Cardiovascular changes in patients with primary aldosteronism after surgical or medical treatment.

BACKGROUND: Data on the cardiovascular middle-term follow-up of patients with primary aldosteronism (PA) are scanty. AIM: To detect the cardiovascular effects of surgery in patients with aldosterone (ALD)-producing adenoma (APA) and of pharmacotherapy in those with bilateral adrenal hyperplasia (BAH), a prospective study involving 60 consecutive patients with PA was performed. MATERIAL/ METHODS: Clinical, biochemical, and cardiovascular assessment was obtained before and after (31.5±4.4 months) surgery or proper medical treatment (32.1±5.0 months) in 19 and 41 patients, respectively. RESULTS: As expected, plasma ALD normalized in all operated patients, while in the other group it did not change. Systolic and diastolic blood pressure decreased (p<0.001) after both treatments. However, absolute and percentage reduction was significantly more pronounced (p<0.01) in operated than in non-operated patients. Left ventricular (LV) mass showed significant reduction after surgery (LV mass g/m(2), p<0.0007; LV mass g/m(2.7), p<0.01), but no change after medical treatment, so that the differences between absolute and percentage values at follow- up were statistically significant (p<0.01) between groups. Basal LV mass/m(2.7) was positively associated with age (p<0.009), body mass index (p<0.0008), drug number (p<0.03), and ALD/plasma renin activity ratio (p<0.01). Allocating the patients according to plasma ALD and cardiac parameters, patients who presented ALD reduction during the study also had a decrement in cardiac mass (p<0.04). CONCLUSIONS: Our data indicate that in patients with PA the removal of ALD excess by surgery in APA is effective in reducing blood pressure and in improving cardiac parameters, while anti-hypertensive therapy in BAH shows less positive impact on cardiovascular system.

Stem cells: their role in breast cancer development and resistance to treatment.

About 20% of the total cells from primary breast tumors could generate palpable tumors in non-obese diabetic severe combined immunodeficient (NOD/SCID) immunocompromised mice. All the tumorigenic cells originate from a normal mammary stem cell. Human mammary stem cells are sensitive to oncogenic mutations and in mouse models they share similarities with breast cancer stem cells (BrCSCs). Tumorigenicity, invasion, progression and metastasization are further BrCSCs properties likely depending on their CD44+/CD24- phenotype. Local invasion and tumor metastasization seem to be facilitated by the epithelial to mesenchymal transition (EMT) program. This program may be reactivated from stable genetic alterations or through exposure of cancer cells to factors present in the surrounding micro-environment, or by an up-regulation of EMT-inducing transcription factors. One main explanation for resistance to treatment by cancer cells is that a rare subpopulation of cells in residual tumors with tumorigenic potential is intrinsically resistant to therapy. Consistent with this hypothesis, in human breast tumors, the subpopulation of tumor-initiating cancer cells with CD44(high)/CD24(low) cell surface-marker profile was found more resistant to cancer therapies (chemo, hormone and radiotherapy) than is the major population of more differentiated breast cancer cells. The reasons for CSC resistance to chemotherapy, hormone therapy and radiotherapy also have been examined and they opened new scenarios for cancer therapy.

Real-time elastosonography: useful tool for refining the presurgical diagnosis in thyroid nodules with indeterminate or nondiagnostic cytology.

BACKGROUND: Indeterminate and nondiagnostic patterns represent the main limitation of fine-needle aspiration (FNA) cytology of thyroid nodules, clinical and echographic features being poorly predictive of malignancy. The newly developed real-time ultrasound elastography (USE) has been previously applied to differentiate malignant from benign lesions. The aim of this study was to get further insights into the role of USE in the presurgical diagnosis of nodules with indeterminate or nondiagnostic cytology. PATIENTS: The study included 176 patients who had one (n=138) or multiple (n=38) nodules with indeterminate or nondiagnostic cytology on FNA, for whom histology was available after thyroidectomy. A total of 195 nodules (142 indeterminate, 53 nondiagnostic) were submitted to USE, and elasticity was scored as 1 (high), 2 (intermediate), or 3 (low). RESULTS: In indeterminate lesions, the score 1, describing high elasticity, was strongly predictive of benignity, being found in 102 of 111 benign nodules and in only one of 31 carcinomas (P<0.0001). By combining the scores 2 and 3, USE had a sensitivity of 96.8% and a specificity of 91.8%. In nodules with nondiagnostic cytology, score 1 was found in 39 of 45 benign nodules and in only one of eight carcinomas (P<0.0001). By combining the scores 2 and 3, USE had a sensitivity of 87.5% and a specificity of 86.7%. CONCLUSIONS: 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.

Beta-catenin activation is not involved in sporadic parathyroid carcinomas and adenomas.

Aberrant accumulation of beta-catenin has been found in various types of human tumors. The aim of this study was to evaluate whether Wnt/beta-catenin signaling is activated in parathyroid carcinomas and adenomas. We studied 154 parathyroid tumors (18 carcinomas (13 with distant metastases), six atypical adenomas, and 130 adenomas). Three normal parathyroid tissues were used as control. Direct sequencing of exon 3 of the CTNNB1 gene showed absence of stabilizing mutations in all the tumors. Immunostaining of beta-catenin was performed in all carcinomas and in 66 adenomas (including three atypical). Normal parathyroid showed a homogeneous distinct outer cell membrane staining in the majority of cells and no nuclear staining. A weak cytoplasmic staining was observed in one case. All tumors showed negative nuclear staining. With the exception of one carcinoma, which had a negative membrane staining, all other samples showed a membrane staining which was similar to that of the normal parathyroid. beta-Catenin expression was heterogeneous with a range of positive cells between 5 and 80%, independently of tumor type. Our results suggest that the Wnt/beta-catenin signaling pathway is not involved in the development of parathyroid carcinomas and adenomas.

Update on the diagnosis and treatment of differentiated thyroid cancer.

During the 1990s, with the general tendency to develop minimally invasive operations, an endoscopic approach has been applied to neck surgery for both parathyroidectomy and thyroidectomy. The most widely spread minimally invasive technique for thyroidectomy is minimally invasive video assisted thyroidectomy (MIVAT), described and developed for the first time at our institution in 1998. Ideal candidates for MIVAT are patients with a thyroid volume lower than 25ml with nodules smaller than 35 mm. Consequently, MIVAT will present restricted indications, being suitable only for the treatment of about 10-15% of the whole standard surgical case load. Thus, together with small follicular lesions, "low risk" papillary carcinoma will result the main indication for MIVAT, being this small cancer usually harboured in normal glands of young females. On the other hand, in case of locally invasive carcinomas and/or lymph node metastasis the procedure must be immediately converted to the conventional technique. MIVAT also is not indicated for the treatment of medullary and anaplastic carcinomas. Recent prospective randomized studies clearly demonstrate that MIVAT allows achieving same clearance at the thyroid bed level and same outcome as conventional technique, when dealing with "low risk" papillary carcinoma. At the same time, patients can benefit from the main advantages of this minimally invasive technique: lower postoperative pain, faster postoperative recovery and excellent cosmetic outcome.

Papillary thyroid cancer, although strongly associated with lymphocytic infiltration on histology, is only weakly predicted by serum thyroid auto-antibodies in patients with nodular thyroid diseases.

OBJECTIVE: We evaluated the association between thyroid autoimmunity and thyroid cancer in a retrospective series of unselected thyroid nodules submitted to fine-needle aspiration (FNA) cytology. DESIGN: Anti-thyroid antibodies (TAb) were measured in patients with multinodular goiter (MNG) and single/isolated thyroid nodule (S/I) submitted to FNA. Thyroid lymphocytic infiltration (LI) on histology was studied in a subgroup of patients submitted to thyroidectomy; 13,021 patients were included: on cytology 622 had papillary thyroid cancer (c- PTC) and 12,399 benign thyroid nodular diseases (c-BTN). LI was evaluated in histological samples of 688 patients: 304 with PTC (h-PTC) and 384 with BTN (h-BTN). RESULTS: TAb prevalence was not different in c-BTN and c-PTC (38.7% vs 35.6%). TAb were more frequent in c-BTN than c-PTC in females with MNG (40.1% vs 32.5%, p=0.02), and in c-PTC than in c-BTN in males with S/I (31.2% vs 20.4%, p=0.02) and, although not significantly, in females younger than 30 yr (35.1% vs 30.7%). The frequency and severity of LI was significantly higher in h-PTC than h-BTN, both in MNG (82.5% vs 45.0%, p<0.001) and S/I (85.6% vs 71.0%, p<0.001), but a higher number of patients with h-PTC had negative circulating TAb, despite the presence of moderate/severe LI. CONCLUSIONS: TAb are weakly associated to PTC in males and young females, while they are more frequent in older females with BTN. The frequency and severity of LI is significantly higher in PTC than in BTN, but in cancer patients TAb are frequently negative, despite the evidence of histological thyroiditis. These data suggest that different kinds of immune response may be involved in PTC and BTN.

Lower levels of TSH are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role.

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 (n=497) or benign thyroid nodular disease (BTND, n=9681). 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 age-dependent development of thyroid autonomy (TSH <0.4 microU/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.

Video-assisted surgery: what is its role in the treatment of thyroid carcinoma?

Thyroid carcinoma can be divided in two main groups, differentiated, with a good prognosis and an average 10 years survival ranging from 70% to 95%, and undifferentiated which is lethal in few months. Differentiated thyroid carcinoma can be distinguished in those variants coming from follicular cells (papillary and follicular) and those from C cell (medullary carcinoma). Surgical approach represents the first step in the treatment of thyroid carcinoma. Minimally-invasive endoscopic technique can be applied only to a minority of case, the so called ''low risk'' carcinoma according to AGES and AMES criteria. During the last ten years many different endoscopic approaches have been proposed for the treatment of thyroid carcinoma and the minimally invasive videoassisted (MIVAT) by Prof Miccoli is undoubtly the one which resulted to be the most successful and spread all over the world. Through a 1.5 cm central skin incision 2 cm above the sternal notch MIVAT allows to perform a total thyroidectomy for low risk papillary carcinoma with a completeness similar to that of conventional thyroidectomy. Using the same central access it is also possible to perfom a prophylactic central neck dissection for RET gene positive carriers. A lateral neck minimally invasive videoassisted lymphadenectomy is under development for those patients with low risk papillary carcinoma and isolated lateral lymph node metastasis.

Perspectives and lessons learned after a decade of minimally invasive video-assisted thyroidectomy.

Minimally invasive video-assisted thyroidectomy (MIVAT) was introduced in our department in 1998. The procedure is based on a unique incision in the central neck, 2 cm above the sternal notch, using small conventional retractors and 2-mm reusable instruments. Hemostasis is achieved by using a Harmonic scalpel. 1,320 (1,136 female and 184 male, ratio 4:1) patients have undergone MIVAT since June 1998. Lobectomy was carried out in 421 patients, while 899 patients underwent total thyroidectomy. In 21 cases (RET oncogene mutation carriers), MIVAT was associated with central compartment lymph node clearance. Mean operative time of lobectomy was 32.3 min (range 20-120 min); for total thyroidectomy it was 44.1 min (range 30-130). Mean time for video-assisted central compartment lymphadenectomy was 57 min. Conversion to standard cervicotomy was required in 30 cases (2.2%); operative complications included transient unilateral recurrent nerve palsy in 35 cases (2.65%) and definitive unilateral recurrent nerve palsy in 15 cases (1.13%). Thirty-eight patients exhibited hypoparathyroidism, which corresponds to 4.2% of total thyroidectomies performed, but only 2 showed permanent hypoparathyroidism. MIVAT can be considered a safe operation offering significant cosmetic advantages and has possible new promising indications such as prophylactic thyroidectomy in RET gene mutation carriers.

Endoscopic bilateral neck exploration versus quick intraoperative parathormone assay (qPTHa) during endoscopic parathyroidectomy: A prospective randomized trial.

BACKGROUND: Quick intraoperative parathormone assay (qPTHa) during paratyroidectomy has become a standard procedure for patients with primary hyperparathyroidism (PHPT). This paper aims to compare endoscopic bilateral neck exploration (BE) versus focused parathyroidectomy plus qPTHa during minimally invasive video-assisted parathyroidectomy (QM). The endpoints of the study are the mean operative time and outcome of the surgical procedure (PTH and calcemia normalization at one and six months postoperatively). METHODS: Forty patients with PHPT, positive to preoperative localization studies (ultrasonography evaluation and (99)Tc-MIBI scan) for a single parathyroid adenoma, were randomly allotted into two groups. In the first group (QM), 20 patients (17 women, three men, mean age 57.6 years) underwent focused endoscopic parathyroidectomy (MIVAP tecnicque) plus qPTHa . In the second group (BE) 20 patients (17 women, three men, mean age 59.6 years) underwent endoscopic parathyroidectomy plus bilateral exploration in order to check the integrity of the remaining glands. RESULTS: There were no significant differences between groups at baseline. No conversion to cervicotomy was required. No postoperative complications were reported. The mean operative time was 32.0 vs 33.1 min [BE and QM group respectively, p = not significant (ns)]. A second macroscopically enlarged gland was removed in four patients in the BE group. Only one out of four glands was reported to be hyperplastic in the final histology. All patients were discharged on the first postoperative day. Calcemia levels were normalized in all patient of both groups, despite persistently high level of serum PTH in one patient in the QM group. CONCLUSIONS: BE can be performed endoscopically, avoiding both the time necessary for qPTHa and its cost, with the same effectiveness, but might in few cases lead to the unjustified removal of parathyroid glands slightly enlarged but not necessarily pathologic.

The impact of thyroidectomy on parathyroid glands: a biochemical and clinical profile.

INTRODUCTION: An evaluation of PTH levels during thyroid surgery may reflect the functional status of the parathyroids and be useful in identifying patients at risk for hypocalcemia. This study aims to monitor the parathyroid function during total thyroidectomy through intra-operative serial samples for calcium and PTH. MATERIALS AND METHODS: Forty-seven patients undergoing total thyroidectomy for different diseases were selected for the study. Patients underwent serum PTH and calcium sampling at the induction of anesthesia (T0) and after the first (T1) and the second (T2) lobectomy. Serum calcium was also drafted 24 h after the operation. RESULTS: Mean PTH at T0, T1, and T2 was, respectively: 32.1 pg/ml, 19.6 pg/ml, and 11.5 pg/ml. PTH was significantly higher at T0 when compared to T1 (p<0.0001). It was also significantly higher at T1 than at T2 (p<0.0001). At T1 PTH levels were below the normal range in 20/47 cases (42.5%) and at T2 in 31/47 cases (66%). Twenty-four h after surgery, 8 patients (17%) demonstrated a biochemical hypocalcemia. A PTH value at T0 in the upper (>70 pg/ml) or in the lower (<20 pg/ml) limits of the normal range was statistically related to post-operative hypocalcemia (p=0.017). DISCUSSION: The study seems to confirm that serum PTH during thyroidectomy does not represent a sensitive tool in precociously identifying hypocalcemic patients. Nevertheless, before surgery, a PTH concentration at the higher or lower normal limit may help to identify patients "at risk" of developing hypocalcemia.

[Surgical timing in bleeding liver adenoma: case report]. / Timing chirurgico nell'adenoma epatico sanguinante: case report.

The diagnosis of liver adenoma, which etiopathogenesis most often involves a prolonged assumption of estrogen (90% of adenomas occurs in women after more than 5 years of estrogen therapy), always imposes a surgical resection. The reason depend from neoplasia characteristics like the malignant evolution (4%) and the high risk of abdominal/intratumoral bleeding (30-50%), that increases during pregnancy and postpartum period. Regression of lesion after discontinuation of hormone therapy is rare and does not remove the degeneration and/or haemorrhagic risk. Liver resection should be performed with appropriate selective endovascular embolization, considering that an inept emergency surgery may impose a greater risk ot the liver, exposing the patient to major risk of morbidity and mortality. The correct timing from embolization to elective surgery is not yet standardized in the literature. The surgeon's personal experience and mainly a careful patient follow-up suggest the timing of surgery after embolization. The authors relate their own experience about the therapeutic strategy and surgical timing in a case of bleeding liver adenoma.

[New technologies in thyroid surgery. Endoscopic thyroid surgery]. / Le nuove tecnologie nella chirurgia tiroidea. Chirurgia endoscopica della tiroide.

The onset of cervicoscopy dates back to the first endoscopic parathyroidectomy in 1996. This operation, along with its several variants, has become a valid option widespread in many important centres. Later on, endoscopic or video assisted thyroidectomy was introduced in spite of the limits imposed by the mass of the gland to remove. It is indicated for a minority of patients for this reason but both parathyroidectomy and thyroidectomy showed some important advantages with respect to conventional surgery, advantages demonstrated also in prospective studies. They are mainly represented by a better cosmetic outcome and a less distressful postoperative course. These approaches proved to be safe and feasible in any surgical background: their complication rate is the same as traditional open surgery in the neck. Very promising seems to be the videoscopic access to neck lymph nodes (central and lateral compartments) whereas other fields of application such as carotid artery surgery and spine surgery still remain object of experimental studies. As far as the lateral neck dissection is concerned the technique is going to be standardized in our centre as a variant of the well known video assisted approach adding a 5 mm trocar placed in the supraclavicular space. By consequence, cervicoscopy has to be considered an important surgical tool which can be further improved but which also has an excellent potentiality.

Clinical features of thyroid autoimmunity are associated with thyroiditis on histology and are not predictive of malignancy in 570 patients with indeterminate nodules on cytology who had a thyroidectomy.

BACKGROUND: The relationship between thyroid autoimmunity and cancer is still uncertain. PATIENTS: We approached this issue in 570 consecutive patients submitted to thyroidectomy for an indeterminate nodule on cytology. Thyroid autoimmunity was defined as positivity of circulating thyroid autoantibodies (TAb), autoimmune hypo- or hyperthyroidism, thyroid hypoechogenicity on ultrasound, and lymphocytic infiltration on histology. RESULTS: TAb were found in 122/570 (21.4%), hypoechogenicity in 115/570 (20.1%), and lymphocytic infiltration in 117/570 (20.5%) of patients. The three features of thyroid autoimmunity were highly concordant: hypoechogenicity was observed in 71/448 (15.8%) patients with negative TAb and in 44/122 (36%) with positive TAb (P < 0.0001); lymphocytic infiltration was found in 53/448 (11.8%) patients with negative TAb and in 64/122 (52.4%) with positive TAb (P < 0.0001); hypoechogenicity on ultrasound was observed in 73/453 (16.1%) patients without, and in 42/117 (35.9%) with lymphocytic infiltration (P < 0.0001). None of these parameters was associated with malignancy. TAb were found in 32/135 (23.7%) patients with carcinoma and in 90/435 (20.6%) with a benign lesion (P = NS); hypoechogenicity was observed in 26/135 (19.2%) patients with carcinoma and in 89/435 (20.4%) patients with benign lesions (P = NS); lymphocytic infiltration was present in 28/135 (20.7%) patients with carcinoma and in 89/435 (20.4%) with benign lesions (P = NS). The frequency of cancer in 11 patients with clinically overt thyroid autoimmune disease did not differ from that observed in the whole study group. CONCLUSION: In this group of patients with indeterminate thyroid nodules at cytology, clinical and pathological criteria of thyroid autoimmunity were strongly concordant and not associated with malignancy.

One-day thyroid surgery: retrospective analysis of safety and patient satisfaction on a consecutive series of 1,571 cases over a three-year period.

Short-stay thyroid surgery (<24 h hospital stay) is becoming increasingly popular but some potentially lethal complications are considered strong arguments against shortening hospitalization after thyroidectomy. The authors reviewed the data of 1,571 patients undergoing one-day thyroid surgery over a 3-year period to determine safety and patient satisfaction. There were 1,244 females and 327 males. Mean age was 43 years. Patient satisfaction was evaluated by a questionnaire given on discharge, while post-discharge surgical recovery was analyzed by the PSR scale. Total thyroidectomy was performed in 1,119 patients (71%), hemithyroidectomy in 450 (29%), isthmusectomy in 2. Morbidity occurred in 152 patients (9.6%). Surgical complications were transient hypocalcemia in 112 cases and permanent hypoparathyroidism in 3; monolateral transient nerve palsy occurred in 10 cases, bilateral in 3; definitive monolateral recurrent palsy in 4 cases. Bleeding requiring re-intervention occurred in 10 cases, wound complications in 5 cases, and intraoperative tracheal lesion in 1 patient. Among complicated patients, 129 (84.8%) were treated after discharge as outpatients. Conversion to inpatient treatment occurred in 28 patients (1.7%) (25 for surgical reasons). Four patients (0.2%) required hospital readmission. Patients were very satisfied in 84.2%, satisfied in 9.5%, poorly satisfied in 4.3%, completely unsatisfied in 2%. Postoperative recovery mean score by PSR scale resulted in 85.14% (0-100%). Our results confirm that the one-day surgery model is safe, effective, and highly agreeable in patients undergoing surgery for thyroid disease.

Role of frozen section associated with intraoperative cytology in comparison to FNA and FS alone in the management of thyroid nodules.

AIMS: The utilization of fine needle aspiration (FNA) biopsy is an accurate and cost-effective method in the diagnosis of thyroid diseases. However, the non-diagnostic cases and cases of suspicious carcinoma remain a dilemma, and in these cases thyroidectomy is usually recommended, even if only 15-20% of these patients really need a thyroidectomy. To avoid unnecessary surgical treatment, frozen section (FS) is usually performed. This method is well recognized, but is not useful for the diagnosis of follicular lesions. Therefore, many authors have tried to increase the specificity and sensibility of intraoperative examination, supporting it with an intraoperative cytological technique (IC). To clarify the role of intraoperative exam (FS and IC), also comparing to FNA, we have reviewed our own experiences. METHODS: In a period covering 6 years (2000-2005), FS was performed in 1,472 cases out of 11,420 total thyroidectomy operations. FS diagnosis and definitive diagnosis, were reviewed and confirmed, moreover, FNA diagnosis and definitive diagnosis were also considered and all intraoperatory cytological slides were reviewed. Diagnostic accuracy was assessed for FNA and FS with or without intraoperative cytology. We compared 1,472 FS diagnoses with their definitive histological diagnosis; 728 FNA out of 1,472 patients with definitive histological diagnosis, and 564 FS associated with IC out of 1,472 patients with definitive diagnosis. RESULTS: The diagnostic accuracy of these three methods were, respectively, 88.8%, 88.8% and 95.7%. CONCLUSION: We can assert that FS associated with IC remains the most accurate technique in the surgical management of thyroid nodules.

Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: results from a series of 505 consecutive patients.

OBJECTIVE: The cytological patterns of follicular and Hupsilonrthle cell nodules are included among the indeterminate results of fine-needle aspiration cytology, because distinction between benign and malignant lesion can only be made on histological criteria. The diagnostic value of atypia at cytology, clinical parameters and echographic patterns were examined to establish the risk of malignancy in 505 patients with follicular and Hupsilonrthle cell thyroid nodules at cytology. DESIGN AND PATIENTS: The study included 505 consecutive patients who had undergone thyroidectomy from the period 2002-2005. RESULTS: Histological diagnosis of malignancy was carried out in 125 of 505 (25%) patients, the follicular variant of papillary carcinoma being the most frequent histotype. Only atypia at cytology (P < 0.0001) and spot microcalcifications at ultrasound (P = 0.009) were predictive of malignancy. Male gender, normal thyroid volume, single nodularity, nodule hypoechogenicity, size and blurred margins were associated with malignancy, although not significantly. An arbitrary clinical score allowed the identification of patients with high (41%, 110 patients) and low (16%, 242 patients) risk of malignancy. Combining the clinical score with the presence of atypia at cytology we could identify 30 patients (6%) in whom the risk of malignancy was as high as 63%. CONCLUSIONS: Twenty-five per cent of patients with a cytological result of follicular and Hupsilonrthle cell thyroid lesion had a final diagnosis of malignancy. Only atypia at cytology and spot microcalcifications at thyroid ultrasound were significantly associated with malignancy. Other clinical parameters and thyroid ultrasound patterns can be used to set up a clinical score useful for predicting the individual risk of malignancy before surgery.