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  • 1
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    Susceptibility and characteristics of infections in patients with glucocorticoid excess or insufficiency: the ICARO tool
    Oxford University Press (OUP) ; 2022
    In:  European Journal of Endocrinology Vol. 187, No. 5 ( 2022-11-01), p. 719-731
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 187, No. 5 ( 2022-11-01), p. 719-731
    Abstract: Registry data show that Cushing's syndrome (CS) and adrenal insufficiency (AI) increase mortality rates associated with infectious diseases. Little information is available on susceptibility to milder forms of infections, especially those not requiring hospitalization. This study aimed to investigate infectious diseases in patients with glucocorticoid disorders through the development of a specific tool. Methods We developed and administered the InfeCtions in pAtients with endocRinOpathies (ICARO) questionnaire, addressing infectious events over a 12-month observation period, to 1017 outpatients referred to 4 University Hospitals. The ICARO questionnaire showed good test–retest reliability. The odds of infection (OR (95% CI)) were estimated after adjustment for confounders and collated into the ICARO score, reflecting the frequency and duration of infections. Results In total, 780 patients met the inclusion criteria: 43 with CS, 32 with adrenal incidentaloma and mild autonomous cortisol secretion (MACS), and 135 with AI, plus 570 controls. Compared to controls, CS was associated with higher odds of urinary tract infections (UTIs) (5.1 (2.3–9.9)), mycoses (4.4 (2.1–8.8)), and flu (2.9 (1.4–5.8)). Patients with adrenal incidentaloma and MACS also showed an increased risk of UTIs (3.7 (1.7–8.0)) and flu (3.2 (1.5–6.9)). Post-dexamethasone cortisol levels correlated with the ICARO score in patients with CS. AI was associated with higher odds of UTIs (2.5 (1.6–3.9)), mycoses (2.3 (1.4–3.8)), and gastrointestinal infections (2.2 (1.5–3.3)), independently of any glucocorticoid replacement dose. Conclusions The ICARO tool revealed a high prevalence of self-reported infections in patients with glucocorticoid disorders. ICARO is the first of its kind questionnaire, which could be a valuable tool for monitoring infections in various clinical settings.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-22-0454
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 2
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    Safety of long-term treatment with cabergoline on cardiac valve disease in patients with prolactinomas
    Oxford University Press (OUP) ; 2013
    In:  European Journal of Endocrinology Vol. 169, No. 3 ( 2013-09), p. 359-366
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 169, No. 3 ( 2013-09), p. 359-366
    Abstract: Cabergoline (CAB) has been found to be associated with increased risk of cardiac valve regurgitation in Parkinson's disease, whereas several retrospective analyses failed to detect a similar relation in hyperprolactinemic patients. The current study aimed at investigating cardiac valve disease before and after 24 and 60 months of continuous treatment with CAB only in patients with hyperprolactinemia. Subjects and methods Forty patients (11 men and 29 women, aged 38.7±12.5 years) newly diagnosed with hyperprolactinemia entered the study. Cumulative CAB dose ranged from 12 to 588 mg (median 48 mg) at 24 months and 48–1260 mg (median 149 mg) at 60 months. All patients underwent a complete trans-thoracic echocardiographic examination. Valve regurgitation was assessed according to the American Society of Echocardiography. Results At baseline, the prevalence of trace mitral, aortic, pulmonic, and tricuspid regurgitations was 20, 2.5, 10, and 40% respectively, with no patient showing clinically relevant valvulopathy. After 24 months, no change in the prevalence of trace mitral ( P =0.78) and pulmonic ( P =0.89) regurgitations and of mild aortic ( P =0.89) and tricuspid ( P =0.89) regurgitations was found when compared with baseline. After 60 months, the prevalence of trace tricuspid regurgitation was only slightly increased when compared with that after 24 months (37.5%; P =0.82), but none of the patients developed significant valvulopathy. No correlation was found between cumulative dose and prevalence or grade of valve regurgitation at both evaluations. Prolactin levels normalized in all patients but one. Conclusion CAB does not increase the risk of significant cardiac valve regurgitation in prolactinomas after the first 5 years of treatment.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-13-0231
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
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  • 3
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    The kidney in acromegaly: renal structure and function in patients with acromegaly during active disease and 1 year after disease remission
    Oxford University Press (OUP) ; 2010
    In:  European Journal of Endocrinology Vol. 162, No. 6 ( 2010-06), p. 1035-1042
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 162, No. 6 ( 2010-06), p. 1035-1042
    Abstract: The GH/insulin-like growth factor 1 axis is physiologically involved in the regulation of electrolytes and water homeostasis by kidneys, and influences glomerular filtration and tubular re-absorption processes. The aim of the study was to investigate renal structure and function in acromegalic patients during active disease and disease remission. Patients Thirty acromegalic patients (15 males and 15 females), aged 32–70 years, were enrolled for the study. Ten de novo patients had active disease, whereas 20 patients showed disease remission 1 year after medical treatment with somatostatin analogs (SA) (ten patients) or surgery (ten patients). Thirty healthy subjects matched for age, gender, and body surface area were enrolled as controls. Results In both active (A) and controlled (C) patients, creatinine clearance ( P 〈 0.001) and citrate ( P 〈 0.05) and oxalate levels ( P 〈 0.001) were higher, whereas filtered Na ( P 〈 0.001) and K ( P 〈 0.001) fractional excretions were lower than those in the controls. Urinary Ca ( P 〈 0.001) and Ph ( P 〈 0.05) levels were significantly increased compared with the controls, and in patients with disease control, urinary Ca ( P 〈 0.001) levels were significantly reduced compared with active patients. Microalbuminuria was significantly increased in active patients ( P 〈 0.05) compared with controlled patients and healthy control subjects. The longitudinal ( P 〈 0.05) and transverse ( P 〈 0.05) diameters of kidneys were significantly higher than those in the controls. In all patients, the prevalence of micronephrolithiasis was higher than that in the controls ( P 〈 0.001), and was significantly correlated to disease duration ( r =0.871, P 〈 0.001) and hydroxyproline values ( r =0.639, P 〈 0.001). Conclusions The results of the current study demonstrated that acromegaly affects both renal structure and function. The observed changes are not completely reversible after disease remission.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-10-0007
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2010
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  • 4
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    Use of late-night salivary cortisol to monitor response to medical treatment in Cushing’s disease
    Oxford University Press (OUP) ; 2020
    In:  European Journal of Endocrinology Vol. 182, No. 2 ( 2020-02), p. 207-217
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 182, No. 2 ( 2020-02), p. 207-217
    Abstract: Monitoring of patients with Cushing’s disease on cortisol-lowering drugs is usually performed with urinary free cortisol (UFC). Late-night salivary cortisol (LNSC) has an established role in screening for hypercortisolism and can help to detect the loss of cortisol circadian rhythm. Less evidence exists regarding the usefulness of LNSC in monitoring pharmacological response in Cushing’s disease. Design Exploratory analysis evaluating LNSC during a Phase III study of long-acting pasireotide in Cushing’s disease (clinicaltrials.gov: NCT01374906). Methods Mean LNSC (mLNSC) was calculated from two samples, collected on the same days as the first two of three 24-h urine samples (used to calculate mean UFC [mUFC]). Clinical signs of hypercortisolism were evaluated over time. Results At baseline, 137 patients had evaluable mLNSC measurements; 91.2% had mLNSC exceeding the upper limit of normal (ULN; 3.2 nmol/L). Of patients with evaluable assessments at month 12 ( n  = 92), 17.4% had both mLNSC ≤ULN and mUFC ≤ULN; 22.8% had mLNSC ≤ULN, and 45.7% had mUFC ≤ULN. There was high variability in LNSC (intra-patient coefficient of variation (CV): 49.4%) and UFC (intra-patient CV: 39.2%). mLNSC levels decreased over 12 months of treatment and paralleled changes in mUFC. Moderate correlation was seen between mLNSC and mUFC (Spearman’s correlation: ρ = 0.50 [all time points pooled]). Greater improvements in systolic/diastolic blood pressure and weight were seen in patients with both mLNSC ≤ULN and mUFC ≤ULN. Conclusion mUFC and mLNSC are complementary measurements for monitoring treatment response in Cushing’s disease, with better clinical outcomes seen for patients in whom both mUFC and mLNSC are controlled.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-19-0695
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 5
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    Global psychological assessment with the evaluation of life and sleep quality and sexual and cognitive function in a large number of patients with acromegaly: a cross-sectional study
    Oxford University Press (OUP) ; 2022
    In:  European Journal of Endocrinology Vol. 187, No. 6 ( 2022-12-01), p. 823-845
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 187, No. 6 ( 2022-12-01), p. 823-845
    Abstract: Acromegaly is associated with somatic disfigurements which impair self-perception of well-being and quality of life. Nowadays, limited data are available on the interplay between hormonal excess and psychological discomfort. The study aimed at investigating the psychological profile, sleep quality, sexual function, cognitive functions, and quality of life in patients with acromegaly. Methods In 223 acromegaly patients from 5 referral centres, global psychological profile, sleep quality, sexual function, cognitive function, and quality of life were investigated. Results Depression was found in ~30% of patients, and anxiety in two-thirds, together with severe discomfort in body image mainly in women. Obstructive sleep apnoea syndrome risk and sleep disorders were found in & gt;50% of patients and daily sleepiness in ~20%. Sexual dysfunction was reported in most of the patients, with the most severe impairment in women. Cognitive functions were compromised in ~10% of cases. Disease duration and patient's age and gender were the main determinants of these psychopathological conditions. Depression (P = 0.047), somatic-affective mood lowering (P = 0.021), state (P  & lt; 0.001) and trait (P = 0.013) anxiety, and body image distortion in body uneasiness test A (P  & lt; 0.001) and B (P = 0.006) were significantly worsened in patients & lt;45 years and slightly worsened in those with disease duration less than 2 years. Male (P  & lt; 0.001) and female (P  & lt; 0.001) sexual function scores were significantly worsened in patients aged & gt;64 years and slightly worsened in those with disease duration for more than 10 years, particularly in presence of cardiometabolic and respiratory complications. Cognitive symptoms were slightly worsened in older patients and in those with long disease duration. Conclusions Acromegaly is associated with a relevant impairment of psychological profile persisting despite remission and long-term medical treatment.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-22-0263
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 6
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    Novel insights in dopamine receptor physiology
    Oxford University Press (OUP) ; 2007
    In:  European Journal of Endocrinology Vol. 156, No. suppl_1 ( 2007-04), p. S13-S21
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 156, No. suppl_1 ( 2007-04), p. S13-S21
    Abstract: The dopaminergic system has a pivotal role in the central nervous system but also plays important roles in the periphery, mainly in the endocrine system. Dopamine exerts its functions via five different receptors, named D 1 –D 5 , belonging to the category of G protein coupled membrane receptors. Dopamine receptors are heterogeneously expressed in different cells, tissues and organs, where they stimulate or inhibit different functions, including neurotransmission and hormone synthesis and secretion. In particular, the dopamineric system has a pivotal role in the physiological regulation of the hypothalamus–pituitary–adrenal axis. Recent data have demonstrated the expression and function of dopamine receptors not only in endocrine organs but also in endocrine tumors, mainly those belonging to the hypothalamus–pituitary–adrenal axis, and also in the so-called ‘neuroendocrine’ tumors. These data confirm the important role of the dopaminergic system in this endocrine axis, as well as in the neuroendocrine system. This review summarizes the main structural and functional characteristics of dopamine receptors, emphasizing the most recent novelties, and focused on the physiological and pathological regulation of the hypothalamus–pituitary–adrenal axis by the dopaminergic system. In addition, the recent findings on the relationship between dopamine receptors and neuroendocrine tumors are summarized.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/eje.1.02353
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2007
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  • 7
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    Beneficial effect of dose escalation of Octreotide-LAR as first-line therapy in patients with acromegaly
    Oxford University Press (OUP) ; 2007
    In:  European Journal of Endocrinology Vol. 157, No. 5 ( 2007-11), p. 579-587
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 157, No. 5 ( 2007-11), p. 579-587
    Abstract: To evaluate the efficacy of dose escalation of Octreotide-long-acting repeatable (LAR) up to 40 mg/month we studied 56 newly diagnosed patients with acromegaly (24 women, 32 men; age 20–82 years). Design Analytical, observational, open and prospective. Methods Three months after LAR treatment beginning with a dose of 20 mg /q28d (every 28 days), 24 patients maintained the same dose (Group A), while 32 required a dose of 30 mg/q28d (Group B). The dose was further increased to 40 mg/q28d in 17 out of the 32 patients of Group B for another 12 months (Group C). Results After 24 months, serum GH and IGF-I levels decreased by 93.1±8.6% (95% confidence limit (CL) 90.8–95.4%) and 62.7±13.4% (95% CL 59.1–66.3%) respectively. Control of GH and IGF-I levels was achieved in 45 patients (80.3%). Tumor shrinkage after 12 months was 49.8±23%; the relative tumor shrinkage during the second 12 months of treatment was 35.3±13.1% and overall tumor volume was 68.1±16.5% (95% CL 63.7–72.5%). Glucose tolerance impaired in eight patients (14.3%): four in Group A and four in Group C (16.7% vs 36.4%, P =0.39). The final dose was predicted by the patient's age at diagnosis ( t =−2.2; P =0.032) and baseline tumor volume ( t =2.1; P =0.043). Conclusion An increase of the LAR dose up to 40 mg/q28d in patients resistant to 30 mg/q28d is followed by greater suppression of GH and IGF-I levels and tumor shrinkage without further significant impairment of glucose tolerance when compared with lower doses. These results suggest that a new dosage schedule of 40 mg every 28 days is applied in patients with acromegaly mostly of young age and with bigger tumors who are likely to be poorly responsive to standard doses of Octreotide-LAR.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-07-0383
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2007
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  • 8
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    Is diabetes in Cushing's syndrome only a consequence of hypercortisolism?
    Oxford University Press (OUP) ; 2014
    In:  European Journal of Endocrinology Vol. 170, No. 2 ( 2014-02), p. 311-319
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 170, No. 2 ( 2014-02), p. 311-319
    Abstract: Diabetes mellitus (DM) is one of the most frequent complications of Cushing's syndrome (CS). The aim of this study was to define the changes in insulin sensitivity and/or secretion in relation to glucose tolerance categories in newly diagnosed CS patients. Design Cross-sectional study on 140 patients with CS. Methods A total of 113 women (80 with pituitary disease and 33 with adrenal disease, aged 41.7±15.7 years) and 27 men (19 with pituitary disease and eight with adrenal disease, aged 38.1±20.01 years) at diagnosis were divided according to glucose tolerance into normal glucose tolerance (CS/NGT), impaired fasting glucose and/or impaired glucose tolerance (CS/prediabetes), and diabetes (CS/DM) groups. Results Seventy-one patients had CS/NGT (49.3%), 26 (18.5%) had CS/prediabetes and 43 (30.8%) had CS/DM. Significant increasing trends in the prevalence of family history of diabetes ( P 〈 0.001), metabolic syndrome ( P 〈 0.001), age ( P 〈 0.001) and waist circumference ( P =0.043) and decreasing trends in HOMA-β ( P 〈 0.001) and oral disposition index (DIo) ( P 〈 0.002) were observed among the groups. No significant trends in fasting insulin levels, area under the curve for insulin (AUC INS ), Matsuda index of insulin sensitivity (ISI-Matsuda) and visceral adiposity index were detected. Conclusions Impairment of glucose tolerance is characterized by the inability of β-cells to adequately compensate for insulin resistance through increased insulin secretion. Age, genetic predisposition and lifestyle, in combination with the duration and degree of hypercortisolism, strongly contribute to the impairment of glucose tolerance in patients with a natural history of CS. A careful phenotypic evaluation of glucose tolerance defects in patients with CS proves useful for the identification of those at a high risk of metabolic complications.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-13-0754
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2014
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  • 9
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    Corticotroph tumor progression after bilateral adrenalectomy (Nelson’s syndrome): systematic review and expert consensus recommendations
    Oxford University Press (OUP) ; 2021
    In:  European Journal of Endocrinology Vol. 184, No. 3 ( 2021-03-01), p. P1-P16
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 184, No. 3 ( 2021-03-01), p. P1-P16
    Abstract: Corticotroph tumor progression (CTP) leading to Nelson’s syndrome (NS) is a severe and difficult-to-treat complication subsequent to bilateral adrenalectomy (BADX) for Cushing’s disease. Its characteristics are not well described, and consensus recommendations for diagnosis and treatment are missing. Methods A systematic literature search was performed focusing on clinical studies and case series (≥5 patients). Definition, cumulative incidence, treatment and long-term outcomes of CTP/NS after BADX were analyzed using descriptive statistics. The results were presented and discussed at an interdisciplinary consensus workshop attended by international pituitary experts in Munich on October 28, 2018. Results Data covered definition and cumulative incidence (34 studies, 1275 patients), surgical outcome (12 studies, 187 patients), outcome of radiation therapy (21 studies, 273 patients), and medical therapy (15 studies, 72 patients). Conclusions We endorse the definition of CTP-BADX/NS as radiological progression or new detection of a pituitary tumor on thin-section MRI. We recommend surveillance by MRI after 3 months and every 12 months for the first 3 years after BADX. Subsequently, we suggest clinical evaluation every 12 months and MRI at increasing intervals every 2–4 years (depending on ACTH and clinical parameters). We recommend pituitary surgery as first-line therapy in patients with CTP-BADX/NS. Surgery should be performed before extrasellar expansion of the tumor to obtain complete and long-term remission. Conventional radiotherapy or stereotactic radiosurgery should be utilized as second-line treatment for remnant tumor tissue showing extrasellar extension
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-20-1088
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 10
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    Determinants of cardiac disease in newly diagnosed patients with acromegaly: results of a 10 year survey study
    Oxford University Press (OUP) ; 2011
    In:  European Journal of Endocrinology Vol. 165, No. 5 ( 2011-11), p. 713-721
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 165, No. 5 ( 2011-11), p. 713-721
    Abstract: The most frequent cause of death in acromegaly is cardiomyopathy. Objective To evaluate determinants of acromegalic cardiomyopathy. Design Observational, open, controlled, retrospective study. Subjects Two hundred and five patients with newly diagnosed active acromegaly (108 women and 97 men; median age 44 years) and 410 non-acromegalic subjects sex- and age-matched with the patients. Main outcome measures Left ventricular (LV) mass index (LVMi), transmitral inflow early-to-atrial (E/A) peak velocity ratio, and LV ejection fraction (LVEF) were measured by Doppler echocardiography to determine the prevalence of LV hypertrophy (LVH), diastolic and systolic dysfunction. The role of age, estimated disease duration, body mass index, GH and IGF1 levels, systolic and diastolic blood pressure, lipid profile and glucose tolerance in determining different features of the acromegalic cardiomyopathy was investigated. Results Compared with controls, the patients had lower E/A, LVEF, high-density lipoprotein (HDL)-cholesterol levels and higher LVMi, total- and low-density lipoprotein (LDL)-cholesterol, triglycerides, glucose and insulin levels, homeostatic model assessment of insulin resistance (HOMA-R) and HOMA-β. The relative risk to develop mild (odds ratio (OR)=1.67 (1.05–2.66); P =0.027) or severe hypertension (OR=1.58 (1.04–2.32); P =0.027), arrhythmias (OR=4.93 (1.74–15.9); P =0.001), impaired fasting glucose/impaired glucose tolerance (OR=2.65 (1.70–4.13); P 〈 0.0001), diabetes (OR=2.14 (1.34–3.40); P =0.0009), LVH (OR=11.9 (7.4–19.5); P 〈 0.0001), diastolic (OR=3.32 (2.09–5.31); P 〈 0.0001) and systolic dysfunction (OR=14.2 (6.95–32.2); P 〈 0.0001), was higher in acromegaly. The most important predictor of LVH ( t =2.4, P =0.02) and systolic dysfunction ( t =−2.77, P =0.006) was disease duration and that of diastolic dysfunction was patient's age ( t =−3.3, P =0.001). Patients with an estimated disease duration of 〉 10 years had a relative risk to present cardiac complications three times higher than patients with estimated disease duration ≤5 years. Conclusions The prevalence of different features of cardiomyopathy is 3.3–14.2 times higher in the acromegalic than in the non-acromegalic population. The major determinant of cardiomyopathy is disease duration.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-11-0408
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2011
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