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PURPOSE: Cushing's disease (CD) is associated with alterations in cardiac geometry and function, shown to be reversible after treatment. Our aim was to study cortisol-related changes in myocardial content in CD at baseline and after treatment using MR myocardial T1 times. MATERIALS AND METHODS: This is a longitudinal study performed in 10 patients with active CD matched with 10 hypertensive and 10 healthy controls. All subjects had MR after CD diagnosis and 6 months after cortisol normalization. The 1.5 Tesla MR protocol included left ventricular geometry and function assessment and MOLLI sequences before and after contrast injection as well as late gadolinium enhancement. RESULTS: At baseline, native myocardial T1 was significantly higher in CD patients compared with controls and the hypertensive group (1056 ± 139 ms versus 929 ± 80 ms, P = 0.023; 1056 ± 139 ms versus 952 ± 51, P = 0.049). After treatment, native and postcontrast myocardial T1 decreased in CD patients versus controls (1056 ± 139 ms versus 832 ± 78, P = 0.006 and 483 ± 69 ms versus 395 ± 39 ms, P = 0.010) reaching values even lower than found in controls (P = 0.038 and P = 0.001, respectively). CONCLUSION: Native myocardial T1 is increased in Cushing's disease independently from hypertension and notably decreases after effective treatment, highlighting its potential to detect subclinical diffuse myocardial involvement in this condition. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:147-156.
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Imagem de Difusão por Ressonância Magnética/métodos , Hidrocortisona/sangue , Interpretação de Imagem Assistida por Computador/métodos , Hipersecreção Hipofisária de ACTH/sangue , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/complicações , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Disfunção Ventricular Esquerda/etiologia , Adulto JovemRESUMO
IMPORTANCE: A paradoxical increase of growth hormone (GH) following oral glucose load has been described in â¼30% of patients with acromegaly and has been related to the ectopic expression of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in somatotropinomas. Recently, we identified germline pathogenic variants and somatic loss of heterozygosity of lysine demethylase 1A (KDM1A) in patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. The ectopic expression of GIPR in both adrenal and pituitary lesions suggests a common molecular mechanism. OBJECTIVE: We aimed to analyze KDM1A gene sequence and KDM1A and GIPR expressions in somatotroph pituitary adenomas. SETTINGS: We conducted a cohort study at university hospitals in France and in Italy. We collected pituitary adenoma specimens from acromegalic patients who had undergone pituitary surgery. We performed targeted exome sequencing (gene panel analysis) and array-comparative genomic hybridization on somatic DNA derived from adenomas and performed droplet digital PCR on adenoma samples to quantify KDM1A and GIPR expressions. RESULTS: One hundred and forty-six patients with sporadic acromegaly were studied; 72.6% presented unsuppressed classical GH response, whereas 27.4% displayed a paradoxical rise in GH after oral glucose load. We did not identify any pathogenic variant in the KDM1A gene in the adenomas of these patients. However, we identified a recurrent 1p deletion encompassing the KDM1A locus in 29 adenomas and observed a higher prevalence of paradoxical GH rise (P = .0166), lower KDM1A expression (4.47 ± 2.49 vs 8.56 ± 5.62, P < .0001), and higher GIPR expression (1.09 ± 0.92 vs 0.43 ± 0.51, P = .0012) in adenomas from patients with KDM1A haploinsufficiency compared with those with 2 KDM1A copies. CONCLUSIONS AND RELEVANCE: Unlike in GIP-dependent primary bilateral macronodular adrenal hyperplasia, KDM1A genetic variations are not the cause of GIPR expression in somatotroph pituitary adenomas. Recurrent KDM1A haploinsufficiency, more frequently observed in GIPR-expressing adenomas, could be responsible for decreased KDM1A function resulting in transcriptional derepression on the GIPR locus.
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Acromegalia , Adenoma , Adenoma Hipofisário Secretor de Hormônio do Crescimento , Hormônio do Crescimento Humano , Neoplasias Hipofisárias , Somatotrofos , Humanos , Neoplasias Hipofisárias/patologia , Acromegalia/metabolismo , Somatotrofos/metabolismo , Somatotrofos/patologia , Hibridização Genômica Comparativa , Hiperplasia/patologia , Estudos de Coortes , Genótipo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma/patologia , Hormônio do Crescimento Humano/metabolismo , Hormônio do Crescimento/metabolismo , Glucose , Histona Desmetilases/genética , Histona Desmetilases/metabolismoRESUMO
STUDY OBJECTIVES: To evaluate sleep, sleepiness, and excessive need for sleep in patients with craniopharyngioma (a suprasellar tumor which can affect sleep-wake systems). METHODS: A retrospective study of all adult patients living with craniopharyngioma referred to the sleep clinic, who received a sleep interview, nocturnal polysomnography, multiple sleep latency tests (MSLT), and 18-h bed rest polysomnography. Their sleep measurements were compared with those of age- and sex-matched healthy controls. RESULTS: Of 54 patients screened with craniopharyngioma, 42 were analyzed, 80% of whom complained of excessive daytime sleepiness. Sleep testing revealed that 6 (14.3%) of them had secondary narcolepsy (including one with cataplexy), and 11 (26.2%) had central hypersomnia associated with a medical disorder. Compared with controls, patients were more frequently obese, had a shorter mean sleep latency on MSLT, and slept longer on the first night. There was a nonsignificant trend for patients with (vs. without) narcolepsy and hypersomnia to be younger, to have a higher body mass index, to be more likely to have received radiation therapy, and to have more severe damage to the hypothalamus after surgery. Treatment with stimulants (modafinil, pitolisant, and methylphenidate) was beneficial in 9/10 patients. CONCLUSIONS: Nearly half of the patients with craniopharyngioma and sleep disorders have a central disorder of hypersomnolence (narcolepsy and hypersomnia), which should be investigated and lead to considerations beyond sleep apnea syndrome in these obese patients.
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Cataplexia , Craniofaringioma , Distúrbios do Sono por Sonolência Excessiva , Narcolepsia , Neoplasias Hipofisárias , Humanos , Adulto , Craniofaringioma/complicações , Estudos Retrospectivos , Narcolepsia/complicações , Distúrbios do Sono por Sonolência Excessiva/complicações , Obesidade/complicações , Neoplasias Hipofisárias/complicaçõesRESUMO
Germline mutations in genes encoding succinate dehydrogenase (SDH) are frequently involved in pheochromocytoma/paraganglioma (PPGL) development and were implicated in patients with the '3PAs' syndrome (associating pituitary adenoma (PA) and PPGL) or isolated PA. However, the causality link between SDHx mutation and PA remains difficult to establish, and in vivo tools for detecting hallmarks of SDH deficiency are scarce. Proton magnetic resonance spectroscopy (1H-MRS) can detect succinate in vivo as a biomarker of SDHx mutations in PGL. The objective of this study was to demonstrate the causality link between PA and SDH deficiency in vivo using 1H-MRS as a novel noninvasive tool for succinate detection in PA. Three SDHx-mutated patients suffering from a PPGL and a macroprolactinoma and one patient with an apparently sporadic non-functioning pituitary macroadenoma underwent MRI examination at 3 T. An optimized 1H-MRS semi-LASER sequence (TR = 2500 ms, TE = 144 ms) was employed for the detection of succinate in vivo. Succinate and choline-containing compounds were identified in the MR spectra as single resonances at 2.44 and 3.2 ppm, respectively. Choline compounds were detected in all the tumors (three PGL and four PAs), while a succinate peak was only observed in the three macroprolactinomas and the three PGL of SDHx-mutated patients, demonstrating SDH deficiency in these tumors. In conclusion, the detection of succinate by 1H-MRS as a hallmark of SDH deficiency in vivo is feasible in PA, laying the groundwork for a better understanding of the biological link between SDHx mutations and the development of these tumors.
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Adenoma , Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Neoplasias Hipofisárias , Prolactinoma , Humanos , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Mutação , Succinato Desidrogenase/genética , Succinato Desidrogenase/metabolismo , Feocromocitoma/genética , Paraganglioma/patologia , Adenoma/genética , Adenoma/patologia , Mutação em Linhagem Germinativa , Espectroscopia de Ressonância Magnética , Neoplasias das Glândulas Suprarrenais/genética , Ácido SuccínicoRESUMO
Objective: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a heterogeneous disease characterized by adrenal macronodules and variable levels of cortisol excess, with not clearly established clinical diagnostic criteria. It can be caused by ARMC5 germline pathogenic variants. In this study, we aimed to identify predictive criteria for ARMC5 variants. Methods: We included 352 consecutive index patients from 12 European centers, sequenced for germline ARMC5 alteration. Clinical, biological and imaging data were collected retrospectively. Results: 52 patients (14.8%) carried ARMC5 germline pathogenic variants and showed a more distinct phenotype than non-mutated patients for cortisol excess (24-h urinary free cortisol 2.32 vs 1.11-fold ULN, respectively, P < 0.001) and adrenal morphology (maximal adrenal diameter 104 vs 83 mm, respectively, P < 0.001) and were more often surgically or medically treated (67.9 vs 36.8%, respectively, P < 0.001). ARMC5-mutated patients showed a constant, bilateral adrenal involvement and at least a possible autonomous cortisol secretion (defined by a plasma cortisol after 1 mg dexamethasone suppression above 50 nmol/L), while these criteria were not systematic in WT patients (78.3%). The association of these two criteria holds a 100% sensitivity and a 100% negative predictive value for ARMC5 pathogenic variant. Conclusion: We report the largest series of index patients investigated for ARMC5 and confirm that ARMC5 pathogenic variants are associated with a more severe phenotype in most cases. To minimize negative ARMC5 screening, genotyping should be limited to clear bilateral adrenal involvement and autonomous cortisol secretion, with an optimum sensitivity for routine clinical practice. These findings will also help to better define PBMAH diagnostic criteria.
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Glândulas Suprarrenais , Hidrocortisona , Glândulas Suprarrenais/patologia , Proteínas do Domínio Armadillo/genética , Humanos , Hiperplasia/genética , Hiperplasia/patologia , Estudos RetrospectivosRESUMO
INTRODUCTION: Hyperthyroid patients who are unresponsive to medical treatment remain a challenging clinical problem. OBJECTIVE: The goal of our study was to evaluate the use of therapeutic plasma exchange (TPE) in hyperthyroid patients and their outcome after TPE. METHOD: We retrospectively reviewed 22 patients who underwent TPE for refractory thyrotoxicosis in our institution: 13 with Graves' disease, 7 with amiodarone-induced thyrotoxicosis (AIT), 1 with toxic goiter, and 1 pregnant patient with familial nonautoimmune thyrotoxicosis. RESULTS: Before TPE, all patients had severe hyperthyroidism, and antithyroid drugs were either contraindicated or not sufficiently effective to restore euthyroidism promptly. After all the TPEs, free T4 (fT4) decreased significantly by 48% (p = 0.001) and fT3 by 52% (p = 0.0001). The median number of TPE sessions per patient was 4 (range: 1-10). There were no complications during the 91 TPE sessions. Total thyroidectomy with no severe side effects was performed on 16/22 patients and 1 other patient was treated with radioactive iodine. One patient died from severe thyrotoxicosis during medical care. The remaining 4 patients were followed up without any radical treatment. For all 7 patients with AIT, iterative TPE led to a significant clinical improvement, and amiodarone was continued for 1 patient. Available treatments were continued between TPE sessions (cholestyramine for 13 patients [60%] and glucocorticoids for 16 patients [73%]). CONCLUSION: TPE allowed a safe decrease of 50% in thyroid hormone levels, and it should be considered for refractory hyperthyroid patients when medical treatments are contraindicated or have failed to restore euthyroidism, irrespective of the etiology of the thyrotoxicosis.
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CONTEXT: Cardiovascular disease is the leading cause of death in patients with Cushing syndrome. Cortisol excess and adverse metabolic profile could increase cardiac fat, which can subsequently impair cardiac structure and function. OBJECTIVE: We aimed to evaluate cardiac fat mass and distribution in patients with Cushing syndrome. METHODS: In this prospective, cross-sectional study, 23 patients with Cushing syndrome and 27 control individuals of comparable age, sex, and body mass index were investigated by cardiac magnetic resonance imaging and proton spectroscopy. Patients were explored before and after biochemical disease remission. Myocardial fat measured by the Dixon method was the main outcome measure. The intramyocardial triglyceride/water ratio measured by spectroscopy and epicardial and pericardial fat volumes were secondary outcome measures. RESULTS: No difference was found between patients and controls in intramyocardial lipid content. Epicardial fat mass was increased in patients compared to controls (30.8 g/m2 [20.4-34.8] vs 17.2 g/m2 [13.1-23.5], Pâ <â .001). Similarly, pericardial fat mass was increased in patients compared to controls (28.3 g/m2 [17.9-38.0] vs 11.4 g/m2 [7.5-19.4], Pâ =â .003). Sex, glycated hemoglobin A1c, and the presence of hypercortisolism were independent determinants of epicardial fat. Pericardial fat was associated with sex, impaired glucose homeostasis and left ventricular wall thickness. Disease remission decreased epicardial fat mass without affecting pericardial fat. CONCLUSION: Intramyocardial fat stores are not increased in patients with Cushing syndrome, despite highly prevalent metabolic syndrome, suggesting increased cortisol-mediated lipid consumption. Cushing syndrome is associated with marked accumulation of epicardial and pericardial fat. Epicardial adiposity may exert paracrine proinflammatory effects promoting cardiomyopathy.
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Adiposidade , Índice de Massa Corporal , Cardiomiopatias/patologia , Síndrome de Cushing/fisiopatologia , Gordura Intra-Abdominal/patologia , Miocárdio/patologia , Pericárdio/patologia , Adulto , Biomarcadores/análise , Glicemia/análise , Cardiomiopatias/epidemiologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
OBJECTIVE: Adrenal ganglioneuromas are rare, differentiated, neuroblastic tumors that originate from the peripheral sympathetic nervous system. Because of their rarity, information is limited, derived from small cases series. Our objective was to characterize this tumor and provide help for its management. METHODS: A retrospective multicenter analysis of adrenal ganglioneuromas from 20 French centers belonging to the COMETE network and one Belgian center. RESULTS: Among the 104 cases identified, 59.6% were women (n = 62/104), median age at diagnosis was 29 years, with 24 pediatric cases. 60.6% (n = 63/104) were incidentalomas. Ganglioneuromas were non-secreting tumors in 90.8% of cases (n = 89/98), whereas the preoperative hormonal evaluation was indeterminate for 9.2% of patients (n = 9/98). CT imaging, performed on 96 patients, revealed large tumors (median diameter of 50 mm) with a non-contrast density > 10 Hounsfield units in 98.1% (n = 52/53) and calcifications in 64.6% of cases (n = 31/48). Increased uptake on 123I-MIBG scintigraphy and 18F-FDG-PET/CT was observed in 26.7% (n = 8/30) and 42.2% (n = 19/45) of the tumors, respectively. All 104 patients underwent surgery. No recurrence was observed among the 42 patients who had an imaging follow-up (mean 29.6 months, median 18 months (4-156)). CONCLUSION: Adrenal ganglioneuromas are large tumors, mostly nonfunctioning, without benign imaging features. Although the duration of follow-up was limited in our series, no recurrence was identified. A review of the literature confirms the absence of postoperative recurrence. Based on all available data, in the absence of special circumstances (genetic form, uncertain histological diagnosis), long-term follow-up is not necessary after complete surgery for patients with an adrenal ganglioneuroma.
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Neoplasias das Glândulas Suprarrenais , Ganglioneuroma , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/terapia , Adulto , Idade de Início , Idoso , Bélgica/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Redes Comunitárias , Feminino , Seguimentos , França/epidemiologia , Ganglioneuroma/diagnóstico , Ganglioneuroma/epidemiologia , Ganglioneuroma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
A 47-year-old woman with a history of surgically treated abdominal paraganglioma and left thigh melanoma underwent an F-FDOPA PET/CT for suspected locoregional recurrence of paraganglioma. F-FDOPA PET/CT disconfirmed this recurrence but revealed 2 FDOPA-avid left inguinal lymph nodes, confirmed on a subsequent F-FDG PET/CT. Excision and pathology characterized these lymph nodes as melanoma metastases. F-FDOPA PET/CT is a widely used and valuable tool in the assessment of paraganglioma, both for staging and recurrence detection. Uptake of FDOPA has only rarely been documented in metastatic melanoma that could be a pitfall for detecting neuroendocrine tumors.
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Di-Hidroxifenilalanina/análogos & derivados , Achados Incidentais , Melanoma/diagnóstico por imagem , Melanoma/secundário , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paraganglioma/patologia , RecidivaRESUMO
CONTEXT: Cardiovascular disease is one of the main causes of morbidity in active acromegaly due to the increased prevalence of risk factors and arterial consequences of increased growth hormone levels. No in vivo study has evaluated the consequences of acromegaly on the retinal microvasculature. OBJECTIVE: The aim of this study was to identify in vivo the presence of morphological alterations of retinal arterioles in subjects with acromegaly. PATIENTS AND METHODS: Single-center retrospective study of a cohort of 60 subjects with acromegaly, matched to 60 controls, who were referred for adaptive optics camera (AOC) from September 2014 to December 2016. Of the subjects with acromegaly, 19 had an active disease (AD) and 41 a controlled disease (CD) based on the IGF1 ratio (IGF1r). Retinal arteriolar remodeling was previously assessed using adaptive optics camera (AOC) in order to measure wall-to-lumen ratio (WLR), wall thickness (WT), internal diameter (ID) and wall cross sectional area (WCSA). RESULTS: WLR was significantly higher in AD subjects compared to CD subjects and controls (AD: 0.311 ± 0.06, CD: 0.279 ± 0.04, controls: 0.281 ± 0.04, P = 0.031). A significant positive correlation was observed between WLR and IGF-1r (R2 = 0.215, P < 0.001), even after adjustment for gender, age, systolic blood pressure (SBP) and the presence of dopamine agonist treatment (R2 = 0.406, P < 0.001). Retinal arteriolar anatomical indices were comparable between CD and controls. CONCLUSION: Active acromegaly is associated with the presence of small retinal arteriolar remodeling. These results provide new perspectives to better stratify cardiovascular risk and consequently optimize treatment in acromegaly.
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Acromegalia/diagnóstico por imagem , Arteríolas/diagnóstico por imagem , Fator de Crescimento Insulin-Like I/metabolismo , Artéria Retiniana/diagnóstico por imagem , Remodelação Vascular , Acromegalia/tratamento farmacológico , Acromegalia/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Óptica , Tamanho do Órgão , Artéria Retiniana/patologia , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Severe hypocalcemia complicating cervical endocrine surgery in patients with gastric bypass can constitute a major concern. When usual therapies fail to maintain calcemia within the normal range without secondary adverse events, reversal of the bariatric surgery should be considered. We herein report the outcomes of laparoscopic revision of bariatric surgeries in two patients suffering from severe resistant hypocalcemia following cervical surgery, requiring in one case recombinant PTH administration and, in the other, daily intravenous calcium injections. The Roux-en-Y gastric bypass was switched to sleeve gastrectomy in the first patient, and in the second patient, the biliopancreatic diversion with duodenal switch was revised, to restore the upper and distal parts of the alimentary tract. Rapid improvement of hypocalcemia was observed in both cases.
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Cirurgia Bariátrica , Derivação Gástrica , Hipocalcemia , Laparoscopia , Obesidade Mórbida , Cirurgia Bariátrica/efeitos adversos , Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos , Humanos , Hipocalcemia/tratamento farmacológico , Hipocalcemia/etiologia , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Redução de PesoRESUMO
PURPOSE: To examine retinal vascular changes in the peripapillary and macular areas in patients with pituitary adenoma (PA) using optical coherence tomography angiography (OCTA). METHODS: Cross-sectional, retrospective study of 17 consecutive PA patients and 16 healthy subjects. All patients underwent a neuro-ophthalmological examination to assess the presence of optic neuropathy (ON). Static automated perimetry (SAP), macular and optic disc structural OCT [retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) thicknesses] and OCTA were performed. Pituitary adenoma (PA) patients with ON were compared to those without ON and to healthy subjects. RESULTS: Optic neuropathy (ON) was found in 16 eyes of nine PA patients. Peripapillary vessel density (ppVD) and macular vessel density (VD) in the superficial vascular plexus were significantly decreased in PA eyes with ON, compared to healthy eyes (45.21 ± 5.69 versus 50.52 ± 2.14% and 43.79 ± 5.03% versus 48.96 ± 2.94%, respectively). No significant difference in VD was observed in the macular deep vascular complex (DVC) between groups. Pituitary adenoma (PA) patients with ON had a mean ppVD reduction by 10.51% compared to healthy subjects. RNFL and GCC thicknesses were significantly reduced in PA eyes with ON compared to the other groups. Peripapillary VD (ppVD) significantly correlated with RNFL thickness and SAP mean deviation. CONCLUSIONS: Optical coherence tomography angiography showed a significant decrease in ppVD and superficial macular VD in PA eyes with ON compared to healthy eyes, according to RNFL and GCC thinning. Together with the absence of DVC alterations, it may provide further insights into neurovascular coupling.
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BACKGROUND: Kennedy's disease (KD), also known as spinal and bulbar muscular atrophy (SBMA), is a rare, adult-onset, X-linked recessive neuromuscular disease caused by CAG expansions in exon 1 of the androgen receptor gene (AR). The objective of the French national diagnostic and management protocol is to provide evidence-based best practice recommendations and outline an optimised care pathway for patients with KD, based on a systematic literature review and consensus multidisciplinary observations. RESULTS: The initial evaluation, confirmation of the diagnosis, and management should ideally take place in a tertiary referral centre for motor neuron diseases, and involve an experienced multidisciplinary team of neurologists, endocrinologists, cardiologists and allied healthcare professionals. The diagnosis should be suspected in an adult male presenting with slowly progressive lower motor neuron symptoms, typically affecting the lower limbs at onset. Bulbar involvement (dysarthria and dysphagia) is often a later manifestation of the disease. Gynecomastia is not a constant feature, but is suggestive of a suspected diagnosis, which is further supported by electromyography showing diffuse motor neuron involvement often with asymptomatic sensory changes. A suspected diagnosis is confirmed by genetic testing. The multidisciplinary assessment should ascertain extra-neurological involvement such as cardiac repolarisation abnormalities (Brugada syndrome), signs of androgen resistance, genitourinary abnormalities, endocrine and metabolic changes (glucose intolerance, hyperlipidemia). In the absence of effective disease modifying therapies, the mainstay of management is symptomatic support using rehabilitation strategies (physiotherapy and speech therapy). Nutritional evaluation by an expert dietician is essential, and enteral nutrition (gastrostomy) may be required. Respiratory management centres on the detection and treatment of bronchial obstructions, as well as screening for aspiration pneumonia (chest physiotherapy, drainage, positioning, breath stacking, mechanical insufflation-exsufflation, cough assist machnie, antibiotics). Non-invasive mechanical ventilation is seldom needed. Symptomatic pharmaceutical therapy includes pain management, endocrine and metabolic interventions. There is no evidence for androgen substitution therapy. CONCLUSION: The French national Kennedy's disease protocol provides management recommendations for patients with KD. In a low-incidence condition, sharing and integrating regional expertise, multidisciplinary experience and defining consensus best-practice recommendations is particularly important. Well-coordinated collaborative efforts will ultimately pave the way to the development of evidence-based international guidelines.
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Atrofia Bulboespinal Ligada ao X , Adulto , Atrofia Bulboespinal Ligada ao X/diagnóstico , Atrofia Bulboespinal Ligada ao X/genética , Consenso , Eletromiografia , Testes Genéticos , Humanos , Masculino , Neurônios Motores , Guias de Prática Clínica como AssuntoRESUMO
CONTEXT: In patients treated with antipsychotics, the rare occurrence of a macroprolactinoma represents a therapeutic challenge. OBJECTIVE: Our aim was to evaluate the efficacy and psychiatric safety of dopamine agonists (DAs) prescribed for large macroprolactinomas in patients with psychosis treated with antipsychotics. DESIGN: This was a multicenter (France and Belgium) retrospective study. PATIENTS: Eighteen patients treated with antipsychotics were included. RESULTS: Under DA, median PRL levels decreased from 1247 (117-81 132) to 42 (4-573) ng/mL (P = 0.008), from 3850 (449-38 000) to 141 (60-6000) ng/mL (P = 0.037) and from 1664 (94-9400) to 1215 (48-5640) ng/mL (P = 0.56) when given alone (n = 8), before surgery (n = 7), or after surgery (n = 6), respectively. The prolactinoma median largest diameter decreased by 28% (0-57) in patients under DAs alone (P = 0.02) but did not change when given after surgery. Optic chiasm decompression was achieved in 82% of patients. Five patients (28%) were admitted for psychotic relapse while receiving DAs (but three of them had stopped antipsychotic treatment at that time). A more severe underlying psychosis, rather than the DA treatment itself, may explain such psychiatric admissions. CONCLUSIONS: Even if the DA efficacy on PRL levels and tumor volume in patients with macroprolactinoma under antipsychotic drugs is less impressive than that typically observed, it may be considered satisfactory for half of our patients, particularly in cases of optic chiasm compression. Psychotic exacerbation was unusual in these patients, occurring mostly in those with the most severe psychotic forms. DAs may therefore be used as antitumor treatment for macroprolactinoma in patients with visual involvement, severe headaches or invasion into the skull base who receive antipsychotics.
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Antipsicóticos/uso terapêutico , Agonistas de Dopamina/efeitos adversos , Agonistas de Dopamina/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Adulto , Bélgica , Interações Medicamentosas , Feminino , França , Humanos , Masculino , Transtornos Mentais/complicações , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/psicologia , Prolactina/sangue , Prolactinoma/patologia , Prolactinoma/psicologia , Transtornos Psicóticos/complicações , Transtornos Psicóticos/tratamento farmacológico , Recidiva , Estudos RetrospectivosRESUMO
The objective of this study was to investigate whether patients with the metabolic syndrome (MetS) and an imbalance in cortisol metabolism express increased urinary albumin excretion compared to those patients with metabolic syndrome alone. Seventy-four patients with MetS were evaluated using a low-dose dexamethasone suppression test (LDDST) to identify disturbed cortisol balance (cortisol levels > 50 nmol/L after LDDST). The level of albumin in the urine was also evaluated. Disturbed cortisol balance was found in 8% of all evaluated patients with MetS. Microalbuminuria was present significantly more often (p<0.01) in those patients with MetS and an imbalance in cortisol metabolism compared with patients suffering MetS alone (urine albumin: 210 mg/L vs. 26 mg/L, respectively, p<0.01). A substantial percentage of patients with MetS had inappropriate cortisol homeostasis. Of importance, excretion of urinary albumin was increased in these patients. This observation may indicate that this subgroup within the MetS population has a higher cardiovascular risk and possible increased endothelial dysfunction, with a subsequent need for stricter control to prevent cardiovascular morbidity and mortality.
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Hiperfunção Adrenocortical/complicações , Albuminúria/etiologia , Hidrocortisona/metabolismo , Síndrome Metabólica/complicações , Biomarcadores/metabolismo , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Masculino , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-IdadeRESUMO
Gangliocytomas are rare and benign neuronal cell tumors, mostly found in the hypothalamic and sellar regions. Their histogenesis is still the subject of discussions. Herein we present a unique case of a pituitary gangliocytoma associated with a prolactinoma and a corticotroph adenoma in a patient affected by MEN1. The histologic study revealed shared features between adenomatous and neuronal cells, supporting the etiological hypothesis of a common origin or a phenomenon of transdifferentiation. Furthermore, gangliocytoma could be a new tumor related to MEN1. The clinical and histologic observations are discussed and the literature on the topic is reviewed.
Assuntos
Adenoma/patologia , Transdiferenciação Celular , Ganglioneuroma/patologia , Neoplasia Endócrina Múltipla Tipo 1/patologia , Células Neuroendócrinas/patologia , Neoplasias Hipofisárias/patologia , Prolactinoma/patologia , Adenoma/diagnóstico , Ganglioneuroma/diagnóstico , Humanos , Masculino , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Prolactinoma/diagnóstico , Adulto JovemRESUMO
OBJECTIVES: Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival. DESIGN: Multicenter retrospective study by members of the French Society of Endocrinology. METHODS: Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included. Most tumors were corticotroph (n = 23) or lactotroph (n = 13), and 14 were carcinomas. Clinical/pathological characteristics of PT, as well as data from treatment evaluation and from the last follow-up were recorded. A partial response was considered as a decrease in the maximal tumor diameter by more than 30% and/or in the hormonal rate by more than 50% at the end of treatment. RESULTS: The median treatment duration was 6.5 cycles (range 2-24), using a standard regimen for most and combined radiotherapy for six. Twenty-two patients (51.2%) were considered as responders. Silent tumor at diagnosis was associated with a poor response. The median follow-up after the end of treatment was 16 months (0-72). Overall survival was significantly higher among responders (P = 0.002); however, ten patients relapsed 5 months (0-57) after the end of TMZ treatment, five in whom TMZ was reinitiated without success. DISCUSSION: Patients in our series showed a 51.2% response rate to TMZ, with an improved survival among responders despite frequent relapses. Our study highlights the high variability and lack of standardization of treatment protocols.
Assuntos
Adenoma Hipofisário Secretor de ACT/tratamento farmacológico , Antineoplásicos Alquilantes/uso terapêutico , Carcinoma/tratamento farmacológico , Dacarbazina/análogos & derivados , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Adenoma Hipofisário Secretor de ACT/patologia , Adenoma Hipofisário Secretor de ACT/prevenção & controle , Adenoma Hipofisário Secretor de ACT/radioterapia , Adulto , Carcinoma/patologia , Carcinoma/prevenção & controle , Carcinoma/radioterapia , Quimiorradioterapia , Estudos de Coortes , Dacarbazina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , França , Humanos , Masculino , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/prevenção & controle , Neoplasias Hipofisárias/radioterapia , Padrões de Prática Médica , Prolactinoma/patologia , Prolactinoma/prevenção & controle , Prolactinoma/radioterapia , Estudos Retrospectivos , Análise de Sobrevida , Temozolomida , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiaçãoRESUMO
Ezetimibe is the first cholesterol absorption inhibitor, a novel class of lipopenic drugs that inhibit intestinal absorption of biliary and dietary cholesterol. From a pathophysiological point of view, combining complementary drugs that act on different cholesterol metabolism pathways is particularly interesting. This interest has been confirmed in clinical studies combining ezetimibe and statins, which inhibit cholesterol synthesis in the liver. Adding ezetimibe (10 mg/d) to statin therapy decreased LDL cholesterol by as much as an additional 20%. It may thus be especially useful in patients who are unable to reach the LDL cholesterol target with diet and statins alone. Ezetimibe is well tolerated and is indicated alone in statin-intolerant patients.
Assuntos
Azetidinas/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Colesterol/metabolismo , Quimioterapia Combinada , Ezetimiba , Fenofibrato/uso terapêutico , Humanos , Hipolipemiantes/uso terapêuticoRESUMO
UNLABELLED: Mitotane (o,p'-DDD) is the standard treatment for advanced adrenocortical carcinoma (ACC). Monitoring of plasma mitotane levels is recommended to look for a therapeutic window between 14 and 20mg/L, but its positive predictive value requires optimization. We report the case of an ACC patient with a history of dyslipidemia treated with mitotane in whom several plasma mitotane levels >30mg/L were found together with an excellent neurological tolerance. This observation led us to compare theoretical or measured o,p'-DDD and o,p'-DDE levels in a series of normolipidemic and dyslipidemic plasma samples to explore potential analytical issues responsible for an overestimation of plasma mitotane levels. We demonstrate an overestimation of mitotane measurements in dyslipidemic patients. Mitotane and o,p'-DDE measurements showed a mean 20% overestimation in hypercholesterolemic and hypertriglyceridemic plasma, compared with normolipidemic plasma. The internal standard p,p'-DDE measurements showed a parallel decrease in hypercholesterolemic and hypertriglyceridemic plasma, suggesting a matrix effect. Finally, diluting plasma samples and/or using phospholipid removal cartridges allowed correcting such interference. LEARNING POINTS: Hypercholesterolemia (HCH) and hypertriglyceridemia (HTG) induce an overestimation of plasma mitotane measurements.We propose a routine monitoring of lipidemic status.We propose optimized methodology of measurement before interpreting high plasma mitotane levels.