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1.
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
2.
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
3.
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
4.
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
6.
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
7.
J Med Case Rep ; 13(1): 85, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30862315

RESUMO

INTRODUCTION: Clinically silent somatotroph adenoma is characterized by elevated serum growth hormone but without the clinical symptoms of acromegaly, and it is considered rare. The natural history is not well understood, progress to symptomatic is uncertain, and treatment strategy has not been established. CASE PRESENTATION: The first patient was a 48-year-old-Asian woman who presented with serum growth hormone 6.99 ng/ml and insulin-like growth factor 1 of 476 ng/ml, but no characteristic features of acromegaly. Five years after initial diagnosis, she presented with acromegalic facial appearance. Transsphenoidal surgery achieved gross total removal and endocrinological remission. The second patient was a 40-year-old-Asian woman who presented with serum growth hormone 31.14 ng/ml and insulin-like growth factor 1 of 709.6 ng/ml, but no characteristic features of acromegaly. Three years after initial diagnosis, she presented with acromegalic facial appearance. Transsphenoidal surgery achieved gross total removal and endocrinological remission. The third patient was a 64-year-old-Asian woman who presented with serum growth hormone 6.0 ng/ml and insulin-like growth factor 1 of 341 ng/ml, but no characteristic features of acromegaly. Eight months after initial diagnosis, hand enlargement was detected. Transsphenoidal surgery achieved gross total removal and endocrinological remission. CONCLUSION: Due to its potential for evolving to symptomatic disease, the risks of surgery and observation for patients with somatotroph adenoma should be carefully compared from the viewpoint of better health outcome.


Assuntos
Acromegalia/etiologia , Adenoma/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma/sangue , Adenoma/cirurgia , Adulto , Doenças Assintomáticas , Biomarcadores/sangue , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Pessoa de Meia-Idade
8.
World Neurosurg ; 126: 570-575, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30862574

RESUMO

BACKGROUND: Acromegaly caused by Rathke cleft cyst (RCC) mimicking a plurihormonal pituitary adenoma (PA) is rare. CASE DESCRIPTION: We report a 71-year-old woman who presented with hyperhidrosis in 2013. Magnetic resonance imaging performed in April 2018 revealed that the patient had a pituitary tumor, and she was referred to our hospital. She presented with an acromegaly-like appearance with mild hypertrophy at her limb extremities. Preoperative blood tests, magnetic resonance imaging, and an endocrine tolerance test indicated that the patient's symptoms satisfied the diagnostic criteria for acromegaly, with a suspected diagnosis of an RCC and growth hormone (GH)-producing PA. Endoscopic transsphenoidal surgery (eTSS) was performed. Permanent pathologic diagnosis showed an RCC mimicking a plurihormonal PA, which was confirmed via immunohistochemistry. Blood sampling 2 months post surgery showed reduced GH (0.41 ng/mL) and increased insulin-like growth factor-1 (IGF-1) (356 ng/mL) levels. In addition, a postoperative endocrine tolerance test revealed a parasitic reaction of GH and secondary adrenocortical hypofunction. No RCC recurrence was found, and the GH (0.32 ng/mL) and previously increased IGF-1 (169 ng/mL) levels were normalized 12 months after eTSS. CONCLUSIONS: We reported a rare case of acromegaly caused by RCC mimicking a plurihormonal PA. This case suggests that inflammation associated with RCC might be involved in the development of adenomatous cells. Postoperative clinical symptoms and elevated fibrinogen and IGF-1 levels later improved. This outcome suggested that the transient increase in IGF-1 2 months after surgery might reflect RCC-induced inflammation.


Assuntos
Acromegalia/etiologia , Cistos do Sistema Nervoso Central/complicações , Hormônios Hipofisários/sangue , Neoplasias Hipofisárias/diagnóstico , Acromegalia/sangue , Adenoma/diagnóstico , Idoso , Cistos do Sistema Nervoso Central/diagnóstico , Cistos do Sistema Nervoso Central/patologia , Cistos do Sistema Nervoso Central/cirurgia , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino , Feminino , Fibrinogênio/análise , Humanos , Hiperidrose/etiologia , Hipofisectomia/métodos , Inflamação , Imagem por Ressonância Magnética , Neuroimagem , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Tomografia Computadorizada por Raios X
9.
Growth Horm IGF Res ; 45: 1-5, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30731342

RESUMO

PURPOSE: Somatostatin analogues (SSAs) can slow down the growth of neuroendocrine tumors. However, the mechanism remains unclear. Recent studies on patients with acromegaly suggest that SSAs may induce apoptosis, increase autophagy, and decrease cell proliferation of pituitary adenoma. Ki-67-labeling index is a marker of cellular proliferation; therefore, decreased levels are associated with inhibition of proliferation. The aim of this study was to evaluate and compare the Ki-67-labeling index of GH-secreting pituitary adenoma tissues in patients who had undergone pituitary surgery twice due to residual or recurrent tumors and had received SSA treatment between the two surgeries. METHOD: Thirty acromegaly patients who met the above criteria were identified and evaluated for the demographic, clinical and radiological features retrospectively. Surgical pathology samples of each operation were stained for Ki-67 and evaluated blindly by a staff pathologist specialized in pituitary diseases. RESULTS: Among patients who received SSA treatment between the first and second operations, the Ki-67 index of the adenoma at the second operation was significantly lower than the Ki-67 index at the first operation. There were no differences in clinical and radiological prognostic markers between the groups with decreased and unchanged Ki-67 index. CONCLUSION: We concluded that SSA treatment appears to decrease Ki-67 proliferation index independent of tumor features, SSA type, dose and treatment duration. This result suggests that SSA treatment may decrease cellular proliferation, supporting the previous studies.


Assuntos
Acromegalia/metabolismo , Adenoma/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Hormônio do Crescimento Humano/metabolismo , Antígeno Ki-67/metabolismo , Procedimentos Neurocirúrgicos/efeitos adversos , Somatostatina/análogos & derivados , Acromegalia/tratamento farmacológico , Acromegalia/etiologia , Adenoma/patologia , Feminino , Seguimentos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Somatostatina/administração & dosagem
10.
World Neurosurg ; 126: e41-e47, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30716503

RESUMO

OBJECTIVE: Long-term effects of endoscopic endonasal transsphenoidal intracapsular debulking and adjuvant somatostatin analogs (SSAs) were evaluated in patients with growth hormone- (GH) secreting pituitary macroadenomas. METHODS: We retrospectively reviewed the medical records of 45 patients with acromegalic macroadenoma who underwent endonasal endoscopic transsphenoidal intracapsular debulking and received adjuvant SSAs (octreotide) between 2006 and 2015 who had >1 year of follow-up. To evaluate the predictive factors for 1 year and long-term biochemical outcomes, univariate and multivariate analyses were performed. RESULTS: Biochemical remission was achieved in 1 year in 20 of the 45 (44.4%) patients, and in 31 of the 45 patients after long-term adjuvant SSA treatment. Tumor control was achieved in 43 of the 45 (93.3%) patients. The univariate analysis showed age (≥55 years), tumor size (diameter ≤1.5 cm), premedication GH levels (≤2.8 ng/mL), premedication insulin-like growth factor 1 levels (≤2-fold of upper limit of normal range), cavernous sinus invasion (Knops grades 2, 3, and 4), and near-total tumor resection were associated with long-term outcomes. The multivariate analysis showed near-total resection was a significant predictor for long-term outcomes (P = 0.019). There were no new pituitary dysfunctions. The observed complications included one case of cerebrospinal fluid leakage and one case of epistaxis requiring intervention. CONCLUSIONS: Intracapsular debulking and adjuvant SSAs are a safe and viable treatment for patients with GH secreting pituitary macroadenoma to achieve biochemical remission and tumor control. Although adjuvant SSA treatment enhances residual tumor control, cavernous sinus invasion impedes the remission of endocrine tumors.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Antagonistas de Hormônios/uso terapêutico , Octreotida/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/cirurgia , Acromegalia/etiologia , Acromegalia/cirurgia , Adulto , Terapia Combinada , Endoscopia/métodos , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
11.
Eur Radiol ; 29(6): 2731-2739, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30506213

RESUMO

OBJECTIVE: To investigate the value of machine learning (ML)-based high-dimensional quantitative texture analysis (qTA) on T2-weighted magnetic resonance imaging (MRI) in predicting response to somatostatin analogues (SA) in acromegaly patients with growth hormone (GH)-secreting pituitary macroadenoma, and to compare the qTA with quantitative and qualitative T2-weighted relative signal intensity (rSI) and immunohistochemical evaluation. METHODS: Forty-seven patients (24 responsive; 23 resistant patients to SA) were eligible for this retrospective study. Coronal T2-weighted images were used for qTA and rSI evaluation. The immunohistochemical evaluation was based on the granulation pattern of the adenomas. Dimension reduction was carried out by reproducibility analysis and wrapper-based algorithm. ML classifiers were k-nearest neighbours (k-NN) and C4.5 algorithm. The reference standard was the biochemical response status. Predictive performance of qTA was compared with those of the quantitative and qualitative rSI and immunohistochemical evaluation. RESULTS: Five hundred thirty-five out of 828 texture features had excellent reproducibility. For the qTA, k-NN correctly classified 85.1% of the macroadenomas regarding response to SAs with an area under the receiver operating characteristic curve (AUC-ROC) of 0.847. The accuracy and AUC-ROC ranges of the other methods were 57.4-70.2% and 0.575-0.704, respectively. Differences in predictive performance between qTA-based classification and the other methods were significant (p < 0.05). CONCLUSIONS: The ML-based qTA of T2-weighted MRI is a potential non-invasive tool in predicting response to SAs in patients with acromegaly and GH-secreting pituitary macroadenoma. The method performed better than the qualitative and quantitative rSI and immunohistochemical evaluation. KEY POINTS: • Machine learning-based texture analysis of T2-weighted MRI can correctly classify response to somatostatin analogues in more than four fifths of the patients. • Machine learning-based texture analysis performs better than qualitative and quantitative evaluation of relative T2 signal intensity and immunohistochemical evaluation. • About one third of the texture features may not be excellently reproducible, indicating that a reliability analysis is necessary before model development.


Assuntos
Acromegalia/diagnóstico , Adenoma/diagnóstico , Algoritmos , Aprendizado de Máquina , Imagem por Ressonância Magnética/métodos , Neoplasias Hipofisárias/diagnóstico , Somatostatina/análogos & derivados , Acromegalia/tratamento farmacológico , Acromegalia/etiologia , Adenoma/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto Jovem
12.
Artigo em Inglês | MEDLINE | ID: mdl-30088454

RESUMO

BACKGROUND AND OBJECTIVE: Giant pituitary adenomas (GPAs) are benign tumours with a diameter ≥ 4 cm [1]. They can cause symptoms and signs due to the possible hyper-secretion of one or more pituitary hormones, and involvement of the surrounding structures whereas the compression of the pituitary itself can lead to hypopituitarism. METHODS: We report on a young woman with acromegaly due to an inoperable giant GH-secreting pituitary adenoma extending to right cavernous sinus, right orbital cavity, ethmoid, right maxillary sinus, sphenoid sinus, clivus and right temporal fossa, in which medical treatment with Octreotide- LAR was able to promptly relieve headache and bilateral hemianopsia due to optic chiasm involvement, improve acromegaly symptoms and, over the time, control tumor expansion, improving fertility and therefore allowing the patient to become pregnant. RESULTS: Octreotide-LAR therapy was withdrawn during pregnancy and the patient did not experience complications and gave birth to a healthy son. On magnetic resonance, the size of the tumor at the end of pregnancy and in the subsequent follow up was not increased. CONCLUSION: The history we report, therefore, confirms previous experiences reporting a possible favourable outcome of pregnancy in patients affected by acromegaly and adds further information about the behaviour of giant pituitary tumors in patients underwent pregnancy.


Assuntos
Adenoma/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Octreotida/uso terapêutico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Acromegalia/diagnóstico , Acromegalia/tratamento farmacológico , Acromegalia/etiologia , Acromegalia/patologia , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/patologia , Adulto , Antineoplásicos Hormonais/uso terapêutico , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Hemianopsia/diagnóstico , Hemianopsia/tratamento farmacológico , Hemianopsia/etiologia , Humanos , Recém-Nascido , Imagem por Ressonância Magnética , Síndromes de Compressão Nervosa/diagnóstico , Síndromes de Compressão Nervosa/tratamento farmacológico , Síndromes de Compressão Nervosa/etiologia , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/patologia , Resultado da Gravidez , Carga Tumoral
13.
Endocrine ; 63(1): 182-187, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30155846

RESUMO

BACKGROUND: Pituitary adenomas and paragangliomas/pheocromocytomas are rare endocrine tumours, which can be sporadic or familial. During many years their coexistence in the same individual was considered a coincidental finding. However, an association between these two entities was recently demonstrated, with the possible involvement of SDHx genes. CASE REPORT: We describe a 57-year-old female patient, who was under surveillance since 1997 for a malignant paraganglioma with vertebral bone metastasis, and harboured a germline frameshift mutation in exon 6 of SDHB gene [c.587-591DelC]. Seventeen years later, she was diagnosed with acromegaly and underwent transesphenoidal endoscopic resection of a somatotropinoma. Three months after surgery she started treatment with lanreotide for residual disease. Despite initial good response, she developed resistance to first generation of somatostatin analogues and treatment had to be switched to pegvisomant. In the immunohistochemical staining, the pituitary adenoma was positive for SDHA expression, while SDHB showed an heterogeneous staining pattern, with areas markedly positive and others with positive and negative cells. CONCLUSIONS: Our findings provide useful data for understanding the link between paragangliomas/pheocromocytomas and somatotropinomas. While we confirm the well-established link between SDHB mutations and paragangliomas/pheocromocytomas, particularly with malignant paragangliomas, the preservation-at least partially-of SDHB expression in the somatotropinoma tissue does not allow drawing definite conclusions about the involvement of the SDHB mutation in pituitary adenoma.


Assuntos
Adenoma/genética , Neoplasias das Glândulas Endócrinas/genética , Mutação da Fase de Leitura/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Paraganglioma/genética , Succinato Desidrogenase/genética , Acromegalia/etiologia , Adenoma/complicações , Adenoma/patologia , Terapia Combinada , Neoplasias das Glândulas Endócrinas/complicações , Neoplasias das Glândulas Endócrinas/patologia , Éxons/genética , Feminino , Mutação em Linhagem Germinativa , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Pessoa de Meia-Idade , Paraganglioma/complicações , Paraganglioma/patologia , Linhagem
14.
Neurosurgery ; 84(3): 717-725, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29757421

RESUMO

BACKGROUND: Stereotactic radiosurgery (SRS) is a treatment option for persistent or recurrent acromegaly secondary to a growth hormone secreting pituitary adenoma, but its efficacy is inadequately defined. OBJECTIVE: To assess, in a multicenter, retrospective cohort study, the outcomes of SRS for acromegaly and determine predictors. METHODS: We pooled and analyzed data from 10 participating institutions of the International Gamma Knife Research Foundation for patients with acromegaly who underwent SRS with endocrine follow-up of ≥6 mo. RESULTS: The study cohort comprised 371 patients with a mean endocrine follow-up of 79 mo. IGF-1 lowering medications were held in 56% of patients who were on pre-SRS medical therapy. The mean SRS treatment volume and margin dose were 3.0 cm3 and 24.2 Gy, respectively. The actuarial rates of initial and durable endocrine remission at 10 yr were 69% and 59%, respectively. The mean time to durable remission after SRS was 38 mo. Biochemical relapse after initial remission occurred in 9%, with a mean time to recurrence of 17 mo. Cessation of IGF-1 lowering medication prior to SRS was the only independent predictor of durable remission (P = .01). Adverse radiation effects included the development of ≥1 new endocrinopathy in 26% and ≥1 cranial neuropathy in 4%. CONCLUSION: SRS is a definitive treatment option for patients with persistent or recurrent acromegaly after surgical resection. There appears to be a statistical association between the cessation of IGF-1 lowering medications prior to SRS and durable remission.


Assuntos
Acromegalia/cirurgia , Adenoma/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Radiocirurgia/métodos , Acromegalia/etiologia , Adenoma/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
J Clin Endocrinol Metab ; 104(3): 856-862, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30285115

RESUMO

Context: The oral glucose tolerance test (OGTT) is considered the most useful method for diagnosing active acromegaly and for patient follow-up after neurosurgery. Despite its widespread use, only a few small studies have so far focused on patients' clinical features associated with different GH responsiveness to OGTT. Objective: We aimed to investigate the association between glucose-induced GH response and endocrine profiles, clinical manifestations, and response to therapy in a large cohort of patients with acromegaly. Patients: According to GH response to OGTT, patients were grouped as paradoxical (GH-Par) or nonparadoxical (GH-NPar), and their clinical and pathological features were compared in terms of pituitary tumor size, invasiveness, biochemical profiles, and response to therapy. Results: The study concerned 496 patients with acromegaly. At diagnosis, those with GH-Par (n = 184) were older than those with GH-NPar (n = 312) (mean ± SD, 44.1 ± 13.7 years vs 40.5 ± 12.7 years; P < 0.01) and had smaller tumors (0.82 vs 1.57 cm3; P < 0.01) that less frequently invaded the cavernous sinus (15% vs 27%; P < 0.01). The GH-Par group also had a higher basal GH per volume ratio (14.3 vs 10.5 µg/L ⋅ cm3; P < 0.05) and a lower incidence of hyperprolactinemia (17% vs 30%; P < 0.01) than the GH-NPar group. Importantly, the GH-Par group had a higher rate of remission in response to somatostatin analogues (52% vs 26%; P < 0.01) and a more marked drop in IGF-1 and GH after 6 months of therapy. Conclusions: Our data strongly suggest that serum GH responsiveness to oral glucose challenge reflects some important biological features of pituitary tumors and that the OGTT may have some prognostic value.


Assuntos
Acromegalia/terapia , Adenoma/terapia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Hormônio do Crescimento Humano/sangue , Somatostatina/administração & dosagem , Acromegalia/sangue , Acromegalia/etiologia , Adenoma/complicações , Administração Oral , Adulto , Feminino , Glucose/administração & dosagem , Teste de Tolerância a Glucose , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Hormônio do Crescimento Humano/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Hipófise/cirurgia , Prognóstico , Somatostatina/análogos & derivados , Resultado do Tratamento
16.
J Clin Endocrinol Metab ; 104(3): 915-924, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30346538

RESUMO

Background: The response to first-generation somatostatin receptor ligands (SRLs) treatment in acromegaly correlates with expression of somatostatin receptor subtype 2 (SSTR2). However, pasireotide shows the highest binding affinity for SSTR subtype 5 (SSTR5). It has been suggested that in acromegaly, SSTR5 expression is better at predicting the response to pasireotide long-acting release (PAS-LAR) treatment than SSTR2 expression. Aim: To investigate in patients with active acromegaly whether response to SRL treatment correlates to PAS-LAR treatment and to what extent SSTR2 and SSTR5 expression are correlated to the response to PAS-LAR treatment. Methods: We included 52 patients from a cohort that initially received SRL treatment, followed by SRL and pegvisomant combination treatment, and finally PAS-LAR treatment. The long-term response to PAS-LAR was evaluated using a PAS-LAR score. In 14 out of 52 patients, somatotroph adenoma tissue samples were available to evaluate SSTR2 and SSTR5 expression using a previously validated immunoreactivity score (IRS). Results: The percentage IGF-I (times the upper limit of normal) reduction, which was observed after SRL treatment, correlated with PAS-LAR response score during follow-up (r = 0.40; P = 0.003; n = 52). After exclusion of SRL-pretreated patients, SSTR2 IRS was positively correlated to PAS-LAR score (r = 0.58; P = 0.039; n = 9), whereas SSTR5 IRS showed no relation (r = 0.35; P = 0.36; n = 9). Conclusions: In a cohort of patients partially responsive to SRLs, the IGF-I-lowering effects of PAS-LAR treatment correlated with the effect of SRL treatment and seemed to be mainly driven by SSTR2 expression instead of SSTR5.


Assuntos
Acromegalia/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Antagonistas de Hormônios/farmacologia , Receptores de Somatostatina/metabolismo , Somatostatina/análogos & derivados , Acromegalia/sangue , Acromegalia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/uso terapêutico , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Antagonistas de Hormônios/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/farmacologia , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Hipófise/patologia , Somatostatina/farmacologia , Somatostatina/uso terapêutico , Resultado do Tratamento
17.
World Neurosurg ; 122: e1291-e1299, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30448582

RESUMO

OBJECTIVE: Little is known about the long-term efficacy, prognostic factors, and tolerability of gamma knife radiosurgery (GKS) for acromegaly. The aim of this study was to investigate long-term hormonal effects, prognostic factors, and tolerability of GKS in patients with growth hormone-secreting adenoma. METHODS: A retrospective multicenter study over 25 years with a median follow-up of 85.2 months was performed. A total of 138 patients from 3 tertiary referral centers in South Korea were included in this study between 1991 and 2017. Main outcome measures were endocrine remission, endocrine control under somatostatin analogues, and hypopituitarism. RESULTS: With a mean follow-up period of 85.2 months (range, 12-304 months), overall median time to the endocrine remission and control under long-acting somatostatin analogues was 138 months and 96 months, respectively. Female sex, normal age-adjusted insulin growth factor-1 (IGF-1) ≤ 2, and GKS as an adjuvant treatment were significantly favorable factors for remission (P = 0.004, P = 0.001, P = 0.010, respectively). The early response group had a significantly lower proportion of normal age-adjusted IGF-1 levels >2 than did the late response group (22.2% vs. 51.7%, P = 0.035); also, the early response group had lower radiation dose than the late response group (24.3 Gy vs. 27.0 Gy, P = 0.003). The incidence of GKS-induced hypopituitarism (1 or more) was 12 of 138 patients (8.6%) at the last follow-up. CONCLUSIONS: In acromegalic patients, women with normal age-adjusted IGF-1 ≤ 2 and GKS as an adjuvant treatment have a better response to GKS. We should take into account the variability of radiosensitivity of the tumor according to the gender and IGF-1 level.


Assuntos
Acromegalia/cirurgia , Neoplasias Hipofisárias/cirurgia , Radiocirurgia , Tempo , Acromegalia/etiologia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Hormônio do Crescimento/biossíntese , Humanos , Hipopituitarismo/etiologia , Hipopituitarismo/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
18.
Am J Case Rep ; 19: 1541-1545, 2018 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-30593586

RESUMO

BACKGROUND The clinical presentation in acromegaly is usually insidious, with headaches or visual disturbances being the most common symptoms. Previous studies have shown higher fibrinogen levels, lower protein C and S activity values, and enhanced platelet function in patients with acromegaly compared to a normal population. Nevertheless, the link between hypercoagulability and acromegaly is often overlooked and rarely reported in the literature. CASE REPORT We report a case of a young man with a massive pulmonary embolism as the initial presentation of acromegaly. Extensive workup excluded other causes of thrombophilia. Furthermore, the diagnosis of acromegaly was confirmed by the patient's clinical features as well as laboratory and radiological testing. A literature review on the link between hypercoagulability and acromegaly was performed. CONCLUSIONS This case report shed light on hypercoagulability as an under-recognized serious complication of acromegaly and paves the road for future studies on this topic.


Assuntos
Acromegalia/diagnóstico , Embolia Pulmonar/etiologia , Acromegalia/etiologia , Adenoma/diagnóstico por imagem , Humanos , Masculino , Neoplasias Hipofisárias/diagnóstico por imagem , Trombofilia/diagnóstico , Trombofilia/etiologia , Adulto Jovem
20.
Endocrinology ; 159(12): 4043-4055, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30395240

RESUMO

Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) plays a key role in GH secretion. In this review, we summarize the current state of knowledge regarding the physiology and molecular machinery of VGCCs in pituitary somatotrophs. We next discuss the possible involvement of Ca2+ channelopathies in pituitary disease and the potential use of Ca2+ channel blockers to treat pituitary disease. Various types of VGCCs exist in pituitary cells. However, because L-type Ca2+ channels (LTCCs) contribute the major component to Ca2+ influx in somatotrophs, lactotrophs, and corticotrophs, we focused on these channels. An increasing number of studies in recent years have linked genetic missense mutations in LTCCs to diseases of the human cardiovascular, nervous, and endocrine systems. These disease-associated genetic mutations occur at homologous functional positions (activation gates) in LTCCs. Thus, it is plausible that similar homologous missense mutations in pituitary LTCCs can cause abnormal hormone secretion and underlying pituitary disorders. The existence of LTCCs in pituitary cells opens questions about their sensitivity to dihydropyridines, a group of selective LTCC blockers. The dihydropyridine sensitivity of pituitary cells, as with any other excitable cell, depends primarily on two parameters: the pattern of their electrical activity and the dihydropyridine sensitivity of their LTCC isoforms. These two parameters are discussed in detail in relation to somatotrophs. These discussions are also relevant to lactotrophs and corticotrophs. High dihydropyridine sensitivity may facilitate their use as drugs to treat pituitary oversecretion disorders such as acromegaly, hyperprolactinemia, and Cushing disease.


Assuntos
Canais de Cálcio/metabolismo , Canalopatias/terapia , Terapia de Alvo Molecular , Doenças da Hipófise/terapia , Adeno-Hipófise/metabolismo , Somatotrofos/metabolismo , Acromegalia/etiologia , Acromegalia/terapia , Animais , Cálcio/fisiologia , Canalopatias/etiologia , Canalopatias/metabolismo , Humanos , Hiperprolactinemia/etiologia , Hiperprolactinemia/terapia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Hipersecreção Hipofisária de ACTH/etiologia , Hipersecreção Hipofisária de ACTH/terapia , Doenças da Hipófise/etiologia , Doenças da Hipófise/metabolismo , Adeno-Hipófise/patologia , Somatotrofos/patologia
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