Relationship between the sonographic appearance of the thyroid and the clinical course and autoimmune activity of Graves' disease.

PURPOSE: The aim of this study was to investigate the relationship between thyroid echogenicity and clinical course/immunologic parameters in Graves' disease. METHODS: Two hundred and six outpatients with Graves' disease (31 men, 175 women; 46 +/- 23 years old) were studied with thyroid sonography and color Doppler sonography. Forty-five patients were treated for active hyperthyroidism, 161 were euthyroid (85 immediately before withdrawal of antithyroid drug at maintenance doses, 76 in stable remission after withdrawal of antithyroid treatment). Free triiodothyronine, free thyroxine, thyrotropin, and disease-specific autoantibodies (antithyrotropin-releasing hormone antibody) were determined in all patients. RESULTS: The ultrasound images were classified on the basis of homogeneous, finely unhomogeneous, or micronodular appearance. The proportion of unhomogeneous plus micronodular patterns was greater in hyperthyroid (77.8%) than in euthyroid patients (62.1%). In the latter group, the pattern distribution was significantly different in patients who were antibody positive relative to patients who were antibody negative (p < 0.01). In the stable remission subgroup, the pattern distribution differed according to thyrotropin levels (p < .01). There was a correlation between echopattern and color Doppler sonography as vascularization variables progressively increased in the transition from homogeneous to unhomogeneous and micronodular echopattern (most evident echotexture changes). CONCLUSIONS: A sonographic-based classification in Graves' disease can distinguish subgroups of patients with different clinical courses and disease activity. This procedure is easy to perform and correlates well with clinical findings.

A singular case of Graves' disease in congenital thyroid hemiagenesis.

We report the observation of an unusual case of Graves' disease associated with thyroid hemiagenesis. A 41-year-old woman who presented with symptoms and clinical signs of hyperthyroidism was discovered to have thyroid hemiagenesia of the left lobe. Thyroid ultrasound scan showed enlargement of the right lobe with a single nodule, and absence of the left lobe; isotope scan showed homogeneous uptake in the single lobe and nodule. Ophthalmopathy, which was absent at presentation, developed after two years; after a further 2 years the patient developed decompensated hypothyroidism requiring thyroxine replacement. This is the first case of Graves' disease in thyroid hemiagenesis evolved to hypothyroidism, and a rare case of thyroid ophthalmopathy accompanying this condition.

Autocrine inhibitory influences of alpha-melanocyte-stimulating hormone in malignant pleural mesothelioma.

Malignant pleural mesothelioma is a highly aggressive tumor arising from the mesothelial cells that line the pleural cavities. This tumor is resistant to most conventional anticancer treatments and appears to be very sensitive to growth-promoting influences of cytokines and growth factors. Identification of natural inhibitory pathways that control growth should aid discovery of novel therapeutic approaches. We hypothesized that alpha-melanocyte-stimulating hormone (alpha-MSH), which is produced by many cell types and antagonizes cytokines and growth factors, could be an endogenous inhibitory molecule in mesothelioma. Twelve mesothelioma cell lines were established from pleural effusions of patients with malignant mesothelioma. Mesothelioma cells were found to express mRNA for proopiomelanocortin and its processing enzymes; release alpha-MSH peptide into supernatants; and express melanocortin 1 receptor (MC1R), the high-affinity receptor for alpha-MSH. Immunoneutralization of MC1R in the cell lines enhanced expression of interleukin-8 (IL-8), IL-6, and transforming growth factor-beta. These molecules promote mesothelioma proliferation and are considered therapeutic targets in this tumor. Coincubation of mesothelioma cells with synthetic alpha-MSH significantly reduced cell proliferation. The present research shows an autocrine-inhibitory circuit based on alpha-MSH and its receptor MC1R. Activation of MC1R by selective peptides or peptidomimetics might provide a novel strategy to reduce mesothelioma cell proliferation by taking advantage of this endogenous inhibitory circuit.