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1.
ANZ J Surg ; 93(3): 550-554, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36537156

RESUMO

BACKGROUND: Maori have an increased incidence of thyrotoxicosis when compvared to non-Maori, however there are limited data on benign non-toxic nodular thyroid disease. AIMS: The aims of this study were to determine the rates of non-toxic multinodular goitre (NTMNG) surgery for Maori and non-Maori and to determine if there were differences in thyroid size between Maori and non-Maori undergoing total thyroidectomy for NTMNG. METHODS: Single centre study of patients undergoing thyroidectomy for NTMNG from 1 December 2006 to 30 November 2016. RESULTS: Maori were overrepresented amongst the 427 patients who underwent surgery for NTMNG at 34% compared to the expected ~17% of the background Maori adult population in the region. At the time of surgery, Maori were younger (P = 0.004) and had a larger thyroid gland (P < 0.001) when compared to non-Maori also undergoing total/near total thyroidectomy. Complication rates were low across all ethnic groups. CONCLUSION: Maori have increased rates of surgery for NTMNG compared to non-Maori and thyroid size is larger at the time of surgery. The reasons for this are currently unknown and more research is required.


Assuntos
Bócio , Doenças da Glândula Tireoide , Adulto , Humanos , Tireoidectomia/efeitos adversos , Bócio/cirurgia , Doenças da Glândula Tireoide/cirurgia , Incidência
2.
J Endocr Soc ; 3(7): 1335-1344, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31286097

RESUMO

BACKGROUND: Maori, the indigenous people of Aotearoa/New Zealand, have an increased incidence of Graves disease and often require more than one radioiodine (RAI) dose, raising the question as to whether surgery may be preferable in this population. However, there is a lack of outcome data after definitive therapy in an indigenous population. AIM: To assess ethnic differences in thyroid status after definitive therapy for Graves disease. METHODS: Single-center retrospective review of patients treated by RAI or thyroidectomy from 1 December 2001 to 31 March 2013. TSH levels at 1, 2, 5, and 10 years after treatment were recorded. RESULTS: A total of 798 patients were included: 589 received RAI, and 209 underwent surgery. Overall, 48% of patients were euthyroid at 1 year after definitive treatment, and 63.5% were euthyroid by 10 years. Maori were less likely to be euthyroid when compared with Europeans at all time points (e.g., 29.7% vs 57.3% at 1 year and 52.2% vs 70.9% at 10 years, P < 0.0005). Maori were more likely to receive more than one dose of RAI compared with Europeans (30.2% vs 14.2%, P < 0.0005). Persistent thyrotoxicosis at 1 year after RAI was seen in 25.8% of Maori compared with 8.3% of Europeans (P < 0.0005). CONCLUSIONS: Maori have lower rates of optimal thyroid levels than their European counterparts at all time points studied. Early disparity was associated with a higher RAI failure rate. Late differences were due to higher rates of untreated hypothyroidism. Overall, euthyroid rates were low, indicating the need for improvement in care, particularly for indigenous peoples.

3.
Am J Surg Pathol ; 43(1): 35-46, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29324469

RESUMO

The gene CDC73 (previously known as HRPT2) encodes the protein parafibromin. Biallelic mutation of CDC73 is strongly associated with malignancy in parathyroid tumors. Heterozygous germline mutations cause hyperparathyroidism jaw tumor syndrome,which is associated with a high life-time risk of parathyroid carcinoma. Therefore loss of parafibromin expression by immunohistochemistry may triage genetic testing for hyperparathyroidism jaw tumor syndrome and be associated with malignant behavior in atypical parathyroid tumors. We share our experience that parafibromin-negative parathyroid tumors show distinctive morphology. We searched our institutional database for parathyroid tumors demonstrating complete loss of nuclear expression of parafibromin with internal positive controls. Forty-three parafibromin-negative tumors from 40 (5.1%) of 789 patients undergoing immunohistochemistry were identified. Thirty-three (77%) were external consultation cases; the estimated incidence in unselected tumors was 0.19%. Sixteen (37.2%) fulfilled World Health Organization 2017 criteria for parathyroid carcinoma and 63% had serum calcium greater than 3mmol/L. One of 27 (3.7%) noninvasive but parafibromin-negative tumors subsequently metastasized. Parafibromin-negative patients were younger (mean, 36 vs. 63 y; P<0.001) and had larger tumors (mean, 3.04 vs. 0.62 g; P<0.001). Not all patients had full testing, but 26 patients had pathogenic CDC73 mutation/deletions confirmed in tumor (n=23) and/or germline (n=16). Parafibromin-negative tumors demonstrated distinctive morphology including extensive sheet-like rather than acinar growth, eosinophilic cytoplasm, nuclear enlargement with distinctive coarse chromatin, perinuclear cytoplasmic clearing, a prominent arborizing vasculature, and, frequently, a thick capsule. Microcystic change was found in 21 (48.8%). In conclusion, there are previously unrecognized morphologic clues to parafibromin loss/CDC73 mutation in parathyroid tumors which, given the association with malignancy and syndromic disease, are important to recognize.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias das Paratireoides/patologia , Proteínas Supressoras de Tumor/biossíntese , Adenoma/complicações , Adenoma/diagnóstico , Adolescente , Adulto , Idoso , Feminino , Fibroma/complicações , Fibroma/diagnóstico , Humanos , Hiperparatireoidismo/complicações , Hiperparatireoidismo/diagnóstico , Neoplasias Maxilomandibulares/complicações , Neoplasias Maxilomandibulares/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/genética , Proteínas Supressoras de Tumor/análise , Proteínas Supressoras de Tumor/genética , Adulto Jovem
4.
N Z Med J ; 131(1468): 69-74, 2018 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-29346358

RESUMO

BACKGROUND: Previously the risk of concomitant thyroid cancer in multinodular goitre (MNG) has been reported as approximately 4%. Cancer risk in toxic MNG was often considered lower than for non-toxic MNG, due to a possible protective effect of TSH suppression. However, recent American data suggest an approximately 18% risk of occult malignancy in both toxic and non-toxic MNG. AIMS: To assess malignancy risk in a New Zealand population undergoing thyroidectomy for MNG. METHODS: Single-centre study of patients undergoing thyroidectomy for MNG from 1 December 2006 to 30 November 2016. RESULTS: Six hundred and two patients underwent surgery for MNG (448 non-toxic and 154 toxic). Of these, 95/602 (16%) had thyroid cancer. After excluding patients operated for preoperative suspicion for cancer, 30/401 (8%) patients with non-toxic MNG and 15/151 (10%) with toxic MNG had unsuspected or occult thyroid cancer (p=0.358). Patients with toxic MNG were less likely to undergo preoperative fine needle aspiration than those with non-toxic MNG (34% vs 52%, respectively p=0.0001). Two-thirds of unsuspected thyroid cancers were incidental micropapillary carcinomas and unlikely to alter survival irrespective of therapy. CONCLUSION: Malignancy rates in MNG are higher than historically reported, although most unsuspected cancers are unlikely to alter mortality even if diagnosis is delayed.


Assuntos
Bócio Nodular/complicações , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/epidemiologia , Adulto , Biópsia por Agulha Fina , Feminino , Bócio Nodular/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Estudos Retrospectivos , Risco , Medição de Risco , Neoplasias da Glândula Tireoide/etiologia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia
5.
ANZ J Surg ; 86(6): 483-6, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25060597

RESUMO

INTRODUCTION: Approximately 5% of all abdominal computed tomography (CT) and magnetic resonance imaging (MRI) scans reveal an adrenal incidentaloma. Although most adrenal incidentalomas are benign non-functioning adenomas, lesions may be hormonally active and/or malignant. The aim of this study was to determine adherence to recommended international guidelines and potential influencing factors when an adrenal incidentaloma is identified in routine clinical practice. METHODS: A retrospective study was performed of all CT and MRI reports from December 2009 to December 2011 using a key phrase search to identify patients with an incidental adrenal lesion. RESULTS: A total of 125 patients with incidental adrenal lesions were identified, of which 74 patients were considered appropriate for further endocrine/radiological workup. Of the 74 patients, only 19 (26%) were initially referred to the endocrine service for investigation; 21/74 (28%) had complete biochemical workup and 24/74 (32%) had imaging follow-up arranged. The reporting radiologist provided advice for follow-up in 31/74 (42%), and action was more likely to be taken when this recommendation was given. Follow-up of the patients who had not received investigation was attempted resulting in assessment of a further 23 patients. Of the 44 patients who have undergone full assessment, four patients were found to have clinically significant lesions (one each of: Cushing's syndrome, phaeochromocytoma, Conn's syndrome and plasmacytoma). CONCLUSION: This study suggests that the majority of adrenal incidentalomas may not be investigated according to current international guidelines. The recommendations by the reporting radiologist appear to influence whether a patient is referred for further investigation.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Fidelidade a Diretrizes , Imageamento por Ressonância Magnética/normas , Tomografia Computadorizada por Raios X/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo
6.
Clin Endocrinol (Oxf) ; 84(4): 558-63, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25982929

RESUMO

OBJECTIVE: There are limited data on the incidence of iodinated contrast-induced thyrotoxicosis, particularly in iodine-deficient regions. The aim of this study was to determine the incidence of iodinated contrast-induced thyrotoxicosis and to determine whether thyrotoxicosis was more common in patients ≥70 years compared to those <70 years of age. DESIGN: A prospective study of adult patients undergoing an outpatient CT with iodinated contrast was performed. MEASUREMENTS: Thyroid function tests (TFTs) and urine iodine measurements were performed prior to the scan. TFTs were repeated at 4- and 8-weeks postscan. Changes in TFTs from baseline were analysed. RESULTS: A total of 102 patients were included in the final analysis. Overall, TSH levels dropped (P = 0·0002), and free T3 (FT3 ) levels increased (P = 0·04) between baseline and week 4 with normalization by week 8; however, these changes were not considered clinically significant. No significant differences in free T4 (FT4 ) occurred in the overall group (P = 0·82). There were no differences in TFTs between baseline and 4 or 8 weeks for those patients aged <70 compared to ≥70 years. Two patients developed new subnormal TSH values. Of these, one had a 90-mm follicular variant papillary thyroid carcinoma diagnosed while the other had a normal thyroid assessment and TSH spontaneously normalized by 12 weeks. CONCLUSIONS: Only 2% of patients developed subclinical hyperthyroidism following a standard dose of iodinated contrast for CT investigations. Given the low incidence of iodine-induced thyrotoxicosis, there is no indication for routine pre- and post-CT thyroid function testing in our region.


Assuntos
Meios de Contraste/intoxicação , Hipertireoidismo/induzido quimicamente , Iodo/deficiência , Iodo/intoxicação , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste/administração & dosagem , Feminino , Humanos , Hipertireoidismo/epidemiologia , Incidência , Iodo/urina , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Pacientes Ambulatoriais/estatística & dados numéricos , Estudos Prospectivos , Testes de Função Tireóidea , Tireotropina/análise , Tiroxina/análise , Fatores de Tempo , Tomografia Computadorizada por Raios X , Tri-Iodotironina/análise
7.
Case Rep Endocrinol ; 2015: 510985, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26257968

RESUMO

Individuals presenting with primary hyperparathyroidism (PHPT) at a young age commonly have an underlying germline gene mutation in one of the following genes: MEN1, CASR, or CDC73. A small number of families with primary hyperparathyroidism have been identified with germline mutations in CDKN1B and those patients with primary hyperparathyroidism have almost exclusively been women who present in middle age suggesting that the age of onset of PHPT in MEN4 may be later than that of MEN1. We present a case of apparently sporadic PHPT presenting in adolescence with single gland disease associated with a novel CDKN1B germline mutation (heterozygote for a missense mutation in exon 1 of the CDKN1B gene (c.378G>C) (p.E126D)). The implication from this case is that CDKN1B germline mutations may be associated with PHPT at an earlier age than previously thought.

8.
J Clin Endocrinol Metab ; 100(8): 3202-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26083822

RESUMO

CONTEXT: Pregnancies complicated by a pheochromocytoma or paraganglioma are very rare, being estimated to occur in 0.007% of all pregnancies. Both the well-being of the mother and fetus need to be considered, and management can be challenging. The optimal management of women with a pheochromocytoma or paraganglioma in pregnancy is not well established. OBJECTIVE: The objective of the study was to assess whether there is a difference in fetal or maternal mortality between pheochromocytomas and paragangliomas in pregnancy. DESIGN: We present an experience of eight pregnancies in four SDHB germline mutation-positive women with sympathetic paragangliomas, followed by a systematic review of the literature to compare the outcome of paragangliomas with that of pheochromocytomas occurring in pregnancy. RESULTS: In our case series, favorable fetal and maternal outcomes were seen in all eight pregnancies. From the systematic review, maternal and fetal mortality were lower in women with paragangliomas, at 3.6% and 12% respectively, compared with 9.8% and 16% in women with pheochromocytomas. CONCLUSION: Pregnant women with paragangliomas may be at a lower risk of adverse outcome than those with pheochromocytomas, but both maternal and fetal mortality rates are still higher than that of the general obstetric population.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Complicações Neoplásicas na Gravidez , Resultado da Gravidez , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/terapia , Adulto , Feminino , Humanos , Paraganglioma/diagnóstico , Paraganglioma/epidemiologia , Paraganglioma/genética , Paraganglioma/terapia , Linhagem , Feocromocitoma/diagnóstico , Feocromocitoma/epidemiologia , Feocromocitoma/genética , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/epidemiologia , Complicações Neoplásicas na Gravidez/genética , Complicações Neoplásicas na Gravidez/terapia , Resultado da Gravidez/epidemiologia , Irmãos , Adulto Jovem
9.
Hum Pathol ; 46(3): 390-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25554089

RESUMO

Many neuroendocrine tumors, including pheochromocytomas (PCs) and paragangliomas (PGLs), express one or more somatostatin receptors (SSTR1-5). A number of studies have reported SSTR expression in PCs and PGLs. However, receptor expression patterns have been conflicting, and until recently, specific monoclonal antibodies were not available against SSTR1-5. The aim of this study was to compare SSTR1-5 expression in succinate dehydrogenase (SDH)-deficient PCs and PGLs (defined as having absent SDHB immunostaining) to those tumors with normal SDHB staining. Immunohistochemistry for SDHB and SSTR1-5 was performed using specific monoclonal antibodies on archived formalin-fixed, paraffin-embedded tissue from patients who had undergone surgery for PC or PGLs. A total of 182 PC/PGLs were included (129 adrenal, 44 extra-adrenal, 9 metastases); 32 tumors were SDH deficient, whereas 150 tumors had positive SDHB staining. SDH-deficient tumors were more likely to demonstrate moderate or strong staining for SSTR2A and SSTR3 when compared with SDH-sufficient tumors (91% versus 49% [P < .0001] and 50% versus 21% [P = .0008], respectively). Immunostaining for the other SSTRs was not different between SDH-deficient and tumors with preserved SDHB staining. SSTR2A and SSTR3 are more likely to be expressed in SDH-deficient PC/PGLs as compared with tumors demonstrating normal SDHB staining pattern. These findings suggest that the role of somatostatin analogue therapy (unlabeled or radiolabeled) should be reexamined in the context of the underlying SDHB immunohistochemistry pattern.


Assuntos
Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Paraganglioma/metabolismo , Feocromocitoma/metabolismo , Receptores de Somatostatina/metabolismo , Succinato Desidrogenase/deficiência , Adulto , Idoso , Complexo II de Transporte de Elétrons , Feminino , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Paraganglioma/secundário , Paraganglioma Extrassuprarrenal/metabolismo , Paraganglioma Extrassuprarrenal/secundário , Feocromocitoma/secundário , Adulto Jovem
10.
Aust N Z J Obstet Gynaecol ; 54(4): 317-21, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24576228

RESUMO

BACKGROUND: Women requiring thyroid hormone replacement after definitive therapy (surgery or radioiodine) for Graves' disease who later conceive require an early increase in levothyroxine dose and monitoring of thyroid hormone levels throughout pregnancy. In addition, as TSH receptor antibodies (TRAb) can cross the placenta and affect the fetus, measurement of these antibodies during pregnancy is recommended. AIM: To review the management of pregnancies following definitive treatment for Graves' disease in order to assess the rates of maternal hypothyroidism and TRAb measurement. MATERIALS AND METHODS: Retrospective chart review of women who had undergone definitive treatment for Graves' disease at a tertiary hospital and subsequently had one or more pregnancies. RESULTS: A total of 29 women were identified, each of whom had at least one pregnancy since receiving definitive treatment for Graves' disease: there were a total of 49 pregnancies (22 in the surgical group and 27 in the radioiodine group). Both groups had high rates of hypothyroidism documented during pregnancy (47 and 50%, respectively). The surgical group was more likely to be euthyroid around the time of conception. Less than half of the women were referred to an endocrinologist or had TRAb measured during pregnancy. Neonatal thyroid function was measured in one-third of live births. One case of neonatal thyrotoxicosis was identified. CONCLUSIONS: Adherence to the current American Thyroid Association guidelines is poor. Further education of both patients and clinicians is important to ensure that treatment of women during pregnancy after definitive treatment follows the currently available guidelines.


Assuntos
Doença de Graves/terapia , Hipotireoidismo/terapia , Radioisótopos do Iodo/uso terapêutico , Complicações na Gravidez/terapia , Tireoidectomia , Adulto , Endocrinologia , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/imunologia , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Recém-Nascido , Cuidado Pós-Natal , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/imunologia , Resultado da Gravidez , Taxa de Gravidez , Cuidado Pré-Natal , Encaminhamento e Consulta , Estudos Retrospectivos , Testes de Função Tireóidea , Adulto Jovem
11.
ANZ J Surg ; 84(4): 231-4, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22985335

RESUMO

BACKGROUND: Graves' disease is a common cause of thyrotoxicosis. Treatment options include anti-thyroid medications or definitive therapy: thyroidectomy or radioactive iodine (I(131) ). Traditionally, I(131) has been the preferred definitive treatment for Graves' disease in New Zealand. Reports of concomitant thyroid cancer occurring in up to 17% of Graves' patients suggest surgery, if performed with low morbidity, may be the preferred option. The aim of this study was to determine the rate of thyroid cancer and surgical outcomes in a New Zealand cohort of patients undergoing thyroidectomy for Graves' disease. METHOD: This study is a retrospective review of Waikato region patients undergoing thyroid surgery for Graves' disease during the 10-year period prior to 1 December 2011. RESULTS: A total of 833 patients underwent thyroid surgery. Of these, 117 were for Graves' disease. Total thyroidectomy was performed in 82, near-total in 33 and subtotal in 2 patients. Recurrent thyrotoxicosis developed in one subtotal patient requiring I(131) therapy. There were two cases of permanent hypoparathyroidism and one of permanent recurrent laryngeal nerve palsy. Eight patients (6.8%) had thyroid cancer detected, none of whom had overt nodal disease. Five were papillary microcarcinomas (one of which was multifocal), two were papillary carcinomas (11 mm and 15 mm) and one was a minimally invasive follicular carcinoma. CONCLUSION: Thyroid cancer was identified in approximately 7% of patients undergoing surgery for Graves' disease. A low complication rate (<2%) of permanent hypoparathyroidism and nerve injury (<1%) supports surgery being a safe alternative to I(131) especially for patients with young children, ophthalmopathy or compressive symptoms.


Assuntos
Doença de Graves/cirurgia , Neoplasias da Glândula Tireoide/etiologia , Tireoidectomia , Adenocarcinoma Folicular/epidemiologia , Adenocarcinoma Folicular/etiologia , Adolescente , Adulto , Idoso , Carcinoma/epidemiologia , Carcinoma/etiologia , Carcinoma Papilar/epidemiologia , Carcinoma Papilar/etiologia , Feminino , Doença de Graves/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Complicações Pós-Operatórias , Estudos Retrospectivos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/epidemiologia , Adulto Jovem
12.
Aust N Z J Obstet Gynaecol ; 52(2): 204-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22188427

RESUMO

Primary hyperparathyroidism (pHPT) in pregnancy may be associated with significant maternal and fetal morbidity and mortality. Medical management of pHPT in pregnancy is limited, and surgery is the only definitive therapeutic option. The ideal timing for surgery is mid-second trimester, but surgery may also be safely performed in the third trimester. Delayed parathyroid surgery may result in a hypercalcaemic crisis postpartum owing to loss of active placental calcium transfer. We present a case of parathyroid carcinoma in pregnancy presenting with pre-eclampsia at 32 weeks' gestation.


Assuntos
Carcinoma/complicações , Hipercalcemia/etiologia , Neoplasias das Paratireoides/complicações , Pré-Eclâmpsia/etiologia , Complicações Neoplásicas na Gravidez , Adulto , Carcinoma/diagnóstico , Carcinoma/cirurgia , Cesárea , Feminino , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/cirurgia , Recém-Nascido , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/cirurgia , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/cirurgia , Terceiro Trimestre da Gravidez , Proteinúria/diagnóstico , Proteinúria/etiologia , Índice de Gravidade de Doença , Ácido Úrico/sangue
13.
Endocr Relat Cancer ; 17(3): 835-46, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20621999

RESUMO

MicroRNAs (miRNAs) are small RNAs ( approximately 22 bp) that post-transcriptionally regulate protein expression and are found to be differentially expressed in a number of human cancers. There is increasing evidence to suggest that miRNAs could be useful in cancer diagnosis, prognosis, and therapy. We performed miRNA microarray expression profiling on a cohort of 12 benign and 12 malignant pheochromocytomas and identified a number of differentially expressed miRNAs. These results were validated in a separate cohort of ten benign and ten malignant samples using real-time quantitative RT-PCR; benign samples had a minimum follow-up of at least 2 years. It was found that IGF2 as well as its intronic miR-483-5p was over-expressed, while miR-15a and miR-16 were under-expressed in malignant tumours compared with benign tumours. These miRNAs were found to be diagnostic and prognostic markers for malignant pheochromocytoma. The functional role of miR-15a and miR-16 was investigated in vitro in the rat PC12 pheochromocytoma cell line, and these miRNAs were found to regulate cell proliferation via their effect on cyclin D1 and apoptosis. These data indicate that miRNAs play a pivotal role in the biology of malignant pheochromocytoma, and represent an important class of diagnostic and prognostic biomarkers and therapeutic targets warranting further investigation.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , MicroRNAs/fisiologia , Feocromocitoma/genética , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Animais , Apoptose , Biomarcadores Tumorais/metabolismo , Western Blotting , Ciclo Celular , Estudos de Coortes , Seguimentos , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Feocromocitoma/metabolismo , Feocromocitoma/patologia , Prognóstico , RNA Mensageiro/genética , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Células Tumorais Cultivadas
14.
Hum Pathol ; 41(6): 805-14, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20236688

RESUMO

Up to 30% of pheochromocytomas and paragangliomas are associated with germline RET, Von Hippel-Lindau (VHL), neurofibromatosis type I (NF1), and succinate dehydrogenase subunits (SDHB, SDHC, and SDHD) mutations. Genetic testing allows familial counseling and identifies subjects at high risk of malignancy (SDHB mutations) or significant multiorgan disease (RET, VHL, or NF1). However, conventional genetic testing for all loci is burdensome and costly. We performed immunohistochemistry for SDHB on 58 tumors with known SDH mutation status. We defined positive as granular cytoplasmic staining (a mitochondrial pattern), weak diffuse as a cytoplasmic blush lacking definite granularity, and negative as completely absent staining in the presence of an internal positive control. All 12 SDH mutated tumors (6 SDHB, 5 SDHD, and 1 SDHC) showed weak diffuse or negative staining. Nine of 10 tumors with known mutations of VHL, RET, or NF1 showed positive staining. One VHL associated tumor showed weak diffuse staining. Of 36 tumors without germline mutations, 34 showed positive staining. One paraganglioma with no known SDH mutation but clinical features suggesting familial disease was negative, and one showed weak diffuse staining. We also performed immunohistochemistry for SDHB on 143 consecutive unselected tumors of which 21 were weak diffuse or negative. As SDH mutations are virtually always germline, we conclude that approximately 15% of all pheochromocytomas or paragangliomas are associated with germline SDH mutation and that immunohistochemistry can be used to triage genetic testing. Completely absent staining is more commonly found with SDHB mutation, whereas weak diffuse staining often occurs with SDHD mutation.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Proteínas de Membrana/genética , Paraganglioma/genética , Feocromocitoma/genética , Succinato Desidrogenase/genética , Adulto , Idoso , Estudos de Coortes , Feminino , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Síndrome , Adulto Jovem
15.
World J Surg ; 34(6): 1254-60, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20091309

RESUMO

BACKGROUND: Pediatric patients present with thyroid nodules less often than adults, but the rate of malignancy is much higher. This study was designed to determine the ability of fine-needle aspiration cytology (FNA) to diagnose accurately and facilitate management of thyroid neoplasms in pediatric patients. METHODS: A retrospective study revealed 110 patients <19 years old who had undergone thyroid surgery and FNA biopsy at two academic institutions over the last 28 years. FNA sensitivity for diagnosing papillary thyroid cancer (PC) and follicular neoplasm (FN) was investigated. RESULTS: Of 110 patients who presented for surgery, 27 had PC and 33 had a FN: 4 follicular carcinomas (FCs) and 29 follicular adenomas (FAs). Among the PCs patients, the FNA results were as follows: 1 (4%) nondiagnostic, 6 (22%) atypical, 2 (7%) benign, and 18 (67%) malignant lesions. The sensitivity of a malignant FNA was 90% for diagnosing a PC. Sensitivity of an atypical FNA was 75% for FCs and 69% for FAs, giving an overall FN sensitivity of 70%. Of the atypical FNA readings, 60% had confirmed histological atypical features, and 19% were malignant. In 95% of the malignant FNA reports, final histology confirmed PC, resulting in a positive predictive value of 95%. CONCLUSIONS: FNA biopsy can reliably diagnose malignancy in pediatric thyroid patients and should be used as a standard technique to indicate surgical treatment. Atypical or suspicious FNA results do not predict cancer effectively, confirming the current accepted practice for adults that diagnostic excision is required to exclude malignancy in pediatric patients.


Assuntos
Biópsia por Agulha Fina/métodos , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
Ann Surg Oncol ; 17(2): 392-400, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19949879

RESUMO

BACKGROUND: The enhancement of metaiodobenzylguanidine single photon emission computed tomography (MIBG SPECT) imaging through the addition of CT images fused with SPECT data (coregistered MIBG SPECT/CT imaging) is new technology that allows direct correlation of anatomical and functional information. We hypothesized that MIBG SPECT/CT imaging would provide additional information and improve diagnostic confidence for the radiological localization of a pheochromocytoma, in particular for patients at high risk of multifocal or recurrent disease. METHODS: A retrospective study of all patients investigated by MIBG SPECT/CT at our institution from 2006 to 2008 for a suspected pheochromocytoma was performed. Each case was compared with conventional radiological investigations to determine whether MIBG SPECT/CT was able to improve diagnostic confidence and provide additional diagnostic information compared with conventional imaging alone. RESULTS: Twenty-two patients had MIBG SPECT/CT imaging for a suspected pheochromocytoma. Fourteen patients had positive MIBG SPECT/CT imaging results correlating with imaging by CT or magnetic resonance imaging in all cases. In six cases, MIBG SPECT/CT provided additional information that altered the original radiological diagnosis. Five patients with a pheochromocytoma-associated germline mutation had multifocal disease excluded by MIBG SPECT/CT. Patients without a germline mutation that had positive biochemistry and a solitary lesion with conventional imaging had no diagnostic improvement with MIBG SPECT/CT imaging. CONCLUSIONS: MIBG SPECT/CT fusion imaging is a sensitive and specific radiological imaging tool for patients suspected to have pheochromocytoma. The particular strengths of MIBG SPECT/CT are detection of local recurrence, small extra-adrenal pheochromocytomas, multifocal tumors, or the presence of metastatic disease.


Assuntos
3-Iodobenzilguanidina , Feocromocitoma/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Feocromocitoma/patologia , Prognóstico , Estudos Retrospectivos
18.
ANZ J Surg ; 79(5): 367-70, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19566519

RESUMO

Laparoscopic adrenalectomy is now accepted as the procedure of choice for the resection of benign adrenocortical tumours, but few studies have assessed whether the outcomes of laparoscopic adrenalectomy for adrenal phaeochromocytoma are similar to that of other adrenal tumour types. This is a retrospective cohort study. Clinical and operative data were obtained from an adrenal tumour database and hospital records. A total of 191 patients had laparoscopic adrenalectomy, of which 36 were for phaeochromocytoma, over a 12-year period. Length of hospital stay (4.8 vs 3.6 days, P= 0.03) and total operating times (183 vs 157 min, P= 0.01) were greater in the laparoscopic phaeochromocytoma resection group. Despite the greater size of the phaeochromocytomas compared to the remaining adrenal tumour types (44 mm vs 30 mm, P < 0.01), however, rate of conversion and morbidity were no different. Laparoscopic adrenalectomy for phaeochromocytoma is a safe procedure with similar outcomes to laparoscopic adrenalectomy for other adrenal tumour types.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Laparoscopia/métodos , Feocromocitoma/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New South Wales , Feocromocitoma/patologia , Estudos Retrospectivos , Estatísticas não Paramétricas , Resultado do Tratamento
19.
ANZ J Surg ; 79(5): 371-7, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19566520

RESUMO

With the widespread use of abdominal imaging, the detection and therefore incidence of adrenal tumours is increasing. The laparoscopic approach to primary surgical resection of adrenal tumours has now become the standard of care. There is scarce published literature regarding the management and outcomes of recurrent adrenal tumours. The aim of the present study was therefore to review the authors' experience with reoperative adrenal surgery. A retrospective review of reoperative adrenalectomy cases identified from the prospectively maintained University of Sydney Endocrine Surgical Unit Database from January 1988 to July 2007 was carried out. There were nine (3.5%) reoperative adrenalectomies in six patients. Two were cases of adrenocortical carcinoma, two involved cases of familial phaeochromocytomas and two cases were due to sporadic phaeochromocytomas. Reoperative adrenal surgery is an uncommon event. During the index surgery for adrenal tumours, all adrenal tissue should be removed and knowledge of the vagaries of adrenal anatomy is essential. Reoperative adrenal surgery is a safe procedure and may confer survival benefit or symptom relief. Lifelong follow up is essential for all patients who have had surgery for functional and malignant adrenal tumours.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Laparoscopia/métodos , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico por Imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , New South Wales , Reoperação , Estudos Retrospectivos
20.
J Surg Res ; 156(1): 70-3, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19577768

RESUMO

BACKGROUND: Thyroid cancer is the most common carcinoma in children, and compared with adults, generally present with more advanced disease. Management is similar between populations, primarily consisting of total thyroidectomy. With similar treatment despite disease severity, we chose to explore the surgical outcome of pediatric patients with thyroid malignancy. METHODS: A review of medical records at two academic institutions revealed 68 patients<19 y of age who underwent surgical resection of a malignant thyroid nodule between 1962 and 2008. RESULTS: Of 68 pediatric surgery patients identified with thyroid malignancy, 50 patients (74%) had a total thyroidectomy. Minor complications were noted in 21% of surgeries with 19% temporary hypocalcemia. Risk of complication was not associated with type of surgery. Patients receiving a lobectomy or subtotal thyroidectomy were at greater risk for needing a second surgical procedure, required by 14 patients (21%). CONCLUSIONS: There was no significant increase in surgical complications with respect to type of surgery, however, patients receiving less than total thyroidectomy were at increased risk of repeat surgery. Total thyroidectomy is recommended as the standard of care for the management of pediatric thyroid cancer.


Assuntos
Carcinoma Papilar/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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