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1.
Dtsch Med Wochenschr ; 146(15): 950-954, 2021 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-34344028

RESUMO

Acromegaly is a rare but severe disorder which is usually due to an excessive secretion of growth hormone (GH) by a pituitary adenoma. Screening mainly relies on the measurement of insulin-like growth factor 1, and confirmatory diagnostics includes a GH suppression test. As delayed diagnosis results in increased morbidity and mortality, we here discuss recently published suggestions regarding the biochemical work-up of suspected cases and the follow-up of co-morbidities. Moreover, new analytical tools (such as automatic identification of typical facial changes using artificial intelligence) are presented, hopefully allowing for an earlier diagnosis in the future. So far, surgery is still regarded as therapy of first choice. In cases without postoperative remission, a new imaging approach (combining sellar magnetic resonance imaging and position emission tomography) may improve the results of repeated surgery. The pharmaceutical arsenal now includes the first orally available somatostatin analogue, and recent data on possible drug combinations and the outcome of radiotherapy are presented. Finally, special attention is paid to older and pregnant patients, as well as certain considerations during the COVID-19 pandemic (where appropriate diagnosis and management of acromegaly is particularly challenging).


Assuntos
Acromegalia/diagnóstico , Acromegalia/cirurgia , Acromegalia/diagnóstico por imagem , Acromegalia/terapia , Adenoma/cirurgia , Comorbidade , Diagnóstico Precoce , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Humanos , Prognóstico
2.
Eur J Endocrinol ; 185(4): 525-538, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34342594

RESUMO

Objective: To report the final long-term safety and efficacy analyses of patients with acromegaly treated with pegvisomant from the ACROSTUDY. Design: Global (15 countries), multicentre, non-interventional study (2004-2017). Methods: The complete ACROSTUDY cohort comprised patients with acromegaly, who were being treated with pegvisomant (PEGV) prior to the study or at enrolment. The main endpoints were long-term safety (comorbidities, adverse events (AEs), pituitary tumour volumes, liver tests) and efficacy (IGF1 changes). Results: Patients (n = 2221) were treated with PEGV for a median of 9.3 years (range, 0-20.8 years) and followed up for a median of 7.4 years (range, 0-13.9 years). Before PEGV, 96.3% had received other acromegaly treatments (surgery/radiotherapy/medications). Before PEGV treatment, 87.2% of patients reported comorbidities. During ACROSTUDY, 5567 AEs were reported in 56.5% of patients and of these 613 were considered treatment-related (in 16.5% of patients) and led to drug withdrawal in 1.3%. Pituitary imaging showed a tumour size increase in 7.1% of patients; the majority (71.1%) reported no changes. Abnormal AST or ALT liver tests occurred in 3.2% of patients. IGF1 normalization rate improved over time, increasing from 11.4% at PEGV start to 53.7% at year 1, and reaching 75.4% at year 10 with the use of ≥30 mg PEGV/day in an increasing proportion of patients. Conclusion: This comprehensive review of the complete cohort in ACROSTUDY confirmed the overall favourable benefit-to-risk profile and high efficacy of PEGV as mono- and combination therapy in patients with an aggressive course/uncontrolled/active acromegaly requiring long-term medical therapy for control.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Acromegalia/epidemiologia , Adenoma/tratamento farmacológico , Adenoma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , História do Século XXI , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
3.
BMJ Case Rep ; 14(8)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404661

RESUMO

Acromegaly is a rare disorder of unregulated hypersecretion of growth hormone that causes cardiovascular, metabolic and respiratory complications. Herein, we describe the case of a middle-aged man admitted to the hospital with severe COVID-19 found to have clinical and biochemical evidence of acromegaly. His respiratory status declined despite initiation of standard treatments, prompting initiation of subcutaneous octreotide. Following initiation of this therapy, he rapidly improved and was discharged from the hospital 2 days later. Subsequent workup revealed a pituitary macroadenoma that was surgically removed, with improvement in his acromegaly symptoms. COVID-19 disease severity is increased by pre-existing diabetes, lung disease and immunosuppression. Although this patient had obstructive sleep apnoea and pre-diabetes, we hypothesise that our patient's acromegaly contributed to his severe course, as reflected by his rapid improvement after starting treatment with subcutaneous octreotide. Acromegaly may predispose to more severe outcomes in patients with COVID-19.


Assuntos
Acromegalia , COVID-19 , Insuficiência Respiratória , Acromegalia/complicações , Acromegalia/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , SARS-CoV-2
4.
Pan Afr Med J ; 38: 394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381538

RESUMO

Acromegaly is, in most cases, caused by growth hormone secreting pituitary adenomas. Those patients often develop different pathologies of the thyroid gland, however, the occurrence of Grave´s disease is quite a rare situation. We report a case of a 64-year-old female patient who presented with signs of hyperthyroidism and imbalance of her diabetes mellitus. On physical examination, she had facial features of acromegaly. Biochemical testing confirmed the suspicion of acromegaly and Grave´s disease, with an elevated insulin-like growth factor-1 and a suppressed thyroid stimulation hormone (TSH) with positive TSH-receptor antibodies. A pituitary Magnetic Resonance Imaging (MRI) was performed, revealing a macro-adenoma and an empty sella. The patient successfully underwent a transsphenoidal surgery and obtained a remission of her hyperthyroidism under anti-thyroid drugs.


Assuntos
Acromegalia/diagnóstico , Síndrome da Sela Vazia/diagnóstico por imagem , Doença de Graves/diagnóstico por imagem , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Antitireóideos/administração & dosagem , Diabetes Mellitus/fisiopatologia , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Fator de Crescimento Insulin-Like I/metabolismo , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tireotropina/metabolismo
5.
Front Public Health ; 9: 693409, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336773

RESUMO

Background: Adherence to therapy is one of the most important elements during the therapeutic process ensuring the predefined therapeutic outcomes. The aim is to analyze the need and importance of treatment adherence guideline for acromegaly patients and the possibilities for its development and implementation in Bulgaria. Methods: A set of methods was applied: (1) a literature review in the electronic database for identification of articles and guidelines related to adherence and acromegaly; (2) analysis of Bulgarian legislative documents; (3) a pilot study for assessment of the level of treatment adherence among hospitalized Bulgarian acromegaly patients in 2018; (4) a plan for development and implementation of specific guideline was created entitled BULMEDACRO - BULgarian guideline for MEdication aDherence assessment and improvement in ACROmegaly. Results: No specific guidelines for evaluation, monitoring, reporting and/or improving adherence in acromegaly patients has been found in the literature. Requirements for regular assessment of the level of adherence, application of appropriate methods for improvement and monitoring are not sufficiently formulated and mandatory. The pilot study confirmed that therapy adherence among Bulgarian patients with acromegaly is relatively high as almost 90% of patients report that they strictly comply with their prescribed treatment regimen. It is necessary, however, a specific guideline focused on the methods for assessment and improvement of adherence, in order to ensure monitoring and follow-up of acromegaly patients. Conclusions: Patients with acromegaly should be the focus of specially designed national programs, initiatives and/or guidelines for regular evaluation and improvement of the adherence level. Despite the difficulties and the lack of an adequate legal basis, successive steps initiated by different stakeholder are needed.


Assuntos
Acromegalia , Acromegalia/diagnóstico , Bulgária/epidemiologia , Protocolos Clínicos , Humanos , Cooperação do Paciente , Projetos Piloto
6.
Intern Med ; 60(15): 2375-2383, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34334589

RESUMO

Objective Glucose-dependent insulinotropic polypeptide (GIP) is speculated to worsen growth hormone (GH) hypersecretion in acromegaly and to be a cause of paradoxical increases in GH (PI-GH) during 75-g oral glucose tolerance testing (75-g OGTT). Dipeptidyl peptidase-4 inhibitors (DPP4is), which increase the circulating concentration of active GIP, are frequently administered to diabetic patients, including those with acromegaly. We aimed to determine whether or not the administration of a DPP4i increases GH concentration, especially in patients demonstrating PI-GH during a DPP4i-OGTT, in which a DPP4i was administered immediately before 75-g OGTT. Methods This prospective cross-sectional study was carried out on acromegalic patients admitted to Hokkaido University hospital between June 2011 and May 2018. The participants underwent both 75-g OGTT and DPP4i-OGTT. For those who underwent surgery, immunohistochemical staining and quantitative polymerase chain reaction (PCR) for the GIP receptor (GIPR) were performed on the resected pituitary adenomas. Results Twenty-five percent of the participants had PI-GH confirmed (3 of 12 cases). Two of the three participants who demonstrated PI-GH exhibited higher circulating GH concentrations during DPP4i-OGTT than during OGTT. The increase in plasma glucose was reduced during DPP4i-OGTT compared to during 75-g OGTT, suggesting that the increase in GH during DPP4i-OGTT was due not to high glucose concentrations but instead increased GIP caused by the administration of DPP4i. The adenoma from one participant with PI-GH displayed positive immunostaining for GIPR and a higher GIPR messenger ribonucleic acid (mRNA) expression than the others. Conclusion DPP4i may enhance the GH secretion response during glucose loading, especially in individuals with PI-GH.


Assuntos
Acromegalia , Inibidores da Dipeptidil Peptidase IV , Hormônio do Crescimento Humano , Acromegalia/tratamento farmacológico , Estudos Transversais , Dipeptidil Peptidases e Tripeptidil Peptidases , Glucose , Hormônio do Crescimento , Humanos , Estudos Prospectivos
7.
Intern Med ; 60(15): 2451-2459, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34334593

RESUMO

We encountered a 70-year-old Japanese woman with neurofibromatosis type 1 (NF1) who had a history of pheochromocytoma and concurrently developed adenomatous goiter, primary hyperparathyroidism, and acromegaly. The patient had a somatotroph adenoma of the adenohypophysis that predisposed her to multinodular goiter. Three parathyroid tumors were detected by cervical ultrasonography and cervicothoracic computed tomography. Genetic analyses did not reveal genetic alterations (e.g. loss-of-function mutation) in the causative genes of endocrine tumors, including MEN1, RET, VHL, CDKN1B, and CDKN2C. The NF1 gene could not be analyzed genetically due to the patient's refusal. The pathophysiologic mechanisms of endocrinopathy concurrence in NF1 remain to be elucidated.


Assuntos
Acromegalia , Neoplasias das Glândulas Suprarrenais , Bócio , Hiperparatireoidismo Primário , Neoplasia Endócrina Múltipla Tipo 1 , Neurofibromatose 1 , Acromegalia/complicações , Acromegalia/diagnóstico , Acromegalia/genética , Idoso , Feminino , Humanos , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/genética , Neurofibromatose 1/complicações , Neurofibromatose 1/genética
8.
Handb Clin Neurol ; 181: 67-74, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34238480

RESUMO

The hypothalamus is functional neuroendocrine tissue that is responsible for the synthesis and secretion of peptide hormones that regulate the pituitary and other endocrine functions. Endocrine tumors of the hypothalamus are rare but they provide a model for tumors that have both structural and functional effects. Patients with hypothalamic endocrine tumors suffer mass effects including headaches, visual disturbances, and endocrine dysfunction due to structural damage to hypothalamic nuclei, which regulate appetite, temperature, diurnal rhythms and emotions. In addition, these tumors can secrete hormones that can cause acromegaly, Cushing disease, hyperprolactinemia, and the syndrome of inappropriate antidiuresis. Morphologic classification of these tumors has provided evidence for two classes of tumors, gangliocytomas that are composed of large neurons and neurocytomas that are comprised of small cells; these resemble the variants of magnocellular and parvocellular neurons in the hypothalamic nuclei. Biomarkers are used to classify these tumors and achieve accurate structure-function correlations. While surgery remains the mainstay of therapy, novel medical and radiopharmaceutical approaches are available for patients with progressive and/or unresectable tumors.


Assuntos
Acromegalia , Ganglioneuroma , Hormônios Hipotalâmicos , Neoplasias Hipotalâmicas , Humanos , Hipófise
9.
J Clin Neurosci ; 90: 105-111, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34275532

RESUMO

BACKGROUND: Any preoperative diagnostic assessment that can predict the success of the operation in acromegaly will provide a positive impact on overall remission rates. The aim of this study is to reveal whether the signal intensity in T2-weighted Magnetic Resonance Imaging can predict postoperative results in acromegaly patients with macroadenoma. METHODS: We analyzed our surgical results in regard to T2-weighted images in newly diagnosed consecutive 124 patients with acromegaly, operated between 2014 and 2019. The T2-intensity of the pure somatotroph macroadenomas was correlated with the clinical, radiological, surgical and histopathological characteristics of the acromegaly patients. RESULTS: We found a predominance of T2-hyperintensity in our series (45%) and the T2-hypointense pure somatotroph adenomas were detected in only 34% of our patients. Total resection was performed in 72% of newly diagnosed acromegaly patients in this series. Accordingly, total resection was achieved in 69% of the T2-hyperintense group, 77% of the T2-hypointense group and 69% of the T2-isointense group. The surgical remission rates for the T2-hyper-, hypo- and isointense groups were 54.5%, 80.7%, and 68.7%, respectively. The surgical remission rate in the T2-hyperintense group was significantly lower than those of hypo- and isointense groups in newly diagnosed acromegaly patients. CONCLUSIONS: This study demonstrates a close relationship between the T2 signal intensity and the surgical remission rates in acromegaly patients with macroadenoma. Preoperative T2-intensity images may predict the probability of post-surgical remission in patients with newly diagnosed acromegaly. Further support fort this idea comes from recent guidelines for acromegaly management in which the potential utility of using T2 intensity to optimize patient management has been emphasized.


Assuntos
Acromegalia/diagnóstico por imagem , Adenoma/diagnóstico por imagem , Neoplasias Hipofisárias/diagnóstico por imagem , Acromegalia/etiologia , Acromegalia/cirurgia , Adenoma/complicações , Adenoma/cirurgia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Zhonghua Yi Xue Za Zhi ; 101(27): 2107-2110, 2021 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-34275245

RESUMO

Acromegaly is a rare disease, and multidisciplinary collaboration is essential for its diagnosis, treatment, and follow-up.In recent years, a series of novel findings have been echieved in clinical studies on acromegaly.Therefore, the China Pituitary Adenoma Specialist council has convened Chinese specialists in neurosurgery, endocrinology, radiology, and radiotherapy to release the Chinese Consensus for the Diagnosis and Treatment of Acromegaly (2021), which aims to promote the standardized and individualized management of acromegaly.Looking back to the past, the consensuses and guidelines have played vital roles in establishing the widely recognized biochemical remission criteria, promoting new drugs and novel therapeutic strategies which are of significance for standardized treatment, and emphasizing the need to focus on the systemic complications of acromegaly and the long-term quality of life. In this editorial, we briefly reviewed the expert consensuses and clinical guidelines on acromegaly at home and abroad, and discussed their important roles in promoting standardized disease management from three aspects including biochemical remission standards, medical treatment, and the diagnosis and treatment of systemic complications.


Assuntos
Acromegalia , Neoplasias Hipofisárias , Acromegalia/diagnóstico , Acromegalia/terapia , China , Consenso , Humanos , Qualidade de Vida
11.
Zhonghua Yi Xue Za Zhi ; 101(27): 2111-2114, 2021 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-34275246

RESUMO

Led by the China Pituitary Adenoma Specialist Council, the Chinese Consensus for the Diagnosis and Treatment of Acromegaly (2021 Edition) is developed combined with the research progress of pituitary growth hormone (GH)-secreting adenoma both at home and abroad, evidence-based evidence of the diagnosis and treatment of acromegaly, and China's national conditions. Based on the guideline for acromegaly (2013 Edition), the new version of consensus emphasizes the importance of multidisciplinary team (MDT) and individual therapy. The criteria for control of acromegaly is discussed. Pathological criteria for the diagnosis of pituitary GH-secreting adenoma is updated. New developments in surgery, drug and radiotherapy are introduced. Meanwhile, the diagnosis and treatment of acromegaly patients concurrent with other particular scenarios, including pregnancy and refractory pituitary GH-secreting adenoma is suggested. This article aims to describe the updated key points of the new version of the consensus, and thus facilitate the clinical implementation of standardized diagnosis and treatment for acromegaly patients.


Assuntos
Acromegalia , Adenoma , Neoplasias Hipofisárias , Acromegalia/diagnóstico , Acromegalia/terapia , Adenoma/diagnóstico , Adenoma/terapia , China , Consenso , Humanos , Fator de Crescimento Insulin-Like I , Estudos Retrospectivos
12.
Curr Opin Endocrinol Diabetes Obes ; 28(4): 419-426, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34101652

RESUMO

PURPOSE OF REVIEW: Discuss recent literature regarding clinical manifestations and comorbidities in acromegaly, with focus on early diagnosis and customized care. RECENT FINDINGS: The mean interval between onset of clinical manifestations and diagnosis is currently 3-5 years. Women, especially younger than 50 years of age, experience longer delays, have lower insulin-like growth factor 1 (IGF-1) levels and larger tumors than men. Development of comorbidities usually precedes the diagnosis and is influenced by age, sex, and biochemical disease activity. Comorbidities other than irreversible osteoarticular structural changes usually improve after acromegaly treatment. In patients with diabetes, the course of hyperglycemia not only depends on biochemical control but also on specific acromegaly therapies. Quality of life is influenced by sex, as well as by acromegaly symptoms, biochemical activity, and treatment. Quality of life remains lower than general population despite biochemical remission. SUMMARY: Early diagnosis can be achieved by suspecting acromegaly based on suggestive clinical scenarios rather than obvious changes in appearance. Personalized care entails a proactive multidisciplinary approach to identify and treat comorbidities while carefully monitoring the effects of acromegaly treatment.


Assuntos
Acromegalia , Medicina de Precisão/métodos , Acromegalia/diagnóstico , Acromegalia/etiologia , Acromegalia/terapia , Comorbidade , Humanos , Qualidade de Vida , Resultado do Tratamento
13.
Expert Opin Drug Deliv ; 18(10): 1501-1512, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34128734

RESUMO

INTRODUCTION: The FDA approval of oral semaglutide for type 2 diabetes (2019) and oral octreotide for acromegaly (2020) is evidence that selected niche peptides can be administered orally if formulated with selected intestinal permeation enhancers. AREAS COVERED: We evaluated the oral octreotide formulation, MYCAPSSA® (Chiasma Pharmaceuticals, Needham, MA, USA). An outline of the current standard of care in acromegaly and the benefits of oral octreotide versus depot injections is provided. We discuss the Transient Permeation Enhancer (TPE®) technology used and detail the safety and efficacy data from animal models and clinical trials. EXPERT OPINION: TPE® is an oily suspension of octreotide that includes a number of excipients that can transiently alter epithelial barrier integrity by opening of intestinal epithelial tight junctions arising from transcellular perturbation. Phase I studies using 20 mg octreotide capsules yielded a relative oral bioavailability of ~0.7% and primary endpoints were achieved in two Phase III studies. The oral octreotide dose required to achieve these endpoints was over 200 times that of the 0.1 mg immediate-release subcutaneous injection, a reminder of the difficulty in achieving oral absorption of macromolecules. Many acromegaly patients will prefer a convenient twice-daily oral formulation of octreotide compared to monthly depot injections.


Assuntos
Acromegalia , Diabetes Mellitus Tipo 2 , Animais , Disponibilidade Biológica , Humanos , Octreotida , Tecnologia
14.
Eur J Endocrinol ; 185(2): 289-297, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34081617

RESUMO

Objective: High insulin-like growth factor 1 (IGF-1) and unsuppressed growth hormone (GH) levels after glucose load confirm the diagnosis of acromegaly. Management of patients with conflicting results could be challenging. Our aim was to evaluate the clinical and hormonal evolution over a long follow-up in patients with high IGF-1 but normal GH nadir (GHn < 0.4 µg/L according to the latest guidelines). Design: Retrospective cohort study. Methods: We enrolled 53 patients presenting high IGF-1 and GHn < 0.4 µg/L, assessed because of clinical suspicion of acromegaly or in other endocrinological contexts (e.g. pituitary incidentaloma). Clinical and hormonal data collected at the first and last visit were analyzed. Results: At the first evaluation, the mean age was 54.1 ± 15.4 years, 34/53 were females, median IGF-1 and GHn were +3.1 SDS and 0.06 µg/L, respectively. In the whole group, over a median time of 6 years, IGF-1 and GHn levels did not significantly change (IGF-1 mean of differences: -0.58, P = 0.15; GHn +0.03, P = 0.29). In patients with clinical features of acromegaly, the prevalence of acromegalic comorbidities was higher than in the others (median of 3 vs 1 comorbidities per patient, P = 0.005), especially malignancies (36% vs 6%, P = 0.03), and the clinical worsening overtime was more pronounced (4 vs 1 comorbidities at the last visit). Conclusions: In patients presenting high IGF-1 but GHn < 0.4 µg/L, a hormonal progression is improbable, likely excluding classical acromegaly in its early stage. However, despite persistently low GH nadir values, patients with acromegalic features present more acromegalic comorbidities whose rate increases over time. Close clinical surveillance of this group is advised.


Assuntos
Acromegalia/diagnóstico , Glucose/administração & dosagem , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Acromegalia/sangue , Acromegalia/metabolismo , Administração Oral , Adulto , Idoso , Estudos de Coortes , Técnicas de Diagnóstico Endócrino , Regulação para Baixo/efeitos dos fármacos , Feminino , Seguimentos , Glucose/efeitos adversos , Teste de Tolerância a Glucose , Hormônios/sangue , Hormônios/metabolismo , Hormônio do Crescimento Humano/efeitos dos fármacos , Humanos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Eur J Endocrinol ; 185(2): 251-263, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061771

RESUMO

Objective: To date, no systematic reviews and meta-analysis on the global epidemiology of acromegaly are available in the literature. The aims of this study are to provide a systematic review and a meta-analysis of the global epidemiology of acromegaly and to evaluate the quality of study reporting for the identified studies. Methods: MEDLINE, EMBASE and The Cochrane Library databases were searched for studies assessing the epidemiology of acromegaly from inception until 31 January 2020. We included original observational studies written in English, reporting acromegaly prevalence and/or incidence for a well-defined geographic area. Two reviewers independently extracted data and performed quality assessments. Prevalence and incidence pooled estimates were derived by performing a random-effects meta-analysis. Results: A total of 32 studies were included in the systematic review, and 22 of them were included in the meta-analysis. The pooled prevalence of acromegaly was 5.9 (95% CI: 4.4-7.9) per 100 000 persons, while the incidence rate (IR) was 0.38 (95% CI: 0.32-0.44) cases per 100 000 person-years. For both prevalence and IR, considerable between-study heterogeneity was found (I2 = 99.3 and 86.0%, respectively). The quality of study reporting was rated as the medium for 20 studies and low for 12 studies. Conclusions: Although the largest amount of heterogeneity was due to the high precision of the studies' estimates, data source and geographic area could represent relevant study-level factors which could explain about 50% of the total between-study variability. Large-scale high-quality studies on the epidemiology of acromegaly are warranted to help the public health system in making decisions.


Assuntos
Acromegalia/epidemiologia , Saúde Global/estatística & dados numéricos , Confiabilidade dos Dados , Projetos de Pesquisa Epidemiológica , Geografia , Humanos , Estudos Observacionais como Assunto/normas , Estudos Observacionais como Assunto/estatística & dados numéricos
16.
Eur J Endocrinol ; 185(2): 313-321, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34085950

RESUMO

Objectives: We aimed to investigate the clinical, biochemical, histological and radiological characteristics as well as the response to somatostatin analogs (SSA) in a large cohort of acromegaly patients with a paradoxical GH response (PR) to oral glucose tolerance test (OGTT). Design: Retrospective study. Methods: Of 110 patients with acromegaly included in our study, 30 (PR+; 27%) had a paradoxical GH increase of more than 25% relative to basal GH levels during OGTT. Results: At diagnosis, PR+ patients were older than PR- patients (52 ± 16 years vs 44 ± 14 years, P < 0.05) and had smaller pituitary tumors (40% microadenomas vs 19%, P < 0.05), which were less often invasive (17% vs 35%, P < 0.05), overall more secreting (insulin-like growth factor-1 (IGF-1)/tumoral surface: 2.35 ULN/cm2 (0.28-9.06) vs 1.08 (0.17-7.87), P = 0.011), and more often hypointense on T2-weighted MRI (92% vs 48%, P = 0.001). While the rate of remission after surgery was similar in the two groups (69%), a better response to SSA treatment was observed in PR+ patients, either before (IGF-1 reduction of > 50% after 3-6 months in 77% vs 49%, P = 0.023) or after surgery (normalization of IGF-1 in 100% vs 44%, P = 0.011). Conclusions: Our study demonstrates that in acromegaly, a paradoxical GH increase during OGTT is associated with particular features of somatotroph adenomas and with a better prognosis in terms of response to SSA.


Assuntos
Acromegalia/diagnóstico , Acromegalia/terapia , Glucose/administração & dosagem , Hormônio do Crescimento Humano/sangue , Acromegalia/sangue , Administração Oral , Adulto , Idoso , Feminino , Seguimentos , Glucose/efeitos adversos , Teste de Tolerância a Glucose , Hormônio do Crescimento Humano/efeitos dos fármacos , Humanos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Regulação para Cima/efeitos dos fármacos
18.
Endocr Pract ; 27(10): 1034-1039, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33940182

RESUMO

OBJECTIVE: Acromegaly is associated with increased morbidity and mortality. Limited data are available on these patients' utilization and costs of health care. This study assessed the impact of acromegaly on employees' health benefit (direct and indirect) costs and absenteeism. METHODS: A retrospective analysis was conducted of drug and medical claims and employer data (from January 2010 to April 2019) of patients with an acromegaly diagnosis and matched controls from a U.S. employee database. Patient claims were tracked for 12 months postdiagnosis (or matched) date. Outcomes were analyzed using separate 2-part regression models, controlling for clinical, demographic, and job-related variables. RESULTS: Forty-seven patients with acromegaly and 940 controls were identified. Cohorts were similar in most demographic and job-related variables. Patients with acromegaly had a significantly higher Charlson comorbidity index score and higher incidence of claims for several comorbidities. Acromegaly drugs represented 16.3% of the acromegaly cohort's total costs. Total health benefit costs were $54 821 higher (P < .05) for patients compared with controls, with direct costs representing 79.8% of the difference. Total indirect costs were higher for patients with acromegaly, with short-term and long-term disability comprising most of the difference between the acromegaly and control groups. Patients with acromegaly had significantly more short-term disability days than controls, but total sick days were similar for the 2 groups. CONCLUSION: The presence of acromegaly was associated with increased direct and indirect employee health benefit costs and increased work absenteeism.


Assuntos
Absenteísmo , Acromegalia , Acromegalia/epidemiologia , Acromegalia/terapia , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Humanos , Estudos Retrospectivos , Licença Médica , Estados Unidos
19.
Endocrine ; 73(3): 667-673, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34019235

RESUMO

OBJECTIVE: An increased prevalence of vertebral fractures (VFs) has been reported in previous studies. The aim of this study was to evaluate the association between bone mineral density (BMD), bone turnover markers, serum sclerostin levels, and vertebral fractures (VFs) in acromegaly patients. We also evaluated the effects of gonadal status, disease activity, treatment modality, age, sex, and body mass index (BMI) on skeletal endpoints. DESIGN: Case-control study. PATIENTS AND MEASUREMENTS: Seventy acromegaly patients (M/F:36/34, mean age 45.5 ± 11.9 years) and 70 controls (M/F:31/39; mean age 45.66 ± 11.9 years) were included. VFs, BMD, calcium metabolism, markers of bone turnover, and sclerostin levels were evaluated. BMD was measured by dual-energy X-ray absorptiometry (Hologic QDR 4500). Conventional lateral radiography of the spine was performed and the Genant method was used for the assessment of fractures of T4-L5 vertebrae. RESULTS: The prevalence of vertebral fractures was higher in acromegalic patients as compared with the control group (72.9 vs. 20%; p < 0.001). Serum phosphate (P) levels (3.46 ± 0.59 mg/dl vs. 3.11 ± 0.44 mg/dl; p < 0.001) and b-cross laps (CTx) levels (0.47 µg/l, range 0.04-2.38 vs. 0.28 µg/l, range 0.11-0.80; p < 0.001) were significantly higher in acromegaly patients than control subjects. Serum sclerostin levels were similar between either acromegaly patients and control subjects or acromegaly patients with VF and without VF. In the means of treatment modality, VFs were more frequent in patients treated with adjuvant gamma knife radiosurgery (GKS) (p = 0.07). In the binary logistic regression analysis, the age of the acromegaly patients, the presence of hypogonadism, and GKS treatment were the factors significantly correlated with the occurrence of spinal fractures. CONCLUSIONS: The prevalence of VFs in patients with acromegaly is higher than in control subjects. Since advanced age, the presence of hypogonadism and GKS treatment were the factors predicting VFs in acromegaly; radiological evaluations should be considered as an emerging tool especially in those patients. Although markers of bone turnover elevated in acromegaly, they were not useful for the prediction of fractures. Serum sclerostin levels showed no discrepancy between the two groups and further studies are required for assessment of sclerostin role in this form of secondary osteoporosis.


Assuntos
Acromegalia , Fraturas da Coluna Vertebral , Absorciometria de Fóton , Acromegalia/complicações , Acromegalia/epidemiologia , Adulto , Densidade Óssea , Estudos de Casos e Controles , Humanos , Vértebras Lombares , Pessoa de Meia-Idade , Prevalência , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia
20.
Anticancer Res ; 41(5): 2669-2680, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952498

RESUMO

BACKGROUND/AIM: The histopathological variability of each type of pituitary adenoma (PA) that causes growth hormone (GH) excess influences the phenotype, radiological characteristics and therapy response of acromegaly patients. We correlated the immunohistochemical (IHC) features of GH-secreting PAs with their clinical, laboratory and imaging data. PATIENTS AND METHODS: We included 32 patients with documented acromegaly; tumour specimens were histologically and IHC examined: anterior pituitary hormones, pituitary-specific transcription factor-1 (PIT-1), Ki-67 labelling index were evaluated. RESULTS: Macroadenomas represented 93.75%. Post-surgery disease control negatively correlated with the maximum initial tumour diameter (p=0.04). Ki-67 did not predict remission. No correlation was found between GH serum levels and IHC expression (p=0.45). PIT-1 was positive in all specimens, two had a weak expression. Four were considered PIT-1 positive plurihormonal adenomas and several had unusual IHC combinations. CONCLUSION: PIT-1 accurately classifies GH-secreting PAs. The IHC classification as well as radiological dimensions and extent influence disease control, probably being the best prognosis factors.


Assuntos
Acromegalia/sangue , Hormônio do Crescimento/sangue , Neoplasias Hormônio-Dependentes/sangue , Neoplasias Hipofisárias/sangue , Acromegalia/complicações , Acromegalia/genética , Acromegalia/patologia , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Antígeno Ki-67/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/patologia , Hormônios Adeno-Hipofisários/sangue , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Período Pré-Operatório , Fator de Transcrição Pit-1/sangue
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