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1.
Ann Endocrinol (Paris) ; 81(5): 482-486, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32822652

RESUMO

BACKGROUND: In acromegaly, chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) exacerbate comorbidities in multiple organs. Differentiated thyroid carcinoma (DTC) has been reported as being a comorbid condition in acromegaly. Acromegaly is usuallysporadic, but 5% of cases may be genetic. The most frequent inheritable form of acromegaly is related to germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Epidemiological data on the relationship between active acromegaly, its familial forms and DTC are sparse. We present the investigation of a FIPA family (familial isolated pituitary adenoma) with homogeneous acromegaly and 6 sporadic acromegaly patients with DTC. PATIENTS AND METHODS: A study of 59 acromegaly patients assessed thyroid nodules on ultrasound and fine-needle aspiration biopsy following the ATA 2015 criteria. We diagnosed 7 differentiated thyroid carcinomas. Resected thyroid carcinoma tissues were stained using an anti-AIP antibody. Analysis of germline and tumor-derived DNA for variants in the AIP and MEN1 genes were performed in the FIPA kindred. RESULTS: We describe one FIPA patient and 6 sporadic acromegaly cases with DTC. The FIPA family (AIP mutation negative) consisted of two sisters, one of whom had a DTC with intermediate risk and incomplete structural response to therapy. In our study, DTC in sporadic acromegaly had a low recurrence rate (6/6), and excellent response to therapy (6/6). Immunohistochemistry for AIP showed similar or increased staining intensity in DTC versus normal thyroid tissue. CONCLUSION: In our cohort of sporadic and familial forms of acromegaly with DTC, AIP did not appear to influence thyroid cancer progression.


Assuntos
Acromegalia/epidemiologia , Adenocarcinoma/epidemiologia , Adenoma/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Acromegalia/diagnóstico por imagem , Acromegalia/etiologia , Acromegalia/patologia , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenoma/complicações , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adulto , Idoso , Argentina/epidemiologia , Biópsia por Agulha Fina , Estudos de Coortes , Comorbidade , Progressão da Doença , Feminino , Mutação em Linhagem Germinativa , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Ultrassonografia
2.
Eur J Endocrinol ; 183(4): 427-437, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32688336

RESUMO

Objective: Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) excess results in both reversible and irreversible musculoskeletal damage, including increased vertebral fracture (VF) risk. The prevalence of VFs is approximately 60% in controlled acromegaly patients, and these VFs can progress in time. We aimed to identify the course of VFs in a cohort of acromegaly patients in long-term remission and their associated risk factors during prolonged follow-up. Methods: Thirty-one patients with acromegaly (49% female, median age 60 years (IQR 53-66)), who were in remission for ≥2 years, were included in this longitudinal, prospective, follow-up study. Spine radiographs of vertebrae Th4 to L4 were assessed for VFs using the Genant score, at baseline, after 2.6 years and 9.1 years. Progression was defined as either a new fracture or a ≥1-point increase in Genant score. Results: The prevalence of VF at baseline was 87% (27/31 patients). Progression of VFs was observed in eleven patients (35.5%) during the 9.1-year follow-up period, with a total incidence rate of 65.5 per 1000 person years (males 59.8 per 1000 person years vs females 71.6 per 1000 person years). Patients treated with surgery or radiotherapy had a higher risk of VF progression in this cohort (P = 0.030). Conclusions: In this cohort of long-term, well-controlled acromegalic patients, the prevalence and progression of VFs was high, showing that the deleterious effects of GH and IGF-1 excess on bone persist despite achievement of longstanding remission.


Assuntos
Acromegalia/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/patologia , Acromegalia/etiologia , Acromegalia/terapia , Adenoma/complicações , Adenoma/epidemiologia , Adenoma/terapia , Adulto , Idoso , Densidade Óssea , Sobreviventes de Câncer/estatística & dados numéricos , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Feminino , Seguimentos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fraturas da Coluna Vertebral/etiologia
3.
Eur J Endocrinol ; 183(1): C1-C4, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32487776

RESUMO

Acromegaly is a debilitating and disfiguring chronic disease, which occurs in both sexes at any age, associated with multiple comorbidities and increased mortality. It is typically caused by a GH-secreting pituitary adenoma that promotes exposure of body tissues to increased concentrations of GH and IGF-I. The diagnosis of acromegaly is still made very late in a substantial number of patients when the disease is already in advanced stages. An epidemiological study from Sweden has elegantly demonstrated that the longer the diagnostic delay in acromegaly, the higher the number of comorbidities. Moreover, about 25% of the Swedish patients had 10 years or more of diagnostic delay and in this group mortality rate was significantly increased. These results reinforce the importance of shortening the latency period between disease onset, diagnosis and treatment to improve patient outcomes. This commentary article discusses strategies to be embraced by the endocrine community to allow early identification of acromegaly among public and health professionals, as internists, primary care clinicians, different specialists and dentists are the first point of contact for most of the patients. We emphasize that acromegaly should be presented as a sporadic, rather than rare, insidious disease, meaning that there is a considerable chance for health professionals to see a patient with acromegaly throughout their careers. The motto 'you must know it to think of it' is advocated in awareness efforts to reduce time to diagnosis, which results in lower rates of morbidity and mortality and might positively impact healthcare costs.


Assuntos
Acromegalia/diagnóstico , Acromegalia/epidemiologia , Neoplasias Hipofisárias/complicações , Acromegalia/etiologia , Diagnóstico Tardio , Feminino , Humanos , Masculino , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia
4.
Eur J Endocrinol ; 182(6): 595-605, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32375119

RESUMO

Objective: T2-signal intensity and somatostatin (SST) receptor expression are recognized predictors of therapy response in acromegaly. We investigated the relationship between these predictors and the hormonal and tumoral responses to long-acting pasireotide (PAS-LAR) therapy, which were also compared with responsiveness to first-generation somatostatin receptor ligands (SRLs). Design: The PAPE study is a cohort study. Methods: We included 45 acromegaly patients initially receiving SRLs, followed by combination therapy with pegvisomant, and finally PAS-LAR. We assessed tumor volume reduction (≥25% from baseline), IGF-1 levels (expressed as the upper limit of normal), and T2-weighted MRI signal and SST receptor expression of the adenoma. Results: Patients with significant tumor shrinkage during PAS-LAR showed higher IGF-1 levels during PAS-LAR (mean (S.D.): 1.36 (0.53) vs 0.93 (0.43), P = 0.020), less IGF-1 reduction after first-generation SRLs (mean (S.D.): 0.55 (0.71) vs 1.25 (1.07), P = 0.028), and lower SST2 receptor expression (median (IQR): 2.0 (1.0-6.0) vs 12.0 (7.5-12.0), P = 0.040). Overall, T2-signal intensity ratio was increased compared with baseline (mean (S.D.): 1.39 (0.56) vs 1.25 (0.52), P = 0.017) and a higher T2-signal was associated with lower IGF-1 levels during PAS-LAR (ß: -0.29, 95% CI: -0.56 to -0.01, P = 0.045). A subset of PAS-LAR treated patients with increased T2-signal intensity achieved greater reduction of IGF-1 (mean (S.D.): 0.80 (0.60) vs 0.45 (0.39), P = 0.016). Conclusions: Patients unresponsive to SRLs with a lower SST2 receptor expression are more prone to achieve tumor shrinkage during PAS-LAR. Surprisingly, tumor shrinkage is not accompanied by a biochemical response, which is accompanied with a higher T2-signal intensity.


Assuntos
Acromegalia/tratamento farmacológico , Adenoma/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Hormônios/uso terapêutico , Somatostatina/análogos & derivados , Acromegalia/sangue , Acromegalia/etiologia , Adenoma/sangue , Adenoma/complicações , Adulto , Estudos de Coortes , Preparações de Ação Retardada , Quimioterapia Combinada , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Ligantes , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Receptores de Somatostatina/sangue , Somatostatina/uso terapêutico , Resultado do Tratamento , Carga Tumoral
5.
J Clin Neurosci ; 71: 26-31, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31859176

RESUMO

An increased serum phosphate (P) level is common in acromegaly patients, however, the relationships among P, growth hormone (GH), insulin-like growth factor 1 (IGF-1) and disease status remain unknown. To reveal these relationships, we examined the association of P with comprehensive clinical data. We measured the serum P, calcium, GH, oral glucose tolerance test-GH (OGTT-GH), IGF-1, and insulin-like growth factor binding protein-3 (IGBP-3) levels in 103 acromegaly patients. SAGIT® was used to assess the disease status comprehensively. Spearman's rank correlation coefficient was obtained to evaluate the associations among the above parameters. Stepwise multiple linear regression analysis was performed to investigate factors independently associated factors with the SAGIT scores. The area under the receiver operating characteristic curve (AUCROC) was used to evaluate the efficacy of the percentage change in the serum phosphate level in predicting remission in patients with postoperatively discordant GH and IGF-1 levels. Hyperphosphatemia was found in 68.9% of patients at baseline. The serum P level was higher in the non-remission group, but no correlation was found between hyperphosphatemia and remission. We revealed a significant correlation between the P level and SAGIT® score in patients both preoperatively (r = 0.659, p = 0.000) and 1-year postoperatively without remission patients (r = 0.534, p = 0.027). All biochemical levels decreased significantly postoperatively, and the GH and OGTT-GH levels achieved early stability (1 month); however, the P, IGF-1 and IGBP-3 levels showed a gradual decline. A percentage change in P of -8.12% is recommended as a cut-off value for predicting remission in patients with postoperatively discordant GH and IGF-1 levels. As a metabolic product which affected by the GH/IGF-1 axis, serum P appears to more closely reflect the comprehensive disease status in acromegaly. When the GH and IGF-1 levels are discordant during follow-up, perioperative change in the P level may be a potential predictor of remission.


Assuntos
Acromegalia/sangue , Fosfatos/sangue , Acromegalia/etiologia , Adenoma/sangue , Adenoma/complicações , Adulto , Feminino , Teste de Tolerância a Glucose , Adenoma Hipofisário Secretor de Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade
6.
Neurosurgery ; 86(5): 656-664, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31384920

RESUMO

BACKGROUND: Targeted stereotactic radiosurgery (SRS) with sparing of the residual pituitary is the traditional radiosurgical method for pituitary adenomas. Whole-sella SRS is an alternative choice for radiologically indeterminate or large adenomas, the safety and efficacy of which has yet to be determined. OBJECTIVE: To determine if whole-sella SRS in acromegaly would have comparable radiographic and biochemical control to targeted SRS. We performed a multicenter, retrospective matched cohort study to compare outcomes between groups. METHODS: We conducted a retrospective review of acromegalic patients who underwent SRS from 1990 to 2016 at 10 centers participating in the International Radiosurgery Research Foundation. Whole-sella and targeted SRS patients were then matched in a 1:1 ratio. RESULTS: A total of 128 patients were eligible for inclusion. Whole-sella patients had a higher pre-SRS random serum growth hormone, larger treatment volume, and higher maximum point dose to the optic apparatus. The rates of initial/durable endocrine remission, new loss of pituitary function, and new cranial neuropathy were similar between groups. Mortality and new visual deficit were higher in the whole-sella cohort, though not statistically significant. CONCLUSION: There was no difference in biochemical remission or recurrence between treatment groups. Although not statistically significant, the higher rates of tumor regression and lower rates of mortality and new visual deficit may suggest consideration of targeted SRS over whole-sella SRS in acromegaly treatment. Further research is needed to determine the association between visual deficits and mortality with whole-sella SRS.


Assuntos
Adenoma/cirurgia , Neoplasias Hipofisárias/cirurgia , Radiocirurgia/métodos , Acromegalia/etiologia , Acromegalia/cirurgia , Adenoma/complicações , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasias Hipofisárias/complicações , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Adulto Jovem
7.
BMC Nephrol ; 20(1): 435, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31771524

RESUMO

BACKGROUND: Experimental studies have demonstrated that hypersecretion of growth hormone (GH) is associated with development of glomerular sclerosis. However, clinical case of such condition is very rare. Here we presented a case of focal segmental glomerulosclerosis (FSGS) associated with acromegaly. CASE PRESENTATION: A 63-year-old man was diagnosed as nephrotic syndrome with minimal change disease for 2 years. Prednisone 1 mg/kg/day for 9 months led to no response. After admission, the second kidney biopsy indicated FSGS (NOS variant). On admission, his acromegalic features were noticed and he complained with a 20-year history of soft tissue swelling of hands and feet. Serum GH and insulin-like growth factor 1 (IGF-1) concentrations were both elevated significantly. An oral glucose tolerance test showed inadequate suppression of serum GH. The presence of a pituitary macroadenoma with a diameter of 1.4 cm by MRI confirmed the diagnosis of acromegaly. Then, the tumor was subtotally removed by trans-sphenoidal surgery. Partial remission of proteinuria was achieved 3 months after surgery and maintained during follow-up, with gradual reduce of corticosteroid. CONCLUSIONS: This rare case suggested that the hypersecretion of GH may participate, at least in part, in FSGS development and progression. Early diagnosis and treatment of acromegaly is beneficial.


Assuntos
Acromegalia , Adenoma , Glomerulosclerose Segmentar e Focal , Hormônio do Crescimento Humano/análise , Fator de Crescimento Insulin-Like I/análise , Rim/patologia , Neoplasias Hipofisárias , Acromegalia/sangue , Acromegalia/diagnóstico , Acromegalia/etiologia , Adenoma/sangue , Adenoma/patologia , Adenoma/cirurgia , Diagnóstico Diferencial , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/terapia , Teste de Tolerância a Glucose , Humanos , Hipofisectomia/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Hipófise/diagnóstico por imagem , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Resultado do Tratamento
8.
Ann Endocrinol (Paris) ; 80 Suppl 1: S10-S18, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31606057

RESUMO

Acromegaly is characterized by increased release of growth hormone (GH) and, consequently, Insulin-Like Growth Factor I (IGF-I), most often by a pituitary adenoma. Prolonged exposure to excess hormone leads to progressive somatic disfigurement and a wide range of systemic manifestations that are associated with increased mortality. Transsphenoidal adenomectomy is the treatment of choice of GH-secreting pituitary tumors but surgical cure is not achieved in around 50% of patients, then adjuvant treatment is necessary. Mortality in acromegaly is normalized with biochemical control and has decreased in the last decade with the increased use of adjuvant therapy. Both GH and IGF-I are currently biomarkers for assessing disease activity in patients with acromegaly. However, discordance between GH and IGF-I results is encountered in a quarter of treated patients. The impacts of such a discrepancy over mortality and morbidity and the risk of biochemical and/or clinical recurrence are unclear. Moreover, despite a good biochemical control, some symptoms persist, leading to a decreased quality of life. Back pain due to vertebral fractures seem to be frequent in these patients and underdiagnosed. In patients with acromegaly, bone mineral density is not a reliable predictor of fracture risk. A more accurate evaluation of bone microstructural alterations associated with GH hypersecretion and vertebral fractures may be provided by new radiological devices analyzing alteration of trabecular microarchitecture, leading to a better prevention. © 2019 Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Les Must de l'Endocrinologie 2019 réalisé avec le soutien institutionnel de Ipsen-Pharma.


Assuntos
Acromegalia/terapia , Garantia da Qualidade dos Cuidados de Saúde , Melhoria de Qualidade , Acromegalia/diagnóstico , Acromegalia/epidemiologia , Acromegalia/etiologia , Adenoma/complicações , Adenoma/epidemiologia , Adenoma/metabolismo , Adenoma/terapia , Técnicas de Diagnóstico Endócrino/tendências , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Hormônio do Crescimento Humano/metabolismo , Humanos , Garantia da Qualidade dos Cuidados de Saúde/métodos , Garantia da Qualidade dos Cuidados de Saúde/tendências
9.
J Med Case Rep ; 13(1): 298, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31540583

RESUMO

BACKGROUND: Focal segmental glomerulosclerosis is characterized by partial (segmental) sclerotic lesions in some glomeruli (focal). Primary focal segmental glomerulosclerosis is generally considered resistant to steroid therapy. However, acromegaly is a disease that causes peculiar facial features, body types, and metabolic abnormalities due to the excessive secretion of growth hormone by a pituitary adenoma. Growth hormone has been reported to be involved in glomerular cell growth, mesangial proliferation, and glomerulosclerosis in the kidney. CASE PRESENTATION: We report a case of a Japanese patient with focal segmental glomerulosclerosis in whom decreased urinary protein was observed after surgical treatment for acromegaly. CONCLUSION: The patient's urinary protein improved as the concentration of growth hormone/insulin-like growth factor 1 decreased.


Assuntos
Acromegalia/cirurgia , Glomerulosclerose Segmentar e Focal/terapia , Proteinúria/terapia , Acromegalia/etiologia , Adenoma/complicações , Adenoma/cirurgia , Hormônio do Crescimento/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia
10.
World Neurosurg ; 132: 161-164, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31505284

RESUMO

BACKGROUND: Double pituitary adenomas are a rare occurrence. Synchronous clinical manifestation is extremely rare. CASE DESCRIPTION: We report a case of a 51-year-old female with symptoms of both hypercortisolism and acromegaly during the past 2 years. Endocrine evaluation confirmed active acromegaly and revealed adrenocorticotropin hormone-dependent hypercortisolemia. Preoperative magnetic resonance imaging of the pituitary demonstrated separated double microadenomas with different intensity. Immunohistochemical analysis of each separate adenoma confirmed an exact diagnosis. The diagnosis of acromegaly and adrenocorticotropin hormone-dependent Cushing's disease was confirmed. CONCLUSIONS: This is the third reported case in the literature of synchronous clinical manifestation of acromegaly and Cushing's disease. Extensive surgical exploration of the sella must be performed to avoid surgical failures from residual tumor. Immunohistochemical analysis is required to confirm an exact diagnosis for each of the double pituitary adenomas.


Assuntos
Adenoma Hipofisário Secretor de ACT/diagnóstico por imagem , Adenoma Hipofisário Secretor de ACT/cirurgia , Acromegalia/diagnóstico por imagem , Acromegalia/etiologia , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipersecreção Hipofisária de ACTH/etiologia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Corticotrofos/metabolismo , Feminino , Humanos , Hidrocortisona/metabolismo , Imuno-Histoquímica , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Somatotrofos/metabolismo , Resultado do Tratamento
11.
Best Pract Res Clin Endocrinol Metab ; 33(2): 101309, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31405752

RESUMO

Pituitary diseases are rare conditions with severe chronic multiorgan and multisystemic morbidity requiring complex multidisciplinary treatment and usually life-long drug treatment. Most cases are caused by functioning or non-functioning pituitary adenoma. From the patient's perspective, the burden of disease is caused by the tumour itself and associated compression symptoms, interventions, hormone excess and deficiencies, systemic manifestations of these endocrine abnormalities and general psychosocial issues that can manifest in patients with a chronic condition. In this review, patient burden is classified according to classic endocrine syndromes, with burden at diagnosis and after long-term remission, and also within the framework of value-based health care and the conceptual model of wellbeing. The recently developed patient-reported outcome measurement tool that helps to evaluate burden of patients is also discussed.


Assuntos
Adenoma , Efeitos Psicossociais da Doença , Neoplasias Hipofisárias , Acromegalia/epidemiologia , Acromegalia/etiologia , Acromegalia/psicologia , Acromegalia/terapia , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/psicologia , Adenoma/terapia , Humanos , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/psicologia , Neoplasias Hipofisárias/terapia , Qualidade de Vida
12.
Endocrine ; 66(2): 310-318, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31368083

RESUMO

PURPOSE: Although well-documented from pathological aspect, the clinical features and outcomes of acromegaly with mammosomatotroph (MSA) and mixed somatotroph-lactotroph adenoma (MSLA) are seldom reported. Thus, in this study, we analyzed and reported the clinical data about MSAs and MSLAs. METHODS: We retrospectively reviewed medical records of patients with acromegaly in our institution during 2008-2017. Growth hormone (GH)-secreting adenomas were categorized into pure somatotroph adenoma (PSA), MSA and MSLA based on inclusion and exclusion criteria. Clinical information and treatment outcomes during follow-up were analyzed by univariate and multivariate methods. RESULTS: Among 94 patients within this cohort, PSAs, MSAs, and MSLAs accounted for 53, 28 and 13 cases, respectively. MSAs often had smaller size, lower frequency of cavernous sinus invasion and higher gross total resection (GTR) rate. MSLAs were characterized by bigger tumor size, higher frequency of preoperative hyperprolactinemia, and lower GTR rate. Thus, MSLAs had worse long-term biological remission rate than MSAs and PSAs (15.4% vs. 50.0% and 26.4%, p = 0.0371). Gender (male, OR = 0.784, p = 0.011) and tumor volume (OR = 0.784, p = 0.020) were independent predictors for long-term biological remission in binary logistic regression. Subgroup analyses indicated that postoperative nadir GH level (GH-7, HR = 1.242, p = 0.001) was the only risk factor for tumor recurrence for patients with GTR. CONCLUSIONS: Our results provide valuable insights into clinicopathological features of acromegaly. MSAs were relatively smaller lesions with better prognosis. MSLAs were more aggressive with massive size, invasiveness and preoperative hyperprolactinemia. Tumor size and GH-7 were significantly associated with biological remission and tumor relapse after GTR, respectively.


Assuntos
Acromegalia/diagnóstico por imagem , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Neoplasias Hipofisárias/diagnóstico por imagem , Prolactinoma/diagnóstico por imagem , Acromegalia/etiologia , Adolescente , Adulto , Idoso , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Prolactinoma/complicações , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
13.
Endocrinol Metab Clin North Am ; 48(3): 569-581, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31345524

RESUMO

Pituitary adenomas are common. The impact of pituitary tumors on fertility are mainly caused by oversecretion and/or undersecretion of pituitary hormones or compression of pituitary stalk and normal pituitary tissue by the tumor. Diagnosing and managing pituitary tumors during pregnancy involve many challenges, including the effect of hormone excess or deficiency on pregnancy outcome, changes in the pituitary or pituitary-related hormones, changes in tumor size, and the impact of various treatments of pituitary tumors on maternal and fetal outcomes. This article discusses the diagnosis and treatment of patients with prolactinomas, acromegaly, Cushing disease, and other pituitary tumors during pregnancy.


Assuntos
Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/terapia , Prolactinoma/diagnóstico , Prolactinoma/terapia , Acromegalia/diagnóstico , Acromegalia/epidemiologia , Acromegalia/etiologia , Acromegalia/terapia , Feminino , Humanos , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/epidemiologia , Gravidez , Prolactinoma/complicações , Prolactinoma/epidemiologia
14.
Horm Res Paediatr ; 91(5): 293-310, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31302655

RESUMO

Tall stature and/or accelerated growth (TS/AG) in a child can be the result of a primary or secondary growth disorder, but more frequently no cause can be found (idiopathic TS). The conditions with the most important therapeutic implications are Klinefelter syndrome, Marfan syndrome and secondary growth disorders such as precocious puberty, hyperthyroidism and growth hormone excess. We propose a diagnostic flow chart offering a systematic approach to evaluate children referred for TS/AG to the general paediatrician. Based on the incidence, prevalence and clinical features of medical conditions associated with TS/AG, we identified relevant clues for primary and secondary growth disorders that may be obtained from the medical history, physical evaluation, growth analysis and additional laboratory and genetic testing. In addition to obtaining a diagnosis, a further goal is to predict adult height based on growth pattern, pubertal development and skeletal maturation. We speculate that an improved diagnostic approach in addition to expanding use of genetic testing may increase the diagnostic yield and lower the age at diagnosis of children with a pathologic cause of TS/AG.


Assuntos
Acromegalia/diagnóstico , Transtornos do Crescimento/diagnóstico , Puberdade Precoce/diagnóstico , Acromegalia/etiologia , Criança , Pré-Escolar , Feminino , Transtornos do Crescimento/etiologia , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/diagnóstico , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/diagnóstico , Masculino , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Puberdade Precoce/etiologia
16.
Endocr J ; 66(10): 853-857, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31189769

RESUMO

Although acromegaly has been reported in patients with Neurofibromatosis type 1 (NF1), these cases have not been associated with growth hormone (GH)-producing somatotroph adenoma, but with optic pathway glioma. A 68 year-old Japanese woman, who had been clinically diagnosed with NF1, was referred to our hospital due to a thyroid tumor and hypercalcemia. Acromegaly was suspected due to her facial features, and subsequent examinations revealed the presence of GH excess with a pituitary tumor, leading to the diagnosis of acromegaly. Histological and immunohistochemical analysis demonstrated an eosinophilic pituitary adenoma with diffuse positivity for GH, indicating typical somatotroph adenoma. In addition, her thyroid tumor was diagnosed histologically as follicular thyroid carcinoma (FTC) with primary hyperparathyroidism (PHPT). To investigate the pathogenesis of this untypical multiple endocrine tumor case of NF1, genetic analysis was performed using peripheral leukocytes and tissue of resected tumors. A heterozygous novel germline nonsense mutation (p.Arg1534*) in exon 35 of the NF1 gene was detected from peripheral leukocytes, which results in a truncated protein lacking the critical domain for GTPase activity, strongly suggesting its causal role in NF1. The loss of heterozygosity (LOH) in exon 35 of the NF1 gene was not detected in the somatotroph adenoma, parathyroid adenoma, and FTC. Although any mutations of the following genes; MEN1, CDKN1B, and PAX8-PPARγ were not detected, a heterozygous GNAS R201C mutation was detected in the somatotroph adenoma. To our knowledge, this is the first rare MEN1-like case of genetically diagnosed NF1 complicated with acromegaly caused by a somatotroph adenoma.


Assuntos
Acromegalia/etiologia , Adenoma/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Neurofibromatose 1/complicações , Adenocarcinoma Folicular/complicações , Adenocarcinoma Folicular/patologia , Adenoma/patologia , Idoso , Códon sem Sentido , Proteínas de Drosophila , Feminino , Genes da Neurofibromatose 1 , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Hiperparatireoidismo/complicações , Japão , Imagem por Ressonância Magnética , Neoplasia Endócrina Múltipla Tipo 1/genética , Neurofibromatose 1/genética , Neurofibromatose 1/patologia , Neoplasias das Paratireoides/genética , Neoplasias das Paratireoides/patologia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/patologia
17.
J Clin Endocrinol Metab ; 104(10): 4879-4888, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31188431

RESUMO

CONTEXT: The most frequent cause of central hypothyroidism (CeH) is pituitary adenomas, but the mechanisms remain unclear. OBJECTIVE: We investigated serum thyroid levels and GH/IGF-1 in central hypothyroidism in untreated patients with pituitary nonfunctioning and GH-secreting adenomas. DESIGN: This was a retrospective cross-sectional study of cases collected from Gunma University and Toranomon Hospitals between 2007 and 2016. PATIENTS: One-hundred thirty-nine cases of nonfunctioning pituitary adenoma (NFPA) and 150 cases of GH-secreting pituitary adenoma (GHPA) were analyzed. MAIN OUTCOME MEASURES: The correlations between thyroid levels, several clinicopathological parameters, and GH/IGF-1 were examined. RESULTS: Twenty-four percent of NFPA patients had CeH. The severity did not correlate with tumor size, age, or sex, and all cases had normal TSH levels. In contrast, only 8.7% of GHPA patients had CeH; approximately half had normal TSH levels and approximately half had low TSH levels. Serum TSH levels in GHPA patients were significantly lower and free T4 (FT4) and free T3 levels were higher than those in patients with NFPA. Furthermore, approximately one-fourth of GHPA patients had normal FT4 and low TSH levels. In addition, serum FT4 levels and serum TSH levels were positively and negatively correlated, respectively, with serum IGF-1 levels. Furthermore, IGF-1 levels in patients with GHPA decreased with age. CONCLUSIONS: (i) NFPA patients with CeH had TSH levels within a normal range. (ii) GHPA patients had a low incidence of CeH, which may be a result of stimulated thyroid function by GH/IGF-1. (iii) We found an age-dependent decrease in serum IGF-1 levels in patients with GHPA.


Assuntos
Acromegalia/epidemiologia , Adenoma/complicações , Adenoma/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Acromegalia/etiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Testes de Função Tireóidea
18.
J Clin Endocrinol Metab ; 104(11): 5478-5482, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31219586

RESUMO

CONTEXT: The treatment of acromegaly resistant to first- and second-line therapies can be extremely challenging. DESIGN: We have described six patients who were successfully treated with a combination therapy of pasireotide and pegvisomant and compared them with a control group of patients resistant to conventional somatostatin analogs (SSAs), whose disease was controlled with other treatment, such as pasireotide (as monotherapy) or pegvisomant (as monotherapy or combined with conventional SSAs). RESULTS: In these six patients, acromegaly was controlled with combined pasireotide and pegvisomant treatment after failure of all other treatments. Compared with the 49 patients in the control group, these six patients had giant and invasive pituitary adenomas (at both the cavernous sinus and other structures). Although not statistically significant, higher growth hormone levels, more elevated Ki-67 expression, greater somatostatin receptor (SSTR) subtype 5 expression, and lower SSTR subtype 2 expression at the diagnosis of acromegaly were detected in patients receiving combination treatment with pasireotide and pegvisomant compared with the control group. CONCLUSION: Our data have reinforced the importance of personalized treatment of patients with acromegaly according to the clinical, biochemical, molecular, and morphological disease markers and suggest that combined treatment with pasireotide and pegvisomant can induce disease control in tumors with low SSTR2 expression, resistant to conventional SSAs (alone or combined with pegvisomant) and to new-generation SSAs alone (pasireotide).


Assuntos
Acromegalia/tratamento farmacológico , Adenoma/tratamento farmacológico , Hormônios/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Neoplasias Hipofisárias/tratamento farmacológico , Somatostatina/análogos & derivados , Acromegalia/etiologia , Adenoma/complicações , Adulto , Quimioterapia Combinada , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Estudos Retrospectivos , Somatostatina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
19.
J Clin Endocrinol Metab ; 104(10): 4667-4675, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31166600

RESUMO

CONTEXT: X-linked acrogigantism (X-LAG), a condition of infant-onset acrogigantism marked by elevated GH, IGF-1, and prolactin (PRL), is extremely rare. Thirty-three cases, including three kindreds, have been reported. These patients have pituitary adenomas that are thought to be mixed lactotrophs and somatotrophs. CASE DESCRIPTION: The patient's mother, diagnosed with acrogigantism at 21 months, underwent pituitary tumor excision at 24 months. For more than 30 years, stable PRL, GH, and IGF-1 concentrations and serial imaging studies indicated no tumor recurrence. During preconception planning, X-LAG was diagnosed: single-nucleotide polymorphism microarray showed chromosome Xq26.3 microduplication. After conception, single-nucleotide polymorphism microarray on a chorionic villus sample showed the same microduplication in the fetus, confirming familial X-LAG. The infant grew rapidly with rising PRL, GH, and IGF-1 concentrations and an enlarging suprasellar pituitary mass, despite treatment with bromocriptine. At 15 months, he underwent tumor resection. The pituitary adenoma resembled the mother's pituitary adenoma, with tumor cells arranged in trabeculae and glandular structures. In both cases, many tumor cells expressed PRL, GH, and pituitary-specific transcription factor-1. Furthermore, the tumor expressed other lineage-specific transcription factors, as well as SOX2 and octamer-binding transcription factor 4, demonstrating the multipotentiality of X-LAG tumors. Both showed an elevated Ki-67 proliferation index, 5.6% in the mother and 8.5% in the infant, the highest reported in X-LAG. CONCLUSIONS: This is a prenatally diagnosed case of X-LAG. Clinical follow-up and biochemical evaluation have provided insight into the natural history of this disease. Expression of stem cell markers and several cell lineage-specific transcription factors suggests that these tumors are multipotential.


Assuntos
Acromegalia/diagnóstico , Adenoma/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Gigantismo/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Diagnóstico Pré-Natal , Acromegalia/etiologia , Acromegalia/patologia , Adenoma/complicações , Adenoma/patologia , Adulto , Feminino , Gigantismo/etiologia , Gigantismo/patologia , Humanos , Lactente , Masculino , Relações Mãe-Filho , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/patologia , Gravidez , Resultado da Gravidez
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