bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary excretion of pyridinium cross‐links in healthy women; the long‐term effects of menopause and oestrogen/progesterone therapy
Authors: Schlemmer A. , Hassager C. , Delmas P. D. , Christiansen C.
Published: March 2008

OBJECTIVES We investigated the effect of the menopause when followed longitudinally for a decade to evaluate whether women with an increased bone loss continue to have elevated urinary excretion of pyridinium cross‐links later in menopause. Furthermore, we investigated the effect of oestrogen/progesterone therapy on the urinary excretion of pyridinium cross‐links.

PARTICIPANTS In the cross‐sectional study: 18 healthy premenopausal, 142 healthy post‐menopausal women and 41 osteopenic post‐menopausal women. In the longitudinal study: 45 healthy post‐menopausal women followed up for 7‐10 years after the menopause; these women were further divided into two equal groups, according to their loss of forearm bone mineral content over 2 years.

In the oestradiol/progesterone double‐blind, placebo‐controlled 2‐year trial: early post‐menopausal women were given either hormone replacement therapy (n = 38) or placebo (n= 16).

MEASUREMENTS The urinary excretion of pyridinoline/ creatinine (Pyr/Cr) and urinary deoxypyridinoline/creatinine (D‐Pyr/Cr), two new markers of bone resorption.

RESULTS Pyr/Cr and D‐Pyr/Cr increased significantly after the menopause (Pyr/Cr, 77%; D‐Pyr/Cr, 98%, P < 0.001). Hormone replacement therapy reversed this increase towards premenopausal levels. Both pyridinium cross‐links remained fairly constant during the first decade of the menopause, when measured in the longitudinal study.

When the women were divided according to loss in forearm BMC., those with a loss greater than 3‐5%/2 years had significantly higher levels of pyridinium cross‐links (P<0.05‐0 01).

Furthermore, both Pyr/Cr and D‐Pyr/Cr were significantly higher in elderly osteopenic women (aged 68‐72 years) than in age‐matched non‐osteopenic women (P<0.01‐0.001).

CONCLUSIONS Both Pyr/Cr and D‐Pyr/Cr, two new markers of bone resorption, increased significantly at the time of the menopause, thereafter remaining fairly constant during the first post‐menopausal decade. Women with increased bone loss continue to have elevated urinary excretion of pyridinium cross‐links during the first decade of the menopause. This post‐menopausal change is reversed by hormone replacement therapy to the premenopausal level.
Interaction of salbutamol with pyridostigmine and arginine on both basal and GHRH‐stimulated GH secretion in humans
Authors: Ghigo E. , Arvat E. , Gianotti L. , Ramunni J. , Maccario M. , Camanni F.
Published: March 2008

OBJECTIVE It is well known that acetylcholine and arginine stimulate GH secretion while activation of β‐adrenergic receptors inhibits GH secretion in man. We aimed therefore to ascertain whether or not the inhibitory influence of β‐adrenergic receptors on GH secretion would over‐ride the stimulatory one of acetylcholine and arginine.

DESIGN We studied the interaction of salbutamol, a β2‐adrenergic agonist (SAL, 0.08 mg/kg orally) with pyridostigmine, a cholinesterase inhibitor (PD, 120 mg orally), or arginine (0.5 g/kg i.v.) on both basal and GHRH (1 μg/kg i.v.)‐stimulated GH secretion.

SUBJECTS Fourteen healthy male volunteers, aged 20–35 years, were studied.

MEASUREMENTS Serum GH was measured in duplicate by immunoradiometric assay.

RESULTS In study A, SAL inhibited the GH response both to GHRH (P < 0.01) and ARG(P<0.002). ARG enhanced the GHRH‐induced GH rise (P<0.01) but its effect was abolished (P<0.02) by SAL pretreatment. In study B, SAL inhibited the GH response both to GHRH (P<0.01) and PD (P< 0.02). PD enhanced the GH response to GHRH (P < 0.01) but its effect was abolished (P<0.05) by SAL pretreatment. In both studies, the GH response to GHRH alone was similar to that to the neurohormone when combined with ARG + SAL or PD + SAL.

CONCLUSION Our results show that β2‐adrenergic activation by salbutamol is able to inhibit not only the GH rise induced by GHRH, arginine and pyridostigmine, but even the potentiating effect of both arginine and pyridostigmine on the GH response to GHRH. They indicate that catecholamines, acetylcholine and arginine play a major role in GH secretion having opposite influences aimed to balance the function of the hypothalamus‐GH‐IGF‐l axis in man.
Appearance of thyroid stimulating antibody and Graves' disease after radioiodine therapy for toxic nodular goitre
Authors: Chiovato Luca , Santini Ferruccio , Vitti Paolo , Bendinelli Giovanna , Pinchera Aldo
Published: March 2008

A patient with toxic nodular goitre is described in whom radioiodine (131I) therapy paradoxically induced typical Graves' disease. This patient had a goitre with two autonomously functioning nodules suppressing uptake by the remainder of the gland. Circulating thyroid peroxidase antibody indicated the coexistence of focal lymphocytic thyroiditis. Radioiodine therapy was followed by the development of severe and persistent Graves' hyperthyroidism associated with diffuse 131I uptake by the gland. A second administration of 131I produced a further worsening of hyperthyroidism, and the appearance of ophthalmopathy. TSH‐receptor antibody and thyroid stimulating antibody were undetectable before 131I, appeared after the first administration of radioiodine, and showed a further increase after the second dose of 131I. We suggest that, in a patient genetically susceptible to thyroid autoimmunity, the release of TSH‐receptor antigenic components from follicular cells damaged by radioiodine therapy triggered an autoimmune response to the TSH‐receptor, thus turning a toxic nodular goitre into Graves' disease.
Glycoprotein hormone α‐subunit secretion in prolactinomas and in non‐functioning adenomas: relation with the tumour size
Authors: Warnet André , Porsova‐Dutolt Irena , Lahlou Najiba , Seret‐Beguet Domlnlque , Lajeunle Ellsabeth , Chanson Phillppe , Wolmant France , Lot Gulllaume , Guillausseau Pierre‐Jean , Roger Marc
Published: March 2008

OBJECTIVE Free giycoproteln hormone α‐subunit plasma levels have been reported to be Increased In glycoprotein hormone‐secreting adenomas and In acromegaly, but rarely In prolactinomas and In only two cases of Cushing's disease. The prevalence of elevated plasma α‐subunit levels. In patients with non‐functioning adenomas is still unclear. In addition, no previous work has described plasma a‐subunit levels. In a comprehensive series of adenomas characterized by In‐vivo secretion and/or Immunocytochemistry.

PATIENTS Thirty‐seven patients with definite prolactinomas and 48 with non‐functioning tumours characterized by Immunocytachemistry were studied, from a series of 145 consecutive patients Including 33 acromegallcs, 18 patients with glycoprotein hormone‐secreting adenomas and 9 with Cushing's disease.

MEASUREMENTS Plasma free α‐subunit was measured by radioimmunoassay in all patients and In a large sample of normal subjects to establish normal ranges according to sex, age and menstrual status. Tumour volume index was the product in cm3 of length, width and height of the adenoma as assessed by computerized tomography or magnetic resonance Imaging.

RESULTS Twelve of the 37 (32%) patients with prolactinomas had Increased plasma a‐subunit levels; their tumours were significantly larger with significantly higher plasma PRL levels than those of patients without Increased plasma α‐subunit levels(P < 0·02). All prolactlnomas above 50 cm3 were associated with α‐subunit secretion, whereas only 6 of 29 smaller tumours were similarly associated. Twelve of the 48 ‘non‐functlonlng’ adenomas actually secreted α‐subunit in vivo: 8 gonado‐trophin‐secreting, 2 ‘pure’α‐secreting, one with negative Immunocytachemistry and one necrotic adenoma. Their volumes were significantly higher than those of adenomas without increased plasma α‐subunit levels (P < 0·04). Plasma α‐subunit levels were increased in the 6 patients with TSH‐secreting adenomas, 8 of 12 with FSH‐secreting adenomas, 11 of 33 acromegalics and none of those with Cushing's disease.

CONCLUSION Plasma free α‐subunit levels were Increased in 49 of 145 patients (34%). For prolactinomas and ‘non‐functioning’ adenomas, α‐subunit hypersecretion was seen more often with larger tumours. Half of the cases with Increased free α‐subunit. In this series were patients harbouring an adenoma which did not stain for an intact glycoprotein hormone.
Serum lactogens possessed normal bioactivity in patients with lactation insufficiency
Authors: Livingstone Verity H. , Gout Peter W. , Crickmer Sean D. , Fox Kelly , Prior Jerllynn C.
Published: March 2008

OBJECTIVE insufficient breast milk is the most common reason for premature termination of breast‐feeding. The causes of lactation insufficiency are usually multifactorial; In a small percentage of cases it Is due to primary lactation failure of unknown origin. The aim of this study was to Investigate whether lactation insufficiency of unknown origin could be caused by serum lactogens that had reduced biological activity.

DESIGN Women with lactation Insufficiency of unknown origin and normal lactating controls were subjected to a standardized breast‐feeding test for assessment of milk production. Thirty minutes later, serum samples were obtained for determination of total lactogen bioactivity, using an in‐vitro bioassay, and levels of prolactin (PRL) and growth hormone (GH) using radiolmmunoassay (RIA).

PATIENTS Twelve lactating mothers with a clinical diagnosis of lactation insufficiency of unknown origin were compared with 12 matched mothers with normal lactation.

MEASUREMENTS The Nb2 lymphoma Cell bioassay was used to measure total lactogen bioactivity In sera. Conventional RIA kits were used to estimate serum PRL and GH concentrations.

RESULTS Mean milk yield on standardized test feed was 21·6 mi for patients and 146·5 mi for controls. In both patient and control groups the total serum lactogen bioactivity ranged from about 150 to 5000 mlU/l, while the serum RIA (PRL + GH) levels ranged from about 350 to over 7000 mlU/l. There was no evidence of lactogens with reduced bioactivity in the patients' sera.

CONCLUSION Lactation insufficiency In the women studied cannot be explained by serum lactogens that possess unusually low bioactivity.
Comparison of changes in bone mineral in idiopathic and secondary osteoporosis following therapy with cyclical disodium etidronate and high dose calcium supplementation
Authors: Orme S. M. , Simpson M. , Stewart S. P. , Oldroyd B. , Westmacott C. F. , Smith M. A. , Belchetz P. E.
Published: March 2008

OBJECTIVE Our clinical practice has been to offer treatment with cyclical disodlum etidronate and high dose calcium supplements (1500–1600 mg/day) to ail female patients with osteoporosis who are unable or unwilling to take hormone replacement therapy (HRT), and male osteoporotics. In a retrospective study we compared the effect of this treatment on measures of bone mineral over a 12‐month period in women wlth post‐menopausal and secondary osteoporosis. We also assessed its effects in 10 male osteoporotics.

DESIGN A retrospective analysis of 83 consecutive patients with osteoporosis who completed 12 months of treatment with disodlum etldronate and calcium and who had a dual energy X‐ray absorptiometry (DEXA) scan at baseline and foilowing 12 months of therapy.

PATIENTS The study Included 73 women (45 post‐meno‐pausal and 28 secondary osteoporotics) and 10 men with established osteoporosis as shown by spinal and femoral bone mineral densities (BMD) > 2 standard deviations (SD) below young normals, and radioiogical evidence of osteoporosis.

MEASUREMENTS Each patient had routine biochemistry at baseline, an X‐ray of thoracic and lumbar spine and a DEXA scan of lumbar spine (L2‐L4) and femoral neck. The DEXA scan was repeated following 12 months of therapy.

RESULTS There was no difference between increase in spinal BMD in the post‐menopausal (5·7%) versus secondary osteoporotic group (6·7%). There was a significant increase in spinal BMD at 12 months in the 10 male osteoporotics (9·0%, P < 0·01). No overall change in femoral neck BMD was noted.

CONCLUSIONS Cyclical disodium etidronate given with hlgh dose calcium supplements is equally effective in increasing spinal bone mineral density in post‐menopausal and secondary osteoporosis. It also results in a significant rise In spinal bone mineral density in male osteoporotics. Whether this produces a reduction in fracture rates is unknown.
The effect of growth hormone replacement on serum lipids, lipoproteins, apolipoproteins and cholesterol precursors in adult growth hormone deficient patients
Authors: Russell‐Jones D. L. , Watts G. F. , Welssberger A. , Naoumova R. , Myers J. , Thompson G. R. , Sönksen P. H.
Published: March 2008

OBJECTIVE Adult patients with growth hormone deflciency are thought to be at higher risk of mortallty from cardiovascular disease. We therefore investlgated the effect of recombinant human growth hormone (rhGH) replacement therapy on fasting serum concentrations of IIplds, lipoproteins and cholesterol precursors in adult growth hormone deficient patients.

DESIGN Double‐blind placebo controlled trial. Patients were randomly allocated to placebo or rhGH replacement therapy (0·018 Ulkglday for 1 month followed by 0·036 Ufkglday for 1 month).

PATIENTS Eighteen patients with severe growth hormone deficiency.

MEASUREMENTS Fasting lipid, lipoprotein and cholesterol precursors (lathosterol and mevalonic acid) were measured at baseline and after 2 months.

RESULTS In the rhGH treated group there was a significant fall in serum cholesterol (P < 0·01) (6·44 ±0·49 to 5·71 ± 0·48 mmol/l), LDL cholesterol (P < 0·02) (4·29 ± 0·49 to 3·62 ± 0·44 mmol/l), LDL cholesterollHDL cholesterol ratio (P < 0·02) (3·99 · 0·62 to 3·26 ± 0·39), apollpo‐protein B (P>0·01 (1·30 ± 0·11 to 1·15 ± 0·11 g/l) and mevalonic acid (P<0·05) (13·4 ±10·96 to 6·21 ± 1·91 μg/l). There were no significant changes In triglycerides, HDL cholesterol, apolipoprotein A1, lipoprotein (a) or lathosterol concentrations. In the GH treated group the rise in serum insulln was inversely correlated wlth the fall in cholesterol (P < 0·05), LDL cholesterol (P < 0·01) and apolipoproteln B (P < 0·01). There were no significant changes in any of the measured variables in the placebo group.

CONCLUSION We conclude that GH may be involved in the regulation of lipid and lipoprotein metabolism and that rhGH replacement therapy of adult GHD patients is associated with beneficial changes in lipid and lipoprotein profiles. The reduction in mevalonic acid is consistent with up‐regulation of hepatic LDL receptors caused by GH and this may explain the fall in LDL cholesterol and apolipoprotein B concentrations.
Serum insulin‐like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin
Authors: Landin‐Wllhelmsen Kerstin , Wllhelmsen Lars , Lappast George , Rosen Thord , Lindstedt Goran , Lundberg Per‐Arne , Bengtsson Bengt‐Áke
Published: March 2008

OBJECTIVE There Is a cllnlcal need for population based reference values for serum Insulin‐like growth factor I (IGF‐I). We have therefore determined serum IGF‐i concentrations In a random population sample from Sweden and have related the levels to age, sex, llfe style factors, blood pressure, body composition, blood llplds, plasma fibrlnogen, Parathyroid hormone (PTH) and osteocalcin.

PATIENTS Wlthln the framework of the WHO MONICA Project In the city of Göteborg, Sweden, 197 men and 195 women aged 25–64 years were studied.

RESULTS Women aged 25–34 years had higher IGF‐I concentration than men (mean 278 vs 227 μg/l) but In the interval 55–64 years values were lower In women than In men (158 vs 171 μg/l). IGF‐I correlated positively with height and inversely with age, body mass Index, systolic blood pressure and total cholesterol in both sexes. Negative relations between IGF‐I and hlgh density llpoprotelncholesterol, as well as with amount of tobacco smoked, were found in men, and between IGF‐I and diastolic blood pressure, triglycerldes and PTH in women. When age was allowed for in multivariate analyses, most of these relations disappeared. However, among men IGF‐l was positively assoclated with flbrlnogen and negatively with age and smoking. IGF‐I was negatively assoclated with age and coffee consumptlon in women.

CONCLUSION The present data can be used as reference values for IGF‐I (at least in Caucasians) for the diagnosis of growth hormone dlsturbances and as guidelines for growth hormone substitution.
Age‐related and gender‐related occurrence of pituitary adenomas
Authors: Mindermann Thomas , Wilson Charles B.
Published: March 2008

OBJECTIVE To evaluate the various types of pituitary adenomas according to sex and age group. Few studies have attempted such an analysis, and most have focused on specific age groups, especially children. Recent data suggest that the frequency of different types of pituitary adenomas varies according to age and sex.

DESIGN A retrospective review of the records of 2230 patients who underwent surgery for a pituitary adenoma at the University of California, San Francisco (UCSF), between January 1969 and June 1993.

METHODS The distribution of tumours was analysed according to age at surgery, sex, and the clinical pheno‐type of the tumour. Age groups were defined as the decades of life.

RESULTS Prolactinomas were the most common tumours (39%), followed by endocrlne‐inactive adenomas, growth‐hormone‐releasing adenomas, and adrenocorficotrophic hormone‐releasing adenomas causing Cushing's disease; ACTH‐releasing adenomas causing Nelson's syndrome and thyrotrophin (TSH)‐releasing adenomas were rare. The female‐to‐male ratio differed considerably between the various adenoma types and between age groups. Prolactinomas, ACTH‐releasing adenomas, and TSH‐releasing adenomas occurred mostly in females; endocrine‐inactive and GH‐releasing adenomas occurred mostly in males. In older age groups, all adenoma types, except for endocrine‐inactive adenomas, tended to assume a more balanced gender distribution. Among patients with prolactinomas, endocrine‐inactive, ACTH‐releasing, and to a lesser extent GH‐releasing adenomas, the greatest discrepancy in gender distribution seemed to coincide with the peak Occurrence of each tumour type. The peak Occurrence was from the second to the fifth decade of life for prolactinomas and from the fourth to the eighth decade for endocrine‐inactlve adenomas. GH‐releasing, ACTH‐releasing, and TSH‐releaslng adenomas were more evenly distributed throughout the adult life span.

CONCLUSIONS The frequency of pitultary adenomas varies greatly according to age and sex. The various adenoma types have thelr peak occurrence in distinctly dlfferent age groups and differ greatly in their female‐to‐male ratios. The female‐to‐male ratio for a given adenoma type varies greatly with age.
Bone mineral density in thyroxine treated females with or without a previous history of thyrotoxicosis
Authors: Franklyn Jayne , Betteridge Joan , Holder Roger , Daykin Jacquie , Lilley John , Sheppard Michael
Published: March 2008

OBJECTIVE The results of studies examining the influence of T4 therapy upon bone mineral density (BMD) are conflicting. This conflict may, in part, reflect Inclusion of patients with varying thyroid disorders. We have therefore examined the influence of preceding thyroid history and T4 therapy on BMD.

DESIGN Case‐control studies of patients on long‐term T4 therapy who have or have not previously received radio‐iodine treatment for thyrotoxicosis, as well as previously thyrotoxic patients who have not required T4 replacement.

PATIENTS Twenty‐seven premenopausal and 60 post‐menopausal females with a past history of thyrotoxicosis and subsequent T4 treated hypothyroidism (group l), 39 post‐menopausal females with a past history of radio‐iodine treated thyrotoxicosis not receiving T4 (group 2) and 22 post‐menopausal females with primary hypothyroidism on T4 (group 3). Female controls individually matched to patients by age and menopausal status.

MEASUREMENTS BMD measured by dual‐energy X‐ray absorptiometry. Serum biochemistry and tests of thyroid function.

RESULTS No significant differences were found in femoral or lumbar spine BMD measurements between premenopausal patients and controls in group 1 or between group 2 patients and controls. Measurements of BMD at all sites were lower in post‐menopausal patients in groups 1 and 2 than in controls; when allowance was made for differences In BMD due to body mass index by analysis of variance, significant reductions in femoral trochanter BMD (3·9%, P <0·05) and lumbar spine (5·6–8·5%, P <0·01) BMD results were found in post‐menopausal females In group 1 and reductions in femoral trochanter (3·9%, P <0·01), Ward's triangle (5·6%, P <0·05) and lumbar spine (8·5%, P <0·01) BMD results in group 2. Separate analysis of BMD results of those with normal or reduced serum TSH did not affect outcome. BMD measurements were not significantly correlated with duration of T4 therapy, T4 dose, or serum free T4 or TSH in any patient group.

CONCLUSIONS Thyroxine therapy alone does not represent a significant risk factor for loss of bone mineral density but there is a risk of bone loss in post‐menopausal (but not premenopausal) females with a previous history of thyrotoxicosis treated with radioiodine.
Mineralocorticoid and glucocorticoid status in idiopathic haemochromatosis
Authors: Walsh C. H. , Murphy A. L. , Cunningham S. , McKenna T. J.
Published: March 2008

OBJECTIVE A number of studies have suggested that both primary (Addison's disease) and secondary adrenal failure may be caused by idiopathic haemochromatosis. There is little information on mineralocorticoid secretion. We have assessed the mineralocorticoid and glucocorticoid status of patients with idiopathic haemochromatosis. DESIGN Cross‐sectional study.

PATIENTS Eighteen males and one female with confirmed idiopathic haemochromatosis were investigated. Seven of the subjects had hepatic cirrhosis and three had hypogonadotrophic hypogonadism.

MEASUREMENTS A short Synacthen (tetracosactrin) test was undertaken in addition to an overnight metyrapone test and an insulin stress test. In addition, plasma aldosterone (PA) and plasma renin activity (PRA) were measured in a group of patients in the basal state and again in the upright position.

RESULTS The short Synacthen test, overnight metyrapone test and insulin stress test were normal In all subjects. The PA, PRA, and PA/PRA ratios In the upright position were not significantly different in the patients with idiopathic haemochromatosis compared to control subjects.

CONCLUSION In this patient population, no abnormality of either the pituitary adrenal axis or mineralocorticoid status was detected. Adrenocortical dysfunction is likely to be exceptionally rare in idiopathic haemochromatosis.
Augmented 17α‐hydroxyprogesterone response to ACTH stimulation as evidence of decreased 21‐hydroxylase activity in patients with incidentally discovered adrenal tumours ('incidentalomas')
Authors: Seppel Thomas , Schlaghecke Reiner
Published: March 2008

OBJECTIVE Recent studies have indicated that the syndrome of congenital adrenal hyperplasia due to 21‐hydroxylase deficiency is closely associated with the development of benign adrenocortical tumours. Tumour formation is thought to be a consequence of ACTH hypersecretion which results from the lack of glucocorticoid synthesis.

The aim of this study was to evaluate 21‐hydroxylase activity in patients with an incidentally discovered adrenal mass ('Incidentaloma') without a history of congenital adrenal hyperplasia.

DESIGN A prospective study of 52 patients admitted to a single hospital.

PATIENTS Fifty‐two consecutive subjects (mean age 56·0 years, range 24–81 years) with an incidentally discovered adrenal tumour were studied.

MEASUREMENTS The 21‐hydroxylase reserve was assessed by intravenous bolus administration of 1‐24 ACTH (tetracosactrin) with measurement of basal and stimulated serum 17α‐hydroxyprogesterone (17‐OHP) concentrations. Impaired 21‐hydroxylase activity was defined as an exaggerated 17‐OHP response, with a 17‐OHP increment exceeding 7‐9nmolll. Basal and stimulated cortisol concentrations, and basal ACTH were also measured.

RESULTS Baseline levels of 17‐OHP were normal in 44 and elevated in 8 subjects. In 37 patients (71·2%), the 17‐OHP increment following ACTH administration exceeded 7·9nmol/l, demonstrating mildly decreased 21‐hydroxylase activity. In these subjects, the peak serum 17‐OHP correlated with the tumour diameter. In the patients with apparently normal 21‐hydroxylase activity, no significant correlation was found between 17‐OHP concentrations and tumour size. All patients had a stimulated serum cortisol above 550 nmol/l reflecting intact adrenal gluco‐corticoid reserve. There were no other differences between the group with exaggerated and the group with normal 17‐OHP Increment. The tumours were removed from two women with augmented 17‐OHP responses and this was followed by normalization of 17‐OHP dynamics.

CONCLUSIONS Biochemical evidence for partial 21‐hydroxyiase defiency is a common finding in patients with an adrenal Incidentaloma, even in the absence of a congential adrenal hyperpiasia history. Exaggerated 17‐OHP increment is not accompanied by decreased adrenal glucocorticoid reserve. Normalization of the 17‐OHP response after surgical treatment suggests that the phenomenon results from reduced 21‐hydroxyiase activity in the tumour, which retains ACTH responsiveness.
Serum lipoprotein lipid profile in women with the polycystic ovary syndrome: relation to anthropometric, endocrine and metabolic variables
Authors: Holte Jan , Bergh Torbjörn , Berne Christian , Lithell Hans
Published: March 2008

OBJECTIVE Although often associated with insulin resistance and glucose intolerance, various lipoprotein abnormalities have been found in polycystic ovary syndrome (PCOS) but not Invariably so when the degree of obesity is taken into account. We have therefore Investigated the serum lipid profile in a group of women with polycystic ovary syndrome with and without obesity. DESIGN Cross‐sectional study of serum lipoprotein lipids and plasma free fatty acids in relation to anthropometric, metabolic and hormonal variables in women with PCOS and weight‐matched controls.

PATIENTS Twenty‐four obese (Pob, mean BMI ± SD 30·6±3·3kg/m2) and 25 non‐obese (Pnob, 22·2 ±2·3kg/m2) women with PCOS. Twenty obese (Cob, 30·2 ± 3·5 kg/m2) and 20 non‐obese (Cnob, 21·4 ± 1·5 kg/m2) controls.

MEASUREMENTS Fasting concentrations of plasma free fatty acids, serum cholesterol and triglycerides in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) In relation to insulin sensitivity index (M/I; assessed with the euglycaemic insulin clamp), glucose tolerance (k‐value; intravenous glucose tolerance test), basal serum hormone concentrations, and body fat distribution (skinfolds and waist hip ratio).

RESULTS Plasma concentrations of free fatty acids were markedly higher in Pob than in the other groups (all P < 0 001). The lipoprotein lipids did not differ between Pob and Cob, or between the non‐obese groups, whereas both obese groups had higher serum concentrations of triglycerides, totally and in VLDL, and lower HDL‐cholesterol than their non‐obese counterparts. Pob also had higher serum levels of total and LDL‐cholesterol than Pnob. Pob had a more pronounced subcutaneous truncal‐abdominal adiposity, higher fasting insulin levels and lower M/I than the other groups, and a lower k‐value than Cob. Cob had higher levels of fasting insulin than Cnob. Free fatty acid levels correlated with the k‐value (inversely) in both women with PCOS and controls, and with M/I (inversely), age and testosterone levels in PCOS. Step‐wise regression analysis for the total population, comparing endocrine, anthropometric and metabolic explanatory variables, showed that the serum levels of HDL‐cholesterol and triglycerides were mainly correlated with body fat distribution (both) and fasting insulin levels (triglycerides), and levels of total and LDL‐cholesterol with BMI and age.

CONCLUSIONS Plasma free fatty acid correlations were markedly increased In obese women with PCOS, closely associated with the lower insulin sensitivity and lower glucose tolerance in these women. In spite of these profound metabolic aberrations, the lipoprotein lipid profile was not significantly more abnormal in obese women with PCOS than in their weight‐matched controls.
The independent effects of polycystic ovary syndrome and obesity on serum concentrations of gonadotrophins and sex steroids in premenopausal women
Authors: Holte Jan , Bergh Torbjörn , Gennarelli Gianluca , Wide Leif
Published: March 2008

OBJECTIVE To investigate the basal levels of gonadotrophins and sex steroids, with special reference to the effects of obesity and body fat distribution, In premenopausal women, both those with polycystic ovary syndrome (PCOS) and those with normal ovaries and regular menstrual cycles.

DESIGN Cross‐sectional study. The separate effects of obesity (and body fat distribution and fasting Insulin levels) and PCOS on endocrine variables were evaluated by means of analysis of covariance.

PATIENTS Sixty‐seven women with anovulatory menstrual cycles and polycystic ovaries according to ultrasonography and 59 women with normal ovaries and regular cycles, both groups covering a wide range of body mass index (BMI, PCOS, 17·6‐37·4, mean 25·7 kg/m2; controls, 18·8‐40·9, mean 25·1 kg/m2).

MEASUREMENTS Serum levels of gonadotrophins, sex steroid hormones, prolactin and GH obtained in the early follicular phase in the controls, fasting insulin levels, anthropometric measures (BMI, skinfolds, waist hip ratio).

RESULTS Mean serum concentrations of LH, andro‐stenedione, testosterone, the free androgen index (FAI; all P < 0·0001) and DHEAS (P < 0·01) were higher, and serum FSH (P < 0·01) and serum SHBG levels lower (P < 0·0001), in the PCOS group than in the controls. Women with PCOS had a more pronounced upper body fat distribution and higher fasting insulin levels than the controls. Independent of PCOS, BMI was positlvely associated with serum levels of FSH (P < 0·001) and negatively with levels of LH (P < 0·05), LH/FSH ratio (P < 0·0001), SHBG (P < 0·0001) and androstenedione (P < 0·01), whereas for levels of testosterone, FAI and DHEAS the impact of obesity differed significantly between the groups. Thus, in the PCOS group, testosterone levels (P < 0·05) and the FAI (P < 0·001) were positively associated with BMI, whereas they were constant throughout the entire range of BMI in the controls. DHEAS levels were positively associated with BMI in the PCOS group (P < 0·05) and negatively in the controls (P < 0·01). Measures of upper body fat were related to testosterone and FAI levels, independent of BMI.

CONCLUSIONS Lower FSH levels were found in women with PCOS than during the early follicular phase of normally ovulating women, suggesting a role in anovulation in PCOS. Obesity itself exerted effects on endocrine variables, with the net result of a reduced LHIFSH ratio and lower serum levels of androstenedione and SHBG in both groups; obesity was associated with increased levels of DHEAS, testosterone and FAI exclusively in the women with PCOS. The results underline the endocrine impact of obesity and body fat distribution and the necessity of applying reference values of BMI matched subjects when establishing the endocrine profile of women with PCOS.
Evaluation of maternal serum immunoreactive inhibin as a first trimester marker of Down's syndrome
Authors: Wallace Euan M. , Harkness Linda M. , Burns Sheila , Liston William A.
Published: March 2008

BACKGROUND AND OBJECTIVE Maternal Serum immunoreactive inhibin has been shown to be significantly elevated in Down's affected pregnancies in the second trimester, suggesting that it may be useful in prenatal diagnosis. We have investigated whether it is similarly elevated in the first trimester.

DESIGN Stored maternal sera from women with Down's affected pregnancies and chromosomally normal control pregnancies were retrieved for analysis. These sera had been collected prospectively at either 11 or 12 weeks gestation as a routine antenatal booking procedure.

SUBJECTS From records, 11 women were identified as having had a Down's pregnancy. For each of these, 4 controls matched for gestation and duration‐of‐storage were also identified.

MEASUREMENTS Two different inhibin immunoassays were evaluated, one using an antibody raised against 31 kDa bovine inhibin and the other, a commercial two‐site assay, using two antibodies directed against two distinct α‐subunit epitopes.

RESULTS Neither assay detected a significant effect of gestation on serum inhibin levels. After combining the data from both gestations, no significant difference between the Down's samples and controls for either assay was detected. However, analysis of the data for each gestation separately revealed that one assay detected a significant difference in inhibln levels between Down's affected and unaffected pregnancies at 11 weeks gestation (mean ± SEM 3186 ± 195 vs 2020 ± 172ng/l, P < 0·01) but not at 12 weeks. The other, commercial, assay did not detect a significant difference at either gestation. In addition, there was poor association between the results of the two assays.

CONCLUSIONS These data suggest that immunoreactive inhibin, as detected by these assays, will not be useful as a late first trimester marker for Down's syndrome and also that these two assays detect different inhibin species in pregnancy serum.
Treatment with GHRH(1‐29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity
Authors: Kirk J. M. W. , Trainer P. J. , Majrowskl W. H. , Murphy J. , Savage M. O. , Besser G. M.
Published: March 2008

OBJECTIVE Therapy with GHRH in patients with mild GH insufficiency appears to be more effective than in those with severe insufficiency. We, therefore, studied the clinical response of children with idiopathic short stature to treatment with GHRH(1‐29)NH2 (GHRHa) for a period of 12 months.

DESIGN Eighteen short pre‐pubertal children (aged 4·3‐11·0 years, 17 male) with idiopathic short stature (height < 3rd centile, peak GH to provocative testing > 20 mu/l) were recruited to receive GHRHa 20 μg/kg by twice daily s.c. injection for one year. One patient was non‐compliant and was withdrawn prior to 3 months of therapy. Pretreatment height velocity was calculated for 12 months and subjects were measured 3‐monthly during therapy. Overnight GH profiles and s.c. GHRH tests (20 μg/kg) were performed at 0, 3, 6 and 12 months of therapy. In addition, an i.v. GHRH test (1 μg/kg) was performed at the start and after 1 month of therapy.

MEASUREMENTS Overnight GH profiles were analysed using the Pulsar program.

RESULTS Mean (SD) height veloclty (HV) increased from 4·8(0·9)cm/year pre‐treatment to 7·2 (1·6)cm/year after 12 months of therapy (P= 0·001). The children growing slowly (HV < 25th centile) before treatment had a greater growth response than those growing normally (HV ≥25th centile) before treatment. Final height prediction increased by a mean (SD) of 3·4(2.6)cm. Overnight GH levels and GH responses to GHRH testing fell during the 12 months of therapy. Fasting blood glucose and insulin levels increased during therapy, as did IGF‐I. Cessation of GHRHa was followed by catch‐down growth during the first 3 months off therapy: mean (SD) HV 3·89(1·82)cm/year (P < 0·44), although the HV after 6 months (4·9(1·0)cm/year) and 12 months (4·4(1·0)cm/year) was not different from pretreatment values.

CONCLUSIONS Short‐term therapy with twice‐daily s.c. injection of GHRHa (20 μg/kg) promoted linear growth in short children who were not GH‐insufficient. The improved height velocity was sustained throughout the 12 months of treatment, followed by catch‐down growth, and returned to pretreatment velocity after cessation of therapy.
Inverse correlation between insulin‐like growth factor binding protein‐I and insulin in patients with acromegaly during treatment with the somatostatin analogue octreotide
Authors: Fredstorp L. , Werner S. , Bang P. , Hall K.
Published: March 2008

OBJECTIVE Previous reports have shown an inverse relation between IGFBP‐1 and Insulin levels In healthy men, patients with insulin dependent diabetes mellitus, and insulinoma. We have investigated whether this inverse relation also exists in acromegaly, before and during treatment with octreotide, and whether changes in IGFBP‐1 levels relate to OH and IGF‐I levels.

DESIGN We studied short‐term treatment with octreotide in a double‐blind placebo‐controlled 14‐day clinical trial.

PATIENTS Eighteen patients with acromegaly were studied.

MEASUREMENTS Plasma GH and serum IGFBP‐1 levels were measured at hourly intervals from 0700 to 1800h before randomization (day 0) and on days 4, 6, 8,14 and 20. Serum insulin was determined at 0700, 0800 and 0900 h, and serum IGF‐I at 0700 h.

RESULTS Octreotide increased the daily mean IGFBP‐1 level by 43% on day 8 and by 35% on day 14. The IGFBP‐1 levels during octreotide were significantly higher (P < 0·05) compared to placebo, 29·9 ± 3·9 vs 19·9 ± 1·7 μg/l (mean ± SEM) on day 8, and 28·3 ± 3·2 vs 19·.9 ± 1·6 μg/l on day 14. Octreotide treatment significantly suppressed the insulin levels on all observation days by 40–48% compared to placebo. There was a significant inverse correlation between IGFBP‐1 levels and insulin levels, both before treatment and on the last day of treatment (r= 0·79, P= 0·04; r=−0·90, P= 0·02, respectively). GH and IGF‐I were significantly decreased in the octreotide group compared to the placebo group during the entire treatment period. The mean of age related standard deviation scores of IGF‐I In the octreotide group decreased from a pretreatment value of 6·47 ± 0·74 to 3·60 ± 1·20 on day 14. There was no significant correlation between IGFBP‐1 levels and levels of GH and IGF‐I, either before or during treatment.

CONCLUSIONS Octreotide treatment, in addition to reducing GH, IGF‐I and insulin levels, is associated with an Increase in IGFBP‐1 concentrations in patients with acromegaly, and it is suggested that the rise in serum IGFBP‐1 Is a consequence of the decrease In insulin secretion.
Endocrine profiles during administration of the new non‐steroidal anti‐androgen Casodex in prostate cancer
Authors: Verhelst J. , Denis L. , Van Vliet P. , Van Poppel H. , Braeckman J. , Van Cangh P. , Mattelaer J. , D'Hulster† O. , Mahler Ch.
Published: March 2008

OBJECTIVE Casodex (Zeneca) is a new potent, long‐acting non‐steroidal anti‐androgen, which produces androgen deprivation by blocking the androgen receptor. We evaluated the endocrine effects of Casodex 150 mg daily given in monotherapy as primary treatment for patients with prostate cancer.

DESIGN As part of a large, multicentre study comparing the therapeutic effects of surgical castration with 150 mg/day Casodex in monotherapy for patients with prostate cancer, a subgroup of 23 patients on Casodex were studied in detail for changes in endocrine parameters. Serum levels of LH, FSH, testosterone, DHT, oestradiol, prolactin, sex hormone binding globulin and free testosterone were measured at the start of therapy and after 1, 4,8,12 and 24 weeks. Effects on libido, sexual activity and the appearance of hot flushes, breast pain and gynaeco‐mastia were recorded.

RESULTS Administration of Casodex resulted in a rise in LH levels in all patients with a mean increase after 24 weeks of 102% (P < 0·001). Mean FSH levels showed a limited increase (7%) after 24 weeks, which was significant only after 1 week (P < 0·001). As a result of the high LH levels, total testosterone levels increased after 24 weeks by 66% (P < 0·001), free testosterone by 57% (P < 0·001) and dihydrotestosterone by 24% (P= 0·0112). Parallel to testosterone, oestradiol levels rose by a mean of 66% (P < 0·001). Mean sex hormone binding globulin and prolactin levels rose by respectively 8% (P= NS) and 65% (P< 0·01).

Despite an increase in testosterone levels, excellent androgen blockade was obtained, as shown by a decrease in prostate specific antigen levels in 22/23 patients. Libido was maintained in 8/11 patients, and sexual activity in 5/6. No patient complained of hot flushes. However, mild gynaecomastia and/or breast tenderness were seen in 48 and 30% of cases respectively.

CONCLUSION Casodex 150 mg/day monotherapy resembles surgical castration in achieving androgen deprivation, despite an increase in LH and testosterone levels. In contrast to castration, libido and sexual activity are usually maintained and hot flushes are rare. However, mild gynaecomastia and/or breast tenderness were noted In 48 and 30% of patients.
Neonatal primary hyperparathyroidism masked by vitamin D deficiency
Authors: Meeran K. , Husain M. , Puccini M. , Scott H. , Dionisi‐Vici C. , Harvey D. R. , Lynn J. , Thakker R. V.
Published: March 2008

Neonatal primary hyperparathyroidism is a life threatening disorder that is associated with severe hypercalcaemia, hypotonia, bone demineralization, fractures and respiratory distress. Treatment consists of total parathyroidectomy and without this affected infants will usually die by the age of three months. We report a patient with neonatal primary hyperparathyroidism who survived without fractures or parathyroidectomy to an age of nine months, and in whom the hypercalcaemia became masked by vitamin D deficiency. At surgery, four‐gland hyperplasia was demonstrated and total parathyroidectomy followed by oral calcitriol treatment has restored well‐being and normocalcaemia. An absence of skeletal complications, a survival beyond three months of age without parathyroidectomy and the masking of the hypercalcaemia by vitamin D deficiency represents a unique combination of metabolic abnormalities in a patient with neonatal primary hyperparathyroidism.
Intrapulmonary shunting causing hypoxaemia in a case of carcinoid syndrome
Authors: Hussain A. , Young E. T. , Greaves J. D. , Hammond P. J. , Hughes J. M. B. , Wallis S. C. , Bloom S. R.
Published: March 2008

A case of metastatic carcinoid syndrome with hypoxaemia is described. The hypoxaemia appeared to be due to intrapulmonary shunting. There was Improvement in resting and exercise arterial oxygen saturations following chemotherapy with streptozotocin and 5‐fluorouracil. This was followed by a decrease in the tumour bulk which may have led to a reduction in the secretion of the vasodilator products responsible for shunting. Some features of this case suggest that the hypoxaemia might have been due to dilatation of precapillary and capillary vessels of the pulmonary micro‐circulation. These features are part of the so‐called ‘hepatopulmonary syndrome', of which this case appears to represent a less severe form.
Ultrasound guided percutaneous ethanol injection in the treatment of cystic thyroid nodules
Authors: Verde Giuseppe , Paplni Enrico , Pacella Claudio M. , Gallotti Cesare , Delpiano Sergio , Strada Sonia , Fabbrini Rossella , Bizzarrl Giancario , Rinaidi Roberta , Panunzi Ciaudio , Geili Darlo
Published: March 2008

OBJECTIVE The management of cystic lesions in the thyroid remains controversial. We examined the efficacy and safety of ultrasound guided percutaneous ethanol injection for the treatment of benign cystic thyroid nodules in euthyroid patients.

STUDY DESIGN (A) Preliminary randomized trial: 20 patients with predominantly cystic thyroid nodules were randomized in two groups and followed up for 1 month. Group 1 underwent fine needle aspiration of the fluid component of the nodules; Group 2 underwent percutaneous ethanol injection at the end of fine needle aspiration of the cyst fluid. (B) Prospective study: 32 patients with the same clinical characteristics (Group 3) were treated by fine needle aspiration and percutaneous ethanol injection, and followed up for 12 months.

METHODS Groups 1 and 2: clinical evaluation, thyroid ultrasonography, thyroid scintiscan and serum thyroid hormone profile were performed before treatment and one month later. Group 3: clinical evaluation, thyroid ultrasonography and serum thyroid hormone profile were performed in basal conditions and 1, 3, 6, 9, 12 months after treatment. Thyroid scintiscan was performed before treatment and 3–6 months later.

RESULTS (A) Randomized study: one month after treatment, nodule volume decrease in Group 2 was significantly higher than In Group 1 (Group 2 median 14·75 range 6–29·9 ml; Group 1: median 3·65 range 0·2–18·5 ml; P < 0·01). Nodule volume reduction was greater than 50% versus baseline in 8 (80%) patients in Group 2 and in 3 (30%) patients in Group 1 (P < 0·01). (B) Prospective study (Group 3): a significant nodule volume reduction (P < 0·01 vs pretreatment) was observed 1 and 12 months after percutaneous ethanol injection (pretreatment: median 14·5, range 1·5–65·8 ml; 1 month: median 3·5, range 0·4–38·9 ml; 12 months: median 2·5, range 0·4–34·5 ml). Nodule volume reduction greater than 50% was recorded in 24 (80%) patients. Groups 1–3: recurrence of cyst fluid was demonstrated by ultrasonography in 8 patients of Group 1, in 3 patients of Group 2 and in 1 patient of Group 3. No relevant adverse effects or significant biochemical changes were observed.

CONCLUSIONS Ultrasound guided percutaneous ethanol injection of cystic thyroid nodules is a safe, low‐cost and effective therapeutic procedure in patients with benign thyroid cystic nodules. Indeed, nodule volume reduction was significantly greater and more frequent in patients treated by percutaneous ethanol Injection than in those patients who underwent fluid aspiration alone. These results were confirmed in a long‐term prospective trial and only one fluid recurrence was observed during 12 months of follow‐up.
Oral progestogen‐only contraception may protect against loss of bone mass in breast‐feeding women
Authors: Caird L. E. , Reid‐Thomas V. , Hannan W. J. , Gow S. , Glasier A. F.
Published: March 2008

BACKGROUND AND OBJECTIVES A worldwide trend towards increasing life expectancy has meant that osteoporosis is emerging as an important public health problem. The loss of bone mineral density and its restoration in association with a premenopausal but physiological hypo‐oestrogenic state may serve as an important model for research into the pathogenesis and prevention of osteoporosis. With this in mind we have undertaken a longitudinal study of changes in bone mineral density over one year in women after childbirth.

DESIGN Observational study of 31 women in the first year following childbirth; 11 intending to breast‐feed and use barrier methods of contraception, 9 Intending to breastfeed and to use the progestogen‐only pill and 10 intending to artificially feed and to use barrier methods.

PATIENTS Recruitment was from the antenatal clinics of the Simpson Memorial Maternity Pavilion. Only non‐smokers who had regular menstrual cycles prior to conception were included.

MEASUREMENTS Bone mineral density was measured at the lumbar spine within 3 weeks of childbirth and repeated at 6 and 12 months post partum. Plasma oestradiol, prolactin and osteocalcin concentrations were measured at each visit.

RESULTS Breast‐feeding women using barrier methods lost a mean ± SE of 4·9 ± 1·5% of bone mineral density In the first 6 months following delivery. This was however reversible since by one year the bone mineral density was no different from that measured immediately post partum. Breast‐feeding women using the progestogen‐only pill lost a significantly smaller percentage of bone mineral density in 6 months and by one year bone mineral density war 2·95 ± 0·75% higher than post partum. Artificially feeding women had a steady Increase in bone mineral density In the first year and bone mineral density was on average 4·3 ± 1·2% higher.

CONCLUSION Breast‐feeding results in a reversible reduction in spinal bone mineral density. The small amounts of gestagen in the progesterone‐only pill would appear to protect against this loss. The mechanism of this loss in bone mineral density and the potentially bone protective effects of gestagens require further study.