bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose and fat metabolism in adults with growth hormone deficiency
Authors: Salomon F. , Cuneo R. C. , Umpleby A. M. , Sönksen P. H. 
Published: March 2008

SummaryOBJECTIVE Adults with long‐standing GH deficiency have a decreased lean body mass and an increased fat mass. We investigated the effects of the abnormal body composition on glucose turnover and fuel metabolism.DESIGN Cross‐sectional analysis.PATIENTS Twenty‐four adults with acquired GH deficiency and a wide range of adiposity (body mass index from 18·8 to 42·3 kg/m2).MEASUREMENTS In the post‐absorptive state glucose turnover was measured following intravenous injection of 3‐3H‐glucose and leucine oxidation was assessed following intravenous injection of 1‐14C‐leuclne. Glucose and fat oxidation were calculated from indirect calorimetry using protein oxidation derived from leucine oxidation.RESULTS Total glucose turnover was 692 ± 146 μmol/min (mean ± SD) and Increased with height (r= 0·70, P= 0·0003) and with lean body mass (LBM) (r= 0·80, P < 0·0001). Glucose turnover expressed per kg LBM was in the published normal range (14·2 ± 2·1 pmol/kg LBM min). Glucose oxidation was 47 ± 27% of glucose turnover and increased with LBM (r= 0·59, P= 0·008) but not with height (r= 0·32, NS). Glucose turnover increased with increasing fat oxidation (r= 0·61, P= 0·006). The non‐oxidative part of glucose turnover was positively correlated with fat oxidation (r= 0·82, P= 0·0001) and inversely with the respiratory quotient (r= ‐0·81, P < 0·0001). Ketone body concentration (r= 0·55, P= 0·03), but not free fatty acid levels (r= 0·21, NS), correlated with fat oxidation. Fasting plasma glucagon levels were elevated (35 ± 13 vs 9 ± 19pmol/l (published controls) and inversely related to lean body mass (r= ‐0·44, P= 0·04).CONCLUSIONS Adults with GH deficiency studied after an overnight fast have changes In glucose and fuel metabolism seen In normal subjects after more prolonged fasting suggesting that adults with hormone deficiency have reduced carbohydrate stores.
Metabolic effects of growth hormone administered subcutaneously once or twice daily to growth hormone deficient adults
Authors: Laursen Torben , Jergensen Jens O. L. , Chrlstiansen Jens S. 
Published: March 2008

SummaryOBJECTIVE The aim of this study was to compare the metabolic effects of GH administered subcutaneously either once or twice daily. The actions of GH might depend upon a pulsatlle pattern of serum GH. Pulsatile and continuous intravenous delivery of GH, however, induce similar short‐term metabolic effects in GH deficient patients. An improved growth response is obtained in GH deficient children when a fixed weekly GH dose Is administered by dally subcutaneous injections instead of twice or thrice‐weekly intramuscular injections. A more pulsatile pattern and serum GH levels above zero might be achieved by further increasing the Injection frequency. Increased daytime GH levels might, however, adversely affect the circadian patterns of metabolic indices, whlch have been demonstrated to be more successfully reproduced by evening compared with morning GH administration.DESIGN AND MEASUREMENTS In a cross‐over study, 8 GH deficient patients (age 16–43 years) were treated with 3IU/m2/24h of human GH. The dose was injected in the evening for 4 weeks and for another 4 weeks two‐thirds was injected in the evening and one‐third in the morning. At the end of each period the patients were admitted to the hospital for 37 hours. Steady‐state profiles of GH, IGF‐I, IGF binding proteins 1 and 3, Insulin, glucose, lipid Intermediates and metabolites were obtained following administration of 3IU/m2 of GH (at 1900 h (one injection) and at 1900 and 0800 h (two injections). RESULTS Similar mean integrated levels of serum GH (mUII) were obtained (7·46 ± 0·84 (one injection) vs 6·46 ±0·62 (two Injections) (P = 0·15). Mean levels ± SEM of serum IGF‐I (μg/I) were significantly increased (P < 0·01) following two daily GH Injections (330·3±48·1 (one Injection) vs 399·1±53·0 (two injections). Serum IGFBP‐3 levels were not signlflcantly different on the two occasions, while levels of the GH Independent IGFBP‐1 (μg/l) were slightly but significantly lower following twice‐dally GH injections (1·61±0·42 vs 1·13 ±0·56, respectively (P < 0·04). The pattern of IGFBP‐1 was opposite to that of insulin. Similar levels of insulin and glucose were obtained with both GH regimens, while levels of non‐esterlfied fatty acids were significantly higher following once‐dally GH injection (P < 0·001).CONCLUSIONS Twice‐dally GH injections, apart from producing a more physiological serum GH profile, were superior to one Injection in increasing serum IGF‐I and decreasing IGFBP‐1 levels. Both of these changes tend to amplify the effects of the administered GH. Twice‐daily Injections, however, resulted Ln lower night‐time levels of lipid Intermediates.
Impaired prolactin response to arginine in patients with hyperthyroidism
Authors: Ciccarelli Enrica , Zini Michele , Grottoll Silvla , Razzore Paola , Portioli Italo , Valcavi Roberto 
Published: March 2008

SummaryOBJECTIVE Reduced PRL responses to TRH or dopamine antagonists have been described in hyperthyroid patients. Arginine stimulates PRL secretion through pathways other than the activation of TRH receptors or dopamine‐dependent mechanisms. We therefore investigated PRL responses to arginine in patients with hyperthyroidism.DESIGN L‐Arginine (30 g Infused over 30 minutes) was administered at time zero.SUBJECTS Sixteen patients with untreated hyperthyroidism due to Graves' disease (8 female and 8 male), with a mean age (± SE) of 31·3 ± 1·4 years (range 23–42), and 12 normal subjects (6 female and 6 male, ages 30·1 ± 2·1 years, range 22–47) were studied. MEASUREMENTS Prolactin was measured by RIA between ‐30 and 120 minutes, at 15‐minute intervals. RESULTS Basal PRL levels were similar in the hyperthyroid patients and normal control subjects. The hyperthyroid women showed blunted PRL responses compared to normal women (peak PRL levels, 364 ± 44mU/l, vs 760 ± 156, P < 0·02). PRL responses to arginine, small but clearly detectable in normal men, were completely abolished in hyperthyroid men (peak PRL levels, 248 ± 48mU/l, vs 112 ± 14, P < 0·01).CONCLUSIONS PRL responses to arginine are impaired in hyperthyroid patients. Therefore, arginine should be added to the list of PRL stimuli whose responses are blunted in hyperthyroidism, inhibition of PRL gene expression, and thus reduced pituitary PRL synthesis and storage, may explain why PRL responses to all secretagogues are reduced in these patients.
Multiple spuriously abnormal thyroid function indices due to heterophilic antibodies
Authors: Fiad T. M. , Duffy J. , McKenna T. J. 
Published: March 2008

SummaryA 57‐year‐old man with a history of liver fibrosis, portal hypertension and hypersplenism had thyroid function assessed because of weight loss. Free T4 (FT4), total T4 (TT4), total T3 (lT3) and TSH were all assayed by enhanced chemiluminescent immunoassay. This demonstrated elevation of all three hormones. Because of the atypical profile obtained and because the patient appeared to be euthyroid, re‐assay of the patient's serum was performed following immunoglobulin precipitation with 50% polyethylene glycol. The levels of T4 and T3 were then found to be within the reference ranges suggesting that the serum contained interfering immunoglobulins. Anti‐immunoglobulin antibodies also neutralized the interfering substances present in the patient's serum. These observations indicate that non‐specific immunoglobulins present in the patient's serum cross‐reacted with the antibodies employed in the assays used, giving rise to spurious results. To our knowledge, this is the first report of artefactual elevation of results obtained by T4, T3 and TSH assays of a serum occurring as a result of interfering immunoglobulins. Their presence became apparent only because of the very rare coincidence of antibodies interfering with more than one assay giving rise to an atypical hormone pattern. The frequency of this phenomenon affecting a single assay and therefore more likely to go undetected, is unknown and is a cause for concern.
A case of hepatoma associated with hypoglycaemia and overproduction of IGF‐II (E‐21): beneficial effects of treatment with growth hormone and intrahepatic adriamycin
Authors: Hunter Steven J. , Daughaday William H. , Callender Michael E. , McKnight John A. , Mcllrath Edwin M. , Teale J. Derrick , Atkinson A. Brew 
Published: March 2008

SummaryWe describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma Insulin‐like growth factor II (IGF‐11) was not elevated although 71% of plasma IGF‐II was present as big IGF‐II (molecular weight 11 kDa) which probably represents a non‐glycated form of pro‐IGF‐II. The GH response to hypoglycaemia was Impaired and plasma levels of both IGF‐l and the GH‐dependent IGF binding protein (IGFBP‐3) were low.A recently described unextracted assay directed against the first 21 amino acids of the E‐domain (E‐21) of proinsulin‐like growth factor‐II (pro‐IGF‐II) allows direct plasma estimation (plasma E‐21) of larger molecular forms of IGF‐II without interference from normal IGF‐II and IGF binding proteins. Basal values were grossly elevated (23·7 and 23·8 nmol/l).Treatment with GH led to an increase in the mean plasma glucose across 24 hours (4·25 ± 0·21 mol/1 (mean ± SEM) before treatment, compared with 4·86mmol/l ± 0·17 following GH (P < 0·01) and a reduction in hypoglycaemic attacks. The treatment was associated with a rise in IGFBP‐3 and small increases in insulin like growth factors. Subsequent treatment with the somatostatin analogue octreotide did not produce a significant change In plasma glucose levels or insulin‐like growth factors.Two courses of Intrahepatic adriamycin restored elevated levels of E‐21 to normal. Total IGF‐II remained normal and IGF‐I Increased. GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels. The patient remained free from hypoglycaemia. Twenty‐four months after his initial presentation he developed malignant ascites. Despite this evidence of tumour progression there was no recurrence of hypoglycaemia, and E‐21 and insulin‐like growth factor concentrations were normal. There was an initial response to intravenous chemotherapy with mithozantrone but subsequently he deteriorated and died 26 months after presentation.We conclude that E‐21 was useful in the diagnosis of this case of non‐islet cell tumour hypoglycaemia. GH was a helpful initlal treatment to prevent hypoglycaemia. However, the most beneficial therapy was Intrahepatic adriamycin which had a marked effect on plasma levels of E‐21. Hypoglycaemia was eliminated. It is possible that the decrease In circulating growth factors also had a beneficial effect on tumour growth, the patient having had a prolonged remission and excellent quality of life before the eventual development of malignant ascites.
Parathyroid hormone and parathyroid hormone‐related protein in the investigation of hypercalcaemia in two hospital populations
Authors: Walls Janet , Ratcliffe Wendy A. , Howell A. , Bundred N. J. 
Published: March 2008

SummaryBACKGROUND AND OBJECTIVE Parathyroid hormone‐related protein (PTHrP) produced by cancers has a central role as a humoral mediator of hypercalcaemia in patients with malignancy. Since the prevalences of hypercalcaemia of malignancy and parathyroid disease reflect the population studied, hypercalcaemia patients from a district general hospital (DGH) and an oncology centre (OC) were studied in order to assess the diagnostic role of assays for serum PTH and plasma PTHrP in different clinical settings.DESIGN A prospective study of consecutive patients presenting with their first episode of hypercalcaemia during an 18‐month period.PATIENTS A total of 123 patients (DGH, n= 69; OC, n= 54) had corrected serum calcium concentrations > 2·65mmol/l.MEASUREMENTS PTH, PTHrP, calcium and albumin were measured together with urine calcium and creatinine, enabling fractional calcium excretion to be assessed. Urine cyclic adenosine monophosphate was also measured.RESULTS Hypercalcaemia was attributed to malignancy alone in 72 patients (DGH, n= 20; OC, n= 52), benign causes in 42 (DGH, n= 42) and parathyroid disease coexisting with malignancy in 9 (DGH, n = 7; OC, n= 2). Plasma PTHrP levels were increased in 59/72 (82%) patients with hypercalcaemia due to malignancy. Measurements of both analytes contributed to a change in the final diagnosis in 12 patients (10%). Thus serum PTH was Increased In seven patients with parathyroid disease coexisting with malignancy, and plasma PTHrP was increased in five patients with previous undiagnosed malignancy. Median survival for patients with parathyroid disease and coexisting malignancy was 13 months compared with 3 months for those with hypercalcaemia due to malignancy alone (P < 0.02).CONCLUSIONS Since hypercalcaemia was attributable to parathyroid disease In 10% of ail patients with malignancy we advise measurement of serum PTH at the Initial presentation of hypercalcaemia in ail patients, while plasma PTHrP may be useful to identify those patients in whom malignancy may not be clinically apparent, or coexist with primary hyperparathyroidism.
Bone metabolism during anti‐thyroid drug treatment of endogenous subclinical hyperthyroidism
Authors: Mudde A. H. , Houben A. J. H. M. , Kruseman A. C. Nieuwenhuijzen 
Published: March 2008

SummaryOBJECTIVE There is recent evidence that both exogenous and endogenous subclinical thyrotoxicoses are associated with decreased bone mineral density. Scanty information is available on bone metabolism in these conditions when euthyroidism is restored. We evaluated the effect of anti‐thyroid drug treatment on bone metabolism in endogenous subclinical hyperthyroidism.DESIGN Prospective follow‐up study over 2 years during treatment with methimazole, with an untreated control group.SUBJECTS Sixteen post‐menopausal women with endogenous subclinical hyperthyroidism associated with multinodular goitre, eight of whom were treated with methimazole.MEASUREMENTS Serum concentrations of free T4, total T3, TSH, osteocalcin, urinary excretion of hydroxyproline and forearm bone mineral density were measured at regular intervals.RESULTS Significant changes in serum osteocalcin concentration or urinary hydroxyproline excretion were not observed in either group. Distal, but not proximal, forearm bone mineral density, expressed as a percentage of the base‐line value, was significantly (P < 0.05) higher in the treated than in the untreated subjects in the second year of treatment.CONCLUSION Treatment with methimazole In post‐menopausal women with endogenous subclinical hyperthyroidism associated with multinodular goitre can prevent excessive loss of bone, at least in the distal forearm.
Loss of the normal relationships between growth hormone, growth hormone‐binding protein and insulin‐like growth factor‐I in adolescents with insulin‐dependent diabetes mellitus
Authors: Clayton Kharen L. , Holly Jeff M. P. , Carlsson Lena M. S. , Jones Jenny , Cheetham Tim D. , Taylor Alistair M. , Dunger David B. 
Published: March 2008

SummaryOBJECTIVE It has been proposed that the dissociation between growth hormone secretion and insulin‐like growth factor‐I (IGF‐I) concentrations in insulin‐dependent diabetes mellitus arises because of partial resistance at the GH receptor. In order to explore this hypothesis further we have examined the relations between IGF‐I, GH‐binding protein (GHBP), and GH secretion in normal subjects and patients with diabetes during puberty.DESIGN AND SUBJECTS Blood samples for the estimation of IGF‐I and GHBP levels were obtained from 104 patients with diabetes and 89 puberty matched controls. Thirty‐four of the controls and 42 of the patients with diabetes also underwent an overnight GH secretory profile with measurements of GH every 15–20 minutes between 2000 and 0800 h.RESULTS In multivariate analysis using sex, puberty stage, and presence or absence of diabetes as dependent variables, diabetes was associated with increased GH levels (F= 23·04, P < 0·001), reduced IGF‐I (F= 10·89, P < 0·001), and reduced GHBP levels (F= 31·36, P < 0·001). A negative relation between GH and GHBP levels (r= ‐0·44, P < 0·01) was found in normal subjects but this was absent in those with diabetes. Both GHBP and IGF‐l levels in the diabetic subjects were correlated with total insulin dose (r= 0·4, P < 0·001, and r= 0·46, P < 0·001, respectively). Yet there was no direct correlation between GHBP and IGF‐I concentrations. The variation in IGF‐I levels was also related to glycosylated haemoglobin levels in the diabetics (r= ‐0·27, P= 0·01). In a stepwise multiple regression analysis insulin dose contributed 23%, HbA1 4·4% and C‐peptide levels 3·7% to the variation in IGF‐I levels.CONCLUSIONS In adolescents with insulin dependent diabetes mellitus, the elevated OH concentrations are associated with low circulating IGF‐l and GHBP concentrations and the normal reciprocal relation between GHBP and GH is no longer evident. Although IGF‐I and GHBP are both related to insulin dose, there is no direct correlation between these variables. This may indicate that GHBP reflects GH receptor numbers but not necessarily post receptor events, and the weak positive correlation between GH and IGF‐I indicates that increased growth hormone secretion may compensate for reduced receptor numbers.
Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin)
Authors: Laron Zvi , Frenkel Jenny , Gil‐Ad Lrit , Klinger Beatrice , Lubin Ernesto , Wuthrich Patrick , Boutignon François , Lengerts Vincent , Deghenghi Romano 
Published: March 2008

SummaryOBJECTIVE Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide.PATIENTS Ten children with familial short stature (FSS) aged 5·5‐15·5 years and two known GH deficient patients aged 24 and 28 years without GH treatment.METHODS All 12 subjects were submitted to i.v. (1 μg/kg) and i.n. (20 μg/kg) hexarelin tests with a one‐week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio‐immunoassays (RIA).RESULTS Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (±SD) being 72·2± 35·5 mU/l for the i.n. test and 79·6 ± 53·0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15–30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response In either test. Plasma TSH decreased in the FSS children from a mean (±SD) of 1.0 ± 0·26 to 0·64±0 2 mU/l (P<0 005) during the i.n. test and from 1·0±0·3 to 0·7±0·3mU/l (P> 0 05) during the I.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1·06±0·38 mU/l to 0·86±0·17 during the i.v. test and from 1·60±0·01 to 1·11±0·06mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests.CONCLUSIONS The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intra‐nasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.
Dopamine and the sick euthyroid syndrome in critical illness
Authors: Van den Berghe Greet , de Zegher Francis , Lauwers Peter 
Published: March 2008

SummaryOBJECTIVE The Sick euthyroid syndrome is a poorly understood hallmark of critical illness. Dopamine is a natural catecholamine with hypophysiotrophic properties, that is used as an inotropic agent of first choice in intensive care medicine. We explored the effect of dopamine infusion (5μg/kg/min) on the sick euthyroid syndrome of critically ill patients.PATIENTS AND DESION In a prospective, randomized, controlled and open‐labelled study of critically ill, adult polytrauma patients (n= 12), we evaluated the effect of prolonged (83–296 hours) dopamine Infusion (5 μg/kg/min i.v.) on the thyroid axis. The effect of brief (15–21 hours) dopamine administration was documented in an additional randomized, controlled, cross‐over study involving 10 patients. The median age of the studied patients was 29 (16–83) years.MEASUREMENTS Serum TSH concentrations were measured by IRMA. The TSH profiles were obtained by blood sampling every 20 minutes for 9 hours during two consecutive nights. Serum T4, T3 and reverse T3 concentrations were measured by RIA once per study night.RESULTS Withdrawal of prolonged dopamine infusion was found to elicit a tenfold increase of serum thyrotrophin concentrations, a 57 and 82% rise of T4 and T3 respectively, and an Increase of the T3/rT3 ratio, resulting in virtual normalization of the thyroid axis within 24 hours. The brief dopamine infusion was documented to have a suppressive effect on the thyroid axis within 24 hours.CONCLUSIONS Dopamine infusion appears to induce or aggravate the sick euthyroid syndrome in critical illness. As a consequence, the sick euthyroid syndrome of severely ill patients receiving dopamine may be not an adaptive mechanism, but a condition of latrogenic hypothyroidism.
Eighty‐six cases of Addison's disease
Authors: Kong Marie‐France , Jeffcoate William 
Published: March 2008

SummaryOBJECTIVES Since there have been no recent reviews of Addison's disease, we have undertaken a retrospective case‐notes review of all identifiable cases in Nottingham to define the prevalence, incidence and causes of Addison's disease. We have also reviewed the criteria for interpretation of the short Synacthen test in diagnosis.DESIGN A retrospective study of all patients coded for the diagnosis and admitted to Nottingham's hospitals between 1 April 1987 and 31 March 1993, identified by the hospital information Services.PATIENTS A total of 86 cases were identifiable of whom 66 were still alive and living in the town.RESULTS AND CONCLUSIONS The calculated prevalence was 110 per million population. The cause was attributed to autoimmune destruction of the adrenal cortex in 81 (93%). There were two cases of metastatic malignancy and three unrelated cases of late onset adrenoleukodystrophy, but none were attributable to tuberculosis. Twenty‐one new cases were diagnosed between 1987 and 1993. The calculated incidence was 5·6 per million per annum. The biochemical bash of the diagnosis was reviewed in there 21 patients and as a result firm criteria are suggested for the interpretation of the short Synacthen test criteria for normality being baseline cortisol > 250 and 30 minute peak > 600 nmol/l, taking Into account clinical circumstances.