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P Miccoli

Publications and source records attributed to P Miccoli.

At least 73 records · Page 4Linked to original sources
PubMed2000

Contrast-enhanced color Doppler ultrasonography in suspected parathyroid lesions.

PURPOSE: To assess the usefulness of US contrast media in the evaluation of patients with primary hyperparathyroidism, with a nodule showing US features of a primary parathyroid lesion but lacking the color Doppler US appearance of a parathyroid mass. MATERIAL AND METHODS: Thirteen patients (7 female, 6 male; age range 51-79 years) were examined with US before and after administration of a stabilized galactose-based microbubble contrast agent. Ten patients underwent surgery and the final histological examination demonstrated parathyroid adenoma in 9 cases and a mesenchymal benign nodule in 1 case. Three nodules were proved to be of thyroid origin at fine-needle aspiration biopsy. RESULTS AND CONCLUSION: The use of a US contrast agent resulted in a diagnostic gain compared to unenhanced studies in 12/13 cases. Color Doppler findings characteristic of parathyroid lesions were observed in 7/13 cases, of thyroid nodules in 4/13 cases, and nonspecific patterns in 2/13 cases. Contrast-enhanced color Doppler US can be proposed in selected patients in whom unenhanced color Doppler provides uncertain findings. Its ideal application should be the evaluation of cervical lesions without detectable intranodular flow at unenhanced Doppler studies. In these cases, the contrast agent helps in visualizing typical color Doppler signals of the parathyroid lesions ("vascular pole" and "mixed pattern").

Adenoma↗
PubMed2000

Surgical and pathological changes after percutaneous ethanol injection therapy of thyroid nodules.

Few data exist on the operative and pathological findings in patients having undergone previous percutaneous ethanol injection (PEI) therapy of thyroid nodules. We report here our experience with 13 patients operated on by the same surgical team. Two pathologists, both blinded to the previous PEI treatment, carried out histological evaluation. Reasons for surgery included PEI failure, suspicion of malignancy, and tracheal compression. The operations did not pose any special problem from the technical point of view, and the postoperative courses were uneventful. One patient who had a second operation developed hypoparathyroidism, and laryngeal nerve palsy was never observed. The histological diagnosis was hyperplastic or adenomatous nodule in 12 cases and papillary thyroid cancer in 1. No difficulty was found in evaluating the nodule capsule and surrounding vessels. In two lesions, nuclear enlargement and clearing were identified in thyroid follicles immediately adjacent to necrotic or scarred areas. These changes were considered reactive. In conclusion, patients previously treated by PEI were operated on without special technical problems. Histological diagnosis was not hindered, and there was no difficulty in ruling out malignant lesions. PEI, however, should be performed only by skilled operators, and incidental ethanol seepage throughout the nodule capsule must be carefully avoided.

Administration, Cutaneous↗
PubMed2000

N-ras mutation in poorly differentiated thyroid carcinomas: correlation with bone metastases and inverse correlation to thyroglobulin expression.

Codon 61 of the N-ras oncogene was screened for mutations in 99 surgically resected thyroid carcinomas by a polymerase chain resection (PCR)-based method (PCR-primer introduced restriction with enrichment of mutant alleles [PCR-PIREMA]). A point mutation of the N-ras oncogene at the codon 61 was detected in 16 of 99 (16.2%) thyroid carcinomas examined by this method. No RAS alteration was detected in the group of 11 medullary thyroid carcinomas, while 3 of 31 (10.0%) papillary carcinomas, 2 of 5 (40%) follicular carcinomas, 8 of 44 (18.2%) poorly differentiated carcinomas, and 3 of 5 (60%) undifferentiated carcinomas showed an activation of N-RAS proto-oncogene. Interestingly, two primary follicular tumors and their corresponding bone metastases, showed N-ras mutations. In the same cases we evaluated the expression of thyroglobulin by immunohistochemical analysis. Although the majority of well-differentiated carcinomas expressed a high level of thyroglobulin, the expression of the same antigen was absent or only occasional weakly positive in 33 of 44 poorly differentiated carcinomas. Interestingly, N-ras mutation was restricted to the group of tumours with low or absent thyroglobulin expression, suggesting that this genetic change is prevalent in less differentiated tumors.

Bone Neoplasms↗
PubMed2000

Cyclin D1 overexpression in thyroid carcinomas: relation with clinico-pathological parameters, retinoblastoma gene product, and Ki67 labeling index.

Cyclin D1 is a G1 cyclin participating in the control of cell cycle progression through interaction with the retinoblastoma gene product (pRB). The overexpression of positive regulators (such as cyclin D1) has been reported in a variety of neoplasms, but their role in thyroid tumorigenesis is yet to be established. In our series of 54 thyroid carcinomas, cyclin D1 overexpression (detected by both immunohistochemistry and by Northern blotting) was correlated with prognostic variables, proliferative activity and pRB. Cyclin D1 overexpression was observed in 35% of thyroid carcinomas with a significantly higher expression of this cyclin in neoplastic tissues than in matched normal parenchyma. In well-differentiated carcinomas, the cyclin D1 mRNA overexpression was inversely correlated with nodal status (p = 0.03), while the protein product was higher in tumors from patients less than 40 than patients over 40 years of age. Inversely, there was no significant correlation with gender and tumor status, pRB and with proliferative activity.

Adenocarcinoma, Follicular↗
PubMed2000

RET rearrangements in papillary thyroid carcinomas and adenomas detected by interphase FISH.

Activation of the RET protooncogene through somatic rearrangements represents the most common genetic alteration in papillary thyroid carcinoma (PTC). Three main rearranged forms of RET have been described: RET/PTC1 and RET/PTC3, which arise from a paracentric inversion of the long arm of chromosome 10, and RET/PTC2, which originates from a 10;17 translocation. We have developed a dual-color FISH approach to detect RET/PTC rearrangements in interphase nuclei of thyroid lesions. By using a pool of three cosmids encompassing the RET chromosome region and a chromosome 10 centromeric probe, we could discriminate between the presence of an inversion (RET/PTC1 and RET/PTC3) or a translocation (RET/PTC2). We have investigated a series of thyroid tissue samples from Italian and French patients corresponding to a total of 69 PTCs and 22 benign lesions. Among PTCs, 13 (18.8%) showed a RET rearrangement, and 11 (15.9%) of these carried an inversion (RET/PTC1 or RET/PTC3) in more than 10% of the nuclei examined. Activated forms of RET were also observed in three adenomas. RT-PCR analysis on the same samples confirmed the presence and the type of rearrangement predicted using FISH analysis. An interesting difference in the frequency and type of RET rearrangements was detected between the Italian and the French patients. Furthermore, we identified a putative novel type of rearrangement in at least one PTC sample. Several PTCs carried a significant number of cells characterized by a trisomy or a tetrasomy of chromosome 10. Overall, the FISH approach in interphase nuclei represents a powerful tool for detecting, at the single cell level, RET/PTC rearrangements and other anomalies involving the RET chromosome region.

Adenoma↗
PubMed2000

Parathyroid expression of calcium-sensing receptor protein and in vivo parathyroid hormone-Ca(2+) set-point in patients with primary hyperparathyroidism.

A reduced expression of calcium-sensing receptor (CaR) messenger ribonucleic acid and protein accompanied by abnormalities in parathyroid cell proliferation and PTH secretion are present in primary hyperparathyroidism. We studied the expression of CaR protein by immunohistochemistry in 36 sporadic parathyroid adenomas and investigated the relationship between CaR expression and several preoperative clinical parameters, including the set-point of Ca(2+)-regulated PTH secretion (measured in vivo). The adenomas were classified in 4 categories according to the intensity of immunohistochemical staining: 5 (14%) showed a CaR staining intensity similar to that of normal parathyroid ( ), 10 (27%) showed moderate staining (++), 16 (45%) showed weak staining (+), and 5 (14%) were negative (-). The intensity of CaR staining was not related to preoperative serum Ca(2+), PTH levels or adenoma volume. Twenty-nine patients underwent preoperatively the calcium infusion test to evaluate the PTH-Ca(2+) set-point. Individual values of PTH-Ca(2+) set-point ranged from 1.38-1.93 mmol/L and were significantly correlated with basal Ca(2+) levels (r = 0.96; P: = 0. 0001) and adenoma volume (r = 0.5; P: = 0.01). The mean PTH-Ca(2+) set-point values were significantly different in the 4 groups of patients classified according to immunohistochemical staining intensity of their adenoma (P: = 0.025; F = 3.78); the mean PTH-Ca(2+) set-point was significantly higher in the groups classified as negative than in those classified as weak or moderate. No correlation was observed between the PTH-Ca(2+) set-point and basal PTH levels or between the percent maximal PTH inhibition and adenoma volume and basal PTH or Ca(2+) levels. In summary, our data suggest that there is a relationship between apparent CaR protein expression and PTH-Ca(2+) set-point abnormality, suggesting that a reduced receptor content might have an important role in the pathogenesis of primary hyperparathyroidism.

Adenoma↗
PubMed2000

Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter.

Toxic multinodular goiter, a heterogeneous disease producing hyperthyroidism, is frequently found in iodine-deficient areas. The pathogenesis of this common clinical entity is still unclear. The aim of the present study was to search for activating TSH receptor (TSHr) or Gs alpha mutations in areas of toxic or functionally autonomous multinodular goiters that appeared hyperfunctioning at thyroid scintiscan but did not clearly correspond to definite nodules at physical or ultrasonographic examination. Surgical tissue specimens from nine patients were carefully dissected, matching thyroid scintiscan and thyroid ultrasonography, to isolate hyperfunctioning and nonfunctioning areas even if they did not correspond to well-defined nodules. TSHr and Gs alpha mutations were searched for by direct sequencing after PCR amplification of genomic DNA. Only 2 adenomas were identified at microscopic examination, whereas the remaining 18 hyperfunctioning areas corresponded to hyperplastic nodules containing multiple aggregates of micromacrofollicules not surrounded by a capsule. Activating TSHr mutations were detected in 14 of these 20 hyperfunctioning areas, whereas no mutation was identified in nonfunctioning nodules or areas contained in the same gland. No Gs alpha mutation was found. In conclusion, activating TSHr mutations are present in the majority of nonadenomatous hyperfunctioning nodules scattered throughout the gland in patients with toxic or functionally autonomous multinodular goiter.

Adenoma↗
PubMed1999

Genetic analysis of the TSH receptor gene in differentiated human thyroid carcinomas.

Somatic mutations of the TSH receptor (TSHR) gene have been identified as the major cause of toxic thyroid adenoma. Recently, point mutations of the same gene have also been described in some differentiated thyroid carcinomas. The aim of the present study was to investigate the presence TSHR gene mutations in a series of thyroid specimens obtained from 22 consecutive patients with differentiated thyroid carcinomas (8 follicular and 14 papillary). Genomic DNA was extracted from fresh-frozen or paraffin-embedded tumor and normal surrounding parenchyma. Two fragments corresponding to the entire exon 10 and one fragment corresponding to exon 9 were amplified by PCR using biotinylated primers. PCR products were purified on streptavidin-coated magnetic beads and subjected to direct sequencing with Sequenase and 35(3)-labeled d-ATP-alphaS. Adenyl-cyclase activity in membrane preparations of 10 papillary carcinomas was also determined. No TSHR mutations were detected in these tumors. A polymorphism that encoded a single amino acid change Asp727Glu was identified in two follicular thyroid carcinomas. Adenyl-cyclase activity was normal in the ten papillary thyroid carcinomas we analyzed. In conclusion, our results suggest that clonal somatic mutations of the TSHR gene do not play a role in the pathogenesis of differentiated thyroid carcinoma.

Adenocarcinoma, Follicular↗
PubMed1999

Minimally invasive surgery for thyroid small nodules: preliminary report.

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.

Adult↗
PubMed1999

[Video-assisted parathyroidectomy: a series of 85 cases].

AIM OF THE STUDY: To verify the feasibility of video-assisted parathyroidectomy, set up the indications and report the results in a series of 85 patients. MATERIAL AND METHODS: From 1997 to 1999, 85 patients affected by primary hyperparathyroidism due to single gland disease, with an adenoma smaller than 35 mm as demonstrated by preoperative imaging, were referred for video-assisted parathyroidectomy. There were 62 females and 23 males. Mean age was 53 years, (range 23-82). Video-assisted parathyroidectomy was associated with intra-operative PTH quick-assay. Calcium testing was controlled before leaving the hospital, 1 month and 3 months later, and postoperative laryngoscopy was performed in all patients. RESULTS: There were five conversions to open cervicotomy: three due to a contra-lateral second adenoma, two because of an intrathyroidal adenoma. The mean operative time for video-assisted procedure was 59 minutes (range: 25-180). Circulating PTH levels 10 minutes after the removal of the affected gland(s) always dropped significantly, and pathological report confirmed the parathyroid nature of the specimens (mean diameter 13 mm, range 7-35). Morbidity consisted of five cases of transient hypocalcemia and one permanent laryngeal nerve paralysis. We registered no persistent or recurrent disease (mean follow-up 12.8 months, range 1-28). CONCLUSIONS: Video-assisted parathyroidectomy is feasible, and its results are similar to those of traditional procedure, while it seems superior as regards postoperative course and aesthetic results. It also allows different strategical decisions even during operation (i.e. bilateral exploration or thyroid lobectomy) by the same approach.

Adenoma↗
PubMed1999

Renin-angiotensin-aldosterone system in primary hyperparathyroidism before and after surgery.

Twenty consecutive unselected patients with proven primary hyperparathyroidism (PH), 26 essential hypertensive (EH) patients, and 13 normotensives were studied. Blood pressure (BP) and, under constant salt intake, plasma renin activity (PRA), parathyroid hormone (PTH), urinary and plasma sodium, potassium, aldosterone (ALD), creatinine, total calcium, and phosphate were measured. Patients with PH were also studied 1 and 6 months after successful surgery. In patients with PH, systolic and diastolic BP was significantly lower (P < .001) than in EH patients and higher (P < .005) than in controls. Eight patients with PH (40%) had BP levels greater than 140/90 mm Hg. PTH and plasma and urinary calcium in patients with PH were significantly (P < .01) higher than in controls, while PRA, ALD, phosphate, potassium, and sodium were superimposable in the three groups. PTH in patients with PH was weakly correlated with PRA (positively) and with plasma potassium (negatively) and was not associated with ALD, calcium, sodium, and BP levels. Surgery was followed by a significant reduction (P < .01) in PTH, calcium, and urinary phosphate and an increase (P < .02) in plasma phosphate, potassium, and sodium, whereas PRA, ALD, urinary potassium and sodium, and BP showed no change. In hypertensive patients with PH, PTH, PRA, and plasma and urinary ALD, calcium, and sodium did not differ from the values in normotensive PH patients, and variations in these humoral parameters after surgery were comparable in the two groups. In conclusion, our results show that hypertension is frequently associated with PH. However, the present data raise doubts about the assumption of a renin-mediated causal relationship between hyperparathyroidism and high BP. Indeed, as a unique finding in favor of the hypothesis of a stimulating role of PTH in renin secretion, we observed only a weak relation between PTH and PRA. Thus, unknown and/or unassessed factors related to parathyroid disease cannot be ruled out to explain the hypertension observed in some patients with PH.

Adult↗
PubMed1999

The course of Graves' ophthalmopathy is not influenced by near total thyroidectomy: a case-control study.

OBJECTIVE: The relationship between the method of treatment of hyperthyroidism due to Graves' disease and the course of Graves' ophthalmopathy is debated. Antithyroid drug therapy is associated with no change, or even amelioration, of ophthalmopathy. Although controversial, radioiodine may be followed by progression of eye disease, preventable by glucocorticoid administration. Whether thyroidectomy affects the course of ophthalmopathy is uncertain. DESIGN: In a case control study, the course of non-severe Graves' ophthalmopathy after thyroidectomy was investigated and the results compared with those observed in patients treated with methimazole. PATIENTS: Thirty patients with Graves' hyperthyroidism and non-severe/absent ophthalmopathy were treated with near-total thyroidectomy (Group 1, Tx), after achievement of euthyroidism with methimazole. After surgery, all patients started levothyroxine replacement therapy. Sixty patients treated with methimazole, matched for age, sex, duration of hyperthyroidism, degree of ocular involvement and smoking habits, were used as controls (Group 2, MMI). MEASUREMENTS: Patients were seen every 1-2 months for 12 months for thyroid tests and ocular evaluation. RESULTS: In Group 1, ocular parameters did not change in 17 of 18 patients with pre-existing ophthalmopathy, and in 12 patients without ophthalmopathy. Eye manifestations worsened only in one (3.3%) patient with pre-existing ophthalmopathy. In Group 2, ocular parameters did not change in 58 patients (33 with, and 25 without ophthalmopathy), while new ophthalmopathy occurred in two without pre-existing eye disease. One of the 30 patients treated by surgery (3.3%) had permanent hypoparathyroidism. CONCLUSIONS: Treatment of Graves' hyperthyroidism with near-total thyroidectomy in patients with non-severe or absent pre-existing ophthalmopathy is not associated in the short term with significant effects on the course of ophthalmopathy.

Adult↗
PubMed1999

Video-assisted versus conventional parathyroidectomy in primary hyperparathyroidism: a prospective randomized study.

BACKGROUND: Several studies demonstrated the feasibility of minimally invasive parathyroidectomy as a treatment for primary hyperparathyroidism. We compared its results with those of traditional surgery in a prospective randomized study. METHODS: From March to November 1998, 38 patients eligible for video-assisted parathyroidectomy (VAP) were referred to us. They were randomly divided into 2 groups: patients of group A underwent a conventional cervicotomy with bilateral exploration and frozen section of the removed adenoma; patients of group B underwent VAP with intraoperative measurement of parathyroid hormone. Operative time, postoperative pain, fever and hypocalcemia, cosmetic result, and costs were compared. Two cases of VAP were performed with locoregional anesthesia. RESULTS: Groups A (18 patients) and B (20 patients) were statistically balanced. Operative time was significantly shorter in group B (57 vs 70 minutes). Cosmetic result was significantly better in group B, which also experienced less postoperative pain (P < .05). No cases of persistent primary hyperparathyroidism were present in either group, but recurrent laryngeal nerve palsy occurred in 1 patient in group B. CONCLUSIONS: Compared with conventional surgery, VAP is associated with a shorter operative time, a better cosmetic result, and a less painful postoperative course.

Adult↗
PubMed1999

Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

Adenoma↗
PubMed1999

No evidence for mutations in the calcium-sensing receptor gene in sporadic parathyroid adenomas.

Inactivating mutations of the calcium-sensing receptor gene (CaR) might explain abnormalities in the regulation of both parathyroid cell proliferation and parathyroid hormone secretion. In a previous study, using RNAse A protection assay, no mutations were identified in a series of parathyroid specimens from patients with primary and secondary hyperparathyroidism, but the analysis was incomplete, since part of exon 6 could not be analyzed. In the present study, we examined the presence of mutations in the CaR gene in 20 parathyroid adenomas using direct sequencing. The entire coding region of the CaR gene was successfully amplified by polymerase chain reaction and directly sequenced. This analysis did not identify CaR gene mutations in any tumors studied. A polymorphism that encoded a single amino acid change (Ala826Thr) was identified in 4 parathyroid adenomas and in 8 of 50 normal unrelated subjects. Loss of heterozygosity studies were also performed on adenomas using markers for the locus of the CaR gene on chromosome 3q. No allelic loss was demonstrated. In conclusion, our results extend previous observation and suggest that clonal somatic mutations of the CaR gene and allelic loss at the CaR locus on chromosome 3q do not play a major role in the pathogenesis of sporadic parathyroid tumors.

Adenoma↗
PubMed1999

A new mutation of the MEN1 gene in an italian kindred with multiple endocrine neoplasia type 1.

OBJECTIVE: To report a new mutation of the multiple endocrine neoplasia type 1 (MEN1) gene in an Italian kindred. DESIGN: The study included the female proband, aged 50 years, affected by primary hyperparathyroidism, insulinoma and prolactinoma, and ten relatives. Blood samples were obtained for biochemical and genetic analyses. Clinical screening tests included serum glucose, ionized calcium, intact parathyroid hormone, GH, insulin and prolactin. The coding sequence, including nine coding exons and 16 splice sites, was amplified by PCR and directly sequenced. RESULTS: Two additional cases of primary hyperparathyroidism were identified among the paternal family members. The sequence analysis showed a heterozygous T to C transition at codon 444 in exon 9, resulting in a leucine to proline substitution (L444P) in the patient and in the two paternal family members with primary hyperparathyroidism. The L444P amino acid change was absent in 50 normal subjects. The mutation determined the loss of a BlnI restriction site of the wild-type sequence and the creation of a new restriction EcoRII site. The patient, but not her paternal affected relatives, also had a common heterozygous polymorphism (D418D) in exon 9. CONCLUSIONS: A new MEN1 mutation (L444P) in exon 9 has been identified; this substitution caused the loss of a BlnI restriction site and the creation of a new EcoRII site.

Antisense Elements (Genetics)↗