bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies
Authors: Tanis Bea C. , Westendorp Rudi G. J. , Smelt Augustinus H. M. 
Published: November 2003

OBJECTIVE The significance of mild hypercholesterolaemia in subclinical hypothyroidism and whether there is beneficial reduction after thyroxine replacement, remain controversial. We aimed to describe the association between hypercholesterolaemia and subclinical hypothyroidism, and to quantify the effect of thyroid substitution therapy by an analysis of previously published intervention studies. DATA SOURCES Intervention studies cited in the Medline database from January 1976 until January 1995, with index terms cholesterol, hypercholesterolaemia, hyperlipidaemia, thyrotrophin (TSH), hypothyroidism, thyroid and human. A total of 148 studies were reviewed. DATA EXTRACTION We recorded the year of publication, study design, number of patients enrolled, mean age, duration of thyroid substitution, normal range of TSH levels, TSH levels pre and post‐substitution treatment and total cholesterol in plasma before and after treatment. DATA ANALYSIS (1) Qualitative description of studies on the relationship between hypercholesterolaemia and hypothyroidism, both subclinical and clinical. (2) Precision weighted pooled estimates of the effect of thyroid substitution therapy on the plasma levels of total cholesterol, in patients with subclinical and overt hypothyroidism. RESULTS Subclinical hypothyroidism was two to three times more frequent in people with an elevated total plasma cholesterol. In addition, the total plasma cholesterol levels were slightly elevated in patients with subclinical dysfunction of the thyroid. Thyroid substitution therapy in patients with subclinical hypothyroidism, restoring the TSH levels to normal, decreased total cholesterol by 0.4 mmol/l (95% confidence interval (CI) 0.2–0.6 mmol/l) independently of the initial plasma level. The effect of thyroid substitution therapy on HDL‐cholesterol in patients with subclinical hypothyroidism was not consistent. The effect of thyroid substitution in patients with overt hypothyroidism was highly dependent on the pretreatment levels of total cholesterol. In these patients substitution therapy decreased total cholesterol by 1.2 mmol/l (95% CI 0.9–1.5 mmol/l) when the plasma levels were elevated up to 8 mmol/l, and by 3.4 mmol/l (95% CI 3.0–3.7) when plasma levels were higher than 8 mmol/l. The high density lipoprotein (HDL)‐cholesterol level decreased and amounted to 0.16 mmol/l (95% CI 0.07–0.24). CONCLUSIONS Thyroid substitution treatment in patients with hypercholesterolaemia and subclinical hypothyroidism decreases total plasma cholesterol by 0.4 mmol/l, but plasma levels remain elevated in most patients. Further treatment with dietary restriction and cholesterol synthesis inhibitors should then be considered.
Calcium‐sensing receptor mutations in familial hypocalciuric hypercalcaemia with recurrent pancreatitis
Authors: Pearce S. H. S. , Wooding C. , Davies M. , Tollefsen S. E. , Whyte M. P. , Thakker R. V. 
Published: November 2003

OBJECTIVE Pancreatitis is an unusual complication of the benign disorder familial hypocalciuric hypercalcaemia (FHH) such that it could represent a distinct subgroup of FHH. In order to study this, we investigated three FHH kindreds with recurrent pancreatitis for mutations of the extracellular calcium‐sensing receptor (CaR) to identify a possible common genetic aetiology for typical FHH and that associated with pancreatitis. PATIENTS AND METHODS Three FHH kindreds (18 affected, 14 unaffected members) in which the proband had presented with recurrent pancreatitis were identified. The entire 3234bp coding region of the CaR gene was examined by direct DNA sequencing using fluorochrome labelled dideoxy‐terminators. Mutations were confirmed and demonstrated to co‐segregate with FHH by restriction enzyme analysis. RESULTS Three novel heterozygous missense mutations (Asn178Asp, Arg220Gln and Pro221Ser) in the extracellular domain of the CaR were identified in each of the probands. These mutations, which co‐segregated with the hypercalcaemia, were not detected as common polymorphisms in 55 unrelated normocalcaemic controls. CONCLUSIONS Familial hypocalciuric hypercalcaemia with recurrent pancreatitis is associated with calcium‐sensing receptor mutations, and thus this variant has the same genetic aetiology as typical familial hypocalciuric hypercalcaemia.
Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon‐α therapy
Authors: Marazuela M. , García‐Buey L. , González‐Fernández B. , García‐Monzón C. , Arranz A. , Borque M. J. , Moreno‐Otero R. 
Published: November 2003

BACKGROUND AND AIMS Hepatitis C virus is involved in the induction of autoimmunity and interferon can also induce hepatic and non‐hepatic autoimmune reactions. This study assessed the prevalence of thyroid autoantibodies and autoimmune thyroid disorders in patients with chronic hepatitis C before and during interferon therapy. PATIENTS AND METHODS We studied prospectively 207 patients positive for anti‐HCV and viral RNA. One hundred and forty‐four of them received a therapeutic trial of one year with interferon‐α. Free thyroxine, TSH and autoantibodies to thyroglobulin and thyroid microsomes were systematically tested at entry and at weeks 12 and 24 in both untreated and treated patients. RESULTS Sixteen of the 207 patients (7.7%) had thyroid dysfunction, including positive antithyroid antibodies in 14 (6.7%) and hypothyroidism in 10 (4.8%) prior to interferon therapy. In addition, during pretreatment evaluation one patient developed clinical hyperthyroidism after transient subclinical hypothyroidism and another had subclinical hyperthyroidism. Prevalences of positive antithyroid antibodies and hypothyroidism were significantly higher in women (14.7 and 10.5%, respectively, vs 0% in men, P < 0.01) and were directly associated with increasing age (P < 0.01). The incidence of thyroid dysfunction was also significantly higher in patients with other autoantibodies such as anti‐nuclear (ANA) (P < 0.01). A trial with interferon was initiated in 144 patients and 8 of 142 (5.6%) without previous thyroid abnormalities developed thyroid dysfunction, including positive antithyroid antibodies in 7 (4.9%) and hypothyroidism in 4 (2.8%) with a prevalence again significantly higher in women (12.7 and 8.3%, respectively, vs 1% in men, P < 0.01) and also directly related to increasing age (P < 0.01). An association was found between the development of thyroid dysfunction during interferon therapy and the presence of other autoantibodies, including ANA, anti‐DNA and anti‐Sjögren’s antibodies (P < 0.01), as well as with the induction of autoimmune hepatitis and Sjögren's syndrome (P < 0.01 and < 0.05 respectively). Thyroid abnormalities were reversed in all patients when interferon therapy was discontinued. CONCLUSIONS No significant association was found between chronic hepatitis C and the presence of thyroid autoimmunity in female patients. On the contrary, interferon therapy induced antithyroid autoantibodies and thyroid dysfunction de novo in patients with chronic hepatitis C without pre‐existing thyroid abnormalities. Thyroid dysfunction secondary to interferon was reversible after discontinuation of therapy.
Hormone replacement therapy is associated with improved arterial physiology in healthy post‐menopausal women
Authors: McCrohon Jane A. , Adams Mark R. , McCredie Robyn J. , Robinson Jacqui , Pike Anne , Abbey Mavis , Keech Anthony C. , Celermajer David S. 
Published: November 2003

OBJECTIVE Oestrogen replacement therapy is associated with a marked reduction in coronary event rates in post‐menopausal women. As older age is associated with progressive arterial endothelial damage, a key event in atherosclerosis, we assessed whether hormone replacement therapy (HRT) with oestrogen alone, or oestrogen and progesterone combined, is associated with improved endothelial function in healthy women after the menopause. DESIGN Using high resolution external vascular ultrasound, brachial artery diameter was measured at rest and in response to reactive hyperaemia, with increased flow causing endothelium‐dependent dilatation (flow‐mediated dilatation). PATIENTS  We investigated 135 healthy women; 40 were pre‐menopausal (mean±SD age/26±6 years, group 1), 40 were post‐menopausal and had never taken HRT (aged 58±3 years; group 2) and 55 were age‐matched post‐menopausal women who had taken HRT for >2 years, from within 2 years of the menopause (aged 57±4 years; group 3). In group 3, 40 women were on combined oestrogen and progesterone and 15 on oestrogen‐only HRT. RESULTS In group 2, flow‐mediated dilatation was significantly reduced compared with group 1 (4.4±3.4 vs 9.6±3.6%, P<0.001), consistent with a decline in arterial endothelial function after the menopause. In group 3, however, flow‐mediated dilatation was significantly better than group 2 (6.2±3.3 vs 4.4±3.4%, P=0.01), suggesting a protective effect of HRT. Flow‐mediated dilatation was similar in women taking oestrogen alone and in those on combined HRT (5.5±2.8 vs 6.5±3.4%, P=0.40). CONCLUSIONS Long‐term HRT is associated with improved arterial endothelial function in healthy post‐menopausal women. This benefit was observed in both the combined hormone replacement and unopposed oestrogen therapy groups. This may explain some of the apparent cardioprotective effect of HRT after the menopause.
Retrospective analysis of long‐term surgical results in acromegaly: preoperative and postoperative factors predicting outcome
Authors: Yamada Shozo , Aiba Tadashi , Takada Kouji , Ozawa Yasunori , Shimizu Taeko , Sawano Shinji , Shishiba Yoshimasa , Sano Toshiaki 
Published: November 2003

OBJECTIVE Sixty‐one of 83 patients with acromegaly treated between 1969 and 1993 were analysed retrospectively to clarify which early postoperative factors were significant predictors of a successful long‐term outcome and which preoperative factors significantly influenced the early postoperative results. PATIENTS Of the 61 patients, 30 were operated on before 1987 and 31 afterwards. A successful long‐term surgical outcome was defined as a long‐term mean basal GH level <6 mU/l (comparable to <3 μg/l), a normal IGF‐I level, and normal GH dynamics. RESULTS Overall, 59% of patients (37% before 1987 and 81% after) had an early postoperative mean basal GH level <6 mU/l, and 56% (29% before 1987 and 77% after) met all three of the specified criteria for a successful long‐term surgical outcome. Statistical analysis confirmed that GH dynamics and postoperative mean basal GH level <6 mU/l were significant predictors of the long‐term surgical outcome, whereas the postoperative IGF‐I level alone was not. On the other hand, abnormal preoperative GH dynamics were normalized in all patients with a postoperative mean basal level <6 mU/l. In addition, there were no patients showing an unsuccessful long‐term outcome in those associated with both the early postoperative mean basal GH level <6 mU/l and normalization of the IGF‐I level. Therefore, measurement of the early postoperative mean basal GH level and the IGF‐I level may be an economical and simple guide to predict the long‐term surgical outcome. Moreover, multivariate analysis indicated that cavernous sinus invasion was an independent significant factor influencing the early postoperative outcome. CONCLUSIONS Successful long‐term surgical outcome may be predicted if early postoperative mean basal GH level is reduced to <6 mU/l (<3 μg/l) and IGF‐I level becomes normal. This study also confirms that early diagnosis and treatment by an experienced endocrinologist and neurosurgeon can improve the operative results in patients with acromegaly.
Smoking and endocrine ophthalmopathy: impact of smoking severity and current vs lifetime cigarette consumption
Authors: Pfeilschifter Johannes , Ziegler Reinhard 
Published: November 2003

OBJECTIVE Smoking has been associated with an increased incidence of endocrine ophthalmopathy (EO). In this study we examined the relation between smoking severity and the incidence of EO symptoms in patients with Graves’ hyperthyroidism. DESIGN Patients were prospectively followed for at least one year after the onset of hyperthyroidism. Smoking and EO status were evaluated at 3−6‐ months intervals. PATIENTS Two hundred and fifty‐three ambulatory patients with recent onset of Graves’ hyperthyroidism were studied. MEASUREMENTS The incidence of total EO symptoms, proptosis, and diplopia at any time point before and after the occurrence of Graves’ hyperthyroidism was assessed by interview and physical examination. RESULTS Smoking was associated with a 1.3‐fold increase in the overall incidence of symptomatic EO, and a 2.6 and 3.1‐fold increase in the incidence of proptosis and diplopia, respectively. The relative risk increased in parallel with the current number of cigarettes smoked per day. In contrast, lifetime tobacco use was not an independent risk factor for the development of EO symptoms. Former smokers had a significantly lower risk for the occurrence of proptosis and diplopia than active smokers with a comparable lifetime cigarette consumption. CONCLUSIONS Our data suggest that current, but not lifetime, tobacco consumption constitutes a risk for the incidence of proptosis and diplopia in patients with Graves’ hyperthyroidism, and that this risk increases with smoking severity.
Thyroid function in idiopathic oedema
Authors: Czapla K. , Farish E. , Haynes E. C. M. , Henderson J. B. , Pelosi A. J. , Dunnigan M. G. 
Published: November 2003

BACKGROUND The role of abnormal thyroid function in the aetiology of idiopathic oedema is unclear. Previous studies of small samples of patients have suggested a high prevalence of latent hypothyroidism and a possible deiodination defect in the conversion of T4 to T3 in this condition. There is a need to clarify the possible significance of abnormal thyroid function in a larger sample of idiopathic oedema patients. OBJECTIVE The study was undertaken to compare basal thyroid function in idiopathic oedema patients and in an age and sex‐matched control group. PATIENTS AND DESIGN After excluding one idiopathic oedema patient and three control subjects with abnormal thyroid function, basal thyroid function was compared in 44 idiopathic oedema patients and in 44 age and sex‐matched controls. MEASUREMENTS Basal thyroid function was assessed in patient and control groups by measuring serum T4, fT4, T3, fT3 and TSH by standard methods. RESULTS There were no significant differences in basal thyroid function between patient and control groups except for an elevated mean fT4 concentration in the idiopathic oedema group (P = 0.03). Exclusion of patients and controls taking oestrogen abolished this difference. T4 : T3 ratios were similar in patient and control groups. CONCLUSION Abnormalities of basal thyroid function are uncommon in patients with idiopathic oedema and appear unrelated to the pathogenesis of this disorder. Similar T4 : T3 ratios between patient and control groups exclude a deiodination defect in idiopathic oedema.
Low‐dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency
Authors: Florkowski C. M. , Collier G. R. , Zimmet P. Z. , Livesey J. H. , Espiner E. A. , Donald R. A. 
Published: November 2003

OBJECTIVE The ob gene product, leptin, is considered to be a marker of adipose tissue mass and a possible homeostatic regulator of body mass. Our objective was to examine the effect of GH replacement on adipose tissue stores and leptin in adult hypopituitarism. SUBJECTS Twenty adults, mean age 47 years (range 20–69) with proven GH deficiency were randomly allocated to either GH (up to 0.25 U/kg/week in daily doses) or placebo for 3 months before cross‐over to the opposite treatment. MEASUREMENTS Body composition was measured by dual‐energy X‐ray absorptiometry (DEXA) in the whole body, trunk and limbs. Plasma leptin was measured by radioimmunoassay at baseline and +2, +4, +8 and +12 weeks in each treatment arm. RESULTS Total body tissue fat (mean±SE) was 30.1±2.2% after GH compared with 31.9±2.2% after placebo, P<0.001 (ANOVA). There were no significant changes in BMI (kg/m2), 29.1±1.3 after placebo vs 28.8±1.2 after GH; or waist to hip ratio (WHR), 0.91±0.01 after both placebo and GH. Baseline plasma leptin showed a significant correlation with baseline BMI, r=0.67, P<0.005 and baseline percentage total body fat, R=0.89, P<0.001. Plasma leptin (adjusted by using baseline percentage total body fat as a covariate) showed a significant linear decrease with time on GH compared with placebo (P=0.03 ANOVA). CONCLUSIONS Plasma leptin and total body fat fall promptly in response to low‐dose replacement of GH in GH‐deficient subjects. Hormone‐induced changes in leptin can occur in humans in the absence of change in body mass index.
Growth hormone response to GHRH, GHRP‐6 and GHRH+GHRP‐6 in patients with polycystic ovary syndrome
Authors: Micić Dragan , Kenderesˇki Aleksandra , Popović Vera , Sˇumarac Mirjana , Zorić Svetlana , Macut Djuro , Dieguez Carlos , Casanueva Felipe 
Published: November 2003

OBJECTIVE Despite improved diagnostic facilities and advanced in vitro studies, the primary causes of the polycystic ovary syndrome (PCOS) have not been resolved. A defect in the regulation of GH secretion has been suggested in PCOS but the available data are limited and the underlying mechanisms remain unknown. In recent years considerable attention has been devoted to non‐classic GH secretagogues and, in particular, to the series of hexapeptides of which GH‐releasing peptide (His‐D‐Trp‐Ala‐Trp‐D‐Phe‐Lys‐NH2, known as GHRP‐6) is the most representative. GHRP‐6 seems to be a promising tool for exploring GH secretory mechanisms and it has been reported that GHRH+GHRP‐6 is a powerful stimulus to GH secretion. Our aim was to investigate the GH responses to GHRH, GHRP‐6 and the administration of GHRH+GHRP‐6 in two groups of patients (normal weight and obese) with PCOS in comparison with matched control groups. DESIGN All subjects were studied three times on different days with GHRH (100 μg i.v.), GHRP‐6 (90 μg i.v.) and GHRH+GHRP‐6 (100μg+90μg). PATIENTS Sixteen women with PCOS and 22 healthy controls were studied. They were divided into four groups according to BMI: Group A (non‐obese PCOS, n=6, age 21.8±1.7 years, BMI 22.1±0.8 kg/m2); Group B: (obese PCOS, n=10, age 12.7±1.3 years, BMI 32.9±2.1 kg/m2); Group C (non‐obese healthy women, n=13, age 26.8±1.5 years, BMI 21.8±0.6 kg/m2) and Group D (obese healthy women, n=9, age 29.4±4.2 years, BMI 35.7±1.3 kg/m2). MEASUREMENTS Serum GH was measured using a time‐resolved fluoroimmunoassay (Delphia, Pharmacia). RESULTS After GHRH administration significant differences were found between GH peaks in Groups A and B (82.4±16.4 vs 20±4.8 mU/l P<0.05) and in AUC for GH between Groups A and B (4667±1061 vs 847±236, P<0.05) while there were no differences between the same groups in GH peak or AUC after GHRP‐6 administration. There were no significant differences in peaks or AUC for GH after GHRH between Groups A and C, nor between Groups B and D. There were significant differences in GH peaks after combined administration of GHRH+GHRP‐6 between Groups A and B (211±26.4 vs 108±17.6, P<0.05) as well as between GH AUC in Groups A and B (12068±2323 vs 5997±1342, P<0.05). There were no differences in GH peaks or AUC for GH after GHRH+GHRP‐6 administration between Groups A and C or Groups B and D. CONCLUSIONS The impaired GH response to GHRH found in obese PCOS patients is a consequence of obesity and could be a functional defect, since it can be overridden with GHRP‐6 administration.
Differential stimulation of corticol and dehydropiandrosterone levels by food in obese and normal subjects: relation to body fat distribution
Authors: Korbonits Márta , Trainer Peter J. , Nelson Marcia L. , Howse Iain , Kopelman Peter G. , Besser G. Michael , Grossman Ashley B. , Svec Frank 
Published: November 2003

BACKGROUND It has been previously shown that food intake elevates circulating ACTH and cortisol levels, but no report has been published regarding the changes in circulating dehydroepiandrosterone (DHEA). DHEA was originally described as a weak androgen, but more recently it has been associated with a wide range of metabolic functions. In addition, previous studies have described a hyper‐responsive hypothalamo‐pituitary‐adrenal axis in obese subjects in response to various stimuli, but the specific response to food has not been studied. SUBJECTS AND DESIGN We studied the effect of food on the hypothalamo‐pituitary‐adrenal axis in 20 subjects of normal body mass index (BMI range 18–25) and also in a group of 12 obese subjects (BMI range 34–61). Levels of glucose, insulin, ACTH, cortisol and dehydroepiandrosterone were measured every 20 minutes. RESULTS A small rise in DHEA accompanies the rise in circulating ACTH and cortisol in response to food in both lean and obese subjects, but DHEA rose independently of cortisol and ACTH on the fasting day. In the obese subjects, food induced a significantly greater change in serum cortisol (peak cortisol rise (mean±SEM); normal‐weight group, 169±14%; obese group, 294±23%) and in the cortisol/DHEA ratio (area under the curve; normal‐weight group, 202±15%; obese group, 292±29%) than in the normal‐weight subjects. This difference was particularly notable in those with central‐type obesity (waist/hip ratio>0.80). A group of the normal, lean female subjects showed no cortisol rise after food intake. CONCLUSION Our results suggest that DHEA may vary independently of circulating cortisol, and that the cortisol response to food is enhanced in obese subjects, particularly in those with central obesity. We speculate that there may be a caused connection between the cortisol response to food in normal subjects, and the subsequent distribution of fat if such subjects overeat sufficiently to become obese.
Bone mineral density in relation to glucocorticoid substitution therapy in adult patients with 21‐hydroxylase deficiency
Authors: Jääskeläinen Jarmo , Voutilainen Raimo 
Published: November 2003

OBJECTIVE There are only limited data on bone mineral density (BMD) in adult patients with 21‐hydroxylase deficiency (21‐OHD). We have defined the effects of different glucocorticoid substitution therapies on BMD and body composition in these patients. DESIGN Cross‐sectional. PATIENTS Thirty‐two adult patients with 21‐OHD. MEASUREMENTS Patients were examined auxologically and biochemically. BMD was examined in the left femoral neck and lumbar vertebrae 2–4 (L2–4) with dual X‐ray absorptiometry. The results were compared with national reference data. RESULTS Mean height was 170.1 cm (−1.36 standard deviation scores (SDS) for the men and 156.3 cm (−1.68 SDS) for the women. These were significantly less (P<0.001) than the mean national final heights. Mean BMD Z‐score ((raw score − population reference mean)/SD) was −0.52 in L2–4 and −0.83 in the left femoral neck. Both these values were significantly less than the reference mean values (P=0.045 and <0.001, respectively). Both current and long‐term mean glucocorticoid doses showed significant negative correlations with BMD in the left femoral neck as well as in L2–4. Patients substituted with hydrocortisone were less often over‐treated and had better BMD Z‐score means than patients substituted with prednisone, prednisolone or dexamethasone. CONCLUSIONS In the follow‐up of patients with 21‐hydroxylase deficiency, care needs to be exercised to keep the glucocorticoid substitution dose to a minimum. In most cases decreased bone mineral density is a result of over‐substitution.