RESUMO
OBJECTIVE: Hypercortisolism in Cushing's syndrome (CS) is associated with impaired health-related quality of life (HRQoL), which may persist despite remission. We used the data entered into the European Registry on Cushing's syndrome (ERCUSYN) to evaluate if patients with CS of pituitary origin (PIT-CS) have worse HRQoL, both before and after treatment than patients with adrenal causes (ADR-CS). METHODS: Data from 595 patients (492 women; 83%) who completed the CushingQoL and/or EQ-5D questionnaires at baseline and/or following treatment were analysed. RESULTS: At baseline, HRQoL did not differ between PIT-CS (n = 293) and ADR-CS (n = 120) on both EuroQoL and CushingQoL. Total CushingQoL score in PIT-CS and ADR-CS was 41 ± 18 and 44 ± 20, respectively (P = .7). At long-time follow-up (>1 year after treatment) total CushingQoL score was however lower in PIT-CS than ADR-CS (56 ± 20 vs 62 ± 23; P = .045). In a regression analysis, after adjustment for baseline age, gender, remission status, duration of active CS, glucocorticoid dependency and follow-up time, no association was observed between aetiology and HRQoL. Remission was associated with better total CushingQoL score (P < .001), and older age at diagnosis with worse total score (P = .01). Depression at diagnosis was associated with worse total CushingQoL score at the last follow-up (P < .001). CONCLUSION: PIT-CS patients had poorer HRQoL than ADR-CS at long-term follow-up, despite similar baseline scoring. After adjusting for remission status, no interaetiology differences in HRQoL scoring were found. Age and presence of depression at diagnosis of CS may be potential predictors of worse HRQoL regardless of CS aetiology.
Assuntos
Adenoma/fisiopatologia , Hidrocortisona/metabolismo , Hipersecreção Hipofisária de ACTH/metabolismo , Hipersecreção Hipofisária de ACTH/fisiopatologia , Adenoma/tratamento farmacológico , Adenoma/metabolismo , Adulto , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Estudos Prospectivos , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
Cushing's syndrome (CS) is associated with serious comorbidities and an increased mortality rate that could be reduced only if strict biochemical control is achieved. The aim of this study was to show the 50-year experience of a single tertiary center in the management of CS patients - the different treatment modalities used over the years and the corresponding outcomes. It was a retrospective study of a large cohort of patients from the Bulgarian CS database: 613 patients (374 with ACTH-dependent and 239 with ACTH-independent CS). Pituitary surgery was applied to 242 patients with Cushing's disease (CD) with initial remission rate of 74% of which 10% relapsed. Approximately 36% manifested with active disease during the long-term follow-up (26% with persistent disease, 10% relapses) most of which were subjected to a secondary treatment (13.6% to pituitary resurgery, 14% to pituitary radiotherapy, and 5.4% to bilateral adrenalectomy). A total of 294 CD patients received medical therapy with overall remission rates for the most commonly used drugs: dopamine agonists 20%, pasireotide 30%, and ketoconazole 63%. Significant improvement of results was achieved by combining drugs with different mechanisms of action. Regardless of the progress in the neurosurgery and radiotherapy techniques and new drugs discovery, the management of patients with CS remains a real challenge for physicians. Not only patients with adrenal carcinoma but also significant percentage of subjects with persistent and recurrent Cushing's disease often require a polymodal approach and the efforts of a multidisciplinary highly qualified, experienced, and motivated team in order to achieve a long-term remission.
Assuntos
Adrenalectomia , Hormônio Adrenocorticotrópico/metabolismo , Terapia Combinada/história , Hipersecreção Hipofisária de ACTH/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Feminino , História do Século XX , História do Século XXI , Humanos , Hidrocortisona , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/metabolismo , Hipersecreção Hipofisária de ACTH/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Pituitary adenomas (PAs) show a broad clinicomorphological spectrum. The proliferation activity, evaluated by MIB-1 labelling index (LI), and p53 expression have been pointed as predictive markers for invasiveness and progression. The aim of this study was to evaluate the proliferation rate and p53 expression and to look for any relationships with the clinical behaviour and follow-up results in a series of Bulgarian patients with PAs. A total of 93 patients with PAs (81 hormone-secreting, 12 non-functioning), who were operated on and followed up for a period of five years, were included. The MIB-1 LI and p53 expressions were determined by immunohistochemistry and correlated with various clinical and tumour variables. The whole group of PAs showed a low proliferation rate with evident variations in a small number of cases (MIB-1 LI - 0.50 ± 0.56, from 0.1 to 3.30). MIB-1 LI correlated with tumour size (p = 0.012) and was positively related with male gender (p = 0.23) and partial surgical resection (p = 0.036). We found no significant differences regarding the age, functional activity, invasion (n = 33), expansion (n = 37) and tumour recurrences (seven cases). Only 10 cases (10.8%) showed a focal, nuclear p53 immunoreactivity. The p53 positive tumours had higher proliferation rate (p = 0.0001) but no relationship with the other clinical and tumour variables. Among all cases, there was only one case with higher MIB-1 LI (3.3%), positive p53 expression and tumour recurrence after surgery. Our results show that most PAs have a low proliferation rate and lack of p53 expression, as well as no relationship with tumour invasion or postsurgical progression.
RESUMO
Cushing's syndrome (CS) is characterized by pathologically elevated free glucocorticoid levels. Endogenous hypercortisolism is usually due to ACTH-secreting pituitary corticotropic adenomas and less often due to ectopic ACTH-secreting neuroendocrine neoplasms or ACTH-independent adrenal cortisol hypersecretion. CS is a serious chronic disease leading to a several-fold increase in cardiovascular morbidity and mortality. Multiple genetic alterations have been described in the setting of sporadic corticotropinoma formation. Changes in the expression profiles have been demonstrated in growth factors and their receptors, cell-cycle regulators and in various genes related to hormonal gene transcription, synthesis and secretion. Sporadic adrenal adenomas and carcinomas may demonstrate dysfunction in genes such as TP53 among others. Cushing's disease can be an inherited condition also. Multiple endocrine neoplasia type 1 (MEN1) and familial isolated pituitary adenomas (FIPA) together account for 5% of pituitary adenomas. Cushing's disease occurs infrequently in an inherited setting in both of these conditions. To date only 2 cases of Cushing's disease have been described in association with mutations in AIP. One case of Cushing's disease has been reported as part of MEN4, a rare MEN1-like syndrome due to mutation in the CDKN1B gene. Carney complex (CNC) due to PRKAR1A mutations in most cases is associated with CS, mainly as a cause of bilateral adrenal hyperplasia. The cAMP signaling pathway is affected in this setting. In recent times the involvement of genes such as PDE11A, PDE8B and others have expanded the spectrum of the genetic pathophysiology of CS.
Assuntos
Neoplasias do Córtex Suprarrenal/genética , Adenoma Adrenocortical/genética , Síndrome de Cushing/genética , Hipersecreção Hipofisária de ACTH/genética , Neoplasias Hipofisárias/genética , Neoplasias do Córtex Suprarrenal/complicações , Adenoma Adrenocortical/complicações , Síndrome de Cushing/etiologia , Humanos , Hipersecreção Hipofisária de ACTH/etiologia , Neoplasias Hipofisárias/complicaçõesRESUMO
BACKGROUND: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. OBJECTIVE: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). PATIENTS AND METHODS: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). RESULTS: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. CONCLUSIONS: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results.
Assuntos
Síndrome de Cushing/tratamento farmacológico , Síndrome de Cushing/cirurgia , Glândulas Suprarrenais/fisiopatologia , Adulto , Idoso , Síndrome de Cushing/fisiopatologia , Bases de Dados Factuais , Europa (Continente) , Feminino , Humanos , Cetoconazol/uso terapêutico , Masculino , Metirapona/uso terapêutico , Pessoa de Meia-Idade , Síndromes Endócrinas Paraneoplásicas , Hipófise/fisiopatologia , Cuidados Pós-Operatórios , Período Pós-Operatório , Qualidade de Vida , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing's syndrome (ERCUSYN), and to examine if their use differs from the current guidelines. PATIENTS AND METHODS: We analyzed data on the diagnostic tests performed in 1341 patients with Cushing's syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS). RESULTS: Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years (P < 0.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years (P < 0.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2 mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1 mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC (P < 0.05). CONCLUSIONS: Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.
Assuntos
Síndrome de Cushing/diagnóstico , Síndrome de Cushing/metabolismo , Testes Diagnósticos de Rotina/normas , Guias de Prática Clínica como Assunto/normas , Sistema de Registros , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Idoso , Síndrome de Cushing/epidemiologia , Testes Diagnósticos de Rotina/estatística & dados numéricos , Europa (Continente)/epidemiologia , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Estatística como Assunto/métodosRESUMO
Various factors influence quality of life (QoL) in acromegaly. Whether disease control and treatment approach are related to QoL is still a matter of debate. The aim of the present study was to evaluate QoL in patients with acromegaly using the disease-specific Acromegaly Quality of Life Questionnaire in respect to disease activity, treatment modalities, and other factors. We studied 212 patients with acromegaly in a cross-sectional manner over a 6-year period in a single tertiary center. As a second step, seventy of the patients who were with active disease at baseline were followed up prospectively and 45 of them were in remission at re-evaluation. In regard to the cross-sectional group, active acromegaly independently predicted worse appearance scores. Prior radiotherapy and older age were independent negative predictors of all scales. Female gender negatively predicted all scales except the appearance domain. Longer duration of remission predicted worse personal relations scores in biochemically controlled patients. The use of somatostatin analog (SSA) was associated with worse personal relations scores, while higher IGF-1 index predicted worse appearance scores in patients with active acromegaly. In the prospective group, achievement of remission independently predicted improvement of the total scale. Lower corresponding baseline scores predicted improvement of the total, physical, and appearance scales, while the absence of hypopituitarism independently predicted improvement of the appearance scale. The use of SSA was associated with improvement of the total and appearance scores. In conclusion, QoL is a multifactorial issue that needs an individualized approach for detection and management.
Assuntos
Acromegalia/psicologia , Acromegalia/terapia , Qualidade de Vida , Acromegalia/radioterapia , Adulto , Idoso , Estudos Transversais , Feminino , Antagonistas de Hormônios/uso terapêutico , Hormônio do Crescimento Humano/sangue , Humanos , Hipopituitarismo/psicologia , Hipopituitarismo/terapia , Fator de Crescimento Insulin-Like I/análise , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Inquéritos e Questionários , Resultado do TratamentoRESUMO
We assessed the value of midnight salivary cortisol for the initial diagnosis of Cushing's syndrome. Sixty-three patients with various causes of Cushing's syndrome (37 with Cushing's disease, 17 with adrenal Cushing's syndrome, and nine with ectopic ACTH syndrome) and 54 control subjects with simple obesity were studied. All patients with Cushing's syndrome excreted more than 90 microg urinary free cortisol (UFC)/d (248 nmol/d), and all controls excreted less than 90 microg/d UFC. All patients with Cushing's syndrome had a midnight salivary cortisol concentration above 2.0 ng/ml (5.52 nmol/liter), whereas only three controls did so [2.0 ng/ml (5.52 nmol/liter); 2.05 ng/ml (5.66 nmol/liter); and 3.6 ng/ml (9.96 nmol/liter)]. This cut-off provides a sensitivity of 100% and a specificity of 96%. In patients with Cushing's syndrome, midnight salivary cortisol concentrations were correlated with UFC collected over the same period of time (0800-0800 h). Salivary cortisol measurements taken every 4 h showed a typical lack of circadian variation. The daily measurement of midnight salivary cortisol concentrations for 2 wk or more in five other out-patients (with obvious Cushing's disease, subclinical adrenal Cushing's syndrome, suspected Cushing's syndrome, pituitary incidentaloma, and prolactinoma) demonstrated the clinical utility of this factor. Measuring midnight salivary cortisol is an easy and noninvasive means of diagnosing hypercortisolism. Its diagnostic accuracy is identical to, if not better than, that of previously described gold standards.
Assuntos
Ritmo Circadiano , Síndrome de Cushing/diagnóstico , Hidrocortisona/análise , Saliva/química , Síndrome de ACTH Ectópico/metabolismo , Adulto , Síndrome de Cushing/etiologia , Síndrome de Cushing/metabolismo , Síndrome de Cushing/urina , Feminino , Humanos , Hidrocortisona/urina , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Concentração Osmolar , Neoplasias Hipofisárias/metabolismo , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Data on the incidence, mortality, and causes of death in patients with Cushing's syndrome (CS) are scarce, due to the rarity of CS. The aim of the study was to analyze mortality in a large cohort of patients of all etiologies and to determine the cause of death. DESIGN: This was a retrospective study of patients with CS, treated over a period of 45 years in the main tertiary referral center in Bulgaria. METHODS: Three hundred and eighty-six patients with CS of all etiologies were included. The main outcome measures were the standardized mortality ratio (SMR) and the cause of death. RESULTS: Mean (S.D.) age at diagnosis was 3813 years; 84% of patients were women; mean follow-up was 85 months (rangE: 0-494 months). The SMR in the CS cohort was 4.05 (95% CI 2.50-5.80) (P<0.0001). The following subgroups did not have a significantly increased SMR: patients with Cushing's disease SMR - 1.88 (95% CI 0.69-4.08), adrenal adenomas 1.67 (95% CI 0.20-6.02), and ACTH-independent bilateral adrenal hyperplasia 1.14 (95% CI 0.21-6.34). Patients with adrenal carcinomas, ectopic CS, and those with CS of undetermined etiology had significantly increased SMR: 48.00 (95% CI 30.75-71.42), 13.33 (95% CI 0.00-24.59), and 4.00 (95% CI 0.48-14.45) respectively (P<0.0001). The significant predictors for mortality were active disease at death, age, male sex, etiology of the disease, and the overall duration of active disease. The major causes of death were vascular events (40%) - cardiovascular 29%, and cerebrovascular 11% - followed by infections (12%). CONCLUSIONS: Patients with CS have increased mortality due to vascular events and infections.
Assuntos
Síndrome de Cushing/mortalidade , Adenoma/complicações , Adolescente , Neoplasias das Glândulas Suprarrenais/complicações , Hiperplasia Suprarrenal Congênita/complicações , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Bulgária/epidemiologia , Carcinoma/complicações , Causas de Morte , Criança , Pré-Escolar , Estudos de Coortes , Síndrome de Cushing/etiologia , Feminino , Previsões , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Adulto JovemRESUMO
Familial isolated pituitary adenoma (FIPA) occurs in families and is unrelated to multiple endocrine neoplasia type 1 and Carney complex. Mutations in AIP account only for 15-25% of FIPA families. CDKN1B mutations cause MEN4 in which affected patients can suffer from pituitary adenomas. With this study, we wanted to assess whether mutations in CDKN1B occur among a large cohort of AIP mutation-negative FIPA kindreds. Eighty-eight AIP mutation-negative FIPA families were studied and 124 affected subjects underwent sequencing of CDKN1B. Functional analysis of putative CDKN1B mutations was performed using in silico and in vitro approaches. Germline CDKN1B analysis revealed two nucleotide changes: c.286A>C (p.K96Q) and c.356T>C (p.I119T). In vitro, the K96Q change decreased p27 affinity for Grb2 but did not segregate with pituitary adenoma in the FIPA kindred. The I119T substitution occurred in a female patient with acromegaly. p27(I119T) shows an abnormal migration pattern by SDS-PAGE. Three variants (p.S56T, p.T142T, and c.605+36C>T) are likely nonpathogenic because In vitro effects were not seen. In conclusion, two patients had germline sequence changes in CDKN1B, which led to functional alterations in the encoded p27 proteins in vitro. Such rare CDKN1B variants may contribute to the development of pituitary adenomas, but their low incidence and lack of clear segregation with affected patients make CDKN1B sequencing unlikely to be of use in routine genetic investigation of FIPA kindreds. However, further characterization of the role of CDKN1B in pituitary tumorigenesis in these and other cases could help clarify the clinicopathological profile of MEN4.
Assuntos
Adenoma/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Neoplasias Hipofisárias/genética , Linhagem Celular Tumoral , Família , Feminino , Variação Genética , Genótipo , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , MutaçãoRESUMO
OBJECTIVE: The European Registry on Cushing's syndrome (ERCUSYN) is designed to collect prospective and follow-up data at EU level on Cushing's syndrome (CS). DESIGN AND METHODS: Baseline data on 481 CS patients (390 females, 91 males; mean age (±s.d.): 44±14 years) collected from 36 centres in 23 countries, including new patients from 2008 and retrospective cases since 2000. Patients were divided into four major aetiologic groups: pituitary-dependent CS (PIT-CS) (66%), adrenal-dependent CS (ADR-CS) (27%), CS from an ectopic source (ECT-CS) (5%) and CS from other aetiologies (2%). RESULTS: Proportion of men in the ECT-CS group was higher than in the other groups (P<0.05). The ADR-CS group was older than the PIT-CS (P<0.05). Prevalence of hirsutism (92%) and diabetes (74%) in ECT-CS was higher than in the other groups (P<0.05 and P<0.01 respectively). PIT-CS had more skin alterations, menstrual irregularities and hirsutism than ADR-CS (P<0.01). Reduced libido was more prevalent in men than women (P<0.01). Prevalence of spine osteoporosis was higher in men than women (P<0.05), and males had more vertebral and rib fractures than females (52 vs 18% for vertebrae; P<0.001 and 34 vs 23% for ribs; P<0.05). ECT-CS consulted a diabetologist more frequently than ADR-CS (P<0.05), while a gynaecologist was consulted more often by women with PIT-CS or ADR-CS than with ECT-CS (P<0.05). Overall, weight gain was more common in women than men (P<0.01). CushingQoL and EuroQoL visual analogue scale scores did not differ between the groups. CONCLUSIONS: The ERCUSYN project demonstrates a heterogeneous clinical presentation of CS at a European level, depending on gender and aetiology.
Assuntos
Síndrome de Cushing/epidemiologia , Adolescente , Neoplasias das Glândulas Suprarrenais/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Ósseas Metabólicas/etiologia , Estudos de Coortes , Síndrome de Cushing/complicações , Síndrome de Cushing/etiologia , Europa (Continente)/epidemiologia , Feminino , Fraturas Ósseas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Prevalência , Estudos Prospectivos , Qualidade de Vida , Sistema de Registros , Estudos RetrospectivosRESUMO
BACKGROUND: Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments. METHODS: We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age. RESULTS: Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas. CONCLUSION: Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação/fisiologia , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/genética , Adulto , DNA/genética , Feminino , Testes Genéticos , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Hipofisárias/patologia , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Adulto JovemRESUMO
CONTEXT: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. OBJECTIVE: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. DESIGN: This study was an international, multicenter, retrospective case collection/database analysis. SETTING: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. PATIENTS: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. RESULTS: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. CONCLUSIONS: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.
Assuntos
Adenoma/genética , Mutação em Linhagem Germinativa , Neoplasias Hipofisárias/genética , Adenoma/patologia , Adenoma/terapia , Fatores Etários , Agonistas de Dopamina/uso terapêutico , Feminino , Humanos , Masculino , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/terapia , Resultado do TratamentoRESUMO
La oftalmía neonatal es un problema de salud pública, la cual ocurre durante las primeras cuatro semanas de vida y cuya etiología principal es la bacteriana. El objetivo de este trabajo es estudiar la flora bacteriana conjuntival del neonato y su respuesta a la profilaxis oftálmica empleada en sala de partos y área quirúrgica del Hospital General del Oeste "Dr. José Gregorio Hernández". Se tomaron 101 muestras de conjuntiva ocular a neonatos antes de colocar la profilaxis oftálmica con gentamicina, realizándose cultivo, gram y sensibilidad in vitro al antibiótico empleado. De 101 muestras , 35 (34,6 por ciento) resultaron positivos y de éstos 33 (94,3 por ciento) fueron de neonatos obtenidos por la vía vaginal, con una diferencia estadísticamente significativa en relación con, los obtenidos por cesárea. El germen más frecuentemente aislado fue la Escherichia coli con un 57,1 por ciento. Aquellos cultivos obtenidos de neonatos productos de embarazos no controlados, 42,3 por ciento resultaron con cultivos positivos, y de los controlados 23,8 por ciento resultaron positivos, con una diferencia estadísticamente significativa. Un 94 por ciento de las bacterias aisladas resultaron sensibles a la gentamicina. La mayor frecuencia de Escherichia coli como parte de la flora bacteriana de la conjuntiva ocular de los neonatos atendidos en este centro, orienta acerca de la importancia del buen control perinatal y del empleo de las medidas de asepsia y antisepsia. El principal mecanismo de aquisición de flora bacteriana conjuntival es a través del paso por el canal del parto. Los gérmenes aislados son sensibles a la gentamicina, lo que demuestra ser una profilaxis oftálmica adecuada