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1.
BMJ Case Rep ; 13(12)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334740

RESUMO

Myasthenia gravis (MG) is a rare and potentially dangerous autoimmune condition, which affects the acetylcholine receptors at the neuromuscular junction of skeletal muscle. MG's diverse symptomatology may readily masquerade as other neurological conditions, posing a diagnostic challenge to clinicians. We describe a 24-year old man who presented to the emergency department with a new onset internuclear ophthalmoplegia. After a series of investigations, we eventually arrived at a diagnosis of MG with pseudointernuclear ophthalmoplegia with an incidentally detected prolactinoma. We explore the literature regarding the pathophysiology of pseudointernuclear ophthalmoplegia, the link between prolactin and autoimmunity and the association between prolactinoma and MG.


Assuntos
Diplopia/etiologia , Miastenia Gravis/diagnóstico , Transtornos da Motilidade Ocular/etiologia , Neoplasias Hipofisárias/diagnóstico , Prolactinoma/diagnóstico , Humanos , Achados Incidentais , Masculino , Miastenia Gravis/complicações , Miastenia Gravis/imunologia , Transtornos da Motilidade Ocular/diagnóstico , Hipófise/diagnóstico por imagem , Hipófise/metabolismo , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/complicações , Prolactina/sangue , Prolactina/metabolismo , Prolactinoma/sangue , Prolactinoma/complicações , Tomografia Computadorizada por Raios X , Adulto Jovem
2.
Medicine (Baltimore) ; 99(40): e22432, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019423

RESUMO

Nesfatin-1 was identified as a satiety factor involved in the regulation of metabolism. Altered levels of circulating nesfatin-1 had been observed in a variety of diseases characterized by energy imbalance. However, there was no published data about nesfatin-1 levels in acromegaly.We evaluated serum nesfatin-1 levels in 13 patients with acromegaly at baseline and postoperatively, and in 21 age- and body mass index (BMI)-matched healthy subjects.Compared with the healthy subjects, patients with acromegaly had significantly increased levels of serum insulin, high-density lipoprotein cholesterol, triglyceride, and growth hormone (GH). Moreover, the acromegaly group had nesfatin-1 levels higher than controls (1.96 ±â€Š0.56 ng/mL vs 0.61 ±â€Š0.10 ng/mL, P = .004). There was a positive correlation of serum nesfatin-1 levels with diastolic blood pressure (r = 0.579, P = .038) and homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.598, P = .031) in patients with acromegaly. While a successful surgery decreased serum GH levels, the serum nesfatin-1 levels did not change in acromegaly (P = .965). At last, we compared serum GH/nesfatin-1 levels with predictive markers for aggressive behaviors in pituitary adenomas. There was no relationship between serum nesfatin-1 levels and tumor's size, Ki-67 index, mutant p53, or MGMT proteins. However, increased serum GH levels were positively correlated with tumors' size (P = .023) and mutant p53 proteins expression (P = .028).Circulating nesfatin-1 was increased in acromegaly, which was involved in metabolism regulation.


Assuntos
Acromegalia/sangue , Nucleobindinas/sangue , Adenoma/sangue , Adenoma/patologia , Adenoma/cirurgia , Adulto , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Curva ROC
4.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 42(1): 33-39, Jan.-Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1055365

RESUMO

Objective: To evaluate body dissatisfaction and distorted body self-image in women with prolactinoma. Methods: Body dissatisfaction and distorted body self-image were evaluated in 80 women with prolactinoma. All patients were in menacme, 34% had normal body mass index (BMI), and 66% were overweight. Most patients (56.2%) had normal prolactin (PRL) levels and no hyperprolactinemia symptoms (52.5%). The Body Shape Questionnaire (BSQ) was used to assess the patients' dissatisfaction with and concern about their physical form, and the Stunkard Figure Rating Scale (FRS) was used to assess body dissatisfaction and distorted body self-image. The patients were divided according to PRL level (normal vs. elevated) and the presence or absence of prolactinoma symptoms. Results: The normal and elevated PRL groups had similar incidences of body dissatisfaction and distorted body self-image. However, symptomatic patients reported a higher incidence of dissatisfaction than asymptomatic patients. Distorted body self-image was less common among symptomatic patients. Conclusion: Symptomatic patients showed higher body dissatisfaction, but lower body self-image distortion. The presence of symptoms may have been responsible for increased body awareness. The perception of body shape could have triggered feelings of dissatisfaction compared to an ideal lean body. Therefore, a distorted body self-image might not necessarily result in body dissatisfaction in women with prolactinomas.


Assuntos
Humanos , Feminino , Adulto , Adulto Jovem , Neoplasias Hipofisárias/psicologia , Hiperprolactinemia/psicologia , Prolactinoma/psicologia , Transtornos Dismórficos Corporais/psicologia , Neoplasias Hipofisárias/sangue , Prolactina/sangue , Escalas de Graduação Psiquiátrica , Valores de Referência , Imagem Corporal/psicologia , Hiperprolactinemia/tratamento farmacológico , Hiperprolactinemia/sangue , Prolactinoma/sangue , Índice de Massa Corporal , Inquéritos e Questionários , Estatísticas não Paramétricas , Agonistas de Dopamina/uso terapêutico , Pessoa de Meia-Idade
5.
Sci Rep ; 10(1): 1334, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992791

RESUMO

The diagnosis of various histological subtypes of pituitary tumors is made using serum based hormone panel test. However, certain subtypes secrete more than one hormone, making the diagnosis ambiguous. Here, we performed 1H-NMR based metabolomic analysis of serum and whole-blood from luteinizing/follicle-stimulating (LH/FSH)-secreting (n = 24), prolactinomas (n = 14), and non-functional (NF) (n = 9) tumors. We found elevated levels of betahydroxybutyrate (BHB) in serum and whole-blood (WB) of prolactinomas (0.481 ± 0.211/0.329 ± 0.228 mM in serum/WB), but it was statistically significant (p ≤ 0.0033, Bonferroni correction) only in serum when compared with LH/FSH-secreting tumor patients (0.269 ± 0.139/0.167 ± 0.113 mM in serum/WB). Phenylalanine in NF tumors was found to be elevated in both serum and WB when compared with prolactinomas but it met the statistical significance criteria (p ≤ 0.0028) only in the serum. Alanine (p ≤ 0.011), tyrosine (p ≤ 0.014) and formate (p ≤ 0.011) were also elevated in NF tumors but none showed statistically significance when compared with prolactinomas. Quantification of BHB and the above amino acids in the circulation may aid in the development of blood-based in vitro diagnostic methods which can supplement the currently used serum hormone panel in the diagnosis of various subtypes of pituitary tumors.


Assuntos
Ácido 3-Hidroxibutírico/sangue , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/diagnóstico , Prolactinoma/sangue , Prolactinoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Curva ROC
6.
BMC Endocr Disord ; 20(1): 18, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996203

RESUMO

BACKGROUND: Apart from PRKAR1A mutations in a subset of cyclical Cushing's syndrome due to primary pigmented nodular adrenocortical disease, the molecular basis of cyclical Cushing's syndrome has not been investigated. We speculated that cyclical Cushing's syndrome may be due to mutations in the clock genes that govern circadian rhythms, including the hypothalamic-pituitary-adrenal axis. CASE PRESENTATION: A 47-year-old man presented with mass effects from a sellar lesion. He was ultimately diagnosed with cyclical Cushing's disease due to a giant corticotrophinoma. We performed whole exome sequencing of germline and tumour DNA, SNP array of tumour DNA and tumour immunohistochemistry in order to detect variants in candidate circadian/pituitary-associated genes. We identified a rare germline missense variant in the aryl hydrocarbon receptor (AHR) gene, which has previously been indirectly linked to pituitary tumorigenesis and clock system disruption. The AHR variant was found in a highly conserved site involved in phosphorylation. It was predicted to be damaging by multiple in silico tools and AHR tumour immunohistochemistry demonstrated loss of the normal nuclear staining pattern, suggestive of an inactivating mutation. We also found a novel, damaging germline missense variant in the retinoid X receptor gamma (RXRG) gene, multiple somatic chromosomal gains (including AHR), and a somatic mutational signature consistent with oncogenesis that may have acted synergistically with the AHR variant. CONCLUSIONS: This is the first report of an AHR variant with predicted pathogenicity in the pituitary adenoma setting. Our preliminary data suggest that the highly conserved AHR gene may represent a link between pituitary tumorigenesis, the hypothalamic-pituitary-adrenal axis and the clock system. Further research may indicate a role for the gene in the development of cyclical Cushing's disease.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Síndrome de Cushing/genética , Síndrome de Cushing/patologia , Polimorfismo de Nucleotídeo Único , Receptores de Hidrocarboneto Arílico/genética , Adenoma/sangue , Adenoma/genética , Adenoma/patologia , Síndrome de Cushing/sangue , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Prognóstico
7.
Acta Neurochir (Wien) ; 162(4): 845-852, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31907611

RESUMO

OBJECTIVE: The aim was to study the prevalence of secondary adrenal insufficiency before and after surgery for non-functioning pituitary adenomas, as well as determine risk factors for developing secondary adrenal insufficiency. A secondary aim was to determine adequate p-cortisol response to a 1-µg Short Synacthen Test after surgery. DESIGN: Longitudinal cohort study. METHODS: One hundred seventeen patients (52/65 females/males, age 59 years) undergoing primary surgery for clinically non-functioning pituitary adenomas were included. P-cortisol was measured in morning blood samples. Three months after surgery, a Short Synacthen Test was performed. RESULTS: All tumours were macroadenomas (mean size 26.9 mm, range 13-61 mm). The surgical indications were visual impairment (93), tumour growth (16), pituitary apoplexy (6) and headache (2). Before surgery, 17% of the patients had secondary adrenal insufficiency (SAI), decreasing to 15% 3 months postoperatively. Risk of SAI was increased in patients operated for pituitary apoplexy (p < 0.001), while age, sex, tumour size and complication rate were not different from the remaining cohort. Three months after surgery, all patients with baseline p-cortisol ≥ 172 nmol/l (6.2 µg/dl) and peak p-cortisol during Short Synacthen Test ≥ 320 nmol/l (11.6 µg/dl) tapered cortisone unproblematically. In patients with intact hypothalamic-pituitary-adrenal axis, p-cortisol peaked < 500 nmol/l (18.1 µg/dl) during Short Synacthen Test in 48% of patient. CONCLUSION: Pituitary surgery is safe and transsphenoidal surgery rarely causes new SAI. Relying solely on morning p-cortisol for diagnosing secondary adrenal insufficiency gives false positives and the Short Synacthen Test remains useful. A peak p-cortisol ≥ 320 during (11.6 µg/dl) Short Synacthen Test indicates a sufficient response, while < 309 nmol/l (11.2 µg/dl) indicates secondary adrenal insufficiency.


Assuntos
Adenoma/cirurgia , Insuficiência Adrenal/diagnóstico , Hidrocortisona/sangue , Neoplasias Hipofisárias/cirurgia , Adenoma/sangue , Adenoma/fisiopatologia , Insuficiência Adrenal/sangue , Adulto , Idoso , Testes Diagnósticos de Rotina , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Período Pós-Operatório
8.
Braz J Psychiatry ; 42(1): 33-39, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31314867

RESUMO

OBJECTIVE: To evaluate body dissatisfaction and distorted body self-image in women with prolactinoma. METHODS: Body dissatisfaction and distorted body self-image were evaluated in 80 women with prolactinoma. All patients were in menacme, 34% had normal body mass index (BMI), and 66% were overweight. Most patients (56.2%) had normal prolactin (PRL) levels and no hyperprolactinemia symptoms (52.5%). The Body Shape Questionnaire (BSQ) was used to assess the patients' dissatisfaction with and concern about their physical form, and the Stunkard Figure Rating Scale (FRS) was used to assess body dissatisfaction and distorted body self-image. The patients were divided according to PRL level (normal vs. elevated) and the presence or absence of prolactinoma symptoms. RESULTS: The normal and elevated PRL groups had similar incidences of body dissatisfaction and distorted body self-image. However, symptomatic patients reported a higher incidence of dissatisfaction than asymptomatic patients. Distorted body self-image was less common among symptomatic patients. CONCLUSION: Symptomatic patients showed higher body dissatisfaction, but lower body self-image distortion. The presence of symptoms may have been responsible for increased body awareness. The perception of body shape could have triggered feelings of dissatisfaction compared to an ideal lean body. Therefore, a distorted body self-image might not necessarily result in body dissatisfaction in women with prolactinomas.


Assuntos
Transtornos Dismórficos Corporais/psicologia , Hiperprolactinemia/psicologia , Neoplasias Hipofisárias/psicologia , Prolactinoma/psicologia , Adulto , Imagem Corporal/psicologia , Índice de Massa Corporal , Agonistas de Dopamina/uso terapêutico , Feminino , Humanos , Hiperprolactinemia/sangue , Hiperprolactinemia/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Prolactina/sangue , Prolactinoma/sangue , Escalas de Graduação Psiquiátrica , Valores de Referência , Estatísticas não Paramétricas , Inquéritos e Questionários , Adulto Jovem
9.
Eur J Endocrinol ; 182(2): 177-183, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31770105

RESUMO

Objective: The association between prolactin level variation and prolactinoma size reduction remains unclear. This study aimed to determine the prolactin level cut-off predictive of a tumor size reduction. Design: Retrospective cohort study. Methods: We reviewed medical records of patients with prolactinoma who received primary cabergoline therapy and for whom complete data on pituitary hormone assays and sellar MRI at baseline and 3 months post treatment were available. We tested whether the certain prolactin level after 3 months post treatment predicted better response. Results: Prolactin levels normalized in 109 (88.6%) of 123 included macroprolactinoma patients. The mean tumor size reduction was 22.9%, and patients in the lowest prolactin tertile (≤0.7) had the highest frequency of tumor size reductions of ≥20% (73.7 vs 52.9% and 45.9% in tertiles 2 (>0.7 to 2.6) and 3 (>2.6 to 20), P = 0.015). Patients with prolactin levels ≤1 ng/mL exhibited larger tumor size reductions vs those with prolactin levels of 1-20 (27.2 ± 18.3% vs 19.5 ± 13.9%, P = 0.014), 1-10 (19.3 ± 13.7%, P = 0.017) and 1-5 ng/mL (19.2 ± 14.3%, P = 0.039). A multivariable logistic regression analysis revealed that a prolactin level ≤1 ng/mL at 3 months and high-dose cabergoline therapy were significantly associated with tumor size reductions of ≥20% (odds ratio (OR): 2.8, 95% confidence interval (CI): 1.2-6.7, P = 0.017; OR: 2.0, 95% CI: 1.0-3.9, P = 0.043). Conclusions: A prolactin level ≤1 ng/mL at 3 months after cabergoline treatment was correlated with a significant tumor size reduction in patients with macroprolactinoma. This finding may help clinical decision making when treating macroprolactinoma patients.


Assuntos
Cabergolina/uso terapêutico , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/tratamento farmacológico , Prolactina/sangue , Prolactinoma/sangue , Prolactinoma/tratamento farmacológico , Adulto , Tomada de Decisões , Feminino , Humanos , Masculino , Neoplasias Hipofisárias/patologia , Prolactinoma/patologia , Estudos Retrospectivos
10.
Pituitary ; 23(1): 16-26, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31659622

RESUMO

PURPOSE: This review aimed to evaluate data on the use of magnetic resonance imaging in the management of prolactinomas. METHODS: Recent literature about prolactinoma behavior and magnetic resonance imaging in the management of prolactinomas is reviewed. RESULTS: A review of evidence regarding prolactinoma pituitary MRI follow-up; techniques and sequences, recent data on possible gadolinium retention, the role and a review of T2-weighted images in the identification of prolactinomas and frequently encountered clinical scenarios, as well as MRI correlation with prolactin secretion, tumor growth and prediction of response to medical therapy are presented. CONCLUSION: The underlying decision to perform serial imaging in prolactinoma patients should be individualized on a case-by-case basis. Future studies should focus on alternative imaging methods and/or contract agents.


Assuntos
Imagem por Ressonância Magnética/métodos , Neoplasias Hipofisárias/diagnóstico por imagem , Prolactinoma/diagnóstico por imagem , Humanos , Neoplasias Hipofisárias/sangue , Prolactina/sangue , Prolactinoma/sangue
11.
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
12.
Chin Med Sci J ; 34(3): 168-176, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601299

RESUMO

Objective To explore circulating biomarkers for screening the invasiveness of non-functioning pituitary adenomas (NF-PAs). Methods The exosomal RNAs were extracted from serum of patients with invasive NF-PA (INF-PA) or noninvasive NF-PA (NNF-PA). Droplet digital PCR was adapted to detect the mRNA expression of candidate genes related to tumor progression or invasion, such as cyclin dependent kinase 6 (CDK6), ras homolog family member U (RHOU), and spire type actin nucleation factor 2 (SPIRE2). Student's t-test was used to analyze the statistical difference in the mRNA expression of candidate genes between the two groups. Receiver operating characteristic (ROC) curve was used to establish a model for predicting the invasiveness of NF-PAs. The accuracy, sensitivity, specificity and precision of the model were then obtained to evaluate the diagnostic performance. Results CDK6 (0.2600±0.0912 vs. 0.1789±0.0628, t=3.431, P=0.0013) and RHOU mRNA expressions (0.2696±0.1118 vs. 0.1788±0.0857, t=2.946, P=0.0052) were upregulated in INF-PAs patients' serum exosomes as compared to NNF-PAs. For CDK6, the area under the ROC curve (AUC) was 0.772 (95% CI: 0.600-0.943, P=0.005), the accuracy, sensitivity, specificity and precision were 77.27%, 83.33%, 75.00% and 55.56% to predict the invasiveness of NF-PAs. For RHOU, the AUC was 0.757 (95% CI: 0.599-0.915, P=0.007), the accuracy, sensitivity, specificity and precision were 72.73%, 83.33%, 68.75% and 50.00%. In addition, the mRNA levels of CDK6 and RHOU in serum exosomes were significantly positively correlated (r=0.935, P<0.001). After combination of the cut-off scores of the two genes, the accuracy, sensitivity, specificity and precision were 81.82%, 83.33%, 81.25% and 62.50%. Conclusions CDK6 and RHOU mRNA in serum exosomes can be used as markers for predicting invasiveness of NF-PAs. Combination of the two genes performs better in distinguishing INF-PAs from NNF-PAs. These results indicate CDK6 and RHOU play important roles in the invasiveness of NF-PAs, and the established diagnostic method is valuable for directing the clinical screening and postoperative treatment.


Assuntos
Adenoma/sangue , Biomarcadores Tumorais/sangue , Quinase 6 Dependente de Ciclina/sangue , Exossomos/metabolismo , Proteínas de Neoplasias/sangue , Neoplasias Hipofisárias/sangue , RNA Mensageiro/sangue , RNA Neoplásico/sangue , Proteínas rho de Ligação ao GTP/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Pituitary ; 22(6): 574-580, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31506907

RESUMO

BACKGROUND: Some laboratory and clinical features are associated with a probability of recurrence after transnasal adenomectomy for Cushing disease (CD). However, there is no consensus on a set of predictors. Rules for prediction of recurrence were not proposed earlier. AIM: To develop prediction model of recurrence/remission after successful neurosurgical treatment for CD. METHODS: Retrospective single-site comparative study included 349 patients (52 men and 297 women) with a verified diagnosis of CD who underwent effective endoscopic transsphenoidal adenomectomy between 2007 and 2014. Clinical and laboratory parameters were evaluated. Laboratory tests were performed using immunochemiluminescent method. Time-to-event analysis and ROC-analysis were applied. Multivariate models were developed using logistic regression and artificial neural network (ANN). RESULTS: Postoperative cortisol and ACTH levels and their combinations cannot be used for prediction of recurrence. ANN for prediction of recurrence within 3 years after successful surgery was developed. Input variables are age, duration of the disease, MRI data on adenoma, morning postoperative levels of ACTH and cortisol, output variable is binary (recurrence/remission). Predictive value for remission is 93%, 95% CI [89%; 96%], and predictive value for recurrence is 85%, 95% CI [71%; 94%]. Web-calculator based on the model is developed and free for use. CONCLUSION: Effective method for prediction of recurrence and long-term remission within 3 years after successful endoscopic transsphenoidal adenomectomy is proposed.


Assuntos
Hipersecreção Hipofisária de ACTH/patologia , Hipersecreção Hipofisária de ACTH/cirurgia , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Procedimentos Neurocirúrgicos , Hipersecreção Hipofisária de ACTH/sangue , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
J Clin Endocrinol Metab ; 104(11): 5453-5461, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31361303

RESUMO

CONTEXT: GH activates agouti-related protein (AgRP) neurons, leading to orexigenic responses in mice. The relationship between serum GH and plasma AgRP, which has been shown to reflect hypothalamic AgRP, has not been evaluated in humans. OBJECTIVE: To test the hypothesis that central stimulatory actions of GH on hypothalamic AgRP could be reflected in plasma AgRP in acromegaly. METHODS: We studied 23 patients with active acromegaly before and for ≤2 years after surgical (n = 13) or GH receptor antagonist therapy with pegvisomant (n = 10), and 100 healthy subjects with morning fasting blood samples for AgRP, leptin, GH, and IGF-1 and anthropometric measurements. RESULTS: The plasma AgRP levels were higher in those with active acromegaly than in the matched healthy subjects [median, 100 pg/mL; interquartile range (IQR), 78 to 139 pg/mL vs median, 63 pg/mL; IQR, 58 to 67 pg/mL; P < 0.0001]. Plasma AgRP decreased from before to after surgery (median, 102 pg/mL; IQR, 82 to 124 pg/mL vs median, 63 pg/mL; IQR, 55.6 to 83 pg/mL; P = 0.0024) and from before to during pegvisomant therapy (median, 97 pg/mL; IQR, 77 to 175 pg/mL vs median, 63; IQR, 61 to 109 pg/mL; P = 0.006). The plasma AgRP level correlated with GH (r = 0.319; P = 0.011) and IGF-1 (r = 0.292; P = 0.002). In repeated measure analysis, AgRP was significantly associated with IGF-1. CONCLUSIONS: Our data have provided evidence of a stimulatory effect of GH on plasma AgRP in humans. The levels were greater in active acromegaly and decreased in parallel with GH and IGF-1 decreases with acromegaly treatment. Data from mice suggest that AgRP may mediate some of the known effects of GH on energy metabolism. This warrants further study in patients with acromegaly and other populations.


Assuntos
Acromegalia/sangue , Proteína Relacionada com Agouti/sangue , Antagonistas de Hormônios/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Receptores da Somatotropina/antagonistas & inibidores , Acromegalia/tratamento farmacológico , Acromegalia/cirurgia , Adenoma/sangue , Adenoma/tratamento farmacológico , Adenoma/cirurgia , Adulto , Feminino , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/cirurgia , Resultado do Tratamento , Adulto Jovem
15.
World Neurosurg ; 130: e765-e774, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31295602

RESUMO

OBJECTIVE: Plurihormonal pituitary adenomas (PPAs) have recently been divided into 2 subtypes: pituitary specific transcription factor 1-positive plurihormonal pituitary adenomas (PIT-1+ PPAs) and plurihormonal adenomas with unusual immunohistochemical combinations (PAwUIC). The purpose of this study was to review patients with PPAs, elucidate their clinicopathologic characteristics, and present the surgical results. METHODS: Records were analyzed for 665 patients who underwent endoscopic endonasal transsphenoidal surgery for pituitary adenomas between 2007 and 2018. Data were reviewed for 27 patients who met the definition of PPAs and delineated regarding clinical, radiologic, pathologic features, and surgical outcomes. RESULTS: Of the 27 patients, 18 had PAwUIC, and 9 patients were diagnosed with PIT-1+ PPAs. Twenty-four patients (88.8%) had macroadenomas, including 6 giant adenomas (≥4 cm) (22.2%). Cavernous sinus invasion was found in 12 patients (44.4%). Pathologic examinations showed high aggressivity in nearly half of the patients. Most patients with PAwUIC (77.8%) had features of nonfunctioning pituitary adenomas, and only 4 had features of hormone-secreting pituitary adenomas. Gross total resection rates were 57.1% for PAwUIC and 77.8% for PIT-1+ PPAs. The remission rate for hormone-secreting pituitary adenomas was 100% in this case series. Mean follow-up was 74.4 ± 33 months (range, 6-121 months) for overall groups. CONCLUSIONS: To our knowledge, this is the first study to describe the clinicopathologic features of newly classified PPAs, which are characterized by aggressive behavior with higher values of percentage of cavernous sinus invasion. Relevant pathologic diagnosis of PPAs is crucial for appropriate management and follow-up.


Assuntos
Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Adenoma/sangue , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Estudos Retrospectivos , Resultado do Tratamento
16.
Medicine (Baltimore) ; 98(26): e16148, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261542

RESUMO

Non-functioning pituitary adenomas (NFPAs) are the most common pituitary tumors, and some exhibit locally invasive or even clinically aggressive behavior. Circular RNAs (circRNAs) are a reinvented class of non-coding RNAs that play important roles in tumor initiation and progression.CircRNA microarray assays were performed in 4 invasive and 4 non-invasive NFPAs, and 4 typically differential expression circRNAs were selected for validation using quantitative reverse transcription-polymerase chain reaction. The diagnostic and prognostic values of tested cirRNAs were further evaluated. Bioinformatics analysis and a literature review of potential miRNAs targets involved in pituitary tumor invasion were performed.A specific circRNA expression profile was detected between invasive and non-invasive NFPAs, including 91 upregulated and 61 downregulated circRNAs in invasive tumors. The dysregulation of the 4 circRNAs has been confirmed. The expression of hsa_circRNA_102597, a downregulated circRNA, was significantly correlated with tumor diameter (P < .05) and Knosp grade (P < .01). Hsa_circRNA_102597 alone or in combined with Ki-67 index was able to accurately differentiate invasive from non-invasive NFPAs as well as predict tumor progression/recurrence. Fourteen aberrantly expressed circRNAs might be involved in the invasiveness of pituitary adenomas via seven predicted potential miRNA targets.CircRNAs are participated in pituitary tumor invasion, and may be used as novel diagnostic and prognostic biomarkers in NFPAs.


Assuntos
Adenoma/sangue , Invasividade Neoplásica/diagnóstico , Neoplasias Hipofisárias/sangue , RNA/sangue , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/sangue , Biologia Computacional , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , RNA Circular , Reação em Cadeia da Polimerase em Tempo Real
17.
World Neurosurg ; 129: e686-e694, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31181361

RESUMO

OBJECTIVE: First-line treatment for prolactin-producing pituitary adenomas is dopamine agonist (DA) therapy. This is the first study to analyze the rate of radiographic and hormonal regression of prolactinomas in response to DA therapy to better understand what time frame we consider DA treatment failure. METHODS: We searched the electronic medical records of 3 tertiary care medical institutions for patients with prolactinomas. The primary outcome was tumor volume and prolactin (PRL) levels at various time points. The secondary outcome was indicators of treatment failure. Modeling by both linear and exponential models was tested to determine potential predictors of response magnitude and treatment failure by multivariate and regression analyses respectively. RESULTS: There were 99 patients (53% male) included in this analysis. The mean patient age was 42.7 years ± 14.5, and mean width/volume of tumor at diagnosis was 12.3 mm and 1.3 cm3, respectively. The mean PRL level at diagnosis was 593.2 ng/mL (79-7913). Modeling indicated a plateau at 68.2% initial volume (95% confidence interval 61.7-73.5) by 12.6 months and a PRL plateau of 21.4 ng/mL (95% confidence interval 0-92.5) by 3.3 months. Multivariate analyses revealed male sex (odds ratio 0.168; P = 0.036) to be a predictor of faster PRL response to DA therapy. CONCLUSIONS: Prolactinomas plateau in PRL levels and the rate of size regression within the first year of DA treatment. Prolactinomas with lack of size regression and failure to reach normalization of PRL levels by 12 months may be considered for other management strategies.


Assuntos
Bromocriptina/uso terapêutico , Cabergolina/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactina/sangue , Prolactinoma/tratamento farmacológico , Adulto , Progressão da Doença , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Prolactinoma/sangue , Prolactinoma/diagnóstico por imagem , Prolactinoma/patologia , Fatores Sexuais , Falha de Tratamento , Carga Tumoral
19.
J Endocrinol Invest ; 42(12): 1401-1406, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31175617

RESUMO

Thyrotropin-secreting pituitary adenomas (TSH-omas) present with signs and symptoms of hyperthyroidism and they are characterized by elevated serum levels of free thyroid hormones with measurable TSH levels. TSH-omas are very infrequent, accounting for less than 1% of all pituitary adenomas, thus representing a very rare cause of hyperthyroidism. For this reason, data collected on these rare disorders are relatively few, but some new researches shed new light on the etiopathogenesis, the diagnosis and the treatment of such a remarkable disease. Since the same biochemical picture is present in the syndromes of thyroid hormone resistance (RTH), in particular in the form of pituitary RTH, failure in distinguishing these clinical entities may lead to improper patient management. Conversely, early diagnosis and correct treatment of TSH-omas may prevent the occurrence of neurological and endocrinological complications, thus leading to a better rate of cure. In the present short review article, the most relevant recent advances in the pathophysiology of TSH-omas are described.


Assuntos
Adenoma/sangue , Hipertireoidismo/sangue , Neoplasias Hipofisárias/sangue , Hormônios Tireóideos/sangue , Tireotropina/sangue , Adenoma/complicações , Adenoma/patologia , Humanos , Hipertireoidismo/etiologia , Hipertireoidismo/patologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/patologia
20.
J Med Case Rep ; 13(1): 183, 2019 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-31202268

RESUMO

BACKGROUND: Prolactinomas are tumors of the pituitary gland that usually respond very well to treatment with cabergoline. Resistance to cabergoline is very rare, but when it occurs, it is a difficult problem to resolve if the tumor is inoperable. CASE PRESENTATION: A 62-year-old white man was treated for a giant macroprolactinoma detected during investigation of a subacute subdural hematoma of the left frontal lobe. The patient was treated with cabergoline for 17 years with a dose ranging from 1.0 mg to 3.5 mg per week. We were not able to normalize his prolactin level, which initially was 14,992 ng/ml and ultimately 1754 ng/ml. The tumor significantly shrank during the follow-up period but persisted. The patient had cardiac valvulopathies that did not worsen. He had an ischemic stroke and developed a psychotic condition that was successfully treated by lowering the cabergoline and administering quetiapine and mirtazapine together. This regimen led to a small increase in the patient's prolactin that returned to previous levels and remained as such until the last medical evaluation. The tumor continued to shrink and had a cystic degeneration in the last evaluation. CONCLUSIONS: Combined use of cabergoline with quetiapine and mirtazapine to treat a psychotic crisis may have contributed to shrinking the tumor in our patient because these antipsychotics have action mediated by growth factors that interfere with growth of pituitary tumors.


Assuntos
Cabergolina , Mirtazapina/administração & dosagem , Neoplasias Hipofisárias , Prolactina/sangue , Prolactinoma , Transtornos Psicóticos , Fumarato de Quetiapina/administração & dosagem , Acidente Vascular Cerebral/complicações , Cabergolina/administração & dosagem , Cabergolina/efeitos adversos , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Prolactinoma/sangue , Prolactinoma/complicações , Prolactinoma/tratamento farmacológico , Prolactinoma/patologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/etiologia , Psicotrópicos/administração & dosagem , Acidente Vascular Cerebral/diagnóstico , Resultado do Tratamento , Carga Tumoral
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