Slow growth of benign thyroid nodules after menopause: no need for long-term thyroxine suppressive therapy in post-menopausal women.

Benign thyroid nodules represent a very common disorder, the management of which is still controversial. The aim of the present work was to evaluate by ultrasound examination the volume changes of thyroid nodules in post-menopausal women presenting single palpable nodular goiter of recent onset (less than 6 months from diagnosis). Forty-three patients received L-T4-treatment, 38 represented the no-treatment group. Long-term follow up (3 and 5 yr) did not show any significant change in the mean volume nodule in these patients. In the no-treatment group, the mean nodule volumes were stable over time from baseline to 5 yr. No significant difference was observed at any follow-up evaluation between thyroid hormone treated and untreated patients. After 1 yr of treatment, a significant decrease (p = 0.0275) in mean nodule volume occurred only for nodules with a baseline volume lower than 1.5 ml. The frequency of clinically relevant nodule size variation showed a more frequent decrease (13.9%) at 1 yr in the L-T4 group, as compared to the no-treatment group (2.6%), while the proportion of increased volume at 1 yr was higher in the untreated than in the L-T4 group (5.3% vs 2.3%). This inverse relationship between the 2 groups was not statistically significant (p = 0.076). In conclusion, an arrest in the growth of benign thyroid nodules occurs in the majority of women after menopause. Only a very limited number of these patients may benefit from thyroid hormone suppressive treatment.

Iodine deficiency in Calabria: characterization of endemic goiter and analysis of different indicators of iodine status region-wide.

The distribution of goiter prevalence in schoolchildren (no.=13,984, age 6-14 yr), the neonatal TSH results obtained from the congenital hypothyroidism screening program and the urinary iodine excretion values (no.=284) were employed for the assessment of iodine deficiency in Calabria, a Southern Italy region. Data were collected during the years 1990-1996. In the inland territory, goiter prevalence ranged from 19 to 64%. At sea level, there was a great variability of goiter prevalence, with values varying from 5.3 to 25.7%. The analysis of the neonatal hypothyroidism screening program data (no.=21,078) showed a 14.8% frequency of TSH levels >5 microU/ml whole blood in newborns from the inland territory and a 14.1% frequency at sea level. Urinary iodine excretion resulted (mean+/-SD) 53.8+/-43.4 microg/l (range: <20 to 189 microg/l) in the inland territory and 89.6+/-59.8 microg/l (range: 26 to 333 microg/l) at sea level. Median urinary iodine excretion values in 13 villages or small towns of the inland territory ranged from 31 to 57 microg/l. In 2 major towns located at sea level, the median iodine excretion values were 72 microg/l in Crotone main city and 94 microg/l in Reggio Calabria main city. The data indicated that moderate, with pockets of severe iodine deficiency is present in the inland region while iodine supply varies from sufficient to marginally low in the coastal areas. Mild iodine deficiency was found in a major town located at sea level.

A large family with hereditary MTC: role of RET genetic analysis in differential diagnosis between MEN 2A and FMTC.

Germline mutations of the RET proto-oncogene cause three different cancer syndromes: multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine neoplasia type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). In the absence of biochemical and/or clinical evidence of pheochromocytoma and hyperparathyroidism, patients with MEN 2A disease display the same phenotype of FMTC disease, although prognosis and clinical management in both affected and unaffected familial members are quite different. We studied a family with hereditary MTC, whose proband was referred to us because of enlarged cervical nodes and increased calcitonin serum levels 28 years after the total thyroidectomy for MTC. Cervical node dissection was carried out and subsequently the presence of MTC metastasis was histologically confirmed. A RET genomic mutation at codon 634 (TGC-->TTC) was identified in the proband and in seven out of 19 familial members studied. Accordingly, a hereditary disease was suggested. However, the strong association of RET mutation at codon 634 with the presence of pheochromocytoma in MEN 2 disease suggested a more rigorous management in all gene carriers. Indeed, during the follow-up pheochromocytoma was subsequently identified in the proband. This finding suggests that all families with a pedigree suggestive of FMTC should be regarded at risk from MEN 2A disease, at least when a critical mutation in the RET cysteine domain is detected.

Thyrotropin receptor gene alterations in thyroid hyperfunctioning adenomas.

Forty-four thyroid autonomously hyperfunctioning adenomas were analyzed to assess the frequency of mutations occurring in the TSH receptor (TSHR). PCR-amplified fragments encompassing the entire exon 10 of the TSHR gene were obtained from the genomic DNA extracted from the tumors and their adjacent normal tissues and were examined by direct nucleotide sequencing. Point mutations were found in 9 of the 44 adenomas examined (20%). One mutation occurred in codon 619 (Asp to Gly), four in codon 623 (three were Ala to Ser, one Ala to Val substitution), two in codon 632 (both Thr to Ile), and two in codon 633 (Asp to Tyr or His). All the alterations were located in a part of the gene coding for an area including the third intracellular loop and the sixth transmembrane domain of the TSH receptor. All mutations were somatic and heterozygotic, and none was simultaneous with alterations of ras or gsp oncogenes. Thus, our data show that in our series of 44 hyperfunctioning thyroid adenomas, a somatic mutation of the TSHR, responsible for the constitutive activation of the cAMP pathway, occurs in 20% of the tumors.