bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of polymorphic alleles of the calcium‐sensing receptor gene with the clinical severity of primary hyperparathyroidism
Authors: Yamauchi Mika , Sugimoto Toshitsugu , Yamaguchi Toru , Yano Shozo , Kanzawa Michiko , Kobayashi Akira , Chihara Kazuo 
Published: March 2003

OBJECTIVE Primary hyperparathyroidism (pHPT) is a heterogeneous disease in its clinical course and severity. Previous studies have suggested an association between the clinical severity of pHPT and the genotypes of vitamin D receptor, oestrogen receptors and PTH molecules. The Ca‐sensing receptor (CaR) is activated by an extracellular calcium ion and controls PTH secretion, and thus polymorphisms of CaR might be associated with the magnitude of PTH secretion and the clinical severity of pHPT. In this study, we examined the relationship between CaR polymorphisms and biochemical markers in pHPT patients.METHODS We analysed 105 Japanese pHPT patients (85 females and 20 males; mean age 55·6 ± 14·0 years). We determined the CaR genotypes of G990R and intron 5 polymorphisms with genomic DNA extracted from peripheral lymphocytes. The intron 5 polymorphism was defined as T/T, T/C and C/C.RESULTS In the G990R polymorphism, serum levels of both intact PTH and alkaline phosphatase (ALP) were significantly higher and the serum level of phosphorus was significantly lower in the RR group than in the GG group. In the intron 5 polymorphism, the T/T group showed significantly lower serum levels of intact PTH and Ca. Furthermore, patients with both the codon 990 RR and the intron 5 C allele (the RRC+ group) had significantly higher serum levels of intact PTH and ALP than did the other patients.CONCLUSIONS The present study is the first to show that CaR polymorphisms of G990R and intron 5 were closely associated with the magnitude of PTH secretion and/or PTH degradation as well as the clinical severity in pHPT patients.
Plasma leptin in chronic fatigue syndrome and a placebo‐controlled study of the effects of low‐dose hydrocortisone on leptin secretion
Authors: Cleare A. J. , O'Keane V. , Miell J. 
Published: March 2003

OBJECTIVEPrevious studies have suggested that chronic fatigue syndrome (CFS) is associated with changes in appetite and weight, and also with mild hypocortisolism. Because both of these features may be related to leptin metabolism, we undertook a study of leptin in CFS.DESIGN(i) A comparison of morning leptin concentration in patients with CFS and controls and (ii) a randomized, placebo‐controlled crossover study of the effects of hydrocortisone on leptin levels in CFS.PATIENTSThirty‐two medication free patients with CFS but not comorbid depression or anxiety. Thirty‐two age, gender, weight, body mass index and menstrual cycle matched volunteer subjects acted as controls.MEASUREMENTSWe measured basal 0900 h plasma leptin levels in patients and controls. All 32 patients were taking part in a randomized, placebo‐controlled crossover trial of low dose (5 or 10 mg) hydrocortisone as a potential therapy for CFS. We measured plasma leptin after 28 days treatment with hydrocortisone and after 28 days treatment with placebo.RESULTSAt baseline, there was no significant difference in plasma leptin between patients [mean 13·8, median 7·4, interquartile range (IQR) 18·0 ng/ml] and controls (mean 10·2, median 5·5, IQR 11·3 ng/ml). Hydrocortisone treatment, for both doses combined, caused a significant increase in leptin levels compared to placebo. When the two doses were analysed separately, only 10 mg was associated with a significant effect on leptin levels. We also compared the hydrocortisone induced increase in leptin between those who were deemed treatment‐responders and those deemed nonresponders. Responders showed a significantly greater hydrocortisone‐induced rise in leptin than nonresponders. This association between a clinical response to hydrocortisone and a greater rise in leptin levels may indicate a greater biological effect of hydrocortisone in these subjects, perhaps due to increased glucocorticoid receptor sensitivity, which may be present in some patients with CFS.CONCLUSIONSWe conclude that, while we found no evidence of alterations in leptin levels in CFS, low dose hydrocortisone therapy caused increases in plasma leptin levels, with this biological response being more marked in those CFS subjects who showed a positive therapeutic response to hydrocortisone therapy. Increases in plasma leptin levels following low dose hydrocortisone therapy may be a marker of pretreatment physiological hypocortisolism and of response to therapy.
Effect of long‐term administration of recombinant human growth hormone (rhGH) on plasma erythropoietin (EPO) and haemoglobin levels in anaemic patients with adult GH deficiency
Authors: Sohmiya Motoi , Kato Yuzuru 
Published: March 2003

OBJECTIVE We investigated the effect of recombinant human GH (rhGH) on erythropoietin (EPO) and haemoglobin (Hb) concentrations in anaemic patients with adult GH deficiency.PATIENTS AND DESIGN rhGH was administrated in 8 patients with adult GH deficiency, three males and five females, aged from 24 to 69 years, mean (± SD) of 48·8 ± 16·4 years, for 1 year by means of continuous subcutaneous infusion (CSI) at a flow rate of 0·036 U/kg/day using a portable syringe pump. Blood samples were obtained in the morning after an overnight fast every week for 1 month, followed by each month before and after the start of rhGH administration.RESULTS Mean (± SE) plasma GH levels increased from 0·24 ± 0·09 µg/l to 2·32 ± 0·23 µg/l 1 week after the start of rhGH administration to maintain a steady state. Plasma IGF‐I levels increased from 70·1 ± 13·8 µg/l to 282·8 ± 70·6 µg/l 1 week after the start of rhGH administration to maintain the steady state. Plasma EPO levels increased from 25·9 ± 2·6 IU/l to 37·6 ± 4·2 IU/l and 34·3 ± 3·6 IU/l at 1 week and 2 weeks after the start of rhGH administration, respectively, and then decreased gradually to 14·9 ± 2·1 IU/l at 10 months after the start of rhGH administration. Reticulocyte counts increased from 0·88 ± 0·06% to 1·49 ± 0·21% at 1 week. Hb concentrations increased from 103 ± 5 g/l to 106 ± 5 g/l at 2 weeks after the start of rhGH administration, and then increased gradually to reach the normal range.CONCLUSIONS We conclude that EPO secretion was stimulated in the initial 2 weeks after the start of CSI of rhGH in anaemic patients with adult GH deficiency. Increased Hb concentrations after long‐term administration of rhGH might be explained by direct stimulatory effects of rhGH and IGF‐I on erythroid cells, which was accompanied by suppressed EPO secretion, in combination with a more generalized indirect impact of rhGH on physical activety. These findings suggest a beneficial effect of rhGH replacement in anaemic patients with adult GH deficiency.
Mutations linked to familial hypokalaemic periodic paralysis in the calcium channel α1 subunit gene (Cav1·1) are not associated with thyrotoxic hypokalaemic periodic paralysis
Authors: Dias da Silva Magnus R. , Cerutti Janete M. , Tengan Célia H. , Furuzawa Gilberto K. , Vieira Teresa C. A. , Gabbai Alberto A. , Maciel Rui M. B. 
Published: March 2003

Summaryobjective To investigate whether patients with thyrotoxic hypokalaemic periodic paralysis (THPP) have the same molecular defect in the calcium channel gene described in familial hypokalaemic periodic paralysis (FHPP), as the symptoms of both diseases are comparable, we analysed, in patients with THPP, the presence of mutations R528H, R1239H and R1239G on the S4 voltage‐sensing transmembrane segment of the α1 subunit of the calcium channel gene (Cav1·1).design and patients Genomic DNA was extracted from peripheral blood from 14 patients with THPP, 13 sporadic cases and one with a family history. An FHPP family was selected as a positive control. The exons bearing the described mutations were amplified by PCR, screened by single‐strand conformation polymorphism (SSCP), and further sequenced.measurements THPP was diagnosed both clinically and through laboratory tests, all patients having elevated levels of thyroid hormones (T4, T3 or free T4), suppressed TSH and plasma potassium below 3·5 mmol/l.results No evidence of the described mutations was found in patients with THPP. Furthermore, we did not detect any mutations in any of the four full S4 voltage‐sensing transmembrane segments of Cav1·1 (DIS4, DIIS4, DIIIS4 and DIVS4) by direct sequencing. However, close to the R528H mutation, we identified two single nucleotide polymorphisms at nucleotides 1551 and 1564 in both familial and sporadic cases with THPP. In addition, we were able to detect the R528H mutation in the DIIS4 transmembrane segment in all members of the FHPP family.conclusion Mutations linked to familial hypokalaemic periodic paralysis in the calcium channel α1 subunit gene (Cav1·1) are not associated with thyrotoxic hypokalaemic periodic paralysis. However, polymorphisms in nucleotides 1551 and 1564 in the exon 11 were found in patients with familial hypokalaemic periodic paralysis and thyrotoxic hypokalaemic periodic paralysis in higher frequency than in controls. The polymorphisms identified within the Cav1·1 gene are associated with thyrotoxic hypokalaemic periodic paralysis and represent a novel finding.
Effects of GH on lipid peroxidation and neutrophil superoxide anion‐generating capacity in hypopituitary adults with GH deficiency
Authors: Smith J. C. , Lang D. , McEneny J. , Evans L. M. , Scanlon M. F. , Young I. , Davies J. 
Published: March 2003

Summaryobjectives  Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro‐atherogenic state associated with adult GHD.design and patients In a randomized, double‐blind, placebo‐controlled study we investigated the effects of GH replacement on low‐density lipoprotein (LDL) oxidation and neutrophil superoxide (O2−) generating capacity in 32 GHD adults (19 males, 13 females; age range 19–64 years) over 3 months. Thirty age‐ and sex‐matched healthy controls were also studied.measurements Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper‐catalysed lag phase of LDL oxidation. Neutrophil O2−generating capacity was assessed by a lucigenin‐based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis.results Compared to controls, GHD subjects had higher LDL cholesterol (4·0 ± 0·8 vs. 3·5 ± 0·9 mmol/l, P < 0·01) and higher triglyceride concentrations (2·3 ± 1·5 vs. 1·1 ± 0·7 mmol/l, P < 0·001) but lower HDL cholesterol (1·1 ± 0·3 mmol/l vs. 1·4 ± 0·4 mmol/l, P < 0·01), lower levels of HPOs (0·72 ± 0·35 vs. 0·92 ± 0·20 µm, P < 0·01) and lower basal (2·5 ± 1·5 vs. 4·5 ± 2·3 mV/5 × 105 neutrophils, P < 0·01) and peak post‐activation levels (23·2 ± 11·1 vs. 34·4 ± 15·6 mV/5 × 105 neutrophils, P < 0·01) of neutrophil O2− generation. GH replacement resulted in an increase in HPOs from 0·70 ± 0·39 to 0·86 ± 0·19 µm (P < 0·05), although there was no change in the lag time of LDL oxidation. Neutrophil O2− generating capacity was enhanced with a rise in basal O2− generation from 2·8 ± 1·4 to 5·4 ± 4·6 mV/5 × 105 neutrophils (P < 0·05) and in peak post‐activation O2− generation from 21·9 ± 9·5 to 35·8 ± 21·7 mV/5 × 105 neutrophils (P < 0·05). LDL cholesterol was reduced from 4·1 ± 0·8 mmol/l to 3·5 ± 0·8 mmol/l (P < 0·01). No significant changes in measured parameters occurred in the placebo group.conclusions Adult GHD is associated with reduced lipid peroxidation and impaired neutrophil O2− generating capacity, both of which are reversible with GH replacement. Our data suggest that: (i) that oxidative stress is not a major feature of the pro‐atherogenic state in hypopituitary adults with GHD and (ii) a role for GH in modulating neutrophil function and leucocyte–lipoprotein interactions.
Anaplastic pseudothyroiditis
Authors: Basaria Shehzad , Udelsman Robert , Tejedor‐Sojo Javier , Westra William H. , Krasner Alan S. 
Published: March 2003

SummaryAnaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumours. It generally presents as a rapidly enlarging thyroid mass and produces local symptoms associated with mass effect. One of the very rare presentations of ATC is thyrotoxicosis. We report a patient with ATC whose course was complicated by severe thyrotoxicosis. His symptoms were controlled with beta‐blockers. Two weeks into hospitalization, the patient became hypothyroid. Histopathology showed destruction of the normal thyroid follicles by the invasion of the tumour. As this form of thyrotoxicosis resembles various thyroiditides, we hereby refer this condition as ‘anaplastic pseudothyroiditis’.
A unique case of combined pituitary hormone deficiency caused by a PROP1 gene mutation (R120C) associated with normal height and absent puberty
Authors: Arroyo Armando , Pernasetti Flavia , Vasilyev Vyacheslav V. , Amato Paula , Yen Samuel S. C. , Mellon Pamela L. 
Published: March 2003

SummaryWe report a 28‐year‐old‐female who presented with primary amenorrhoea, absence of puberty, obesity and normal stature. The subject was clearly short as a child, with a height more than 2 SD below normal until the age of 15 years. The pubertal growth spurt failed to develop. She continued growing at a prepubertal rate until growth ceased at the age of 20 years, reaching her final adult height of 157 cm (SDS −0·86) without hormonal treatment. A combined pituitary hormone stimulation test of anterior pituitary function showed deficiencies of GH, LH and FSH, and low normal serum levels of TSH and PRL. Magnetic resonance imaging revealed a hypoplastic pituitary with markedly reduced pituitary height. In addition, a whole body dual energy X‐ray absorptiometry scan showed high levels of body fat (54%). Combined pituitary hormone deficiencies with a hypoplastic pituitary suggested the diagnosis of a Prophet of Pit‐1 (PROP1) gene mutation. Normal stature in this case, however, confounded this diagnosis. Sequencing of PROP1 revealed homozygosity for a single base‐pair substitution (C to T), resulting in the replacement of an Arg by a Cys at codon 120 (R120C) in the third helix of the homeodomain of the Prop‐1 protein. To our knowledge, this is the first report of a patient with a mutation in the PROP1 gene that attained normal height without hormonal treatment, indicating a new variability in the PROP1 phenotype, with important implications for the diagnosis of these patients. We suggest that this can be explained by (i) the presence of low levels of GH in the circulation during childhood and adolescence; (ii) the lack of circulating oestrogen delaying epiphyseal fusion, resulting in growth beyond the period of normal growth; and (iii) fusion of the epiphyseal plates, possibly as a result of circulating oestrogens originating from peripheral conversion of androgens by adipose tissue.
Timing of onset of growth hormone deficiency is a major influence on insulin‐like growth factor I status in adult life
Authors: Lissett C. A. , Murray R. D. , Shalet S. M. 
Published: March 2003

Summaryobjective Several reports have suggested that IGF‐I levels in patients with childhood‐onset (CO) GH deficiency are lower than those observed in patients with adult‐onset (AO) GH deficiency. However, these reports are unsatisfactory as there are several differences between the cohorts studied other than the timing of onset of GH deficiency; in particular, the patients were not matched for equal severity of GH deficiency. We have pursued this question further by examining the IGF‐I standard deviation score (SDS) in patients with CO and AO GH deficiency, with equal degrees of severity of GH deficiency, as defined by the peak GH response to the insulin tolerance test (ITT).patients and measurements IGF‐I SDS were compared in 146 non acromegalic patients (69 male), aged 15·7–76·6 years (median 33·4 years), bone mass index (BMI) 27·8 ± 5·8 kg/m2, with severe GH deficiency (peak GH response < 9 mU/l to insulin‐induced hypoglycaemia). Patients were subdivided by timing of onset of GH deficiency and the peak GH response to the ITT (GH response ≤ 1 mU/l, group 1; > 1–3 mU/l, group 2; > 3–6 mU/l, group 3; > 6–8·9 mU/l, group 4).results The IGF‐I SDS (mean value ± SD) in the CO group (n = 63) as a whole was significantly lower than that found in the AO group (n = 83) (−3·7 ± 2·8 vs.−1·55 ± 2·2, respectively; P < 0·0001). Despite this, there was no significant difference in the peak GH response to an ITT between the two cohorts (2·8 ± 2·3 mU/l in the AO cohort and 2·6 ± 2·2 mU/l in the CO cohort; P = 0·5). When the cohorts were subdivided by severity of GH deficiency, there remained a significant difference in IGF‐I SDS in groups 1 (P < 0·0001), 2 (P = 0·05) and 3 (P < 0·05), but there was no significant difference between the AO and CO cohorts in group 4. The peak GH response to an ITT was similar in the AO and CO cohorts in all groups (P = 0·8, 0·8, 0·9 and 0·3 in groups 1–4, respectively).Although increasing severity of hypopituitarism was associated with a decline in IGF‐I SDS in the CO cohort (P < 0·01), this was not the case in the AO cohort (P = 0·3).conclusion These data support the hypothesis that there is an innate difference between adult patients with either CO or AO GH deficiency that cannot be explained solely by variation in the severity of GH deficiency. A possible explanation is that childhood GH deficiency programmes the subsequent relationship between GH and IGF‐I in adult life or that the body composition changes, which are more severe in AO GH deficiency, influence IGF‐I status.
Suppression of puberty with long‐acting goserelin (Zoladex‐LA): effect on gonadotrophin response to GnRH in the first treatment cycle
Authors: Trueman Julie A. , Tillmann Vallo , Cusick Colin F. , Foster Peter , Patel Leena , Hall Catherine M. , Price David A. , Clayton Peter E. 
Published: March 2003

Summarybackground and objectives Depot GnRH analogues are widely used in the treatment of precocious puberty, or suppression of relatively early puberty where growth or psychosocial well‐being may be compromised. One example is Zoladex (Z goserelin 3·6 mg), which can be given every 4 weeks. This injection frequency may not always achieve adequate suppression of pubertal signs. A long‐acting form, Zoladex‐LA 10·8 mg, has now been introduced with a potential duration of action of 12 weeks. In order to assess the efficacy of Zoladex‐LA in gonadotrophin suppression we have measured LH and FSH responses to GnRH at diagnosis and 8 and 12 weeks after injection in a group of children treated with Zoladex‐LA for central precocious or early puberty.methods Forty‐nine children (40 girls) with clinical evidence of central precocious puberty (CPP) or early puberty (EP) were started on Zoladex‐LA, either de novo (n = 29) or on changing from Zoladex. Ages at diagnosis ranged from 1·7 to 10·6 years (median 7·8 years). Twenty‐three had a structural cause with abnormality on magnetic resonance/computerized tomography (MR/CT) head scan, nine had a syndrome or nonspecific brain injury, and in 17 the cause was idiopathic.results At diagnosis, in the de novo group, median peak LH was 13·6 IU/l and median peak FSH was 12·0 IU/l. By 12 weeks gonadotrophins were suppressed to 0·9 and 0·8 IU/l, respectively. In the previously treated group, median peak LH at diagnosis was 12·8 IU/l and median peak FSH was 15·0 IU/l with suppression to 0·8 and 1·1 IU/l, respectively, at 12 weeks. In the latter group peak FSH was higher than peak LH at both 8 and 12 weeks (P < 0·05) and there was a significant rise in peak LH (P < 0·05) and FSH (P = 0·01) between 8 and 12 weeks. There was no correlation between age at diagnosis and peak LH or FSH at 8 or 12 weeks. Nevertheless, individual patients in both groups showed evidence of incomplete gonadotrophin suppression at 12 weeks.conclusion Zoladex‐LA induces a significant reduction in gonadotrophins over 12 weeks. However, there are individuals, particularly those previously on Zoladex, in whom gonadotrophin suppression is waning by 12 weeks. As found with Zoladex, some children with precocious puberty treated with Zoladex‐LA may require increased injection frequency, although correlation with clinical evidence of suppression needs to be studied further.
Growth hormone (GH) replacement therapy in GH‐deficient women during pregnancy
Authors: Wirén Lena , Boguszewski Cesar Luiz , Johannsson Gudmundur 
Published: March 2003

Summaryobjective The present recommendation is to discontinue GH replacement therapy in hypopituitary women, as they become pregnant. We report our experience of managing GH deficiency with GH replacement therapy in pregnant hypopituitary women.patients and measurements Eight hypopituitary women, median age 30·5 years (range 20–39 years), were followed prospectively during 12 distinct pregnancies. Six women were receiving replacement therapy for other pituitary hormone deficiencies and five pregnancies were achieved with ovulation induction therapy. GH replacement therapy was maintained at the same pregestational dose during the first trimester, with a gradual decrease of the dose during the second trimester and discontinuing the treatment at the beginning of the third trimester. Serum IGF‐1 levels were measured in four selected pregnancies at three different points, one in each trimester of gestation.results Seven pregnancies resulted in normal vaginal deliveries and five had programmed Caesarian sections. The median gestation age at time of delivery was 40 weeks (range 33–42 weeks). Newborns had a median birthweight SD score of −0·37 (range −1·93 to 1·21) and a median birthlength SD score of 0·07 (range −2·73 to 1·53). No congenital malformations were observed. Three women were able to breastfeed their babies. Before gestation, the median daily dose of GH was 0·5 mg (range 0·3–0·8 mg) and the median serum IGF‐1 was 37·5 nmol/l (range 7·6–54·5 nmol/l). IGF‐1 levels were fairly constant in the first and second trimesters of gestation, showing an increment during the last trimester, when GH treatment was discontinued.conclusion The GH replacement regimen presented for pregnant women with GH deficiency was safe. No major side‐effects and no negative influences on maternal and fetal outcome were observed.