bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case of papillary carcinoma of the thyroid with more than 30 years long‐term asymptomatic pulmonary metastases
Authors: Maruyama Masayuki , Sugenoya Akira , Kobayashi Shinya , Masuda Hiroyuki , Shimizu Tadahiro , Lida Futoshi 
Published: March 2008

SummaryThis is a case report of a patient with thyroid cancer with asymptomatic pulmonary metastases, and without obvious progression over 34 years.The patient, a 47‐year‐old male, was shown to have miliary shadows on chest radiographs from the age of 13; indeed, he was temporarily treated for pulmonary tuberculosis without success. A tumour appeared in the right neck in December 1988 (at age 47). A diagnosis of lymph node metastasis of papillary carcinoma of the thyroid was made by biopsy; he then underwent total thyroidectomy with radical dissection of the neck (April 1989). However, the bilateral metastatic lymph nodes in the neck had invaded the vasculature, preventing complete dissection. Post‐operative whole body 131I scintigraphy revealed diffuse intensive uptake in the bilateral lung fields, demonstrating for the first time that the pulmonary lesions were metastases of the thyroid cancer. He remains under periodic effective treatment with 131I.
Proinsulin, proinsulin intermediate and insulin in cystic fibrosis
Authors: Hamdi I. , Green M. , Shneerson J. M. , Palmer C. R. , Hales C. N. 
Published: March 2008

SummaryOBJECTIVE We determined the changes in insulin, intact proinsulin and 32‐33 split proinsulin as markers of β cell damage in assessing the state of carbohydrate intolerance in patients with cystic fibrosis.DESIGN Measurements of insulin, proinsulin and 32‐33 proinsulin concentrations in cystic fibrosis following oral glucose tolerance test (OGTT).SUBJECTS Sixteen cystic fibrosis patients attending the chest outpatient clinic for follow‐up, age range 14–42 years, and 14 healthy controls matched for age and body mass index.MEASUREMENTS Insulin, intact proinsulin and 32‐33 split proinsulin were measured immunoradiometrically at 0, 30, 60, 90 and 120 minutes after an OGTT. Glucose and HbA1 were also measured.RESULTS Cystic fibrosis patients were divided into two groups according to their OGTT results: those with diabetes mellitus or impaired glucose tolerance and those with normal glucose tolerance.Insulin concentrations and insulin/glucose ratios at 30 minutes were lower in both cystic fibrosis groups in comparison with the control. There was also a significant increase in the time to reach peak insulin levels in both cystic fibrosis groups.Fasting intact proinsulin concentrations and the proportion of proinsulin‐like molecules were significantly higher in cystic fibrosis with diabetes mellitus or impaired glucose tolerance than in the control group, but not in the normal glucose tolerance cystic fibrosis group. There was no significant difference in the plasma concentrations of 32‐33 split proinsulin amongst the three groups.CONCLUSIONS Abnormal β cell function in cystic fibrosis patients was reflected initially in a diminished 30‐minute insulin response to oral glucose. A significant rise in fasting intact proinsulin and the proportion of proinsulin‐like molecules was seen only in cystic fibrosis patients who had progressed to impaired glucose tolerance or diabetes mellitus. Cystic fibrosis patients with normal glucose tolerance showed changes intermediate between the control and the other group.
Effect of varying concentrations of follicle stimulating hormone on the production of gonadotrophin surge attenuating factor (GnSAF) in women
Authors: Messinis I. E. , Lolis D. , Papadopoulos L. , Tsahallna Th. , Papanikolaou N. , Seferiadis K. , Templeton A. A. 
Published: March 2008

SummaryOBJECTIVE We studied the time‐course of production of gonadotrophin surge attenuating factor (GnSAF) in relation to varying serum concentrations of FSH in women. DESIGN Normally cycling women were investigated in four cycles, i.e. a spontaneous cycle treated with placebo (cycle P) and three cycles treated with three different FSH dosages (1 ampoule, cycle 1; 3 ampoules, cycle 3 and 6 ampoules, cycle 6). Placebo or FSH were given as a single i.m. injection on cycle day 2 (0900 h). The response of LH to an i.v. injection of 10 μg GnRH (GnSAF bioactivity) was investigated 4, 8, 12 and 24 hours after the injection of placebo or FSH.PATIENTS Six normally ovulating women with long‐standing unexplained infertility were studied. The women were used as their own controls during the cycle treated with placebo.MEASUREMENTS Pituitary response to GnRH was calculated as the net increase in LH at 30 minutes (ΔLH) above the basal value.RESULTS Serum FSH concentrations increased after the injection of FSH in a dose dependent manner. Compared with cycle P, Δ LH was significantly attenuated in cycle 3 and cycle 6 at 8,12 and 24 hours and in cycle 1 at 12 hours after the injection of FSH. Basal concentrations of oestra‐diol (E2) and LH did not differ significantly among the four cycles at any point except in cycle 6 at 24 hours after the FSH injection when E2 values were significantly higher and LH values significantly lower than in cycle‐P.CONCLUSIONS These results suggest that GnSAF bioactivity increases significantly as early as 8 hours from a single injection of FSH before any significant increase in serum E2 values. We conclude that in women the effect of FSH on the production of GnSAF in the early follicular phase is concentration dependent.
Calcitonin gene‐related peptide in small cell lung carcinomas
Authors: Schifter Søren , Johannsen Lis , Bunker Chris , Brickell Paul , Bork Ellen , Lindeberg Henning , Faber Jens 
Published: March 2008

SummaryOBJECTIVE Calcitonin gene‐related peptide (CGRP) is a regulatory peptide encoded by the calcitonin gene. CGRP is expressed in increased amounts by the cells of medullary thyroid carcinomas and has been demonstrated by immunohistochemistry to occur in neuroendocrine cells and nerve fibres of lung tissue.MEASUREMENTS Serum CGRP levels were measured in patients with small cell lung carcinomas before treatment (n= 74) and immediately before the second course of chemotherapy (n= 30). In‐situ hybridization and immunohistochemistry were performed on tumour tissue and CGRP was extracted from two tumours and characterized by gel chromatography and high pressure liquid chromatography.RESULTS Serum CGRP levels were elevated in small cell lung carcinomas when compared with healthy controls of similar age and sex (median values 55.0 vs 36.6 pmol/l, P<0.001), and 27% had levels above the upper normal range. Serum CGRP levels decreased following the initial course of chemotherapy (P < 0.05) but remained elevated when compared to the controls (P < 0.001). In‐situ hybridization for CGRP mRNA was positive in three of 17 tumours and immunohistochemistry was positive in seven of 31 tumours investigated. CGRP immunoreactivity extracted from two tumours was characterized by gel chromatography and high pressure liquid chromatography. A major part of the immunoreactivity was demonstrated to represent the intact molecule.CONCLUSIONS We found that patients with small cell lung carcinomas had elevated concentration of serum calcitonin gene‐related peptide but only 27% had values above the upper normal range. Serum CGRP is therefore of limited value as a tumour marker. Intact CGRP can be extracted from tumour tissue, but in‐situ hybridization and immunohistochemistry showed positive reactions in only a few of the tumours investigated. The elevated serum CGRP levels are therefore likely to be largely of extratumoral origin.
Relation between phenotype and intra‐cellular thyroid hormone effect in patients with altered peripheral thyroid hormone sensitivity
Authors: Kvetny J. , Bollerslev J. 
Published: March 2008

SummaryOBJECTIVE We wished to ascertain whether different phenotypic appearances in patients with altered cellular sensitivity to thyroid hormones were related to the type of altered intra‐cellular thyroid hormone effect.DESIGN Blood samples were obtained from two members of a family suffering from generalized thyroid hormone resistance (GTHR) for hormone assays and examination of the cellular thyroid hormone effect, and the results compared with results from other families with signs of altered peripheral thyroid hormone sensitivity.PATIENTS Two members of a family with thyroid hormone resistance and nine normal persons were studied.MEASUREMENTS Basal thyroid hormone function tests were measured. The thyroid hormone effect on mononuclear blood cells was determined by measuring the thyroid hormone stimulated oxygen consumption and glucose uptake.RESULTS The two family members appeared phenotypically normal except for nodular goitre. Thyroid hormone stimulated glucose uptake was depressed whereas thyröid hormone stimulated oxygen consumption was normal.CONCLUSION Comparison of the present results of the cellular examination in two patients with GTHR, with the results obtained in other families with altered peripheral thyroid hormone sensitivity, suggest that the classic GTHR (phenotype: normal or with goitre) is linked to impaired thyroid hormone stimulated glucose uptake, whereas in patients with osteopetrosis, the thyroid hormone insensi‐tivity seems located at the mitochondrial level (impaired thyroid hormone stimulated oxygen consumption).
Effects of growth hormone therapy on the developmental changes of follicle stimulating hormone and insulin‐like growth factor‐I serum concentrations in Turner's syndrome
Authors: Bourguignon Jean‐Pierre , Gérard Arlette , Deby‐Dupont Ginette , Franchlmont Paul 
Published: March 2008

SummaryOBJECTIVE The aim was to investigate whether, in the absence of gonads, GH could bring forward the age of neuroendocrine activation resulting in onset of puberty. DESIGN In girls with Turner's syndrome, we evaluated the effects of GH therapy on developmental changes in FSH serum concentrations used as an indicator of neuroendocrine maturation in the absence of gonads.PATIENTS Thirty‐nine girls with Turner's syndrome aged 4.0‐17.1 years were treated using GH (25 IU/m2 week) for 1 year.MEASUREMENTS Serum levels of FSH and IGF‐I were measured before initiation of GH therapy and 12 months later, after interruption of GH treatment for 2 days.RESULTS Pretreatment FSH levels were low between 6 and 10 years and increased markedly at 10‐11 years of age. This pattern was unchanged after 1 year of GH therapy. Pretreatment IGF‐I levels were positively correlated with age and they were uniformly increased after 1 year of GH therapy.CONCLUSIONS Our data suggest that GH and its effector, IGF‐I, do not influence the timing of the onset of puberty through an effect on its neuroendocrine control.
An audit of dynamic function tests: errors in the timing of blood specimens
Authors: Barth J. H. , Page M. D. , Bailey I. R. 
Published: March 2008

SummaryOBJECTIVE The interpretation of dynamic endocrine investigations is dependent on the timing of blood sampled after a stimulus. We have studied the accuracy with which doctors adhered to a prescribed protocol. DESIGN A new request form for dynamic tests was designed to include both the planned and the actual time of blood sampling in order to allow assessment of the variance of sample timing.MEASUREMENTS We followed 152 investigation procedures comprising 791 planned specimens. A total number of 627 timing intervals could be analysed of which 366 timing intervals did not differ from the planned Interval. Protocols were divided into long and short (greater or less than 6 hours) and into those governed by clock times or ‘stopwatch’, i.e. minutes elapsed, Intervals. RESULTS A total of 22% specimens were taken more than 10 minutes earlier or later than planned. Six per cent of specimens were taken more than 30 minutes earlier or later than planned.CONCLUSIONS The data presented in this study suggest that in order to improve the interpretative accuracy of dynamic tests, it would appear prudent to pay more attention to the accuracy of sample timing. New dynamic test publications should include time tolerance for the normal response.
Severe peripheral neuropathy and elevated plantar pressures causing foot ulceration in pituitary gigantism
Authors: Jennings A. M. , Robinson A. , Kandler R. H. , Betts R. P. , Ryder R. E. J. , Cullen D. R. 
Published: March 2008

SummaryWe report two patients with treated pituitary gigantism and peripheral neuropathy, one of whom has chronic foot ulceration. Detailed neurophysiologfcal assessment was performed on both patients. The patient with foot ulceration had clinical and neurophysiological evidence of severe neuropathy, whereas the patient without ulceration had only neurophysiological abnormalities. The sweating response to acetylcholine was markedly impaired in the feet of both patients, suggesting pedal autonomic denervation. Neither patient had evidence of diabetes mellitus and detailed investigation failed to reveal an alternative cause of peripheral neuropathy. Optical pedobarography revealed abnormally high pressure (>10 kg/cm2) under the metatarsal heads of both patients, one such area coinciding with the area of ulceration. Thus in pituitary gigantism elevated plantar pressures may contribute to the development of foot ulceration when severe peripheral neuropathy Is present. Furthermore, as in diabetes mellitus, impaired sweating may also increase the risk of ulceration as the resultant dry skin may develop fissures.
The effect of recombinant human insulin‐like growth factor‐I treatment on growth hormone secretion in two subjects with growth hormone insensitivity (Laron syndrome)
Authors: Cotterill Andrew M. , Camacho‐Hübner Cecilia , Holly Jeffrey M. P. , Savage Martin O. 
Published: March 2008

SummaryOBJECTIVE Growth hormone (GH) secretion Is increased in conditions of GH insensitivity such as Laron syndrome, with elevation of both basal and peak levels. We have studied the effect of recombinant IGF‐I therapy on the pattern of GH secretion in two subjects with GH insensitivity.SUBJECTS Two pubertal subjects with GH insensitivity (female, 16.4 years, breast stage 3; male 13.6 years, genital stage 2) were investigated after 6 months of IGF‐I therapy (120 μg/kg twice daily s.c. at 0800 and 1900 h). GH profiles taken before the start of IGF‐I therapy, when both subjects were prepubertal (aged 14 0 and 11 5 years respectively), were used for comparison.METHODS GH profiles were performed with blood samples taken every 20 minutes between 2000 and 0800 h from an indwelling cannula.MEASUREMENTS Serum samples were assayed for GH by immunoradiometric assay and IGF‐I, IGFBP‐1 and insulin by radioimmunoassay.RESULTS Before IGF‐I therapy, GH profile studies demonstrated pulsatile GH secretion. Basal GH was elevated with no value falling below the limit of detection of the assay and an increase in peak levels (maximum 203 and 206 μ/I at 0000 h and 0020 h respectively). After 6 months IGF‐I therapy, the GH profiles were significantly different. With the onset of puberty a further increase in GH secretion would have been expected; nevertheless, following administration of IGF‐I at 1900 h, GH secretion decreased with a reduction in mean overnight GH levels from 65 to 33 μ/l and 53 to 11 μ/l respectively. GH pulsatility was also suppressed in the two subjects, for the first 3.5 and 6 hours overnight respectively. Pulsatile GH secretion then returned with peak levels reaching 130 and 63 μ/l respectively.Prior to therapy IGF‐I levels were at the lower limit of assay detection. On IGF‐I therapy serum IGF‐I levels reached a peak within 3 hours (298 and 438 μg/l) coinciding with the suppression of GH secretion. IGF‐I levels fell rapidly overnight to 92 and 101 μg/l at 0800 h prior to the next injection. The fall in serum IGF‐I coincided with the return of GH secretion.IGFBP‐1 levels increased overnight both before and during IGF‐I therapy, rising from 24 to 83 and 22 to 110 μg/l before therapy and 13 to 60 and 13 to 71 μg/l during therapy. This rise in IGFBP‐1 appeared to be inversely related to the fall in serum insulin levels overnight and appeared not to be affected by IGF‐I therapy.CONCLUSION GH secretion is suppressed by exogenous IGF‐I therapy in GH insensitive subjects. The failure to maintain high serum IGF‐I levels overnight, presumably due to a persisting defect in serum IGFBP‐3 levels, was associated with an early return of GH secretion. These findings may have implications for the dose and regimen of IGF‐I therapy in subjects with growth hormone insensitivity.
The cellular and molecular basis of the ectopic ACTH syndrome
Authors: White A. , Clark A. J. L. 
Published: March 2008

SummaryIn recent years the techniques of molecular and cellular biology have made it possible to begin to dissect the origins and behaviour of the ACTH‐secreting tumour cell. It is becoming apparent that these tumours represent undifferentiated neuroendocrine cells, and it may be that their peptide‐secreting properties may have no more sinister oncological significance. However, an autocrine role for β‐endorphin may confer a selective growth advantage on the POMC‐expressing cell. It is still not clear why glucocorticoids fail to inhibit the POMC gene in these extra‐pituitary tumours despite the presence of glucocorticoid receptors. This may not be resolved until the mechanism for inhibition of POMC by glucocorticoids in the normal pituitary is understood, although it is tempting to speculate that a mutation in the glucocorticoid receptor or a tissue specific interaction is responsible for the resistance of POMC observed in the ectopic ACTH syndrome.In studying the peptides secreted by the extra‐pituitary tumours responsible for the ectopic ACTH syndrome it would appear that direct measurement of ACTH precursors and comparison with the circulating concentrations of ACTH can give valuable information on the percentage of tumours which do not effectively process the ACTH precursors. However, far more data have to be collected on patients with occult tumours in order to identify whether this type of processing is tissue specific. Nevertheless, these studies provide useful insights into the mechanisms of intracellular signalling and regulation in such tumours which may identify unique pharmacological tools to inhibit ACTH secretion or more importantly tumour growth.
Melatonin stimulates growth hormone secretion through pathways other than the growth hormone‐releasing hormone
Authors: Valcavi Roberto , Zini Michele , Maestroni Georges J. , Conti Ario , Portioli Italo 
Published: March 2008

SummaryOBJECTIVE There is evidence that melatonin plays a role in the regulation of GH secretion. The aim of this study was to investigate the neuroendocrine mechanisms by which melatonin modulates GH secretion. Thus we assessed the effect of oral melatonin on the GH responses to GHRH administration and compared the effects of melatonin with those of pyridostigmine, a cholinergic agonist drug which is likely to suppress hypothalamic somatostatin release.DESIGN The study consisted of four protocols carried out during the afternoon hours. Study 1: oral melatonin (10 mg) or placebo were administered 60 minutes prior to GHRH (100 μg i.v. bolus). Study 2: GHRH (100 μg i.v. bolus) or placebo were administered at 0 minutes; oral melatonin or placebo were given at 60 minutes and were followed by a second GHRH stimulus (100 μg i.v. bolus) at 120 minutes. Study 3: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions. Study 4: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions 60 minutes prior to a submaximal dose (3 μg i.v. bolus) of GHRH.SUBJECTS Four groups of eight normal male subjects, ages 22–35 years, were randomly assigned to each protocol.MEASUREMENTS Growth hormone was measured by RIA at 15‐minute intervals.RESULTS Oral melatonin administration had a weak stimulatory effect on GH basal levels. Prior melatonin administration approximately doubled the GH release induced by supramaximal (100 μg) or submaximal (3 μg) doses of GHRH. Melatonin administration restored the GH response to a second GHRH challenge, given 120 minutes after a first GHRH i.v. bolus. The GH releasing effects of pyridostigmine, either alone or followed by GHRH, were greater than those of melatonin. However, the simultaneous administration of melatonin and pyridostigmine was not followed by any further enhancement of GH release, either in the absence or in the presence of exogenous GHRH.CONCLUSIONS Our data indicate that oral administration of melatonin to normal human males increases basal GH release and GH responsiveness to GHRH through the same pathways as pyridostigmine. Therefore it is likely that melatonin plays this facilitatory role at the hypothalamic level by inhibiting endogenous somatostatin release, although with a lower potency than pyridostigmine. The physiological role of melatonin in GH neuroregulation remains to be established.
Urinary growth hormone excretion in the assessment off children with disorders of growth
Authors: Skinner A. M. , Clayton P. E. , Price D. A. , Addison G. M. , Soo A. 
Published: March 2008

SummaryOBJECTIVE We wished to evaluate the use of urinary GH measurements when compared to conventional GH provocation tests in the assessment of short children.DESIGN Children presenting for the first time to a regional growth clinic were assessed clinically by one observer. Investigations comprising standard GH provocation tests and measurement of urinary GH were undertaken to exclude GH deficiency.PATIENTS Fifty‐eight children aged 58‐16 years were enrolled. Ten were diagnosed on clinical assessment as GH deficient, 43 had delayed growth and/or familial short stature, and five had idiopathic short stature; the 48 children in the last two groups were defined as short normal.MEASUREMENTS GH secretion was evaluated by two standard provocation tests and by the measurement of GH in five overnight urine collections. A normal peak GH concentration was defined as <16 μ/l. The values for urinary GH excretion were compared to normal ranges (2 standard deviations from the mean), established in healthy schoolchildren of normal stature.RESULTS All children considered GH deficient on clinical grounds had low peak GH concentrations on provocation tests, while 8/10 had low values of urinary GH excretion. All short normal children with normal peak GH concentrations (n= 36) on provocation tests and 11/12 children with low peak GH concentrations had urinary GH excretion within the normal range. There was therefore a significant difference in the classification of‘normal’GH secretion in the two tests. If the clinical diagnosis was used as the standard by which GH tests were Judged, the predictive value of a positive urinary GH test in the diagnosis of GH deficiency was 89% compared with 45% for GH provocation tests.CONCLUSION The use of urinary growth hormone measurements leads to the classification of more children with disorders of growth having adequate GH secretion than that derived from GH provocation tests.