Unsaturated acyl chains dramatically enhanced cellular uptake by direct translocation of a minimalist oligo-arginine lipopeptide.

The recurring issue with cell penetrating peptides is how to increase direct translocation vs. endocytosis, to avoid premature degradation. Acylation by a cis unsaturated chain (C22:6) of a short cationic peptide provides a new rational design to favour diffuse cytosolic and dense Golgi localisations.

Bcgitis and vaccine-derived poliovirus infection in a patient with a novel deletion in RAG1 binding site.

A girl who developed severe BCGitis and vaccine-derived poliovirus infection was discovered to have a novel deletion of RAG1. A neonatal screening program for SCID would identify affected infants at birth, before live vaccines are administered.

Streptococcus pneumoniae: elusive mechanisms of the body's defense systems.

Streptococcus pneumoniae is one of the most important human pathogens. It represents the most frequent cause of pneumonia, meningitis, sinusitis and otitis. After the PCV7 vaccine introduction, a serotypic switch was noticed. This phenomenon led to the replacement of the seven serotypes contained in the vaccine with other less common ones, some of which are invasive or characterised by antibiotic-resistance. This replacement is only partially due to the vaccination. Many causes have been suggested to explain this effect: apearance of new serotypes, diffusion of minority serotypes and replacement of common serotypes due to natural secular trend. Pneumococcus has a promiscuous "sex life", characterized by homologous recombinations within the same species and also between different species. This fact can unlock the secret of how these pathogens can develop antibiotic or vaccine-resistance. The serotypic switch involves big loci that are responsible for capsular polysaccharide synthesis. The most important region of the genome involved in this process is near the gene tetM. The same mechanisms are also responsible for antibiotic resistance. In recent years the growth of penicillin, macrolides and clindamycine resistance has been noticed. It is also important to underline that multidrug-resistant bacteria isolation has increased. In conclusion, to obtain more information about bacteria composition and evolution, antibiotic-resistance and vaccine response, it is fundamental to improve the epidemiological surveillance of pneumococcal infections using modern molecular diagnostic techinques.

Recombinant human TSH (rhTSH) in 2009: new perspectives in diagnosis and therapy.

Thyrotropin stimulating hormone (TSH) exerts a physiological stimulus to growth, function and ability to take up iodine of both normal and malignant follicular cells. For this reason, the metastases deriving from well differentiated thyroid cancer (DTC) can be effectively treated with radioiodine but this procedure requires a strong TSH stimulus that can be obtained by withdrawing the L-thyroxine (LT4) therapy. However, both the social and personal life of patients while they are withdrawing the LT4 therapy are heavily affected by hypothyroidism. After more than a decade since the development of recombinant human TSH (rhTSH), this molecule has been introduced in the clinical practice (1998 in USA and 2001 in Europe) as a safe and reliable alternative to LT4 withdrawal. For several years the main clinical application of rhTSH was for diagnostic purposes (i.e. thyroglobulin stimulation) but, after the more recent demonstration of its efficacy in preparing DTC patients for radioiodine post surgical thyroid remnant ablation, also this application has been officially recognized worldwide. The validity of rhTSH has been also demonstrated in stimulating metastatic thyroid cancer cells but this employment is not yet officially approved and it can be used only in patients with contraindication to hypothyroidism (i.e. "compassionate use"). Other possible uses of rhTSH stimulation are related to its ability to enhance both 18FDG uptake during PET scan of metastatic DTC patients and the effectiveness of conventional chemotherapy. The aim of this review was to recall how the rhTSH has been developed and progressively introduced in the clinical management of DTC patients.

Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma.

Recombinant human TSH (rhTSH)-stimulated thyroglobulin (Tg) measurement and (131)I whole body scan (WBS) have been validated as informative tests in the postsurgical follow-up of differentiated thyroid carcinoma. We report the diagnostic accuracy of Tg measurement and diagnostic WBS, alone or in combination, after rhTSH stimulation in a retrospective, consecutive series of patients undergoing follow-up for differentiated thyroid cancer. Routine procedures also include neck ultrasound in every patient and post-therapy WBS when indicated. We studied 340 consecutive patients with differentiated thyroid carcinoma, previously treated with near-total thyroidectomy and (131)I thyroid ablation, scheduled for routine diagnostic tests. At baseline on L-T(4)-suppressive therapy, 294 patients had undetectable (<1 ng/ml) serum Tg and negative anti-Tg autoantibodies (TgAb), 25 patients had undetectable serum Tg and positive TgAb, and 21 patients had detectable serum Tg and negative TgAb. These patients were tested for the presence of active disease by rhTSH stimulation. The results of our study showed that rhTSH-stimulated Tg alone had a diagnostic sensitivity of 85% for detecting active disease and a negative predictive value (NPV) of 98.2%. After adding the results of neck ultrasound, sensitivity increased to 96.3%, and the NPV to 99.5%. rhTSH-stimulated WBS had a sensitivity of only 21% and a NPV of 89%. The combination of rhTSH-stimulated Tg and WBS had a sensitivity of 92.7% and a NPV of 99%. We conclude that the rhTSH-stimulated Tg test combined with neck ultrasonography has the highest diagnostic accuracy in detecting persistent disease in the follow-up of differentiated thyroid carcinoma. A detectable level of serum Tg on L-T(4), its conversion from undetectable to detectable after rhTSH, and/or a suspicious finding at ultrasound will allow the identification of patients requiring therapeutic procedures without the need for diagnostic WBS.

Prediction of disease status by recombinant human TSH-stimulated serum Tg in the postsurgical follow-up of differentiated thyroid carcinoma.

Stimulation with recombinant human TSH (rhTSH) has been introduced in clinical practice as an effective alternative to thyroid hormone withdrawal for the diagnostic follow-up (Tg measurement and 131-iodine whole-body scan) of patients with differentiated thyroid cancer. The present study was specifically aimed to evaluate the utility of rhTSH-stimulated serum Tg measurements in patients with undetectable serum Tg values, on L-T(4) therapy, as the only test to differentiate patients with persistent disease from patients who are disease-free. We studied 72 consecutive patients with differentiated thyroid cancer, previously treated with near-total thyroidectomy and 131-I thyroid ablation. Admission criteria were: an undetectable (<1 ng/ml) serum Tg, on L-T(4) therapy, and negative anti-Tg antibodies. The study design consisted of a Tg-stimulation test after rhTSH, during L-T(4), followed by diagnostic WBS and serum Tg measurement off L-T(4). After rhTSH, serum Tg remained undetectable in 41 of 72 patients (56.9%). A negative rhTSH Tg test agreed with an undetectable hypo-Tg in 36 of 41 cases (87.8%), all without evidence of metastatic disease at hypo-WBS. In 5 of 41 cases (12.2%), hypo-Tg was detectable (1.1-7.8 ng/ml), in association with negative hypo-WBS or faint uptake in the thyroid bed. Serum Tg converted from undetectable to detectable after rhTSH in 31 of 72 patients (43.1%), with a peak Tg ranging between 1.2 and 23.0 ng/ml. Hypo-Tg was always detectable in these patients (100% concordance), and it was significantly higher than rhTSH-stimulated Tg (P < 0.0002). Hypo-WBS was positive in 23 of 31 patients (74.2%), showing thyroid residues in 12, cervical lymph nodes in 7, and lung metastases in 4 cases. In 8 of 31 cases, hypo-WBS was negative, despite detectable serum Tg. Thus, rhTSH-stimulated Tg was able to detect all cases of documented local or distant metastases. In conclusion, our data indicate that, in patients with undetectable basal levels of serum Tg, rhTSH-stimulated Tg represents an informative test to distinguish disease-free patients (not requiring WBS) from diseased patients (requiring further diagnostic and/or therapeutic procedures).

Outcome of differentiated thyroid cancer with detectable serum Tg and negative diagnostic (131)I whole body scan: comparison of patients treated with high (131)I activities versus untreated patients.

Detectable serum Tg levels associated with negative diagnostic (131)I whole body scan are not infrequently found in patients with differentiated thyroid cancer. Several researchers have shown that in these patients the administration of high (131)I activity (100 mCi or more) increases the sensitivity of a posttherapy diagnostic (131)I whole body scan performed a few days later and allows the detection of neoplastic foci not seen with diagnostic doses of (131)I. Empirical radioiodine treatment has also been advocated by some researchers, but its therapeutic effect is controversial. In our institute, positive serum Tg/negative diagnostic (131)I whole body scan patients were not treated with high (131)I activities before 1984; afterward, almost all patients with positive serum Tg/negative diagnostic (131)I whole body scan patients were treated with radioiodine, and a posttherapy diagnostic (131)I whole body scan was performed. In the present retrospective study we compared the outcome of these two groups of patients, 42 treated and 28 untreated, followed for mean periods of 6.7 +/- 3.8 and 11.9 +/- 4.4 yr, respectively. In the treated group the first posttherapy diagnostic (131)I whole body scan was negative in 12 patients and positive in 30 patients. (131)I treatment was further administered only in the latter group. At the end of follow-up in treated patients a complete remission (normalization of serum Tg off L-thyroxine and negative diagnostic (131)I whole body scan) was observed in 10 patients (33.3%). In 9 cases (30%) posttherapy diagnostic (131)I whole body scan became negative, and serum Tg was reduced but still detectable; in 11 patients (36.6%) serum Tg was detectable, and posttherapy diagnostic (131)I whole body scan was positive. The resolution of (131)I uptake in lung metastases was observed in 8 of 9 cases (88.8%) and in cervical node metastases in 11 of 18 cases (61.1%). In patients treated only once because the posttherapy diagnostic (131)I whole body scan was negative (n = 12), 2 patients (16.7%) were in apparent remission, 7 (58.3%) had detectable Tg values without evidence of disease, 2 (16.7%) showed lymph node metastases in the mediastinum, and 1 patient (8.3%) died because of lung metastases. Of the 28 untreated patients, none with radiological evidence of disease, serum Tg off L-thyroxine therapy became undetectable in 19 cases (67.9%), significantly reduced in 6 cases (21.4%), and unchanged or increased in 3 patients (10.7%), 1 of whom developed lung metastases 14 yr after the diagnosis. In summary, our results indicate that in patients with detectable serum Tg and negative diagnostic (131)I whole body scan, treatment with high doses of (131)I may have therapeutic utility in patients with lung metastases and, to a lesser extent, in those with lymph node metastases. However, in view of the frequent normalization of Tg values in untreated patients, we believe that treatment with (131)I should be considered according to the result of the first posttherapy scan. If positive in the lung, (131)I treatment should be continued up to total remission; surgical treatment should be preferred in patients with node metastases, and no treatment should be used in those with thyroid bed uptake or no uptake.

Radioiodine treatment of metastatic differentiated thyroid cancer in patients on L-thyroxine, using recombinant human TSH.

OBJECTIVE: This study tested the hypothesis that administration of human recombinant thyroid-stimulating hormone (rhTSH: Thyrogen, thyrotropin alpha) could promote iodine-131 ((131)I) uptake in the therapy for metastatic or locally invasive differentiated thyroid cancer (DTC), obviating L-thyroxine suppressive therapy (L-T4) withdrawal and hypothyroidism in patients with advanced disease. METHODS: Twelve totally (or almost completely) thyroidectomized adults, nine of whom had received earlier therapy after L-T4 withdrawal, underwent (131)I treatment while euthyroid on L-T4, after rhTSH administration. Nine underwent diagnostic whole-body scanning (WBS) after two consecutive daily i.m. injections (0.9 mg) of rhTSH. They then received an identical second course of rhTSH to promote therapeutic (131)I uptake. Post-therapy WBS was performed one week later. Three patients received only rhTSH (131)I therapy. RESULTS: Administration of rhTSH promoted (131)I uptake in all patients, as demonstrated by post-therapy WBS. Administration of rhTSH also promoted a significant increase in serum thyroglobulin (Tg) concentrations. According to the most recent measurements, 3-12 months after therapy, serum Tg levels fell in four, and stabilized in two out of eleven patients. Upon additional rhTSH-WBS 8 months post-study, a reduction in one metastatic site was noted in one patient. The rhTSH was well tolerated, with mild, transient fever and/or nausea occurring in only a minority of patients. Individuals with bone metastases experienced degrees of peritumoral pain and swelling that were similar (though more short-lived) to those seen in the same or other patients after L-T4 withdrawal. CONCLUSIONS: Administration of rhTSH is a safe, successful tool for inducing (131)I uptake in local and metastatic DTC lesions, and avoids L-T4 withdrawal, preserving metabolic homeostasis and preventing the debilitating effects of hypothyroidism.

Use of surgical gamma probe for the detection of lymph node metastases in differentiated thyroid cancer.

BACKGROUND: Patients with differentiated thyroid cancer (DTC) after total or near-total thyroidectomy require 131I therapy. After surgery the persistence of lymph node metastases in our series of patients was frequent (30%). Such patients are preferentially treated with radioiodine and shifted to surgical reintervention when the nodal lesions persist after two 131I treatments. AIM: Use of an intraoperative radioactive probe (C-TraK) to allow a more radical surgical approach in thyroid cancer patients submitted to surgery for lymph node metastases. METHODS AND RESULTS: After adequate withdrawal of L-thyroxine suppressive therapy six patients were given high 131I doses followed by post-therapy WBS which demonstrated cervical activity in 5 patients and peri-jugular activity in 1. Surgery with the help of a gamma probe allowed to detect and remove all metastatic nodes. After excision all surgical specimens showed higher radioactive counts with respect to the background. The post-surgical scan showed the disappearance of all areas of 131I uptake. Histology confirmed the presence of metastatic lesions from papillary thyroid cancer. CONCLUSIONS: We conclude that the use of a gamma probe can be successful in patients with metastatic neck lesions resistant to 131I treatment, particularly in patients with nonpalpable lesions.

Clinical experience with recombinant human thyroid-stimulating hormone (rhTSH): serum thyroglobulin measurement.

Only normal or neoplastic thyroid follicular cells produce and secrete the prohormone, thyroglobulin (Tg). For some 25 years, elevated serum concentrations of Tg therefore have been employed as a post-operative marker for well-differentiated thyroid carcinoma. The aim of serum Tg measurement is to identify patients requiring: A) further testing to confirm the presence and to determine the stage, site and functionality of tumour; and/or B) further treatment. Serum Tg testing has the advantages of superior sensitivity to radioiodine whole-body scanning (WBS), lack of false positive readings, simplicity, speed, low cost, precision and wide availability. However, major limitations of serum Tg testing are interference by serum anti-Tg antibodies and decreased sensitivity during THST. To obviate this last drawback, the use of recombinant human thyroid-stimulating hormone (rhTSH) has been clinically investigated as a preparative adjunct to serum Tg testing in the diagnostic follow-up of well-differentiated thyroid cancer. A large, multicentre international Phase III study now has confirmed evidence from earlier Phase I/II and Phase III trials and established the safety and efficacy of rhTSH in stimulating Tg release by residual and neoplastic thyroid tissue. This confirmatory study has clearly shown that 1) rhTSH administration significantly increases sensitivity of serum Tg measurement in patients on THST; and 2) by permitting sensitive diagnostic follow-up with serum Tg measurement and/or radioiodine WBS during THST, rhTSH administration improves patient comfort and quality of life compared to THST withdrawal. Thus use of the drug in diagnostic follow-up recently has received regulatory approval in the United States, and such approval is pending in the European Union. With regulatory approval, rhTSH is likely to gain an important role as a preparative adjunct to serum Tg testing in everyday practice.

Influence of plant genotype on the selection of nodulating Sinorhizobium meliloti strains by Medicago sativa.

We analysed the genetic diversity of 270 Sinorhizobium meliloti strains isolated from nodules of three different Medicago sativa varieties, planted in three different Italian soils, combining the Analysis of Molecular Variance (AMOVA) with the Random Amplified Polymorphic DNA (RAPD) technique to estimate variance among RAPD patterns with the aim to draw an objective description of the population genetic structure. Results indicated that a general intraspecific genetic diversity was globally distributed among all the population, however a very high level of diversity was found among strains nodulating different Medicago sativa varieties. Moreover the distribution of the RAPD haplotypes among the plant varieties also showed to be non-random. The overall data indicated that the plant genotype is a major factor in shaping the genetic structure of this natural Rhizobium population.

Outcome of thyroid function in Graves' patients treated with radioiodine: role of thyroid-stimulating and thyrotropin-blocking antibodies and of radioiodine-induced thyroid damage.

UNLABELLED: We investigated the interrelationship and the influence of thyroid-stimulating antibodies (TSAb), TSH-blocking antibodies (TSHBAb), and of radioiodine (131I)-induced thyroid damage in the early (within 1 yr) outcome of thyroid function in hyperthyroid patients with Graves' disease (GD) treated with 131I. TSAb, TSHBAb, and ultrasound thyroid volume (as an index of thyroid damage) were simultaneously measured before and at 1, 3, 6, and 12 months after 131I in 31 GD patients. One year after radioiodine, 9.7% of patients were hyperthyroid (Hyper-group), requiring methimazole; 12.9% were euthyroid (Eu-group); and 77.4% were hypothyroid (Hypo-group). Pretreatment thyroid volume in the Eu-group and Hyper-group was significantly greater (P = 0.009) than in the Hypo-group. Pre-131I TSAb levels were higher in the Hyper-group vs. the Hypo-group (P = 0.01) or the Eu-group (P = 0.03). A significant post-131I increase in TSAb levels occurred in 66% of patients developing hypothyroidism but not in those remaining hyperthyroid. After 131I, TSHBAb appeared in 7 patients, in all but one associated with high levels of TSAb. One year after radioiodine: 1) the mean percent reduction in thyroid volume was greater in the Hypo-group (80.7%) or the Eu-group (83.5%) than in the Hyper-group (35.7%) (P = 0.007 and 0.0033 respectively); 2) hypothyroid patients had smaller (P = 0.0058) post-131I thyroids than hyperthyroid patients; and 3) TSAb were still elevated in 75% hypothyroid patients, but all of them had a thyroid volume < or = 8 mL, indicating major postradioiodine gland damage. IN CONCLUSION: 1) the early outcome of thyroid function after 131I for GD is mainly related to pretreatment thyroid volume and to the degree of its reduction after therapy; 2) high TSAb levels before 131I are associated with a relative resistance to therapy; 3) a postradioiodine increase in TSAb levels is related to the development of hypothyroidism; and 4) the concomitant appearance of TSHBAb and disappearance of TSAb are not frequent after 131I and play a role in the development of early postradioiodine hypothyroidism only in a minority of patients.

Treatment of solitary autonomous thyroid nodules by percutaneous ethanol injection: results of an Italian multicenter study. The Multicenter Study Group.

Percutaneous intranodular ethanol injection (PEI) has been proposed for the therapy of autonomously functioning thyroid nodules. In 1992, an Italian multicenter study was undertaken to confirm the usefulness and the feasibility of this procedure. The study included 429 patients: 242 (56.4%) were affected by a toxic adenoma (TA) and 187 (43.5%) by pretoxic adenoma (PTA). Free thyroid hormone levels (FT4, FT3) and thyroid stimulating hormone (TSH) were measured before and 3, 6, 12 months after the end of treatment; thyroid ultrasound and thyroid scintiscan were performed in the majority of patients before and after treatment. Patients underwent 2-12 sessions of ethanol injection under sonographic guidance (median 4). The total amount of ethanol administered per patient (1.5 mL/mL nodular volume) was 2-50 mL (mean +/- SD, 17 +/- 9 mL), and the amount per each injection was 1-8 mL (3.2 +/- 1.3 mL). The treatment was judged successful when both TSH and free thyroid hormone serum levels returned within the normal range and recovery of tracer uptake in extranodular tissue was observed at scintiscan, at any time during the follow-up period. The treatment was considered unsuccessful when no change was observed at scintiscan and/or serum TSH levels remained less than 0.4 mU/L. A successful treatment was achieved in 66.5% of patients with TA and in 83.4% of patients with PTA, when assessed after a 12-month follow-up. In all cases a reduction of the nodular size was observed. Almost all positive results were obtained in nodules whose initial volume was less than 15 mL; large nodules responded less favorably. The treatment was generally well tolerated, only transient side-effects, mainly local pain at the time of injection, were observed. Once normalization of scintigraphic image and of FT4, FT3 and TSH serum concentrations was achieved, no recurrence of hyperthyroidism nor development of hypothyroidism were observed for the length of the study. In conclusion, percutaneous ethanol injection for treatment of autonomously functioning thyroid nodules is effective and safe. Better results are obtained in patients with PTA than in patients with TA, particularly when the initial volume of the nodule is less than or equal to 15 mL. PEI may be considered as an alternative to surgery and to radioiodine for treatment of autonomously functioning thyroid nodules.

Prolonged treatment of hirsutism with flutamide alone in patients affected by polycystic ovary syndrome.

Hirsutism is a common symptom of women affected by polycystic ovary syndrome (PCOS). The effectiveness of the antiandrogen flutamide alone was studied in 25 patients affected by PCOS with severe hirsutism for a period of 24 months. Seventeen of these patients had not been treated before and eight had had previous but unsatisfactory therapy. Nineteen patients showed a normal body weight (BMI < 25 kg/m2) whereas six were obese (BMI > 35 kg/m2). A chemical and endocrinological evaluation and an assessment of the degree of hirsutism, assigned by Ferriman-Gallwey score (mean 22 +/- 3.038), was performed under baseline conditions. Patients started treatment with flutamide (Eulexin, Schering-Plough, Kenilworth, USA) at the dose of 500 mg daily. A chronobiological assessment of gonadotropin episodic secretion and of gonadotropin response to GnRH challenge (10 micrograms in bolus) was done before and on day 7 of flutamide administration. During treatment, our patients showed a marked and significant reduction of hirsutism starting from a score of 6 and reaching the maximum (9.6 + 2.1) at 24 months of therapy. No relevant hormonal changes or side-effects were observed during therapy. Our data demonstrate that hirsutism in PCOS can rapidly and markedly respond to treatment with flutamide alone without important side-effects even if administered for a long period.

Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine.

UNLABELLED: The aim of the present study was to assess whether 131I therapy for differentiated thyroid carcinoma (DTC) can affect endocrine testicular function. METHODS: Serum follicle-stimulating hormone (FSH) and testosterone (T) concentrations were measured in 103 patients periodically submitted for radioiodine therapy for residual or metastatic disease. Mean follow-up was 93.7 +/- 54 mo (range 10-243 mo). RESULTS: Mean FSH values in 131I-treated patients tested after their last treatment were 15.3 +/- 9.9 mU/ml, significantly higher than those of 19 untreated patients (6.5 +/- 3.1 mU/ml). Considering the mean +3 s.d. FSH of untreated subjects as the upper limit of normal range, 36.8% of the patients had an abnormal increase in serum FSH. Longitudinal analysis performed in 21 patients showed that the behavior of FSH in response to 131I therapy was not universal. Six patients had no change or a slight increase in serum FSH after 131I administration; eleven patients had a transient increase above normal values 6-12 mo after 131I treatment, with return to normal levels in subsequent months. The administration of a second dose was followed by a similar increase in FSH levels. Finally, four patients, followed for a long period of time and treated with several 131I doses, showed a progressive increase in serum FSH, which eventually became permanent. Semen analysis, performed in a small subgroup of patients, showed a consistent reduction in the number of normokinetic sperm. No change was found in serum T levels between treated and untreated patients. CONCLUSIONS: Our results indicate that 131I therapy for thyroid carcinoma is associated with transient impairment of testicular germinal cell function. The damage may become permanent for high-radiation activities delivered year after year and might pose a significant risk of infertility.

Outcome of 309 patients with metastatic differentiated thyroid carcinoma treated with radioiodine.

From 1969 to 1990 there were 309 patients with differentiated thyroid carcinoma (241 papillary and 68 follicular) treated with radioactive iodine for functioning node metastases alone (n = 191) or distant metastases (n = 118) with or without node metastases. These patients represented 32.7% of 945 patients treated in our institution during the same period. Initial treatment included near-total thyroidectomy and 131I ablation of postsurgical thyroid residue, followed by L-thyroxine suppressive therapy. At the end of follow-up (mean 5.8 years), 146 patients (76.4%) in the group with nodal metastases were considered cured, as assessed by clinical and laboratory evaluation including whole body scan (WBS) and serum thyroglobulin (Tg) levels; 32 patients (16.7%) had persistent disease. Loss of 131I uptake in persistent metastatic lesions occurred in five patients (2.6%), and newly developed distant metastases occurred in eight patients (4.2%). Of the patients with distant metastases, 36.4% were cured by 131I. Distant metastases from papillary carcinomas had a higher cure rate than follicular carcinomas (p < 0.01). The metastases of four patients (5.2%) lost the property to take up radioiodine. Lung and bone metastases detectable by WBS but not by radiography were most likely to be cured by 131I. The overall survival at the end of follow-up was 95.8% in patients with only lymph node metastases and 76.0% in those with distant metastases. Tumor-related deaths were 3.6% and 23.7%, respectively. Our data indicate that 131I therapy is highly effective in the treatment of lymph node metastases from differentiated thyroid carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous aspiration and ethanol sclerotherapy for thyroid cysts.

Benign thyroid cysts often recur after aspiration; the effectiveness of tetracycline instillation in the case of recurrence has been questioned. We, therefore, tested the efficacy of percutaneous ethanol injection in 20 patients with "pure" cyst relapsing after aspiration. After evacuation, 95% ethanol was instilled under sonographic guidance and re-aspirated 5 min later. The procedure was performed twice for larger cysts. Follow-up studies were carried out after 1, 3, 6, and 12 months. In case of recurrence at 1 month, patients (n = 5) were submitted to a second session. A slight burning sensation was the only adverse effect. No recurrences were observed at 3 and 6 month follow-up; only one patient with recurrence after 1 month had relapsed at 12 months. A significant shrinkage (P < 0.0001 vs. pretreatment) was observed in all other cases at 12 months; cysts were not detectable in seven patients (35%). No significant variations in thyroid hormone levels were detected during treatment or follow-up. Serum thyroglobulin levels markedly increased 3 h after ethanol injection. One month after treatment, thyroglobulin returned to pretreatment levels, thus excluding progressive thyroid damage. Percutaneous ethanol injection may prove a safe and effective tool for the therapy of thyroid cysts.

[Radiometabolic therapy of the autonomous thyroid nodule]. / Terapia radiometabolica del nodulo tiroideo autonomo.

The aim of this paper is to synthetically focus on current views on the use of radioiodine for the treatment of hyperthyroidism in single autonomously functioning thyroid nodules (AFN). Radioiodine administration represents a simple and effective alternative to surgical ablation of AFN, especially in elderly patients with small nodules (< 3 cm diameter). Radioiodine is very selectively accumulated in the thyroid, where it can deliver its energy without virtually affecting any other organ. Since its first use in 1942, 131I is (as Na131I) still the radioisotope of choice, due to easy availability and to its peculiar physical characteristics. These include a short half-life (8 days) and a spectrum of radiation (mainly of the beta type) with an optimal energy delivery in the nodule and with low penetration in the surrounding tissue. The effectiveness of radioiodine administration in permanently correcting hyperthyroidism in AFN has been demonstrated in many studies and may reach 80% with a single dose administration. The optimal dose has not been completely defined, but may be empirically calculated taking into account the weight of the nodule (evaluated by scintiscan or ultrasound) and the radioiodine uptake after 24 hours. In our and in many other institutions, indications to radioiodine treatment are currently the following: age > 35-40 years, diameter of the nodule < 3 cm and/or serious general diseases contraindicating surgical treatment. The only absolute contraindication to radioiodine treatment is pregnancy, due to the possible mutagenic effects on the foetus and to the extreme sensitivity of the foetal thyroid to radioiodine after the 10th week of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: a clue to the diagnosis of metastatic differentiated thyroid cancer.

We studied the feasibility of employing the measurement of thyroglobulin (Tg) in the washout of the needle used to perform the fine needle aspiration cytology (FNA-Tg) for the differential diagnosis of nonthyroidal neck masses of unknown etiology. We studied 35 patients presenting for 1 or more neck lumps outside the thyroid gland. A previous history of treated differentiated thyroid cancer (DTC) was given by 23 patients and of nonthyroidal malignancy by 3 patients. FNA-Tg was measured in the Tg-free serum used to wash out the needle employed for the cytology. Finally, all patients were treated by surgery. FNA-Tg was always detectable in 14 patients with thyroid cancer metastases demonstrated by histology, with a mean (+/- SD) of 27,087 +/- 37,622 ng/FNA (P less than 0.002) compared to patients without thyroid cancer metastases (mean +/- SD, 12.1 +/- 4.8 ng/FNA in 7 cases; undetectable in 14 cases). Assuming 21.7 ng/FNA (the mean +/- 2 SD of the negative patients) as the cut-off value, all patients with metastases from DTC were detected by FNA-Tg. FNA-Tg had better negative predictive value than cytology, since this last technique gave 10 inconclusive results, comprising 2 false negative results in patients with metastases from DTC. Our results indicate that elevated concentrations of FNA-Tg in nonthyroidal neck nodes strongly suggest the diagnosis of metastases from DTC.