Abstract:
CONTEXT:Glucokinase (GCK) phosphorylates and thereby "traps" glucose in cells, thus serving as a gatekeeper for cellular glucose metabolism, particularly in hepatocytes and pancreatic beta cells. In humans, activating GCK mutations cause familial hyperinsulinaemic hypoglycaemia (GCK-HH), leading to keen interest in the potential of small-molecule glucokinase activators (GKAs) as treatments for diabetes mellitus. Many such agents have been developed; however, observation of side effects including hypertriglyceridaemia and hepatic steatosis has delayed their clinical development. OBJECTIVE:To describe the clinical presentation and metabolic profiles of affected family members in a kindred with familial hyperinsulinism of adult presentation due to a known activating mutation in GCK. DESIGN:Clinical, biochemical and metabolic assessment, and GCK sequencing in affected family members. RESULTS:In the 60-year-old female proband, hyperinsulinaemic hypoglycaemia (blood glucose 2·1 mmol/mol, insulin 18 pm) was confirmed following 34 h of fasting; however, abdominal computed tomography (CT), pancreatic MRI, endoscopic ultrasound, octreotide scintigraphy and selective arterial calcium stimulation failed to localize an insulinoma. A prolonged OGTT revealed fasting hypoglycaemia that was exacerbated after glucose challenge, consistent with dysregulated glucose-stimulated insulin release. A heterozygous activating mutation, p.Val389Leu, in the glucokinase gene (GCK) was found in the proband and four other family members. Of these, two had been investigated elsewhere for recurrent hypoglycaemia in adulthood, while the other two adult relatives were asymptomatic despite profound hypoglycaemia. All three of the available family members with the p.Val389Leu mutation had normal serum lipid profiles, normal rates of fasting hepatic de novo lipogenesis and had hepatic triglyceride levels commensurate with their degree of adiposity. CONCLUSION:Activating GCK mutations may present in late adulthood with hyperinsulinaemic hypoglycaemia and should be considered even in older patients being investigated for insulinoma. Normal circulating lipids, rates of hepatic de novo lipogenesis and appropriate hepatic triglyceride content for degree of adiposity in the patients we describe suggest that even lifelong GCK activation in isolation is insufficient to produce fatty liver and metabolic dyslipidaemia.
journal_name
Clin Endocrinol (Oxf)journal_title
Clinical endocrinologyauthors
Challis BG,Harris J,Sleigh A,Isaac I,Orme SM,Seevaratnam N,Dhatariya K,Simpson HL,Semple RKdoi
10.1111/cen.12517subject
Has Abstractpub_date
2014-12-01 00:00:00pages
855-61issue
6eissn
0300-0664issn
1365-2265journal_volume
81pub_type
杂志文章abstract:CONTEXT:Data on quantification and regulation of adipsin in human cerebrospinal fluid (CSF) are sparse, and the physiological role of adipsin as an adipokine crossing the blood-brain barrier (BBB) is uncertain. OBJECTIVES:This study quantified adipsin concentrations in paired serum and CSF samples of patients undergoi...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.12856
更新日期:2016-02-01 00:00:00
abstract:OBJECTIVE:To assess the relationship between circulating leptin levels, bone mineral content and density in the elderly. DESIGN:A cross-sectional study. PATIENTS:A cohort of 92 men and 171 women, with ages ranging from 68 to 75 years, selected as a healthy and normal functioning group, in the city centre of Verona. ...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.2003.01808.x
更新日期:2003-07-01 00:00:00
abstract:BACKGROUND:A number of surgical series have been reported on the treatment of acromegaly and their results vary widely. The acceptable definition of remission has changed in recent years and it is known, though in a small series, that growth hormone levels of > 5 mU/l are still associated with an increased mortality fr...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.1999.00760.x
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND:Efficacy of the GH-receptor antagonist pegvisomant (PEG) has differed between preclinical and observational studies mainly due to dose adjustment and IGF-I normalization criteria. An escape phenomenon has also been described, but its definition and underlying causes have not been fully established. OBJECTIV...
journal_title:Clinical endocrinology
pub_type: 杂志文章,多中心研究
doi:10.1111/cen.12993
更新日期:2016-04-01 00:00:00
abstract:OBJECTIVE:Constitutional delay of growth and puberty (CDGP) is a tempo variant with a good prognosis. Healthy late-maturing adolescents grow slower than postulated by age-related references, and therefore, CDGP is frequently confused with growth hormone deficiency (GHD). For differential diagnosis, height velocity refe...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.14358
更新日期:2021-02-01 00:00:00
abstract:OBJECTIVE:PTH(1-84) secretion in normal male subjects follows a circadian rhythm. The control of this rhythm is multifactorial with both neuroendocrine and chemical influences. The aim of this study was to assess the effect of a 96-hour fast on the circadian rhythm of PTH(1-84), serum calcium, phosphate and nephrogenou...
journal_title:Clinical endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2265.1994.tb02493.x
更新日期:1994-04-01 00:00:00
abstract::Computed tomography of the pituitary fossa was performed in 12 patients with primary hypothyroidism before and after thyroxine treatment. In three, herniation of the diaphragma sellae precluded accurate measurement of the density of the hypophysis. Eight of the remaining patients showed abnormally increased density of...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1985.tb02997.x
更新日期:1985-05-01 00:00:00
abstract:OBJECTIVE:We evaluated menopausal symptoms, menstrual cycle bleeding characteristics and reproductive hormones for their associations with thyroid stimulating hormone (TSH) concentrations in women at the mid-life from five ethnic groups. METHODS:This report is from the baseline evaluation of the Study of Women's Healt...
journal_title:Clinical endocrinology
pub_type: 杂志文章,多中心研究
doi:10.1046/j.1365-2265.2003.01718.x
更新日期:2003-03-01 00:00:00
abstract::Raised activity of the LH axis caused by activating mutations of LH receptor gene presents with precocious puberty in boys, analogous to the presentation of LH secreting pituitary adenomas (Faggiano et al., 1983; Ambrosi et al., 1990). LH "hyperactivity' in females appears to have no effect. Hyperactivity of the FSH a...
journal_title:Clinical endocrinology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2265.1996.8680879.x
更新日期:1996-12-01 00:00:00
abstract:OBJECTIVE:We investigated the content and compared the molecular forms of parathyroid hormone-related protein in tumour tissue, plasma and pleural fluid. DESIGN:Measurement of parathyroid hormone-related protein in tumour extracts and biological fluids and comparison of the elution profiles of parathyroid hormone-rela...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1993.tb01008.x
更新日期:1993-03-01 00:00:00
abstract:OBJECTIVES:Localization of ectopic ACTH-secreting tumours causing Cushing syndrome (ECS) is essential for clinical management, yet often difficult. [68 Ga]-DOTATATE PET/CT ([68 Ga]-DOTA-(Tyr3 )-octreotate)] is an FDA-approved high-resolution diagnostic tool for imaging neuroendocrine tumours. Data on the clinical utili...
journal_title:Clinical endocrinology
pub_type: 杂志文章,多中心研究
doi:10.1111/cen.14008
更新日期:2019-08-01 00:00:00
abstract:OBJECTIVE:We investigated interindividual differences in the shape, slope and setpoint of the pituitary-thyroid axis (PTA) in normal persons. Based on these physiological data we propose a novel bivariate concept for the interpretation of thyroid function tests which is less biased by interindividual differences in the...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1993.tb01758.x
更新日期:1993-07-01 00:00:00
abstract::Seven women with primary amenorrhoea and hyperprolactinaemia were treated with bromocriptine. All the women had started to develop secondary sex characteristics at normal age but pubertal development stopped and menarche did not occur. Radiological signs of a pituitary tumour were found in all the women. Before the pi...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1979.tb01360.x
更新日期:1979-02-01 00:00:00
abstract:OBJECTIVE:No single histological or molecular marker is diagnostic for malignant phaeochromocytomas and paragangliomas (PPGLs). This study aimed to establish and evaluate a prognostic nomogram to improve the prediction of metastatic probability in individual PPGL patients. METHODS:Three hundred and 47 consecutive PPGL...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.13357
更新日期:2017-08-01 00:00:00
abstract:OBJECTIVE:Pseudohypoparathyroidism type Ia (PHP-Ia) is a hereditary disorder characterized by resistance to multiple hormones that work via cAMP such as PTH and TSH, accompanied by typical skeletal features including short stature and brachydactyly, termed Albright hereditary osteodystrophy (AHO). In affected kindreds,...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2007.03025.x
更新日期:2008-02-01 00:00:00
abstract::The effect of oral glucose (40 g/m2 body surface area) on the leucocyte 22Na efflux rate constants (ERC) was studied in 13 normal weight and 10 obese subjects. The ouabain-sensitive 22Na ERC was higher in leucocytes isolated from fasting obese subjects (median [range] for obese 2.77 [2.33-3.11] vs normals 1.91 [1.57-2...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1987.tb01161.x
更新日期:1987-09-01 00:00:00
abstract:OBJECTIVE:The autoimmune thyroid diseases, Graves disease and autoimmune hypothyroidism, result from a complex interaction between genetic, environmental and endogenous factors. The genetic loci conferring susceptibility remain unclear. A recent report has demonstrated an association between a microsatellite polymorphi...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.1997.1710996.x
更新日期:1997-05-01 00:00:00
abstract:OBJECTIVES:The role of androgen decline in the sexual activity of adult males is controversial. To clarify whether sexual function would benefit from testosterone (T) treatment in men with partially or severely reduced serum T levels, we conducted a systematic review and meta-analysis of placebo-controlled studies publ...
journal_title:Clinical endocrinology
pub_type: 杂志文章,meta分析,评审
doi:10.1111/j.1365-2265.2005.02350.x
更新日期:2005-10-01 00:00:00
abstract:OBJECTIVE:To examine the factors influencing the levels of sex hormone-binding globulin (SHBG) in normal postmenopausal women by assessing the relationship between SHBG and measured anthropometric, metabolic and hormonal variables. DESIGN:Cross-sectional, observational study. SUBJECTS AND METHODS:Seventy normal postm...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.2001.01183.x
更新日期:2001-01-01 00:00:00
abstract::A review of the genetics of male undermasculinization must encompass a description of the embryology of the genital system. The dimorphism of sex development consequent upon the formation of a testis and the subsequent secretion of hormones to impose a male phenotype is highlighted. Thus, an understanding of the cause...
journal_title:Clinical endocrinology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2265.2002.01430.x
更新日期:2002-01-01 00:00:00
abstract::Thirteen normal children, seven males and six females, during early puberty (I-II according to Tanner), have been studied. Each subject was injected at weekly intervals and in random order with 100 micrograms of LHRH, 0.2 mg/kg of naloxone and 0.9% saline in single bolus. The gonadotrophin response was evaluated. The ...
journal_title:Clinical endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2265.1984.tb00086.x
更新日期:1984-03-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to investigate the diagnostic performance of pre-operative staging ultrasound (US) according to body mass index (BMI) in patients with papillary thyroid carcinoma (PTC) PATIENTS AND METHODS: This retrospective study included 625 patients with PTC who underwent pre-operative staging U...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.12638
更新日期:2015-10-01 00:00:00
abstract:OBJECTIVE:To assess current provision of specialist and transitional paediatric endocrine services in the UK and Ireland. DESIGN:A questionnaire was sent to paediatric endocrinologists requesting details of patients receiving GH and also details of specialist and transitional services. RESULTS:Of 72 questionnaires re...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2006.02546.x
更新日期:2006-07-01 00:00:00
abstract:OBJECTIVE:The insulin tolerance test (ITT) has been suggested as the gold standard for diagnosing GH deficiency (GHD). The ITT is, however, potentially hazardous. Glucose monitoring during the ITT varies between centres and there is surprisingly little information on the actual level of blood glucose nadir and the dura...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2006.02436.x
更新日期:2006-02-01 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::There is evidence that the porcine TSH receptor contains essential disulphide bridge(s) which can be disrupted by dithiothreitol (DTT). The aim of the present study was to determine whether exposure of intact thyroid cells to DTT leads to altered thyroid stimulation. TSH-stimulated iodine organification in cultured po...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1987.tb00798.x
更新日期:1987-04-01 00:00:00
abstract:OBJECTIVE:Recent studies have suggested that patients receiving thyroxine are at increased risk of osteoporosis. We set out to measure bone mineral densities in two groups of post-menopausal women receiving thyroxine replacement therapy (those with serum TSH levels persistently suppressed or non-suppressed) and to comp...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1993.tb02404.x
更新日期:1993-11-01 00:00:00
abstract:INTRODUCTION:The present clinical investigation uses a high-precision GH immunofluorometric assay to examine the postulate that principally the amplitude mode of GH secretory control is disrupted in adults with GH deficiency. PATIENTS AND METHODS:To this end, we investigated GH secretory dynamics in a cohort of 19 adu...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.0300-0664.2001.01433.x
更新日期:2002-01-01 00:00:00
abstract::Serum prolactin concentrations were measured in nine untreated hypothyroid infants and 23 euthyroid controls. In the former group the serum prolactin concentrations were tenfold higher than the controls (352 vs 34 micrograms/l), declining gradually upon treatment. Although serum prolactin concentrations can be mildly ...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1986.tb03269.x
更新日期:1986-03-01 00:00:00
abstract:OBJECTIVE:Complications of childhood cirrhosis include abnormal growth and malnutrition, associated with abnormalities in circulating IGFs and IGFBPs. Controlled studies suggest that intensive enteral feeding enhances nutritional status. The aim was to ascertain whether nasogastric feeding improves nutritional status i...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.2000.00934.x
更新日期:2000-02-01 00:00:00