specific parameters of body composition as well as risk factors of metabolic disturbances, were then examined.The extracellular domain of the exon 3‐retaining and ‐deleted isoforms of the GHR are released as E3(+)GHBP and E3(–)GHBP into the peripheral circulation. Furthermore, both molecular species do not show any correlation to each other (r = 0·67) and their relative proportion in blood is gender‐dependent with a higher E3(–)GHBP proportion in females (P < 0·01). E3(+)GHBP appears to have a considerably stronger correlation to indicators (BMI, fat mass, waist circumference) and metabolic risk factors (fasting insulin, uric acid, triglycerides, apolipoprotein B, diastolic blood pressure) of adiposity than E3(–)GHBP, indicating differences in their functional significance.The availability of assays for the determination of GHBP isoforms may be very important for the study of the GH receptor and its soluble extracellular domain, GHBP.
Effect of Sandostatin® LAR® on serum leptin levels in patients with acromegaly
Authors: Tan K. C. B. , Tso A. W. K. , Lam K. S. L. 
Published: March 2003

Serum leptin levels are decreased in patients with acromegaly and rise after GH is normalized by surgical treatment. We have evaluated the effect of Sandostatin® LAR® on leptin levels in acromegalic patients since there are recent data to suggest that somatostatin, in addition to its GH lowering effect, also reduces serum leptin levels in humans.Nineteen patients with active acromegaly were studied. Eleven patients received monthly injection of Sandostatin® LAR® and eight patients underwent transsphenoidal surgery. Serum concen‐trations of leptin, GH, IGF‐1 and insulin were measured before and after treatment.Serum leptin concentrations were lower in patients with active acromegaly than controls matched for age, sex and body mass index (BMI) [2·79 µg/l (2·60) vs. 4·41 µg/l (5·07); median (inter‐quartile range); P < 0·01]. A positive correlation between serum leptin concentrations and BMI was observed in the controls (r = 0·46, P < 0·05) but not in the acromegalic patients before treatment (r = 0·32, ns). In the group of patients treated with Sandostatin® LAR®, a marked reduction in GH and IGF‐1 was achieved by week 8 and GH and IGF‐1 remained suppressed throughout the 6 months of treatment. There was no change in BMI. A significant increase in leptin levels only became evident after 6 months of treatment [2·99 µg/l (2·60) vs. 4·21 µg/l (3·84), P < 0·05]. Leptin levels also significantly increased after transsphenoidal surgery [3·05 µg/l (5·73) vs. 5·19 µg/l (4·93), P < 0·05]. The positive correlation between serum leptin concentrations and BMI was restored in acromegalic patients both after treatment with Sandostatin® LAR® (r = 0·62, P < 0·05) and after surgery (r = 0·81, P < 0·05).Leptin concentrations were decreased in patients with active acromegaly and lowering GH by either Sandostatin® LAR® or transsphenoidal surgery led to an increase in leptin concentrations.
Autoimmune polyendocrine syndrome type 1 (APS I) in Norway
Authors: Myhre Anne Grethe , Halonen Maria , Eskelin Petra , Ekwall Olov , Hedstrand Håkan , Rorsman Fredrik , Kämpe Olle , Husebye Eystein S. 
Published: March 2003

OBJECTIVEThe aim of the present study was to investigate Norwegian patients with autoimmune polyendocrine syndrome type I (APS I), with respect to occurrence and clinical presentation, reactivity towards different autoantigenes and mutations in the autoimmune regulator (AIRE) gene.PATIENTSTwenty Norwegian patients from 15 families with APS I (11 males, nine females; mean age 26 years, range 4–54) were included by contacting all major hospitals in Norway.METHODSClinical data was collected from both patients and their physicians by the use of questionnaires and patient records. Autoantibodies were analysed using radioimmunoassays based on antigen synthesized by in vitro transcription and translation. AIRE mutations were determined by DNA sequence analysis.RESULTSThe prevalence of APS I in Norway was estimated to be about 1 : 80 000 individuals. We found about the same distribution of disease characteristics as has been reported in Finnish patients. The diagnosis was delayed in many individuals. In two thirds of the cases, the patients were admitted in Hospital with acute adrenal insufficiency or hypocalcaemic crisis. Forty percent of these patients already had one of the main disease manifestations. Four different mutations in the AIRE gene were found in the Norwegian cohort. A 13‐bp deletion in exon 8 (1085–1097del) was the most frequent mutation, present in 22/40 (55%) of the alleles. Eighty‐five percent of the patients had either autoantibodies against 21 hydroxylase or aromatic l‐amino acid decarboxylase. Five of eight women (age > 13 years) had ovarian failure, and all of these had antibodies against side‐chain cleavage enzyme (P = 0·0002).CONCLUSIONNorwegian patients with APS I clinically resemble patients from Finland and other European countries. The diagnosis APS I must be considered in children and adolescents with chronic mucocutaneous candidiasis, autoimmune adrenocortical failure or hypoparathyroidism in order to avoid fatal complications. Analysis of autoantibodies and mutational analysis of the AIRE gene are valuable diagnostic tools, especially in the early stages of the disease.
A comparison between low‐dose (1 µg), standard‐dose (250 µg) ACTH stimulation tests and insulin tolerance test in the evaluation of hypothalamo–pituitary–adrenal axis in primary fibromyalgia syndrome
Authors: Kırnap M. , Çolak R. , Eser C. , Özsoy O. , Tutus A. , Kelestimur F. 
Published: March 2003

OBJECTIVE Primary fibromyalgia syndrome (PFS) is a nonarticular rheumatological syndrome characterized by disturbances in the hypothalamo–pituitary–adrenal (HPA) axis. The site of the defect in the HPA axis is a matter of debate. Our aim was to evaluate the HPA axis by the insulin‐tolerance test (ITT), standard dose (250 µg) ACTH test (SDT) and low dose (1 µg) ACTH test (LDT) in patients with PFS.DESIGN AND PATIENTS Sixteen patients (13 female, three male) with PFS were included in the study. Sixteen healthy subjects (12 female, four male) served as matched controls. ACTH stimulation tests were carried out by using 1 µg and 250 µg intravenous (i.v.) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. The ITT was performed by using i.v. soluble insulin, and serum glucose and cortisol levels were measured before and after 30, 60, 90 and 120 min. The 1 µg and 250 µg ACTH stimulation tests and the ITT were performed consecutively.RESULTS Peak cortisol responses to both the low dose test (LDT) and standard dose test (SDT) (589 ± 100 nmol/l; 777 ± 119 nmol/l, respectively) were lower in the PFS group than in the control group (1001 ± 370 nmol/l; 1205 ± 386 nmol/l, respectively) (P < 0·0001). Peak cortisol responses to ITT (730 ± 81 nmol/l) in the PFS group were lower than in the control group (1219 ± 412 nmol/l) (P < 0·0001). Six of the 16 patients with PFS had peak cortisol responses to LDT lower than the lowest peak cortisol response of 555 nmol/l obtained in healthy subjects after LDT. There was a significant difference between the peak cortisol responses to LDT (589 ± 100 nmol/l) and peak cortisol responses to ITT (730 ± 81 nmol/l) in the PFS group (P < 0.0001). Peak cortisol responses to SDT (777 ± 119 nmol/l) were similar to peak cortisol responses to ITT (730 ± 81 nmol/l) in the PFS group.CONCLUSION We conclude that the perturbation of the HPA axis in PFS is characterized by underactivation of the HPA axis. Some patients with PFS may have subnormal adrenocortical function. LDT is more sensitive than SDT or ITT in the investigation of the HPA axis to determine the subnormal adrenocortical function in patients with PFS.
The contribution of IGF‐I to skeletal integrity in postmenopausal women
Authors: Muñoz‐Torres Manuel , Mezquita‐Raya Pedro , Lopez‐Rodriguez Francisca , Torres‐Vela Elena , De Dios Luna Juan , Escobar‐Jimenez Fernando 
Published: March 2003

OBJECTIVES The pathogenic role of the decline in serum concentrations of IGF‐I in postmenopausal osteoporosis is not fully elucidated. We investigated the associations among IGF‐I, bone mineral density (BMD), ultrasound parameters and prevalence of vertebral fractures in postmenopausal women.DESIGN A cross‐sectional study.PATIENTS One hundred and fifty‐four ambulatory postmenopausal women (61 ± 7 years) referred for osteoporosis screening.MEASUREMENTS IGF‐I was measured by radioimmunoassay and BMD using dual‐energy X‐ray absorptiometry. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at calcaneus were measured by a quantitative ultrasound system.RESULTS IGF‐I was significantly lower in osteoporotic subjects and correlated positively with BMD, BUA and SOS. After adjusting for age, years since menopause and body mass index, IGF‐I accounted for 8·5% of the variance at lumbar spine BMD, 4·6% at femoral neck and 7·1% at calcaneal BUA. BUA was associated with IGF‐I independently of BMD. IGF‐I was lower in women with vertebral fractures (91 ± 39 µg/l vs. 114 ± 44 µg/l; P = 0·003). The osteoporosis densitometric criteria (t‐score ≤ −2·5 SD) was the most strongly independent associated variable with prevalent vertebral fractures [odds ratio (OR): 3·3 (1·4–7·6)], followed by IGF‐I levels below 75th percentile [OR: 3 (1–8·8)].CONCLUSIONS Our study shows that IGF‐I is strongly associated with bone mineral density and reflects aspects of bone quality. The contribution of IGF‐I to skeletal integrity in postmenopausal women is clinically relevant.
Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults
Authors: Gómez José Manuel , Espadero Rosa María , Escobar‐Jiménez Fernando , Hawkins Federico , Picó Antonio , Herrera‐Pombo José Luis , Vilardell Enric , Durán Alejandra , Mesa Jordi , Faure Eduardo , Sanmartí Anna 
Published: March 2003

Summaryobjective To investigate the GH response to glucagon in adult patients with GH deficiency and in controls compared with the GH response to the insulin tolerance test (ITT) in patients with GH deficiency and to determine whether the use of glucagon results in a diagnostic utility test.patients and design Seventy‐three patients with adult GH deficiency and organic hypothalamic‐pituitary disease were recruited, along with 46 controls. The patients were divided into five groups according to the number of associated hormone deficiencies present.measurements Hypopituitary subjects underwent assessment of GH secretory status by the ITT, the glucagon test and measurement of serum IGF‐I concentration. Controls underwent the glucagon test. After the ITT, glucose and GH levels were measured at baseline, 30, 60 and 90 minutes, and after glucagon at baseline, 90, 120, 150, 180, 210 and 240 minutes.results The highest GH value after the ITT in the patient group was 3 µg/l (0·76 ± 0·82 µg/l), and after the glucagon test the highest GH peak value was 2·9 µg/l (0·64 ± 0·79 µg/l). A correlation was found between the GH peak and the progressive number of hormone deficiencies. After the glucagon test, the GH peak obtained in the controls at 180 minutes was 9·8 ± 4·6 µg/l and, on an individual basis, none of the 46 controls failed to achieve peak GH levels higher than 3 µg/l. In the controls, a negative correlation was observed between the GH response to glucagon and age (r = –0·389, P = 0·0075) and body mass index (r = –0·329, P = 0·0254). The accuracy of the glucagon test for differentiating patients from controls, estimated by receiver operating characteristics (ROC) curve methodology, showed that the cut‐off of 3 µg/l for the GH peak provides 100% sensitivity and 100% specificity and is a reliable decision threshold.conclusions The glucagon GH test is reliable and provides a clear separation between GH‐deficient and normal adults. A single glucagon test with a cut‐off of 3 µg/l for the GH peak is diagnostic of GH deficiency in adults and could be considered and studied as an alternative to the ITT.