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1.
Yonsei Med J ; 61(3): 257-261, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32102127

RESUMO

Esthesioneuroblastoma as a source of ectopic Cushing's syndrome is rare, and to the best of our knowledge, only 20 cases have been reported worldwide. A 46-year-old healthy man visited a local clinic for general weakness and hyposmia, and underwent examination with serial endocrinological workup and brain imaging. 68Gallium-DOTA-TOC positron emission tomography scan was helpful where diagnosis of sellar MRI and inferior petrosal sinus sampling were discordant. Combined transcranial and endoscopic endonasal approach surgery was performed, and a diagnosis of esthesioneuroblastoma was given.


Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Síndrome de Cushing/complicações , Estesioneuroblastoma Olfatório/complicações , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/patologia , Estesioneuroblastoma Olfatório/diagnóstico por imagem , Estesioneuroblastoma Olfatório/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Cuidados Pós-Operatórios , Tomografia Computadorizada por Raios X
2.
Clin Nucl Med ; 44(11): 881-882, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31524683

RESUMO

Approximately 5% to 15% cases of endogenous Cushing syndrome are due to ectopic adrenocorticotrophic hormone (ACTH)-producing neuroendocrine tumors, which are commonly located in bronchopulmonary system, thymus, and gastrointestinal tract including pancreas. Although carcinoid tumors of the appendix are revealed in 0.3% of patients undergoing routine appendectomy, ACTH-secreting appendicular carcinoid is a rare entity. We present a case of a 22-year-old woman with ectopic ACTH-dependent Cushing syndrome due to an appendicular carcinoid, which was localized with the help of Ga-DOTATATE PET/CT scan.


Assuntos
Neoplasias do Apêndice/complicações , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/etiologia , Compostos Organometálicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Síndrome de Cushing/patologia , Feminino , Humanos , Adulto Jovem
3.
BMC Endocr Disord ; 19(1): 68, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253144

RESUMO

BACKGROUND: Endogenous Cushing's syndrome, a rare endocrine disorder, characterised by chronic cortisol hypersecretion, results in neuropsychiatric disturbances and in cognitive deficits, which are only partially reversible after the biochemical remission of the disease. CASE PRESENTATION: We report a case of a woman with a profound cognitive deficit and a gradual functional decline caused by Cushing's disease of at least 10 years duration. The neurosurgical resection of her 2 mm adrenocorticotropic hormone (ACTH) secreting pituitary microadenoma resulted in a successful resolution of the patient's hypercortisolism and a significant recovery of her neurocognitive function. The patient's progress was evaluated using serial clinical observations, functional assessments, Mini-Mental Status exams and through the formal neuropsychological report. Furthermore, the patient's recovery of her neurocognitive function was reflected by a sustained improvement in the patient's specific structural brain abnormalities on radiological imaging. CONCLUSIONS: This report illustrates the importance of early detection and treatment of Cushing's syndrome in order to prevent neurocognitive impairment and neuropsychiatric disorders which are associated with an endogenous cortisol hypersecretion. The long term adverse effects of severe hypercortisolaemia on brain function and the pathophysiological mechanisms responsible for the structural and functional changes in brain anatomy due to glucocorticoid excess are reviewed.


Assuntos
Síndrome de Cushing/cirurgia , Transtornos Neurocognitivos/complicações , Adenoma Hipofisário Secretor de ACT/diagnóstico por imagem , Adenoma Hipofisário Secretor de ACT/cirurgia , Encéfalo/diagnóstico por imagem , Cognição , Síndrome de Cushing/complicações , Síndrome de Cushing/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Transtornos Neurocognitivos/cirurgia , Indução de Remissão , Fatores de Tempo
4.
Nucl Med Commun ; 40(5): 539-544, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30973841

RESUMO

OBJECTIVE: This study aimed to present a proper understanding of the fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) value in localizing the primary lesion in adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome in a relatively large case cohort. PATIENTS AND METHODS: This retrospective study included 47 patients with ACTH-dependent Cushing syndrome, who underwent an F-FDG PET/CT examination in our hospital from November 2010 to January 2018. The serum cortisol, 24 h urine cortisol, serum ACTH, and high-dose dexamethasone suppression test were measured in all the patients. Bilateral inferior petrosal sinus sampling was performed in 28/47 patients. Pituitary magnetic resonance imaging and whole-body F-FDG PET/CT were performed in all patients. RESULTS: Serum ACTH at 8 a.m. higher than 161.8 pg/ml as the cut-off value showed the best diagnostic accuracy (73.9%) for the successful localization of the primary lesions. In Cushing disease patients, the pituitary maximum standardized uptake value F-FDG PET/CT (n=11) did not show significant differences compared with that in ectopic ACTH syndrome (EAS) patients (n=20). In terms of EAS, the descending order of maximum standardized uptake value was 13.2±8.3 (4.8-26.4) in pancreatic neuroendocrine tumors (n=4), 7.1±2.4 (3.5-10.1) in mediastinal carcinoid (n=11), and 2.0±0.1 (1.9-2.2) in bronchial carcinoid (n=4). This study first reported the F-FDG PET/CT images of ACTH-secreting olfactory neuroblastoma. CONCLUSION: Serum ACTH level determines the success rate of localization of the primary ACTH-secreting tumor in ACTH-dependent syndrome. F-FDG PET/CT plays a role in localizing the site for EAS, although it plays a limited role in Cushing disease.


Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/metabolismo , Fluordesoxiglucose F18 , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
6.
J Vet Intern Med ; 33(1): 72-78, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30536676

RESUMO

BACKGROUND: Spontaneous hypercortisolism or Cushing's syndrome in dogs is either pituitary or adrenal dependent, but concurrent pituitary and adrenal hypercortisolism also has been reported. OBJECTIVE: To determine how often concurrent pituitary and adrenal lesions are present in dogs with spontaneous hypercortisolism. ANIMALS: Two hundred one client-owned dogs with spontaneous hypercortisolism. METHODS: Retrospective study. Pre- and post-contrast computed tomography (CT) scans of the pituitary and adrenal glands were performed in dogs with confirmed hypercortisolism. RESULTS: In dogs with dexamethasone-suppressible hypercortisolism (122/201), 78 dogs (64%) had an enlarged pituitary gland (median pituitary height/brain area [P/B], 0.43 × 10-2 mm-1 ; range, 0.32-1.21 × 10-2 mm-1 ). Two of these 78 dogs had concurrent adrenal lesions. In the remaining dogs (44/122; 36%), the pituitary gland was not enlarged. In the dexamethasone-resistant group (79/201), the pituitary gland was enlarged in 47 dogs (59%; median P/B, 0.57 × 10-2 ; range, 0.32-1.50 × 10-2 mm-1 ). Eight of these 47 dogs (17%) had concurrent adrenal lesions. In the remaining 32 dexamethasone-resistant dogs (41%), the pituitary gland was not enlarged. Among them, 27 dogs had adrenal lesions and suppressed ACTH concentrations consistent with adrenal-dependent hypercortisolism and 5 dogs were diagnosed with pituitary-dependent hypercortisolism. CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent pituitary and adrenal lesions were present in 5% of all dogs with hypercortisolism and in 10% of the dexamethasone-resistant dogs. Diagnostic imaging of both pituitary and adrenal glands should be included in the diagnostic evaluation of every dog with spontaneous hypercortisolism to obtain information needed for estimation of prognosis and choosing the optimal treatment.


Assuntos
Córtex Suprarrenal/diagnóstico por imagem , Síndrome de Cushing/veterinária , Doenças do Cão/diagnóstico por imagem , Hipófise/diagnóstico por imagem , Córtex Suprarrenal/patologia , Animais , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/patologia , Doenças do Cão/patologia , Cães , Feminino , Masculino , Hipófise/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/veterinária
7.
Endocr J ; 66(2): 175-180, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30568069

RESUMO

Cushing's syndrome (CS) is a clinical syndrome characterized by hypercortisolemia. Cyclic Cushing's syndrome (CCS), which exhibits a periodic or irregular increasing pattern in cortisol, is a rare type of Cushing's syndrome. A 37-year-old man came to our hospital because of repeated dizzy spells, weakness and hypercortisolemia lasting two weeks. Endocrinological examinations indicated CCS with periodic and intermittent increases in cortisol. Enhanced computed tomography (CT) revealed space occupying lesions on the upper lobe of left lung, and biopsy eventually proved that these were pulmonary carcinoid tumors with ectopic ACTH secretion, which was subsequently manifested a Cushing's syndrome. PET-CT, ultrasound and biopsy of the thyroid gland indicated bilateral thyroid papillary carcinoma. CT scan showed bilateral nodular hyperplasia of the adrenal gland. Enhanced magnetic resonance imaging (MRI) confirmed that the high signal disappeared on the posterior lobe of the pituitary gland and that the pituitary stalk shifted left, which was suspected to be non-functional pituitary microadenoma. The patient underwent surgery involving resection of the left upper pulmonary lobe and the mediastinal lymph node around the hilus pulmonis, which resulted in complete remission of CCS. The patient then chose elective surgery for the thyroid papillary carcinoma. An analysis of the patient's genomic DNA identified a novel mutation in PDE11A: c.2032 (exon 12) G > A, which is associated with primary pigmented nodular adrenocortical disease (PPNAD). This is a novel mutation which has been no previous public clinical report on this mutation as it relates to this disease.


Assuntos
Síndrome de Cushing/etiologia , Neoplasias Pulmonares/complicações , Tumores Neuroendócrinos/complicações , Câncer Papilífero da Tireoide/complicações , Neoplasias da Glândula Tireoide/complicações , Adulto , Síndrome de Cushing/diagnóstico por imagem , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Tumores Neuroendócrinos/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem
10.
J Cancer Res Ther ; 14(Supplement): S812-S814, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30249912

RESUMO

In general, paragangliomas are symptomatic tumors, which may be clinically taken for other tumors, benign or malignant lesions. Paragangliomas of the nasal cavity and paranasal sinuses are an extremely rare entity and what is even rarer is its association with ectopic adrenocorticotropic hormone production. We report this very rare case to highlight the rare association of Cushing's syndrome with nasal paraganglioma and the importance of total surgical resection in its treatment.


Assuntos
Síndrome de Cushing/cirurgia , Cavidade Nasal/cirurgia , Paraganglioma/cirurgia , Seios Paranasais/cirurgia , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/patologia , Paraganglioma/diagnóstico por imagem , Paraganglioma/patologia , Seios Paranasais/diagnóstico por imagem , Seios Paranasais/patologia
11.
Eur J Endocrinol ; 179(5): 307-317, 2018 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-30108093

RESUMO

OBJECTIVE: Glucocorticoid excess is one of the most important causes of bone disorders. Bone marrow fat (BMF) has been identified as a l new mediator of bone metabolism. Cushing syndrome (CS), is a main regulator of adipose tissue distribution but its impact on BMF is unknown. The objective of the study was to evaluate the effect of chronic hypercortisolism on BMF. DESIGN: This was a cross-sectional study. Seventeen active and seventeen cured ACTH-dependent CS patients along with seventeen controls (matched with the active group for age and sex) were included. METHODS: the BMF content of the femoral neck and L3 vertebrae were measured by 1H-MRS on a 3-Tesla wide-bore magnet. BMD was evaluated in patients using dual-energy X-ray absorptiometry. RESULTS: Active CS patients had higher BMF content both in the femur (82.5±2.6%) and vertebrae (70.1±5.1%) compared to the controls (70.8±3.6%, p=0.013 and 49.0±3.7% p=0.005, respectively). In cured CS patients (average remission time of 43 months), BMF content was not different from controls at both sites (72.3±2.9% (femur) and 46.7%±5.3% (L3)). BMF content was positively correlated with age, fasting plasma glucose, HbA1c, triglycerides and visceral adipose tissue in the whole cohort and negatively correlated with BMD values in the CS patients . CONCLUSIONS: Accumulation of BMF is induced by hypercortisolism. In remission patients BMF reached values of controls. Further studies are needed to determine whether this increase in marrow adiposity in CS is associated with bone loss.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Adiposidade/fisiologia , Densidade Óssea/fisiologia , Medula Óssea/diagnóstico por imagem , Síndrome de Cushing/diagnóstico por imagem , Absorciometria de Fóton , Adulto , Estudos Transversais , Feminino , Colo do Fêmur/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Espectroscopia de Prótons por Ressonância Magnética
12.
J Neurosurg ; 131(2): 532-538, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-30117768

RESUMO

OBJECTIVE: Gamma Knife radiosurgery (GKS) is typically used after failed resection in patients with Cushing's disease (CD) and acromegaly. Little is known about the upfront role of GKS for patients with CD and acromegaly. In this study, the authors examine the outcome of upfront GKS for patients with these functioning adenomas. METHODS: An international group of 7 Gamma Knife centers sent pooled data from 46 patients (21 with CD and 25 with acromegaly) undergoing upfront GKS to the coordinating center of the study for analysis. Diagnosis was established on the basis of clinical, endocrine, and radiological studies. All patients were treated on a common radiosurgical platform and longitudinally followed for tumor control, endocrine remission, and hypopituitarism. Patients received a tumor median margin dose of 25 Gy (range 12-40.0 Gy) at a median isodose of 50%. RESULTS: The median endocrine follow-up was 69.5 months (range 9-246 months). Endocrine remission was achieved in 51% of the entire cohort, with 28% remission in acromegaly and 81% remission for those with CD at the 5-year interval. Patients with CD achieved remission earlier as compared to those with acromegaly (p = 0.0005). In patients post-GKS, the pituitary adenoma remained stable (39%) or reduced (61%) in size. Hypopituitarism occurred in 9 patients (19.6%), and 1 (2.2%) developed third cranial nerve (CN III) palsy. Eight patients needed further intervention, including repeat GKS in 6 and transsphenoidal surgery in 2. CONCLUSIONS: Upfront GKS resulted in good tumor control as well as a low rate of adverse radiation effects in the whole group. Patients with CD achieved a faster and far better remission rate after upfront GKS in comparison to patients with acromegaly. GKS can be considered as an upfront treatment in carefully selected patients with CD who are unwilling or unable to undergo resection, but it has a more limited role in acromegaly.


Assuntos
Acromegalia/diagnóstico por imagem , Acromegalia/cirurgia , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/cirurgia , Internacionalidade , Radiocirurgia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Clin Nucl Med ; 43(10): 769-770, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30036246

RESUMO

Ectopic Cushing syndrome constitutes approximately 10% of all patients with Cushing syndrome. The clinical features of hypercortisolism result from elevated levels of adrenocorticotropic hormone produced by a tumor. The present case presented with clinical and biochemical parameters suggestive of Cushing syndrome with normal pituitary and adrenals on imaging. Ga-DOTANOC PET/CT done to localize an ectopic adrenocorticotropic hormone-producing tumor revealed metastatic medullary carcinoma of the thyroid as the culprit lesion.


Assuntos
Hormônio Adrenocorticotrópico/biossíntese , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/metabolismo , Compostos Organometálicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Carcinoma Neuroendócrino/complicações , Carcinoma Neuroendócrino/patologia , Síndrome de Cushing/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/patologia
16.
JCI Insight ; 3(8)2018 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-29669941

RESUMO

Mutations in the gene encoding the protein kinase A (PKA) catalytic subunit α have been found to be responsible for cortisol-producing adenomas (CPAs). In this study, we identified by whole-exome sequencing the somatic mutation p.S54L in the PRKACB gene, encoding the catalytic subunit ß (Cß) of PKA, in a CPA from a patient with severe Cushing syndrome. Bioluminescence resonance energy transfer and surface plasmon resonance assays revealed that the mutation hampers formation of type I holoenzymes and that these holoenzymes were highly sensitive to cAMP. PKA activity, measured both in cell lysates and with recombinant proteins, based on phosphorylation of a synthetic substrate, was higher under basal conditions for the mutant enzyme compared with the WT, while maximal activity was lower. These data suggest that at baseline the PRKACB p.S54L mutant drove the adenoma cells to higher cAMP signaling activity, probably contributing to their autonomous growth. Although the role of PRKACB in tumorigenesis has been suggested, we demonstrated for the first time to our knowledge that a PRKACB mutation can lead to an adrenal tumor. Moreover, this observation describes another mechanism of PKA pathway activation in CPAs and highlights the particular role of residue Ser54 for the function of PKA.


Assuntos
Adenoma/enzimologia , Síndrome de Cushing/diagnóstico por imagem , Proteínas Quinases Dependentes de AMP Cíclico/genética , Hidrocortisona/metabolismo , Adenoma/metabolismo , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Insuficiência Adrenal/etiologia , Adrenalectomia/métodos , Adulto , Domínio Catalítico/genética , Síndrome de Cushing/patologia , Síndrome de Cushing/cirurgia , Proteína Receptora de AMP Cíclico/metabolismo , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico , Feminino , Holoenzimas/metabolismo , Humanos , Mutação , Resultado do Tratamento , Sequenciamento Completo do Exoma/métodos
17.
Ann Endocrinol (Paris) ; 79(2): 75-81, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29525561

RESUMO

Ectopic adrenal adenoma causing chronic Cushing's syndrome (CS) is a rare phenomenon. Diagnosis is usually made years after disease onset because of the insidious nature of the ectopic adrenal gland and because it overlaps with common symptoms, such as overweight and hypertension, in the general population (Kreitschmann-Andermahr et al., 2015). Here, we report the case of a 46-year-old male with a 15-year history of severe hypertension, facial plethora, and centripetal obesity. During treatment for herpes zoster, the patient presented with severe hypokalemia and flaccid paralysis, characteristic changes associated with CS. The serum cortisol level was elevated and baseline adrenocorticotrophic hormone (ACTH) was suppressed. After administration of the low-dose overnight dexamethasone suppression test, plasma cortisol was 38.9µg/dL. A contrast computed tomography (CT) scan revealed normal adrenal glands and significant tumor adjacent to the right renal hilum measuring ∼3.6×2.3cm. The tumor was removed through retroperitoneoscopy, and pathological examination confirmed adrenocortical adenoma and myelolipoma metaplasia. The serum potassium level gradually became normal after surgical removal of the mass. In the current report, we have reviewed the pertinent literature and highlighted the importance of considering ectopic adrenal adenoma in the differential diagnosis of chronic CS with nonspecific symptoms.


Assuntos
Adenoma/metabolismo , Neoplasias das Glândulas Suprarrenais/metabolismo , Adenoma/complicações , Adenoma/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais , Adrenalectomia , Hormônio Adrenocorticotrópico/sangue , Coristoma , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/etiologia , Síndrome de Cushing/metabolismo , Dexametasona/farmacologia , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
18.
BMC Med Genet ; 19(1): 49, 2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29587644

RESUMO

BACKGROUND: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing's syndrome (CS). BMAH is predominantly believed to be caused by two mutations, a germline and somatic one, respectively, as described in the two-hit hypothesis. In many familial cases of BMAH, mutations in armadillo repeat containing 5 (ARMC5), a putative tumor suppressor gene, are thought to induce the disorder. The objective of this study was to report a case in which the patient presented with BMAH induced by a novel heterozygous germline ARMC5 mutation (c. 517C > T, p. Arg173*) alone rather than a two-hit mutation. CASE PRESENTATION: A 51-year-old woman was identified with masses in the bilateral adrenals. Serum cortisol levels were increased significantly both in the morning (08:00 AM) and late at night (24:00 AM), while plasma adrenocorticotropic hormone was normal. The patient underwent a left adrenalectomy and histopathology substantiated the BMAH diagnosis. WES of the germline DNA discovered a novel heterozygous germline ARMC5 mutation (c. 517C > T, p. Arg173*) and in silico analysis predicted that the mutation significantly impaired protein function, resulting in inactivated ARMC5. Subsequently, WES of the tumor specimen identified 79 somatic single nucleotide polymorphisms (SNPs)/insertion-deletion (indel) mutations, including 32 missense/nonsense/splice/stop-loss mutations. None of these mutations were CS-related. CONCLUSIONS: A novel germline ARMC5 mutation (c. 517C > T, p. Arg173*) was identified that induced BMAH alone without a second mutation. ARMC5 sequencing may improve the identification of clinical forms of BMAH and allow earlier diagnosis of this disease.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Síndrome de Cushing/genética , Mutação em Linhagem Germinativa , Proteínas Supressoras de Tumor/genética , Hiperplasia Suprarrenal Congênita/diagnóstico por imagem , Hormônio Adrenocorticotrópico/sangue , Proteínas do Domínio Armadillo , Síndrome de Cushing/diagnóstico por imagem , Feminino , Heterozigoto , Humanos , Hidrocortisona/sangue , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único
19.
Clin Endocrinol (Oxf) ; 88(2): 209-216, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29115003

RESUMO

CONTEXT: Abdominal visceral adiposity and central sarcopenia are markers of increased cardiovascular risk and mortality. OBJECTIVE: To assess whether central sarcopenia and adiposity can serve as a marker of disease severity in patients with adrenal adenomas and glucocorticoid secretory autonomy. DESIGN: Retrospective cohort study. PATIENTS: Twenty-five patients with overt Cushing's syndrome (CS), 48 patients with mild autonomous cortisol excess (MACE) and 32 patients with a nonfunctioning adrenal tumour (NFAT) were included. METHODS: Medical records were reviewed, and body composition measurements (visceral fat [VAT], subcutaneous fat [SAT], visceral/total fat [V/T], visceral/subcutaneous [V/S] and total abdominal muscle mass) were calculated based on abdominal computed tomography (CT). RESULTS: In patients with overt CS, when compared to patients with NFAT, the V/T fat and the V/S ratio were increased by 0.08 (P < .001) and by 0.3 (P < .001); however, these measurements were decreased by 0.04 (P = .007) and 0.2 (P = .01), respectively, in patients with MACE. Total muscle mass was decreased by -10 cm2 (P = .02) in patients with overt CS compared to patients with NFAT. Correlation with morning serum cortisol concentrations after dexamethasone suppression testing revealed that for every 28 nmol/L cortisol increase there was a 0.008 increase in V/T (P < .001), 0.02 increase in the V/S fat ratio (P < .001) and a 1.2 cm2 decrease in mean total muscle mass (P = .002). CONCLUSIONS: The severity of hypercortisolism was correlated with lower muscle mass and higher visceral adiposity. These CT-based markers may allow for a more reliable and objective assessment of glucocorticoid-related disease severity in patients with adrenal adenomas.


Assuntos
Tecido Adiposo/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Adenoma Adrenocortical/patologia , Síndrome de Cushing/patologia , Músculo Esquelético/patologia , Tecido Adiposo/diagnóstico por imagem , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Adenoma Adrenocortical/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal/fisiologia , Síndrome de Cushing/diagnóstico por imagem , Feminino , Humanos , Hidrocortisona/sangue , Gordura Intra-Abdominal/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
20.
Endocr J ; 65(3): 269-279, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29279458

RESUMO

Primary macronodular adrenal hyperplasia (PMAH), also known in the past as bilateral macronodular adrenalhyperplasia or adrenocorticotropin (ACTH)-independent macronodular adrenal hyperplasia, is a rare type of Cushing's syndrome (CS) and is associated with bilateralenlargement of the adrenal glands. It accounts for <1% of all endogenous cases of CS. In order toidentify the pathogenic mutations in the causative gene of (AIMAH pedigrees, Whole-genome sequencing of three patients in family I was used to retrieve candidate causative genes. Meanwhile, the causative gene was identified by Sanger sequencing from the two pedigrees. Sequencing of ARMC5 exons of three patients was carried out to identify somatic mutations. Moreover, haploid clone of one tumor DNA sample was conducted. ARMC5 was the causative gene of two pedigrees confirmed by whole-genome sequencing (WGA) and Sanger sequencing. The variant sites of the two families were c.C943T (p.R315W) and c.C1960T (p.R654X), respectively. Autosomal dominant inheritance of AIMAH was confirmed by genotypes of one family member. Several somatic mutations were discovered in tumor DNA samples. In addition, haploid clone of tumor DNA was confirmed by germline mutation and somaticmutation, which suggested the pathogenic mechanism of "two-hit-model." ARMC5 was the causative gene of AIMAH pedigrees. This AIMAH in this study presented autosomal dominant inheritance, fitting to Mendelian inheritance law. However, the pathogenic mode of this disease showed as compound heterozygote.


Assuntos
Glândulas Suprarrenais/diagnóstico por imagem , Síndrome de Cushing/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Proteínas do Domínio Armadillo , Síndrome de Cushing/diagnóstico por imagem , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Tomografia Computadorizada por Raios X , Sequenciamento Completo do Genoma
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