Global skeletal uptake of technetium-99m methylene diphosphonate in female patients receiving suppressive doses of L-thyroxine for differentiated thyroid cancer

This study was carried out in order to investigate the possible detrimental effects on bone of levothyroxine (L-T-4) suppressive therapy in female patients who had undergone surgery for differentiated thyroid cancer (DTC), Twenty female (14 premenopausal and 6 postmenopausal) patients receiving L-T-4 suppressive therapy for DTC were studied. The sample was selected in such a way as to avoid factors influencing bone metabolism other than L-T-4. All patients were monitored by sensitive thyroid-stimulating hormone, free triiodothyronine and free thyroxine assays throughout the follow-up. Nineteen healthy (12 premenopausal and 7 postmenopausal) matched women served as controls, In all subjects bone turnover was evaluated by the measurement of global skeletal uptake of technetium-99m methylene diphosphonate (GSU); bone mineral density (BMD) was measured by quantitative computed tomography at the lumbar spine (LS) and by dual-energy X-ray absorptiometry both at the LS and at three femoral sites: the femoral neck, Ward's triangle and the greater trochanter, No significant difference was found in either GSU or BMD between patients (treated for an average period of 68 months) and controls in the whole sample or in any subgroup, Furthermore, no correlations were found between either GSU or BMD and the duration of therapy, daily doses of L-T-4 Or results Of thyroid function tests, Our data show that carefully monitored L-T-4 therapy does not influence skeletal turnover (directly reflected by GSU) or the bone density of the spine and femur

Age-related changes in the global skeletal uptake of technetium-99m methylene diphosphonate in healthy women

A short-term evaluation of global skeletal uptake (GSU) of technetium-99m methylene diphosphonate (MDP) was performed in 40 healthy female subjects with a wide age range in order to investigate the clinical performance of the technique and to detect the age-related changes in bone turnover, The results obtained were compared with measurements of the main biochemical markers of skeletal metabolism. We found that GSU increases progressively with age, independently of concomitant changes in renal function; significant correlations with biochemical markers of bone formation were also found, Therefore, the method appears to provide useful information concerning the bone turnover rate, and is also applicable to elderly people owing to its simplicity

Predictive value of recombinant human TSH stimulation and neck ultrasonography in differentiated thyroid cancer patients

Background: Serum thyroglobulin (Tg) stimulation by recombinant human TSH (rhTSH), in combination with neck ultrasonography (US), is an important tool in the first follow-up of differentiated epithelial cell thyroid carcinoma (DTC) patients. The objective of this study was to investigate if a second rhTSH stimulation, performed 2-3 years later, is of clinical utility in the follow-up of these patients. Methods: One hundred and one consecutive ambulatory DTC patients were studied. The great majority of them (89/101) were low-risk patients, being stage I or II at tumor node metastasis (TNM) staging classification. All study patients had been treated by surgery and radioiodine ablation, and exhibited, at first rhTSH follow-up, either undetectable Tg (≤1 ng/mL) (rhTSH1-Tg-, n = 89 patients considered as free of disease) or low Tg (>1-5 ng/mL) (rhTSH1-Tg+, n = 12 patients considered with uncertain prognosis), with no US evidence of residual disease. In all patients, serum Tg measurement after a second rhTSH stimulation and neck US were performed. Results: At the second follow-up, all 89 rhTSH1-Tg-patients showed a negative US, and Tg became low positive only in one case, whereas it remained undetectable in the other patients. The overall negative predictive value of rhTSH1-Tg- was, then, 98.9%. Out of the remaining 12 patients (i.e., rhTSH1-Tg+ patients), 2 showed disease persistence/recurrence (with a positive predictive value of rhTSH1-Tg+ of 16.7%) and 6 became Tg-. Conclusions: A second rhTSH stimulation is useless in DTC patients who were rhTSH-Tg and imaging negative at first follow-up, while it is suggested in patients with detectable, although low, rhTSH-Tg levels at first follow-up: in the absence of clinical or US evidence of disease persistence, these patients should not be retreated by radioiodine, but simply scheduled for a later rhTSH stimulation. © Copyright 2008, Mary Ann Liebert, Inc

Coexistence of multiple endocrine neoplasia type 1 and type 2 in a large Italian family

To describe the coexistence of mutations of both the multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) genes in a large Italian family and evaluate if it could be associated with more aggressive clinical manifestations of the two syndromes. Blood samples were obtained for genetic and biochemical analyses. The RET gene exons (8, 10, 11, 13, 14, 15, 16, 18) and the MEN1 coding regions, including the exon-intron boundaries, were amplified by PCR and directly sequenced. We identified two germline mutations in the proband: the first one, K666M, located at the exon 11 of RET proto-oncogene and the second one, IVS4+1G > T, located in the MEN1 gene. The functional characterization of IVS4+1G > T variation, located in the splicing donor site of exon 4 of MEN1 gene, caused the in-frame junction of exon 3 to exon 5, thus obtaining a shorter protein. The same proband's germline mutations were found in 16 relatives out of 21 screened subjects: 8 carried IVS4+1G > T, 4 RET K666M, and 4 both the mutations. This is the second report in literature of coexistence in the same family of germline mutations of both RET proto-oncogene and MEN1 gene. The simultaneous presence of the two mutations was not apparently associated with more aggressive diseases, since at last follow-up all patients appeared to be disease-free or well compensated by medical therapy; finally, no one exhibited metastatic diseases