bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of olfactory dysfunction in carriers of X‐linked Kallmann's syndrome
Authors: Kirk J. M. W. , Grant D. B. , Savage M. O. , Besser G. M. , Bouloux P.‐M. G. 
Published: March 2008

SummaryOBJECTIVE The aim of the study was to test the hypothesis that clinically unaffected female carriers of X‐linked Kallmann's syndrome have an olfactory defect.DESIGN Assessment of the olfactory threshold to seven standard odorants, each at a concentration of 1‐10‐8mol/1.PATIENTS Five families with X‐linked Kallmann's syndrome (KS) were tested, containing 19 males with KS, and 9 female carriers. Related but unaffected males (n= 8) were used as a control group, and in addition seven patients with Turner's syndrome (XO) were assessed.MEASUREMENTS The olfactory threshold was taken as the lowest concentration at which each odorant was clearly distinguished from control (liquid paraffin). The threshold for each odorant was compared between the subject groups using the non‐parametric Mann‐Whitney test.RESULTS All patients with KS were anosmic to all odorants. The female carriers had hyposmla, with a significant reduction in the olfactory threshold to putrid, peppermint, floral and pungent odorants compared to control subjects, and to peppermint, floral and pungent odorants compared to subjects with Turner's syndrome. The latter had olfactory thresholds which were statistically identical with the control group.CONCLUSIONS Obligate female carriers of X‐linked Kallmann's syndrome are hyposmic compared to control subjects. The overlap between the two groups, however, makes olfactory testing unreliable as a diagnostic test.
Optimal frequency of administration of pamidronate in patients with hypercalcaemia of malignancy
Authors: Wimalawansa* Sunil J. 
Published: March 2008

SummaryOBJECTIVE Hypercaicaemia of malignancy (HM) is a common metabolic complication associated with cancer. The hypocaicaemic effects of medications used to reduce serum calcium levels in HM are short lived and relapse in hypercaicaemia is not uncommon. Pamidronate is one of the most commonly used bisphosphonates in the treatment of HIM but there are no specific guidelines for the frequency of use of this drug in recurrent hypercalcaemia. This study was conducted to assess the optimum frequency of pamidronate therapy necessary to maintain normocalcaemia in patients with HM.DESIGN AND PATIENTS Thirty‐four patients With HM were randomly allocated into two groups and treated with intravenous pamidronate administered every 14th or 21st day for 16 weeks (n= 17 each group). Serum calcium and urinary hydroxyproline creatinine ratio were measured at weekly intervals.RESULTS The calcium‐lowering effect of pamidronate was apparent by 48 hours and normocalcaemia was maintained for an average of 15 days. When the drug was administered every 3 weeks, hypercalcaemia and associated symptoms developed in 50% of patients (22 separate episodes) during the 3rd week, before the next dose of pamidronate. The incidence of symptomatic hypercalcaemia was significantly decreased (10%, 8 separate episodes, P < 0·01) and survival was improved (P< 0·05) in patients who received pamidronate every 2nd week, thereby minimizing the unpleasant and potentially dangerous effects of hypercalcaemia.CONCLUSIONS Intravenous pamidronate 60 mg/dose, administered every two weeks, can maintain normocalcaemia in the vast malority of patients with hypercalcaemia of malignancy.
Serum lipoproteins in acromegaly before and 6‐15 months after transsphenoidal adenomectomy
Authors: Oscarsson Jan , Wiklund Olov , Jakobsson Karl‐Erlk , Petruson Björn , Bengtsson Bengt‐Åke 
Published: March 2008

SummaryOBJECTIVES Acromegaly is a rare disorder characterized by over‐secretion of GH, most often because of a pituitary adenoma. The disease is associated with disturbances in lipoprotein metabolism and an increased cardiovascular mortality. The aim of the present study was to investigate whether treatment of acromegaly results in changes in serum concentrations of lipids and apolipoproteins, Including lipoprotein(a) (Lp(a)).DESIGN Fourteen patients with clinical features of acromegaly and Increased GH secretion were studied 1‐10 months before and 6‐15 months after transsphenoidal adenomectomy in an open study.PATIENTS Three patients had diabetes mellitus before surgery and two of these patients had normalized serum glucose levels post‐operatively. Mean and baseline plasma GH levels were determined from 24‐hour GH profiles. Serum samples were taken in the morning after an overnight fast. All patients were normocholesterolaemic, and four patients were hypertriglyceridaemic before treatment.RESULTS Mean plasma GH levels decreased from 34·5 ±7·4 to 2·1 ±0·4 μ/l (mean ±SEM). Serum IGF‐I, insulin and free T3 levels decreased and serum SHBG concentrations Increased post‐operatively. There was no effect of treatment on serum cholesterol concentrations, but serum triglyceride concentrations decreased. Serum apollpoprotein (apo) B and apoE levels were unaffected by treatment. Serum apoA‐I levels increased and Lp(a) levels decreased post‐operatively.CONCLUSIONS Successful treatment of acromegaly, resulting in normal mean GH values (< 5mU/l) and/or normal responsiveness to TRH, have beneficial effects on serum lipoproteins with increased serum apoA‐I levels and decreased serum levels of triglycerides and Lp(a). These effects seem to be independent of improvement In glucose tolerance, since patients with diabetes mellitus before surgery and normal fasting blood glucose levels post‐operatively had similar lipoprotein responses to treatment as those with normal fasting blood glucose levels before surgery.
Growth hormone administration stimulates energy expenditure and extrathyroidal conversion of thyroxine to triiodothyronine in a dose‐dependent manner and suppresses circadian thyrotrophin levels: studies in GH‐deficient adults
Authors: Jørgensen J. O. L. , Møller J. , Laursen T. , Ørskov H. , Christiansen J. S. , Weeke J. 
Published: March 2008

SummaryOBJECTIVE The impact of exogenous GH on thyroid function remains controversial although most data add support to a stimulation of peripheral T4 to T3 conversion. For further elucidation we evaluated iodothyronine and circadian TSH levels in GH‐deficient patients as part of a GH dose‐response study.PATIENTS Eight GH‐deficient adults, who received stable T4 substitution due to central hypothyroidism; two patients, who were euthyroid without T4 supplementation were studied separately.DESIGN All patients were initially studied after at least 4 weeks without GH followed by 3 consecutive 4‐week periods in fixed order during which they received daily doses of 1, 2 and 41U of GH/m2 body surface area. The patients were hospitalized for 24 hours at the end of each period.MEASUREMENTS Circulating total and free concentrations of T4 and T3, total rT3 and TSH were measured once at the end of each study period. Circadian TSH levels were recorded during the period without GH and during GH treatment with 2 IU GH.RESULTS Highly significant GH dose‐dependent increases in total and free T3 and a reduction in rT3 were observed. The T3/T4 ratio also increased with increasing GH dosages (P < 0·001). In seven patients subnormal T3 levels were recorded in the period off GH, despite T4 levels well within the normal range. Resting energy expenditure also increased and correlated with free T3 levels (r= 0·47, P < 0·05). The Circadian TSH levels exhibited a significant nocturnal increase during the period without GH, whereas GH therapy significantly suppressed the TSH levels and blunted the circadian rhythm (mean TSH levels (mU/I) 0·546 ± 0·246 (no GH) vs 0·066 ± 0·031 (21U GH) (P < 0·05)). The two euthyroid non‐T4 substituted patients exhibited qualitatively similar changes in ail parameters.CONCLUSIONS GH adminstration stimulated peripheral T4 to T3 conversion in a dose‐dependent manner. Serum T3 levels were subnormal despite T4 substitution when the patients were off GH but normalized with GH therapy. Energy expenditure increased with GH and correlated with free T3 levels. GH caused a significant blunting of serum TSH. These findings suggest that GH plays a distinct role in the physiological regulation of thyroid function in general, and of peripheral T4 metabolism in particular.
The effect of oestradiol implants on regional and total bone mass: a three‐year longitudinal study
Authors: Ryde S. J. S. , Bowen‐Simpkins K. , Bowen‐Simpkins P. , Evans W. D. , Morgan W. D. , Compstont J. E. 
Published: March 2008

SummaryOBJECTIVE Although there is evidence from cross‐sectional studies that percutaneous oestrogen administration protects against menopausal bone loss, few longitudinal data are available. We have examined the effect of 3 years' treatment with percutaneous oestradiol on total body calcium, spinal trabecular bone mineral density and radial bone mineral content in post‐menopausal women.DESIGN and PATIENTS Twenty‐nine post‐menopausal women, aged 37–55 years, who had undergone hysterectomy and had experienced the onset of menopausal symptoms within the previous 2 years, were studied before and for 3 years during hormone replacement with oestradiol implants, given at approximately 6‐monthly intervals.MEASUREMENTS Total body calcium was measured by prompt gamma neutron activation analysis, spinal trabecular bone mineral density by quantitative computed tomography and radial bone mineral content by single‐photon absorptiometry.RESULTS There was a significant increase in the mean total body calcium, spinal trabecular bone mineral density and radial bone mineral content over the 3 years of the study. The mean (± SEM) percentage change per annum was +2 4% (±0.8) for total body calcium (P <0 01), + 3.3% (±0.6) for spinal trabecular bone mineral density (P < 0.001) and +12% (± 0.6) for radial bone mineral content (P < 0 05).CONCLUSIONS Percutaneous oestradiol replacement therapy prevents menopausal bone loss and is associated with a sustained and significant increase in total body calcium, spinal trabecular bone mineral density and radial bone mineral content over a 3‐year treatment period. Oestradiol implants thus have skeletal effects comparable to those of oral or transdermal oestrogens.
Impaired glucose tolerance and insulin insensitivity in primary hyperparathyroidism
Authors: Kumar S. , Olukoga A. O. , Gordon C. , Mawer E. B. , France M. , Hosker J. P. , Davies M. , Boulton A. J. M. 
Published: March 2008

SummaryOBJECTIVE A high prevalence of diabetes mellitus has been shown in patients with primary hyperparathyroidism (PHPT). However, it is unclear whether this is related to the metabolic abnormalities in PHPT or to the presence of other risk factors for glucose intolerance in these patients. The aim of our study was to determine whether glucose intolerance and insulin insensitivity occur in subjects with PHPT who do not have other risk factors for diabetes mellitus.DESIGN Cross‐sectional study of glucose metabolism in PHPT patients without other risk factors for diabetes mellitus, compared to age and body mass index (BMI) matched healthy subjects.SUBJECTS Nineteen non‐obese, non‐diabetic, normotensive patients with PHPT and 11 age and BMI matched healthy subjects.MEASUREMENTS The continuous infusion of glucose test was used to assess glucose tolerance. Plasma glucose and insulin were measured during a 1‐hour continuous infusion of glucose (5 mg/kg ideal body weight/min); insulin sensitivity and beta‐cell function were derived from the glucose and insulin data by mathematical modelling. Fasting serum concentrations of parathyroid hormone, ionized calcium and 1,25‐dihydroxyvitamin D (1,25(OH)2D) were measured in all subjects.RESULTS PHPT patients attained higher plasma glucose levels at the end of the glucose infusion (median 9.0 (interquartile range 8.1–9.8) mmol/l) than did controls (7.9 (7.1–8.9) mmol/l, P<0.05), and 8 (42%) PHPT patients had impaired glucose tolerance. Insulin sensitivity was lower in PHPT (60.3% (49.8–85.4)) than in controls (113.7% (89.3–149.2), P<0.001); beta‐cell function was not different in PHPT subjects. PHPT subjects with impaired glucose tolerance had reduced beta‐cell function compared to PHPT subjects with normal glucose tolerance (89.9% (70.5–106.4) vs 120% (98.8–156.6) respectively, P<0.05). No significant correlations were found between insulin sensitivity and PTH (rs=−0.21), 1,25(OH)2D (rs=−0.14), ionized calcium (rs=–0.11) and inorganic phosphate (rs= 0.34). Beta‐cell function did not correlate with PTH (rs= 0.15), 1,25(OH)2D (rs= 0.04), ionized calcium (rs= 0.23) or inorganic phosphate (r,=− 0.35).CONCLUSION Insulin insensitivity is present in PHPT even in the absence of hypertension and obesity, and may be the cause of glucose intolerance and diabetes. PHPT subjects with reduced beta‐cell function are more likely to develop glucose intolerance.
The HLA association with Graves' disease is sex‐specific in Hong Kong Chinese subjects
Authors: Cavan D. A. , Penny M. A. , Jacobs K. H. , Kelly M. A. , Jenkins D. , Mijovic C. , Chow C. , Cockram C. S. , Hawkins B. R. , Barnett A. H. 
Published: March 2008

SummaryOBJECTIVE Graves' disease is associated with different HLA genes in Caucasians and the Chinese, in whom the HLA associations may be stronger in males than females. Common HLA‐associated susceptibility in both races may occur at the HLA‐DQ loci. The aims of this study were to examine the HLA‐A, B, DR and DQ associations with Graves' disease in a Hong Kong Chinese population and to determine whether the HLA associations differ between the sexes and between subjects with and without thyrotoxic periodic paralysis.DESIGN HLA‐A, B and DR types were determined by serological typing and DQA1 and DQB1 alleles by oligonucleotide probing of the respective enzymatically amplified gene.PATIENTS Ninety‐seven Chinese patients with Graves' disease (31 males with, 35 males without and 31 females without thyrotoxic periodic paralysis) and 105 racially matched healthy controls.MEASUREMENTS Frequencies of HLA types/alleles at each locus were compared between patients and controls and between the Graves' subgroups using the χ2 test.RESULTS HLA‐B46, DR9 and DQB1*0303 were associated with Graves' disease in males only; these associations were weaker in males with thyrotoxic periodic paralysis. DR12, DQA1*0401 and DQB1*0301 were protective, regardless of sex or the presence of thyrotoxic periodic paralysis. The positive HLA associations in the Hong Kong Chinese were distinct from those in Caucasians whereas the protective haplotype was similar to that described in Caucasians.CONCLUSIONS These findings call in question the role of HLA genes in disease susceptibility but suggest a role for HLA in protection from Graves' disease.
Stimulation of extraocular muscle fibroblasts by cytokines and hypoxia: possible role in thyroid‐associated ophthalmopathy
Authors: Metcalfe R. A. , Weetman A. P. 
Published: March 2008

SummaryOBJECTIVE Smoking is a risk factor for the development of thyroid‐associated ophthalmopathy, an inflammatory process primarily affecting the fibroblasts in extraocular muscles. We wished to determine whether the extraocular muscle fibroblasts are more sensitive than dermal fibroblasts to T‐cell derived cytokines, as a reason for this anatomical localization, and whether hypoxia alters fibroblast function, as one explanation for the susceptibility conferred by smoking.DESIGN Fibroblasts derived from the skin or extraocular muscles of healthy subjects were cultured with cytokines under normal (5% CO2:95% air) and hypoxic (5% C02:95% N2) conditions.MEASUREMENTS Glycosaminoglycan, protein and DNA synthesis were measured by assessing incorporation of d‐6‐3H‐glucosamine, 3H‐amino acids, and 3H‐thymidine respectively.RESULTS α‐lnterferon and interleukin‐6 had no effect on fibroblasts, γ‐Interferon, tumour necrosis factor and inter‐leukin‐1 stimulated glycosaminoglycan synthesis; this effect was greater in orbital than in dermal fibroblasts with γ‐interferon and interleukin‐1 (P<0.05). The same cytokines stimulated total protein with a greater response in orbital fibroblasts with γ‐interferon. Interleukin‐1 inhibited DNA synthesis in orbital fibroblasts but stimulated DNA synthesis in dermal fibroblasts (P< 0.01); tumour necrosis factor also displayed a differential effect (P<0.01). Hypoxia caused a significant increase in glycosaminoglycan, protein and DNA synthesis in both types of fibroblasts, under both basal and cytokine‐treated conditions (P < 0.05).CONCLUSIONS Extraocular muscle fibroblasts respond differently from dermal fibroblasts following cytokine stimulation, which may explain in part the anatomical localization of ophthalmopathy. Hypoxia stimulates fibroblasts and this could contribute, as an enhancing factor, to the adverse effects of smoking on thyroid eye disease.
Growth hormone releasing hormone 1‐44 NH2 and 1‐40 OH levels in normal subjects during growth hormone stimulation tests
Authors: Page M. D. , Dieguez C. , Valcavi R. , Koppeschaar H. P. F. , Scanlon M. F. 
Published: March 2008

SummaryOBJECTIVE Little is known about the relative circulating concentrations of growth hormone releasing hormone (GHRH) 1‐44 NH2 and 1‐40 OH in response to dynamic GH stimulation. We therefore studied the concentrations of growth hormone‐releasing hormone (GHRH) 1‐44 NH2 and 1‐40 OH in the peripheral plasma of normal male subjects during GH stimulation tests.DESIGN Tests were performed at 0900 h after an overnight fast. Stimulation tests, commenced at 0 minutes, included α‐adrenergic activation with adrenaline (10 μg/min from 0 to 30 minutes) following β‐blockade with propranolol (1.5 mg/min from ‐10 to 0 minutes), α2‐adrenergic activation with clonidine 150 μg i.v., insulin hypoglycaemia (0.15 U/kg soluble insulin), l‐arginine infusion (30 g from 0 to 30 minutes), l‐dopa (500 mg orally) and oral glucose (100 g). SUBJECTS Groups of healthy male volunteers aged 20‐42 years, all within 10% of ideal body weight. MEASUREMENTS Serum GH and plasma GHRH 1‐44 NH2 and 1‐40 OH were measured at intervals for between 60 and 390 minutes, depending on the stimulation test. RESULTS There were no significant changes in either GHRH 1‐44 or 1‐40 following a‐adrenergic activation with propranolol/adrenaline infusion, a2‐adrenergic activation with i.v. clonidine, insulin‐induced hypoglycaemia or arginine infusion despite the expected rise in GH levels.After oral glucose, GH was initially suppressed with a late rise. There were no changes in GHRH 1‐44 or 1‐40 levels during either phase of this response. After l‐dopa GH levels peaked at 90 minutes, 24.5 ± 11.0 mU/l (mean ± SEM). At 0 minutes GHRH 1‐44 and 1‐40 levels were 3.25 ± 0.89 and 4.93 ± 1.28 pmol/l respectively and rose in both cases, peaking at 60 minutes at 4.23 ± 1.01 and 7.55 ± 1.80 pmol/l (P < 0.05). At no time was there any evidence of differential secretion of GHRH 1‐44 or 1‐40.CONCLUSIONS We have confirmed previous studies demonstrating a small rise in GHRH before the GH response to l‐dopa. However, in all other situations of pharmacological stimulation of GH release we were unable to detect any significant changes in GHRH 1‐44 or 1‐40 levels. It seems most likely that peripheral GHRH does not reflect hypothalamic secretion. As yet there is no evidence for differential release of GHRH 1‐44 and 1‐40.
Energy expenditure and body composition in growth hormone deficient adults on exogenous growth hormone
Authors: Chong P. K. K. , Jung R. T. , Scrimgeour C. M. , Rennie M. J. , Paterson C. R. 
Published: March 2008

SummaryOBJECTIVES We assessed whether the obesity observed in growth hormone deficient adults is maintained by a reduction in energy expenditure. We studied the effects of exogenous growth hormone on energy expenditure and body composition.DESIGN We performed an open study with growth hormone administered at 0 5 units per kilogram ideal body weight per week for 3 months.PATIENTS Seven growth hormone deficient adults were studied. Thirty‐eight healthy volunteers had their resting metabolic rate measured, with seven of them proceeding to have their total energy expenditure assessed.MEASUREMENTS Total energy expenditure was measured by the doubly labelled water method (D2018), resting metabolic rate by ventilated hood indirect calorimetry, and fat free mass from the dilution volume of oxygen‐18. Body composition and components of energy expenditure were assessed before, at 2 weeks and at the end of the 3‐month treatment period on exogenous growth hormone.RESULTS Growth hormone deficient adults did not have a low total energy expenditure compared to healthy controls (13 12 vs 12 75 MJ/24 h) with only one patient expending less than 10 MJ/24 h. None had a resting metabolic rate lower than the 95% confidence limits of normality. The amount of energy expended on physical activity and thermogenesis was significant (6 54 MJ/24 h) and was similar to healthy controls (6 47 MJ/24 h).Resting metabolic rate increased by 15 9% after 14 days on exogenous growth hormone and was elevated 12‐1% after 3 months treatment but the ratio to fat‐free mass remained unaltered. Total energy expenditure increased by 13 4% after 14 days therapy. Fat‐free mass increased significantly after 3 months treatment by (mean) 4 5 kg with no change in fat mass and no loss in body weight.CONCLUSIONS Obesity maintenance in growth hormone deficient adults is not a consequence of reduced total energy expenditure or a reduced exercise energy output. There was also no evidence for an energy sparing mechanism. Energy expenditure was increased by exogenous growth hormone but was not associated with a loss in fat mass or body weight suggesting the need for dietetic advice for those already obese at the outset of therapy.
Pituitary stone: two cases of densely calcified thyrotrophin‐secreting pituitary adenomas
Authors: Webster Jonathan , Peters John R. , John Rhys , Smith Jeanne , Chan Vivien , Hall Reg , Scanlon Maurice F. 
Published: March 2008

SummaryCalcification is a well recognized but relatively uncommon feature of prolactin‐secreting, growth hormone‐secreting and non‐functional pituitary tumours. It varies in extent, but rarely exceeds a tiny amount histologically or radiologicatly. Thyrotroph adenomas are the rarest of the secretory pituitary tumours, accounting for less than 1% of cases, and partial calcification of such lesions has been reported in only three cases. We describe two patients in whom the clinical and biochemical features indicated the presence of a TSH‐secreting adenoma and radiology demonstrated a large ‘pituitary stone’. One patient, a 59‐year‐old female, initially presented with hyperthyroidism, aged 18, and was rendered euthyroid by two subtotal thyroidectomies before a pituitary lesion was suspected, over 20 years later. Autonomous secretion of thyrotropin was demonstrated by dynamic tests, and the failure of exogenous T3 to reduce the serum TSH. In the absence of tumour expansion and compressive symptoms, pituitary surgery was not undertaken. At the age of 56, she developed symptoms of intermittent ataxia and diplopia, culminating in a focal seizure, and was found on CT scan to have, in addition to the pituitary lesion, a parasagittal meningioma. This was successfully removed at craniotomy.In the second patient, a 42‐year‐old male, the finding of hyperthyroidism in association with an elevated TSH concentration led to the discovery of a pituitary stone which was removed transethmoidally, together with surrounding adenomatous tissue which stained positively for TSH on immunocytochemistry.We suggest that calcific changes may be at least as common in TSH‐secreting tumours as in other pituitary adenoma subtypes and may occur to the extent of ‘pituitary stone’ formation. The possible association between meningiomas and pituitary adenomas is discussed.