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1.
Endocrine ; 74(2): 387-395, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34036515

RESUMO

PURPOSE: Ectopic ACTH syndrome (EAS) is rare. We established a national cohort to increase awareness and address unmet needs. METHODS: The Finnish national EAS cohort includes 60 patients diagnosed in 1997-2016. We assessed clinical features, diagnostic work-ups, treatments, incidence, and outcomes of subgroups occult tumor (OT), well-differentiated neuroendocrine tumor G1/G2 (NETG1/G2) and NET G3/neuroendocrine carcinoma (NETG3/NEC). RESULTS: The distribution of OT, NETG1/G2, and NETG3/NEC was 10 (17%), 20 (33%), and 30 (50%), respectively; and median follow-up 22 months (0-249). Annual incidence (0.20-0.93 per million inhabitants) and tumor subgroups (OT vs. NEC) varied across the country. The longest diagnostic delay from EAS onset to radiological tumor identification was 48 months. In NET/NEC, 6/50 (12%) were diagnosed 1-24 years before EAS onset. Osteoporotic fractures (32%) and severe infections (55%) were common. The CRH stimulation test accurately diagnosed EAS in 25/31 (81%). Metyrapone (≤6 g daily, prescribed in 88%) was well tolerated. In NETG1/G2, 13/20 (65%) underwent curative resection of the primary tumor; four experienced recurrence within 2-12 years. In OT, 70% underwent bilateral adrenalectomy. Five-year overall survival in OT, NETG1/G2, and NETG3/NEC was 90%, 55%, and 0%, respectively (P < 0.001). Morning cortisol, hypokalemia, infections, metastatic disease, and acute onset were negative, whereas resection of the primary tumor and bilateral adrenalectomy were positive predictors of survival. CONCLUSIONS: NET/NEC may precede EAS onset by several years. In NETG1/G2, recurrences may occur > 10 years after successful primary surgery. Tumor subgroup (OT, NETG1/G2, NEC) was an independent predictor of survival.


Assuntos
Síndrome de ACTH Ectópico , Tumores Neuroendócrinos , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de ACTH Ectópico/epidemiologia , Diagnóstico Tardio , Finlândia/epidemiologia , Humanos , Recidiva Local de Neoplasia
3.
Eur J Endocrinol ; 183(6): 539-550, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33055298

RESUMO

OBJECTIVE: Endocrine Society guidelines recommend adrenal venous sampling (AVS) in primary aldosteronism (PA) if adrenalectomy is considered. We tested whether functional imaging of adrenal cortex with 11C-metomidate (11C-MTO) could offer a noninvasive alternative to AVS in the subtype classification of PA. DESIGN: We prospectively recruited 58 patients with confirmed PA who were eligible for adrenal surgery. METHODS: Subjects underwent AVS and 11C-MTO-PET without dexamethasone pretreatment in random order. The lateralization of 11C-MTO-PET and adrenal CT were compared with AVS in all subjects and in a prespecified adrenalectomy subgroup in which the diagnosis was confirmed with immunohistochemical staining for CYP11B2. RESULTS: In the whole study population, the concordance of AVS and 11C-MTO-PET was 51% and did not differ from that of AVS and adrenal CT (53%). The concordance of AVS and 11C-MTO-PET was 55% in unilateral and 44% in bilateral PA. In receiver operating characteristics analysis, the maximum standardized uptake value ratio of 1.16 in 11C-MTO-PET had an AUC of 0.507 (P = n.s.) to predict allocation to adrenalectomy or medical therapy with sensitivity of 55% and specificity of 44%. In the prespecified adrenalectomy subgroup, AVS and 11C-MTO-PET were concordant in 10 of 19 subjects with CYP11B2-positive adenoma and in 6 of 10 with CYP11B2-positivity without an adenoma. CONCLUSIONS: The concordance of 11C-MTO-PET with AVS was clinically suboptimal, and did not outperform adrenal CT. In a subgroup with CYP11B2-positive adenoma, 11C-MTO-PET identified 53% of cases. 11C-MTO-PET appeared to be inferior to AVS for subtype classification of PA.


Assuntos
Radioisótopos de Carbono/metabolismo , Hiperaldosteronismo/diagnóstico por imagem , Hiperaldosteronismo/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Córtex Suprarrenal/diagnóstico por imagem , Córtex Suprarrenal/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
4.
J Clin Pathol ; 71(2): 129-134, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28801349

RESUMO

AIMS: Widespread use of high-resolution imaging techniques and thus increased prevalence of adrenal lesions has made diagnostics of adrenocortical tumours an increasingly important clinical issue. In non-metastatic tumours, diagnosis is based on histology. New or enhanced information for clinicopathological diagnosis, revealing the malignant potential of the tumour, could emerge by means of biomarkers. The connection of proto-oncogene c-myc to adrenocortical neoplasias is poorly known, although the Wnt/beta-catenin pathway, one of the signalling pathways leading to induction of c-myc expression, has been connected to development of adrenocortical neoplasias. We studied c-myc expression in adrenocortical tumours and investigated molecules associated with the signalling pathway of c-myc, including cell cycle-related proteins p27, cyclin E and cyclin D1. METHODS: We studied 195 consecutive adult patients with 197 primary adrenocortical tumours. Histopathological diagnosis was determined by Weiss score and the novel Helsinki score. C-myc, cyclin D1, cyclin E and p27 expressions were determined by immunohistochemistry. RESULTS: Benign adenomas showed prominent nuclear c-myc expression comparable to that of normal adrenocortical cells, whereas carcinomas showed increased cytoplasmic expression. Strong cytoplasmic and weak nuclear c-myc expressions associated with malignancy and adverse outcome. C-myc staining did not correlate with cyclin E. Cyclin D1 correlated with cytoplasmic c-myc expression and to a lesser extent with nuclear c-myc. P27 correlated with cytoplasmic c-myc, but not with nuclear c-myc. P27 correlated with cyclin E. CONCLUSIONS: Strong cytoplasmic c-myc expression and weak nuclear expression in adrenocortical tumours associated with malignancy and shorter survival.


Assuntos
Adenoma/diagnóstico , Neoplasias do Córtex Suprarrenal/diagnóstico , Biomarcadores Tumorais/metabolismo , Carcinoma/diagnóstico , Proteínas Proto-Oncogênicas c-myc/metabolismo , Adenoma/metabolismo , Adenoma/mortalidade , Adenoma/patologia , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/metabolismo , Carcinoma/mortalidade , Carcinoma/patologia , Ciclina D1/metabolismo , Ciclina E/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proto-Oncogene Mas , Transdução de Sinais , Análise de Sobrevida
5.
Duodecim ; 133(9): 881-5, 2017.
Artigo em Finlandês | MEDLINE | ID: mdl-29240322

RESUMO

We describe the first Finnish case of hepatitis C associated osteosclerosis. In which the patient's bone symptoms and bone density were resolved with hepatitis C treatment. Suspecting the possibility of osteosclerosis underlying bone pains in a hepatitis C patient is well-founded, although osteoporotic fractures are a more common problem.


Assuntos
Antivirais/uso terapêutico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Osteosclerose/tratamento farmacológico , Osteosclerose/etiologia , Densidade Óssea , Finlândia , Humanos , Masculino , Osteosclerose/diagnóstico por imagem
6.
Obes Surg ; 26(9): 2161-2167, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26843084

RESUMO

BACKGROUND: Few studies have examined weight loss sustainability after sleeve gastrectomy (SG). The purpose of this study was to determine long-term outcome after SG and gastric bypass (GBP) and learn whether preoperative weight loss and binge eating behavior can be used to predict outcome. MATERIALS AND METHODS: Together, 257 patients (64 % women) were operated, 163 by GBP and 94 by SG. Binge eating was assessed by binge eating scale (BES) and preoperative weight loss was advised to all, including very low-calorie diet for 5 weeks. Postoperative visits took place at 1 and 2 years, and long-term outcome was at median 5 years (range 2.29-6.85). Multivariate linear regression analysis was used to predict outcome at 2-year and long-term control. RESULTS: Median age was 48 years, weight 141.1 kg, and BMI 48.2 kg/m(2). Preoperative weight loss was median 4.9 % before GBP and 3.8 % before SG, P = 0.04. Total weight loss at year one was 24.1 % in GBP and 23.7 % in SG (P = 0.40), at year two 24.4 and 23.4 % (P = 0.26), and at long-term control 23.0 and 20.2 % (P = 0.006), respectively. Weight was analyzed in 93, 88, and 89 % of those alive, respectively. BES did not predict weight outcome, but larger preoperative weight loss predicted less postoperative weight loss at 2 years. CONCLUSION: On long term, weight loss was better maintained after GBP compared with SG. Binge eating behavior was not a significant predictor, but larger preoperative weight loss predicted less postoperative weight loss for the next 2 years.


Assuntos
Bulimia/epidemiologia , Gastrectomia/estatística & dados numéricos , Derivação Gástrica/estatística & dados numéricos , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Redução de Peso/fisiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Resultado do Tratamento
7.
Endocrinol Metab (Seoul) ; 30(4): 481-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26354488

RESUMO

BACKGROUND: Current guidelines for follow-up of adrenal incidentalomas are extensive and hampered by lack of follow-up studies. We tested the hypothesis that small lipid-rich adrenal incidentalomas, initially characterized by tumor size <40 mm and <10 Hounsfield units (HUs) on unenhanced computed tomography (CT) may not demonstrate excessive growth/hormonal hypersecretion on follow-up. METHODS: Sixty-nine incidentalomas in 56 patients were restudied with unenhanced CT and screening for hypercortisolism (dexamethasone suppression test [DST], plasma adrenocorticotropic hormone) and pheochromocytoma (24-hour urinary metanephrines and normetanephrines) 5 years later. Primary hyperaldosteronism was excluded at base-line. RESULTS: Tumor (n=69) size was similar before and after 5 years follow-up (19±6 mm vs. 20±7 mm). Mean tumor growth was 1±2 mm. Largest increase in tumor size was 8 mm, this tumor was surgically removed and histopathology confirmed cortical adenoma. DST was normal in 54 patients and two patients (3.6%) were still characterized by subclinical hypercortisolism. Initial tumor size was >20 mm for the patient with largest tumor growth and those with subclinical hypercortisolism. All patients had normal 24-hour urinary metanephrines and normetanephrines. Low attenuation (<10 HU) was demonstrated in 97% of 67 masses re-evaluated with unenhanced CT. CONCLUSION: None of the patients developed clinically relevant tumor growth or new subclinical hypercortisolism. Biochemical screening for pheochromocytoma in incidentalomas demonstrating <10 HU on unenhanced CT is not needed. For such incidentalomas <40 mm, it seems sufficient to perform control CT and screen for hypercortisolism after 5 years.

8.
Duodecim ; 131(12): 1145-52, 2015.
Artigo em Finlandês | MEDLINE | ID: mdl-26245044

RESUMO

Disorders of water balance are manifested as hyponatremia, polyuria or hypernatremia. While a diagnostic scheme is useful in the exploration of hyponatremia, the urgency of restoration of hyponatremia is essential in the treatment. Regardless of the therapeutic method, strong diuresis is predictive of too rapid restoration of hyponatremia. There are many causes for an increased need to pass urine. Polyuria is in question if the volume of urine collected over a 24-hour period has increased. After excluding diabetes and other common causes of polyuria, the osmolality of the first urine voided in the morning reflects the ability of the kidneys to concentrate urine. A water deprivation test is helpful in the differential diagnosis of the causes of polyuria.


Assuntos
Hipernatremia/diagnóstico , Hiponatremia/diagnóstico , Poliúria/diagnóstico , Diagnóstico Diferencial , Humanos , Hipernatremia/fisiopatologia , Hiponatremia/fisiopatologia , Poliúria/fisiopatologia , Fatores de Risco
9.
Hum Pathol ; 46(3): 404-10, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25582500

RESUMO

Histopathologic diagnosis of adrenocortical tumors is based on adverse features that indicate malignant potential. Proliferation index has served as a supplemental tool in assessing the malignant potential of adrenocortical tumors. None of the current histologic classification systems can sufficiently accurately predict tumors' metastatic potential. We studied 177 consecutive adult patients with primary adrenocortical tumors operated on at Helsinki University Central Hospital between 1990 and 2003, all patients with a minimum follow-up of 5 years. We determined for each tumor the Weiss score and the Weiss revisited score by Aubert. Proliferation index was measured by computer-assisted image analysis. Each of the 9 Weiss criteria and the proliferation index were then used to establish a scoring system to predict the metastatic potential of adrenocortical tumors. Use of stepwise regression analysis led us to propose a calculation: 3 × mitotic rate (>5/50 high-power fields) + 5 × presence of necrosis + proliferation index in the most proliferative area of the tumor. Using a cutoff value of 8.5, the new scoring system was able to diagnose metastatic adrenocortical carcinoma with 100% sensitivity (confidence interval [CI], 76.8%-100%) and 99.4% specificity (CI, 96.6%-100%). The corresponding sensitivity of the Weiss system was 100% (CI, 76.8%-100%), and specificity, 90.2% (CI, 84.6%-94.3%), with sensitivity of the Weiss revisited system at 100% (CI, 76.8%-100%) and specificity at 96.9% (CI, 93.0%-99.0%). The new Helsinki score thus was accurate in predicting the metastatic potential of adrenocortical tumors.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/secundário , Neoplasias do Córtex Suprarrenal/química , Neoplasias do Córtex Suprarrenal/mortalidade , Carcinoma Adrenocortical/química , Carcinoma Adrenocortical/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Biópsia com Agulha de Grande Calibre , Diagnóstico Diferencial , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Estimativa de Kaplan-Meier , Antígeno Ki-67/análise , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Invasividade Neoplásica/patologia , Segunda Neoplasia Primária , Prognóstico , Curva ROC , Análise de Regressão , Sensibilidade e Especificidade , Taxa de Sobrevida , Adulto Jovem
10.
Ann Clin Biochem ; 52(Pt 4): 428-33, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25249663

RESUMO

INTRODUCTION: Dietary serotonin increases urinary secretion of 5-HIAA. A falsely elevated 5-HIAA may lead to incorrect suspicion of a neuroendocrine tumour. Therefore, we determined the effect and duration of dietary serotonin on serum 5-HIAA concentration. We also studied the distribution of 5-HIAA in serum fractions. METHODS: We used serum samples from healthy volunteers (31 women and four men). All test subjects avoided serotonin-containing foods for three days before sample collection. They then ate either pineapple, banana, kiwi fruit, tomato or walnuts and additional blood samples were taken after 2, 4, 6, 24, 48 and 72 h. To study the distribution of 5-HIAA in serum, samples from a healthy individual, a test person who had ingested walnuts, and from a neuroendocrine tumour patient were fractionated by gel filtration chromatography. The fractions were analysed for 5-HIAA. RESULTS: Serum 5-HIAA concentration increased significantly (P ≤ 0.001) within 2 h after ingestion of serotonin-containing food. After 2 h, 5-HIAA concentration started to decrease and reached the baseline concentration within 24 h. A calculated half-life of 5-HIAA in circulation was 1.3 h. In fractionated serum, 5-HIAA was found not only in free form but also in the albumin and α2-globulin fractions. CONCLUSIONS: The increase of serum 5-HIAA caused by dietary serotonin is significant but transient. Therefore, serotonin-containing foods should be avoided for one day before blood sampling. In serum, 5-HIAA is free and apparently bound to albumin. Minor amounts were also found in the α2-globulin fraction. Our liquid chromatography tandem mass spectrometry assay measures free 5-HIAA in serum.


Assuntos
Dieta , Ácido Hidroxi-Indolacético/sangue , Serotonina/administração & dosagem , Serotonina/metabolismo , Adulto , Idoso , Cromatografia Líquida , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Albumina Sérica , Albumina Sérica Humana , Soroglobulinas , Espectrometria de Massas em Tandem , Adulto Jovem
11.
J Clin Endocrinol Metab ; 99(9): 3044-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24823466

RESUMO

CONTEXT: CDC73 mutations frequently underlie the hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism (FIHP), and parathyroid carcinoma. It has also been suggested that CDC73 deletion analysis should be performed in those patients without CDC73 mutations. OBJECTIVE: To investigate for CDC73 deletion in a family with FIHP previously reported not to have CDC73 mutations. PATIENTS AND METHODS: Eleven members (six affected with primary hyperparathyroidism and five unaffected) were ascertained from the family, and multiplex ligation-dependent probe amplification was performed to detect CDC73 deletion using leukocyte DNA. RESULTS: A previously unreported deletion of CDC73 involving exons 1-10 was detected in five affected members and two unaffected members who were 26 and 39 years of age. Two affected members had parathyroid carcinomas at the ages of 18 and 32 years, and they had Ki-67 proliferation indices of 5 and 14.5% and did not express parafibromin, encoded by CDC73. Primary hyperparathyroidism in the other affected members was due to adenomas and atypical adenomas, and none had jaw tumors. Two affected members had thoracic aortic aneurysms, which in one member occurred with parathyroid carcinoma and renal cysts. CONCLUSION: A previously unreported intragenic deletion of exons 1 to 10 of CDC73 was detected in a three-generation family with FIHP, due to adenomas, atypical adenomas, and parathyroid carcinomas. In addition, two affected males had thoracic aortic aneurysms, which may represent another associated clinical feature of this disorder.


Assuntos
Adenoma/genética , Fibroma/genética , Deleção de Genes , Hiperparatireoidismo/genética , Neoplasias Maxilomandibulares/genética , Neoplasias das Paratireoides/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Saúde da Família , Feminino , Humanos , Masculino , Linhagem , Fenótipo
12.
BMC Health Serv Res ; 14: 26, 2014 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-24444378

RESUMO

BACKGROUND: In Finland diabetologists have long been concerned about the level of diabetes care as the incidence of type 1 diabetes and complicated type 2 diabetes is exceeding the capacity of specialist clinics. We compared the outcome of diabetes care in two middle-sized Finnish municipalities with different models of diabetes care organisation in public primary health care. In Kouvola the primary health care of all diabetic patients is based on general practitioners, whereas in Nurmijärvi the follow-up of type 1 and most complicated type 2 diabetic patients is assigned to a general practitioner specialised in diabetes care. METHODS: Our study population consisted of all adult diabetic patients living in the municipalities under review.We compared the use and costs of public diabetes care, glycemic control, blood pressure, LDL-cholesterol level, the application of the national guidelines and patient satisfaction. The main outcome measures were the costs and use of health care services due to diabetes and its complications. RESULTS: In Nurmijärvi, where diabetes care was centralised, more type 1 diabetic patients were followed up in primary health care than in Kouvola, where general practitioners need more specialist consultations. The centralisation resulted in cost savings in the diabetes care of type 1 diabetic patients. Although the quality of care was similar, type 1 diabetic patients were more satisfied with their follow-up in the centralised system. In the care of type 2 diabetic patients the centralised system required fewer specialist consultations, but the quality and costs were similar in both models. CONCLUSIONS: The follow-up of most diabetic patients - including type 1 diabetes - can be organised in primary health care with the same quality as in secondary care units. The centralised primary care of type 1 diabetes is less costly and requires fewer specialist consultations.


Assuntos
Diabetes Mellitus/terapia , Atenção Primária à Saúde/organização & administração , Qualidade da Assistência à Saúde , Adolescente , Adulto , Idoso , Atenção à Saúde/economia , Atenção à Saúde/estatística & dados numéricos , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus/economia , Diabetes Mellitus Tipo 1/economia , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 2/terapia , Finlândia/epidemiologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Modelos Organizacionais , Atenção Primária à Saúde/economia , Atenção Primária à Saúde/normas , Atenção Primária à Saúde/estatística & dados numéricos , Adulto Jovem
13.
Clin Chim Acta ; 428: 38-43, 2014 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-24211728

RESUMO

BACKGROUND: Serum 5-hydroxyindoleacetic acid (5-HIAA) could replace the determination of 24-h urinary 5-HIAA for diagnosis and follow-up of neuroendocrine tumors (NETs). We developed and validated a straightforward liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for serum 5-HIAA. METHODS: We used serum samples from healthy volunteers (n=136) and patients suspected or followed for NET (n=129). Samples were spiked with 5-HIAA-D2, extracted and quantified by LC-MS/MS. We studied the effects of sample storage, sample device, a meal and diurnal variation on serum 5-HIAA. Furthermore, we established a reference range for serum 5-HIAA and compared our assay with a urinary 5-HIAA HPLC assay and a commercial plasma chromogranin A (CgA) immunoassay. RESULTS: Our LC-MS/MS assay is sensitive (LOQ 5 nmol/L), has a wide assay range (5-10,000 nmol/L) and short analysis time (7 min). 5-HIAA in serum is stable for several days in various temperatures and during five freeze-thaw cycles. We found no diurnal variation (p ≥ 0.20) and a meal had no effect on serum 5-HIAA (p=0.89). We suggest an upper reference limit of 123 nmol/L for serum 5-HIAA. The area under curve (AUC) in receiver operator characteristics (ROC) analysis was 0.83 for urinary 5-HIAA, 0.81 for serum 5-HIAA and 0.76 for CgA, respectively. CONCLUSIONS: The LC-MS/MS assay for serum 5-HIAA discriminates between healthy individuals and patients with NET and is well suited for the diagnosis and follow-up of NETs.


Assuntos
Biomarcadores Tumorais/sangue , Ácido Hidroxi-Indolacético/sangue , Tumores Neuroendócrinos/sangue , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico , Adulto Jovem
14.
Duodecim ; 129(15): 1590-7, 2013.
Artigo em Finlandês | MEDLINE | ID: mdl-24163978

RESUMO

The study group consisted of 96 patients who had used a medication for type 2 diabetes; of them, 33 had undergone gastric sleeve surgery and 63 bypass surgery. Both surgical methods resulted in a similar weight loss among the patients. In follow-up 39 out of 88 patients were able to manage without antidiabetic drugs two years after surgery. The costs of antidiabetic drugs two years after surgery were 79% lower than before the operation. Weight reduction surgery decreases the need for antidiabetic drugs. The greatest cost-efficiency is achieved by targeting weight-loss operations to patients using insulin therapy.


Assuntos
Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia/métodos , Derivação Gástrica/métodos , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Adulto , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/cirurgia , Fatores de Risco , Resultado do Tratamento , Redução de Peso
15.
J Clin Pathol ; 66(12): 1076-80, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23908452

RESUMO

BACKGROUND: Characterisation of adrenal tumours is an important clinical problem. Unenhanced CT is the primary imaging modality to assess the nature of these lesions. AIMS: To study the correlation between unenhanced CT attenuation value and the specific histopathology, as well as the proportion of lipid-poor eosinophilic cells in adrenocortical tumours. METHODS: We studied retrospectively primary adrenocortical tumours that had been operated on at Helsinki University Central Hospital between 2002 and 2008. Of 171 tumours, 79 had appropriate preoperative CT scans and were included in the study. We evaluated the unenhanced CT attenuation values (Hounsfield units, HU) of these tumours and determined their histopathological diagnosis by the Weiss scoring system. We also assessed the proportion of lipid-poor eosinophilic cells for each tumour. RESULTS: Unenhanced CT attenuation value (HU) in adrenocortical tumours correlated well with the proportion of lipid-poor eosinophilic cells (rs=0.750, p<0.001). HU and Weiss score also had a correlation (rs=0.582, p<0.001). CONCLUSIONS: Unenhanced CT attenuation value correlates well with the percentage of lipid-poor eosinophilic cells, but unenhanced CT attenuation value fails to differentiate between benign lipid-poor adenomas and malignant adrenocortical tumours. All adrenocortical tumours with unenhanced CT attenuation value ≤10 HU are histologically benign lipid-rich tumours.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Adenoma Adrenocortical/diagnóstico por imagem , Eosinofilia/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma/química , Adenocarcinoma/diagnóstico , Adolescente , Neoplasias do Córtex Suprarrenal/química , Neoplasias do Córtex Suprarrenal/diagnóstico , Adenoma Adrenocortical/química , Adenoma Adrenocortical/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Lipídeos/análise , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
16.
Eur J Endocrinol ; 168(1): K9-K18, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23076843

RESUMO

OBJECTIVE: Generalized glucocorticoid resistance is characterized by impaired cortisol signaling, resulting from mutations of the glucocorticoid receptor (GR) gene NR3C1. The objective of our study was to identify the causative mutation in a patient with clinical manifestations compatible with generalized glucocorticoid resistance and to determine the functional consequences of the mutation. The possible occurrence of NR3C1 mutations in a selected group of hypertensive subjects with low plasma renin and aldosterone levels was also explored. PATIENTS: The proband, a male athlete, was diagnosed with hypertension associated with low plasma renin activity and low serum aldosterone concentration at the age of 27 years. Liddle's syndrome was suspected and the patient was treated with amiloride with initial success. Subsequent examinations revealed elevated serum cortisol and ACTH levels, with resistance to suppression with low doses of dexamethasone. After identification of an NR3C1 mutation in the proband, the available family members and 51 nonrelated hypertensive subjects with low plasma renin and aldosterone concentrations were also studied. RESULTS: A two-nucleotide deletion in exon 9α, predicted to cause a frameshift mutation (p.L773VfsX25) in the hormone-binding domain of the GR, was identified in the patient in a heterozygous form. Affected brother and father died of premature coronary heart disease. Functional studies in COS-1 cells showed that this mutation eliminates both ligand-binding and transactivation ability of the receptor. No pathogenic NR3C1 mutations were identified in 51 unrelated hypertensive patients with low plasma renin and aldosterone levels. CONCLUSION: We identified a novel frameshift mutation in NR3C1 as the cause of glucocorticoid resistance. The mutation eliminates the functional activity of the GR, as studied by in vitro experiments. Mutations in NR3C1 do not seem to be common causes for hypertension with low renin and aldosterone levels.


Assuntos
Aldosterona/sangue , Hipertensão/genética , Erros Inatos do Metabolismo/genética , Receptores de Glucocorticoides/genética , Renina/sangue , Adulto , Animais , Sequência de Bases , Células COS , Doença da Artéria Coronariana/genética , Feminino , Mutação da Fase de Leitura , Humanos , Masculino , Receptores de Glucocorticoides/deficiência , Deleção de Sequência
17.
Endocr Pathol ; 24(1): 25-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23233312

RESUMO

We describe a rare case of ectopic Cushing's syndrome that recurred 6 years after resection of a thymic neuroendocrine carcinoma. We discuss reasons for the differing clinical presentations, management, hormone profiles, as well as immunopathology. A 41-year-old male developed acute-onset Cushing's syndrome. Clinical presentation and laboratory results were compatible with ectopic adrenocorticotropin hormone (ACTH) production. Computerized tomography (CT) showed a 3.6 cm thymic tumor which was successfully resected. Plasma ACTH (P-ACTH) normalized the first postoperative day. Histopathology demonstrated a well-differentiated neuroendocrine carcinoma with diffuse positivity for ACTH and focal corticotropin-releasing hormone (CRH) reactivity in a few scattered cells. The patient was in remission for 6 years. He then again presented with acute-onset Cushing's syndrome. Fluorine-labeled dihydroxyphenylalanine ((18)F-DOPA) PET/CT showed local uptake in the mediastinum and he underwent repeat resection. However, P-ACTH remained increased (613 ng/l) and 24-h urinary cortisol was 36,720 nmol, suggesting incomplete tumor removal or metastatic spread. Metyrapone treatment was initiated but then withdrawn because the patient spontaneously recovered and cortisol metabolism gradually normalized within 3 weeks. Histopathology demonstrated a recurrent neuroendocrine carcinoma with the same features as the previous lesion but this time CRH was strongly positive in more numerous cells. Normalization of P-ACTH after primary surgery was compatible with ectopic ACTH production. However, the delayed fall in P-ACTH and serum cortisol is compatible with ectopic CRH production and stimulation of pituitary ACTH secretion, which gradually resolved. Although ectopic CRH production is very rare, the unusual dynamics illustrated here should raise the possibility of CRH production by a neuroendocrine tumor.


Assuntos
Síndrome de ACTH Ectópico/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Síndrome de Cushing/metabolismo , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/cirurgia , Neoplasias do Timo/metabolismo , Neoplasias do Timo/cirurgia , Adulto , Síndrome de Cushing/patologia , Progressão da Doença , Dopamina/análogos & derivados , Humanos , Hidrocortisona/metabolismo , Antígeno Ki-67 , Masculino , Tumores Neuroendócrinos/patologia , Compostos Radiofarmacêuticos , Neoplasias do Timo/patologia
18.
PLoS One ; 7(6): e39450, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22724017

RESUMO

BACKGROUND: Congenital hypogonadotropic hypogonadism (HH) is a rare cause for delayed or absent puberty. These patients may recover from HH spontaneously in adulthood. To date, it is not possible to predict who will undergo HH reversal later in life. Herein we investigated whether Finnish patients with reversal of congenital hypogonadotropic hypogonadism (HH) have common phenotypic or genotypic features. METHODS AND FINDINGS: Thirty-two male HH patients with anosmia/hyposmia (Kallmann Syndrome, KS; n = 26) or normal sense of smell (nHH; n = 6) were enrolled (age range, 18-61 yrs). The patients were clinically examined, and reversal of HH was assessed after treatment withdrawal. KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, WDR11, GNRHR, GNRH1, KISS1R, KISS1, TAC3, TACR3, and LHß were screened for mutations. Six HH patients (2 KS, 4 nHH) were verified to have reversal of HH. In the majority of cases, reversal occurred early in adulthood (median age, 23 yrs; range, 21-39 yrs). All had spontaneous testicular growth while on testosterone replacement therapy (TRT). One nHH subject was restarted on TRT due to a decline in serum T. Two reversal variants had a same GNRHR mutation (R262Q), which was accompanied by another GNRHR mutation (R139H or del309F). In addition, both of the KS patients had a mutation in CHD7 (p.Q51X) or FGFR1 (c.91+2T>A). CONCLUSIONS: Considerable proportion of patients with HH (8% of KS probands) may recover in early adulthood. Spontaneous testicular enlargement during TRT was highly suggestive for reversal of HH. Those with the GNRHR mutation R262Q accompanied by another GNRHR mutation may be prone to reversal, although even patients with a truncating mutation in CHD7 or a splice-site mutation in FGFR1 can recover. We recommend that all adolescents and young adults with congenital HH should be informed on the possibility of reversal.


Assuntos
DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Hipogonadismo/congênito , Hipogonadismo/genética , Mutação , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptores LHRH/genética , Adolescente , Adulto , Genótipo , Terapia de Reposição Hormonal , Humanos , Hipogonadismo/terapia , Síndrome de Kallmann/genética , Masculino , Fenótipo , Adulto Jovem
19.
J Nucl Med ; 52(12): 1855-63, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22052128

RESUMO

UNLABELLED: Serum calcitonin and carcinoembryonic antigen (CEA) are markers of recurrent or persistent disease in medullary thyroid cancer (MTC). However, conventional imaging often fails to localize metastatic disease. Our aim was to compare fluorine-labeled dihydroxyphenylalanine ((18)F-DOPA) and (18)F-FDG PET/CT with multidetector CT (MDCT) and MRI in recurrent or persistent MTC. METHODS: Nineteen MTC patients with increased calcitonin or CEA on follow-up (mean ± SD, 93 ± 91 mo; range, 4-300 mo) after primary therapy were prospectively imaged with 4 techniques: (18)F-DOPA PET/CT, (18)F-FDG PET/CT, MDCT, and MRI. Images were analyzed for pathologic lesions, which were surgically removed when possible. The correlation between the detection rate for each method and the calcitonin and CEA concentrations and histopathologic findings was investigated. RESULTS: On the basis of histology and follow-up, one or more imaging methods accurately localized metastatic disease in 12 (63%) of 19 patients. The corresponding figures for (18)F-DOPA PET/CT, (18)F-FDG PET/CT, MDCT, and MRI were 11 (58%) of 19, 10 (53%) of 19, 9 (47%) of 19, and 10 (59%) of 17, respectively. Calcitonin and CEA correlated with (18)F-DOPA PET/CT (P = 0.0007 and P = 0.0263, respectively) and (18)F-FDG PET/CT findings (both P < 0.0001). In patients with an unstable calcitonin doubling time (n = 8), (18)F-DOPA and (18)F-FDG PET/CT were equally sensitive. In contrast, for patients with an unstable CEA doubling time (n = 4), (18)F-FDG PET/CT was more accurate. CONCLUSION: For most MTC patients with occult disease, (18)F-DOPA PET/CT accurately detects metastases. In patients with an unstable calcitonin level, (18)F-DOPA PET/CT and (18)F-FDG PET/CT are complementary. For patients with an unstable CEA doubling time, (18)F-FDG PET/CT may be more feasible. MRI is sensitive but has the highest rate of false-positive results.


Assuntos
Di-Hidroxifenilalanina/análogos & derivados , Fluordesoxiglucose F18 , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Calcitonina/metabolismo , Antígeno Carcinoembrionário/metabolismo , Carcinoma Neuroendócrino , Proliferação de Células , Feminino , Seguimentos , Humanos , Antígeno Ki-67/metabolismo , Cinética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Recidiva , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
20.
Duodecim ; 127(13): 1361-5, 2011.
Artigo em Finlandês | MEDLINE | ID: mdl-21834340

RESUMO

Insufficient drinking during summer heat may lead to dehydration, but excessive drinking, on the other hand, may also be dangerous. In dehydration, the kidneys decrease urinary secretion by maximally concentrating the urine. When this first-line defense for dehydration has been utilized, thirst will slowly appear and the dehydration will eventually be compensated by drinking. In summer heat, decreased urine volumes are thus the first sign of dehydration and need of drinking. There is thus no use of waiting for the feeling of thirst in summer heat, as rehydration is then already long overdue.


Assuntos
Desidratação/prevenção & controle , Ingestão de Líquidos , Hidratação/métodos , Temperatura Alta , Estações do Ano , Sede , Água , Humanos , Micção
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