bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of DHEA replacement on bone mineral density and body composition in elderly women and men
Authors: Villareal Dennis T. , Holloszy John O. , Kohrt Wendy M. 
Published: March 2003

OBJECTIVEDehydroepiandrosterone (DHEA) is a precursor for both oestrogens and androgens. Its marked decline with ageing may influence age‐related changes in tissues influenced by sex hormones. The aim of this study was to determine the effects of DHEA replacement on bone mineral density (BMD) and body composition in elderly women and men with low serum DHEA sulphate (DHEAS) levels.DESIGNProspective 6 month trial of oral DHEA replacement, 50 mg/day.PATIENTSExperimental subjects were 10 women and eight men, aged 73 ± 1 years. Control subjects were 10 women and eight men, aged 74 ± 1 years.MEASUREMENTSBMD, body composition, serum markers of bone turnover, serum lipids and lipoproteins, oral glucose tolerance, serum IGF‐I, total serum oestrogens and testosterone.RESULTSBMD of the total body and lumbar spine increased (mean ± SEM; 1.6 ± 0.6% and 2.5 ± 0.8%, respectively; both P ≤ 0.05), fat mass decreased (− 1.3 ± 0.4 kg; P < 0.01) and fat‐free mass increased (0.9 ± 0.4 kg; P ≤ 0.05) in response to DHEA replacement. DHEA replacement also resulted in increases in serum IGF‐I (from 108 ± 8 to 143 ± 7 μg/l; P < 0.01) and total serum testosterone concentrations (from 10.7 ± 1.2 to 15.6 ± 1.8 nmol/l in the men and from 2.1 ± 0.2 to 4.5 ± 0.4 nmol/l in the women; both P ≤ 0.05).CONCLUSIONSThe results provide preliminary evidence that DHEA replacement in those elderly women and men who have very low serum DHEAS levels can partially reverse age‐related changes in fat mass, fat‐free mass, and BMD, and raise the possibility that increases in IGF‐I and/or testosterone play a role in mediating these effects of DHEA.
Management of a pregnant patient with Graves' disease complicated by thionamide‐induced neutropenia in the first trimester
Authors: Davison S. , Lennard T. W. J. , Davison J. , Kendall‐Taylor P. , Perros P. 
Published: March 2003

A 31‐year‐old woman presented with neutropenia due to thionamide drug therapy for Graves' disease. She also reported 8 weeks of amenorrhoea and had a positive pregnancy test. Her drug therapy was discontinued and her neutropenia resolved uneventfully. The hyperthyroidism recurred a week later. After consideration of all treatment options, it was decided to observe until 14 weeks when an elective thyroidectomy was planned. Mother and fetus were monitored closely and both tolerated moderate hyperthyroidism well. At 14 weeks the patient underwent a total thyroidectomy after rendering her euthyroid with a short course of sodium ipodate. Labour was induced at 41 weeks. Delivery was complicated by fetal distress and precipitated a forceps delivery. A 3250 g male infant was born with poor Apgar score and required 2 h of ventilation. At 1 year, the child had reached all developmental milestones at appropriate times.Both mother and fetus may tolerate moderate thyrotoxicosis well in early pregnancy, an alternative that should be considered when thionamide drug therapy is contraindicated.
An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic–pituitary disease
Authors: Leong K. S. , Walker A. B. , Martin I. , Wile D. , Wilding J. , MacFarlane I. A. 
Published: March 2003

OBJECTIVE The insulin tolerance test (ITT) is usually regarded as the ‘gold standard’ for the assessment of the hypothalamic–pituitary axis (growth hormone (GH) and ACTH) but must be used with caution and is contra‐indicated in certain groups of patients. The glucagon stimulation test (GST) has previously been shown to be a good alternative when the ITT is contra‐indicated and like the ITT stimulates both GH and ACTH secretion. There is however limited data on the use of the GST in patients with hypothalamic–pituitary disease.DESIGN AND PATIENTS An audit of 500 GST was performed in 374 patients with hypothalamic–pituitary disease. Glucagon was administered via the subcutaneous route and bloods were taken at times 0 90 120 150 180 210 and 240 minutes.RESULTS In the vast majority peak GH (84·4%) and cortisol (93%) responses occurred between 120 and 180 minutes Little information was obtained from the 240 minute sample. The medical supervision required was minimal and the side‐effects encountered during this test were mild; 20% of the tests were associated with nausea occasionally with vomiting sweating or headaches. Four patients fainted but recovered quickly.CONCLUSIONS This large audit has shown that the glucose stimulation test is well tolerated and can easily be performed in an out‐patient setting with minimal medical supervision. The 240 minute sample added little additional information and could be omitted.
Decreased dopaminergic tone and increased basal bioactive prolactin in men with human immunodeficiency virus infection
Authors: Parra Adalberto , Ramírez‐Peredo Jorge , Larrea Fernando , Cabrera Víctor , Coutiño Blanca , Torres Indiana , Angeles Angélica , Pérez‐Romano Beatriz , Ruiz‐Argüelles Guillermo , Ruiz‐Argüelles Alejandro 
Published: March 2003

OBJECTIVE The aims of the study were: (1) to assess dopaminergic tone in a group of HIV infected men and the bioactivity and the molecular species of their circulating PRL in comparison with healthy men and (2) to search for a correlation between serum PRL and CD4+ T lymphocytes and viral load.DESIGN In a cross‐sectional study the effect of acute dopaminergic blockade with intravenous metoclopramide on serum PRL (both immunoreactive and biologically active), TSH and PRL circulating molecular isoforms was evaluated.PATIENTS Twenty untreated HIV infected men category C2 or C3, mean (SD) age 26·9 (6·3) years, were compared to 14 clinically healthy HIV‐negative men, age 25·4 (2·3) years.MEASUREMENTS Under fasting conditions and following metoclopramide administration duplicate measurements of serum immunoreactive PRL, bioactive PRL (PRL dependent Nb2 lymphoma cell assay) and immunoreactive TSH were performed. The molecular species of circulating PRL were determined by immunoblot analysis, CD4+ T lymphocytes by flow cytometry and the viral load using a nucleic acid sequence‐based amplification assay.RESULTS In HIV infected men fasting bioactive (but not immunoreactive) PRL was higher (P = 0·03), but the stimulated PRL (both immunoreactive and bioactive) was lower than in healthy men throughout the test (P ≤ 0·01). Fasting serum TSH was similar in HIV‐infected and healthy men while its response to metoclopramide was absent in the former but not in the latter (P = 0·049). A 23·5‐kD PRL was the predominant circulating isoform both in patients and healthy men. Considering HIV‐infected and healthy men, CD4+ T lymphocytes correlated negatively with fasting bioactive PRL (P = 0·008) and positively with the area under the PRL (both immunoreactive and bioactive) curves (P < 0·001). The viral load was negatively correlated with the area under the curve of the bioactive/immunoreactive ratio (P = 0·008).CONCLUSIONS The raised fasting bioactive PRL, the diminished response of both immunoreactive and bioactive PRL and the absent TSH response to metoclopramide in HIV infected men, suggest the existence of a decreased, but not absent dopaminergic tone. A monomeric form of PRL was the predominant circulating species, as in healthy men, and this hormone seems to be associated both with CD4+ T lymphocytes and the viral load.
Desmopressin stimulation test before and after pituitary surgery in patients with Cushing's disease
Authors: Losa Marco , Mortini Pietro , Dylgjeri Suela , Barzaghi Raffaella , Franzin Alberto , Mandelli Carlo , Giovanelli Massimo 
Published: March 2003

OBJECTIVE The desmopressin test has been proposed as a useful tool for the differential diagnosis of Cushing's disease. The aim of our study was to investigate, in a large series of patients with Cushing's disease, the incidence of a positive ACTH and cortisol response to desmopressin. Moreover, we repeated the test soon after surgery to verify its usefulness in the assessment of early and late surgical results.PATIENTS AND METHODS One hundred and seven consecutive patients with Cushing's disease, 89 female and 18 male patients, with a mean age of 37·2 ± 1·3 years, were studied. All patients, except three, repeated the test 5–6 days after surgery. Desmopressin (10 µg) was injected i.v. and blood samples were drawn 15, 30, 45 and 60 minutes thereafter. Plasma ACTH and serum cortisol were measured in duplicate by commercially available immunoassays. A positive response to desmopressin was considered to be a plasma ACTH and serum cortisol increment of at least 30% and 20% above baseline, respectively.RESULTS Mean basal plasma ACTH level was 17·3 ± 1·7 pmol/l and rose to a peak level of 42·7 ± 4·9 pmol/l at 15 minutes Mean basal serum cortisol level was 574 ± 19 nmol/l and rose to a peak level of 814 ± 28 nmol/l at 45 minutes. ACTH and cortisol incremental changes were inversely correlated with their respective basal levels. Ninety patients (84·1%) had an ACTH and 84 patients (78·5%) had a cortisol response to desmopressin. Several clinical and demographic characteristics were not significantly different among desmopressin responders and non responders, except that basal ACTH and cortisol levels were significantly higher in desmopressin non responders (27·2 ± 8·3 pmol/l, 781 ± 86 nmol/l) than in desmopressin responders (15·4 ± 1·2 pmol/l, 535 ± 14 nmol/l). Disappearance of the ACTH and cortisol response to desmopressin after surgery occurred in 50 of 87 (57%) ACTH responders and in 57 of 81 (70·4%) cortisol responders, respectively. However, concordance between the desmopressin test and surgical outcome was not complete. Indeed, 18 patients considered in remission still showed an ACTH increase after desmopressin and, on the contrary, four patients with disappearance of the ACTH response had persistence of hypercortisolism. During follow‐up monitoring, three patients, who had persistence of the ACTH response to desmopressin, relapsed 24, 38 and 54 months after surgery.CONCLUSIONS Desmopressin administration elicits a significant rise in ACTH and cortisol levels in the majority but not all patients with Cushing's disease. There is a good, but not complete, concordance between the response to the desmopressin test and the surgical outcome. Our preliminary data show that persistence of the ACTH response to desmopressin in the early postoperative period might be associated with a higher risk of late relapse.
Fat distribution in obese women is associated with subtle alterations of the hypothalamic–pituitary–adrenal axis activity and sensitivity to glucocorticoids
Authors: Duclos M. , Gatta B. , Corcuff J.‐B. , Rashedi M. , Pehourcq F. , Roger P. 
Published: March 2003

OBJECTIVES Obesity with abdominal body fat distribution (A‐BFD) and hypothalamic‐pituitary‐adrenal (HPA) axis activity are somehow linked, but the exact interactions still need clarification. Obese subjects display normal circulating plasma cortisol concentrations with normal circadian rhythms. However, when the HPA axis is pharmacologically challenged, body fat distribution matters and then A‐BFD obese women differ from those with subcutaneous body fat distribution (P‐BFD). We hypothesized that lower dose provocative and suppressive tests than those used to diagnose hypercortisolism of tumour origin or adrenal insufficiency would shed some light on the characteristics of the HPA axis activity in relation with body fat distribution.PATIENTS AND METHODS Fifty premenopausal obese women were grouped according to their body fat mass distribution. Their plasma cortisol responses to (i) two low doses of dexamethasone (0·25 and 0·5 mg) with (ii) low dose of the ACTH analogue tetracosactrin (1 µg) were assessed. Salivary cortisol was also determined during the ACTH test.RESULTS A‐BFD differed from P‐BFD women in terms of HPA axis responsiveness. They had comparatively: (i) increased nocturnal cortisol excretion (9·38 ± 2·2 vs. 6·82 ± 0·91 nmol/µmol creatinine, A‐BFD vs. P‐BFD, respectively, P = 0·03); (ii) increased salivary cortisol response to ACTH stimulation (1 µg) [salivary cortisol peak: 33·4 (14·1–129) vs. 28·5 (13·2–42·8) nmol/l; salivary AUC: 825 (235–44738) vs. 537 (69–1420) nmol/min/l; A‐BFD vs. P‐BFD, P = 0·04 for both]; and (iii) increased pituitary sensitivity to dexamethasone testing [postdexamethasone (0·25 mg) plasma cortisol levels: 163 (26–472) vs. 318 (26–652) nmol/l and postdexamethasone (0·5 mg) plasma cortisol levels: 26 (26–79) vs. 33 (26–402) nmol/l; A‐BFD vs. P‐BFD, P = 0·01 for both).CONCLUSIONS These data demonstrate differences in the HPA axis activity and sensitivity to glucocorticoids between obese women differing in their body fat distribution, with both enhanced negative and positive feedback in those with abdominal obesity. Several mechanisms may explain these differences: central vs. peripheral hypotheses. Thus, abdominal obesity does not appear to be linked solely to one pathophysiological hypothesis.
Ventilation threshold as a measure of impaired physical performance in adults with growth hormone excess
Authors: Thomas Scott G. , Woodhouse Linda J. , Pagura Sonia M. , Ezzat Shereen 
Published: March 2003

Summaryobjective Fatigue is a prominent symptom among patients with GH excess and acromegaly. Identifying the physiological basis of such complaints and obtaining objective measures to quantify their severity remains an ongoing challenge. We investigated whether submaximal measures of aerobic performance can be used to assess GH excess‐associated fatigue objectively.design and patients To investigate this possibility we examined the relation between physical function and physical capacity in 12 patients with active acromegaly and persistent fatigue before and after 3 and 6 months of treatment with the long‐acting somatostatin analogue octreotide (LAR®).measurements Heart rate (HR) and rating of perceived exertion (RPE using Borg’s 10‐point scale) were measured during a 160‐metre self‐paced walk test (SPW). Maximum oxygen uptake (VO2max) and ventilation threshold (VeT: a measure of work rate when breathlessness develops) were measured during a progressive treadmill test to fatigue or symptom‐limited maximum. The Profile Of Mood States questionnaire (POMS) was used to quantify subjective feelings of fatigue and vigour. Morning fasting levels of GH and IGF‐I were measured using immunoassay of serum samples.results SPW speed at a fast pace of 1·69 ± 0·18 m/s was achieved with higher than normal HR (112 ± 15/min; normal = 102) and RPE (2·4 ± 1·2). Similar to GH‐deficient adults, VO2max (22·6 ± 6·4 ml.kg−1.min−1; normal ~30 ml.kg−1.min−1) and VeT (13·1 ± 2·9 ml.kg−1.min−1; predicted normal ~16 ml.kg−1(min−1) were low. However, VeT occurred at a normal fraction of VO2max (VeT/VO2max = 0·58). VeT was significantly increased and plasma IGF‐I levels reduced following 3 and 6 months of octreotide LAR® treatment. Reduction in circulating IGF‐I levels was correlated with improvement in reported vigour (r = 0·85) and VeT (r = 0·65) (P < 0·05).conclusions Our findings demonstrate impairment in physical function and physical capacity consistent with the perception of increased fatigue among acromegalic patients. These objective measures of compromised physical function are similar to the changes that we have reported previously in adults with GH deficiency. Taken together, these data suggest that a narrow window for GH/IGF‐I levels is required to maintain optimal physical function.
Isoflavone supplementation and endothelial function in menopausal women
Authors: Hale Georgina , Paul‐Labrador Maura , Dwyer James H. , Merz C. Noel Bairey 
Published: March 2003

Summaryobjective Despite strong observational evidence for a beneficial role of oestrogen in cardiovascular disease, recent trial results suggest that hormone replacement therapy (HRT) may have adverse effects in menopausal women with established coronary heart disease. Isoflavones are oestrogen analogues found in plants with oestrogen‐like properties and, because of a favourable side‐effect profile, may be ideal alternatives to HRT with respect to cardiovascular benefits. Endothelial function is a marker of cardiovascular health. We aimed to determine the effect of isoflavones on endothelial function using the brachial artery reactivity test.design and measurements Twenty‐nine healthy menopausal women underwent entry and exit brachial artery reactivity testing following randomization to 2 weeks of an oral soy isoflavone concentrate containing 80 mg of soy isoflavones (Archer Daniel Midland Inc., IL, USA) or placebo.results At study exit, there was no difference between placebo and isoflavone groups with respect to flow‐mediated dilation (%FMDmax), change (entry to exit) in %FMDmax or response to nitroglycerine (%TNG). Subgroup analyses assessing lipid and oestrogen effects did not produce any significant results.conclusions These results suggest that short‐term oral isoflavone supplements do not improve endothelial function in healthy menopausal women.
Thyrotoxicosis induced by alpha‐interferon therapy in chronic viral hepatitis
Authors: Wong Vincent , Fu Angela Xi‐Li , George Jacob , Cheung N. Wah 
Published: March 2003

Summarybackground and objective It has been well documented that treatment of chronic hepatitis B and C infection with interferon alpha (IFN‐α) can lead to the induction of thyroid autoantibodies and hypothyroidism. Thyrotoxicosis, however, is less frequently observed and less well characterized.patients and methods We reviewed the medical records of patients who developed thyrotoxicosis while receiving IFN‐α for either chronic hepatitis B or C infection at Westmead Hospital between 1996 and March 2001.results Ten patients (four males and six females) were found to have biochemical thyrotoxicosis. The patients could be divided into two groups with different characteristics. The first group consisted of six patients who had clinical manifestations consistent with Graves’ disease, with either diffuse uptake in thyroid scintigraphy and/or positive thyroid‐stimulating antibodies. They all required prolonged treatment with antithyroid medications. The second group included three patients who had transient thyrotoxicosis, with progression to hypothyroidism after resolution of thyrotoxicosis.conclusion Our study suggests that IFN therapy may provoke two different forms of thyrotoxicosis: a Graves’ disease picture or a biphasic thyroiditis pattern. The two entities should be differentiated, as they have different implications for treatment.
Gender and age influence the relationship between serum GH and IGF‐I in patients with acromegaly
Authors: Parkinson C. , Renehan A. G. , Ryder W. D. J. , O'Dwyer S. T. , Shalet S. M. , Trainer P. J. 
Published: March 2003

Summarybackground In patients with acromegaly serum IGF‐I is increasingly used as a marker of disease activity. As a result, the relationship between serum GH and IGF‐I is of profound interest. Healthy females secrete three times more GH than males but have broadly similar serum IGF‐I levels, and women with GH deficiency require 30–50% more exogenous GH to maintain the same serum IGF‐I as GH‐deficient men. In a selected cohort of patients with active acromegaly, studied off medical therapy using a single fasting serum GH and IGF‐I measurement, we have reported previously that, for a given GH level, women have significantly lower circulating IGF‐I.objective To evaluate the influence of age and gender on the relationship between serum GH and IGF‐I in an unselected cohort of patients with acromegaly independent of disease control and medical therapy.methods Sixty (34 male) unselected patients with acromegaly (median age 51 years (range 24–81 years) attending a colonoscopy screening programme were studied. Forty‐five had previously received pituitary radiotherapy. Patients had varying degrees of disease control and received medical therapy where appropriate. Mean serum GH was calculated from an eight‐point day profile (n = 45) and values obtained during a 75‐g oral glucose tolerance test (n = 15). Serum IGF‐I, IGFBP‐3 and acid‐labile subunit were measured and the dependency of these factors on covariates such as log10 mean serum GH, sex, age and prior radiotherapy was assessed using regression techniques.results The median calculated GH value was 4·7 mU/l (range 1–104). A significant linear association was observed between serum IGF‐I and log10 mean serum GH for the cohort (R = 0·5, P < 0·0001). After simultaneous adjustment of the above covariates a significant difference in the relationship between mean serum GH and IGF‐I was observed for males and females. On average, women had serum IGF‐I levels 11·44 nmol/l lower than men with the same mean serum GH (P = 0·03, 95% CI 1·33–21·4 nmol/l). Age significantly influenced the relationship and for a given serum GH, IGF‐I was estimated to fall by 0·37 nmol/l per year (P = 0·04, 95% CI 0·015–0·72).conclusions In keeping with previous observations of relative GH resistance in normal and GH‐deficient females we have observed lower serum IGF‐I levels for equivalent mean serum GH levels in females patients with acromegaly. This gender‐dependent difference is independent of disease activity and the use of concomitant medical therapy. Additionally, we have demonstrated that for a given serum GH level, age significantly influences IGF‐I concentrations in patients with acromegaly. These data have important implications for the use of serum IGF‐I and GH as markers of disease activity in acromegaly.
Bone metabolism markers and bone mass in healthy pubertal boys and girls
Authors: Van Coeverden S. C. C. M. , Netelenbos J. C. , De Ridder C. M. , Roos J. C. , Popp‐Snijders C. , Delemarre‐van de Waal H. A. 
Published: March 2003

Summaryobjective During puberty, bone growth and mineralization as well as bone turnover increase dramatically. The relation between height velocity and bone turnover is already known, but there are few studies in which both bone metabolism markers and bone mass throughout puberty have been measured.design Semi‐longitudinal study. In 155 healthy boys (12·0 ± 1·5 years; range 8·8–15·7 years) and 151 healthy girls (11·2 ± 1·6 years; range 8·2–14·0 years) markers of bone formation and bone resorption were measured as well as sex steroids, IGF‐1 and IGF‐BP3, together with bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine, femur and total body during puberty. All bone measurements were repeated after 1 year.results BMC and BMD increased throughout puberty in both sexes. Bone turnover markers increased significantly until maximum values were reached at stage G4 in boys and stage B3 in girls. Height velocity (HV) had a similar changing pattern. Sex steroids and IGF‐1 increased and reached adult values at pubertal stage 4. The correlations between bone metabolism markers and BMC were highly significant in boys, while correlations between bone metabolism markers and the increase in BMC over 1 year were significant in both sexes, as was observed for the correlations with HV.conclusions Our data suggest that bone metabolism markers are good predictors of bone mass in boys and of bone mass increase in both sexes. In early puberty, sex steroids stimulate the pubertal growth spurt in conjunction with GH and IGF‐1. The fast increase in height gives rise to an increase in bone turnover and bone mineral apposition. It is known that at the end of puberty high levels of oestradiol inhibit chondrocyte proliferation. This leads to a decline in height velocity and bone turnover. Bone mass still increases under the influence of sex steroids and IGF‐1. The data in our study confirm previous reports that markers of bone turnover relate positively to height velocity.