bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuromuscular symptoms and dysfunction in subclinical hypothyroid patients: beneficial effect of L‐T4 replacement therapy
Authors: Monzani Fabio , Caraccio Nadia , Del Guerra Paolo , Casolaro Arturo , Ferrannini Eleuterio 
Published: March 2003

DESIGN, PATIENTS AND MEASUREMENTSThe presence of neuromuscular symptoms was ascertained by questionnaire in 33 consecutive patients with subclinical hypothyroidism (sHT) as compared to 44 age‐ and sex‐matched controls. Blood was sampled for PTH, magnesium, phosphate, and total and ionized calcium determination. Patients reporting three or more symptoms were also studied by surface electromyography (sEMG). The study was repeated following a six‐month L‐T4 course.RESULTSNeuromuscular symptoms were significantly more frequent in patients than in controls (P = 0.0001), and correlated with TSH values (r = 0.52; P = 0.0001). Among patients showing three or more symptoms (n = 11), sEMG documented the presence of repetitive discharges in 8 patients. L‐T4 therapy led to a significant improvement of symptoms (P = 0.0001); persistent repetitive discharges were no longer observed. Total and ionized calcium values, always within the normal limits, were significantly lower in patients than controls (P < 0.0001). An inverse relationship was observed between ionized calcium and: TSH values (r = −0.69, P = 0.0001); the number of neuromuscular symptoms (r = −0.53, P = 0.0001). L‐T4 replacement induced a significant increase in both total and ionized calcium levels (P < 0.01 and P < 0.0001, respectively).CONCLUSIONSNeuromuscular symptoms and dysfunction are rather common in subclinical hypothyroidism, and may be associated with abnormalities in serum calcium balance and surface electromyography. The ability of L‐T4 treatment to reverse all these changes suggests that subclinical hypothyroidism patients may require early therapy not only to prevent progression to frank hypothyroidism, but also to improve their neuromuscular dysfunction.
The insulin‐like growth factor‐I (IGF‐I) gene in individuals born small for gestational age (SGA)
Authors: Johnston Linda B. , Leger Juliane , Savage Martin O. , Clark Adrian J. L. , Czernichow Paul 
Published: March 2003

OBJECTIVETo investigate the association of genetic variation of the insulin‐like growth factor‐I (IGF‐I) gene with birth size small for gestational age (SGA).SUBJECTSWe have studied a cohort of 120 SGA patients and 147 appropriate for gestational age (AGA) controls from Haguenau, France.METHODSPCR‐SSCP analysis was performed to detect sequence variation in the coding region of the IGF‐I gene. Microsatellite markers near the IGF‐I gene (intronic and D12S78) were selected and amplified to perform further analysis by association studies.RESULTSA novel polymorphism in intron 2 was discovered, but allele‐specific PCR analysis in the 120 SGA patients and 147 AGA controls found no association between this polymorphism and birth size SGA. Chi squared (χ2) analysis found no statistically significant association between the allele distribution of the microsatellite markers in the SGA subjects and the AGA controls. Power calculations estimate that the D12S78 marker has an 80% chance of detecting a 10–15% difference.CONCLUSIONSThese studies suggest that genetic variation of IGF‐I alone does not result in birth size small for gestational age in this population. Thus, if this gene influences fetal size, it plays only a minor role in a multifactorial disorder which involves other genetic and environmental factors.
The prevalence of thyroid dysfunction in a population with borderline iodine deficiency
Authors: Knudsen Nils , Jørgensen Torben , Rasmussen Susanne , Christiansen Erik , Perrild Hans 
Published: March 2003

OBJECTIVEWe lack information on the influence of borderline iodine deficiency on the occurrence of thyroid dysfunction. Iodine deficiency has been reported to facilitate the development of toxic nodular goitre, whereas a high iodine intake may increase the prevalence of autoimmune hypothyroidism.SUBJECTS AND METHODSIn a cross‐sectional study of a random sample of the general population in our region with borderline iodine defficiency 2656 (65%) of 4073 men and women aged 41 to 71 years participated. Records were made of previous thyroidal illness. Blood samples were drawn for thyroid parameters and TPO Ab values. Iodine and creatinine was assessed in casual urine samples.RESULTSPrevious or present hyperthyroidism was reported by 1.4% of the participants whereas 0.6% had unknown biochemical hyperthyroidism. All cases of undiagnosed hyperthyroidism were among women. Previously diagnosed and treated hypothyroidism was reported by 1.0% and undiagnosed hypothyroidism was found in 0.4%. Subclinical hyperthyroidism was found in 1.3% and subclinical hypothyroidism in 0.7%. TPO Ab titres >200 kU/l were found in 16.9% of the women and 6.6% of the men, and 83% of participants with TSH >5 mU/l had TPO Ab titres >200 kU/l. Participants with TPO Ab titres between 100 and 200 kU/l had no increased frequency of thyroid dysfunction. The median iodine excretion rate was estimated as 103 μg/day. Serum TSH values were higher in women than in men and showed higher dispersion in women as well as in old age. Serum free T3 was found to be higher in women than in men and increased with age. Serum free T4 showed no sex difference but values increased with increasing age.CONCLUSIONIn our region with borderline iodine deficiency more than 5% of the general population has clinical or subclinical thyroid dysfunction. We found a relatively high prevalence of hyperthyroidism, especially previously undiagnosed disease, but a low prevalence of hypothyroidism as would be expected in an area of iodine deficiency. Hypothyroidism was related to TPO Ab titres of >200 kU/l. Thyroid hormone levels varied with age and sex.
GH substitution does not alter the pulsatile pattern of LH in amenorrhoeic growth hormone deficient women
Authors: De Boer  , Van Der Veen  , Schoemaker  
Published: March 2003

OBJECTIVEGH substitution in GH‐deficient (GHD) children promotes pubertal development. In some GHD women, secondary amenorrhoea occurs after discontinuation of GH treatment. This study was designed to investigate whether GH substitution directly influences the GnRH pulse generator. For this reason, the pulsatile release of LH was studied in amenorrhoeic GHD women before and during GH substitution.DESIGNGH deficiency was confirmed by an insulin tolerance test. During a 24‐h period, blood samples were drawn every 10 min for determination of LH, FSH and GH levels. Oestradiol and IGF‐1 were determined at 1000 h and 2200 h. After the first test day, patients started with GH substitution, 0.25 IU/kg/week. During month 6 of GH treatment, the 24 h blood sampling was repeated.SUBJECTSTen amenorrhoeic GH‐deficient women participated in the trial. All were diagnosed as GH deficient during childhood or adolescence. Eight of them had been treated with GH during childhood. Seven women suffered from primary amenorrhoea and three from secondary amenorrhoea. Six women were started with GH substitution after the first test day (according to randomization in a larger study).MEASUREMENTSLH and GH were determined every 10 min and FSH every 60 min. LH pulse detection was conducted using a validated statistical method.RESULTSPrior to GH treatment, the LH pulse interval did not show a diurnal pattern as found during normal pubertal development. During GH treatment, IGF‐1 levels rose significantly. No differences were found in mean LH, LH pulse amplitude and LH pulse interval before and during GH treatment. Oestradiol levels did not change either.CONCLUSIONSGH substitution in amenorrhoeic GH‐deficient women does not alter the pulsatile pattern of LH. This may suggest that GH treatment does not influence central nervous system control of gonadotropin secretion in GHD patients.
Osteoporosis and fractures in Turner syndrome–importance of growth promoting and oestrogen therapy
Authors: Landin‐Wilhelmsen Kerstin , Bryman Inger , Windh Marianne , Wilhelmsen Lars 
Published: March 2003

OBJECTIVETurner syndrome (TS) is a chromosomal aberration (45,X) characterized by endogenous oestrogen deficiency and short stature. The aim was to study body composition, bone mineral density, fracture frequency, social and life style factors and biochemical bone markers, as well as hormones, in adults with TS in comparison with a female random population sample.PATIENTSSeventy women with TS responded to questionnaires. They underwent physical examination, bone mineral density measurement with Dual Energy X‐ray Absorptiometry (DEXA) and blood sampling. Mean age was 31 ± 12 (range 16–71) years. A random population sample of women from the WHO MONICA Project, Göteborg (25–64 years) served as controls (n = 740).RESULTSWomen with TS were shorter than the controls and had lower body weight and lean body mass (P < 0.0001). Body mass index and waist/hip circumference ratio were higher in TS (P < 0.0001). Osteoporosis was present in seven TS women, six above 45 years of age. None of these had received oestrogen substitution continuously. Fractures (all types) were reported by 11 (16%) TS women (six (50%) above 45 years) compared with 5% in the population sample (P < 0.001). Four TS women with fractures had osteoporosis, all above 45 years of age. Osteoporosis and fractures did not differ between women with the 45,X karyotype and those with mosaicism. Impaired hearing was reported by 40%, and 73% wore glasses. Six percent among TS were smokers compared with 25% in the population (P < 0.001). TS women reported a lower degree of leisure time physical activity than controls (P < 0.001). Parathyroid hormone and osteocalcin were higher among TS (P < 0.02 and 0.001). Insulin‐like growth factor‐I was similar. Ninety‐one percent of all TS had oestrogen substitution and 96% of TS below 25 years of age had received growth hormone treatment.CONCLUSIONOsteoporosis and fractures were common above, but not below, 45 years of age in Turner syndrome. It is probable that modern therapy, including growth promoting and continuous oestrogen therapy, will prevent osteoporotic fractures in the future.
Role of oestrogen in male sexual behaviour: insights from the natural model of aromatase deficiency
Authors: Carani Cesare , Rochira Vincenzo , Faustini‐Fustini Marco , Balestrieri Antonio , Granata  
Published: March 2003

OBJECTIVEIn order to evaluate the role of oestrogens on human male sexual behaviour, the gender‐identity, psychosexual orientation and sexual activity of a man with a congenital lack of oestradiol resulting from an inactivating mutation of the aromatase P450 gene was investigated. The psychosexual and sexual behavioural evaluations were performed before and during testosterone treatment and before oestradiol treatment, during three phases of different dosages of oestradiol treatment.DESIGNThe study was performed before (phase A) and during (phase B) testosterone enanthate treatment (250 mg i.m. every 10 days, for 6 months), during testosterone withdrawal (phase C), and during each of the following transdermal oestradiol treatments: 50 μg twice a week for 6 months (phase D); 25 μg twice a week for 9 months (phase E), and 12.5 μg twice a week for 9 months (phase F).MEASUREMENTSSexual behaviour was investigated by a sexological interview and by a 2‐month self‐reported daily diary performed during each phase of the protocol study. Furthermore, during each oestradiol treatment (phase C, D, E and F), a study of depression, anxiety trait and sexual behaviour was performed by the Beck Depression Inventory (BDI), the Spielberger Trait Anxiety Inventory (STAI) and the Golombok‐Rust Inventory of Sexual Satisfaction (GRISS), respectively. Sexual orientation and gender‐identity were evaluated by the BEM Sex Role Inventory (BSRI). Serum testosterone and oestradiol were measured during each phase of the study.RESULTSBefore oestradiol treatment (phase C), serum oestradiol was undetectable, while it rose to 356.1, 88.1 and 55.1 pmol/l during phases D, E and F, respectively. Before any oestradiol treatment, during phase D, phase E and phase F serum testosterone was 18.13, 0.72, 14.3 and 18.51 nmol/l, respectively. The patient's gender‐identity as assessed by BSRI and by the sexological interview was clearly male. The psychosexual orientation evaluated by BSRI, by the sexological interview and by the analysis of the self‐filled diary was heterosexual. Relevant modification of the patient's sexual behaviour occurred only during oestrogen treatment. This was more evident during both phase E and phase F, and concerned the behavioural parameters with an increase of libido, frequency of sexual intercourse, masturbation and erotic fantasies. A reduction of BDI and STAI scores was detected during the oestrogen phases.CONCLUSIONSThe study of the sexual behaviour in this man with aromatase deficiency suggests that oestrogens in humans do not affect gender‐identity and sexual orientation but could have a role in male sexual activity.
FHIT and TSG101 in thyroid tumours: aberrant transcripts reflect rare abnormal RNA processing events of uncertain pathogenetic or clinical significance
Authors: McIver Bryan , Grebe Stefan K. G. , Wang Liang , Hay Ian D. , Yokomizo  , Liu Wanguo , Goellner John R. , Grant Clive S. , Smith David I. , Eberhardt Norman L. 
Published: March 2003

OBJECTIVEThe chromosomal regions containing the two putative tumour suppressors, fragile histidine triad gene (FHIT) and tumour suppressor gene 101 (TSG101), are deleted frequently in thyroid tumours. We therefore analysed FHIT and TSG101 transcripts in a group of advanced thyroid tumours to establish their role in thyroid tumorigenesis.DESIGNRetrospective analysis of FHIT and TSG101 mRNA transcripts and genomic DNA from cryo‐preserved thyroid tumours. TP53, previously shown at the genomic level not to be mutated in this cohort of tumours, served as a control.PATIENTSWe analysed nine follicular thyroid carcinomas (FTC), six papillary thyroid carcinomas and six follicular adenomas (FA) and histologically normal thyroid tissue from four of the FA patients.MEASUREMENTSSingle stage and nested reverse transcription polymerase chain reaction (RT‐PCR) products of FHIT, TSG101, and TP53 were analysed by agarose or polyacrylamide gel electrophoresis and sequenced. Genomic DNA was also analysed by polymerase chain reaction and sequencing (FHIT) or by Southern blotting (TSG101). Clinical data were correlated with the results of the mutation analysis.RESULTSTruncated FHIT transcripts were observed frequently alongside full length transcripts with nested RT‐PCR, most often in FTC, while single stage RT‐PCR revealed only normal length transcripts in all tumours. Similar results were obtained for TP53, while abnormal TSG101 transcripts were detectable by single stage RT‐PCR. Sequence analysis of the truncated FHIT and TSG101 transcripts revealed mainly exon skipping and alternate RNA processing events. Only a single point mutation (of TSG101) was found. Southern blotting for the TSG101 gene, and PCR amplification and sequencing of the FHIT gene showed no evidence of genomic abnormalities in either case, and there was no evidence of splice site mutations in the FHIT gene, suggesting that the truncated transcripts result from altered RNA processing. There was no relationship between tumour stage, grade or survival and the presence of FHIT or TSG101 abnormalities.CONCLUSIONSTruncated FHIT and TSG101 transcripts in thyroid tumours reflect alternate mRNA splicing events, rather than genomic deletions. Such abnormal RNA processing seems to be common and widespread in thyroid neoplasms, as similar results were obtained by analysis of transcripts of TP53, which we had previously shown not to be mutated in these specimens. Although a pathogenetic role for these aberrant transcripts remains possible, no correlation was found with stage, histological grade or outcome in this small group of advanced thyroid malignancies. Relaxation of mRNA splice control appears to be a feature of follicular cell‐derived thyroid neoplasms.
Management of the nontoxic multinodular goitre: A European questionnaire study
Authors: Bonnema Steen J. , Bennedbæk Finn N. , Wiersinga Wilmar M. , Hegedüs Laszlo 
Published: March 2003

BACKGROUND AND OBJECTIVEThe optimum management strategy for the patient with a multinodular nontoxic goitre is still a matter of debate. Our aim was to assess the attitudes towards management of such patients throughout Europe by means of a questionnaire.DESIGNThe questionnaire was circulated to all clinician members of the European Thyroid Association (ETA). A case report was followed by diagnostic investigations and choice of therapy in the index case (a 42‐year‐old woman with an irregular nontender bilaterally enlarged thyroid of 50–80 g and no clinical suspicion of malignancy). Eleven variations of the basic case report were proposed in order to evaluate the impact on management of each alteration.SUBJECTS AND METHODSOne hundred and sixty‐seven members replied to the letter, and 120 individuals from 22 countries completed the questionnaire (corresponding to approximately two‐thirds of the clinical members of the ETA).RESULTSBased on the index case, serum TSH was the routine choice of 100%, and serum free T4/T4‐index was included by 74%. Serum TPO autoantibodies, Tg autoantibodies and calcitonin were measured by 65%, 49% and 32%, respectively. The median number of blood tests used was four (range 1–11). Considerable intercountry variations were seen in the preferred imaging methods. Ninety‐one percent of the clinicians would use at least one imaging modality. Ultrasound (US) was used by 84%, thyroid scintigraphy by 76%, and both methods by 69%. US had first priority (53% vs. 19% for scintigraphy). If scintigraphy was performed, fine‐needle aspiration cytology was routinely used by 17% (inhomogeneous uptake) and 95% (dominant ‘cold’ area), and 63% used US‐guidance. L‐T4 treatment was supported by 52% of the clinicians, iodine supplementation by 4%, radioiodine by 6% and surgery by 10%. In the case of a suppressed serum TSH, radioiodine treatment was preferred by 44%, while surgery was the favoured recommendation in four clinical variations with a large goitre or suspicion of malignancy. Marked differences between the countries were suggested by L‐T4 therapy being the dominant treatment in Italy, France and Germany in contrast to the prevailing use of radioiodine in Denmark and a wait and see policy in the UK.CONCLUSIONSFundamental differences between European countries exist as regards diagnosis and treatment of the multinodular nontoxic goitre suggesting difficulties in reaching a consensus.
Serum inhibin B levels in community‐dwelling elderly men1
Authors: Mahmoud  , Goemaere  , De Bacquer  , Comhaire  , Kaufman  
Published: March 2003

BACKGROUND AND OBJECTIVEAgeing in men is accompanied by a decline of Leydig cell function, with a 50% decrease of the population means for serum free testosterone between age 25 and 75 years. Information on Sertoli cell function and spermatogenesis in the elderly is scarce. Studies on seminal parameters in ageing men have suggested that spermatogenesis may be fairly well maintained in the elderly, but they included mostly selected subjects and only few men over 60 years. More systematic studies are lacking. The aim of the present study was to assess serum inhibin B levels in elderly men as an index of global Sertoli cell function and spermatogenic activity.SUBJECTS AND MEASUREMENTSSpecific immunoassays were used to determine serum levels of inhibin B, gonadotrophins, testosterone and oestradiol in blood obtained between 0800 and 1000 h. from 189 ambulatory, community‐dwelling elderly men (age: 70–85 years) and, for comparison, from 51 middle–aged (35–54 years) and 50 young (< 35 years) controls.RESULTSAll age groups combined, serum inhibin B was only weakly negatively correlated to age (Spearman correlation coefficient: − 0.17; P < 0.01) and more strongly to serum FSH (− 0.52; P < 0.001). In a multiple regression analysis serum FSH, but not age or serum free testosterone, emerged as an independent determinant of serum inhibin B levels. An age‐related decline of median inhibin B levels in the study population was essentially limited to the younger age groups, with stable levels between age 35 and 79 years, and only a modest further decrease thereafter. There was a progressive age‐related increase of serum FSH across age groups with, consequently, a marked decrease of the serum inhibin B : FSH ratio. The prevalence of men presenting with low serum inhibin B (below 10th percentile for inhibin B levels in men < 35 years), indicative of deficient Sertoli cell function and spermatogenesis, increased most strikingly between men < 35 years and those 35–54 years, which contrasts with the more progressive increase at an older age of the prevalence of low serum (free) testosterone.CONCLUSIONGlobal testicular Sertoli cell function and spermatogenic activity, as assessed indirectly through serum inhibin B levels, appear to be well maintained in ambulatory elderly men, albeit there are age‐related alterations at the level of the Sertoli cells as indicated by a progressive increase of testicular drive by pituitary FSH.
Cardiovascular risk markers in hypothalamic amenorrhoea
Authors: Miller Karen K. , Grinspoon Steven , Klibanski Anne 
Published: March 2003

OBJECTIVETo determine whether women with oestrogendeficiency due to hypothalamic amenorrhoea (HA) would demonstrate a lipid and lipoprotein pattern similar to that seen in menopause with higher total cholesterol (TC), LDL, triglyceride and Lp(a) and lower HDL levels than women with regular menstrual cycles.DESIGNCross‐sectional.PATIENTSFifty subjects: 21 women with HA and 30 eumenorrhoeic controls (NL) matched for age, BMI and fat‐free mass.MEASUREMENTSLipid and lipoprotein levels.RESULTSThere was a significant difference in Lp(a) levels in the HA group between women with >19% fat intake and those <19% fat intake (352 ± 231 vs. 116 ± 62 mg/l, P = 0.006). Percent fat intake was the most significant determinant of Lp(a) levels in HA, accounting for 51% of the variation in Lp(a) levels. Mean HDL levels were higher in the women with HA compared with the controls (1.3 ± 0.3 vs. 1.1 ± 0.2 mmol/l, P = 0.002). There was no significant difference between the groups in TC [4.4 ± 0.9 (HA) vs. 4.1 ± 0.8 mmol/l (NL), P > 0.05], LDL [2.8 ± 0.6 (HA) vs. 2.7 ± 0.7 mmol/l (NL), P > 0.05], triglycerides [1.8 ± 0.5 (HA) vs. 1.7 ± 0.5 mmol/l (NL), P > 0.05] or Lp(a) [234 ± 199 (HA) vs. 247 ± 222 (NL) mg/l, P > 0.05] levels.CONCLUSIONReduced Lp(a) levels were associated with low dietary fat in women with HA. Moreover, in contrast to menopausal oestrogen deficiency, young women with HA and oestrogen deficiency have increased levels of HDL and no increases in TC, LDL and triglycerides. These data suggest that the negative effects of oestrogen deficiency on cardiovascular risk factors may be modified in women with hypothalamic amenorrhoea.