Prevalence and clinical spectrum of nonsecretory medullary thyroid carcinoma in a series of 839 patients with sporadic medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is characterized by the synthesis and secretion of calcitonin (Ct). MTC without Ct secretion has been reported on rare occasions. The aim of this study was to analyze the prevalence and clinical spectrum of nonsecretory MTC in two tertiary centers that cared for 839 patients with sporadic MTC. METHODS: Clinical, biochemical, histological, and immunohistological findings, and somatic RET mutations were analyzed, and long-term follow-up was documented. RESULTS: Seven patients with nonsecretory MTC were identified among 839 patients with sporadic MTC; thus, the prevalence rate of nonsecretory MTC was 0.83%. In these seven patients, Ct and carcinoembryonic antigen (CEA) levels were normal when MTC was initially diagnosed in the patients, despite advanced tumor stage. Ct and CEA levels remained undetectable in four patients; recurrence was indicated in one patient after 10 years of follow-up by routine anatomic imaging and increased CEA levels, and Ct levels became slightly elevated during follow-up, despite massive tumor load, in the remaining two patients. The diagnosis of MTC was confirmed by positive immunohistochemistry for Ct, CEA, and chromogranin A. A high Ki67 proliferation index (PI) (three patients) and a high proportion of RET 918-mutated cells (four patients), as well as poorly differentiated histology, were associated with aggressive biological behavior of the MTC. The prognosis for nonsecretory MTC varied between long-term survival (12.5 years) and rapid progression leading to death within 1.75 years after diagnosis. CONCLUSIONS: The prevalence of nonsecretory MTC was low (0.83% of patients with MTC). Diagnosis was often made at a clinically advanced tumor stage. The histological and immunohistological characteristics and the clinical course and prognosis of nonsecretory MTC are markedly heterogeneous. A high Ki-67 PI and a large proportion of cells with RET 918 mutations are associated with a poor prognosis.

A coisa (das ding) em kant, freud e lacan como fundamento do ser

A psicanálise, desde sua origem, afirma um sujeito, considerando também sua inserção na sociedade em que vive. Sendo assim, as reflexões filosóficas acompanham o ideário da psicanálise. O delineamento das variáveis, as quais interagem no campo da psicanálise, tem por sua vez, despertando o interesse da filosofia, embora ambas as leituras mantenham seus próprios fins especulativos. Este trabalho se propõe a investigar alguns conceitos, desenvolvidos pela psicanálise, as quais continuam a inquietar as discussões filosóficas. A Coisa (das Ding), O Outro (das Andere), A Negação (die Verneinung) e a Suspensão (die Aufhebung) são oss temas escolhidos com o fim de uma delimitação metológica. Por meio das leituras de Kant, Freud, Lacan e Hegel, os fundamentos destes conceitos são identificados, bem como as intervenções feitas por outros autores, os quais possibilitam melhor encaminhamento para tais leituras. Por fim, atráves das considerações obtidas em ambos os campos, é feita uma breve leitura dos conflitos sociais decorrentes da negação do reconhecimento do Outro(AU)

Psychoanalysis, since its origin, has affirmed a subject, considering also their integration into society where he lives. Thus, the philosophical reflections follow thw ideas of psychoanalysis. The desing variables, which interact in the field of psychoanalisis, has in turn attracted the interest of philosophy, although they both maintain their own readings speculative purposes. This study aims to investigate some concepts developed by psychoanalysis, which continue to unsettle the philosophical discussions. The Thing (das Ding), The Other (das Andere), Denial (Verneinung) and suspension (Aufhebung) are the topics chosen for the purpose of defining a methodology. Through readings of Kant, Freud, Lacan and Hegel, the basis of these concpts are identified and interventions made by other authors, which can improve the referral to such readings. Finally, by the consideretions taken in both fields, is a brief reading of the social conflicts arising from denial of recognition of the Other(AU)

Inactivating calcium-sensing receptor mutations in patients with primary hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (HPT) is characterised by autonomous secretion of PTH from enlarged parathyroid glands leading, in most patients, to asymptomatic hypercalcaemia. Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder caused by inactivating mutations in the calcium-sensing receptor (CaSR) gene; it is characterised by lifelong and usually asymptomatic hypercalcaemia. Establishing the correct diagnosis is important because surgery can be curative in HPT, but ineffective in FHH. There is overlap in the diagnostic criteria for the two disorders and some patients carrying inactivating mutations in the CaSR gene, which is suggestive of FHH, also have HPT with hyperplastic parathyroid glands or adenomas. DESIGN AND PATIENTS CaSR gene mutations were analysed and clinical and biochemical parameters evaluated in 139 consecutive outpatients presenting with hypercalcaemia and suspected of having HPT. RESULTS: Six different mutations of the CaSR gene were found in eight patients. In four patients, classical FHH was suspected based on clinical and biochemical results and was confirmed by the CaSR mutations. In the other four patients, HPT was diagnosed based on the biochemical profile or symptoms; in these four patients, the parathyroids were operated on and single adenomas were histologically confirmed. In all four patients, serum calcium decreased postoperatively; and in three patients, serum calcium normalised postoperatively. The CaSR mutations in these patients were R25X, E250K and Q926R. CONCLUSION: The coexistence of HPT and FHH in four of 139 patients suggests a pathogenetic role of CaSR mutations in HPT. Despite also having a CaSR mutation, these patients benefited from parathyroid surgery.

Severe form of thyroid hormone resistance in a patient with homozygous/hemizygous mutation of T3 receptor gene.

Resistance to thyroid hormone syndrome (RTH) is a rare disorder, usually inherited as an autosomal dominant trait. Patients with RTH are usually euthyroid but can occasionally present with signs and symptoms of thyrotoxicosis or rarely with hypothyroidism. Affected individuals are usually heterozygous for mutations in the thyroid hormone receptor beta gene (TR-beta). We present a patient with RTH found to be homo-/hemizygous for a mutation in the TR-beta gene. The single nucleotide substitution I280S (1123T-->G) was present either on both alleles or in a hemizygous form with complete deletion of the second allele. The I280S mutation was recently reported in a heterozygous patient. The severe phenotype with seriously impaired intellectual development, hyperkinetic behaviour, tachycardia, hearing and visual impairment is probably due to the dominant negative effect of the I280S mutant protein and the absence of any functional TR-beta.