bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of plasma low density lipoprotein subfractions to oestrogen replacement therapy following surgical menopause
Authors: Griffin Bruce , Farish Elizabeth , Walsh David , Barnes Judith , Caslake Muriel , Shepherd James , Hart David
Published: March 2008

OBJECTIVE Epidemiological studies suggest that postmenopausal oestrogen replacement reduces the incidence of cardiovascular disease. The purpose of this study was to establish the effects of oestrogen replacement therapy on subfractions of plasma low density lipoprotein in bilaterally oophorectomized women.

DESIGN In a placebo controlled, double‐blind study, patients were randomized on a two to one basis to receive either oestradiol valerate (2 mg/day) or placebo respectively for a period of 16 weeks.

PATIENTS Seventeen women aged 28–51 years who had all had hysterectomy and bilateral oophorectomy at least 2 months before recruitment were assigned to either the active (n= 12) or placebo (n= 5) group.

MEASUREMENTS Plasma lipids, lipoproteins, apolipoproteins and LDL subfractions were determined immediately before and after the treatment period. LDL subfractions were isolated directly from plasma by density gradient ultracentrifugation within 24 hours. Non‐parametric statistical analysis was carried out within each group using Wilcoxon's signed rank test for matched pairs.

RESULTS After 16 weeks of treatment, HDL cholesterol, apo A‐1 and HDL‐2 were increased in the group receiving oestrogen (HDL cholesterol +12%, P < 0.01; apo A‐I + 14%, P < 0.01; HDL‐2 + 24%P < 0.01). While there were no significant changes in serum cholesterol, LDL cholesterol or triglycerides, the proportion and concentration of the least dense LDL‐I subtraction was decreased significantly (‐27%, P < 0.05). The LDL subtraction of intermediate density (LDL‐II) was decreased in eight subjects, while small, dense LDL‐III was unaffected. Overall, these changes resulted in an apparent shift in the distribution of LDL subfractions towards small, dense LDL‐III, although there was no net increase in the latter.

CONCLUSION In view of a similar and characteristic response of LDL subfractions to hypolipidaemic drugs that enhance the clearance of LDL via the LDL receptor, the present findings suggest that oestrogen promotes the preferential removal of LDL‐I and II by activating LDL receptors. As this effect is normally associated with a reduction in the circulating level of LDL, it should not be regarded as an unfavourable response to oestrogen replacement therapy.
Insulin‐like growth factor‐l blood levels in severely burned patients: effects of time post injury, age of patient and severity of burn
Authors: Abribat Thierry , Brazeau Paul , Davignon Isabelle , Garrel Dominique R.
Published: March 2008

OBJECTIVES Insulin‐like growth factor‐l (IGF‐I) is a polypeptide growth factor that stimulates protein synthesis. The aims of this study were to determine (1) the effect of a severe burn on blood IGF‐I levels and (2) the variables controlling IGF‐I level variations during recovery of these hypermetabolic patients.

PATIENTS Eleven patients, nine men and two women (age range 22–55 years) were studied for 25 days following a severe burn (18–75% of total body surface area, mean 36%). Nitrogen balances were recorded daily and total IGF‐I levels were measured every 3 days.

MEASUREMENTS IGF‐I was extracted from serum using a validated formic acid‐acetone methodology, then measured by a double antibody radioimmunoassay. IGF‐I levels were compared to those of a reference healthy population.

RESULTS Within 24 hours following injury, IGF‐I levels were low in all patients when compared to normal values for the same age range (mean ± SEM of all patients, 131 ± 26 μ g/I) They remained low for the first week (days 4 and 7, 109 ±16 μg/I), then increased to reach normal values at the end of the study period (days 10–16,144 ± 19 μg/l, P= 0 005 when compared to days 4–7; days 19–25, 206 ±30 μg/l, P= 0 008 when compared to days 10–16). IGF‐I levels were negatively correlated with age in the second phase of recovery only (days 10–16, r= ‐0–70, P<005; days 19–25, r= ‐0 75, P<0 01) and with severity of burn between days 19 and 25 (r= ‐0 62, P<0 05). The presence of bronchial burn injury tended to lower IGF‐I blood concentration (P= 0 08). Whereas IGF‐I concentrations increased in the later phase of recovery, nitrogen balances did not. As a result, there was no significant correlation between these parameters.

CONCLUSIONS IGF‐I levels followed a biphasic pattern in severely burned patients. They dropped dramatically in response to the traumatic shock, then increased during recovery. The degree of increase was dependent on the age of the patient and on the severity of the burn, but was not associated with an improvement in the nitrogen balance.
Reversibility of thyroid dysfunction induced by recombinant alpha interferon in chronic hepatitis C
Authors: Baudin Eric , Marcellin Patrick , Pouteau Michèle , Colas‐Linhart Nicole , Le Floch Jean‐Pierre , Lemmonier Catherine , Benhamou Jean‐Pierre , Bok Bernard
Published: March 2008

OBJECTIVE Thyroid dysfunction has been reported as a complication of interferon therapy. The aim of our study was to assess the risk factors and reversibility of thyroid disorders induced by interferon therapy.

DESIGN Prospective study.

PATIENTS A series of 68 patients with chronic hepatitis C completed a therapeutic trial of interferon alpha 2b (IFN), randomized for dose adaptation, lasting for 24 weeks.

MEASUREMENTS TSH and autoantibodies against thyroid were looked for at (‐ 2) weeks and 24 weeks in all patients. Blood samples obtained at (‐2), 12, and 24 weeks were stored for additional hormonal studies in patients who developed thyroid dysfunction. Such patients with thyroid dysfunction were followed up for at least one year.

RESULTS Only one out of 68 patients had abnormal TSH levels, and two had thyroid autoantibodies prior to interferon therapy. Eight patients (12%) developed thyroid dysfunction (five hypothyroidism and three hyperthyroidism) during treatment. In four patients (all of them with thyroid dysfunction, P< 0‐001) antimicrosomal, antithyro‐globulin, and/or anti‐TSH receptor antibodies appeared during interferon therapy. All patients recovered normal thyroid function within 15 years after interferon withdrawal.

No pretreatment risk factor was identified. The patients with thyroid dysfunction did not significantly differ from the others as regards the dose of interferon they received or the rate of normalization of transaminases.

CONCLUSION (i) A 12% incidence of thyroid dysfunction was observed under interferon therapy: (ii) secondary appearance under interferon therapy of elevated thyroid autoantibodies was a risk factor; (iii) the thyroid disorders induced by interferon were reversible.
Short and long‐term cardiovascular effects of growth hormone therapy in growth hormone deficient adults
Authors: Thuesen Leif , Jergensen Jens O. L. , Müller Jern R. , Kristensen Bent Ø. , Skakkebk Nieis E. , Vahi Nina , Christiansen Jens S.
Published: March 2008

OBJECTIVE Since GH substitution therapy is now available for adult GH deficient patients, information on the cardiovascular effects of GH substitution has assumed major clinical interest. We have therefore assessed cardiovascular effects of short and long‐term growth hormone substitution therapy in these patients.

PATIENTS AND MEASUREMENTS Doppler echocardiography was performed in 21 GH deficient patients after 4 months placebo and 4 months GH therapy, in a double blind cross‐over study. In an open design study, 13 patients were reinvestigated following 16 months and 9 patients following 38 months of GH therapy. Twenty‐one age and sex‐matched normal control subjects were also investigated.

RESULTS Heart rate was increased in placebo treated patients as compared to controls. After 4 months of GH treatment, heart rate showed a further Increase (10%, P<0·01) and seemed to remain elevated after 16 months of OH therapy. Systolic and diastolic blood pressures were significantly lower in placebo treated patients than in controls, and did not change significantly after OH treatment. The left ventricular diastolic diameter was reduced in patients as compared to controls, but increased after 4 months GH therapy (P>0·05) and seemed to increase further during prolonged GH treatment. Cardiac index was at the same level in controls and in placebo‐treated patients, but increased by 20% following OH therapy and remained elevated after 16 and 38 months (P < 0·05) of GH substitution.

CONCLUSION Following GH substitution in GH deficient adult patients, left ventricular diastolic dimensions increased and seemed to normalize, while heart rate and cardiac output were found to be increased to supra‐normal levels.
Effects of oestrogen on progesterone synthesis and arachidonic acid metabolism in human luteal cells
Authors: Fisch B. , Rose M. P. , Elder M. G. , Winston R. M. L. , Margara R. A. , Hillier S. G.
Published: March 2008

OBJECTIVE Locally produced oestrogens and prostaglandins (PGs) are implicated in the regulation of luteal lifespan in the human ovary. This study (1) assesses direct effects of these factors on progesterone synthesis in isolated luteal cells, and (2) explores interactions between luteal age and treatment with gonadotrophin or oestrogen on the metabolism of arachidonic acid (prostaglandin precursor) by steroidogenic luteal cells in vitro.

DESIGN Primary monolayer cultures of human luteal cells obtained at different stages of the luteal phase were used to investigate the effect of oestradiol, catechol oestrogens (2‐ and 4‐hydroxyoestradiol), diethylstilboestrol, PGE2 and PGF2x on basal and human chorionic gonadotrophin (hCG) stimulated progesterone production in vitro. The role of PGs as modulators of luteal cell function was further investigated by studying the metabolic fate of radioactively labelled arachidonic acid in hormone treated (oestradiol and hCG) and control cultures, assessed by high performance liquid chromatography.

ATIENTS Corpora lutea were enucleated from nine women with regular ovulatory cycles undergoing microsurgical reversal of tubal sterilization. Granulosa cell aspirates were obtained from three patients undergoing in‐vitro fertilization treatment.

RESULTS PGE2 and PGF2α, at various concentrations did not have a consistent effect, whereas oestradiol, diethylstilboestrol (and 2‐hydroxyoestradiol in early luteal cell cultures) significantly inhibited basal and hCG stimulated progesterone biosynthesis. Evidence for direct inhibition of 3β‐hydroxysteroid dehydrogenase enzymic activity by oestradiol was obtained. Both major metabolic pathways of arachidonic acid (lipoxygenase and cyclo‐oxygenase) were operative in steroidogenic luteal cells recovered throughout the luteal phase. The ratio of PGE2 to PGF2 synthesis in vitro by human luteal cells from endogenously incorporated arachidonic acid did not change significantly with corpus luteum age, with PGE2 tending to predominate. Oestradiol treatment shifted arachidonic acid metabolism from the lipoxygenase towards the cyclo‐oxygenase pathway in cells isolated from ageing corpora lutea.

CONCLUSIONS Oestradiol, at relatively high concentrations, is a potent inhibitor of basal and hCG induced luteal cell steroidogenesis in vitro. No support is provided for the concept that luteolysis is mediated by local production of PGF2α. The putative luteolytic effect of oestradiol may entail reduced metabolism of arachidonic acid to lipoxygenase derived products by luteal cells rather than direct stimulation of prostaglandin production by itself.
Transport of thyroxine into cultured hepatocytes: effects of mild non‐thyroidal illness and calorie restriction in obese subjects
Authors: Lim Chen‐Fee , Docter Roel , Krenning Eric P. , van Toor Hans , Bernard Bert , de Jong Marion , Hennemann Georg
Published: March 2008

OBJECTIVE Inhibitors of cellular T4 transport leading to diminished plasma T3 production have been identified as 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF) and indoxyl sulphate in uraemia and bilirubin and non‐esterified fatty acids (NEFA) in critically ill patients with hyperbilirubinaemia. We question whether other factors are responsible for the altered thyroid hormone parameters observed in mild illness and during calorie restriction.

PATIENTS We studied (I) 18 non‐uraemic patients with non‐thyroidal illness (NTI) (T4 5±60, T3 ±1 1 and rT3 ±0 45 nmoI/I) with serum molar ratios of bilirubin:albumin ±0 17 and NEFA:albumin ±2 6. These molar ratios have been shown to be the minimum ratios which inhibited T4 transport into rat hepatocytes; (ii) four obese euthyroid subjects on 600 kcal/day for 10–14 days. This diet is known to inhibit the unidirectional T4 transport into human liver in vivo.

MEASUREMENTS We measured iodide production from 125I‐T4 by incubating rat hepatocytes with 10% human serum. The deiodination of T4 was used as an index of cellular transport of T4 in vivo.

RESULTS The mean iodide production from 125I‐T4 by rat hepatocytes in the presence of 10% serum from NTI patients (98±17%, mean±SD) was not significantly different from the normals (100 ±9%). Calorie restriction in euthyroid obese subjects resulted in a small but significant reduction (‐12%) of iodide production. Calorie restriction increased the total serum NEFA by 91 %.

CONCLUSIONS Our study demonstrates that CMPF, indoxyl sulphate, bilirubin and NEFA are not responsible for the inhibition of T4 tissue uptake in patients with mild illness. In addition, studies with calorie restricted obese subjects indicate that high concentration of NEFA during calorie restriction inhibits T4 tissue uptake. This inhibition may partly explain the lower plasma T3 during calorie restriction.
Decreased psychological well‐being in adult patients with growth hormone deficiency
Authors: Rosén Thord , Wirén Lena , Wilhelmsen Lars , Wiklund Ingela , Bengtsson Bengt‐Åke
Published: March 2008

OBJECTIVE Besides effects on body composition, bone mineral content and lipid metabolism, GH seems to influence quality of life, according to previous studies of limited numbers of patients with GH deficiency of childhood and adult origin. In this study psychological well‐being was assessed in a large number of patients with GH deficiency of adult origin.

DESIGN A follow‐up study of patients with hypopituitarism on routine replacement therapy with l‐thyroxine, cortisone acetate and sex steroids.

PATIENTS Eighty‐six patients (51 men, mean age 55.4 years and 35 women, mean age 54.9 years) diagnosed as having growth hormone deficiency on the basis of low IGF‐I concentration or a maximum GH response less than 5 mU/l after an insulin/glucagon tolerance test.

MEASUREMENTS Quality of life was measured with a self‐rating questionnaire, the Nottingham Health Profile, and the results were compared with the results from 86 controls matched for age, gender, marital status and socioeconomic class. Furthermore, the observed and expected number of disablement pensions were calculated.

RESULTS The mean total score of the patients was higher, i.e. worse (P<0.05), than that of the matching controls, indicating a higher level of perceived health problems among the patients. There were higher scores (poorer life quality) for energy (P<0.001), social isolation (P<0.01), emotional reaction (P= 0.056) and sex life (P<0.001) among patients compared with controls. Finally, the observed number of disablement pension among the patients tended to be higher than expected (19 vs 12.4, P= 0.09).

CONCLUSIONS Adult patients with GH deficiency have a decreased psychological well‐being in terms of energy, social isolation and emotional reaction and a disturbed sex life compared with normals. Furthermore, there is a tendency to a higher frequency of early retirement.
Hyperthyroidism secondary to a pituitary adenoma secreting TSH, FSH, alpha‐subunit and GH
Authors: Patrick A. W. , Atkin S. L. , MacKenzie J. , Foy P. M. , White M. C. , MacFarlane I. A.
Published: March 2008

A 51‐year‐old man had been treated for hyperthyroidism with antithyroid drugs for 8 years. He was then found to have a large pituitary adenoma with biochemical evidence of overproduction of TSH, FSH and alpha‐subunit. Subsequent immunocytochemical and tissue culture studies confirmed secretion of these hormones. In addition, the tumour stained for GH and was capable of GH production in vitro. This combination of hormones produced by a pituitary adenoma has not been previously reported.
Clinical and anatomical spectrum in XX sex reversed patients. Relationship to the presence of Y specific DNA‐sequences
Authors: Boucekkine C. , Toublanc J. E. , Abbas N. , Chaabouni S. , Ouahid S. , Semrouni M. , Jaubert F. , Toublanc M. , McElreavey K. , Vilain E. , Fellous M.
Published: March 2008

OBJECTIVE Testicular differentiation can occur in the absence of the Y chromosome giving XX sex‐reversed males. Although Y chromosomal sequences can be detected in the majority of male subjects with a 46,XX karyotype, several studies have shown that approximately 10% of patients lack Y material including the SRY gene. The aim of this study was to see if the classification of XX sex‐reversed individuals into three groups, Y‐DNA‐positive phenotypically normal XX males, Y‐DNA‐negative XX males with genital ambiguities and Y‐DNA‐negative true hermaphrodites can be applied to our cases.

DESIGN Endocrinological and genetic studies were conducted in 20 XX sex‐reversed patients.

PATIENTS Twenty patients with various phenotypes were studied. They were between 20 days and 35 years old. Ten presented ambiguous external genitalia (Prader's stages II to IV). After laparotomy or gonadal biopsy, the diagnosis was 46, XX true hermaphroditism in five, and XX male in 15.

MEASUREMENTS Blood samples were obtained from all patients for hormonal and molecular studies. Basal levels of testosterone, oestradiol and pituitary gonadotrophins were measured by RIA, In addition, two stimulation tests were performed: gonadotrophin stimulation with GnRH and testicular stimulation with hCG. Several Y‐specific DNA sequences of the short arm of the Y chromosome were analysed by Southern blot and polymerase chain reaction methods.

RESULTS In this study, three categories of XX sex‐reversed individuals were observed: phenotypically normal males with or without gynaecomastia, males with genital ambiguities, and true hermaphrodites. Endocrinological data were similar in XX males and in true hermaphrodites. Testosterone levels exhibited normal (n= 9) or decreased (n= 11) values. The hCG response was low. FSH and LH were elevated in 13 patients. Molecular analysis in ten patients showed varying amounts of Y material including the Y boundary and SRY. Ten patients with various phenotypes lacked Y chromosomal DNA. There was no relation between Leydig cell function (as indicated by testosterone levels before or after hCG stimulation) and the presence of Y chromosome material.

CONCLUSION Although the presence of Y‐specific DNA generally results in a more masculinized phenotype, exceptions do occur. In the Y‐DNA‐negative group, complete or incomplete masculinization in the absence of SRY suggests a mutation of one or more downstream non‐Y, testis‐determining genes.
Osmoregulation of vasopressin and thirst: comparison of 20% mannitol with 5% saline as osmotic stimulants in healthy man
Authors: Phillips E. M. G. , Butler T. , Baylls P. H.
Published: March 2008

OBJECTIVE Osmoregulation is normally studied using a 5% saline Infusion. This may be deleterious in fluid overloaded patients. Twenty per cent mannitol is another osmotic stimulant. This study aimed to compare 20% mannitol infusion with 5% saline as an osmotic stimulant to thirst and vasopressin secretion in normal volunteers.

DESIGN AND PATIENTS Eight healthy volunteers studied on 2 occasions in random order. Each study involved a 2‐hour Infusion period of either hypertonic (5%) saline (0·06 ml/kg/h) or hypertonic (20%) mannitol (0·07ml/kg/h).

MEASUREMENTS Plasma vasopressin (pVp), plasma sodium, plasma osmolality (pOsm), haematocrit (HCT), blood pressure, thirst, blood glucose and volume drunk at end of infusion.

RESULTS Five per cent saline infusion stimulated significantly higher levels of pOsm, pVp and thirst than 20% mannitol. Plasma sodium rose significantly during 5% saline infusion and fell during 20% mannitol infusion. HCT fell and mean arterial pressure rose in both infusions but the changes were not clinically significant. Plecewise linear regression analysis defined the overall threshold for pVp release for the two solutions as 5% saline, 292 mosm/kg and 20% mannitol, 291 mosm/kg, and the post threshold slope as 5% saline, 0·46 pmol/l pVp per mom and 20% mannitol, 0·30 pmol/l pVp per mosm. The threshold for thirst onset was 5% saline, 291 mosm/kg and 20% mannitol, 290 mosm/kg, and the post threshold slope, 5% saline, 0·58 cm thirst per mosm and 20% mannitol, 0·28 cm thirst per mom. The differences between the calculated osmotic thresholds and slopes post threshold for the two infusions were not significant for the pVp versus pOsm relationship. The difference between the cumulative volume drunk following the two infusions did not reach statistical significance. Mannitol caused a significant diuresls.

CONCLUSIONS Twenty per cent mannitol infusion is an effective osmotic stimulant to thirst and vasopressin release in normal individuals, but is less potent than 5% saline Infusion.
Increased insulin sensitivity in patients with aldosterone producing adenoma
Authors: Ishimori Masatoshi , Takeda Noriyuki , Okumura Syouji , Murai Toshihiro , Inouye Hiroshi , Yasuda Keigo
Published: March 2008

OBJECTIVE Primary aldosteronism is a recognized endocrine cause of glucose intolerance. A blunted insulin response to glucose in patients with primary aldosteronism is well known, but insulin sensitivity has not been thoroughly determined. We investigated insulin sensitivity and insulin secretion in patients with aldosterone producing adenoma.

DESIGN Glucose tolerance and insulin responses to glucose were evaluated using a standard 75 g oral glucose tolerance test in patients with aldosterone producing adenoma before and after surgery, and in control subjects. Parameters for insulin resistance (HOMA‐R) and pancreatic β‐cell function (HOMA‐βF) were derived from a homeostasis model assessment.

PATIENTS Fifteen patients with aldosterone producing adenoma and 41 control subjects with normal glucose tolerance matched for age and body mass index, were studied. Eight patients were re‐evaluated after surgical removal of the adenoma. In 5 patients 125I‐insulin binding to erythrocytes was also measured.

MEASUREMENTS Plasma glucose was measured by a glucose oxidase method. Plasma insulin, aldosterone and renin activity were measured by radioimmunoassay.

RESULTS Both fasting plasma glucose and insulin were lower in the patients than in the controls. Although the areas under the curve for plasma glucose during the oral glucose tolerance test did not differ, that for plasma insulin was less in the patients with hyperaldosteronism. Insulin sensitivity was increased in the patients, as evidenced by decreased HOMA‐R compared with controls, while HOMA‐βF was comparable between the groups. 125I‐insulin binding to erythrocytes was higher in 5 patients than in 19 normal controls. After surgical removal of adenoma, neither fasting plasma glucose nor the glucose area under the curve during the oral glucose tolerance test changed. However, fasting plasma insulin and the insulin area under the curve increased significantly. HOMA‐R increased and HOMA‐βF remained unaltered.

CONCLUSION Insulin sensitivity was increased in untreated patients with aldosterone producing adenoma. Enhanced insulin receptor binding may contribute to this increased insulin sensitivity.
Development and validation of a radioimmunoassay for follistatin in human serum
Authors: Gilfillan Christopher P. , Robertson David M.
Published: March 2008

OBJECTIVE Follistatin (FS/FSH‐suppresslng protein/activin‐bindlng protein) Is a single‐chain glycoprotein, structurally distinct from inhibin, that has been shown to have inhibin‐like activity in suppressing FSH secretion both in vivo and in vitro. The aim of these studies was to develop and validate a radioimmunoassay (RIA) for FS In human serum, and to describe the physiological variations of serum FS In humans.

PATIENTS Serum was collected from normal men, and normal women In the follicular and luteal phases of the menstrual cycle. Clinical samples were also collected from male patients with hypogonadism, post‐menopausal women and pregnant women in the first, second and third trimesters.

MEASUREMENTS A RIA for FS In human serum was developed using antisera raked against purified bovine FS and using bovine FS as tracer and standard. Serial dilutions of serum were non‐parallel to purified bovine FS standard in the RIA. The addition of sodium dodecyl sulphate (SDS 0·05%) to the assay buffer resolved the non‐parallelism suggesting that the interference of serum in the RIA was an assay matrix effect. To characterize the serum FS immunoactivity further, serum was fractionated by gel filtration on Sephadex G‐100. At neutral pH, FS immunoactivity eluted as a major peak in the molecular weight range > 200 kDa. In 0·1 M HCI, a second peak of FS immunoactivity eluted in the molecular weight range 30–60 kDa consistent with the known sizes of FS. This suggested that FS was dissociating from a larger complex. Fractions taken from the low molecular weight region diluted in parallel with bovine FS In contrast with fractions from the high molecular weight region which were non‐parallel. It Is concluded that the non‐parallelism of human serum in the FS RIA is due to the binding of serum FS to an unknown high molecular weight factor. This interference is eliminated by the Inclusion of 0·05% SDS in the assay buffer. The RIA in 0·05% SDS has been applied to the description of the normal and pathophysiological varlations of FS In human serum.

RESULTS There were no significant differences between FS levels In serum from hypogonadal men, normal women In the follicular phase of the menstrual cycle, post‐menopausal women and pregnant women from the first, second and third trimesters. FS levels in serum of women in the luteal phase of the menstrual cycle were significantly lower than all other groups. FS levels in normal men were significantly higher than those in both luteel phase women and women in the first trimester of pregnancy (P < 0.05).

CONCLUSIONS These findings argue against a role for circulating follistatin in the control of gonadotrophin secretion and suggest that the gonads and/or conceptus are not the primary source of follistatin immunoactivity in serum. The lower follistatin levels in the luteal phase of the menstrual cycle remain unexplained.
Relations of endogenous anabolic hormones and physical activity to bone mineral density and lean body mass in elderly men
Authors: Rudman Daniel , Drinka Paul J. , Wilsont Charles R. , Mattson Dale E. , Scherman Francis , Cuisinier Mary C. , Schultz Shiela
Published: March 2008

OBJECTIVES It has been proposed that declining activities of the somatotrophic or gonadotrophic axes, or sedentary life style, are partial causes for geriatric losses of bone mineral density (BMD) and of lean body mass (LBM). The present study tested these hypotheses by determining, in both free‐living and institutionalized elderly men, the correlations of bone mineral density (BMD), total body bone mineral content (TBBMC) and lean body mass (LBM) with the following predictor variables: age, body mass index, body weight, serum insulin‐like growth factor I (IGF‐I), serum testosterone, habitual physical activity and mobility.

SUBJECTS Forty‐nine independent, community‐dwelling older men, and 49 men of similar age residing in two Veterans Administration extended care facilities. The age range was 58–95 years.

MEASUREMENTS Serum IGF‐I and testosterone were measured by radioimmunoassay. Habitual physical activity in the independent men and mobility in the institutionalized men were estimated by standard instruments. LBM and bone status at nine skeletal sites were determined by dual X‐ray absorptiometry.

RESULTS The BMD and TBBMC values of the free living men were 4–20% higher than those of the institutionalized men. In the independent old men, serum testosterone was the strongest predictor of BMD and TBBMC, while age was the only predictor of LBM. In the chronically institutionalized men, age, body weight and immobility were the strongest predictors of body composition, and testosterone was correlated only with femoral neck BMD.

CONCLUSIONS In aging independent men, low levels of testosterone are associated with demineralization of the skeleton. Immobility and under‐weight are associated with the osteopenia of old men residing in nursing homes. In this cross‐sectional study of elderly men, there was no evidence of a relation of the somatotrophic axis to bone status or LBM, or of the gonadotrophic axis to LBM.
Serum thyreoglobulin: an early indicator of autoimmune post‐partum thyroiditis
Authors: Parkes A. B. , Black E. G. , Adams H. , John R. , Richards C. J. , Hall R. , Lazarus J. H.
Published: March 2008

OBJECTIVE The aim of this study was to assess whether autoimmune thyroid damage in post‐partum thyroiditis was accompanied by a significant rise in the concentration of thyroglobulin in the serum and whether its measurement could be useful In the prediction of the risk and severity of an episode of post‐partm thyroid dysfunction.

PATIENTS Fifty‐one women, who had taken part in a larger survey of post‐partum thyroiditis, were selected at random for this study. Fourteen women without elevated circulating thyroid autoantibodies and 21 with raised thyroid autoantibodies remained euthyroid throughout the post‐partum year. A third group of 14 women had raised thyroid autoantibody levels and showed one or more episodes of thyroid dysfunction during the course of the first year post partum.

MEASUREMENTS Thyroid autoantibodies were measured by ELISA, free T3 and free T4 by the Amerlex M method and TSH by an immunoradiometrlc method. Serum thyroglobulin was measured by a method free from interference by circulating endogenous thyroglobulin autoantibodies. Thyroid ultrasonography was performed using a General Electric RT3600 scanner operating at 7.5 MHz.

RESULTS Fourteen control women had a mean serum thyroglobulin concentration of 3.3 μg/l (SD 4.4; range <1–12jxg/l; 95% confidence interval up to 6.0μg/l). Twenty‐one thyroid autoantibody positive euthyroid women had a mean serum thyroglobulin level of 5.8 μgl I (SD 6.2; range <1–36 μg/l) which was not significantly different from that seen in the control group. Sixteen thyroid autoantibody positive women who showed one or more episodes of thyroid dysfunction during the postpartum period had a mean serum thyroglobulin of 31 μg/l (SD 24–8; range up to 88 μg/l) and this was significantly elevated compared with both the control and antibody positive groups (P < 0.001). Serum thyroglobulin concentrations at 3 months post partum correlated with the degree of post‐partum hypothyroidism (as indicated by the maximum TSH and the minimum free thyroxine concentrations post partum) and, in those cases where thyroid ultrasound examinations were performed, with the degree of lymphocytic infiltration of the thyroid gland.

CONCLUSIONS The data presented in this paper confirm the destructive nature of post‐partum thyroiditis and indicate that the measurement of serum thyroglobulin concentration could assist in the identification of those women at risk of post‐partum thyroiditis.
Less acidic forms of luteinizing hormone are associated with lower testosterone secretion in men on haemodialysis treatment
Authors: Mitchell Robert , Bauerfeld Christian , Schaefer Franz , Schärer Karl , Robertson William R.
Published: March 2008

OBJECTIVE Men with chronic renal failure treated by haemodialysis have raised levels of bioactive LH (B‐LH) and immunoreactive LH (I‐LH) but reduced B‐LH: I‐LH (B: I) ratio and testosterone (T) secretion. This study investigated the LH isoform distribution in serum from normal adult males and males on regular haemodialysis treatment.

DESIGN Four blood samples (2 ml) were obtained at 15‐minute intervals from a group of men on regular haemodialysis treatment. These samples were part of a larger pulse profile series and showed no evidence of LH pulsatility. The serum was pooled for each Individual patient. Blood (10 ml) was also drawn randomly from healthy male volunteers. The sera were chromatofocused on a 4‐ml mono‐P column attached to a fast performance liquid chromatography system. This procedure separates the LH isoforms according to their isoelectric point. The pH gradient was between pH 7 and pH 4.

PATIENTS The five men with chronic renal failure were aged between 18 and 40 years and had been on haemodialysis for a mean of 10 months (5–20). They were sampled the night prior to a dialysis session. The five normal healthy volunteers had never had any endocrine disorder diagnosed.

MEASUREMENTS An immunoradiometric assay and a commercially available (Delfia) immunofluorimetric assay were employed for detection of LH In the sera and in chromatofocusing fractions. B‐LH and testosterone were also measured in the sera.

RESULTS Hormone data (mean±SEM for normal and renal subjects respectively) were 15.5 IU/I±1.2 and 26.9 ±7.2 (B‐LH), 6 0 IU/I±0.3 and 16.5±4.8 (irmaLH), 5.7 ±0.5 and 13.6 ±4.8 (lluorLH), 25.2nmol/l±2.0 and 12.1 ±1.2 (T). The serum B:l ratios were 2.6±0.1 and 2.6±0.2 (controls, irmaLH and fluorLH respectively) and 1.7 ± 0.1 and 2.1 ± 0.1 (chronic renal failure group). Recovery of LH from the column was 111 ±12% (mean±SEM)by IRMA and 104 ±7% by IFMA for the ten FPLC runs. The median pi for the LH distribution measured by both assays was in the region 6.54–6.40 for subjects with chronic renal failure and 6.09–5.95 tor controls. Median pi was negatively correlated to the B‐LH:irmaLH (P<0.0001) and B‐LH:fluorLH ratios (P = 0.002) in the serum. Furthermore, the proportion of isoforms recovered in the pH region 6.25–5.50 increased with increasing T levels in the serum (P<0.004).

CONCLUSION The distribution of LH in serum of men on haemodialysis is more basic than in normal men. The greater the proportion of more acidic LH species, particularly those with a pi of between 5.50‐6.25, the higher the ratio of LH bioactivity to immunoactivity and consequently testosterone levels.
Successful localization of an occult ACTH‐secreting bronchial carcinoid tumour with 111indium‐DTPA labelled octreotide
Authors: Tsagarakis S. , Giannakenas C. , Vassilakos P. J. , Platis O. , Belenis I. , Kaskarelis J. , Rontoyiannl D. , Thalassinos N.
Published: March 2008

Ectopic ACTH secretion due to occult carcinoid tumours is an occasional cause of ACTH dependent Cushing's syndrome. In many cases the ectopic source may be obvious, but sometimes no obvious source is evident, the so‐called occult ectopic syndrome. Due to their small size, localization of such occult tumours, particularly bronchial carcinoids, may be extremely difficult. Whole body CT and verious sampling studies have been used but are not always successful in determining the site of such lesions. We report a 40‐year‐old patient with the ectopic ACTH syndrome due to a 0.6‐cm bronchial carcinoid tumour which was successfully localized by 111indium‐DTPA labelled octreotide scintigraphy.
Hypogonadotrophic hypogonadism with hyposmia, X‐linked ichthyosis, and renal malformation syndrome
Authors: Martul P. , Plneda J. , Levllllers J. , Vszquez J. A. , Rodriguez‐Soriano J. , Loridan L. , Diaz‐Perez J. L.
Published: March 2008

OBJECTIVE The aim of this study was the endocrinological, enzymatic, and genetic evaluation of a family with a complex syndrome associating hypogonadotrophic hypogonadism with hyposmia, X‐linked Ichthyosis and renal malformation.

DESIGN Hypothalamic‐pituritary‐testicular function, offaction, steroid sulphatase activity, and morphological renal studies were assessed. DNA molecular analyses were carried out In all the patients.

PATIENTS Two brothers and their maternal uncle showed the clinical picture of congenital Ichthyosis, hypogonadism, hyposmia and unilateral renal maldevelopment. MEASUREMENTS LH and FSH were determined by RIA basally and after GnRH stimulation, and the test repeated after a period of GnRH priming. Testosterone response to hCG was measured. Arylsulphatase C assay was performed as a measure of steroid sulphatase activity. DNA amplification analysis and Southern blot analysis of four Xp22.3 loci were performed.

RESULTS Low levels of gonadotophins, basally and after acute GnRH, Increased clearly after GnRH priming. Low testosterone levels Increased promptly after hCG. Subnormal levels of arylsulphatase C were detected. Hyposmia and renal hypoplasia or aplasia were demonstrated. A large Xp 22.3 deletion Including the genes responsible for X‐linked Ichthyosls (steroid sulphatase deficiency) and Kallmann syndrome was demonstrated.

CONCLUSIONS The absence of the gene encoding steroid sulphatase accounts for the X‐linked Ichthyosis in these patients, whereas the absence of the Kallmann syndrome gene accounts for hypogonadism, anosmia and for the single kidney found In two of the three patients.
Life events, daily stresses and coping in patients with Graves' disease
Authors: Kung Annie W. C.
Published: March 2008

OBJECTIVE The contribution of stress to the aetiology of Graves' disease (GD) remains controversial. We have therefore examined life events, dally stress and coping in patients with this disease. We wished to determine whether the clinical presentation of Graves' hyperthyroidism is associated with preceding stressful events.

DESIGN A prospective controlled study. Ninety‐five patients with newly diagnosed GD were compared to matched controls.

METHOD A self‐reporting questionnaire recalling life events, dally stress and coping In the twelve months preceding the diagnosis.

RESULT More Graves' disease patients than controls reported negative events (P<0·0005), whereas the number of subjects reporting positive events and neutral events were similar in both groups. Graves' disease patients also experienced more negative events (P<0·0001) and perceived them with higher ratings (P<0·0001). Each group had similar coping ability In terms of the number of coping methods and magnitude of utilization of these methods. Similarly, Graves' disease patients reported more dally hassle (P<0·0001) and had higher hassle scores (P<0·0001).

CONCLUSION Patients with Graves' disease experienced greater psychological stress and adverse events prior to the onset of the disease. As stress may alter the immune system, it could play an important role in precipitating the disease in subjects predisposed to auto‐immune thyroid disorders.
Effects of quinagolide (CV 205‐502), a selective D2‐agonist, on vascular reactivity in patients with a prolactin‐secreting adenoma
Authors: Bodmer C. W. , Atkln S. L. , Savage M. W. , Masson E. A. , White M. C.
Published: March 2008

BACKGROUND Quinagolide (CV 205 502) Is a dopamine D2‐receptor agonist which has proved effective In the treatment of prolactinomas, reducing both serum PRL and tumour size. Some of Its D2‐receptor effects are mediated via α‐adrenoceptors, which have a major influence on the control of vascular tone. The aim of this study was to examine the influence of quinagolide on In‐vivo dorsal hand vein vascular responses to noradrenaline In patients with a prolactinoma.

DESIGN AND PATIENTS Seven female patients with prolactinomas (age 37 (28‐46) years), Intolerant of bromocriptine, were studied before and after 3 months treatment with quinagolide (0.75‐1.5 mg/day). Patients were otherwise disease free, were taking no other medication, and had been on no other medication (Including bromocriptine) for at least 3 months prior to enrolment into the study.

MEASUREMENTS Vascular responses to locally infused noradrenaline were measured In dorsal hand veins using an established technique. PRL, oestradiol, FSH, LH, blood pressure and body mass Index were also measured before and after 3 months treatment.

RESULTS Quinagolide significantly reduced PRL in all 7 patients (1795 (696‐4680) (mean (range)) vs 488 (290‐868) mU/l, P=0.001), with no effect on the other parameters, including mean arterial pressure (88 (2) vs 87 (4) mmHg, P=0.6). Vascular reactivity to noradrenaline was significantly increased after 3 months therapy: log10 dose estimated to cause 50% vasoconstriction (ED50) 1.37 (0.12) vs 0.85 (0.12) ng/mln (P=0.003; a lower ED50 indicates less noradrenaline Is required to constrict the vein by 50%).

CONCLUSIONS Vasoconstrictor responses to noradrenaline were increased in all patients after 3 months treatment with quinagolide. Peripheral veins carry α‐adrenoceptors analogous to those of systemic resistance vessels. If this increased vasoconstrictor response In patients with prolactinomas was occurring in hypophyseal vessels, It would lead to reduced tumour blood supply. Quinagolide may therefore reduce tumour blood flow, which may be one factor responsible for its effectiveness In these patients.
Effect of daily low dose mifepristone on the ovarian cycle and on dynamics of follicle growth
Authors: Cameron Sharon T. , Thong K. Joo , Baird David T.
Published: March 2008

BACKGROUND AND OBJECTIVE The antiprogestin mifepristone has been shown to disrupt folliculogenesis and endometrial maturation and, therefore, has the potential to be used as a novel form of contraception. The purpose of this study was to Investigate further the effects of daily administration of a low dose of mifeprlstone (2mg) on the ovarian cycle and on the dynamics of follicle growth. SUBJECTS Six healthy female voiunteers were given 2mg mifepristone dally for 30 days following an ovulatory control cycle.

MEASUREMENTS Follicle growth was monitored with transvaginal ultrasonography and hormonal measurements in blood and urine were used to monitor effects on the ovarian cycle. In addition, concentrations of cortisol and ACTH in serum were measured to assess the effects of mifeprlstone on the pituitary‐adrenal axis. RESULTS Treatment with mifepristone retarded the follicular growth rate In all women (P= 0.01). Ovulation was inhibited in 4 of 6 subjects and appeared to be mediated through an effect on the hypothalamo‐pituitary axis, as no surge of FSH or LH occurred. In these subjects the domlnant follicle continued to grow and developed into a persistent follicle. In two cases the persistent follicle remained functional and ovulation occurred soon after stopping treatment. In the remaining two subjects, the dominant follicle developed into a non‐functioning cyst (>30mm) which persisted for one month after the end of the post‐treatment cycle. In the two subjects who ovulated, the LH surge was delayed by 6 and 7 days but was followed by a luteal phase of normal length. There was no significant change in the concentration of ACTH or cortisol suggesting that treatment with mifepristone in this dose has little if any effect on the pituitary‐adrenal axis.

CONCLUSlON These findings add further evidence to support the contraceptive potential of mlfepristone through effects on follicular development and on the menstrual cycle.
Long‐term effects of insulin‐like growth factor (IGF)‐I treatment on serum IGFs and IGF binding proteins in adolescent patients with growth hormone receptor deficiency
Authors: Wilson Kristin F. , Fielder Paul J. , Guevara‐Agulrre Jaime , Cohen Plnchas , Vasconez O. , Martinez V. , Martinez A. , Rosenbloom Arlan L. , Rosenfeld Ron G.
Published: March 2008

OBJECTIVE The aim of this investigation was to study the effect of relatively high dose IGF‐I therapy given for several months, on serum levels of IGF‐I, IGF‐II and IGFBP‐3, and on IGF‐I pharmacokinetics In patients with growth hormone insensitivity due to GH receptor dysfunction.

DESIGN AND PATIENTS Two adolescent subjects from Ecuador were treated with recombinant IGF‐I at a dosage of 120μg/kg s.c. twice dally, in combination with a GnRH analogue for 8 months.

MEASUREMENTS Serum was sampled at baseline and at 3–8 months, for determination of IGF‐I, IGF‐II and IGFBP‐3 by radioimmunoassay, and for evaluation of IGFBPs and IGFBP‐3 protease activity by Western ligand blot and protease assay, respectively.

RESULTS Peak serum IGF‐I levels ranged from 272 to 492μg/l. Mean serum IGF‐II levels were decreased concurrently with the increase in IGF‐I. Serum IGFBP‐3 levels failed to rise with prolonged IGF‐I treatment. There was no apparent change In the half‐life of IGF‐I during the treatment period.

CONCLUSIONS IGF‐I administration does not increase serum levels of IGFBP‐3 or significantly alter IGF‐I pharmacokinetics.
Recombinant human insulin‐like growth factor‐I decreases serum lipoprotein(a) concentrations in normal adult men
Authors: Oscarsson Jan , Lundstam Ulf , Gustafsson BJörn , Wilton Patrick , Edén Staffan , Wlklund Olov
Published: March 2008

OBJECTIVE Lipoproteln(a) is a lipoprotein fraction associated with atherosclerosis. The serum concentration of llpoprotein(a) has been shown to be mainly genetically determined but recently evidence for hormonal regulation has been presented. The aim of the present study was to Investigate the effects of insulin‐like growth factor‐I on serum lipoproteins, especially lipoprotein(a).

DESIGN The effects of one week of IGF‐I treatment were studied in an open trial.

SUBJECTS Ten healthy men, who participated In a pharmacokinetic study, were given recombinant human Insulin‐like growth factor‐I (40 μg/kg/day) as daily subcutaneous Injections.

MEASUREMENTS Serum samples for measurements of lipoproteins were taken after an overnight fast before and after 7 days of treatment.

RESULTS There was a decrease in serum lipoproteln(a) concentration (18.5±5.5%) in nine of the subjects, and a slight increase In one of the subjects with the lowest concentrations. Also serum apolipoprotein (b) (6.3±2.2%), serum cholesterol (10.6±1.8%) and serum triglyceride (14.8±4.8%) concentrations decreased. An unexpected finding was that fasting serum glucose concentrations Increased (13±4%).

CONCLUSION Insuiln‐like growth factor‐I is involved in the regulation of lipoprotein(a) concentrations, which might have novel therapeutic Implications.