Aggressive metastatic follicular thyroid carcinoma with anaplastic transformation arising from a long-standing goiter in a patient with Pendred's syndrome.

In this article we describe detailed pathological and molecular genetics studies in a consanguineous kindred with Pendred's syndrome. The index patient was a 53-year-old female patient with congenital deafness and goiter. Her parents were first-degree cousins. She had a large goiter (150 g) that had been present since childhood. One of her sisters and a niece are also deaf and have goiter as well. The presence of Pendred's syndrome was confirmed by a positive perchlorate test and the demonstration of a Mondini malformation. Thyroid function tests (under levothyroxine [LT4] therapy) were in the euthyroid range with a thyrotropin [TSH] level of 2.8 microU/mL (0.2-3.2), a serum total thyroxine (T4) of 90 nmol/L (54-142), and a serum total triiodothyronine (T3) of 2.7 nmol/L (0.8-2.4). Total thyroidectomy was performed, and the mass in the right lobe was found to have invaded adjacent tissues. The histopathological findings were consistent with a follicular carcinoma with areas of anaplastic transformation and lung metastasis. The patient was treated twice with 100 mCi 131iodine (3,700 MBq) and received suppressive doses of LT4. Postoperatively, the serum thyroglobulin (Tg) levels remained markedly elevated (2,352 to 41,336 ng/mL). The patient died of a sudden severe episode of hemoptysis. Sequence analysis of the PDS gene performed with DNA from the two relatives with Pendred's syndrome revealed the presence of a deletion of thymidine 279 in exon 3, a point mutation that results in a frameshift and a premature stop codon at codon 96 in the pendrin molecule. We concluded that prolonged TSH stimulation because of iodine deficiency or dyshormonogenesis in combination with mutations of oncogenes and/or tumor suppressor genes, may result in the development of follicular thyroid carcinomas that undergo transformation into anaplastic cancers. It is likely that these pathogenetic mechanisms have been involved in the development of aggressive metastatic thyroid cancer in this unusual patient with Pendred's syndrome.

Role of endothelins on lymphocyte accumulation in allergic pleurisy.

Endothelins participate in different aspects of inflammatory reactions, including edema formation and eosinophil accumulation in allergic reaction. In this study, we demonstrated a role for endogenous endothelins in eosinophil and T lymphocyte recruitment and cytokine secretion in a murine model of allergic inflammation. Intrathoracic stimulation with endothelin-1 triggered a neutrophil accumulation at 4 h, concomitant with an increase of CD4+ and CD8+ T lymphocyte populations. Antigen challenge in sensitized animals leads to an increase in eosinophil and mononuclear cell numbers at 24 h. Treatment with ETA receptor antagonist (BQ123) inhibited antigen-induced eosinophil and mononuclear cell migration, whereas the selective ETB receptor antagonist BQ-788 was ineffective. The latter effect of BQ-123 was due to inhibition of CD4+ and CD8+ T lymphocytes. Treatment with BQ-123 also inhibited interleukin-5 levels in the exudate and plasma as well as intracellular staining of interleukin-4, interleukin-5, and interferon-gamma in CD4+ lymphocytes. These findings suggest that endogenous endothelins contribute to allergic inflammation by modulating lymphocyte recruitment and cytokine production.