RESUMO

PURPOSE: To evaluate clinical, laboratory, radiological, therapeutic, and prognostic characteristics of patients with acromegaly according to the size of the growth hormone (GH)-secreting pituitary adenoma at diagnosis. METHODS: Observational, retrospective, single-center study of patients with acromegaly followed at a tertiary center. Data were collected regarding clinical presentation, characteristics of the adenoma in the magnetic resonance imaging, GH and IGF-1 levels, and disease control after surgery or adjuvant treatment (normal IGF-1 levels). Patients were divided according to the adenoma size at diagnosis in: group I < 10 mm; II 10-19 mm; III 20-29 mm; IV 30-39 mm; and V ≥ 40 mm. Comparisons were made between the groups, and correlations of tumor size with disease parameters, ROC curves, and logistic regression analyses were performed to investigate tumor size and confounding factors that could impact the outcomes. RESULTS: 117 patients were studied [59 women, age at diagnosis 43 ± 13 years; group I = 11 patients (9%); group II 54 (46%); group III 34 (29%); group IV 10 (9%); group V 8 (7%)]. Hypopituitarism, cavernous sinus invasion, GH levels, and use of somatostatin receptor ligands had their prevalence increased according to the adenoma size. Age showed a negative correlation with tumor size. A tumor diameter around 20 mm was the best predictor for the presence of hypopituitarism, invasiveness, need of adjuvant therapies, and poorer disease control. CONCLUSION: Adenomas < 20 mm showed lower morbidity and better therapeutic response in acromegaly, while those ≥ 20 mm had similar clinical, therapeutic, and prognostic behavior.

RESUMO

INTRODUCTION: Pituitary neuroendocrine tumors (PitNETs) represent 15-18.2% of all intracranial tumors. Their clinical presentation can range from chronic headache, visual defects, hypopituitarism to hormone excess syndromes. PitNETS are commonly classified as functioning neuroendocrine tumors (F-PitNETs) and non-functioning neuroendocrine tumors (NF-PitNETs). At the moment, new classification has emerged based on cell lineages. Almost 50% of all patients with PitNETs require surgical intervention, and about 25% of these have residual and persistent disease that may require additional management. SUBJECTS AND METHODS: A retrospective cohort of medical records of patients with PitNETs, aiming to describe the incidence of recurrence of patients who received surgical treatment over a 12 month follow up period at San Jose Hospital (SJH) in Bogotá, Colombia, over an observation period of 10 years. Furthermore, clinical presentation, biochemical characteristics and immunohistochemistry, postoperative complications are detailed. RESULTS: Eight hundred and eighty-seven patients with pituitary tumors were included in the cohort; 83% (737/887) had a diagnosis of PitNET. Of these, 18.9% (140) received surgical management. The majority 58% (98/140) had nonfunctional-PitNETs (NF-PitNETs), followed by growth-hormone-secreting pituitary adenoma (22.1%; 33/140), adrenocorticotropic- hormone-secreting pituitary adenoma (9.3%; 13/140), and prolactinomas (9.3%; 13/140). A recurrence was found in 45.71% (64/140), subclassified as biochemical in 15.71% (22/140), controlled with medications in 20% (28/140), and remission occurred in 18.57% (26/140). CONCLUSION: Clinical presentation and incidence of recurrence in patients with PitNETs in a referral center in Colombia are similar to other surgical cohorts with low cure rates and high recurrence.

Assuntos

RESUMO

Introducción: El síndrome de McCune-Albright (SMA) es una enfermedad rara caracterizada por la triada: manchas cutáneas de color café con leche, displasia fibrosa poliostótica y pubertad precoz. Puede afectar a diversos ejes hormonales, entre ellos el de la hormona de crecimiento (GH), pudiendo asociarse a acromegalia. Reporte de caso: describimos el caso de una mujer de 44 años, con pubertad precoz periférica, hemorragia uterina anormal, crecimiento de manos y pies, prognatismo, prominencia frontal, manchas café con leche y tumoraciones pétreas en cara y antebrazos. Resultados: Apoyados con exámenes laboratoriales y de imágenes, se llegaron a los diagnósticos de acromegalia, hipogonadismo hipogonadotropo y síndrome de McCune-Albright. La paciente fue sometida a tratamiento quirúrgico con persistencia de enfermedad clínica y laboratorial. Conclusión: El diagnóstico y tratamiento oportunos de la acromegalia y sus complicaciones brindará un mejor pronóstico a los pacientes con SMA.

Background: McCune-Albright syndrome (MAS) is a rare disease characterized by the triad: café-au-lait skin spots, polyostotic fibrous dysplasia, and precocious puberty. It can affect various hormonal axes, including growth hormone (GH), and may be associated with acromegaly. We describe the case Case report:of a 44-year-old woman with peripheral precocious puberty, abnormal uterinebleeding, growthof thehands and feet, prognathism, frontal prominence, café-au-lait spots, and stony tumorsonthefaceandforearms.Supportedby Results:laboratory and imaging tests, the diagnoses of acromegaly, hypogonadotropic hypogonadism and McCune-Albright syndrome were reached. The patient underwent surgical treatment with persistence of clinical and laboratory disease. Conclusion: Timely diagnosis and treatment of acromegaly and its complications will provide a better prognosis for patients with MAS

RESUMO

Background: Classification of growth hormone (GH) - secreting tumors by the granular pattern might predict their clinical behavior in acromegalic patients. There are several other prognostic factors. Aim: To compare the features at presentation and cure rates of patients with GH secreting tumors according to the granular pattern, and to define independent prognostic factors for surgical treatment in these patients. Material and Methods: A retrospective, observational study of 85 active acromegalic patients surgically treated in two medical centers. Results: Seventy-four patients (87%) were classified as having densely granulated (DG) and 11 (13%) as sparsely granulated (SG) tumors. The latter were less active biochemically, had a higher rate of macroadenoma and cavernous sinus invasion and had a lower rate of biochemical cure than the DG group. Several characteristics were associated with disease persistence but only age (Odds ratio (OR) = 0.93) and cavernous sinus invasion (OR = 21.7) were independently associated in the logistic regression model. Conclusions: The sparsely granulated pattern is associated with a more aggressive behavior, but the main determinants of prognosis are age and cavernous sinus invasion.

Assuntos

RESUMO

ABSTRACT Objective The aim of this study was to evaluate the results of the endoscopic transsphenoidal technique for growth hormone (GH)-secreting adenomas. Methods A retrospective analysis based on medical records of 23 acromegalic patients submitted to endoscopic transsphenoidal surgery. Biochemical control was defined as basal GH < 1ng/ml, nadir GH < 0.4ng/ml after glucose load and age-adjusted IGF-1 normal at the last follow-up. Results The overall endocrinological remission rate was 39.1%. While all microademonas achieved a cure, just one third of macroadenomas went into remission. Suprasellar extension, cavernous sinus invasion and high GH levels were associated with lower rates of disease control. The most common complication was diabetes insipidus and the most severe was an ischemic stroke. Conclusion The endoscopic transsphenoidal approach is a safe and effective technique to control GH-secreting adenomas. The transcavernous approach may increase the risk of complications. Suprasellar and cavernous sinus extensions may preclude gross total resection of these tumors.

RESUMO Objetivo O objetivo do estudo é analisar os resultados da cirurgia de ressecção endoscópica transesfenoidal para adenomas secretores do hormônio do crescimento (GH). Métodos Revisão retrospectiva baseada em análise de prontuários de 23 pacientes acromegálicos submetidos à cirurgia endoscópica. Remissão foi definida por GH < 1ng/ml, nadir de GH ≤ 0,4ng/ml no teste oral de tolerância a glicose e IGF-1 normal para idade. Resultados A taxa de remissão endocrinológica foi 39,1%. Enquanto todos microadenomas alcançaram controle hormonal, apenas um terço dos macroadenomas obtiveram remissão. Extensão suprasselar, invasão do seio cavernoso e altos níveis de GH foram associados a menores taxas de controle da doença. A complicação mais comum foi diabetes insipidus e a mais grave foi acidente vascular encefálico isquêmico. Conclusão A abordagem endoscópica transesfenoidal é segura e efetiva para controle de adenomas hipofisários secretores de GH. A abordagem ao seio cavernoso pode aumentar a morbidade da cirurgia. Extensões suprasselares e no seio cavernoso podem dificultar a ressecção completa e o controle da doença.

Assuntos

RESUMO

CONTEXT: Pituitary macroadenomas are rare intracranial tumors. In a few cases, they may present aggressive behavior and invade the sphenoid sinus and nasal cavity, causing unusual symptoms. In this paper, we report an atypical case of pituitary adenoma presenting as a nasal mass. CASE REPORT: The patient was a 44-year-old woman who had had amenorrhea and galactorrhea for ten months, with associated nasal obstruction, macroglossia and acromegaly. Both growth hormone and prolactin levels were increased. Magnetic resonance imaging showed a large mass originating from the lower surface of the pituitary gland, associated with sella turcica erosion and tumor extension through the sphenoid sinus and nasal cavity. Histopathological analysis demonstrated a chromophobe pituitary adenoma with densely packed rounded epithelial cells, with some atypias and rare mitotic figures. There was no evidence of metastases. CONCLUSION: Macroadenoma invading the nasal cavity is a rare condition and few similar cases have been reported in the literature. This study contributes towards showing that tumor extension to the sphenoid sinus and nasopharynx needs to be considered and investigated in order to make an early diagnosis when atypical symptoms like nasal obstruction are present. .

CONTEXTO: Macroadenomas hipofisários são tumores intracraniais raros. Em alguns casos, podem apresentar comportamento agressivo e invadir o seio esfenoidal e a cavidade nasal, causando sintomas não usuais. Neste relato de caso, descrevemos um caso atípico de adenoma hipofisário manifestando-se como uma massa nasal. RELATO DE CASO: A paciente de 44 anos, do sexo feminino, apresentava amenorreia e galactorreia por 10 meses associando-se a obstrução nasal, macroglossia e acromegalia. Os níveis do hormônio de crescimento e de prolactina apresentaram-se aumentados. Ressonância magnética mostrou uma grande massa originada da superfície inferior da glândula hipofisária associada com erosão da sela túrcica e extensão do tumor através do seio esfenoidal e cavidade nasal. Análise histopatológica demonstrou adenoma hipofisário cromófobo com células epiteliais arrendondadas densamente agrupadas com algumas atipias e escassas figuras de mitose. Não houve evidências de metástase. CONCLUSÃO: O macroadenoma invasivo para a cavidade nasal é uma condição rara e há poucos relatos similares descritos na literatura. Este trabalho contribui para mostrar que, na presença de sintomas atípicos como a obstrução nasal, a extensão para o seio esfenoidal e para a nasofaringe deve ser considerada e investigada para um diagnóstico precoce. .

Assuntos

RESUMO

Objective: Analyzing the rate of structural complications after transsphenoidal surgery for removal of growth hormone (GH) secreting pituitary adenomas. Methods: Retrospective study of 58 patients who underwent microscopic transsphenoidal neurosurgery for GH secreting pituitary adenomas exeresis in Curitiba, Parana state, Brazil, between 1998 and 2011 by the same neurosurgeon. The Criteria for diagnosis of complications were clinical. Results: Five (8,6%) of the 58 patients who underwent transsphenoidal surgery developed postoperative anatomical complications, which was due to sixth cranial nerve palsy (3,4%), surgical wound infection (1,7%) and CSF fistula (3,4%). Conclusion: The rate of postoperative complications observed in the present study is likely the literature review. There is a drop in the rate of complications with increasing experience of the neurosurgeon.

Objetivo: Analisar a taxa de complicações anatômicas após cirurgia transesfenoidal para remoção de adenoma hipofisário produtor de hormônio do crescimento (GH). Métodos: Estudo retrospectivo de 58 pacientes operados por microcirurgia transesfenoidal para exérese de adenomas pituitários produtores de GH em Curitiba, Paraná, Brasil, entre 1998 e 2011, realizados pelo mesmo neurocirurgião. Diagnóstico das complicações foi clínico. Resultados: Dos 58 pacientes submetidos à cirurgia transesfenoidal, 5 (8,6%) desenvolveram complicações anatômicas, 3,4% foram em decorrência de paresia temporária do sexto nervo craniano, 1,7%, de infecção da ferida operatória, e 3,4%, de fístula liquórica. Conclusão: A taxa de complicações pós-operatórias observada no presente estudo está semelhante à da revisão literária. Há uma queda no índice de complicações conforme aumenta a experiência do neurocirurgião.

Assuntos

RESUMO

O artigo descreve o Sistema do Hormônio de Crescimento (GH), enfatizando suas possíveis ações nas células da epiderme, nas estruturas da derme e na cicatrização de feridas cutâneas. Para tanto, fez-se uma revisão dos conhecimentos sobre o hormônio do crescimento, seu receptor, a proteína carreadora deste hormônio e demais proteínas envolvidas no mecanismo que o GH utiliza para a sua manifestação nos tecidos cutâneos.

This paper describes the growth hormone system, emphasizing its possible effects on epidermal cells, dermal structures and wound healing. A review of the literature was conducted on studies concerning the growth hormone molecule, its receptor and carrier proteins and the other proteins involved in the mechanisms of its manifestation in dermal tissue.

Assuntos

RESUMO

A acromegalia é doença insidiosa e desfigurante caracterizada por um crescimento desproporcional dos ossos das mãos, pés e do crânio devido à exposição crônica a altos níveis de hormônio de crescimento (GH) e de seu efetor insuline growth factor 1 (IGF-1). Trata-se de uma doença rara, com incidência estimada de 3-4 casos por milhão, com prevalência de aproximadamente 50 casos por milhão de pessoas. A principal causa da acromegalia é a presença de um tumor hipofisário secretor de GH (somatotropinoma). Caso o somatotropinoma ocorra durante a infância ou adolescência, antes do fechamento das epífises dos ossos longos, a criança crescerá longitudinalmente de forma descontrolada, caracterizando a forma clínica gigantismo. Na grande maioria dos casos a acromegalia se apresenta na forma esporádica, entretanto casos familiais da doença podem ocorrer associados à Neoplasia Endócrina Múltipla tipo 1 (NEM-1), ao complexo de Carney (CNC) e à acromegalia familial isolada (IFS). Os genes responsáveis pela NEM-1 (MEN1) e CNC (PRKAR1A) foram clonados há mais 10 anos, entretanto etiologia molecular da IFS permaneceu desconhecida até recentemente. Vierimaa et al. (2006) combinaram estudos de ligação por análise de polimorfismos e estudos de expressão gênica e identificaram mutações no gene AIP em famílias com acromegalia não-NEM-1 e não-CNC; além de perda de heterozigose (LOH) nos somatotropinomas dos pacientes com mutação AIP. No presente estudo, investigamos o gene AIP em três famílias brasileiras com IFS e em seus tumores (hipofisários e não-hipofisários). Descrevemos uma nova mutação AIP (Y268X) em uma família brasileira com IFS, confirmando o papel desse novo gene na predisposição a tumores hipofisários. A partir de dados gerados em uma extensa revisão da literatura, sugerimos que os tumores hipofisários familiais isolados são doenças multigênicas que possuiriam um gene principal, mas que sofreriam influência de outros genes/loci ainda pouco caracterizados...

Acromegaly is a rare disfigurating and insidious disease characterized by enlargement of hands, feet and skull bones due to excess of growth hormone (GH) secreted by a pituitary tumor (somatotropinoma). The majority of the cases with acromegaly is sporadic, however it may occur in association with inherited disorders as Multiple Endocrine Neoplasia type 1 (MEN1), Carney complex (CNC) and Isolated Familial Somatotropinoma (IFS). The genes associated with MEN1 syndrome (MEN1) and CNC (PRKAR1A) have been described more than a decade ago, however until very recently the molecular etiology of IFS remained unknown. Using a combined strategy of single nucleotide polymorphism (SNP) analysis and gene expression analysis, Vierimaa et al. (2006) described mutations in the AIP gene occurring in families with acromegaly not associated with MEN1 and CNC. In the current study, we investigated three Brazilian families with IFS and were able to describe two germline mutations in the AIP gene, confirming the role of this new gene in the predisposition to familial somatotropinoma. We revised the literature of genetic studies of isolated pituitary adenoma syndromes, which indicated a genetic heterogeneity as well as possible multigenic inheritance for these diseases. Thus, we investigated the role of several genes/loci (SSTR2, SSTR5, CDKN1B, AHR, PRKAR1A, PTTG, PROP1, MEG3, RB1 and 2p16) selected as potentially acting as phenotypic modulators in IFS. Our data indicate that AIP-mutated patients are prone to pituitary disease, however it is necessary the co-segregation of markers located at oncogenic regions to the development of the pituitary tumors and manifestation of the disease. Herein, we also present the first somatic analysis of non-pituitary tumors of AIP-mutated patients. A potential role of AIP, which is implicated in the cAMP pathway, could not be excluded in the development of an adrenocortical carcinoma.

Assuntos