We demonstrated that the presence of a somatic RET mutation correlates with a worse outcome of MTC patients, not only for the highest probability to have persistence of the disease, but also for a lower survival rate in a long-term follow up. More interestingly, the presence of a somatic RET mutation correlates with the presence of lymph node metastases at diagnosis, which is a known bad prognostic factor for the definitive cure of MTC patients.

Our data suggest that BRAF V600E mutation is associated with high-risk PTC and in particular in follicular variant with invasive tumor growth.

Context:It is unclear whether patients with asymptomatic primary hyperparathyroidism (PHPT) do better with parathyroidectomy (PTx) as compared with conservative medical management. Objective:The aim of the study was to evaluate the beneficial effect of PTx vs. conservative management in patients with mild asymptomatic PHPT. Design:We conducted a prospective, randomized study. Setting:The study took place at a referral center. Patients:We studied 50 patients who did not meet any guidelines for parathyroid surgery as recommended by the National Institutes of Health Consensus Development Conference on Asymptomatic PHPT.Intervention: Patients were randomly assigned to PTx or no PTx and were evaluated at 6 months and at 1 yr. Main Outcome Measures:We compared changes (percentage of basal) of lumbar spine bone mineral density (BMD) between the two groups at 1 yr. Results:The change in BMD at lumbar spine was greater after PTx (ϩ4.16 Ϯ 1.13 for PTx vs. Ϫ1.12 Ϯ 0.71 for no PTx; P ϭ 0.0002). The change in BMD at the total hip was also significantly greater in the PTx group (ϩ2.61 Ϯ 0.71 for PTx vs. Ϫ1.88 Ϯ 0.60 for no PTx; P ϭ 0.0001). There was no difference in BMD after 1 yr between both groups at the one-third radius site. In comparison with those who did not undergo surgery, the PTx subjects, after 1 yr, showed significant differences in four quality of life measures as determined by the 36-item short form health survey scale: bodily pain (P ϭ 0.001), general health (P ϭ 0.008), vitality (P ϭ 0.003), and mental health (P ϭ 0.017). Conclusions:In patients with mild asymptomatic PHPT, successful PTx is followed by an improvement in BMD and quality of life.

No abstract

We investigated the involvement of the HRPT2 gene by loss of heterozygosity analysis and direct sequencing in a kindred with hyperparathyroidism-jaw tumor syndrome (HPT-JT) and three kindreds with familial isolated primary hyperparathyroidism (FIHP). Seven patients with sporadic parathyroid cancers and 35 with parathyroid adenomas with no family history of primary hyperparathyroidism or HPT-JT were also studied. A germline heterozygous substitution G to A was found in the donor splice site of intron 1 in one of the three FIHP families. No mutations were identified in the HPT-JT kindred. A somatic HRPT2 mutation was found in four of seven patients with parathyroid cancers, two of which were unreported frameshift mutations (195insT and 195insA) in exon 2. Consistent with recent findings, two of seven patients with sporadic parathyroid cancer had germline mutations. Four adenomas showed loss of heterozygosity at HRPT2, whereas a somatic HRPT2 mutation was found in one. In conclusion, we provide additional evidence for a strong association between HRPT2 gene mutations and sporadic parathyroid cancer. The finding that two of the seven patients with sporadic parathyroid cancer carried an HRPT2 germline mutation suggests that they might have occult HPT-JT. Our results also confirm the need for testing HRPT2 gene in FIHP families.

Cytological assessment of cold thyroid nodules cannot exclude malignancy in case of follicular tumors. Many follicular nodules undergo surgery although most of them later on prove to be benign. We report a new minimally invasive video-assisted approach (MIVA) for the treatment of thyroid lesions with a diameter minor than 3 cm. Ten females and 2 males (mean age: 37 yr) with a cold thyroid nodule and a cytological diagnosis of microfollicular tumor were selected for MIVA hemythyroidectomy. The procedure was carried out through a 15 mm incision with needlescopic instruments and a 30 infinity 5-mm endoscope. Mean operative time was 87 min (range 60-120). No complications were registered. Cosmetical result was excellent in all patients. MIVA hemythyroidectomy is safe and effective; indications and limits of this new procedure require further studies.

Higher TSH values, even within normal ranges, have been associated with a greater risk of thyroid malignancy. The relationship between TSH and papillary thyroid cancer (PTC) has been analyzed in 10 178 patients submitted to fine needle aspiration of thyroid nodules with a cytology of PTC (nZ497) or benign thyroid nodular disease (BTND, nZ9681). In 942 patients, submitted to surgery (521 from BTND and 421 from PTC), the histological diagnosis confirmed an elevated specificity (99.6%) and sensitivity (98.1%) of cytology. TSH levels were significantly higher in PTC than in BTND both in the cytological and histological series and also in patients with a clinical diagnosis of multinodular goiter (MNG) and single/isolate nodule (S/I). A significant agedependent development of thyroid autonomy (TSH !0.4 mU/ml) was observed in patients with benign thyroid disease, but not in those with PTC, diagnosed both on cytology and histology. In patients with MNG, the frequency of thyroid autonomy was higher and the risk of PTC was lower compared to those with S/I. In all patients, the presence of thyroid auto-antibodies (TAb) was associated with a significant increase of TSH. However, both in TAb positive and TAb negative patients TSH levels were significantly higher in PTC than in BTND. Our data confirm a direct relationship between TSH levels and risk of PTC in patients with nodular thyroid diseases. Thyroid autonomy conceivably protects against the risk of PTC, while thyroid autoimmunity does not play a significant role.

USE may represent an important tool for the diagnosis of thyroid cancer in nodules with indeterminate or nondiagnostic cytology and may prove useful in selecting patients who are candidates for surgery.