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1.
Artigo em Inglês | MEDLINE | ID: mdl-32410303

RESUMO

OBJECTIVE: Comprehensive data about patients with bilateral pheochromocytoma are limited. We aimed to describe the clinical presentation, genetic analysis, treatment and outcomes of patients with bilateral pheochromocytoma. DESIGN: A retrospective study at a tertiary care centre. PATIENTS: All patients with bilateral pheochromocytoma evaluated at Mayo Clinic in Rochester, Minnesota between January 1951 and December 2015. MEASUREMENTS: Tumour size, genetic testing, plasma/urine metanephrines and catecholamines. RESULTS: A total of 94 patients (51% women) were diagnosed with bilateral pheochromocytoma at a median age at first presentation of 31 years (range, 4-70). Bilateral disease was noted in 8.0% of pheochromocytoma patient overall and 37.5% of patients 18 years of younger. Most patients presented with synchronous tumours (80%). Median time to metachronous tumours was 4.5 years (range, 1-38). Genetic disease was identified in 75 (80%) patients, including MEN 2A (42.6%), VHL (19.1%), MEN 2B (9.6%) and NF1 (8.5%). Excess catecholamines were present in 97% of patients. Patients with synchronous pheochromocytoma commonly underwent simultaneous bilateral adrenalectomy (99%), and 18 (24%) had cortical-sparing surgery. Multicentric tumours were reported in 23 of 77 (30%) patients with available data. Recurrent disease was found in 9.6% of patients, and 8.5% developed metastatic disease. Median follow-up was 8.5 years. At the study conclusion, 4 patients had died due to pheochromocytoma or adrenalectomy. CONCLUSIONS: Bilateral pheochromocytoma occurred in 7.0% of adults with pheochromocytoma and 37.5% of paediatric patients. Genetic disease was identified in 80% of patients, predominantly MEN2A. Multicentric tumours were common, but most were still cured following adrenalectomy.

2.
Neurosurgery ; 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32267504

RESUMO

BACKGROUND: Stereotactic radiosurgery (SRS) is a safe and effective treatment for acromegaly. OBJECTIVE: To improve understanding of clinical and dosimetric factors predicting biochemical remission. METHODS: A single-institution cohort study of nonsyndromic, radiation-naïve patients with growth hormone-producing pituitary adenomas (GHA) having single-fraction SRS between 1990 and 2017. Exclusions were treatment with pituitary suppressive medications at the time of SRS, or <24 mo of follow-up. The primary outcome was biochemical remission-defined as normalization of insulin-like growth factor-1 index (IGF-1i) off suppression. Biochemical remission was assessed using Cox proportional hazards. Prior studies reporting IGF-1i were assessed via systematic literature review and meta-analysis using random-effect modeling. RESULTS: A total of 102 patients met study criteria. Of these, 46 patients (45%) were female. The median age was 49 yr (interquartile range [IQR] = 37-59), and the median follow-up was 63 mo (IQR = 29-100). The median pre-SRS IGF-1i was 1.66 (IQR = 1.37-3.22). The median margin dose was 25 Gy (IQR = 21-25); the median estimated biologically effective dose (BED) was 169.49 Gy (IQR = 124.95-196.00). Biochemical remission was achieved in 58 patients (57%), whereas 22 patients (22%) had medication-controlled disease. Pre-SRS IGF-1i ≥ 2.25 was the strongest predictor of treatment failure, with an unadjusted hazard ratio (HR) of 0.51 (95% CI = 0.26-0.91, P = .02). Number of isocenters, margin dose, and BED predicted remission on univariate analysis, but after adjusting for sex and baseline IGF-1i, only BED remained significant-and was independently associated with outcome in continuous (HR = 1.01, 95% CI = 1.00-1.01, P = .02) and binary models (HR = 2.27, 95% CI = 1.39-5.22, P = .002). A total of 24 patients (29%) developed new post-SRS hypopituitarism. Pooled HR for biochemical remission given subthreshold IGF-1i was 2.25 (95% CI = 1.33-3.16, P < .0001). CONCLUSION: IGF-1i is a reliable predictor of biochemical remission after SRS. BED appears to predict biochemical outcome more reliably than radiation dose, but confirmatory study is needed.

3.
Endocr Pract ; 25(4): 340-352, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30995432

RESUMO

Objective: To describe outcomes of patients with giant prolactinoma (≥4 cm) and identify predictors of therapeutic response. Methods: In this retrospective study, complete biochemical and structural response were defined as prolactin (PRL) ≤25 ng/mL and no visible tumor at follow-up, respectively. Results: Giant prolactinoma (median size, 4.8 cm [range, 4 to 9.8 cm]; median PRL, 5,927 ng/mL [range, 120 to 100,000 ng/mL]) was diagnosed in 71 patients. Treatments included: dopamine agonists (DAs) (n = 70, 99%), surgery (n = 30, 42%), radiation (n = 10, 14%), and somatostatin analogs (n = 2, 3%). Patients treated with DA monotherapy were older compared with those who received subsequent therapies (47 years vs. 28 years; P = .003) but had similar initial PRL and tumor size. Surgically managed patients were younger compared with the nonsurgical group (35 years vs. 46 years; P = .02) and had lower initial PRL (3,121 ng/mL vs. 6,920 ng/mL; P = .02), yet they had similar tumor response. Hypopituitarism was more common following surgery compared to medical management: adrenal insufficiency (69% vs. 27%; P<.001), hypothyroidism (67% vs. 38%; P = .02), growth hormone deficiency (24% vs. 6%; P = .04), and diabetes insipidus (17% vs. 3%; P = .04). Therapeutic response did not correlate with sex, age, initial PRL, tumor size, or first-line therapy mode. At median follow-up of 4.8 years, the median PRL was 18.3 ng/mL (range, 0.6 to 12,680 ng/mL), and final volume was 0.9 cm3 (range, 0 to 43.0 cm3). In those with available data, 36/65 (55%) patients achieved PRL normalization, and 16/61 (26%) had no visible tumor at follow-up. Conclusion: Most patients with giant prolactinoma have excellent response to DA. Sex, age, initial PRL, and tumor size do not predict therapeutic response. Abbreviations: BRC = bromocriptine; CAB = cabergoline; CSF = cerebrospinal fluid; DA = dopamine agonist; MRI = magnetic resonance imaging; PRL = prolactin.


Assuntos
Neoplasias Hipofisárias , Prolactinoma , Adulto , Bromocriptina , Agonistas de Dopamina , Ergolinas , Humanos , Pessoa de Meia-Idade , Prolactina , Estudos Retrospectivos
4.
Clin Chem ; 64(11): 1636-1645, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30068692

RESUMO

BACKGROUND: Previously defined thresholds for total testosterone (TT) concentrations to screen for androgen-producing tumors (APTs) have used RIA, which can be less accurate in women. We aimed to define diagnostic thresholds to screen for APTs or postmenopausal pathologic hyperandrogenism using TT concentrations measured by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). METHODS: We performed a retrospective cohort study on all women with TT ≥3.5 nmol/L and all postmenopausal women presenting with hyperandrogenism between 2004 and 2014 at the Mayo Clinic in Rochester, MN. RESULTS: Of the 369 women with TT ≥3.5 nmol/L, 89 were included and subdivided into 3 groups based on their clinical diagnosis [21 (24%), APT; 16 (18%), postmenopausal pathologic hyperandrogenism; 52 (58%), polycystic ovary syndrome]. The source of the APT was more frequently ovarian (81%, n = 17) than adrenal (19%, n = 4). The diagnostic threshold using ROC analysis for TT to identify APT in women with severe biochemical hyperandrogenemia was ≥5.1 nmol/L (sensitivity, 90%; specificity, 81%). In a second analysis of a cohort of postmenopausal women only presenting with symptoms or signs of hyperandrogenism, median TT was significantly higher in the postmenopausal pathologic hyperandrogenism group (APT and ovarian hyperthecosis) vs the idiopathic hyperandrogenism group (4.9 vs 0.8 nmol/L; P < 0.01). In postmenopausal women, the diagnostic threshold for pathologic hyperandrogenism was TT ≥2.2 nmol/L (sensitivity, 100%; specificity, 86%). CONCLUSIONS: The diagnostic threshold for TT concentration as measured by LC-MS/MS to identify APT in women with biochemical severe hyperandrogenemia was TT ≥5.1 nmol/L. In postmenopausal women, the diagnostic threshold for pathologic hyperandrogenism was lower (TT ≥2.2 nmol/L).


Assuntos
Hiperandrogenismo/sangue , Neoplasias Ovarianas/sangue , Síndrome do Ovário Policístico/sangue , Pós-Menopausa/sangue , Testosterona/sangue , Cromatografia Líquida , Estudos de Coortes , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hiperandrogenismo/diagnóstico por imagem , Hormônio Luteinizante/sangue , Neoplasias Ovarianas/diagnóstico por imagem , Ovariectomia , Síndrome do Ovário Policístico/diagnóstico por imagem , Estudos Retrospectivos , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem
5.
J Clin Endocrinol Metab ; 103(12): 4419-4427, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30032193

RESUMO

Context: Testosterone (T) increases GH secretion in older men with a relative lack of T, in hypogonadal men of all ages, and in patients undergoing sex reassignment. The role of estradiol (E2) in men is less well defined. Objective: To assess the contribution of aromatization of T to spontaneous nocturnal and stimulated GH secretion. Participants: Four groups of healthy older men (N = 74, age range 57 to 77 years) were studied. The gonadotropic axis was clamped with the gonadotropin-releasing hormone antagonist degarelix. Three groups received T and one group placebo addback. Two T-replaced groups were treated with anastrozole (an aromatase inhibitor) and either placebo or E2 addback. Main Outcome Measures: Ten-minute GH concentration profiles were quantified by deconvolution analysis, after overnight (2200 to 0800 hours) sampling, and after combined IV injection of GHRH (0.3 µg/kg) and GHRH-2 (0.3 µg/kg) and withdrawal of a 2-hour somatostatin infusion (1 µg/kg/h). Results: E2 addback during aromatase inhibition increased basal (P = 0.046), pulsatile (P = 0.020), and total (P = 0.018) GH secretion by 60% to 70%. E2 did not potentiate GH secretory stimuli. Logarithmically transformed pulsatile GH secretion correlated strongly and positively with concurrent E2 concentrations overall (P = 0.028) and under anastrozole treatment (P = 0.005). Conclusion: E2 administration in older men transdermally stimulates overnight pulsatile GH secretion. The exact site of E2 action cannot be ascertained from these experiments but may include hypothalamic loci involved in GH regulation, especially because GH secretagogue effects on somatotrope pituitary cells were not affected.


Assuntos
Envelhecimento/metabolismo , Estradiol/administração & dosagem , Hormônio do Crescimento Humano/metabolismo , Hipogonadismo/tratamento farmacológico , Testosterona/administração & dosagem , Administração Cutânea , Adulto , Idoso , Envelhecimento/efeitos dos fármacos , Anastrozol/administração & dosagem , Aromatase/metabolismo , Inibidores da Aromatase/administração & dosagem , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Hormônio Liberador de Hormônio do Crescimento/administração & dosagem , Voluntários Saudáveis , Hormônio do Crescimento Humano/sangue , Humanos , Hipogonadismo/induzido quimicamente , Hipogonadismo/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , Placebos/administração & dosagem , Testosterona/metabolismo
6.
Endocr Pract ; 24(7): 668-676, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30048170

RESUMO

OBJECTIVE: Uncontrolled acromegaly is associated with increased morbidity and mortality. Despite multimodal therapeutic options, adequate control can be challenging and lead to prolonged exposure to growth hormone excess. The aim of this study was to assess treatment patterns and outcomes in patients with acromegaly following surgery at a single institution. METHODS: A retrospective analysis of response to treatment modalities for patients with a new diagnosis of acromegaly at the Mayo Clinic in Rochester, Minnesota, from 1995-2015. RESULTS: A total of 245 patients with newly diagnosed acromegaly (mean age at diagnosis, 47 ± 14 years; mean follow-up, 5.5 ± 5 years) were evaluated. Primary surgical intervention was performed in 236 patients; 117 (54%) did not achieve remission. Among those with ≥3 months follow-up, 76/217 (35%) patients required three or more forms of treatment. Mean tumor size at diagnosis was 1.6 ± 0.8 cm (80% macroadenomas), and 35% (75/217) had cavernous sinus invasion on pre-operative imaging. The most common second-line treatment was radiation treatment (RT) (50%, 59/117). Among those with persistent disease following surgery, a normal insulin-like growth factor 1 (IGF-1) was achieved in 52% (61/117), with a median time to acromegaly control of 4.5 years. The rate of IGF-1 normalization was 2.1-fold higher in those who received RT compared to those who did not. CONCLUSION: In patients with persistent acromegaly following surgery, multiple treatment modalities, including RT, may be required to achieve remission. Treatment outcome uncertainty and the need for multiple interventions add to the disease burden associated with persistent acromegaly. ABBREVIATIONS: CI = confidence interval; GH = growth hormone; IGF-1 = insulin like growth factor-1; KM = Kaplan-Meier; RT = radiation treatment.


Assuntos
Acromegalia , Adulto , Terapia Combinada , Hormônio do Crescimento Humano , Humanos , Fator de Crescimento Insulin-Like I , Pessoa de Meia-Idade , Minnesota , Estudos Retrospectivos , Resultado do Tratamento
7.
World Neurosurg ; 116: e733-e737, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29800686

RESUMO

INTRODUCTION: No study has volumetrically examined resection degree and recurrence in pituitary macroadenoma (PMA). We analyzed the impact of volumetric tumor resection on prediction of tumor recurrence and retreatment in a cohort of patients with nonfunctioning PMA ≥2 cm. METHODS: Records were reviewed from 1998-2008 for patients with null cell or nonsecreting PMA ≥2 cm. Inclusion criteria were surgically resected PMA and ≥4 years' follow-up or recurrence before 4 years. Seventy-eight patients were found. PMA tissue volume preoperatively and postoperatively was quantified by a board-certified neuroradiologist. Extent of resection (EOR) was calculated. The primary end point was tumor recurrence with a secondary end point of treated tumor recurrence. RESULT: Median age was 58 (20-85). Forty-one (53%) had no tumor recurrence at a median of 113 (48-203) months. Thirty-seven (47%) patients had tumor recurrence with a median time of 55 (9-176) months. On univariate analysis, increasing age, decreasing preoperative and postoperative volumes, and increasing EOR were statistically significant for decreasing the risk of recurrence or treated recurrence. On multivariate analysis, only age and EOR remained significant. Receiver operating characteristic showed EOR <86% was associated with PMA regrowth. Kaplan-Meier analysis demonstrated a statistically significant difference for recurrence comparing groups by EOR ≥86% or <85%. CONCLUSIONS: We found younger age and increasing EOR are significant predictors of tumor regrowth and retreatment. These results indicate EOR assessment may have a role in large PMA. Further study with volumetric analysis is needed in a larger cohort of patients.


Assuntos
Adenoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias Hipofisárias/cirurgia , Adenoma/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasia Residual , Neoplasias Hipofisárias/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
J Endocr Soc ; 2(2): 154-165, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29383334

RESUMO

Context: Estrogens amplify spontaneous and stimulated growth hormone (GH) secretion, whereas they diminish GH-dependent insulin-like growth factor (IGF)-I in a dose-dependent manner. Selective estrogen receptor modulators (SERMs), including tamoxifen and toremifene, are widely adjunctively used in breast and prostate cancer. Although some endocrine effects of tamoxifen are known, few data are available for toremifene. Objective: To explore sex-dependent effects of toremifene on spontaneous 10-hour overnight GH secretion, followed by GH-releasing hormone-ghrelin stimulation. Additionally, effects on IGF-I, its binding proteins, and sex hormone-binding globulin (SHBG) were quantified. Participants and Design: Twenty men and 20 women, within an allowable age range of 50 to 80 years, volunteered for this double-blind, placebo-controlled prospective crossover study. Ten-minute blood sampling was done for 10 hours overnight and then for 2 hours after combined GH-releasing hormone-ghrelin injection. Main Outcome Measures: Pulsatile GH and stimulated GH secretion, and fasting levels of IGF-I, IGF-binding protein (IGFBP)1, IGFBP3, and SHBG. Results: Toremifene did not enhance pulsatile or stimulated GH secretion, but decreased IGF-I by 20% in men and women. IGFBP3 was unchanged, whereas while IGFBP1 and SHBG increased in both sexes to a similar extent. Conclusions: The expected rise in spontaneous and stimulated GH secretion under the diminished negative feedback restraint of powered IGF-I favors a central inhibitory antiestrogenic effect of toremifene. Estrogenic effects of toremifene on the liver were present, as evidenced by increased IGFBP1 and SHBG levels. Men and women responded to this SERM comparably.

9.
Clin Endocrinol (Oxf) ; 88(1): 30-36, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28815667

RESUMO

OBJECTIVE: Evidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and 18 F-fluorodeoxyglucose (18 FDG) positron emission tomography (PET)/CT imaging in a high-risk population for adrenal malignancy using an optimal reference standard. DESIGN: Retrospective cohort study. METHODS: Imaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra-adrenal malignancy. RESULTS: Unenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7-15) cm and median radiodensity was 33 (-21-78) Hounsfield units (HU). Radiodensity of >10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 100%. 18 FDG-PET/CT was performed in 89 patients; median tumour size was 2.1 (0.7-9.2) cm. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median=10 [2.3-29.4] vs 3.7 [1.4-24.5], respectively, P<.0001). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median=3 [0.74-13.4] vs 1.2 [0.5-6.6], respectively, P<.0001). 18 FDG-PET/CT ALR >1.8 diagnosed malignancy with a sensitivity of 87%, specificity of 84%, PPV of 85% and NPV of 86%. CONCLUSION: Noncontract CT radiodensity of ≤10 HU excludes malignancy even in a high-risk population. For indeterminate adrenal lesions, given a superior specificity, 18 FDG-PET/CT could be considered as a second stage imaging study.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/normas , Tomografia Computadorizada por Raios X/normas , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
10.
Endocr Pract ; 23(12): 1402-1407, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29144794

RESUMO

OBJECTIVE: While the left adrenal gland is readily accessible via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), data regarding the utility of EUS-FNA in the diagnosis of adrenal lesions remain limited. We aimed to ( 1) describe the clinical context, adverse event rate, and diagnostic performance of EUS-FNA, and ( 2) compare the safety profile and diagnostic accuracy of EUS-FNA with percutaneous adrenal biopsy. METHODS: Single-center, retrospective cohort study. Medical records of patients who underwent adrenal EUS-FNA from 2005-2016 were reviewed. Biopsy outcomes were evaluated using a predefined reference standard. Results were compared to patients who underwent percutaneous biopsy (n = 419; 1994-2014) at the same institution. RESULTS: A total of 121 patients underwent EUS-FNA of 122 adrenal lesions (left [n = 121]; right [n = 1]; mean lesion size, 1.8 cm). Cytology was positive for malignancy in 35 (29%), suspicious for malignancy in 1 (1%), atypical in 1 (1%), negative for malignancy in 81 (66%), and nondiagnostic in 4 (3%). No adverse events were reported. EUS-FNA diagnosed metastasis with a sensitivity of 100%, specificity of 97.4%, positive predictive value of 91.7%, and negative predictive value of 100%. When compared to percutaneous biopsy, lesion size (1.8 cm vs. 3.7 cm; P<.001) and biopsy site (99% vs. 62% left adrenal; P<.001) were significantly different. EUS-FNA adverse event rate was lower than percutaneous biopsy (0% vs. 4%; P = .024), but nondiagnostic rates were similar (3.3% vs. 4.8%; P = .48). CONCLUSION: EUS-FNA is a sensitive technique to sample adrenal lesions in patients at high risk for adrenal metastasis with fewer adverse events compared to percutaneous biopsy. ABBREVIATIONS: CI = confidence interval CT = computed tomography EUS-FNA = endoscopic ultrasound-guided fine-needle aspiration NPV = negative predictive value PPV = positive predictive value TUS = transabdominal ultra-sound.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/secundário , Glândulas Suprarrenais/patologia , Citodiagnóstico/métodos , Ultrassonografia de Intervenção , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/efeitos adversos , Biópsia por Agulha Fina/métodos , Citodiagnóstico/efeitos adversos , Feminino , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Ultrassonografia de Intervenção/efeitos adversos
11.
J Clin Endocrinol Metab ; 102(7): 2611-2619, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28368521

RESUMO

Background: Adrenocorticotropic hormone (ACTH) secretion is controlled by unobservable hypothalamic corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) pulses. Clamping exogenous CRH or AVP input could allow indirect quantification of the impact of the endogenous heterotypic hormone. Methods: We conducted a randomized, double-blind, placebo-controlled, crossover study in 28 healthy adults (16 men). Volunteers underwent a sex-steroid clamp and a cortisol clamp. ACTH was measured over 10 hours by 10-minute sampling during each of four randomized intravenous (IV) secretagogue clamps (i.e., continuous IV CRH, AVP, both peptides, or saline). Desensitization was tested by bolus injection of the noninfused peptide. Results: Mean ± standard error of the mean 10-hour ACTH concentrations (ng/L) in the sex-combined analysis were: saline, 32 ± 4.6; AVP, 29 ± 4.6; CRH, 67 ± 6.2; and CRH-AVP, 67 ± 8.8 (any CRH vs AVP or saline, P < 0.0001). CRH and AVP increased approximate entropy (relative randomness) of ACTH release (P < 0.0001). Bolus AVP injection after CRH infusion yielded a 2.5-hour ACTH concentration of 46 ± 4.3, exceeding that seen after bolus CRH or saline injection (26 ± 3.3 and 24 ± 3.6, respectively; P = 0.002 and 0.001). Sex hormone clamps did not influence ACTH levels. Conclusions: A CRH, but not AVP, clamp yields sustained pulsatile ACTH secretion with high ACTH secretory-burst mass and randomness. After 10-hour CRH infusion, bolus AVP but not CRH, evoked marked ACTH release, likely caused by heterotypic sensitization of corticotropes by CRH. Similar interactions might underlie chronic stress states.


Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Arginina Vasopressina/administração & dosagem , Hormônio Liberador da Corticotropina/administração & dosagem , Leuprolida/administração & dosagem , Hormônio Adrenocorticotrópico/sangue , Idoso , Constrição , Estudos Cross-Over , Método Duplo-Cego , Feminino , Seguimentos , Hormônios Esteroides Gonadais/metabolismo , Humanos , Hidrocortisona/sangue , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores de Tempo
13.
J Neurosurg ; 127(6): 1277-1287, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28084914

RESUMO

OBJECTIVE Nelson-Salassa syndrome (NSS) is a rare consequence of bilateral adrenalectomy (ADX) for refractory hypercortisolism due to Cushing disease (CD). Although classically defined by rapid growth of a large, invasive, adrenocorticotropin hormone (ACTH)-secreting pituitary tumor after bilateral ADX that causes cutaneous hyperpigmentation, visual disturbance, and high levels of ACTH, clinical experience suggests more variability. METHODS The authors conducted a retrospective chart review of all patients 18 years and older with a history of bilateral ADX for CD, adequate pituitary MRI, and at least 2 years of clinical follow-up. Statistical tests included Student's t-test, chi-square test, Fisher's exact test, multivariate analysis, and derived receiver operating characteristic curves. RESULTS Between 1956 and 2015, 302 patients underwent bilateral ADX for the treatment of hypercortisolism caused by CD; 88 had requisite imaging and follow-up (mean 16 years). Forty-seven patients (53%) had radiographic progression of pituitary disease and were diagnosed with NSS. Compared with patients who did not experience progression, those who developed NSS were significantly younger at the time of CD diagnosis (33 vs 44 years, p = 0.007) and at the time of bilateral ADX (35 vs 49 years, p = 0.007), had larger tumors at the time of CD diagnosis (6 mm vs 1 mm, p = 0.03), and were more likely to have undergone external-beam radiation therapy (EBRT, 43% vs 12%, p = 0.005). Among NSS patients, the mean tumor growth was 7 mm/yr (SE 6 mm/yr); the median tumor growth was 3 mm/yr. Prevalence of pathognomonic symptoms was low; the classic triad occurred in 9%, while hyperpigmentation without visual field deficit was observed in 23%, and 68% remained asymptomatic despite radiographic disease progression. NSS required treatment in 14 patients (30%). CONCLUSIONS NSS is a prevalent sequela of CD after bilateral ADX and affects more than 50% of patients. However, although radiological evidence of NSS is common, it is most often clinically indolent, with only a small minority of patients developing the more aggressive disease phenotype characterized by clinically meaningful symptoms and indications for treatment. Young age at the time of CD diagnosis or treatment with bilateral ADX, large tumor size at CD diagnosis, and EBRT are associated with progression to NSS and may be markers of aggressiveness.


Assuntos
Adrenalectomia/efeitos adversos , Síndrome de Nelson/diagnóstico , Adolescente , Adulto , Idoso , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Síndrome de Nelson/diagnóstico por imagem , Síndrome de Nelson/etiologia , Hipersecreção Hipofisária de ACTH/cirurgia , Estudos Retrospectivos , Adulto Jovem
14.
Clin Endocrinol (Oxf) ; 86(1): 141-149, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27460956

RESUMO

OBJECTIVE: Individuals with neurofibromatosis type 1 (NF1) are at an increased risk of developing a pheochromocytoma or paraganglioma (PHEO/PGL). However, the best case detection strategy is unknown. Our objectives were to describe the prevalence, clinical presentation and outcomes of PHEO/PGL associated with NF1 and formulate case detection testing recommendations for PHEO/PGL. DESIGN: A retrospective cohort study from 1959 to 2015, Tertiary medical centre. PATIENTS AND MEASUREMENTS: We studied 41 patients with NF1 and PHEO/PGL who were identified using the PHEO/PGL and NF1 databases: 3289 and 1415 patients, respectively. Our main outcome measures were prevalence of PHEO/PGL in NF1 and occurrence of bilateral, recurrent, or metastatic disease and method of PHEO/PGL detection (symptoms vs incidental vs biochemical case detection testing). RESULTS: The prevalence of PHEO/PGL in patients with NF1 was 2·9%. The 41 patients included 23 men (56%) and 18 women. The median age at diagnosis was 41·0 years (range 14-67). The median tumour size was 3·4 cm (range 0·8-9·5). Bilateral PHEO was identified in 17% (n = 7) of patients, all women. Metastatic or recurrent disease occurred in 7·3% (n = 3). In the last 25 years, PHEO/PGL was diagnosed after incidental finding on computed imaging in 31% of patients (n = 11). Only three patients (7·3%) had PHEO/PGL discovered because of biochemical case detection testing. CONCLUSION: We recommend patients with NF1 have biochemical case detection testing for PHEO/PGL every 3 years starting at age 10 to 14 years. Biochemical case detection testing should also be carried out prior to elective surgical procedures and conception.


Assuntos
Neurofibromatose 1/complicações , Paraganglioma/etiologia , Feocromocitoma/etiologia , Adolescente , Adrenalectomia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Paraganglioma/epidemiologia , Feocromocitoma/epidemiologia , Feocromocitoma/cirurgia , Prevalência , Estudos Retrospectivos , Adulto Jovem
15.
Endocr Pract ; 23(1): 37-45, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27682355

RESUMO

OBJECTIVE: Prolactinomas are primarily treated with medical therapy. Given the efficacy of dopamine agonists (DAs), surgery has remained a second-line treatment option. Despite medical therapy, some tumors display resistance and/or patients maybe intolerant of DA and require alternative treatment options. We examined the indications, efficacy, and safety of pituitary surgery for the treatment of prolactinomas. METHODS: We performed a retrospective analysis of all patients who had surgery for a prolactinoma at our institution from January 1993 to October 2014. RESULTS: Seventy-eight patients (46 females, mean age 32 years) with a median follow-up of 12 months were analyzed. Macroprolactinomas accounted for 65% (51/78) of tumors. The most common indication for surgery in microprolactinomas was medication intolerance (37%, 10/27) and medication failure (33%, 17/51) in macroprolactinomas. DA therapy had been tried in 76% (59/78) patients prior to surgery. Following surgery, long-term remission was seen in 72% (18/25) of micro-adenomas and 20% (10/49) of macro-adenomas (32% [10/32] in those without cavernous sinus invasion). Despite persistent disease in those with macro-adenomas (34% [13/38]) were able to remain off medication. Early surgical failure was more common in males (P = .004) and those with large (P≤.001) or atypical (P = .003) adenomas. CONCLUSION: Surgery can result in prolonged remission in 72% of microprolactinomas. Despite lower remission rates among macroprolactinomas, a third of patients with persistent disease did not require medical therapy. Therefore, surgery remains an alternative effective treatment option, particularly for those who are intolerant or resistant to medical therapy. ABBREVIATIONS: ACTH = adrenocorticotropic hormone CI = confidence interval CSF = cerebrospinal fluid DA = dopamine agonist IQR = interquartile range MIB-1 = methylation inhibiting binding protein-1 VF = visual field.


Assuntos
Procedimentos Neurocirúrgicos , Neoplasias Hipofisárias/cirurgia , Prolactinoma/cirurgia , Adulto , Bromocriptina/uso terapêutico , Cabergolina , Agonistas de Dopamina/uso terapêutico , Ergolinas/uso terapêutico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Prolactinoma/diagnóstico por imagem , Prolactinoma/tratamento farmacológico , Prolactinoma/patologia , Indução de Remissão , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
16.
Endocr Pract ; 23(1): 17-31, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27631672

RESUMO

OBJECTIVE: Various glucocorticoid (GC) regimens have been used in the treatment of patients with adrenal insufficiency, yet the differences between such regimens on health outcomes are unclear. We performed a systematic review and meta-analysis to compare the effects of GC regimens on quality of life (QoL), bone density, incidence of adrenal crisis, and death. In pediatric studies, we also searched for final adult height. METHODS: We searched 6 databases through July 2016. Studies were selected and appraised by independent reviewers. Data were pooled using the profile likelihood random-effects model. RESULTS: We included 34 studies. We found no difference in QoL scores between higher (≥30 mg/day of hydrocortisone [HC] equivalence) vs. lower daily doses (<30 mg/day of HC equivalence) (P = .15) or based on frequency of daily dosing (once, twice or thrice daily). Extended-release (1 study), dual-/modified-release (3 studies), and continuous subcutaneous (3 studies) forms of GCs were associated with higher QoL scores. There was no significant association between dose and type of GC and the incidence of adrenal crises. The effect on bone mineral density was heterogeneous. No data were available on mortality or final adult height in children. The quality of evidence was low due to increased risk of bias, imprecision, and heterogeneity. CONCLUSION: Extended-/dual-release, and continuous subcutaneous forms of GC may be associated with higher QoL scores. However, this is derived from short-term and imprecise evidence, warranting low confidence. ABBREVIATIONS: AI = adrenal insufficiency BMD = bone mineral density GC = glucocorticoids HC = hydrocortisone QoL = quality of life RCT = randomized controlled trial.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Glucocorticoides/administração & dosagem , Terapia de Reposição Hormonal/métodos , Hidrocortisona/administração & dosagem , Administração Oral , Adulto , Estatura , Densidade Óssea , Criança , Doença Crônica , Preparações de Ação Retardada , Glucocorticoides/uso terapêutico , Humanos , Hidrocortisona/uso terapêutico , Infusões Subcutâneas , Mortalidade , Qualidade de Vida , Resultado do Tratamento
17.
Endocr Pract ; 23(2): 132-140, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27819767

RESUMO

OBJECTIVE: Image-guided thermal ablation of adrenal metastases has been increasingly used for local tumor control. This procedure has been associated with hypertensive urgency; however, endocrine complications have not been clearly described. Our objective was to assess the hemodynamic behavior and risk for adrenal insufficiency related to adrenal ablation. Additionally, we sought to understand the utility of preprocedural α-blockade to prevent periprocedural hemodynamic complications. METHODS: This was a retrospective study of patients undergoing image-guided ablation of adrenal metastases between 2003 and 2015 at our institution. We reviewed electronic medical records to obtain clinical information, including α-blockade preparation, periprocedural hemodynamic parameters, interventions, and postablation adrenal function. RESULTS: Thermal ablation was performed in 58 patients (46 men [79%]; median age, 66 years) with 60 adrenal metastases ablated in 62 sessions. Alpha-blockade was used pre-ablation in 49 (79%) sessions; it was associated with less hypertensive urgency (23 [47%] for α-blockade vs. 10 [77%] for no α-blockade; P = .048) but higher need for vasopressors (22 [45%] for α-blockade vs. 1 [8%] for no α-blockade; P = .02) during ablation. Adrenal insufficiency occurred in 13 (22%) patients, of whom 10 had history of contralateral adrenalectomy or metastases, and only 3 of 13 had a normal-appearing contralateral adrenal gland. CONCLUSION: Hemodynamic changes during ablation of adrenal metastases are common. Pre-ablation α-blockade decreases the severity of the hypertensive episode, at the expense of higher need for vasopressors periprocedurally. Adrenal function should be assessed after adrenal metastasis ablation, as adrenal insufficiency may occur after such treatment. ABBREVIATIONS: ACTH = adrenocorticotropic hormone BP = blood pressure CT = computed tomography DBP = diastolic blood pressure HR = heart rate IQR = interquartile range IV = intravenous MAP = mean arterial pressure MWA = microwave ablation RFA = radiofrequency ablation SBP = systolic blood pressure.


Assuntos
Neoplasias das Glândulas Suprarrenais/secundário , Neoplasias das Glândulas Suprarrenais/cirurgia , Cirurgia Assistida por Computador/métodos , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Insuficiência Adrenal/epidemiologia , Insuficiência Adrenal/etiologia , Adrenalectomia , Antagonistas Adrenérgicos alfa/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Criocirurgia/métodos , Feminino , Hemodinâmica , Humanos , Hipotensão/etiologia , Hipotensão/prevenção & controle , Complicações Intraoperatórias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Vasoconstritores/uso terapêutico
18.
Eur J Endocrinol ; 175(6): R283-R295, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27450696

RESUMO

OBJECTIVE: Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with subclinical Cushing's syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: (i) determine the effect of adrenalectomy compared with conservative management on cardiovascular risk factors in patients with SCS and (ii) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS vs those with a nonfunctioning (NF) adrenal tumor. METHODS: MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trial were searched on 17 November 2015. Reviewers extracted data and assessed methodological quality in duplicate. RESULTS: We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared with conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI: 4.3-27.8) and diabetes mellitus (RR 3.9, 95% CI: 1.5-9.9), but not dyslipidemia (RR 2.6, 95% CI: 0.97-7.2) or obesity (RR 3.4, 95% CI: 0.95-12). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients); however, insufficient data exist for comparison to patients with SCS. CONCLUSIONS: Available low-to-moderate-quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and compared with conservative management.


Assuntos
Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/tendências , Doenças Cardiovasculares/epidemiologia , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/cirurgia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Síndrome de Cushing/diagnóstico , Seguimentos , Humanos , Fatores de Risco
19.
J Clin Endocrinol Metab ; 101(11): 4298-4304, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27459535

RESUMO

BACKGROUND: Systemic concentrations of T, estradiol (E2), GH, IGF-1, and IGF binding protein-3 decline in healthy aging individuals. Conversely, T and E2 stimulate GH and IGF-1 production in hypogonadal patients. HYPOTHESIS: Because E2 stimulates GH secretion, putatively via the nuclear estrogen receptor-α and E2 and GH fall with menopause, we postulated that diminished endogenous E2 contributes to low GH output in older women. LOCATION: The study was conducted at the Mayo Center for Clinical and Translational Science. STUDY DESIGN: This was a randomized, double-blind, controlled study in 60 healthy postmenopausal women treated with the following: 1) double placebo; 2) anastrozole, a potent inhibitor of aromatase-enzyme activity, which mediates E2 synthesis from T; and/or 3) fulvestrant, a selective estrogen receptor-α antagonist. METHODS: GH pulse generation was quantified by frequent GH sampling before and after short-term iv somatostatin infusion, thought to induce hypothalamic GHRH-mediated rebound-like GH secretion. RESULTS: On anastrozole, E2 fell from 3.1 ± 0.35 pg/mL to 0.36 ± 0.04 pg/mL, and estrone from 13 ± 1.4 pg/mL to 1.9 ± 0.01 pg/mL (P < .001) by mass spectrometry. Estrogen values were unchanged by fulvestrant. T concentrations did not change. One-hour peak GH rebound after somatostatin infusion declined markedly during both estrogen-deprivation schedules (P < .001). Mean (150 min) maximal GH rebound decreased comparably (P < .001). Measures of GH rebound correlated negatively with computed tomography-estimated abdominal visceral fat (all P < .05). CONCLUSION: These data suggest a previously unrecognized dependence of hypothalamo-pituitary GH regulation on low levels of endogenous estrogen after menopause.


Assuntos
Inibidores da Aromatase/farmacologia , Estradiol/análogos & derivados , Estradiol/metabolismo , Antagonistas do Receptor de Estrogênio/farmacologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Hormônio do Crescimento Humano/metabolismo , Nitrilos/farmacologia , Pós-Menopausa/sangue , Somatostatina/farmacologia , Triazóis/farmacologia , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Inibidores da Aromatase/administração & dosagem , Método Duplo-Cego , Estradiol/administração & dosagem , Estradiol/farmacologia , Antagonistas do Receptor de Estrogênio/administração & dosagem , Feminino , Fulvestranto , Humanos , Pessoa de Meia-Idade , Nitrilos/administração & dosagem , Somatostatina/administração & dosagem , Triazóis/administração & dosagem
20.
Clin Endocrinol (Oxf) ; 85(5): 710-716, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27248805

RESUMO

OBJECTIVE: The role of percutaneous adrenal biopsy in a high-risk population for adrenal malignancy has not been fully investigated. Our aim was to describe the clinical presentation leading to the adrenal biopsy and evaluate the diagnostic performance, complications and non diagnostic rate of adrenal biopsy. DESIGN: Single-centre, retrospective cohort study. PATIENTS AND MEASUREMENTS: Medical records of patients who underwent adrenal biopsy between 1994 and 2014 were reviewed. Adrenal biopsy outcome was compared to a predefined reference standard. RESULTS: Biopsy was performed in 418 patients [62% men, median age 69 years (range, 15-91)] on 419 adrenal lesions, median size 3·1 cm (range, 0·6-24). The main indication for adrenal mass biopsy was (349/419, 83%) suspected adrenal metastasis from a known or suspected extra-adrenal primary source. Only 116 of 419, 28% of cases had prebiopsy biochemical testing for pheochromocytoma. Biopsy-related complications occurred in 4% of the patients. Histology revealed a metastasis in 231 of 419 (55%), benign adrenal tissue in 137 of 419 (33%), adrenocortical carcinoma in eight of 419 (2%), other lesions in 23 of 419 (5%) including seven cases of pheochromocytoma and six cases of infectious process. Biopsy was nondiagnostic in 20 of 419 (5%). All adrenal masses with unenhanced radiodensity ≤10 HU (42/137, 31%) proved to be benign adrenal adenomas. Adrenal biopsy diagnosed malignancy with a sensitivity of 88·5%, specificity of 91·5%, positive predictive value of 93·4% and negative predictive value of 85·5%. CONCLUSION: When used in the appropriate clinical setting, adrenal biopsy is a powerful tool in the diagnostic algorithm of the evaluation of adrenal masses with features suspicious for malignancy. Efforts to increase awareness to perform biochemical testing for pheochromocytoma prior to adrenal biopsy are needed.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Biópsia/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/efeitos adversos , Biópsia/métodos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Feocromocitoma/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
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