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OBJECTIVE: The basis of thyroid nodule diagnostics is ultrasound-guided fine needle biopsy with cytological evaluation (FNC) if ultrasound appearance is not clearly benign. The aim of this study was to investigate the predictive potential of dedicated, expert high-resolution ultrasound, to see if histopathological entities of thyroid nodules can be diagnosed without invasive FNC biopsies. DESIGN: Prospective case-cohort study. METHODS: 187 patients with 221 thyroid nodules were examined with ultrasound and prospectively assigned to the expected histopathological diagnosis: colloid nodule, adenomatoid colloid nodule, follicular adenoma, follicular carcinoma, follicular variant of papillary thyroid carcinoma, papillary thyroid carcinoma, or other thyroid cancer. In 101 of these, we later obtained histopathological reports for comparison. RESULTS: Overall accuracy for classification into discrete histopathological categories by expert ultrasound was 71.3% and Cohen's Kappa was 0.62. The sensitivity and specificity for detecting malignancy were 97.3% and 78.1%. The diagnostic accuracy for malignancy was 85.1%. ACR-TIRADS scores for the same nodules had a sensitivity of 97.3%, specificity of 26.6%, and accuracy of 52.5%. CONCLUSION: Dedicated expert high-resolution ultrasound without FNC can reliably distinguish benign vs malignant nodules, but also differentiate between several histopathological entities in thyroid nodules. There is potential for a reduction in the number of invasive FNC biopsies and diagnostic operations.
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Background: After seven decades of levothyroxine (LT4) replacement therapy, dosage adjustment still takes several months. We have developed a decision aid tool (DAT) that models LT4 pharmacometrics and enables patient-tailored dosage. The aim of this was to speed up dosage adjustments for patients after total thyroidectomy. Methods: The DAT computer program was developed with a group of 46 patients post-thyroidectomy, and it was then applied in a prospective randomized multicenter validation trial in 145 unselected patients admitted for total thyroidectomy for goiter, differentiated thyroid cancer, or thyrotoxicosis. The LT4 dosage was adjusted after only two weeks, with or without application of the DAT, which calculated individual free thyroxine (fT4) targets based on four repeated measurements of fT4 and thyrotropin (TSH) levels. The individual TSH target was either <0.1, 0.1-0.5, or 0.5-2.0 mIU/L, depending on the diagnosis. Initial postoperative LT4 dosage was determined according to clinical routine without using algorithms. A simplified DAT with a population-based fT4 target was used for thyrotoxic patients who often went into surgery after prolonged TSH suppression. Subsequent LT4 adjustments were carried out every six weeks until target TSH was achieved. Results: When clinicians were guided by the DAT, 40% of patients with goiter and 59% of patients with cancer satisfied the narrow TSH targets eight weeks after surgery, as compared with only 0% and 19% of the controls, respectively. The TSH was within the normal range in 80% of DAT/goiter patients eight weeks after surgery as compared with 19% of controls. The DAT shortened the average dosage adjustment period by 58 days in the goiter group and 40 days in the cancer group. For thyrotoxic patients, application of the simplified DAT did not improve the dosage adjustment. Conclusions: Application of the DAT in combination with early postoperative TSH and fT4 monitoring offers a fast approach to LT4 dosage after total thyroidectomy for patients with goiter or differentiated thyroid cancer. Estimation of individual TSH-fT4 dynamics was crucial for the model to work, as removal of this feature in the applied model for thyrotoxic patients also removed the benefit of the DAT.
Assuntos
Algoritmos , Técnicas de Apoio para a Decisão , Cálculos da Dosagem de Medicamento , Terapia de Reposição Hormonal , Hipotireoidismo/tratamento farmacológico , Tireoidectomia/efeitos adversos , Tiroxina/administração & dosagem , Tiroxina/farmacocinética , Biomarcadores/sangue , Tomada de Decisão Clínica , Monitoramento de Medicamentos , Feminino , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Noruega , Valor Preditivo dos Testes , Estudos Prospectivos , Suécia , Tireotropina/sangue , Tiroxina/sangue , Resultado do TratamentoRESUMO
BACKGROUND: Hypercalcemia of malignancy is relatively common in several cancers. However, in colorectal cancer, paraneoplastic phenomena that cause hypercalcemia is uncommon. In the few cases that are reported, secretion of parathyroid hormone-related peptide mediates the effect. We describe the first case of severe hypercalcemia mediated by intact parathyroid hormone secretion from a bone metastasis of colorectal origin. This was a diagnostic and therapeutic challenge. CASE PRESENTATION: A 68-year-old male treated for rectal adenocarcinoma 10 years earlier developed a bone metastasis. After initial treatment of the metastasis with surgery and irradiation, he developed a relapse with severe hypercalcemia and corresponding elevated parathyroid hormone levels. The workup showed no signs of parathyroid adenomas, but the metastasis produced intact parathyroid hormone. The hypercalcemia was successfully treated by irradiation and osteoclast inhibitor, and the patient received chemotherapy. Survival was 24 months from the onset of hypercalcemia. CONCLUSIONS: Proper diagnosis of the uncommon endocrine disturbance allowed targeted therapy and avoidance of neck exploration for wrongly suspecting primary hyperparathyroidism. Intact parathyroid hormone should be measured in cases of malignant hypercalcemia.
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Adenocarcinoma/terapia , Neoplasias Ósseas/terapia , Hipercalcemia/patologia , Síndromes Paraneoplásicas/patologia , Hormônio Paratireóideo/sangue , Radioterapia/efeitos adversos , Neoplasias Retais/terapia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Adenocarcinoma/patologia , Idoso , Neoplasias Ósseas/secundário , Humanos , Hipercalcemia/sangue , Hipercalcemia/etiologia , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Síndromes Paraneoplásicas/sangue , Síndromes Paraneoplásicas/etiologia , Prognóstico , Neoplasias Retais/patologiaAssuntos
Neoplasias da Mama , Mama , Neoplasias da Mama/cirurgia , Humanos , Mastectomia , Mastectomia SegmentarRESUMO
Grid cells are topographically organized in the sense that, within the dorsal part of the medial entorhinal cortex, the scale of the grid increases systematically with anatomical distance from the dorsal border of this brain area. The ventral limit of the spatial map is currently not known. To determine if the grid map extends into the intermediate and ventral parts of the medial entorhinal cortex, we recorded activity from entorhinal principal cells at multiple dorsoventral levels while rats shuttled back and forth on an 18 m long linear track. The recordings spanned a range of more than 3 mm, covering approximately three quarters of the dorsoventral extent of the medial entorhinal cortex. Distinct periodic firing fields were observed at all recording levels. The average interpeak distance between the fields increased from approximately 50 cm in the most dorsal part to approximately 3 m at the most ventral recording positions. The increase in grid scale was accompanied by a decrease in the frequency of theta modulation and the rate of phase precession. The increase in average spacing and field size was approximately linear but this relationship coincided with a substantial increase in the variability of each measure. Taken together, the observations suggest that the spatial scale of the grid representation increases progressively along most of the dorsoventral axis of the medial entorhinal cortex, mirroring the topographical scale expansion observed in place cells in the hippocampus.
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Potenciais de Ação/fisiologia , Córtex Entorrinal/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Percepção Espacial/fisiologia , Animais , Mapeamento Encefálico , Simulação por Computador , Córtex Entorrinal/citologia , Masculino , Rede Nervosa/citologia , Orientação/fisiologia , Ratos , Ratos Long-Evans , Ritmo TetaRESUMO
To determine how spatial scale is represented in the pyramidal cell population of the hippocampus, we recorded neural activity at multiple longitudinal levels of this brain area while rats ran back and forth on an 18-meter-long linear track. CA3 cells had well-defined place fields at all levels. The scale of representation increased almost linearly from <1 meter at the dorsal pole to approximately 10 meters at the ventral pole. The results suggest that the place-cell map includes the entire hippocampus and that environments are represented in the hippocampus at a topographically graded but finite continuum of scales.
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Hipocampo/fisiologia , Células Piramidais/fisiologia , Percepção Espacial , Potenciais de Ação , Algoritmos , Animais , Mapeamento Encefálico , Eletrodos Implantados , Hipocampo/citologia , Aprendizagem , Modelos Lineares , Masculino , Ratos , Ratos Long-Evans , Comportamento Espacial , Ritmo TetaRESUMO
Place-specific firing in the hippocampus is determined by path integration-based spatial representations in the grid-cell network of the medial entorhinal cortex. Output from this network is conveyed directly to CA1 of the hippocampus by projections from principal neurons in layer III, but also indirectly by axons from layer II to the dentate gyrus and CA3. The direct pathway is sufficient for spatial firing in CA1, but it is not known whether similar firing can also be supported by the input from CA3. To test this possibility, we made selective lesions in layer III of medial entorhinal cortex by local infusion of the neurotoxin gamma-acetylenic GABA. Firing fields in CA1 became larger and more dispersed after cell loss in layer III, whereas CA3 cells, which receive layer II input, still had sharp firing fields. Thus, the direct projection is necessary for precise spatial firing in the CA1 place cell population.