| 1. |
- Tancredi, Mauro, et al.
(författare)
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Prevalence of primary aldosteronism among patients with type 2 diabetes
- 2017
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 87:3, s. 233-241
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Tidskriftsartikel (refereegranskat)abstract
- Context: Diabetes and hypertension coexist in 40%-60% of individuals with type 2 diabetes. The coexistence of these two conditions is associated with increased risk of retinopathy, nephropathy and cardiovascular disease. Objective: To investigate the prevalence of primary aldosteronism (PA) in a general cohort of persons with type 2 diabetes. Design: Cross-sectional study involving six diabetes outpatient clinics in Sweden. Patients: were enrolled individuals with type 2 diabetes between February 2008 and December 2013. Measurements: Plasma aldosterone concentrations (PAC pmol/L) and direct renin concentrations (DRC mIU/L) were measured. Patients with increased aldosterone renin ratios (ARR) > 65 were further evaluated for PA. Results: Of 578 consecutively screened patients with type 2 diabetes, 27 were treated with mineralocorticoid receptor antagonists (MRA) and potassium-sparing diuretics not further evaluated. Among the remaining 551 patients, 38 had increased ARR, including 22 who were clinically indicated for PA tests and 16 who were not further evaluated due to severe comorbidities and old age. There were five (0.93%) patients with confirmed PA after computerized tomography and adrenal venous sampling. Patients with PA had higher systolic blood pressure (P=.032) and lower potassium levels (P=.027) than those without PA. No significant association was found between plasma aldosterone and diabetic complications. Conclusions: The prevalence of PA in an unselected cohort of patients with type 2 diabetes is relatively low, and measures of plasma aldosterone are not strong risk factors for micro-and macrovascular diabetic complications.
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| 2. |
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| 3. |
- Evang, Johan Arild, et al.
(författare)
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Reduced levels of E-cadherin correlate with progression of corticotroph pituitary tumours
- 2011
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Ingår i: Clinical Endocrinology. - Oxford : Wiley. - 0300-0664 .- 1365-2265. ; 75:6, s. 811-818
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:Loss of E-cadherin is an important marker of epithelial tumour progression. The aims of this study were to explore whether E-cadherin expression and localization correlate to corticotroph tumour progression, relate the expression of the E-cadherin gene (CDH1) to immunohistochemical E-cadherin staining pattern, and study whether the E-cadherin levels were correlated to methylation status of the CDH1 promoter region.DESIGN:Immunohistochemical analyses of E-cadherin protein were performed, as was RT-qPCR of the CDH1 and the POMC genes. Methylation pattern of the promoter region of CDH1 was measured using pyrosequencing of bisulfite-treated DNA.PATIENTS:Forty-five patients operated at a tertiary referral centre in Oslo, Norway. Adenoma tissue sections and RNA samples from patients with verified Cushing's disease or Nelson's syndrome were collected.MEASUREMENTS:Expression of E-cadherin mRNA and protein in pituitary corticotroph adenomas and average percentage of methylated cytosines in a cytosine-phosphate-guanosine island of the CDH1 promoter.RESULTS:Correlations were observed between tumour progression and both nuclear expression of E-cadherin and reduced CDH1 mRNA. The E-cadherin expression was not determined by the methylation pattern of the CDH1 promoter.CONCLUSIONS:Corticotroph tumour progression was associated with reduced expression of the epithelial marker E-cadherin.
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| 4. |
- Fougner, Stine Lyngvi, et al.
(författare)
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Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly
- 2012
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Ingår i: Clinical Endocrinology. - Malden : Wiley. - 0300-0664 .- 1365-2265. ; 76:1, s. 96-102
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT:Somatotroph adenomas have been classified into densely granulated (DG) and sparsely granulated (SG) tumours with a transitional, intermediate group. Gsp oncogenes are activating mutations in the Gsα subunit gene, found in approximately 40% of somatotroph adenomas.OBJECTIVES:To explore granulation pattern and presence of gsp oncogene in acromegaly with correlations to clinical and biochemical variables and to the effect of treatment with somatostatin analogues (SA), as well as to describe granulation pattern in adenomas with and without SA pretreatment.DESIGN/SETTINGS/PATIENTS:Seventy-eight patients with active acromegaly were included. Long-term SA efficacy was evaluated in 29 patients treated preoperatively and in ten treated postoperatively. Granulation pattern was examined, as were immunohistochemical analyses for E-cadherin and SSTR2a. Protein levels of E-cadherin and SSTR2a were measured (Western blot). Gsp mutation analysis was available for 74 adenomas.RESULTS:DG adenomas and the transitional group had higher serum levels of IGF-1 per tumour volume than SG (P = 0·009; P = 0·005). Acute and long-term SA responses were lower in SG (P = 0·001; P = 0·043). No correlation between gsp mutation and granulation was found, and no difference in granulation pattern according to preoperative SA treatment was demonstrated. A significant correlation between granulation and E-cadherin was found, where SG had lowest immunohistochemical expression, substantiated by protein levels, and a highly significant gradient was observed from DG, through the transitional group, to SG.CONCLUSIONS:Densely granulated adenomas were highly responsive to somatostatin analogues in contrast to SG adenomas. The transitional group behaved clinically more like DG adenomas. However, based on E-cadherin, a marker of dedifferentiation, the transitional group seemed to be a true intermediate.
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| 5. |
- Johansson, Per, 1966, et al.
(författare)
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Mild dementia is associated with increased adrenal secretion of cortisol and precursor sex steroids in women.
- 2011
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Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 75:3, s. 301-308
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Tidskriftsartikel (refereegranskat)abstract
- Context Sex steroid levels decrease with increasing age, but little is known whether this is of importance for the age-related decline in cognitive function. Design and patients A cross-sectional study of 50 (26 men) consecutive patients under primary evaluation of cognitive impairment (D group) and 18 (9 men) matched healthy controls (C group). Measurements Sex steroid and precursor levels were determined in serum and, when measurable, in cerebrospinal fluid (CSF) using gas chromatography/mass spectroscopy (GC-MS) or liquid chromatography/mass spectroscopy (LC-MS). Sex hormone binding globulin (SHBG) and cortisol concentrations were measured using conventional assays. Results Patients in the D group had higher 24-h urine cortisol levels and increased serum levels of dehydroepiandrosterone (DHEA) and its sulphate ester dihydroepiandrosterone sulphate (DHEAS), androsterone (ADT), and oestrone (E1) and its sulphate ester E1S, compared with the controls. When men and women were analysed separately, increased serum concentrations of E1 and E1S were observed in both D men and D women, whereas increased levels of other sex steroids and cortisol were seen only in D women. Conclusions In both D men and women, serum E1 and E1S levels were increased, whereas other changes were gender specific and only seen in D women. Further studies are needed to determine whether these changes are a cause of, or merely a consequence of, cognitive impairment in elderly subjects.
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| 6. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Long-term cardiovascular effects of growth hormone treatment in GH-deficient adults. Preliminary data in a small group of patients.
- 1996
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Ingår i: Clinical endocrinology. - 0300-0664. ; 45:3, s. 305-14
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Tidskriftsartikel (refereegranskat)abstract
- The long-term cardiovascular effects of GH administration in adults are of major clinical importance, given the increasing use of such treatment. We have evaluated long-term cardiovascular effects of recombinant human GH (rhGH) substitution in GH deficient men.S.c. rhGH 0.5 U/kg/week or placebo was administered in a 6-month double-blind, cross-over study, followed (after a year without substitution) by a 42-month period of open GH substitution.We evaluated 7 GH-deficient men serially and compared the results with 21 men matched in terms of age and height.Investigations included exercise tests and Doppler-echocardiography to determine exercise capacity and cardiovascular performance.Heart rate and systolic blood pressure at rest increased with GH substitution to the level of the controls, as did diastolic blood pressure after an initial reduction. Age-adjusted exercise capacity increased during the study and we found no evidence of ischaemic heart disease on exercise ECG. Stroke volume increased with GH substitution, thereby normalizing the initially reduced cardiac index. There was no significant change in left atrial or ventricular internal dimensions, systolic function as measured by fractional shortening, or diastolic function as measured by isovolumic relaxation time and left ventricular filling (A/E ratio). However, a lower atrial emptying index than that seen among controls might indicate some diastolic disturbance and there was a definite increase in left ventricular wall thickness compared with controls (to 25.1 +/- 1.5 vs 19.7 +/- 0.4 mm, P < 0.001).We found that GH substitution in GH-deficient adults had a beneficial effect on physical performance and cardiac output. The concomitant increase in left ventricular mass index might be an effect of an excessive substitution dose.
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| 7. |
- Rastrelli, Giulia, et al.
(författare)
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Symptomatic androgen deficiency develops only when both total and free testosterone decline in obese men who may have incident biochemical secondary hypogonadism : Prospective results from the EMAS
- 2018
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 89:4, s. 459-469
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Limited evidence supports the use of free testosterone (FT) for diagnosing hypogonadism when sex hormone–binding globulin (SHBG) is altered. Low total testosterone (TT) is commonly encountered in obesity where SHBG is typically decreased. We aimed to assess the contribution of FT in improving the diagnosis of symptomatic secondary hypogonadism (SH), identified initially by low total testosterone (TT), and then further differentiated by normal FT (LNSH) or low FT (LLSH). Design: Prospective observational study with a median follow-up of 4.3 years. Patients: Three thousand three hundred sixty-nine community-dwelling men aged 40-79 years from eight European centres. Measurements: Subjects were categorized according to baseline and follow-up biochemical status into persistent eugonadal (referent group; n = 1880), incident LNSH (eugonadism to LNSH; n = 101) and incident LLSH (eugonadism to LLSH; n = 38). Predictors and clinical features associated with the transition from eugonadism to LNSH or LLSH were assessed. Results: The cumulative incidence of LNSH and LLSH over 4.3 years was 4.9% and 1.9%, respectively. Baseline obesity predicted both LNSH and LLSH, but the former occurred more frequently in younger men. LLSH, but not LNSH, was associated with new/worsened sexual symptoms, including low desire [OR = 2.67 (1.27-5.60)], erectile dysfunction [OR = 4.53 (2.05-10.01)] and infrequent morning erections [OR = 3.40 (1.48-7.84)]. Conclusions: These longitudinal data demonstrate the importance of FT in the diagnosis of hypogonadism in obese men with low TT and SHBG. The concurrent fall in TT and FT identifies the minority (27.3%) of men with hypogonadal symptoms, which were not present in the majority developing low TT with normal FT.
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| 8. |
- Tjörnstrand, Axel, et al.
(författare)
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Pre- and postoperative Ga-68-DOTATOC positron emission tomography for hormone-secreting pituitary neuroendocrine tumours
- 2021
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Ingår i: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265. ; 94:6, s. 956-967
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Somatostatin receptors (SSTRs) are potential targets for detecting pituitary neuroendocrine tumours (PitNETs) that can be visualized effectively with Ga-68-labelled PET tracers. With this study, we have evaluated the diagnostic properties of such a tracer, Ga-68-DOTATOC, in patients with hormone-producing PitNETs before and after surgery. Design/Methods This prospective case-control study presents preoperative positron emission tomography (PET) and histopathological data in 18 patients with somatotroph (n = 8), corticotroph (n = 7) and thyrotroph (n = 3) PitNETs. Patients were scanned pre- and postoperatively with Ga-68-DOTATOC PET. For the postoperative part of the study, patients with gonadotroph tumours (n = 7) were also included. Fifteen pituitary healthy controls underwent the same protocol once. The maximum standard uptake value (SUVmax) was analysed in manually outlined regions around the tumour in patients and around the pituitary gland in controls. specimens were collected during surgery in subjects for assessment of adenohypophyseal tumour cell type and the SSTR expression. Results Thyrotroph tumours showed higher uptake (median SUVmax 41.1; IQR 37.4-60.0) and corticotroph tumours lower uptake (SUVmax 6.8; 2.6-9.3) than normal pituitary gland (SUVmax 13.8; 12.1-15.5). The uptake in somatotroph tumours (SUVmax 15.9; 11.6-19.7) was similar to the uptake in the pituitary gland. There was a strong correlation between SUVmax and SSTR2 expression (r = .75 (P < .01)). In the postoperative evaluation, PET was able to correlate tracer uptake with biochemical cure and noncure in patients with an abnormal postoperative magnetic resonance image and a preoperative tumour uptake SUVmax > 13.8. Conclusions Ga-68-DOTATOC PET can be used to detect thyrotroph tumours in the pre- and postoperative imaging assessment. Corticotroph tumours had a significantly lower uptake compared to the pituitary gland but without a distinct increased tumour uptake the clinical postoperative value is limited.
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| 9. |
- Andersson, Björn, 1939, et al.
(författare)
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Short-term changes in bone formation markers following growth hormone (GH) treatment in short prepubertal children with a broad range of GH secretion
- 2015
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Ingår i: Clinical Endocrinology. - : Wiley: 12 months. - 0300-0664 .- 1365-2265. ; 82:1, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesGrowth hormone (GH) promotes longitudinal growth and bone modelling/remodelling. This study investigated the relationship between levels of bone formation markers and growth during GH treatment in prepubertal children with widely ranging GH secretion levels. MethodsThe study group comprised 113 short prepubertal children (mean ageSD, 937213years; 99 boys) on GH treatment (330 +/- 006g/kg/day) for 1year. Blood samples were taken at baseline and 1 and 2weeks, 1 and 3months, and 1year after treatment start. Intact amino-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BALP) and osteocalcin were measured using an automated IDS-iSYS immunoassay system. ResultsIntact amino-terminal propeptide of type I procollagen (PINP), BALP and osteocalcin, increased in the short-term during GH treatment. PINP after 1week (P=000077), and BALP and osteocalcin after 1month (Pless than00001 and P=00043, respectively). PINP levels at 1 and 3months correlated positively, and osteocalcin levels at 1week and percentage change after 1month correlated negatively, with first year growth response. No significant correlations were found between BALP and first year growth. Multiple regression analysis showed that bone marker levels together with auxological data and insulin-like growth factor binding protein-3 explained the variation in first year growth response to 36% at start, 32% after 2weeks and 48% at 3months. ConclusionShort-term increases in levels of the bone formation markers PINP, BALP and osteocalcin showed different temporal patterns, but all correlated with first year growth response during GH treatment. These markers may be a useful addition to existing prediction models for growth response.
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| 10. |
- Evang, J Arild, et al.
(författare)
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HDAC2 expression and variable number of repeats in exon 1 of the HDAC2 gene in corticotroph adenomas
- 2010
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 73:2, s. 229-235
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Alterations in protein expression of histone deacetylase 2 (HDAC2) have been demonstrated in various neoplasms, and lack of nuclear expression of HDAC2 has previously been shown in some human and canine corticotroph adenomas. This study aimed to examine HDAC2 expression in a Norwegian cohort of corticotroph adenomas, screen for exonic HDAC2 gene variants in the adenomas and correlate the results with clinical data.PATIENTS AND DESIGN: Forty-four patients with verified Cushing's disease or Nelson's syndrome, positive ACTH staining and tissue available for immunohistochemistry and/or DNA sequencing were included. Ninety-four controls were chosen from the Norwegian Bone Marrow Registry.RESULTS: Histone deacetylase 2 expression examined by immunohistochemistry was strongly reduced in 3/30 adenomas. There were no association between HDAC2 expression and clinical variables. A previously unidentified insertion of three bases in a region coding for a polyserine cluster in exon 1 of the HDAC2 gene was identified in 6/32 adenomas. No other mutations in HDAC2 exons were found. Examination of DNA extracted from peripheral blood confirmed germ-line origin of the exon 1 insertion. The same insertion was also found in 28/94 of the controls (i.e., not significantly different from the patients).CONCLUSIONS: Strongly reduced HDAC2 protein expression was confirmed in a small portion of corticotroph tumours. Mutations in HDAC2 exons are unlikely to play an important role in the development of corticotroph adenomas.
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