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1.
PLoS One ; 19(5): e0303138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38722890

RESUMO

Human T-cell leukemia virus type I (HTLV-I) is an oncogenic virus whose infection can cause diverse diseases, most notably adult T-cell leukemia/lymphoma (ATL or ATLL), an aggressive and fatal malignancy of CD4 T cells. The oncogenic ability of HTLV-I is mostly attributed to the viral transcriptional transactivator Tax. Tax alone is sufficient to induce specific tumors in mice depending on the promotor used to drive Tax expression, thereby being used to understand HTLV-I tumorigenesis and model the tumor types developed in Tax transgenic mice. Tax exerts its oncogenic role predominantly by activating the cellular transcription factor NF-κB. Here, we report that genetic deletion of NF-κB1, the prototypic member of the NF-κB family, promotes adrenal medullary tumors but suppresses neurofibromas in mice with transgenic Tax driven by the HTLV-I Long Terminal Repeat (LTR) promoter. The adrenal tumors are derived from macrophages. Neoplastic macrophages also infiltrate the spleen and lymph nodes, causing splenomegaly and lymphadenopathy in mice. Nevertheless, the findings could be human relevant, because macrophages are important target cells of HTLV-I infection and serve as a virus reservoir in vivo. Moreover, the spleen, lymph nodes and adrenal glands are the most common sites of tumor cell infiltration in HTLV-I-infected patients. These data provide new mechanistic insights into the complex interaction between Tax and NF-κB, therefore improving our understanding of HTLV-I oncogenic pathogenesis. They also expand our knowledge and establish a new animal model of macrophage neoplasms and adrenal tumors.


Assuntos
Produtos do Gene tax , Vírus Linfotrópico T Tipo 1 Humano , Macrófagos , Camundongos Transgênicos , Animais , Camundongos , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Macrófagos/metabolismo , Macrófagos/virologia , Produtos do Gene tax/metabolismo , Produtos do Gene tax/genética , Humanos , Neoplasias das Glândulas Suprarrenais/virologia , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Subunidade p50 de NF-kappa B/genética , Sequências Repetidas Terminais/genética
2.
J Zhejiang Univ Sci B ; 25(5): 410-421, 2024 Mar 12.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38725340

RESUMO

Pheochromocytomas and paragangliomas (PPGLs) cause symptoms by altering the circulation levels of catecholamines and peptide hormones. Currently, the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines. In this study, we used ultra-performance liquid chromatography (UPLC)/quadrupole time-of-flight mass spectrometry (Q-TOF MS) analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients. We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla. Through conducting two steps of metabolomics analysis, we identified 111 differential metabolites between the healthy group and the patient group, among which 53 metabolites were validated. By integrating the information of differential metabolites and differentially expressed genes, we inferred that the cysteine-methionine, pyrimidine, and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm. The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma, whereas the pyrimidine pathway showed no significant difference. Finally, we developed an optimized diagnostic model of two metabolites, L-dihydroorotic acid and vanylglycol. Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.


Assuntos
Neoplasias das Glândulas Suprarrenais , Cisteína , Metionina , Feocromocitoma , Pirimidinas , Tirosina , Feocromocitoma/metabolismo , Feocromocitoma/sangue , Humanos , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/sangue , Pirimidinas/metabolismo , Metionina/metabolismo , Tirosina/metabolismo , Tirosina/sangue , Cisteína/metabolismo , Masculino , Metabolômica/métodos , Feminino , Pessoa de Meia-Idade , Adulto , Redes e Vias Metabólicas
3.
Pan Afr Med J ; 47: 88, 2024.
Artigo em Francês | MEDLINE | ID: mdl-38737225

RESUMO

Ectopic ACTH-secreting pheochromocytoma is a very rare cause of Cushing´s syndrome, posing diagnostic and therapeutic challenges. We here report the case of a female patient with suspected severe Cushing´s syndrome associated with melanoderma, arterial hypertension resistant to triple therapy and unbalanced diabetes treated with insulin therapy. Biologically, urinary ethoxylated, 24-hour urinary free cortisol and ACTH were very high. Imaging showed a 3.5 cm left adrenal mass. The patient underwent left adrenalectomy after medical preparation, with good clinico-biological outcome. Anatomopathological examination confirmed the diagnosis of pheochromocytoma. This case study highlights the importance of measuring methoxylated derivatives in any patient with ACTH-dependent Cushing´s syndrome associated with an adrenal mass. The aim is to ensure early treatment and avoid life-threatening complications.


Assuntos
Neoplasias das Glândulas Suprarrenais , Adrenalectomia , Hormônio Adrenocorticotrópico , Síndrome de Cushing , Feocromocitoma , Humanos , Feocromocitoma/diagnóstico , Feocromocitoma/metabolismo , Feocromocitoma/complicações , Feminino , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/complicações , Síndrome de Cushing/etiologia , Síndrome de Cushing/diagnóstico , Adrenalectomia/métodos , Hormônio Adrenocorticotrópico/metabolismo , Hidrocortisona/metabolismo , Hipertensão/etiologia , Pessoa de Meia-Idade , Adulto
4.
BMJ Case Rep ; 17(4)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599794

RESUMO

Catecholamine surge and haemodynamic derangements are normally expected during the surgery for pheochromocytoma and benign functioning adrenal tumours. This male patient in his 50s underwent radical nephrectomy for renal cell carcinoma. The patient had no comorbidities. Three hours into the surgery, during electrocauterisation of the upper pole of the kidney, the patient's blood pressure unexpectedly spiked to 180/110 mm Hg, which was immediately followed by a decrease in heart rate to 35-38 beats/min. The surgeons were instructed to briefly halt the surgical manipulation. The blood pressure returned to the pre-surge level within 30-45 s. The surgery was completed without further complications, and the patient had an uneventful recovery. The episode is suggestive of the probability that the electrocauterisation of the upper pole of the kidney led to the accidental cauterisation of the adrenal gland, resulting in a transient catecholamine surge, increase in blood pressure and reflex bradycardia suggesting norepinephrine release. Treating bradycardia with atropine in such situations can exacerbate the effects of catecholamines and lead to dangerous tachyarrhythmias. The case report highlights the importance of vigilant monitoring during electrocauterisation of the upper pole of the kidney, invasive arterial blood pressure monitoring in detecting and recording such occurrences and cautiously selecting a treatment plan.


Assuntos
Neoplasias das Glândulas Suprarrenais , Neoplasias Renais , Humanos , Masculino , Neoplasias das Glândulas Suprarrenais/cirurgia , Bradicardia , Catecolaminas , Hemodinâmica , Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Pessoa de Meia-Idade
5.
Am J Case Rep ; 25: e943005, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38582958

RESUMO

BACKGROUND 21-hydroxylase deficiency, an essential enzyme for glucocorticoid and mineralocorticoid synthesis, is the cause of congenital adrenal hyperplasia (CAH) in more than 95% of cases. It is an autosomal recessive disorder encoded by the CYP21A2 gene, categorized into classical forms, which encompass the salt-wasting (SW) and simple virilizing (SV) forms, as well as the nonclassical form (NC). The aim of medical treatment is to replace missing glucocorticoids and, if necessary, mineralocorticoids, while also reducing elevated adrenal androgens. CASE REPORT We present the case of a 42-year-old woman with CAH who discontinued therapy during adolescence and was admitted to hospital with fatigue, nausea, and severe abdominal pain. A CT scan showed an extreme enlargement of the adrenal glands. Laboratory tests revealed elevated levels of 17-hydroxyprogesterone and other adrenal androgens, along with normal plasma metanephrine levels. Decreased morning cortisol levels suggested partial adrenal insufficiency requiring glucocorticoid replacement therapy. Due to the development of several serious complications and clinical deterioration, the multidisciplinary team recommended bilateral removal of masses measuring 300×250×200 mm on the right side and 250×200×200 mm on the left side. Histological and immunochemical examination confirmed the presence of giant myelolipomas with adrenal cortex hyperplasia. CONCLUSIONS Adrenal tumors, particularly myelolipomas, have a higher prevalence in patients with CAH. Our case report provides further evidence of the suspected link between non-compliant CAH therapy and the development of myelolipomas, along with promotion of their pronounced growth.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hiperplasia Suprarrenal Congênita , Lipoma , Mielolipoma , Adulto , Feminino , Humanos , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Glândulas Suprarrenais , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/genética , Glucocorticoides/uso terapêutico , Mielolipoma/diagnóstico , Mielolipoma/cirurgia , Mielolipoma/complicações , Esteroide 21-Hidroxilase/genética
7.
BMC Urol ; 24(1): 90, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637748

RESUMO

BACKGROUND: Laparoscopic adrenalectomy is widely performed for a number of hormone-producing tumors and postoperative management depends on the hormones produced. In the present study, we conducted a retrospective analysis to clarify the risk factors for postoperative complications, particularly postoperative fever after laparoscopic adrenalectomy. METHODS: We analyzed 406 patients who underwent laparoscopic adrenalectomy at our hospital between 2003 and 2019. Postoperative fever was defined as a fever of 38 °C or higher within 72 h after surgery. We investigated the risk factors for postoperative fever after laparoscopic adrenalectomy. RESULTS: There were 188 males (46%) and 218 females (54%) with a median age of 52 years. Among these patients, tumor pathologies included 188 primary aldosteronism (46%), 75 Cushing syndrome (18%), and 80 pheochromocytoma (20%). Postoperative fever developed in 124 of all patients (31%), 30% of those with primary aldosteronism, 53% of those with pheochromocytoma, and 8% of those with Cushing syndrome. A multivariate logistic regression analysis identified pheochromocytoma and non-Cushing syndrome as independent predictors of postoperative fever. Postoperative fever was observed in 42 out of 80 cases of pheochromocytoma (53%), which was significantly higher than in cases of non-pheochromocytoma (82/326, 25%, p < 0.01). In contrast, postoperative fever developed in 6 out of 75 cases of Cushing syndrome (8%), which was significantly lower than in cases of non-Cushing syndrome (118/331, 35.6%, p < 0.01). CONCLUSION: Since postoperative fever after laparoscopic adrenalectomy is markedly affected by the hormone produced by pheochromocytoma and Cushing syndrome, it is important to carefully consider the need for treatment.


Assuntos
Neoplasias das Glândulas Suprarrenais , Síndrome de Cushing , Hiperaldosteronismo , Laparoscopia , Feocromocitoma , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Adrenalectomia/efeitos adversos , Síndrome de Cushing/cirurgia , Feocromocitoma/cirurgia , Estudos Retrospectivos , Estudos de Casos e Controles , Laparoscopia/efeitos adversos , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Fatores de Risco , Hiperaldosteronismo/cirurgia , Hormônios
8.
JAMA Netw Open ; 7(4): e246453, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38619841

RESUMO

Importance: It is unclear whether nonfunctional adrenal tumors (NFATs) are associated with fractures. Objective: To analyze fracture frequencies in individuals with NFATs. Design, Setting, and Participants: A national retrospective cohort study was conducted in patients with NFATs diagnosed in Sweden between January 1, 2005, and December 31, 2019, and control participants without adrenal tumors followed up until death or the end of 2019. Individuals with a diagnosis of adrenal hormonal excess or previous malignant tumors were excluded. Sensitivity analyses were performed in subgroups of individuals with a combination of gallbladder, biliary tract, and pancreas diseases (for whom it was assumed that controls would also have undergone computed tomography) and 3- and 12-month survival free of malignant tumors after the NFAT diagnosis. The data were analyzed from September to November 2023. Exposures: Diagnosis of NFATs. Main Outcomes and Measures: Main study outcomes were prevalence and incidence of fractures after adjustment for sex, age, and comorbidities. Secondary outcomes were fragility fractures, fractures with fall on the same level, and fracture locations (distal arm and vertebral and hip fractures). Fracture incidence after adrenalectomy was also studied. Results: Among 20 390 patients, 12 120 (59.4%) were women, and the median (IQR) age was 66 (57-73) years; among 125 392 controls, 69 994 (55.8%) were women, and the median (IQR) age was 66 (57-73) years. Previous fractures were more common in patients diagnosed with NFATs compared with controls (4310 of 20 390 [21.1%] vs 20 323 of 125 392 [16.2%]; odds ratio [OR], 1.39; 95% CI, 1.34-1.45; adjusted OR [AOR], 1.27; 95% CI, 1.23-1.33). During the follow-up period (median [IQR], 4.9 [2.2-8.2] years), incident fractures were more common in patients with NFATs (3127 of 20 390 [15.3%] vs 16 086 of 125 392 [12.8%]; hazard ratio [HR], 1.40; 95% CI, 1.34-1.45; adjusted HR [AHR], 1.27; 95% CI, 1.22-1.33). An association between NFATs and vertebral fractures was found (AOR, 1.51; 95% CI, 1.33-1.72; AHR, 1.83; 95% CI, 1.60-2.09). In men younger than 50 years, NFATs were associated with fractures (AOR, 1.45; 95% CI, 1.21-1.74; AHR, 1.48; 95% CI, 1.20-1.82). There was no association among individuals who had undergone adrenalectomy (AHR, 1.12; 95% CI, 0.90-1.38). The association between NFATs and fractures remained significant and of similar magnitude in all sensitivity analyses. Conclusions and Relevance: In this cohort study, NFATs were associated with fractures, particularly among younger men; thus, patients with NFATs should have bone health evaluation with appropriate treatment and monitoring, especially in younger men.


Assuntos
Neoplasias das Glândulas Suprarrenais , Fraturas do Quadril , Masculino , Humanos , Feminino , Idoso , Prevalência , Estudos de Coortes , Incidência , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/epidemiologia
9.
Zhonghua Nei Ke Za Zhi ; 63(4): 378-385, 2024 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-38561283

RESUMO

Objective: To analyze the clinical characteristics and prognosis of patients with primary aldosteronism (PA) associated with subclinical Cushing syndrome (SCS). Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Chongqing Medical University in China. Patients with PA were included between January 2014 and December 2022. According to the results of 1-mg overnight dexamethasone suppression test, the patients were divided into the PA group and PA associated with SCS (PA/SCS) group. The demographic information, hormone levels, and follow-up results were analyzed. Independent sample t-test, chi-square test and Mann-Whitney U test were used for data comparison. Results: A total of 489 PA patients were enrolled in this study, of which 109 had PA/SCS (22.3%). Patients with SCS were on average older (54.4±10.7 vs. 47.4±11.0, P<0.001); had a larger proportion of women (69.7%, 76/109 vs. 57.4%, 218/380; P=0.020); and a longer duration of hypertension [96 (36, 180) vs. 60 (12, 120) months, P=0.001] than patients without SCS. There were 215 and 51 patients in the PA group and PA/SCS group, who completed adrenalectomy and follow-up, respectively. The remission rate of autonomous cortisol secretion in the PA/SCS group was 85.3% (29/34). There was no significant difference in the remission rate of autonomous aldosterone secretion among patients between the PA/SCS and PA group (94.1%, 48/51 vs. 94.4%, 203/215; P=1.000), while the clinical remission rate in the PA/SCS group was lower than that in the PA group (39.2%, 20/51 vs. 61.9%, 133/215; P=0.003). Conclusions: SCS is common in PA patients (22.3%), and the clinical remission rate is low. Screening using the 1-mg overnight dexamethasone suppression test is recommended for all patients with PA.


Assuntos
Neoplasias das Glândulas Suprarrenais , Síndrome de Cushing , Hiperaldosteronismo , Humanos , Feminino , Síndrome de Cushing/complicações , Síndrome de Cushing/diagnóstico , Neoplasias das Glândulas Suprarrenais/complicações , Estudos Retrospectivos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico , Prognóstico , Dexametasona/uso terapêutico , Aldosterona
10.
Front Endocrinol (Lausanne) ; 15: 1336128, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650714

RESUMO

Purpose: Surgery is the only way to cure pheochromocytoma; however, postoperative hemodynamic instability is one of the main causes of serious complications and even death. This study's findings provide some guidance for improved clinical management. Patients and methods: This study was to investigate the factors leading to postoperative hemodynamic instability in the postoperative pathology indicated pheochromocytoma from May 2016 to May 2022. They were divided into two groups according to whether vasoactive drugs were used for a median number of days or more postoperatively. The factors affecting the postoperative hemodynamics in the perioperative period (preoperative, intraoperative, and postoperative) were then evaluated. Results: The median number of days requiring vasoactive drug support postoperatively was three in 234 patients, while 118 (50.4%) patients required vasoactive drug support for three days or more postoperatively. The results of the multivariate analysis indicated more preoperative colloid use (odds ratio [OR]=1.834, confidence interval [CI]:1.265-2.659, P=0.001), intraoperative use of vasoactive drug (OR=4.174, CI:1.882-9.258, P<0.001), and more postoperative crystalloid solution input per unit of body weight per day (ml/kg/d) (OR=1.087, CI:1.062-1.112, P<0.001) were risk factors for predicting postoperative hemodynamic instability. The optimal cutoff point of postoperative crystalloid use were 42.37 ml/kg/d. Conclusion: Hemodynamic instability is a key issue for consideration in the perioperative period of pheochromocytoma. The amount of preoperative colloid use, the need for intraoperative vasoactive drugs, and postoperative crystalloid solution are risk factors for predicting postoperative hemodynamic instability (registration number: ChiCT2300071166).


Assuntos
Neoplasias das Glândulas Suprarrenais , Hemodinâmica , Feocromocitoma , Complicações Pós-Operatórias , Feocromocitoma/cirurgia , Feocromocitoma/fisiopatologia , Humanos , Feminino , Masculino , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Hemodinâmica/fisiologia , Pessoa de Meia-Idade , Adulto , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos de Coortes , Adrenalectomia/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Idoso , Vasoconstritores/uso terapêutico , Soluções Cristaloides/administração & dosagem
11.
BMJ Case Rep ; 17(4)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38670572

RESUMO

Pheochromocytoma is a chromaffin cell-derived adrenal medullary tumour and usually presents with paroxysms of hypertension, palpitations, sweating and headache due to excessive catecholamine release. These tumours can also secrete a variety of bioactive neuropeptides and hormones other than catecholamines, resulting in unusual clinical manifestations. We report a female in her mid-30s who presented with fever, anaemia, thrombocytosis and markedly elevated inflammatory markers. The fever profile, including cultures, was negative. Contrast-enhanced CT of abdomen showed a large solid-cystic right adrenal lesion with elevated plasma-free normetanephrine levels suggestive of pheochromocytoma. The fever persisted despite empirical antibiotics and antipyretics. Interleukin-6 (IL-6) levels were elevated (41.2 pg/mL (3-4 pg/mL)). She was initiated on naproxen (NPX) at a dose of 250 mg two times per day. The patient responded to NPX, and after stabilisation, she underwent an adrenalectomy. There was a complete resolution of fever with normalisation of IL-6 levels postoperatively.


Assuntos
Neoplasias das Glândulas Suprarrenais , Adrenalectomia , Interleucina-6 , Feocromocitoma , Humanos , Feocromocitoma/complicações , Feocromocitoma/cirurgia , Feocromocitoma/sangue , Feminino , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/sangue , Interleucina-6/sangue , Adulto , Naproxeno/uso terapêutico , Febre/etiologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Tomografia Computadorizada por Raios X
12.
BMJ Case Rep ; 17(4)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38670570

RESUMO

With only 15 reported cases, anastomosing haemangioma of adrenal is a rare entity and usually presents as adrenal incidentaloma. A hypertensive, diabetic, non-smoker man in his late 60s presented with irritative voiding symptoms. On evaluation, he was found to have a urinary bladder mass and left adrenal incidentaloma measuring 8 cm. Metabolic evaluation confirmed it to be non-functional.The patient underwent transurethral resection of bladder tumour with left laparoscopic adrenalectomy. Intraoperatively, the adrenal tumour was highly vascular with multiple feeder vessels. Grossly it was soft, encapsulated with focal grey-brown areas. Microscopically, most of adrenal gland was replaced by anastomosing proliferating capillary vessels within framework of non-endothelial supporting cells reminiscent of splenic sinusoids. The tumour was positive for CD-31, CD-34, Glut-1 and SMA.Anastomosing haemangioma is a benign entity but it must be differentiated from angiosarcoma. Characteristic imaging features are not yet defined and is, therefore, difficult to diagnose preoperatively.


Assuntos
Neoplasias das Glândulas Suprarrenais , Adrenalectomia , Hemangioma , Humanos , Masculino , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Hemangioma/cirurgia , Hemangioma/diagnóstico , Hemangioma/complicações , Adrenalectomia/métodos , Diagnóstico Diferencial , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia
14.
Front Endocrinol (Lausanne) ; 15: 1370525, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596218

RESUMO

Introduction: Endocrine hypertension (EHT) due to pheochromocytoma/paraganglioma (PPGL), Cushing's syndrome (CS), or primary aldosteronism (PA) is linked to a variety of metabolic alterations and comorbidities. Accordingly, patients with EHT and primary hypertension (PHT) are characterized by distinct metabolic profiles. However, it remains unclear whether the metabolomic differences relate solely to the disease-defining hormonal parameters. Therefore, our objective was to study the association of disease defining hormonal excess and concomitant adrenal steroids with metabolomic alterations in patients with EHT. Methods: Retrospective European multicenter study of 263 patients (mean age 49 years, 50% females; 58 PHT, 69 PPGL, 37 CS, 99 PA) in whom targeted metabolomic and adrenal steroid profiling was available. The association of 13 adrenal steroids with differences in 79 metabolites between PPGL, CS, PA and PHT was examined after correction for age, sex, BMI, and presence of diabetes mellitus. Results: After adjustment for BMI and diabetes mellitus significant association between adrenal steroids and metabolites - 18 in PPGL, 15 in CS, and 23 in PA - were revealed. In PPGL, the majority of metabolite associations were linked to catecholamine excess, whereas in PA, only one metabolite was associated with aldosterone. In contrast, cortisone (16 metabolites), cortisol (6 metabolites), and DHEA (8 metabolites) had the highest number of associated metabolites in PA. In CS, 18-hydroxycortisol significantly influenced 5 metabolites, cortisol affected 4, and cortisone, 11-deoxycortisol, and DHEA each were linked to 3 metabolites. Discussions: Our study indicates cortisol, cortisone, and catecholamine excess are significantly associated with metabolomic variances in EHT versus PHT patients. Notably, catecholamine excess is key to PPGL's metabolomic changes, whereas in PA, other non-defining adrenal steroids mainly account for metabolomic differences. In CS, cortisol, alongside other non-defining adrenal hormones, contributes to these differences, suggesting that metabolic disorders and cardiovascular morbidity in these conditions could also be affected by various adrenal steroids.


Assuntos
Neoplasias das Glândulas Suprarrenais , Cortisona , Síndrome de Cushing , Diabetes Mellitus , Hipertensão , Paraganglioma , Feocromocitoma , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Hidrocortisona/metabolismo , Estudos Retrospectivos , Síndrome de Cushing/complicações , Esteroides , Neoplasias das Glândulas Suprarrenais/complicações , Hipertensão/complicações , Feocromocitoma/complicações , Paraganglioma/complicações , Catecolaminas , Desidroepiandrosterona
15.
Zhonghua Yi Xue Za Zhi ; 104(14): 1174-1179, 2024 Apr 09.
Artigo em Chinês | MEDLINE | ID: mdl-38583049

RESUMO

Objective: To analyze the clinical features of patients with metastatic pheochromocytoma/paraganglioma (PPGL). Methods: A follow-up study. The clinical data of 250 patients with metastatic PPGL treated at Peking Union Medical College Hospital from January 2018 to August 2023 were retrospectively analyzed, including 124 males and 126 females. The clinical features and treatment status of patients with metastatic PPGL were summarized and analyzed. Kaplan-Meier survival curve was used to evaluate patients' prognosis. Results: The age of onset, age of diagnosis, and age of tumor metastasis in patients with metastatic PPGL were (33.1±14.2) years, (35.4±15.2) years, and (40.7±15.3) years, respectively. Metastasis occurred in 26.4%(66/250) of patients at the time of initial diagnosis. Among patients without metastases at the time of initial diagnosis, the time from primary tumor resection to metastasis[M(Q1, Q3)] was 5.0 (3.0, 9.0) years, among which 20.1%(37/184) of patients had metastases more than 10 years after surgery. Most patients showed increased 24-hour urinary norepinephrine and plasma normetanephrine, accounting for 78.2%(176/225) and 78.7%(85/108), respectively. 42.3%(69/163) of patients had increased neuron specific enolase (NSE)levels. Germline mutations were screened in 201 patients, of which 55.2%(111/201) had germline pathogenic mutations. In patients with gene mutations, 76.5%(85/111) had SDHB mutations. 52.0%(130/250) of metastatic PPGL patients had primary sites outside the adrenal gland, with the Ki-67 index of 5% (3%, 8%). There were 85.6%(214/250) patients had multisystem metastasis, with bone metastasis being the most common site of metastasis, accounting for 60.8%(152/250). In terms of treatment, 32.8%(75/229) of patients underwent two treatment regimens and 8.7%(20/229) of patients underwent three treatment regimens. Most patients had a good prognosis, with a 5-year and 10-year survival rate of 88.0% and 84.0%, respectively. However, some patients had rapid disease progression, and as of August 2023, 30 patients died, and the time from diagnosis to death in deceased patients was 2.0 (1.0, 4.0) years. Conclusions: Patients with metastatic PPGL have a high rate of germline mutations, especially those with SDHB mutations. The metastatic PPGL is usually multisystem metastasis with the characteristics of mostly paraganglioma, large lesion diameter and high Ki-67 index.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Feocromocitoma/diagnóstico , Seguimentos , Estudos Retrospectivos , Antígeno Ki-67 , Paraganglioma/diagnóstico , Paraganglioma/genética , Paraganglioma/patologia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Succinato Desidrogenase/genética
16.
Sci Rep ; 14(1): 8044, 2024 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580769

RESUMO

The crosstalk between the chromaffin and adrenocortical cells is essential for the endocrine activity of the adrenal glands. This interaction is also likely important for tumorigenesis and progression of adrenocortical cancer and pheochromocytoma. We developed a unique in vitro 3D model of the whole adrenal gland called Adrenoid consisting in adrenocortical carcinoma H295R and pheochromocytoma MTT cell lines. Adrenoids showed a round compact morphology with a growth rate significantly higher compared to MTT-spheroids. Confocal analysis of differential fluorescence staining of H295R and MTT cells demonstrated that H295R organized into small clusters inside Adrenoids dispersed in a core of MTT cells. Transmission electron microscopy confirmed the strict cell-cell interaction occurring between H295R and MTT cells in Adrenoids, which displayed ultrastructural features of more functional cells compared to the single cell type monolayer cultures. Adrenoid maintenance of the dual endocrine activity was demonstrated by the expression not only of cortical and chromaffin markers (steroidogenic factor 1, and chromogranin) but also by protein detection of the main enzymes involved in steroidogenesis (steroidogenic acute regulatory protein, and CYP11B1) and in catecholamine production (tyrosine hydroxylase and phenylethanolamine N-methyltransferase). Mass spectrometry detection of steroid hormones and liquid chromatography measurement of catecholamines confirmed Adrenoid functional activity. In conclusion, Adrenoids represent an innovative in vitro 3D-model that mimics the spatial and functional complexity of the adrenal gland, thus being a useful tool to investigate the crosstalk between the two endocrine components in the pathophysiology of this endocrine organ.


Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Humanos , Glândulas Suprarrenais/metabolismo , Catecolaminas/metabolismo , Cromograninas/metabolismo
17.
Medicine (Baltimore) ; 103(17): e37916, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669419

RESUMO

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with diverse clinical presentations. Alterations in energy expenditure state are commonly observed in patients with PPGL. However, the reported prevalence of hypermetabolism varies significantly and the underlying mechanisms and implications of this presentation have not been well elucidated. This review discusses and analyzes the factors that contribute to energy consumption. Elevated catecholamine levels in patients can significantly affect substance and energy metabolism. Additionally, changes in the activation of brown adipose tissue (BAT), inflammation, and the inherent energy demands of the tumor can contribute to increased resting energy expenditure (REE) and other energy metabolism indicators. The PPGL biomarker, chromogranin A (CgA), and its fragments also influence energy metabolism. Chronic hypermetabolic states may be detrimental to these patients, with surgical tumor removal remaining the primary therapeutic intervention. The high energy expenditure of PPGL has not received the attention it deserves, and an accurate assessment of energy metabolism is the cornerstone for an adequate understanding and treatment of the disease.


Assuntos
Neoplasias das Glândulas Suprarrenais , Metabolismo Energético , Paraganglioma , Feocromocitoma , Humanos , Metabolismo Energético/fisiologia , Feocromocitoma/metabolismo , Paraganglioma/metabolismo , Neoplasias das Glândulas Suprarrenais/metabolismo , Catecolaminas/metabolismo , Tecido Adiposo Marrom/metabolismo , Cromogranina A/metabolismo
18.
J Pediatr Endocrinol Metab ; 37(5): 482-485, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38618883

RESUMO

OBJECTIVES: Childhood cancer survivors are at risk for premature ovarian insufficiency, especially after treatment with alkylating agents. The objective of this report is to highlight a case in which this phenomenon caused a false-positive pregnancy test. CASE PRESENTATION: A workup was performed in a 14-year-old girl with a positive pregnancy test. She was diagnosed with stage IV neuroblastoma of the left adrenal gland at the age of 4 years. She received extensive treatment, including alkylating agents, and had been diagnosed with premature ovarian insufficiency. An LH/hCG suppression test was performed using high dose 17 bèta-estradiol: hCG levels normalized. CONCLUSIONS: The pregnancy test was false-positive due to production of low amounts of hCG by the pituitary gland as a result of high LH concentrations following premature ovarian insufficiency. It may be helpful to perform the LH/hCG suppression test to prove pituitary origin of the hCG overproduction.


Assuntos
Insuficiência Ovariana Primária , Humanos , Feminino , Insuficiência Ovariana Primária/diagnóstico , Insuficiência Ovariana Primária/patologia , Adolescente , Gravidez , Testes de Gravidez , Neuroblastoma/complicações , Neuroblastoma/patologia , Neuroblastoma/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Reações Falso-Positivas , Hormônio Luteinizante/sangue , Prognóstico
20.
Clin Nucl Med ; 49(6): 587-588, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557426

RESUMO

ABSTRACT: Prostate carcinoma (PC) is the second most common malignant tumor in males globally. The metastatic spread of PC usually involves the pelvic and abdominal lymph nodes and the skeletal system. Cutaneous metastases are exceedingly uncommon and typically manifest themselves late in the disease course, considered as ominous sign with limited treatment options and a poor prognosis. We describe a patient wherein 68 Ga-PSMA-11 PET/CT detected multiple uncommon metastatic sites in the cutaneous region of the scrotum, penis, and thigh, as well as in the subcutaneous region of anterior abdominal wall, and in bilateral adrenal glands. These findings served as a theranostic tool for selecting 177 Lu-PSMA-617 treatment for these extremely rare metastatic sites.


Assuntos
Neoplasias das Glândulas Suprarrenais , Isótopos de Gálio , Radioisótopos de Gálio , Lutécio , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Neoplasias Cutâneas , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/secundário , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Ácido Edético/análogos & derivados , Progressão da Doença , Radioisótopos/uso terapêutico , Dipeptídeos/uso terapêutico , Idoso , Oligopeptídeos , Tela Subcutânea/diagnóstico por imagem , Tela Subcutânea/patologia , Medicina de Precisão
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