Francesco Fonderico

Pamidronate improves the quality of life and induces clinical remission of bone metastases in patients with thyroid cancer

Skeletal metastases from thyroid cancer are poorly responsive to medical or radioiodine treatment. Bone destruction in skeletal metastases results from osteoclast-induced bone resorption. Therefore, a new approach in the therapy of bone metastases consists in using aminobisphosphonates, such as pamidronate, which are potent inhibitors of osteoclastic activity. In the present study, 10 thyroid cancer patients with painful osteolytic bone metastases were administered pamidronate (90 mg, as a 2 hour intravenous infusion) monthly for 12 consecutive cycles. Bone pain, quality of life, performance status, analgesic consumption and disease staging were evaluated before and during the trial. The patients who had been administered pamidronate showed a significant decrease in bone pain (P = 0.0052). Performance status improved nearly significantly (P = 0.051), while the quality of life showed a remarkable amelioration. However, no significant decrease in analgesic consumption was recorded. Partial radiographic response of bone lesions was observed in 2/10 patients. The side effects of pamidronate were mild and transient. In conclusion, monthly infusion of pamidronate is a well-tolerated treatment that induces significant relief from bone pain and improves the quality of life of thyroid cancer patients with symptomatic and osteolytic bone metastases.

Thyroid Nodules Treated with Percutaneous Radiofrequency Thermal Ablation: A Comparative Study

PURPOSE Percutaneous radiofrequency thermal ablation (RTA) was reported as an effective tool for the management of thyroid nodules (TNs). The aim of this study was to investigate the effects of RTA and to establish whether they were treatment-related by comparison with a matched, untreated control group. PATIENTS AND METHODS The study population included 40 patients with compressive TNs: 22 had nontoxic TNs, and 18 had toxic TNs and were treated with methimazole. In all patients, a fine-needle aspiration cytology was performed to exclude a thyroid malignancy. STUDY DESIGN Twenty patients were treated with RTA (group A), and 20 others did not receive any treatment (group B). At baseline, age, gender, and TN features did not differ significantly between groups. All patients were clinically, biochemically, and morphologically evaluated at baseline and after 1, 3, 6, and 12 months. RESULTS TN volume significantly decreased in group A (1.8 ± 0.3 ml at 12 months vs. 13.3 ± 1.8 ml at baseline; P < 0.0001) and remained stable in group B [11.7 ± 1.5 ml at 12 months vs. 11.2 ± 1.5 ml at baseline; P = not significant (NS)]. At 3-, 6-, and 12-month evaluations, TN volume was significantly lower in group A than in group B (P < 0.005). At the end of the follow-up, pressure symptoms were improved in all patients in group A but persisted unchanged in group B. In group A, hyperthyroidism completely recovered in 40% and improved in 40% of patients with toxic TNs, whereas it persisted in all patients with toxic TNs in group B. RTA was safe and well tolerated in all patients. CONCLUSIONS RTA induced a marked TN volume shrinkage resulting in parallel improvement of pressure symptoms. In most patients with toxic TNs, hyperthyroidism significantly improved as well. RTA may represent a valid therapeutic approach in patients with TNs not receiving conventional treatments.

Evaluation of goiter endemia by ultrasound in schoolchildren in Val Sarmento (Italy)

Ultrasonography is an excellent and objective method for assessing thyroid volume, especially in children where clinical evaluation is inaccurate. The aim of this study was to evaluate the presence of goiter by thyroid ultrasound and palpation in 244 schoolchildren, 6 to 14 years old, living in some rural villages of Val Sarmento, a mountain area of Basilicata, Italy. In 1996 we revealed the presence of endemic goiter in 25% of the schoolchildren evaluated by palpation, according to World Health Organization (WHO) criteria, and in 15.9% of the schoolchildren evaluated by ultrasonography (7.5 MHz linear probe). The median urinary iodine excretion, taken from an extemporaneous sample of the first urines in the morning, was 62.2 μg/l. This study includes Val Sarmento, an area with mild-moderate grade (Grade I) of iodine deficiency, suggesting the need for iodine prophylaxis. Furthermore, it proves that the measurement of thyroid volume by ultrasonography is an essential instrumental method for a correct epidemiological study of endemic goiter, particularly in areas where there is mild iodine deficiency.

Osteoporosis and Thyrotropin-Suppressive Therapy: Reduced Effectiveness of Alendronate

BACKGROUND Many reports of the effect of exogenous thyroxine therapy on bone mineral density (BMD) show a relationship between excess thyroid hormone administration and osteoporosis. The aim of this study was to evaluate the effect of antibone resorptive agents, in particular alendronate (ALN) on BMD in postmenopausal osteoporotic women with thyroid carcinoma who were receiving long-term thyrotropin (TSH)-suppressive therapy with thyroxine. METHODS Seventy-four postmenopausal women with low BMD (T-score < or =-2.5) and differentiated thyroid carcinoma on long-term TSH-suppressive therapy (TSH > or =0.05 and < or =0.1 microU/mL) for about 3-9 years were selected for the study. The patients were divided into three groups according to the length of levothyroxine (LT(4)) treatment prior to the beginning of the study: group A (TSH-suppressive therapy for about 3 years), group B (for about 6 years), and group C (for about 9 years). These patients were compared with 74 matched women not taking LT(4). All patients and controls were treated with bisphosphonates, calcium, and vitamin D for 2 years and evaluated. RESULTS After 24 months of treatment group A showed a 7.8% increase in lumbar BMD; group B, a 4.6% increase; and group C, a 0.86% increase. In the control group BMD increased 8.2%. A significant difference was found in both lumbar and femoral BMD increase among the three groups: group C had a lower BMD increase than group A (p < 0.001) and B (p < 0.001). CONCLUSIONS In postmenopausal women who were receiving adequate amounts of calcium and vitamin D in their diet ALN was less effective for those who were also receiving TSH-suppressive doses of LT(4) for either 6 or 9 years. The positive effect of ALN on BMD was less for longer periods of LT(4) treatment. It seems likely that other bisphosphonates would also be less effective in increasing BMD in postmenopausal women receiving TSH-suppressing doses of LT(4).

Improvement of Bone Physiology and Life Quality Due to Association of Risedronate and Anastrozole

The endocrine therapy is the new frontiers of many breast cancers hormone sensitive. Hormone therapy for treating women with hormone receptor-positive cancer suppresses breast cancer growth either by reducing estrogen synthesis or by interfering with the action of estrogen within tumor cells. In this prospective randomized observational study we investigate the effect of adjuvant anastrozole in monotherapy or associated with risedronate on bone physiology and quality of life in postmenopausal, hormone-sensitive early breast cancer women at mild to moderate risk of fragility fractures. Methods : 84 women were randomly assigned to receive anastrozole alone (group A) or anastrozole plus oral risedronate (group A+R). At baseline and after 24 months lumbar spine (LS) and femoral neck (FN) BMD were evaluated with dual-energy x-ray absorptiometry and health-related quality of life (HRQoL) was examined using the short-form healthy survey. Results : After 24 months, the group A+R has showed a significant increase in T-score for LS (p < 0.05) and for FN (p < 0.05) whereas women of group A had a statistically significant rate of bone loss both in LS T-score (p < 0.05) and in FN (p < 0.05). A significant change in T-score BMD was seen for group A+R compared with group A at the LS (p = 0.04) and at FN (p = 0.04). Finally, group A+R showed an overall significant improvement of health profile (SF-36) in group A (p = 0.03). Conclusion : Postmenopausal breast cancer women with osteopenia during treatment with anastrozole have considerable risk of developing osteoporosis during the first 2 years; preventive measures such as healthy lifestyle and daily supplements of calcium and vitamin D alone seem to be insufficient in holding their bones healthy. Our findings suggest the usefulness of addition of risedronate in order to prevent aromatase inhibitors-related bone loss, not only in case of high-risk of fractures, but also for women at mild-moderate risk. This determines a significant improvement in bone health and a positive impact on HRQoL.

Clinical outcome in differentiated thyroid carcinoma and microcarcinoma

INTRODUCTION Due to the frequent use of neck ultrasonography, the incidence of differentiated thyroid microcarcinoma (DTMC), defined as a lesion with greatest dimension ≤1 cm, is increasing worldwide. Although DTMC generally has a lower aggressivity and a better prognosis than differentiated thyroid carcinoma (DTC), some cases of clinically aggressive DTMC were found. The aim of this study is to compare the rate of recurrence in DTMC and DTC, during a 3-year follow-up. METHODS Patients with differentiated thyroid carcinoma, who underwent total thyroidectomy and postoperative (131)I-RAI ablation, were stratified according to lesion diameter (DTC for diameter > 1 cm or DTMC ≤ 1 cm). After surgery, patients underwent a 3-year follow-up. Recurrent disease was defined on the basis of positive biochemical (Tg > 2 ng/ml under TSH-suppression or after rhTSH-stimulation) and/or imaging (US, WBS, CT, PET/CT) findings. RESULTS 449 patients have been included in the final analysis. Linfoadenectomy rate and RAI ablative dose were significantly higher in DTC than in DTMC (32.7% vs. 22.4%, p = 0.018 and 112.3 ± 21 vs. 68.3 ± 24.1 mCi, p < 0.001). During the follow-up, 50 carcinoma recurrences occurred, more frequent in DTC than in DTMC (15.6% vs. 7.6%, p = 0.010). After adjustment for gender, age, rate of lymph node dissection and 131I dose of RAI treatment, the difference in the risk of recurrence was no longer significant among DTC and DTMC patients (HR: 1.585, 95% CI 0874-2877, p = 0.130). CONCLUSIONS The prediction of disease severity cannot be based exclusively on lesion diameter. A more careful therapeutic approach and follow-up should be recommended in DTMC patients.