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Treatment with amiodarone is associated with changes in thyroid function tests, but also with thyroid dysfunction (amiodarone-induced hypothyroidism, AIH, and amiodarone-induced thyrotoxicosis, AIT). Both AIH and AIT may develop in apparently normal thyroid glands or in the presence of underlying thyroid abnormalities. AIH does not require amiodarone withdrawal, and is treated with levothyroxine replacement if overt, whereas subclinical forms may be followed without treatment. Two main types of AIT are recognized: type 1 AIT (AIT 1), a form of iodine-induced hyperthyroidism occurring in nodular goitres or latent Graves disease, and type 2 AIT (AIT 2), resulting from destructive thyroiditis in a normal thyroid gland. Mixed/indefinite forms exist due to both pathogenic mechanisms. AIT 1 is best treated with thionamides that may be combined for a few weeks with sodium perchlorate to make the thyroid gland more sensitive to thionamides. AIT 2 is treated with oral glucocorticoids. Once euthyroidism has been restored, AIT 2 patients are followed up without treatment, whereas AIT 1 patients should be treated with thyroidectomy or radioiodine. Mixed/indefinite forms of AIT are treated with thionamides. Oral glucocorticoids can be added from the beginning if a precise diagnosis is uncertain, or after a few weeks if response to thionamides alone is poor. The decision to continue or to stop amiodarone in AIT should be individualized in relation to cardiovascular risk stratification and taken jointly by specialist cardiologists and endocrinologists. In the presence of rapidly deteriorating cardiac conditions, emergency thyroidectomy may be required for all forms of AIT.

Permanent congenital hypothyroidism (CH) is a common disease that occurs in 1 of 3,000-4,000 newborns. Except in rare cases due to hypothalamic or pituitary defects, CH is characterized by elevated levels of thyroid-stimulating hormone (TSH) resulting from reduced thyroid function. When thyroid hormone therapy is not initiated within the first two months of life, CH can cause severe neurological, mental and motor damage. In 80-85% of cases, CH is associated with and presumably is a consequence of thyroid dysgenesis (TD). In these cases, the thyroid gland can be absent (agenesis, 35-40%), ectopically located (30-45%) and/or severely reduced in size (hypoplasia, 5%). Familial cases of TD are rare, even though ectopic or absent thyroid has been occasionally observed in siblings. The pathogenesis of TD is still largely unknown. Although a genetic component has been suggested, mutations in the gene encoding the receptor for the thyroid-stimulating hormone (TSHR) have been identified in only two cases of TD with hypoplasia. We report mutations in the coding region of PAX8 in two sporadic patients and one familial case of TD. All three point mutations are located in the paired domain of PAX8 and result in severe reduction of the DNA-binding activity of this transcription factor. These genetic alterations implicate PAX8 in the pathogenesis of TD and in normal thyroid development.

The aim of the present study was to establish the usefulness of conventional thyroid ultrasonography (US) and color flow-doppler (CFD) sonography in the assessment of 'cold' thyroid nodules. One hundred and four consecutive patients with thyroid nodules who were to undergo surgery were examined by US and CFD before thyroidectomy. Conventional US evaluated the presence of a halo sign, hypoechogenicity and microcalcifications. The vascular pattern on CFD was classified as follows: Type I, absence of blood flow; Type II, perinodular blood flow; Type III, marked intranodular blood flow. On histology, 30 nodules were diagnosed as malignant (carcinoma, CA) and 74 as benign nodules (BN). On US, the echographic pattern most predictive for malignancy was absent halo sign, which was found in 20/30 CA and in 17/72 BN (P ¼ 0.0001; specificity 77.0%; sensitivity 66.6%). The most specific combination on US, absent halo sign/microcalcifications, was found in 8/30 CA and in 5/74 BN (P < 0.005; specificity 93.2%, sensitivity 26.6%). The Type III pattern on CFD was found in 20/30 CA and 38/74 BN (not statistically significant). The combination of absent halo sign on US with Type III pattern on CFD was found in 15/30 CA and in 8/74 BN (P < 0.0001; specificity 89.0%, sensitivity 50.0%). The combination of absent halo sign/microcalcifications on US with Type III pattern on CFD was the most specific combination of the two techniques, being found in 5/30 CA and in only 2/74 BN (P < 0.01; specificity 97.2%, sensitivity 16.6%).In conclusion, findings on US and CFD become highly predictive for malignancy only when multiple signs are simultaneously present in a thyroid nodule. Thus the predictive value of these techniques increases at the expense of their sensitivity. Only in a small proportion of patients with thyroid carcinoma is US and CFD information highly predictive of malignancy.