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11. |
Thyroid peroxidase: evidence for disease gene exclusion in Pendred's syndrome |
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Clinical Endocrinology,
Volume 44,
Issue 4,
1996,
Page 441-446
Eleanor Gausden,
John A. L. Armour,
Beth Coyle,
Rebecca Coffey,
Ze'ev Hochberg,
Marcus Pembrey,
Keith E. Britton,
Ashley Grossman,
William Reardon,
Richard Trembath,
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摘要:
OBJECTIVE Pendred's syndrome is an association between congenital neurosensory deafness and goitre with abnormal discharge of iodide following perchlorate challenge, indicating a defect of iodide organification. Although Pendred's syndrome may cause up to 7.5% of all cases of congenital deafness, the molecular basis of the association between the hearing loss and the thyroid organification defect remains unknown. We chose to investigate the role of the thyroid peroxidase (TPO) gene as the genetic defect in Pendred's syndrome.DESIGN A highly informative variable number tandem repeat (VNTR), located 1.5kb downstream of exon 10 of the TPO gene,was used to search for genetic linkage in multiple sibships affected by Pendred's syndrome.PATIENTS Seven kindreds were recruited from the UK, each with at least two affected members. We have also examined a large inbred Israeli family with two affected offspring and five unaffected children.MEASUREMENTS Individuals were assigned affected status based on the characteristic clinical features of Pendred's syndrome, namely the presence of congenital sensorineural hearing loss and the appearance in early life of a goitre. Additionally, at least one affected member from each sibship had a characteristic positive perchlorate discharge test (Morgans&Trotter, 1958). PCR amplification of genomic DNA at the TPO VNTR allowed assignment of genotypes to each individual and the calculation of a two‐point LOD scoreRESULTS In six of the nine sibships analysed we found obligatory recombination between TPO and Pendred's syndrome. Non‐complementation observed in affected parents with an affected offspring excluded TPO in an affected sibship with genotype sharing and supports a hypothesis of genetic homogeneity for Pendred's syndrome. In two sibships, mutation of the TPO gene as the cause of Pendred's syndrome could not be excluded.CONCLUSIONS These data suggest that defects at the thyroid peroxidase locus on chromosome 2 are not the major cause of Pen
ISSN:0300-0664
DOI:10.1046/j.1365-2265.1996.714536.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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12. |
Urinary excretion of pyridinoline and deoxypyridinoline measured by immunoassay in hypothyroidism |
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Clinical Endocrinology,
Volume 44,
Issue 4,
1996,
Page 447-451
Hirotoshi Nakamura,
Tomoko Mori,
Rieko Genma,
Yoshikazu Suzuki,
Hiroko Natsume,
Shinichiro Andoh,
Ryo Kitahara,
Shinsuke Nagasawa,
Kozo Nishiyama,
Teruya Yoshimi,
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摘要:
OBJECTIVE We measured pyridinium cross‐links, markers of bone resorption, by an enzyme‐linked immunosorbent assay (ELISA) in hypothyroid patients to see whether bone resorption was reduced in hypothyroidism and whether it increased with T4 treatment.DESIGN AND PATIENTS Eight hypothyroid patients, whose initial TSH levels were 268.1 ± 87.7 mU/l (mean ± SE), were treated with T4 (100μg/day). Urinary excretion of pyridinium cross‐links was assayed before and after T4 treatment.MEASUREMENTS Pyrilinks and Pyrilinks‐D kits were used. The Pyrilinks assay measures free forms of pyridinoline and deoxypyridinoline together (PYD), while the Pyrilinks‐D assay measures deoxypyridinoline (DPD) alone. The Pyrilinks reference ranges for normal subjects are 8–24nmol/mmol creatinine in males and 10–28nmol/mmol creatinine in normal premenopausal females. The DPD reference ranges obtained from normal men and women aged 40–50 years were 3.20 ± 0.75 (mean ± SD) nmol/mmol creatinine and 4.55 ± 1.22 nmol/mmol creatinine, respectively.RESULTS The sensitivity of the assay was enhanced by simply using less diluted urine samples. Concentrations of both compounds of the urinary pyridinium cross‐links were low in untreated hypothyroid patients and increased gradually as thyroid hormone status improved from hypothyroidism to euthyroidism. One month after treatment when the TSH levels in the patients were still as high as 74.4 ± 44.5 mU/l, urinary PYD excretion has increased to 2.6 times the pretreatment level. When the TSH levels of the patients decreased below 10 mU/l, both PYD and DPD increased significantly to 3.8 and 3.3 times pretreatment values, respectively.CONCLUSIONS Although hyperthyroidism or excess treatment with thyroid hormone has been known to induce bone resorption, this is the first report that urinary excretion of pyridinium cross‐links is reduced in hypothyroidism and is normalized by p
ISSN:0300-0664
DOI:10.1046/j.1365-2265.1996.691513.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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13. |
Glucose turnover, fuel oxidation and forearm substrate exchange in patients with thyrotoxicosis before and after medical treatment |
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Clinical Endocrinology,
Volume 44,
Issue 4,
1996,
Page 453-459
Niels Møller,
Søren Nielsen,
Birgit Nyholm,
Niels Pørksen,
K. George,
M. M. Alberti,
Jørgen Weeke,
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摘要:
OBJECTIVE Accelerated metabolism is a hallmark of thyrotoxicosis, but the underlying bioche mical mechanisms are incompletely understood and the majority of studies have investigated normal subjects rendered only modestly hyperthyroid for a brief period of time. We have therefore studied a group of thyrotoxic patients using several different techniques.DESIGN Twelve patients with newly diagnosed diffuse (10 patients) or nodular (2 patients) toxic goitre (10 women, 2 men; age 42.8 ± 3.2 years; BMI 21.6 ±0.7 kg/m2) before (‘pretreatment’) and after (‘treated’) 11.2 ± 1.0 weeks treatment with methimazole and compared these patients to a control group (‘control’) of 11 subjects (9 women, 2 men; age 40.5 ± 3.9 years; BMI 22.5 ± 1.0 kg/m2). All were studied for 3 hours in the basal state, using indirect calorimetry, isotope dilution for the measurement of glucose turnover and the forearm technique for assessment of muscle metabolism.RESULTS Prior to treatment patients with thyrotoxicosis were characterized by increased (P < 0.05) levels of T3 (3.75 ± 0.23 nmol/l (pretreatment), 1.89 ± 0.08 (treated) and 1.75 ± 0.11 (control)), resting energy expenditure (130.5 ± 3.5 (pretreatment), 107.7 ± 2.7 (treated) and 106.3 ± 3.1 (control), % of predicted), protein oxidation (0.67 ± 0.03 (pretreatment), 0.54 ± 0.06 (treated) and 0.46 ± 0.05 (control), mg/kg/min), lipid oxidation (1.34 ± 0.08 (pretreatment), 1.00 ± 0.06 (treated) and 1.02 ± 0.04 (control), mg/kg/min), endogenous glucose production (2.51 ± 0.13 (pretreatment), 1.86 ± 0.12 (treated) and 1.85 ± 0.12 (control), mg/kg/min), non‐oxidative glucose turnover (1.28 ± 0.16 (pretreatment), 0.75 ± 0.18 (treated) and 0.71 ± 0.11 (control), mg/kg/min) and a 50% increase in total forearm blood flow. Glucose oxidation (1.23 ± 0.09 (pretreatment), 1.13 ± 0.10 (treated) and 1.21 ± 0.11 (control) mg/kg/min), exchange of substrates in the muscles of the forearm and circulating levels of insulin, C‐peptide, growth hormone or glucagon were not influenced by hyperthyroidism. Propranolol (20 mg thrice daily) given to 7 of the patients for 2 days did not affect circulating levels of thyroid hormones, energy expenditure or glucose turnover rates.CONCLUSIONS These results suggest that all major fuel sources contribute to the hypermetabolism of thyro
ISSN:0300-0664
DOI:10.1046/j.1365-2265.1996.692514.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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14. |
The impact of liver transplantation on endocrine status in men |
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Clinical Endocrinology,
Volume 44,
Issue 4,
1996,
Page 461-466
Stephan Madersbacher,
Georg Ludvik,
Thomas Stulnig,
Thomas Grünberger,
Ulrich Maier,
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摘要:
OBJECTIVE There are few longitudinal data on the endocrine changes which occur after liver transplantation. We have therefore studied the impact of orthotopic liver transplantation (oLTX) on the hypothalamic–pituitary–gonadal hormone axis and sex steroid metabolism in men.PATIENTS AND STUDY DESIGN Ten male patients with end‐stage liver failure due to alcohol induced cirrhosis (n = 2), virus‐induced cirrhosis (n=5), primary biliary cirrhosis (n=1) and idiopathic cirrhosis (n=2) were included in a prospective study analysing the impact of oLTX on endocrine status. They were studied before and after oLTX with a mean follow‐up of 11.6 months (range 4–23) following transplantation.MEASUREMENTS Serum levels of LH, FSH, testosterone (TE), free TE, PRL, cortisol, oestradiol (E2) and sex hormone binding globulin (SHBG) were analysed with commercially available radioimmunoassays in all individuals before and after oLTX. Gonadotrophin releasing hormone stimulation tests were done in 5 patients before and after oLTX. Additionally, a complete urological assessment with a detailed questionnaire on sexual function was obtained from all individuals.RESULTS Prior to oLTX, endocrine status was invariably abnormal, the most prominent finding being a pathological decrease of TE in 90% and of free TE in all cases. After successful oLTX, all individuals had physiological levels of TE and of free TE which increased twofold (P<0.01) and tenfold (P<0.000 1), respectively. Additionally, serum gonadotrophin (LH/FSH) levels increased in the majority of patients, while E2decreased following oLTX. Endocrine changes extended beyond the hypothalamic–pituitary–gonadal hormone axis, as shown by a decrease in PRL (P<0.02) and SHBG (P<0.01) after transplantation. GnRH tests revealed normal stimulation of LH and FSH before and after oLTX in all cases. Libido, potency and frequency of sexual intercourse improved significantly after oLTX in the majority of patients.CONCLUSIONS These findings demonstrate the ability of the hypothalamic–pituitary–gonadal hormone axis and sex steroid metabolism to resume physiological function following orthotopic liver transplantation in men. Correspondingly, sexual function returns to normal in the majority of patients, despite significant alterations prior to
ISSN:0300-0664
DOI:10.1046/j.1365-2265.1996.698519.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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15. |
Expression of the transferrin receptor in human anterior pituitary adenomas is confined to gonadotrophinomas |
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Clinical Endocrinology,
Volume 44,
Issue 4,
1996,
Page 467-471
S. L. Atkin,
H. E. Burnett,
V. L. Green,
M. C. White,
M. Lombard,
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摘要:
OBJECTIVE The human pituitary gland is affected selectively by conditions associated with iron deposition, but the mechanisms for this are unknown. In this study we have determined whether the transferrin receptor, which mediates iron uptake by cells, could be detected immunocytochemically in human pituitary adenomasin vitro.PATIENTS Data were derived from 35 patients undergoing transsphenoidal surgery and included 13 with clinically non‐functioning adenomas, 15 with acromegaly, 4 prolactinomas, 2 patients with Cushing’s disease and one patient with Nelson’s syndrome.MEASUREMENTS Transferrin receptor immunopositivity was determined for each adenoma in dispersed cell culture using a specific monoclonal antibody.RESULTS Eight of 13 clinically functionless adenomas showed immunopositive transferrin receptor expression, whilst adenomas from 15 patients with acromegaly, 4 prolactinomas, 2 Cushing’s syndrome and one patient with Nelson’s syndrome were negative. The eight transferrin receptor positive tumours were gonadotrophinomas and accounted for eight of the nine tumours which secreted and immunostained for FSH; all eight also secreted and immunostained for LH.CONCLUSIONS These findings may reflect a special requirement for iron by gonadotrophin secreting cells in comparison to other pituitary cell types and this could underlie the reasons why in the normal pituitary these cells are especially susceptible to malfunction in iron overload syndromes such as genetic haemochromatosis
ISSN:0300-0664
DOI:10.1046/j.1365-2265.1996.696516.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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16. |
A comparison between short ACTH and insulin stress tests for assessing hypothalamo‐pituitary‐adrenal function |
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Clinical Endocrinology,
Volume 44,
Issue 4,
1996,
Page 473-476
F. Ammari,
B. G. Issa,
E. Millward,
M. F. Scanlon,
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摘要:
OBJECTIVE Insulin‐induced hypoglycaemia is the standard method for assessment of the hypothalamo‐pituitary‐adrenal (HPA) axis of patients with pituitary or hypothalamic disease. It has been claimed that a normal cortisol response to the 30‐minute ACTH stimulation test (AST) obviates the need to perform the insulin stress test (IST) in these patients. The objective of our study was to compare both tests in a group of consecutive patients with pituitary disease.SUBJECTS AND METHODS Thirty patients with pituitary disease were evaluated by standard IST (0.1 U of soluble insulin/kg body weight,i.v.) after fasting from midnight and AST (250μg synacthen, i.v.). In the IST, a plasma glucose of<2.2mmol/l was taken as the hypoglycaemic threshold and blood was collected at 0, 30, 60, 90 and 120minutes. In the AST blood was collected at 0 and 30minutes. Serum cortisol was measured by standard radioimmunoassay and glucose by the glucose oxidase method. Cortisol responses to the stimuli were compared at cut‐off levels of 550, 500, 450 and 400nmol/l.RESULTS At 550nmol/l, out of 30 patients, 17 showed an abnormal IST of whom 9 had normal responses to AST (53%). At 500nmol/l, 12 patients had an abnormal IST of whom 6 had normal AST (50%). At 450nmol/l, of 9 patients with an abnormal IST, 5 had a normal AST (56%). At 400nmol/l, 5 patients had an abnormal IST all of whom (100%) showed a normal AST.CONCLUSION There is a clear discrepancy between the results of the two tests at different cortisol cut‐off levels. The ACTH stimulation test is not reliable for assessing the HPA axis in patients with pituitary disease and the insulin stress test remains
ISSN:0300-0664
DOI:10.1046/j.1365-2265.1996.712533.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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17. |
Steroid 5α‐reductase 2 deficiency: virilization in early infancy may be due to partial function of mutant enzyme |
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Clinical Endocrinology,
Volume 44,
Issue 4,
1996,
Page 477-482
G. Forti,
A. Falchetti,
S. Santoro,
D. L. Davis,
J. D. Wilson,
D. W. Russell,
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摘要:
Male pseudohermaphroditism due to steroid 5α‐reductase deficiency is the consequence of mutations in the gene encoding the type 2 isoenzyme. Most (60%) affected subjects have homozygous mutations, and the remainder are compound heterozygotes or presumed compound heterozygotes. We report an Italian subject with phenotypic and endocrine features of 5α‐reductase 2 deficiency who is homozygous for a substitution mutation (H231R). Although close consanguinity is not present, genealogical data demonstrated that the parents are distantly related, and both parents and the maternal grandmother are heterozygous carriers of the mutation. The fact that this particular mutation results in the formation of an enzyme with considerable residual activity may explain in part the significant degree of virilization that took place in this subject in early infancy. This same mutation (H231R) is present in heterozygous form in two other families, an African‐American family and an American family of northern European
ISSN:0300-0664
DOI:10.1046/j.1365-2265.1996.673496.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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18. |
ACTH independent Cushing's syndrome occurring in siblings |
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Clinical Endocrinology,
Volume 44,
Issue 4,
1996,
Page 483-488
Shiro Minami,
Hitoshi Sugihara,
Jun Sato,
Atsushi Tatsukuchi,
Yuichi Sugisaki,
Hironobu Sasano,
Ichiji Wakabayashi,
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摘要:
Familial Cushing's syndrome due to ACTH independent bilateral macronodular adrenocortical hyperplasia occurring in siblings is reported. The proband was a 69‐year‐old woman who presented with a typical Cushingoid appearance. The serum cortisol level was elevated, with a loss of diurnal rhythm, and the plasma ACTH level was undetectable. Dynamic testing showed no suppression of urinary 17‐OHCS by high dose dexamethasone and no stimulation by metyrapone. An abdominal CT scan showed bilateral adrenal enlargement. The patient died of a subarachnoid haemorrhage, and autopsy revealed a massively thickened adrenal cortex composed of nodules up to 3.5 cm in diameter. A pituitary adenoma was not found. We learned that the patient's elder brother was also diagnosed at 59 years of age with Cushing's syndrome due to bilateral macronodular adrenocortical hyperplasia. His plasma cortisol levels were not suppressed by high dose dexamethasone and the plasma ACTH level was undetectable. Screening of the available family members by administering 1 mg dexamethasone at midnight and performing abdominal CT scan revealed impaired suppressibility of serum cortisol associated with enlarged bilateral adrenal glands in a 64‐year‐old sister and a 54‐year‐old brother. The 64‐year‐old sister was considered as a possible ‘affected’ case in the early stages of development, because the basal level of ACTH was not suppressed and hyperplasia of the bilateral adrenal glands as revealed by
ISSN:0300-0664
DOI:10.1046/j.1365-2265.1996.682504.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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19. |
Short stature, GH deficiency and social status |
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Clinical Endocrinology,
Volume 44,
Issue 4,
1996,
Page 489-490
Alessandro Sartorio,
Enrico Molinari,
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ISSN:0300-0664
DOI:10.1046/j.1365-2265.1996.700522.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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20. |
Effects of gonadal androgens on adrenal androgen levels |
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Clinical Endocrinology,
Volume 44,
Issue 4,
1996,
Page 490-491
Maurizio Cutolo,
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ISSN:0300-0664
DOI:10.1046/j.1365-2265.1996.t01-1-700522.x
出版商:Blackwell Science Ltd
年代:1996
数据来源: WILEY
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