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1.
Endocr Relat Cancer ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34609950

RESUMO

Central adrenal insufficiency (AI) due to isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) has been recently associated with immune checkpoint inhibitor (ICI) therapy. Our aim was to analyze the prevalence, clinical characteristics, and therapeutic outcomes in cancer patients with IAD induced by ICI therapy. A retrospective and multicenter study was performed. From a total of 4,447 cancer patients treated with ICI antibodies, 37 (0.8%) [23 men (62.2%), mean age 64.7 ± 8.3 years (range 46-79 yr)] were diagnosed with IAD. The tumor most frequently related to IAD was lung cancer (n=20, 54.1%), followed by melanoma (n=8, 21.6%). The most commonly ICI antibody inhibitor reported was nivolumab (n=18, 48.6%), pembrolizumab (n=16, 43.2%) and ipilimumab (n=8, 21.6%). About half of the patients (n=19, 51.4%) had other immune-related adverse events, mainly endocrine adverse effects (n=10, 27.0%). IAD was diagnosed at a median time of 7.0 months (IQR, 5-12) after starting immunotherapy. The main reported symptom at presentation was fatigue (97.3%), followed by anorexia (81.8%) and general malaise (81.1%). Mean follow-up time since IAD diagnosis was 15.2 ± 12.5 months (range 0.3-55 months). At last visit all patients continued with hormonal deficiency of ACTH. Median overall survival since IAD diagnosis was 6.0 months. In conclusion, IAD is a rare but a well-established complication associated with ICI therapy in cancer patients. It develops around 7 months after starting treatment, mainly anti-PD1 antibodies. Recovery of the corticotropic axis function should not be expected.

2.
Clin Endocrinol (Oxf) ; 95(5): 735-743, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34323296

RESUMO

BACKGROUND: Cushing's syndrome (CS) is associated with skeletal muscle structural and functional impairment which may persist long-term despite surgical removal of the source of cortisol excess. Prevalence of sarcopenia and its impact on Health-Related-Quality of Life (HRQoL) in 'cured' CS is not known. There is a need to identify easy biomarkers to help the clinicians recognise patients at elevated risk of suffering sustained muscle function. PATIENTS AND METHODS: We studied 36 women with CS in remission, and 36 controls matched for age, body mass index, menopausal status, and level of physical activity. We analysed the skeletal muscle mass using dual-energy X-ray absorptiometry, muscle fat fraction using two-point Dixon magnetic resonance imaging and muscle performance and strength using the following tests: hand grip strength, gait speed, timed up and go and 30-s chair stand. We assessed HRQoL with the following questionnaires: SarQoL, CushingQoL, SF-36. We calculated the sarcopenia index (SI; serum creatinine/serum cystatin C × 100). RESULTS: Prevalence of sarcopenia, according to the European Working Group on Sarcopenia in Older People (EWGSOP), was greater in CS as compared with controls (19% vs. 3%; p < .05). Patients with sarcopenia had a lower SarQoL score than those without sarcopenia (61 ± 17 vs. 75 ± 14; p < .05), and scored worse on the items pain, easy bruising and worries on physical appearance (p < .05 for all comparisons) of the CushingQoL questionnaire. Patients with sarcopenia had poorer physical functioning on SF-36 than those without sarcopenia (60 ± 23 vs. 85 ± 15; p < .01). SI was lower in patients with sarcopenia than those without (71 ± 3 vs. 77 ± 2; p = .032), and was associated with intramuscular fatty infiltration, worse performance on the 30-s chair stand test, slower gait speed, and worse muscle weakness-related HRQoL, as measured using the SarQoL questionnaire (p < .05). The optimised cut-off value for the SI ratio to diagnose sarcopenia was 72, which yielded a sensitivity of 73% and a specificity of 90%. CONCLUSIONS: Sarcopenia is common in patients with CS in long-term remission, and associated with impaired quality of life. The SI is a potential biomarker allowing clinicians to identify patients at high risk of muscle dysfunction.

3.
Eur J Endocrinol ; 185(4): 485-496, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313605

RESUMO

Objective: Pituitary adenomas (PA) are rare in young patients, and additional studies are needed to fully understand their pathogenesis in this population. We describe the clinical and genetic characteristics of apparently sporadic PA in a cohort of young patients. Design: Clinical and molecular analysis of 235 patients (age ≤ 30 years) with PA. Clinicians from several Spanish and Chilean hospitals provided data. Methods: Genetic screening was performed via next-generation sequencing and comparative genomic hybridization array. Clinical variables were compared among paediatric, adolescent (<19 years) and young adults' (≥19-30 years) cohorts and types of adenomas. Phenotype-genotype associations were examined. Results: Among the total cohort, mean age was 17.3 years. Local mass effect symptoms were present in 22.0%, and prolactinomas were the most frequent (44.7%). Disease-causing germline variants were identified in 22 individuals (9.3%), more exactly in 13.1 and 4.7% of the populations aged between 0-19 and 19-30 years, respectively; genetically positive patients were younger at diagnosis and had larger tumour size. Healthy family carriers were also identified. Conclusions: Variants in genes associated with syndromic forms of PAs were detected in a large cohort of apparently sporadic pituitary tumours. We have identified novel variants in well-known genes and set the possibility of incomplete disease penetrance in carriers of MEN1 alterations or a limited clinical expression of the syndrome. Despite the low penetrance observed, screening of AIP and MEN1 variants in young patients and relatives is of clinical value.


Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/genética , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Chile/epidemiologia , Estudos de Coortes , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Lactente , Recém-Nascido , Perda de Heterozigosidade , Masculino , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/genética , Espanha/epidemiologia , Adulto Jovem
4.
Artigo em Inglês | MEDLINE | ID: mdl-34219264

RESUMO

OBJECTIVE: Gamma knife radiosurgery (GKRS) has proven to be an effective adjuvant treatment for patients with acromegaly. We performed the present study to investigate, which would be the outcome of GKRS, independently on the response to somatostatin receptor ligand (SRL). DESIGN: Retrospective, observational study. PATIENTS: Ninety-six patients with active acromegaly were included. MEASUREMENTS: The cumulative probability of normalisation of insulin-like growth factor 1 (IGF-1) levels after GKRS was assessed by the Kaplan-Meier method. The association of several clinical characteristics with GKRS outcomes was explored with the use of a Cox proportional-hazard model with the relative hazard ratio and 95% confidence interval (CI). RESULTS: Resistance to SRL occurred in 39 of the 96 patients (40.6%). After GKRS, patients resistant to SRL had a 5- and 10-year probability of remission of 40.7% (95% CI: 23.7%-57.7%) and 75.9% (95% CI: 57.9%-93.9%), respectively. Patients responding to SRL had a 5- and 10-year probability of remission of 46.8% (95% CI: 32.2%-61.4%) and 58.1% (95% CI: 41.5%-74.7%), respectively. The difference was not significant (p = .48 by the log-rank test). Multivariate Cox analysis confirmed that the only independent variables associated with GKRS outcome were basal growth hormone (GH; p = .001) and IGF-1 multiple of the upper limit of normal levels before GKRS (p = .013). CONCLUSION: We demonstrate for the first time that the responsiveness to SRL has no effect on the probability to obtain remission of acromegaly after GKRS. The remission of disease occurred more frequently in patients who had lower GH and IGF-1 levels before GKRS.

5.
Eur J Endocrinol ; 185(1): 167-177, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33950861

RESUMO

Introduction: Patients with acromegaly show musculoskeletal symptoms which may persist despite disease control. Increased i.m. fat fraction is a known cause of muscle dysfunction in several disorders. Objective: To assess the degree of fat fraction in thigh muscles of controlled acromegaly patients and its relationship with muscle dysfunction. Methods: In a cross-sectional study, we included 36 patients with controlled acromegaly and 36 matched controls. We assessed the percentage of fat fraction in each thigh muscle, using MRI 2-point Dixon sequence, and muscle performance and strength using the gait speed, timed up and go, 30-s chair stand, and hand grip strength tests. We evaluated joint symptoms using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). Results: Intramuscular fat fraction was greater in patients than controls (P < 0.05 for muscle compartments, rectus femoris (RF), vastus intermedius (VI), adductor magnus (AM) and semimembranosus). Patients had slower gait speed and poorer performance on the 30-s chair stand and timed up and go tests than controls (P < 0.05). The greater fat fraction in the combined anterior-posterior compartment and in each muscle was associated with worse performance on timed up and go (P < 0.05). The fat fraction in the anterior-posterior compartment predicted performance on timed up and go after adjusting for muscle area, IGF-I and WOMAC functional and pain scores (ß = 0.737 P < 0.001). Conclusions: Patients with controlled acromegaly have greater thigh i.m. fatty infiltration, which is associated with muscle dysfunction. Futures studies are needed to elucidate the mechanisms underlying this relationship.


Assuntos
Acromegalia , Tecido Adiposo/metabolismo , Músculos/fisiologia , Acromegalia/metabolismo , Acromegalia/fisiopatologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Exercício Físico/fisiologia , Feminino , Força da Mão/fisiologia , Humanos , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Músculos/metabolismo
6.
J Clin Endocrinol Metab ; 106(7): e2816-e2818, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-33838046
7.
J Clin Med ; 10(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809035

RESUMO

The most common form of congenital adrenal hyperplasia (CAH) results from a deficiency of the 21-hydroxylase enzyme (21-OHD), presenting with a broad spectrum of clinical phenotypes according to the CYP21A2 gene mutations. Of the 59 patients with suspected CAH, 62.7% presented a positive genetic result. Of them, 78.4% and 18.9% presented with non-classical and classical forms, respectively. An overall phenotype-genotype correlation of 88.9% was observed. Biochemically, 17-hydroxiprogesterone concentrations were significantly higher in genetically confirmed patients. Genetically, 36 patients presented with previously reported pathogenic variants, and one presented a new variant in homozygosis. Among the 74 alleles tested, point mutations were found in 89.2% and large rearrangements were found in the rest. The most prevalent pathogenic variant was p.(Val282Leu). The inclusion of relatives revealed one further case. Interestingly, 87.5% of relatives were carriers of a pathogenic variant, including two siblings initially classified as genetically positive. In addition, the study of male partners with gestational desire identified several carriers of mild mutations. Studying the allelic distribution of the variants also allowed for reclassifying one patient. In conclusion, a genetic approach including Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA) analysis, and allelic distribution of the pathogenic variants represents a beneficial tool for better classifying patients with 21-OHD.

8.
Curr Opin Endocrinol Diabetes Obes ; 28(3): 325-329, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33764929

RESUMO

PURPOSE OF REVIEW: The aim of this article is to review and discuss recent evidence of psychological complications in Cushing's syndrome. RECENT FINDINGS: Recent research has described the presence of depression, anxiety, posttraumatic stress disorder, mania, bipolar disorder and psychotic symptoms in patients with Cushing's syndrome. Furthermore, the perspective of patients' partners has also been emphasized. SUMMARY: Recent literature highlights the importance of screening for psychological alterations in Cushing's syndrome, as these alterations can be present in many patients, having a high impact in daily life. Depression is a very common symptom, although in rare cases, patients can also present mania or psychosis. Some studies highlight the importance of screening for organic disease (including Cushing's syndrome) in patients with unexpected or first onset psychiatric symptoms. Finally, the perspective of the patients' partners makes it clear that the partners can also suffer due to the disease of the patient. Intervention programmes involving patient's partners could be helpful to improve both patient and partner wellbeing.


Assuntos
Síndrome de Cushing/psicologia , Transtornos Mentais/diagnóstico , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Humanos , Transtornos Mentais/etiologia , Cônjuges
9.
Best Pract Res Clin Endocrinol Metab ; 35(1): 101505, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33707083

RESUMO

Measurement of Health-Related Quality of Life (HRQoL) is emerging as an important clinical endpoint which complements diagnostic workup and contributes to place patients at the centre of the decision-making process through the recognition of their needs, concerns, goals and expectations. Chronic excessive cortisol exposure in Cushing's syndrome (CS) causes severe physical and psychological morbidity which invariably affects HRQoL during the active phase of the disease and even after successful treatment. This sustained deterioration of patient's wellbeing is partly related to the persistence of several features associated with prior cortisol excess, including affective disorders, cognitive dysfunctions and negative illness perception. The aim of this review is to summarize the most recent evidence on HRQoL in CS, including the main determinants of its impairment and the results of some educational programs specifically addressed to improve patient's coping abilities. The preliminary results of an unpublished survey on patient's unmet needs will also be presented.


Assuntos
Síndrome de Cushing/epidemiologia , Síndrome de Cushing/psicologia , Qualidade de Vida , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Síndrome de Cushing/complicações , Síndrome de Cushing/diagnóstico , Humanos , Hidrocortisona/sangue , Morbidade , Qualidade de Vida/psicologia
10.
Endocrine ; 71(3): 569-577, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33544353

RESUMO

Patients' perceptions on quality of care and gaps in diagnosis/management of rare endocrine diseases (RED) were collected in a 21-item questionnaire, answered on-line in the patients' language. There were 598 (66% females) responses from 29 countries reflecting pituitary, adrenal, thyroid, parathyroid, gonadal, genetic and autoimmune diseases. While in 36% a diagnosis was made in <1 year, in 28% it took >5 years. In 64% it took 2-7 professionals for a correct diagnosis, after which in >50% a specialist/specific treatment was available within 1 month; 60% were satisfied with current treatment. Most (59-67%) would have liked access to psychological support, social worker, dietician or physiotherapist/rehabilitation specialists. Half were satisfied with information received, treatment and health care follow-up; 87% contacted patient/support groups; 78% agreed that "The personal limitations related to the disease, impact on my everyday quality of life". Conclusion: Diagnostic delay in RED is still unsatisfactory in Europe, as well as specific needs impacting QoL.


Assuntos
Doenças do Sistema Endócrino , Qualidade de Vida , Diagnóstico Tardio , Atenção à Saúde , Doenças do Sistema Endócrino/diagnóstico , Doenças do Sistema Endócrino/terapia , Europa (Continente) , Feminino , Humanos , Masculino , Percepção , Inquéritos e Questionários
11.
Clin Endocrinol (Oxf) ; 94(5): 811-819, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32978826

RESUMO

OBJECTIVE: Large somatotrophic adenomas depict poor response to somatostatin receptor ligands (SRLs). Debulking has shown to enhance SRLs effect in some but not all cases and tumour volume reduction has been proposed as the main predictor of response. No biological studies have been performed so far in this matter. We aimed to identify molecular markers of response to SRLs after surgical debulking in GH-secreting adenomas. DESIGN: We performed a multicenter retrospective study. PATIENTS: 24 patients bearing large GH-producing tumours. MEASUREMENTS: Clinical data and SRLs response both before and after surgical debulking were collected, and 21 molecular biomarkers of SRLs response were studied in tumour samples by gene expression. RESULTS: From the 21 molecular markers studied, only two of them predicted enhanced SRLs response after surgery. Tumours with improved response to SRLs after surgical debulking showed lower levels of Ki-67 (MKI67, FC = 0.17 and P = .008) and higher levels of RAR-related orphan receptor C (RORC) (FC = 3.1 and P Ë‚ .001). When a cut-off of no detectable expression was used for Ki-67, the model provided a sensitivity of 100% and a specificity of 52.6% with an area under the curve of 65.8%. Using a cut-off of 2 units of relative expression of RORC, the prediction model showed 100% of sensitivity and specificity. CONCLUSIONS: High levels of RORC and low levels of Ki-67 identify improved SRLs response after surgical debulking in large somatotropic adenomas. To determine their expression would facilitate medical treatment decision-making after surgery.

12.
Eur J Endocrinol ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33320830

RESUMO

Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform. AIMS: 1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD. DESIGN: On-line survey in endocrine centres throughout Europe. PATIENTS AND METHODS: Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018. RESULTS: Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved. CONCLUSION: Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.

13.
Front Endocrinol (Lausanne) ; 11: 577173, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329385

RESUMO

Context: Hypertension is a major cardiovascular risk factor related to increased mortality in acromegaly. Surgical cure of acromegaly is associated with improvement in blood pressure levels, however little is known about the effect of pegvisomant (PEGV) treatment in patients with hypertension. This analysis evaluates outcomes in patients with hypertension and acromegaly included in ACROSTUDY. Methods: ACROSTUDY is a global non-interventional surveillance study of long-term treatment with PEGV, monitoring its safety and efficacy. The cohort was retrospectively divided in two subgroups: patients with and without hypertension. Stepwise logistic regression and Kaplan-Meyer analyses were performed for testing predictors of mortality. Results: The total cohort included 2,090 patients with acromegaly treated with PEGV who were followed for a median of 6.8 years (range up to 12.1 years). In ACROSTUDY there were 1,344 patients with hypertension (52.3% males). This subgroup was older, had a higher BMI, and higher prevalence of diabetes, hyperlipidemia, and cardiovascular disease (CVD) when compared to patients without hypertension. During ACROSTUDY, 68 deaths were reported in the hypertension cohort, vs 10 in the cohort without hypertension. Both CVD (p<0.0001) and anterior pituitary deficiencies (p=0.0105) at study entry independently predicted mortality in patients with acromegaly and hypertension; Kaplan-Meier analysis confirmed that CVD significantly impairs survival. Conclusions: Hypertension is common in patients with acromegaly and significantly increases mortality, especially when there is concomitant CVD. These data suggest that treatment goals should extend beyond IGF-I normalization, and include optimisation of substitution of pituitary deficiencies and scrutinous screening and treatment of CVD.


Assuntos
Acromegalia/complicações , Doenças Cardiovasculares/mortalidade , Hipertensão/mortalidade , Acromegalia/tratamento farmacológico , Acromegalia/patologia , Adulto , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/análogos & derivados , Humanos , Hipertensão/etiologia , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
14.
Neuroendocrinology ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33040060

RESUMO

BACKGROUND: Craniopharyngioma (CP) is a rare tumor in the elderly whose clinical features and prognosis are not well known in this population. AIM: To evaluate the clinicopathological features and therapeutic outcomes of CP diagnosed in the elderly. PATIENTS AND METHODS: A retrospective, multicenter, national study of CP patients diagnosed over the age of 65 years and surgically treated was performed. RESULTS: From a total of 384 adult CP patients, we selected 53 (13.8%) patients [27 women (50.9%), mean age 72.3 ± 5.1 years (range 65-83 yr)] diagnosed after the age of 65 years. The most common clinical symptoms were visual field defects (71.2%) followed by headache (45.3%). Maximum tumor diameter was 2.9 ± 1.1 cm. In most patients, the tumor was suprasellar (96.2%) and mixed (solid-cystic) (58.5%). The surgical approach most commonly used was transcranial surgery (52.8%) and more than half of the patients (54.7%) underwent subtotal resection (STR). Adamantinomatous CP (ACP) and papillary CP (PCP) were present in 51% and 45.1%, respectively, with mixed forms in the remaining. Surgery was accompanied by an improvement in visual field defects and in headaches; however, pituitary hormonal hypofunction increased, mainly at the expense of an increase in the prevalence of diabetes insipidus (DI) (from 3.9% to 69.2%). Near-total resection (NTR) was associated with a higher prevalence of DI compared with subtotal resection (87.5 vs 53.6%, p=0.008). Patients were followed for 46.7±40.8 months. Mortality rate was 39.6% with a median survival time of 88 (95% CI, 57-118) months. DI at last visit was associated with a lower survival. CONCLUSION: CP diagnosed in the elderly shows a similar distribution by sex and histologic forms than that diagnosed at younger ages. At presentation visual field alterations and headaches are the main clinical symptoms which improve substantially with surgery. However, surgery, mainly NTR, is accompanied by worsening of pituitary function, especially DI, which seems to be a predictor of mortality in this population.

15.
Endocr Relat Cancer ; 27(6): 375-389, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32302973

RESUMO

Pharmacologic treatment of acromegaly is currently based upon assay-error strategy, the first-generation somatostatin receptor ligands (SRL) being the first-line treatment. However, about 50% of patients do not respond adequately to SRL. Our objective was to evaluate the potential usefulness of different molecular markers as predictors of response to SRL. We used somatotropinoma tissue obtained after surgery from a national cohort of 100 acromegalic patients. Seventy-one patients were treated with SRL during at least 6 months under maximal therapeutic doses according to IGF1 values. We analyzed the expression of SSTR2, SSTR5, AIP, CDH1 (E-cadherin), MKI67 (Ki-67), KLK10, DRD2, ARRB1, GHRL, In1-Ghrelin, PLAGL1 and PEBP1 (RKIP) by RT-qPCR and mutations in GNAS gene by Sanger sequencing. The response to SRL was categorized as complete response (CR), partial (PR) or non-response (NR) if IGF1 was normal, between >2<3 SDS or >3 SDS IGF1 at 6 months of follow-up, respectively. From the 71 patients treated, there were 27 CR (38%), 18 PR (25%) and 26 NR (37%). SSTR2, Ki-67 and E-cadherin were associated with SRL response (P < 0.03, P < 0.01 and P < 0.003, respectively). E-cadherin was the best discriminator for response prediction (AUC = 0.74, P < 0.02, PPV of 83.7%, NPV of 72.6%), which was validated at protein level. SSTR5 expression was higher in patients pre-treated with SRL before surgery. We conclude that somatotropinomas showed heterogeneity in the expression of genes associated with SRL response. E-cadherin was the best molecular predictor of response to SRL. Thus, the inclusion of E-cadherin in subsequent treatment-decision after surgical failure may be useful in acromegaly.

16.
Neuroendocrinology ; 110(9-10): 882-888, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101858

RESUMO

Over the last 2 decades, advances in the diagnosis and management of pituitary diseases have made it possible to attain an endocrine "cure" in a large proportion of patients. In other words, tumors can be excised or controlled with drugs, mass effects of the lesion on surrounding structures can be solved, and pituitary deficiencies can be substituted with all relevant hormones. While this is considered a satisfactory outcome for health care providers, patients often suffer from an aftermath of prior endocrine dysfunction exposure, with irreversible effects, both physically and psychologically, which have a great impact on their everyday life. Diagnostic delay, often of several years, adds a negative impact on health perception. This affects their social, professional, and family domains and determines their future life. Understanding that this may occur is important, and health care providers should offer information to prepare the patient for this difficult journey, especially in the case of acromegaly, Cushing disease, or hypopituitarism. In order to maintain a good quality of life (QoL) in the long-term, patients need to adapt to this new situation, something that may be difficult, since they often cannot continue with all the activities and rhythm they used to do. Depression is often the consequence of maladaptation to the new situation, leading to impaired QoL.

17.
J Clin Endocrinol Metab ; 105(5)2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31912154

RESUMO

CONTEXT: Muscle weakness is common in patients with Cushing's syndrome (CS) and may persist after the resolution of hypercortisolism. Intramuscular fatty infiltration has been associated with the deterioration of muscle performance in several conditions. OBJECTIVES: To quantify the degree of fatty infiltration in the thigh muscles of "cured" CS patients and evaluate the relationship between intramuscular fatty infiltration and physical performance. DESIGN: This was a cross-sectional study. SETTING: Tertiary referral center. PATIENTS: Thirty-six women with CS in remission, and 36 controls matched for age, BMI, menopausal status, and level of physical activity. MAIN OUTCOME MEASURES: We analyzed the percentage fat fraction (FF) of the thigh muscles in the anterior, posterior, and combined anterior and posterior compartments using MRI and 2-point Dixon sequence. We assessed muscle function and strength using the following tests: gait speed (GS), timed up and go (TUG), 30-second chair stand, and hand grip strength. RESULTS: Fat fraction in all the compartments analyzed was increased in patients as compared with controls. The performance on TUG, 30-second chair stand, and GS was more impaired in CS patients versus controls. In patients, greater FF was negatively associated with performance on functional tests. Fat fraction in the combined anterior and posterior compartments predicted performance on TUG (ß 0.626, P < 0.000) and GS (ß -0.461, P = 0.007), after adjusting for age, BMI, menopausal status, and muscle mass. CONCLUSIONS: Thigh muscle fatty infiltration is increased in "cured" CS patients and is associated with poorer muscle performance. Future studies are needed to establish therapeutic strategies to improve muscle weakness in these patients.


Assuntos
Tecido Adiposo/metabolismo , Síndrome de Cushing , Músculo Esquelético/metabolismo , Desempenho Físico Funcional , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Adiposidade/fisiologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/metabolismo , Síndrome de Cushing/fisiopatologia , Síndrome de Cushing/terapia , Feminino , Força da Mão , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Indução de Remissão , Coxa da Perna
18.
Eur J Endocrinol ; 181(5): 461-472, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31480014

RESUMO

Objective: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality. Methods: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years. Results: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment. Conclusion: Mortality rate was highest in patients with ectopic CS. Infectious diseases were the commonest cause of death soon after diagnosis, emphasizing the need for careful clinical vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.


Assuntos
Síndrome de Cushing/mortalidade , Doenças das Glândulas Suprarrenais/etiologia , Doenças das Glândulas Suprarrenais/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Estudos de Coortes , Comorbidade , Síndrome de Cushing/complicações , Complicações do Diabetes/mortalidade , Europa (Continente)/epidemiologia , Feminino , França/epidemiologia , Humanos , Infecções/complicações , Infecções/mortalidade , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/etiologia , Doenças da Hipófise/mortalidade , Sistema de Registros , Fatores Sexuais , Adulto Jovem
19.
Endocr Connect ; 8(1): 39-49, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640713

RESUMO

Background Biochemical control of GH/IGF-I excess in acromegaly (ACRO) is associated with persistent impairment of trabecular microstructure leading to increased risk of vertebral fractures. Circulating miRNAs modulate the activity of osteoblasts and osteoclasts, and may be potential biomarkers of osteoporosis. Aims Identify differentially expressed miRNAs in the serum of patients with controlled ACRO vs controls and correlate miRNA levels with both biochemical and structural bone parameters. Patients and methods Twenty-seven patients with controlled ACRO (11 males, 16 females; mean age, 48 ± 5 years; BMI, 28 ± 4 kg/m2) and 27 age-, gender- and BMI-matched controls were recruited. Areal BMD at lumbar spine and femur, and trabecular bone score were assessed; volumetric BMD was measured by quantitative computed tomography QCT-Pro (Mindways). Twenty miRNAs, chosen by their putative role in bone, were quantified in serum using real-time qPCR. Results In ACRO patients, miR-103a-3p and miR-191-5p were found overexpressed, whereas miR-660-5p was underexpressed (P < 0.001). miR-103a-3p levels were negatively associated with both trabecular vBMD at trochanter and serum osteoprotegerin concentrations (P < 0.05) and positively with vitamin D concentrations (P < 0.01) and total cross-sectional area of the femoral neck (P < 0.05). miR-660-5p levels were correlated with both trabecular vBMD at trochanter and OPG concentrations (P < 0.05), but were negatively associated with vitamin D levels (P < 0.05). A negative correlation between miR-103-a-3p and miR-660-5p was found in both groups (P < 0.001). Conclusions Circulating miR-103a-3p and miR-660-5p are differentially expressed in controlled ACRO patients and associated with bone structural parameters. miRNAs may be one of the mechanisms involved in the pathogenesis of bone disease and could be used as biomarkers in ACRO patients.

20.
Clin Endocrinol (Oxf) ; 90(1): 184-191, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30267589

RESUMO

OBJECTIVE: Impaired quality of life (QoL) in primary hyperparathyroidism (PHPT) is commonly present. Patients may complain about nonspecific neurocognitive symptoms which can be difficult to quantify. Two different disease-specific questionnaires have been developed, that is, the parathyroid assessment of symptoms score (PAS) and the primary hyperparathyroidism quality of life (PHPQoL). Using these two questionnaires, we assessed relationship between QoL and biochemical indices in PHPT and effects of parathyroidectomy (PTX). DESIGN: A prospective cohort study. METHODS: Patients with PHPT diagnosed from 2015 to 2017 were asked to answer the questionnaires before and 12 months after PTX. Biochemistry was obtained on both occasions. RESULTS: A total of 104 PHPT patients answered PAS and PHPQoL questionnaires at baseline, with a median age of 64 years (73% females). PHPQoL score correlated inversely with ionized calcium and PTH at baseline (P Ë‚ 0.04). Total PAS and PHPQoL score did not differ between those with and without osteoporosis, renal calcifications and impaired renal function. Based on levels of ionized calcium, PHPQoL differed significantly between patients with mild- and moderate-severe hypercalcemia (P = 0.01). Fifty-three patients answered PAS and PHPQoL 12 months after PTX showing an improved QoL at follow-up (Pall  Ë‚ 0.02). Stratifying patients into groups based on levels of ionized calcium showed a significantly improved PHPQoL score in patients with mild (˂1.45 mmol/L) as well as moderate-severe hypercalcemia (≥1.45 mmol/L) at follow-up (Pall  Ë‚ 0.03). CONCLUSION: Quality of life improved 12 months after PTX in PHPT patients. Impaired QoL seems to be associated with the degree of hypercalcemia rather than organ manifestations attributable to PHPT.


Assuntos
Hiperparatireoidismo Primário/cirurgia , Paratireoidectomia/métodos , Qualidade de Vida , Adulto , Cálcio/sangue , Cálcio/farmacologia , Estudos de Coortes , Feminino , Humanos , Hipercalcemia , Hiperparatireoidismo Primário/psicologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
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