bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerated bone loss in post‐menopausal women with mild primary hyperparathyroidism
Authors: Grey Andrew B. , Stapleton Joanne P. , Evans Margaret C. , Reid Ian R. 
Published: November 2003

OBJECTIVES Osteopenia is regarded as an indication for parathyroidectomy in primary hyperparathyroidism. However, uncertainty exists as to the extent and degree of the skeletal effects in those with mild disease. We sought to determine whether mild primary hyperparathyroidism affects the rate of bone loss in post‐menopausal women. DESIGN Prospective 2‐year comparison of rates of bone loss throughout the skeleton in 17 post‐menopausal women with untreated mild asymptomatic primary hyperparathyroidism, and 48 age‐matched, eucalcaemic controls. RESULTS The women with primary hyperparathyroidism had a greater annual rate of loss of bone mineral density (BMD) of the total body (mean ± SE, primary hyperparathyroidism −1.15 ± 0.31%, controls −0.39 ± 0.10%; P = 0.04) and its spine subregion (primary hyperparathyroidism −2.08 ± 0.88%, controls 0.04 ± 0.35%; P = 0.02). Lumbar spine BMD tended to decline in the primary hyperparathyroidism group (−0.35 ± 0.33%) in contrast to the control group (+ 0.28 ± 0.22%) (P = 0.10). There were no significant differences between the groups in rates of change of BMD in the legs or the proximal femur. In the primary hyperparathyroidism group, the rate of total body bone loss in the eight women known at study entry to have had long‐standing (>5 years) primary hyperparathyroidism was −1.52 ± 0.61%/year, similar to that of the whole group. CONCLUSION Primary hyperparathyroidism is associated with an increased rate of loss of total body bone mineral density in post‐menopausal women. Prolonged disease duration is therefore likely to be associated with an increasing risk of osteopenia, such that skeletal surveillance and interventions designed to reduce bone loss should be considered.
Adrenal autoantibodies and organ‐specific autoimmunity in patients with Addison's disease
Authors: Söderbergh A. , Winqvist O. , Norheim I. , Rorsman F. , Husebye E. S. , Dolva Ø. , Karlsson F. A. , Kämpe O. 
Published: November 2003

OBJECTIVE Autoimmune destruction of the adrenal gland is the major cause of idiopathic Addison's disease, but the significance of 21‐hydroxylase autoantibodies and their correlation with the presence of other autoantibodies have not so far been investigated in a larger population of patients with Addison's disease. We have now characterized a cohort of patients with idiopathic Addison’s disease (n=97) regarding the specificity of autoantibodies against the adrenal cortex and, as Addison's disease can be either an isolated condition or part of a polyendocrine disorder, we investigated the presence of organ‐specific polyendocrine autoimmunity in this patient population. DESIGN Cross‐sectional study. MEASUREMENTS Autoantibodies were analysed with indirect immunofluoresence (IF) on tissue preparations, ELISA and in Western blots using bacterially expressed proteins. RESULTS Eighty‐four per cent (81/97) of the patient sera recognized the steroid‐producing cells of the adrenal cortex in indirect IF. The antigen was identified as 21‐hydroxylase by 72% (70/97) of the patient sera in Western blots. Seven sera that were negative on adrenocortical IF identified 21‐hydroxylase on Western blot, while eight IF‐positive sera were 21‐hydroxylase‐negative. Five sera weakly recognized 17α‐hydroxylase in Western blots, but all of these were also positive for 21‐hydroxylase. In 13 cases (12 women), the sera also reacted with testicular Leydig cells, and nine of these identified the side‐chain cleavage (SCC) enzyme. Other clinically evident organ‐specific autoimmune disorders were present in 40% of the 97 patients and abnormal titres of organ‐specific antibodies were found in 60% of the patients. CONCLUSIONS In idiopathic Addison's disease, autoantibodies against 21‐hydroxylase are found in a majority of cases and this represents an important diagnostic tool. The enzyme 17α‐hydroxylase does not seem to constitute a major autoantigen in Addison's disease. In a subgroup of patients with autoantibodies to gonads, antibodies to SCC are produced, often in parallel with antibodies to 21‐hydroxylase. In yet another subgroup the specificity of autoantibodies giving positive immunofluorescence is still unknown. Three patients revealed a polyendocrine syndrome which clinically resembles autoimmune polyendocrine syndrome (APS) type I, but serologically corresponds to APS type II. Polyendocrine disorders are often associated with Addison's disease, and screening, including quantification of autoantibodies, may help to identify those at risk of developing associated autoimmune disorders.
Clinical examination is not an accurate method of defining the presence of goitre in schoolchildren
Authors: Lisbôa Hugo R. K. , Gross Jorge L. , Orsolin Ademir , Fuchs Sandra 
Published: November 2003

OBJECTIVE There are few published data on thyroid size and body size variables in children. We aimed to develop an index for normal thyroid size in schoolchildren using ultrasonography and to evaluate the accuracy of clinical examination in the diagnosis of goitre. DESIGN A study to screen and diagnose goitre SUBJECTS A population based sample of 1094 schoolchildren aged 6–14 years (556 boys and 538 girls) were submitted to clinical examination of the thyroid. One hundred and nineteen were considered to have goitre. Ultrasonography was performed in 85 who agreed to participate in the study and in 62 schoolchildren selected randomly from those thought to have no goitre. MEASUREMENTS Clinical examination and definition of goitre were performed according to WHO criteria. Thyroid volume was measured by ultrasonography (7.5 MHz transducer). RESULTS The gland volume of 62 schoolchildren without goitre on clinical examination showed a positive correlation with body surface area, age and skinfold thickness. When these factors were entered in multiple regression analysis, only body surface area remained associated with thyroid volume. The upper limit (95th percentile) of the ratio of thyroid volume to body surface area (Ecobody index) was 6.2 ml/m2. Taking this index as the standard criterion, the performance parameters of clinical examination for the detection of goitre in the 1094 schoolchildren were: sensitivity 41%, specificity 91%, positive predictive value 27% and negative predictive value 95%. CONCLUSIONS Clinical examination of the thyroid is unreliable in establishing the presence of goitre in schoolchildren because it tends to overestimate thyroid size. Nevertheless, it can be used as a screening test. Ultrasonography should be performed when the thyroid gland is thought to be enlarged.
Divergence between growth hormone responses to insulin‐induced hypoglycaemia and growth hormone‐releasing hormone in patients with non‐functioning pituitary macroadenomas and hyperprolactinaemia
Authors: Beentjes John A.M , Tjeerdsma Geert , Sluiter Wim J. , Dullaart Robin P.F. 
Published: November 2003

OBJECTIVE The GH responses to the insulin tolerance test (ITT) and growth hormone‐releasing hormone (GHRH) may yield different results in patients with pituitary lesions. The GH responses to these stimuli were compared in patients with untreated non‐functioning pituitary macroadenomas, who represent an important cause of GH deficiency. DESIGN Analysis of peak GH to ITT and to 100 μg GHRH in relation to an elevated PRL level (> 200 mIU/l for males and > 600 mIU/l for females) as an indication of hypothalamic‐pituitary dysregulation, as well as in relation to other anterior pituitary hormone deficiencies. A peak GH < 5 μg/l in either test indicated GH deficiency. PATIENTS Twenty females and 14 males (median age 52 (23−77) years) evaluated preoperatively in a university hospital setting. RESULTS In the whole group the median peak GH to GHRH (3.6 (0.9−26.3) μg/l) was higher than to ITT (1.6 (0.2−7.8) μg/l, P < 0.001). This difference was seen only in 19 patients with concomitant hyperprolactinaemia (P < 0.001). When hyperprolactinaemia was present, an insufficient GH peak was demonstrated by ITT in 16 cases and by GHRH stimulation in 7 cases (P < 0.01). The frequency of an insufficient GH peak by ITT (13 cases) and by GHRH (14 cases) was similar in the normoprolactinaemic patients. In addition, 9 of 10 patients with an impaired response to ITT and a normal response to GHRH were hyperprolactinaemic compared to 7 of 19 patients with GH deficiency as assessed by both stimuli (P < 0.02). Peak GH to ITT was lower in 24 patients with, compared to 10 patients without, other hormonal deficiencies (1.4 (0.2−5.6) vs 3.0 (1.0−7.8) μg/l, P < 0.02), but was not related to elevated PRL. In contrast, GHRH‐stimulated GH was higher in hyperprolactinaemic than in normoprolactinaemic patients (5.9 (1.6−26.3) vs 2.9 (0.9−5.4) μg/l, P < 0.001) and was not related to the presence of other pituitary hormone deficiencies. Analysis of covariance confirmed that peak GH to ITT was negatively associated with the presence of other pituitary hormone deficiencies (P < 0.01), whereas peak GH to GHRH was positively related to an elevated PRL level (P < 0.02). Basal GH was positively correlated with PRL (Rs = 0.36, P < 0.05). CONCLUSIONS This study demonstrates that ITT and GHRH tests cannot be used interchangeably in diagnosing GH deficiency in patients with non‐functioning pituitary macroadenoma and hyperprolactinaemia. If the ITT is considered to be the reference test, GH deficiency as assessed by GHRH can be missed in patients with hyperprolactinaemia. This disparity is probably due to a different mechanism of action of these stimuli. Hyperprolactinaemia may be associated with a diminished somatostatin tone, leading to a higher basal and GHRH‐stimulated GH, without having an effect on peak GH to ITT.
Oral prednisolone supplement abolishes the acute adverse effects following initiation of depot bromocriptine therapy
Authors: Jenkins Paul J. , Jain Ajay , Jones Sharon L. , Besser G. M. , Grossman A. B. 
Published: November 2003

OBJECTIVE Although an effective treatment for hyperprolactinaemia, initiation of bromocriptine therapy may be associated with significant acute side‐effects in some patients, particularly nausea, vomiting and postural hypotension. These may be minimized by initial treatment with i.m. depot bromocriptine (Parlodel‐LAR, Sandoz, Basel, Switzerland), but adverse effects following the first injection may still be a significant problem. Following the observation that cortisol deficient patients were subject to an increased incidence of severe side‐effects on initiation of bromocriptine therapy, we have evaluated whether concurrent administration of oral prednisolone to patients without cortisol deficiency might reduce adverse effects. DESIGN Double‐blind placebo‐controlled trial with prednisolone (20 mg) prior to, and 16 hours after, depot injection of i.m. bromocriptine (50 or 100 mg). PATIENTS Twenty‐one consecutive patients with hyperprolactinaemia (serum prolactin >1000 mU/l on 3 separate occasions) who were due to start depot bromocriptine and who had a normal cortisol response to insulin‐induced hypoglycaemia. MEASUREMENTS Symptoms at 0, 16 and 40 hours after injection were assessed using visual linear analogue scales and both inter and intra‐group scores were compared by non‐parametric tests. RESULTS Depot bromocriptine was associated with the significant occurrence of light‐headedness and lethargy in the placebo‐administered group by 16 hours, and also with nausea and nasal congestion by 40 hours. These symptoms did not occur in the prednisolone‐administered group. CONCLUSIONS Concurrent oral administration of prednisolone significantly reduces the incidence of acute adverse effects following depot bromocriptine. Two 20 mg doses of prednisolone given at 12‐hour intervals may be used to avoid dopamine‐agonist‐induced adverse effects at the initiation of treatment with depot bromocriptine, and may also be of value in the treatment of side‐effects associated with other dopamine agonist drugs.
Body composition in growth hormone deficient adults over the age of 60 years
Authors: Toogood Andrew A , Adams Judith E , O'Neill Paul A , Shalet Stephen M 
Published: November 2003

OBJECTIVE Elderly patients with hypothalamic‐pituitary disease exhibit a reduction in GH secretion distinct from the decline in GH secretion related to age. GH deficiency in young adults causes a change in body composition, with increased fat mass (FM) and reduced fat free mass (FFM), similar to that seen as a result of the normal ageing process. The aim of this study was to determine whether organic GH deficiency in elderly patients may cause changes in body composition beyond those due to ageing. SUBJECTS Twenty‐one patients (15 male) with documented pituitary disease and 24 controls (17 male) matched for age, height, weight and BMI, all over the age of 60, in whom GH status had been defined by a 24‐hour GH profile and an arginine stimulation test. MEASUREMENTS Serum was taken for fasting IGF‐I and IGFBP‐1 estimations. Total and regional FM and FFM were determined using dual‐energy X‐ray absorptiometry. RESULTS FM (median (range)) was increased in the patients, 27.76 (19.25–50.24) vs 21.23 (8.81–49.15) kg in the controls (P < 0.005). FM was significantly increased in the arms, legs and trunk in the patients compared with the controls. The proportion of fat deposited centrally did not differ significantly between the two groups (57.0% (47.6–65.1) in the patients vs 55.3% (44.1–63.8) in the controls, P = 0.25). There was an inverse relation between total FM and serum IGFBP‐1 present in the patients, ρ = −0.632, P < 0.005, and in the controls ρ = −0.467, P < 0.05, but the relation between total FM and area under the GH profile was significant only in the controls (ρ = −0.651, P < 0.001) and not in the patients. FFM (51.19 (26.96–69.18) kg in the patients vs 51.55 (32.35–60.53) kg in the controls, P = 0.99) and serum IGFBP‐1 levels did not differ significantly between the two groups. CONCLUSION Organic growth hormone deficiency causes changes in body composition beyond the changes associated with the ageing process. These changes differ from those seen in younger GH deficient adults in that they are limited to an increase in FM with no change in FFM. These findings indicate that even in the elderly, in whom GH secretion is normally very low, the additional imposition of GH deficiency due to organic disease has significant biological impact.
Outcome of transsphenoidal surgery for acromegaly using strict criteria for surgical cure
Authors: Sheaves R. , Jenkins P. , Blackburn P. , Huneidi A. H. , Afshar F. , Medbak S. , Grossman A. B. , Besser G. M. , Wass J. A. H. 
Published: November 2003

OBJECTIVE Previous studies of surgical treatment for acromegaly have used varied criteria for ‘cure’, but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer‐term outcome for patients not offered further treatment when post‐operative levels of GH < 5 mU/l were achieved. DESIGN We studied a retrospective group of patients who underwent transsphenoidal surgery for acromegaly at St Bartholomew’s Hospital between 1985 and 1993. PATIENTS One hundred consecutive patients (53 male, mean age 46 years, range 18–68 years) undergoing transsphenoidal surgery for acromegaly were assessed. The patients were followed for a mean of 3.8 years (range 0.5–8 years) after operation. MEASUREMENTS GH levels are represented as a mean value from a four‐point day curve taken at 0830, 1300, 1700 and 1900h. ACTH reserve was assessed basally and, if this was normal, with the insulin tolerance or glucagon tests. TSH, T4, PRL, LH, FSH, testosterone or oestradiol and plasma and urine osmolality were also measured. RESULTS Post‐operatively, 42% of patients achieved a mean GH level of < 5 mU/l. The success of surgery was related to the preoperative GH level; 65% of the patients with preoperative GH levels < 20 mU/l but only 18% of the patients with GH levels > 100 mU/l achieved post‐operative GH values < 5mU/l. In addition, tumour size influenced the outcome of surgery with 61% of patients with a microadenoma but only 23% of patients with a macroadenoma achieving post‐operative GH levels of < 5 mU/l. Of the 42 patients considered in remission postoperatively (mean GH < 5 mU/l), 32 were available for long‐term follow‐up and were not offered any further treatment: only one of these has shown evidence of mild biochemical recurrence after a mean follow‐up of 3.8 years (range 0.5–8).  There were no peri‐operative deaths. Two patients required surgical repair for CSF leaks and there were eight documented cases of meningitis. Permanent diabetes insipidus was noted in eight patients post‐operatively. New anterior pituitary deficiency occurred in 21% of patients following surgery; 73% had unaltered pituitary function and in 6% recovery of partial hypopituitarism was noted. CONCLUSIONS The stated outcome of surgery depends on the criteria adopted. Safe GH levels (mean levels < 5 mU/l) can be achieved in 42% of an unselected series of patients with acromegaly and if the tumour is a microadenoma this figure rises to 61%. Based on the current evidence it is safe not to offer further treatment to those patients in whom post‐operative GH < 5 mU/l are achieved.
Clinical and biochemical investigations and molecular analysis of subjects with mutations in the androgen receptor gene
Authors: Weidemann Wolfgang , Linck Birgit , Haupt Heike , Mentrup Birgit , Romalo Gabriela , Stockklauser Karin , Brinkmann Albert O. , Schweikert Hans‐Udo , Spindler Klaus‐Dieter 
Published: November 2003

OBJECTIVE Androgen insensitivity syndromes (AIS) in subjects with 46,XY karyotype and normal or even elevated androgen blood levels are characterized by various aberrations in male differentiation and virilization. AIS is often accompanied by a broad spectrum of abnormal binding characteristics of the androgen receptor (AR). In order to investigate the correlation between the degree of virilization defect and the type of androgen binding abnormalities and/or the nature of the mutation in the AR gene, we determined androgen binding characteristics of the AR protein and the sequence of the AR gene in clinically and biochemically well characterized patients with various degrees of androgen resistance. DESIGN AND PATIENTS The activity of 5α‐reductase and the binding of androgen to its receptor (KD‐values, Bmax, thermolability) were determined in genital skin fibroblasts from 20 patients with various degrees of defects in virilization (2 CAIS, complete AIS; 18 PAIS, partial AIS patients). The AR gene of these 20 subjects was characterized by PCR‐SSCP analysis. In case of aberrant electrophoretic mobility the corresponding exon was sequenced. RESULTS The 2 patients with CAIS and 7 with PAIS showed a mutation in the AR gene. In two, the mutation was in the DNA binding domain, and in all others in the ligand binding domain. In 11 patients with severe virilization defects no abnormal behaviour was detected in the PCR‐SSCP. Transcriptional activation studies of two mutant ARs revealed that an approximately tenfold higher androgen concentration (methyltrienolone) is necessary to achieve maximal response as compared to the wild type AR. CONCLUSIONS There is no obvious relation between the degree of androgen resistance and the binding parameters of the AR and/or the nature of mutation in the AR gene. Androgen insensitivity syndrome can occur despite normal androgen binding and presumably non‐mutated AR genes. Even if there is abnormal binding of androgen and/or a mutation in the AR gene there is no clear‐cut relationship between these parameters and the degree of virilization defects. Thus, in a proportion of patients, neither the determination of binding parameters of the AR nor the detection of mutations in the AR gene are sufficient to understand the mechanisms underlying the androgen insensitivity syndrome.
Effects of oral and transdermal oestrogen replacement therapy on plasma levels of insulin‐like growth factors and IGF binding proteins 1 and 3: a cross‐over study
Authors: Helle S. I. , Omsjø I. H. , Cwyfan Hughes S. C. , Botta L. , Hüls G. , Holly J. M. P. , Lønning P. E. 
Published: November 2003

OBJECTIVE Conflicting results have been reported on the effects of oral and transdermal oestrogen replacement therapy on IGF‐I, while little information exists regarding the effects on IGFBP ‐1 and ‐3. In this study we evaluated the effects of oral and transdermal oestrogens on these parameters in post‐menopausal women in a randomized cross‐over study. PATIENTS A group of 14 post‐menopausal women were randomized to receive progestin‐opposed oestrogen replacement therapy administered orally (Trisekvens Novo: 17β‐oestradiol 2 mg daily on days 1–22 and 1 mg daily on days 23–28, norethisterone 1 mg days 13–22) or transdermally (Estracomb CIBA: oestradiol 50 μg/24 h on days 1–28, norethisterone 250 μg/24 h on days 15–28) for 6 months after which they were crossed over to the alternative treatment option. Fasting blood samples were obtained before treatment, and after 3, 6, 9 and 12 months on treatment. MEASUREMENTS IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐3, oestradiol and norethisterone were analysed by radioimmunoassays. In addition, IGFBPs were evaluated with Western ligand blots (WLB) in a subgroup of 12 patients. RESULTS Plasma levels of oestradiol were not significantly different during oral and transdermal treatment. Norethisterone levels were below the detection limit in all situations in 8 patients, while 6 patients had detectable levels in one or several samples during treatment. Oral treatment caused a significant decrease (16%, P<0.005) in IGF‐I and a non‐significant decrease in IGFBP‐3. A similar effect was observed when samples containing detectable levels of norethisterone were excluded from the analysis. No significant effect on IGFBP‐1 was observed when all samples were included in the analysis. However, when samples with detectable norethisterone were excluded IGFBP‐1 increased by 46% (P<0.01) during oral therapy. Contrary, transdermal treatment with oestrogens did not influence any of the parameters measured. None of the treatments had any effect on plasma IGF‐II levels or IGFBP profile evaluated by WLB. CONCLUSIONS Treatment with oral hormone replacement therapy significantly suppresses plasma IGF‐I levels and increases plasma IGFBP‐1 while transdermal treatment had no influence. This may be due to the route of administration, as plasma oestradiol levels showed little difference between the groups. The effect of oral oestrogens on IGFBP‐1 seems to be attenuated by progestins.