bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroxine suppressive therapy decreases bone mineral density in post‐menopausal women
Authors: Kung Annie W. C. , Lorentz Theodore , Tam Sidney C. F. 
Published: March 2008

SummaryOBJECTIVE Hyperthyroidism is associated with increased bone turnover and decreased bone mass. This study aimed to evaluate the bone mineral density (BMD) of post‐menopausal women on long‐term thyroxine suppressive therapy.DESIGN An age and sex‐matched cross‐sectional study.PATIENTS Thirty‐four post‐menopausal women with carcinoma of thyroid, post total thyroidectomy nd M ablation, on L‐T4 for 12 2 ± 6–6 years (mean±SD). Controls were 34 age‐matched healthy Southern Chinese women.MEASUREMENTS Total body and regional BMDs were determined by dual‐energy X‐ray absorptiometry. Bone turnover was assessed by biochemical markers.RESULTS In the thyroxine treated group, total body mineral content was significantly lower than the controls (1652±356 vs 1994±270 g meaniSD,P<0 005). They also had lower BMDs in the lumbar spine, femoral neck, trochanter and Ward's triangle (0 75 ± 0 15 vs 0 92 ± 0 16 g/ cm2, P<0005; 0–62±0–12 vs 0–70±0–12 g/cm2,P<0–01; 0–55±0–14 vs 063±015 g/cm2, P<0.001; 055±014 vs 0–63 ±0–14 g/cm2, P < 0.005 respectively.) The thyroxine treated group also had higher serum alkaline phosphatase and osteocalcin levels as well as urinary hydroxypro‐line excretion, suggesting that they had high turnover bone loss. However, the Z‐scores of the various regional BMDs were correlated only with the serum osteocalcin level and showed no correlation with the serum thyroxine level or with the dosage or duration of thyroxine treatment. CONCLUSION Long‐term thyroxine suppressive therapy was associated with bone loss and preventive therapy may be indicated in these post‐menopausal women at risk of osteoporosis.
A long‐term follow‐up study of patients with non‐toxic diffuse goitre in Japan
Authors: Hara Takeshi , Tamai Hajime , Mukuta Toshio , Fukata Shuji , Kuma Kanji , Nakagawa Tetsuya 
Published: March 2008

SummaryOBJECTIVE Although non‐toxic diffuse goitre is a common disorder, little is known of the clinical course of patients. We therefore decided to investigate the long‐term clinical outcome of patients with non‐toxic diffuse goitre.DESIGN A retrospective study.PATIENTS Of 850 patients with non‐toxic diffuse goitre who met our criteria and were seen in our thyroid clinic between 1977 and 1985, 108 who had been followed for from 5 to 14 years (mean 8 years) were entered in this study. All patients fulfilled our criteria having soft diffuse goitres, normal serum TSH and T4 concentrations, and undetectable antithyroglobulin and antithyroid microsomal antibodies.MEASUREMENTS A family history of thyroid disease was obtained and the occurrence of Graves' ophthalmopathy was noted. Serum TSH and T4 concentrations, and antithyroglobulin and antithyroid microsomal antibodies were measured during the follow‐up period. Thyroidal radioactive iodine uptake (RAIU), serum free T4 and free T3 concentrations, and TSH binding inhibitory immunoglobulin (TBII) activities were determined in all patients who were subsequently found to have abnormal serum TSH or T4 concentrations or signs of Graves' ophthalmopathy.RESULTS Thirty‐six of the 108 patients (33%) had a family history of autoimmune thyroid disease. Elevated serum T4 or free T4 concentrations and depressed serum TSH concentrations were found in six patients during the follow‐up period. Hyperthyroid Graves' disease was diagnosed in four of the six patients, subacute thyroiditis in one, and transient post‐partum thyrotoxicosis in one. Hypothyroidism was found in one patient who was diagnosed as having transient post‐partum hypothyroidism. Euthyroid Graves' disease was diagnosed in one patient. Furthermore, six of these eight patients had a family history of autoimmune thyroid disease in first‐degree relatives.CONCLUSION During a prolonged follow‐up period of patients with non‐toxic diffuse goitre, Graves' disease was found in five of 108 patients (four hyperthyroid Graves' and one euthyroid Graves'), post‐partum thyroid dysfunction in two, and subacute thyroiditis in one. Six of these eight patients had a family history of autoimmune thyroid disease in first‐degree relatives. Long‐term follow‐up is necessary for patients with non‐toxic diffuse goitre, especially those who have a family history of autoimmune thyroid disease.
Leucine metabolism in patients with Cushing's syndrome before and after successful treatment
Authors: Bowes S. B. , Benn J. J. , Scobie I. N. , Umpleby A. M. , Lowy C. , Sönksen P. H. 
Published: March 2008

SummaryOBJECTIVE Results from studies on the effect of glucocor‐ticosteroids on protein turnover in both rat and man have been conflicting. The aim of this study was to investigate the primary cause of muscle wasting in patients with Cushing's syndrome.DESIGN Studies of whole body 1‐14C‐leucine turnover in patients with Cushing's syndrome before and after successful treatment, and in control subjects.PATIENTS Eleven patients with Cushing's syndrome before and after (n= 5) treatment and 11 control subjects.MEASUREMENTS Whole body 1‐14C‐leucine turnover to determine leucine metabolic clearance rate, leucine production rate, leucine oxidation rate and leucine incorporation into protein.RESULTS Plasma leucine concentration (mean ± SEM 100 ± 6 μ mol/l), leucine metabolic clearance rate (9.97 ± 0.11 μ mol/min/kg), leucine turnover (0.98 ± 0.11 μ mol/min/kg) and leucine incorporation into protein (0.71 ± 0.09 μ mol/min/kg) were all significantly reduced in patients with Cushing's syndrome compared with control subjects (122 ± 6 μ mol/l, P < 0.05; 13.61 ± 1.27 μ mol/min/kg, P < 0.05; 1.65 ± 0.12 μ mol/min/kg, P < 0.05; 1.46 ± 0.10 μ mol/min/kg, P < 0.001, respectively). Leucine oxidation rate was similar in the patients with Cushing's syndrome and control subjects. When leucine metabolism was expressed in terms of lean body mass (LBM) in five patients with Cushing's syndrome and 11 control subjects, leucine MCR, leucine turnover and leucine oxidation were not significantly different in the two groups. However, leucine incorporation into protein was significantly reduced (P< 0.001) in the patients with Cushing's syndrome (1.07 ± 0.20 μ mol/min kg LBM) compared with control subjects (1.95 ± 0.11 μ mol/min/kg LBM).CONCLUSION We conclude from these studies that the muscle wasting associated with Cushing's syndrome is primarily due to a reduction in protein synthesis.
Necrosis of a phaeochromocytoma associated with spontaneous remission of diabetes and hypertension
Authors: Zanin Lucia , Rossi GianPaolo , Poletti Alessandro , Piotto Andrea , Chiesura‐Corona Matteo , Pessina Achille C. 
Published: March 2008

SummaryThe diagnosis of phaeochromocytoma is sometimes difficult since its clinical presentation is quite variable. We report a 52‐year‐old woman who presented with acute diabetes mellitus and severe hypertension, which spontaneously disappeared. MIBG‐scintigraphy and urine and plasma catecholamines were normal. At surgery, a largely necrotic phaeochromocytoma was found. Pathological examination demonstrated extensive avascular necrosis, which had occurred spontaneously without any major symptoms.
Alternate‐day GnRH therapy for ovarian hypofunction induced by weight loss: treatment of six patients who remained amenorrhoeic after weight gain
Authors: Kotsuji Fumikazu , Kubo Makoto , Takeuchi Yuzuru , Tominaga Toshiro 
Published: March 2008

Summary objective Body weight loss has an adverse effect on the pituitary‐ovarian function, and no restoration of the function occurs in 20–30% of patients even after the recovery of body weight. In the present study, the efficacy of alternate‐day GnRH therapy was investigated in six patients whose pituitary‐ovarian function had not recovered at 15 months to 6 years after the recovery of body weight.DESIGN Synthetic GnRH (100 μg) was injected intramuscularly on alternate days for a total of 12 doses. On the completion of GnRH administration the efficacy of clomi‐phene‐human chorionic gonadotrophin (hCG) therapy was evaluated. A GnRH loading test and evaluation of LH secretion patterns were also performed to investigate the changes in hypothalamic‐pituitary‐ovarian function secondary to GnRH treatment.RESULTS All six patients ovulated in response to clomiphene‐hCG therapy after 1–3 courses of GnRH treatment. The ovulatory response to clomiphene‐hCG continued during follow‐up periods of 5 months to 5 years. The initial hormonal change induced by GnRH treatment was a rise in the basal serum FSH level and a return of the FSH response to GnRH loading. This was followed by an increase in serum LH and the return of LH response to GnRH loading. In all six patients, pulsatile LH secretion was absent before starting GnRH treatment. GnRH treatment produced LH pulses in five of the six patients, although the pulse frequency was less than that in normally cycling women. A further increase in the pulse frequency was observed during clomiphene therapy.CONCLUSIONS Alternate‐day GnRH administration is effective in inducing responsiveness to clomiphene in patients with anovulation secondary to weight loss.
Effects of norethisterone on bone related biochemical variables and forearm bone mineral in post‐menopausal osteoporosis
Authors: Horowitz Michael , Wishart Judith M. , Need Allan G. , Morris Howard A. , Nordin B. E. Christopher 
Published: March 2008

SummaryOBJECTIVE Progestogens may be a useful therapeutic alternative to oestrogen in the treatment of post‐menopausal osteoporosis. The purpose of this study was to determine the effects of norethisterone on forearm bone mineral content and bone related biochemical variables in patients with post‐menopausal osteoporosis.DESIGN/PATIENTS The effects of treatment with norethisterone (5 mg/day) on bone related biochemical variables was determined in 44 women with post‐menopausal osteoporosis. The effects of norethisterone on forearm bone mineral content (FMC) were evaluated by serial measurements in 39 of these women.MEASUREMENTS We measured forearm mineral content, forearm mineral density, forearm fat content and fat‐corrected forearm mineral density. Biochemical measurements included plasma calcium and plasma calcium fractions (ionized, protein bound, complexed and ultrafiltr‐able), alkaline phosphatase, bicarbonate, phosphate, albumin and globulins, serum parathyroid hormone, osteocalcin and 1,25‐dihydroxyvitamin D, radiocalcium (45Ca) absorption and fasting urinary calcium/creatinine, sodium/creatinine, phosphate/creatinine and hydroxypro‐line/creatinine molar ratios.RESULTS After 4 months of treatment norethisterone produced a fall in plasma calcium (mean ± SEM from 2 40 ± 0 14 to 2 32 ± 0 13 mmol/l, P < 0 001), primarily in the non‐ionized calcium, due to a decrease in plasma bicarbonate (from 29 ± 0–28 to 27 ± 0–28 mmol/l, P < 0 001). There were decreases in urinary calcium/creatinine (from 0 41 ± 0 03 to 019 ± 0 02, P < 001) and sodium/creatinine (from 15 ± 11to10 ± 0 93, P< 0 001) molar ratios and a rise in the renal tubular maximum for calcium reabsorption (TmCa) (from 2 36 ± 0 041 to 2 55 ± 0 059 mmol/l of glomerular filtrate, P < 0 001). Plasma phosphate, urinary phosphate/creatinine and tubular maximum for phosphate reabsorption (TMP) all fell (P<001). Both the urinary hydroxyproline/creatinine (P < 0 001) and plasma alkaline phosphatase (P < 0 001) fell. Serum parathyroid hormone rose from 41 ±0 36 to 5‐5 ±0–51 pmol/l (P < 0 02) and radiocalcium absorption increased from 0 67 ±0 08 to 0 81 ±0 10 fx/h (P < 0 01). There was no change in serum 1,25‐dihydroxy vitamin D. After treatment with norethisterone for 4 months there was an increase in forearm bone mineral content (P<0 05) and a decrease in forearm fat content (P < 002). After two years treatment with norethisterone fat‐corrected forearm bone mineral content rose (mean change 17‐0 ± 5‐5 mg/cm, P < 0 01).CONCLUSIONS These results suggest that norethisterone prevents bone loss in post‐menopausal osteoporosis by decreasing bone turnover, has a vitamin‐D independent effect on intestinal calcium absorption, and increases serum parathyroid hormone levels.
Tissue resistance to 1,25‐dihydroxyvitamin D without a mutation of the vitamin D receptor gene
Authors: Hewison M. , Rut A. R. , Kristjansson K. , Walker R. E. , Dillon M. J. , Hughes M. R. , O'Riordan J. L. H. 
Published: March 2008

SummaryOBJECTIVE Hereditary vitamin D resistant rickets (HVDRR) is characterized by severe rickets and is often accompanied by alopecia. Mutations in the gene encoding the vitamin D receptor have been found in this condition. In a patient with the characteristic phenotype we have investigated the functional defect and sequenced the gene to seek a mutation.DESIGN Patient and control cell lines prepared from skin fibroblasts and peripheral blood lymphocytes were used to measure binding of 1,25(OH)2D3 and to isolate vitamin D receptor mRNA. VDR cDNA was sequenced and transfected into receptor defective cells.PATIENT A child with alopecia diagnosed as having rickets due to resistance to 1,25(OH)2D3.MEASUREMENTS Cytosolic binding and nuclear association of 1,25(OH)2D3 were determined in patient and control cells, and functional response to 1,25(OH)2D3 assessed by measurement of 24‐hydroxylase activity. VDR mRNA was prepared, reverse transcribed, and cDNA sequenced. VDR cDNA was also transfected into VDR‐deficient CV‐1 cells and functional response to 1,25(OH)2D3 assessed by co‐transfection with a chloramphenicol acetyltransferase (CAT) reporter plasmid.RESULTS VDR from the patient were able to bind 1,25(OH)2D3 but showed no nuclear localization resulting in an absence of functional response to 1,25(OH)2D3. Sequencing revealed that the VDR coding region was normal. Expression studies of the patient's VDR showed functionally normal VDR as evidenced by normal trans‐activation in the presence of 1,25(OH)2D3.CONCLUSION These data indicate a new cause of tissue resistance to 1,25(OH)2D3 which occurs in the absence of mutations in the coding region of VDR gene and which is characterized by defective nuclear localization of this receptor.
The effect of morphine and naloxone administration on maternal oxytocin concentration in late pregnancy
Authors: Lindow Stephen W. , van der Spuy Zephne M. , Hendricks M. Salie , Nugent Fiona A. , Dunne Timothy T. 
Published: March 2008

SummaryOBJECTIVE Modification of the inhibitory control of oxytocin secretion by endogenous opiates in late pregnancy may be one of the factors involved in the onset of labour. The interrelationships between exogenously administered opioids and oxytocin may demonstrate activity of this control mechanism.This study was undertaken to investigate the effect of an opiate and an opiate antagonist on maternal oxytocin levels in late pregnancy.DESIGN Patients were randomized to receive either morphine (5 mg), naloxone (2.4 mg) or sterile water (1 ml) intravenously.PATIENTS Thirty women with singleton pregnancies greater than 36 weeks gestation who were not in labour were studied.MEASUREMENTS Blood for peripheral oxytocin levels was sampled every 2.5 minutes for 15 minutes before and 15 minutes after administration of the assigned substance. Oxytoxin was measured by radioimmunoassay. Peripheral β‐endorphin levels were measured at the beginning and end of the study.RESULTS There was no significant change in the maternal oxytocin concentration after administration of either morphine, naloxone or sterile water compared to pretreatment levels. β‐Endorphin levels did not change significantly, either from the beginning to the end of the study, or between groups.CONCLUSION In late pregnancy exogenous opiates and opiate antagonists have no effect on maternal peripheral oxytocin levels.
Hypercalcaemia due to parathyroid hormone‐related protein: long‐term circulating levels may not reflect tumour activity
Authors: Savage Mark W. , Fraser William D. , Bodmer Charles W. , Ginty Andrew F. , Gallagher James A. , Robinson John , Williams Gareth 
Published: March 2008

SummaryParathyroid hormone‐related protein is responsible for the hypercalcaemia caused by many tumours. Measurement of parathyroid hormone‐related protein is becoming more accessible with the introduction of commercial assays. We report a case of hypercalcaemia of malignancy secondary to parathyroid hormone‐related protein in a woman with renal carcinoma. The parathyroid hormone‐related protein was assayed using a new immuno‐radiometric assay. We demonstrated an initial fall in parathyroid hormone‐related protein and calcium levels after surgery and a rise in both before clinical relapse. However, the clinical relapse was itself associated with a fall in serum parathyroid hormone‐related protein, nephrogenous cAMP and calcium, suggesting that the tumour had stopped producing parathyroid hormone‐related protein or perhaps that post‐translational processing had occurred as the tumour advanced. The tumour was investigated for parathyroid hormone‐related protein mRNA content using reverse transcriptase polymerase chain reaction, both at diagnosis in surgically removed material, and using post‐mortem specimens. The level of parathyroid hormone‐related protein mRNA, while present, was much reduced in the recurrent tumour suggesting that active parathyroid hormone‐related protein production fell substantially as the tumour advanced. This case suggests that, although demonstration of parathyroid hormone‐related protein in hypercalcaemia is useful for diagnosis, tumoral secretion of this product may alter.
Lymphocytic traffic and homing into target tissue and the generation of endocrine autoimmunity
Authors: Pozzilli P. , Carotenuto P. , Delltala G. 
Published: March 2008

SummaryEndocrine autoimmunity is known to be characterized by the presence of specific autoantibodies and from the histopathological point of view by lymphocytic inflitration in the target tissue. The presence of mononuclear cell infiltrates is the pathological hallmark of most endocrine diseases characterized by an autoimmune process directed against antigens expressed on endocrine cells. Infiltrating cells can usually be detected by biopsy or by using other, non‐invasive, techniques. However, in endocrine tissue such as the islets of Langerhans and the adrenal glands it is difficult to perform biopsies and diagnosis of the autoimmune process is dependent mainly upon detection of specific autoantibodies. A crucial aspect of endocrine autoimmunity and of all processes of organ specific autoimmunity is why and how lymphocytes migrate from primary lymphoid tissue to their specific targets. This occurs mainly through contact with specific adhesion molecules which enable lymphocytes to adhere to the endothelial vessels. In close proximity to the target tissue. In this review we discuss the homing of peripheral mononuclear cells into target endocrine tissues and the mediating role of adhesion molecules.
Ovarian stromal hypertrophy in hyperandrogenic women
Authors: Dewailly Didler , Robert Yann , Helln Isabelle , Ardaens Yves , Thomas‐Desrousseaux Patricla , Lemaltre Laurent , Fossati Plerre 
Published: March 2008

SummaryOBJECTIVE By using vaginal endosonography, ovarian stromal hypertrophy has been shown to be a strong diagnostic feature of polycystic ovarian syndrome and related states. However, this sign is difficult to quantify and to correlate with other findings because of its subjectivity. We have evaluated the use of computer assisted analysis of ultrasound scans to provide more objective measurements of ovarian structure and size.DESIGN We used a computer assisted method for the reading of ultrasound scans. It allowed selective calculation of the stromal area by subtraction of the cyst area from the total ovarian area on a longitudinal ovarian section.PATIENTS A consecutive series of 57 patients with hyper‐androgenism (group 1), 17 patients with hypothalamic anovulation (group 2) and 20 normal women (group 3).RESULTS By computerized measure, 75% patients from group 1 had a bilateral stromal area above the mean +2 SD (700 mm2) of women from group 3. All patients from group 2 were below this threshold. Serum LH level was above the normal range in 45% patients from group 1. The stromal area correlated positively with the serum A4‐androstenedione (r= 047, P < 0.005) and 17α‐hydroxy‐progesterone (r= 039, P < 0.005) levels, exclusively in group 1. It did not correlate with the basal serum testosterone, LH or Insulin levels. The cyst area did not correlate with any hormonal parameter.CONCLUSION Ovarian stromal hypertrophy is a frequent and specific feature of hyperandrogenism. It correlates with the ovarian androgenic dysfunction. Its presence is not always linked with elevated serum Immunoreactive LH levels. Further data are needed to elucidate the role of insulin and ovarian growth factors.
Androgen suppressive effect of GnRH agonist in ovarian hyperthecosis and virilizing turnours*
Authors: Pascale Mirae‐Mirakian , Pugeat Michel , Roberts Marc , Rousset Hugues , Déchaud Hanri , Dutrleux‐Berger Nicole , Tourniaire Jacques 
Published: March 2008

SummaryOBJECTIVE Recent studies have suggested that androgen secretion by ovarian virllizing tumours may be gonadotrophin dependent. The aim of this study was to investigate the suppressive effect of GnRH agonist administration on androgen secretion. In women with such tumours.DESIGN AND PATIENTS A single 1.m. Injection Of D‐Trp‐6‐GnRH (GnRHa), 3·75 mg, was given to five unrelated patients referred for clinical symptoms of virilization with plasma testosterone (T) levels greater than 7 nmol/l but with normal dehydroeplandrosterone sulphate (DHEAS) levels. Diagnoses of adrenal tumour or a non‐classical 21‐hydroxylase deficiency were screened for by the dexamethasone suppression test, ACTH stimulation test and adrenal CT scanning, and were ruled out in all patients. The one premenopausal patient received cyproterone acetate in a dose of 50 mg twice dally for 3 weeks, starting 1 week before GnRHa administration.MEASUREMENT Testosterone, androstenedione (A), DHEAS, 17‐hydroxyprogesterone (OHP), LH and FSH plasma concentrations were measured by radioimmunoassay of blood samples taken before and 3 weeks after GnRHa.RESULTS In each patient, GnRHa suppressed gonadotrophin levels and reduced T and A to the range for normal control women. With these results, and because accurate localization of an ovarian androgen secreting tumour could not be achieved by pelvic ultrasonography and CT scanning, exploratory laparotomy was undertaken. A Sertoll‐Leydig cell tumour was found in the premenopausal patient, and granulosa cell tumour, hllus cell tumour and two hyperthecoses in the four post‐menopausal patients. After bilateral ovarlectomy and hysterectomy in the post‐menopausal woman and after unilateral ovarlectomy in the premenopausal women, androgen levels were normalized.CONCLUSIONS In virllized women, the findings of Increased serum testosterone with normal gonadotrophin levels and GnRHa suppression of gonadotrophins leading to normalization of testosterone levels, suggest that various ovarlan androgen‐secreting tumours, as well as hyperthecosis, are not autonomous but apparently depend upon continuous gonadotrophin stimulation.