Abstract:
BACKGROUND:Mutations in CYP21A2 lead to deficiency of 21-hydroxylase and can have either severe or moderate effects on phenotype, which can be prevented by early treatment. We studied long-term effects of this deficiency on phenotype in patients who had not been treated for prolonged periods and correlated these phenotypes with the mutations found in our patients. OBJECTIVE:To assess the correlation between genotype and phenotype in untreated patients with 21-hydroxylase deficiency. DESIGN:Subjects with 21-hydroxylase deficiency were selected from a large population of Indonesian patients with disorders of sexual differentiation. CYP21A2 mutations in these patients were correlated with their phenotype in terms of genital development and steroid hormone levels. PATIENTS:Fifteen 46,XX patients with ages between 1 and 33 years, of whom 12 had never been treated before. MEASUREMENTS:Mutations in CYP21A2, genital phenotype and steroid hormone levels. RESULTS:We found in all patients CYP21A2 mutations which affect enzyme activity, with a relatively high allele frequency of R356W (40%), I172N (20%) and IVS2 - 1A > G (13%). Clitoris length was directly correlated with levels of testosterone, but not with age. The phenotype was not always concordant with the genotype: different phenotypes (mild to severe virilization) were found in sibling pairs with the mutations IVS2 - 13A > G or I172N. The high frequency of homozygous mutants for R356W in patients aged from 1 to 11 years old is remarkable, as this mutation has been described only in salt-wasting patients. In our study, this mutation caused a urogenital sinus in three out of seven cases, whereas in the remaining cases the labia were at least partially fused. This mutation caused severe virilization with remarkably high serum levels of renin. We found one novel substitution in intron 2 (IVS2 - 37A > G), containing the branch site, which is likely to affect the CYP21-enzyme. Two additional intron 2 substitutions were discovered, which are supposed to affect the 21-hydroxylase (i.e. IVS2 + 33A > C and IVS2 + 67C > T). CONCLUSION:We conclude that a correlation exists between the concentration of androgens and the extent of virilization. However, there was no clear correlation between genotype and phenotype, except for the mutation R356W.
journal_name
Clin Endocrinol (Oxf)journal_title
Clinical endocrinologyauthors
Goossens K,Juniarto AZ,Timmerman MA,Faradz SM,Wolffenbuttel KP,Drop SL,de Jong FHdoi
10.1111/j.1365-2265.2009.03550.xsubject
Has Abstractpub_date
2009-11-01 00:00:00pages
628-35issue
5eissn
0300-0664issn
1365-2265pii
CEN3550journal_volume
71pub_type
杂志文章abstract:OBJECTIVE:The use of ergot-derived dopamine agonists (DA) to treat patients with prolactinomas has not been associated with an increased risk of significant heart valve dysfunction. Accordingly, the present study evaluated whether the long-term use of DA for hyperprolactinaemia may be associated with increased risk of ...
journal_title:Clinical endocrinology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2265.2011.04326.x
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Growth hormone treatment in children with idiopathic short stature (ISS) leads to growth acceleration in the first years, but the effect on final height is still poorly documented. We therefore studied the long-term effect of GH therapy in children with idiopathic short stature. DESIGN:We have...
journal_title:Clinical endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2265.1995.tb02644.x
更新日期:1995-04-01 00:00:00
abstract:OBJECTIVE:Cranial irradiation frequently results in growth hormone (GH) deficiency. Patients with radiation-induced GH deficiency usually remain responsive to exogenous growth hormone releasing hormone, implying radiation damages the hypothalamus rather than the pituitary. Little is known about the effect of cranial ir...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1994.tb02525.x
更新日期:1994-08-01 00:00:00
abstract::Twenty-four hyperprolactinaemic women were treated for 6 months with the new, non-ergot, long-acting dopamine agonist, CV 205-502. The treatment resulted in normalization of PRL secretion in 17 of the 24 women at once-daily doses of 0.05 to 0.15 mg of the drug. Sixteen of these women as well as 4 of those who remained...
journal_title:Clinical endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2265.1988.tb01225.x
更新日期:1988-09-01 00:00:00
abstract:OBJECTIVE:Polymorphisms in the thyroid transcription factor forkhead factor E1 (FOXE1) gene have been implicated in the genetic susceptibility to differentiated thyroid cancer, but little is known about their effect on tumour characteristics. The objective of this study was to determine the contribution of the FOXE1 po...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.13166
更新日期:2017-02-01 00:00:00
abstract:OBJECTIVES:There is growing evidence for the association between bone mineral density (BMD) and vascular calcification, which is related to cardiovascular disease. Coronary multidetector row computed tomography (MDCT) is a noninvasive tool developed to evaluate coronary status precisely. We used MDCT to evaluate this a...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2009.03535.x
更新日期:2009-11-01 00:00:00
abstract:OBJECTIVE:The body adiposity index (BAI) has been recently proposed as an alternative index to body mass index (BMI) and waist circumference (WC) to evaluate adiposity in adults, with special focus on its ability to discriminate gender specificities on adiposity. Endothelial dysfunction, circulating endothelial cells (...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.12195
更新日期:2013-11-01 00:00:00
abstract:OBJECTIVE:There is increasing evidence for the role of cytokines in pituitary differentiated function and tumorigenesis, but the spectrum of cytokines found in the pituitary is unknown. Therefore profiles of cytokine expression were determined in different human anterior pituitary adenoma sub-types. DESIGN:The reverse...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.1996.d01-1554.x
更新日期:1996-08-01 00:00:00
abstract::Nine acromegalic patients were treated by the somatostatin analogue SMS 201-995 octreotide (Sandostatin (octreotide), Sandoz, Basle, Switzerland] 250 micrograms/day in 4 divided s.c. injections (50 + 50 + 50 + 100 micrograms) for 1 month, 250 micrograms/24 has continuous s.c. infusions for another month and thereafter...
journal_title:Clinical endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2265.1989.tb00266.x
更新日期:1989-06-01 00:00:00
abstract::A radioimmunoassay (RIA) procedure was devised for the estimation of PRL in eluates of dried whole blood from filter paper. Levels of PRL were measured in newborn blood obtained during the first week of life from 530 infants of normal birthweight (greater than 2500 g) with normal T4 values, 114 infants of normal birth...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1986.tb03253.x
更新日期:1986-01-01 00:00:00
abstract:UNLABELLED:A diagnosis of bilateral pheochromocytoma warrants exclusion of hereditary pheochromocytoma. OBJECTIVE:To describe the first case of a bilateral pheochromocytoma associated with V804M mutation in the RET proto-oncogene. PATIENTS:The index case was a 54-year-old man with bilateral adrenal masses discovered ...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2007.02830.x
更新日期:2007-07-01 00:00:00
abstract::Thirty-three samples of follicular fluid (FF) were collected from 14 patients with the polycystic ovary (PCO) syndrome and matched for FF-volume with small follicles collected from subjects with normal ovaries. The median (range) FF concentration of insulin-like growth factor 1 (IGF1) in the group with PCO, 0.42 (0.13...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1990.tb00879.x
更新日期:1990-04-01 00:00:00
abstract::The urine clearance of TRH after intravenous injection in man has been measured by radioimmunoassay. Between 4.4 percent and 10.7 percent of the dose was excreted within 90 min, the majority within 30 min. The TRH excreted was immunochemically and chromatographically indistinguishable from synthetic TRH and was inacti...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1975.tb01549.x
更新日期:1975-07-01 00:00:00
abstract::Long-term bromocriptine treatment was discontinued in thirty-seven women with hyperprolactinaemic amenorrhoea. After cessation of therapy thirty of the thirty-seven women became hyperprolactinaemic again with amenorrhoea or anovulatory bleeding. Seven of the women continued to have regular ovulatory menstruation but o...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1982.tb03175.x
更新日期:1982-06-01 00:00:00
abstract:OBJECTIVE:There is a lack of normal reference data on urinary GH (u-GH) excretion in children. We have investigated the impact of age, gender, pubertal development and body mass on reference values for u-GH excretion in normally growing non-obese and obese children. STUDY DESIGN:u-GH levels were evaluated in 1153 heal...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.1999.00728.x
更新日期:1999-06-01 00:00:00
abstract:OBJECTIVE:Non-tumour causes of hyperprolactinaemia, including prolactin-elevating drugs, must be excluded. There is a general view that such drugs are unlikely to raise serum PRL above 3000 mU/I, but the literature is confusing. We report 8 patients receiving treatment with neuroleptic drugs, whose serum PRL concentrat...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.1998.00569.x
更新日期:1998-10-01 00:00:00
abstract:OBJECTIVE AND DESIGN:The immediate early gene locus AP-1, incorporating the cellular oncogenes c-fos and c-jun (and their oncoprotein products Fos and Jun respectively) play a key role in regulating cell growth and differentiation. The myc-gene is also known to promote cell growth. In order to investigate the possible ...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1994.tb02453.x
更新日期:1994-01-01 00:00:00
abstract:OBJECTIVE:Abnormal serum liver function tests are common in patients with untreated thyrotoxicosis, even prior to the initiation of antithyroidal medications that may worsen the severity of the abnormal serum liver biochemistries. There is a wide range of the incidence of these abnormalities in the published literature...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.13312
更新日期:2017-05-01 00:00:00
abstract:OBJECTIVE:The level of growth hormone (GH), growth hormone secretogogue (GHS) and GHS receptor (GHSR) messenger ribonucleic acid (mRNA) expression has been reported as being higher in GH-producing pituitary adenomas than in other types of pituitary adenomas. Recently, ghrelin, an endogenous ligand specific for GHSR, wa...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.2001.01286.x
更新日期:2001-06-01 00:00:00
abstract:OBJECTIVE:Heterozygous inactivating mutations of the calcium-sensing receptor (CaR) gene cause familial hypocalciuric hypercalcaemia (FHH), a generally benign disorder characterized by mild to moderate PTH-dependent hypercalcaemia. We aimed to identify the causative CaR mutations in three families with FHH and examine ...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2006.02512.x
更新日期:2006-05-01 00:00:00
abstract:CONTEXT:It is unclear if people who develop stress hyperglycaemia have underlying abnormal glucose metabolism, an exaggerated hormonal response to stress, or both. Similarly, it is unknown whether stress hyperglycaemia predicts future glucose intolerance. OBJECTIVE:To determine the relationship between illness severit...
journal_title:Clinical endocrinology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2265.2009.03654.x
更新日期:2010-02-01 00:00:00
abstract:OBJECTIVE:To compare the relative utility of GH stimulation tests and assays of spontaneous GH secretion as predictors of change in height standard deviation score at the end of GH treatment in children with short stature. PATIENTS AND METHODS:We retrospectively studied 116 children (67 boys and 49 girls) with subnorm...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.2003.01773.x
更新日期:2003-07-01 00:00:00
abstract::Radioiodine has been in use for over 60 years as a treatment for hyperthyroidism. Major changes in clinical practice have occurred with the realization that accurate dosimetry is incapable of avoiding the risks of hypothyroidism, while more accurate assessment of the risks of other adverse effects of radioiodine such ...
journal_title:Clinical endocrinology
pub_type: 杂志文章,实务指引
doi:10.1111/j.1365-2265.2007.02841.x
更新日期:2007-06-01 00:00:00
abstract:OBJECTIVE:We examined the obesity phenotype most strongly associated with increased plasma concentrations of sTNFR2, and compared which of the two markers, TNF-alpha or sTNFR2, better predicts indices of plasma glucose-insulin homeostasis. DESIGN, PATIENTS AND MEASUREMENTS:Plasma sTNFR2 levels were measured in a sampl...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2009.03671.x
更新日期:2010-03-01 00:00:00
abstract::Familial neurohypophysial diabetes insipidus (FNDI) is a rare autosomal dominant syndrome stemming from the absence of arginine vasopressin (AVP). More than thirty-five different germline mutations in the arginine vasopressin-neurophysin II gene have been reported. These mutations are either in the signal peptide or s...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.2003.01667.x
更新日期:2003-01-01 00:00:00
abstract::Although vasomotor instability or hot flushes are a well-known occurrence in women with natural or artificially-induced menopause, they have not previously been described in children. We report three children in different stages of puberty who developed vasomotor instability following surgery involving the hypothalami...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1983.tb00592.x
更新日期:1983-06-01 00:00:00
abstract:CONTEXT:Primary hyperparathyroidism is a common condition and results in hypercalcaemia, especially in older women. Thus, it is critical to obtain a robust estimate for the upper limit of the reference interval for albumin-adjusted serum calcium in the general population. The current reference interval in use in the UK...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.14326
更新日期:2021-01-01 00:00:00
abstract:OBJECTIVE:Serum thyroglobulin (Tg) is a marker of residual differentiated thyroid cancer (DTC) after total thyroidectomy; however, circulating antithyroglobulin antibodies (TgAb) may interfere with the immunoassay for Tg. Ultrasensitive assays may have a more significant role in detecting circulating Tg in the context ...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.12736
更新日期:2016-02-01 00:00:00
abstract:OBJECTIVE:Although autoantibody production is a key feature of autoimmunity, it is not known whether variation in autoantibody production and clearance pathways is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa) molecule is involved in the clearance of autoantibodies and a functional single nucl...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2010.03780.x
更新日期:2010-07-01 00:00:00
abstract::Eight patients with treated Addison's disease were studied whilst receiving different doses of fludrocortisone together with a constant intake of glucocorticoid. Plasma renin activity (PRA), blood pressure, pulse rate and plasma potassium and urea concentrations were measured after 2-week periods on each dose. In two ...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1979.tb02107.x
更新日期:1979-05-01 00:00:00