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C Marcocci

Publications and source records attributed to C Marcocci.

At least 55 records · Page 3Linked to original sources

[Orbital decompression in Grave's disease: comparison of techniques].

Grave's ophthalmopathy is an inflammatory, autoimmune disorder often associated with Grave's disease. The inflammatory infiltration involves the retrobulbar fatty tissue and the extrinsic eye muscles, causing proptosis, extraocular muscle dysfunction and often diplopia. Orbital decompression is an effective treatment in such cases, particularly when resistant to drugs and external radiation therapy. This work compares the results of orbital decompression performed by removing: a) the medial and lateral walls (Mourits technique) in 10 patients (19 orbits) and b) the medial and lower walls (Walsh-Ogura technique) in 17 patients (31 orbits). The results show that removing the floor of the orbit enables better reduction of proptosis but more easily leads to post-operative diplopia. Thus it proves necessary to combine the two techniques, modifying the surgical approach on a case-by-case basis.

Decompression, Surgical↗

Cigarette smoking and treatment outcomes in Graves ophthalmopathy.

BACKGROUND: It is unclear whether smoking affects the course of Graves ophthalmopathy and therapeutic outcomes. OBJECTIVE: To observe smoking behavior in a randomized study of the effect of radioiodine therapy on ophthalmopathy and in a case series of patients with Graves ophthalmopathy receiving orbital radiation therapy and glucocorticoids. DESIGN: Randomized, single-blind study of smoking and mild ophthalmopathy after radioiodine therapy (study 1) and a retrospective cohort study of the association between smoking and response of severe ophthalmopathy to treatment (study 2). SETTING: University medical center. PATIENTS: 300 patients with mild ophthalmopathy (study 1) and 150 patients with severe ophthalmopathy (study 2). INTERVENTION: In study 1, patients received radioiodine alone or radioiodine and a 3-month course of oral prednisone (initial dosage, 0.4 to 0.5 mg/kg of body weight per day). In study 2, patients received high-dose oral prednisone for 6 months (initial dosage, 80 to 100 mg/d) and underwent orbital radiation therapy by linear accelerator (cumulative dose, 20 Gy per eye over 2 weeks). MEASUREMENTS: Degree of ophthalmopathy was assessed by overall evaluation (inflammatory changes, proptosis, extraocular muscle dysfunction, corneal involvement, and optic neuropathy). RESULTS: In study 1, ophthalmopathy progressed in 4 of 68 nonsmokers (5.9% [95% CI, 3% to 9%]) and 19 of 82 smokers (23.2% [CI, 13% to 33%]) who received radioiodine alone (P = 0.007). Ophthalmopathy was alleviated in 37 of 58 nonsmokers (63.8% [CI, 51% to 78%]) and 13 of 87 smokers (14.9% [CI, 10% to 26%]) who received radioiodine plus prednisone (P < 0.001). In study 2, 61 of 65 nonsmokers (93.8% [CI, 90% to 98%]) and 58 of 85 smokers (68.2% [CI, 57% to 78%]) responded to treatment (P < 0.001). CONCLUSIONS: Cigarette smoking increases the risk for progression of ophthalmopathy after radioiodine therapy and decreases the efficacy of orbital radiation therapy and glucocorticoid therapy.

Adult↗

Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy.

BACKGROUND: The chief clinical characteristics of Graves' disease are hyperthyroidism and ophthalmopathy. The relation between the two and the effect of treatment for hyperthyroidism on ophthalmopathy are unclear. METHODS: We studied 443 patients with Graves' hyperthyroidism and slight or no ophthalmopathy who were randomly assigned to receive radioiodine, radioiodine followed by a 3-month course of prednisone, or methimazole for 18 months. The patients were evaluated for changes in the function and appearance of the thyroid and progression of ophthalmopathy at intervals of 1 to 2 months for 12 months. Hypothyroidism and persistent nyperthyroiaism were promptly corrected. RESULTS: Among the 150 patients treated with radioiodine, ophthalmopathy developed or worsened in 23 (15 percent) two to six months after treatment. The change was transient in 15 patients, but it persisted in 8 (5 percent), who subsequently required treatment for their eye disease. None of the 55 other patients in this group who had ophthalmopathy at base line had improvement in their eye disease. Among the 145 patients treated with radioiodine and prednisone, 50 (67 percent) of the 75 with ophthalmopathy at base line had improvement, and no patient had progression. The effects of radioiodine on thyroid function were similar in these two groups. Among the 148 patients treated with methimazole, 3 (2 percent) who had ophthalmopathy at base line improved, 4 (3 percent) had worsening of eye disease, and the remaining 141 had no change. CONCLUSIONS: Radioiodine therapy for Graves' hyperthyroidism is followed by the appearance or worsening of ophthalmopathy more often than is therapy with methimazole. Worsening of ophthalmopathy after radioiodine therapy is often transient and can be prevented by the administration of prednisone.

Adolescent↗

Bcl-2, p53 and MIB-1 expression in normal and neoplastic parathyroid tissues.

An altered control of the mechanisms involved in cell proliferation and programmed cell death (apoptosis) might play an important role in parathyroid tumorigenesis. We evaluated by immunohistochemistry the expression of bcl-2 and p53 proteins, as markers of apoptosis control, and MIB-1, as marker of cell proliferation, in a series of normal and neoplastic parathyroid tissues. The specimens were 33 normal parathyroids, 43 parathyroid adenomas and 3 parathyroid carcinomas. Results were scored as positive when more than 1% of cells were stained for MIB-1 and p53, and more than 10% for bcl-2. All normal parathyroids showed numerous bcl-2 positive cells (> or = 80%), low proliferation rate (MIB-1) and no p53 protein expression. Twenty-four (55%) adenomas were bcl-2 positive; in 16 of these the number of positive cells was high (> 50%) and immunoreactivity was diffusely distributed within the adenoma; 8 cases showed a zonal staining pattern, in which groups of stained cells were surrounded by negative cells. Nineteen adenomas (45%) and all carcinomas were bcl-2 negative. A high proliferative rate (MIB-1) was found in all carcinomas and 4 adenomas (9%); all MIB-1 positive adenomas were bcl-2 negative. p53 was negative in all specimens. No significant differences in serum calcium and intact PTH levels nor in tumor size were found between bcl-2 negative and bcl-2-positive and MIB-1-positive and MIB-1-negative adenomas. An inverse, but not statistically significant (p = 0.06) correlation was observed between the percentage of bcl-2 positive cells and serum calcium level in parathyroid adenomas. In conclusion, parathyroid adenomas are a heterogeneous group of lesions in which the pattern of bcl-2 and MIB-1 protein expression ranges between that of normal parathyroid (bcl-2 positivity and MIB-1 negativity) and that of parathyroid carcinoma (bcl-2 negativity and MIB-1 positivity). The question of whether the finding of the MIB-1 positive-bcl-2 negative phenotype identifies a subgroup of clinically more aggressive adenomas remains to be established.

Adenoma↗

Endoscopic parathyroidectomy: report of an initial experience.

BACKGROUND: Preoperative localization of parathyroid lesions and intraoperative quick parathyroid hormone (PTH) assay have been proposed to minimize the extent of operation in primary hyperparathyroidism. To this purpose, endoscopic procedures have been introduced recently. METHODS: During a period of 13 months, 39 of 65 consecutive patients with primary hyperparathyroidism were selected for endoscopic parathyroidectomy on the basis of the following criteria: preoperative echographic diagnosis of a single adenoma, absence of nodular goiter, and no prior neck operations. Unilateral neck exploration and excision of the adenoma was performed through a gasless procedure combined with intraoperative PTH measurements. Mean follow-up after the operation was 7 months (range 1 to 13 months). RESULTS: Thirty-nine parathyroid adenomas were removed; the mean diameter was 21 mm (range 5 to 30 mm). The mean operative time was 65 minutes (range 30 to 180 minutes). In all cases PTH concentration decreased significantly. Patients who underwent endoscopic parathyroidectomy had less postoperative pain compared with patients who underwent conventional hemithyroidectomy. At follow-up, serum calcium and PTH levels were normal in all cases. CONCLUSIONS: Endoscopic parathyroidectomy proved to be a feasible surgical procedure that can be performed in an acceptable operative time with an excellent cosmetic result. The gasless approach avoided any emphysema.

Adult↗

Endoscopic parathyroidectomy by a gasless approach.

Endoscopic approach for the treatment of primary hyperparathyroidism is one of the new fields of interest for minimally invasive surgery. The removal of the parathyroid gland can be achieved either by a gas or gasless technique. Massive carbon dioxide (CO2) diffusion and absorption has been reported to occur during the gas procedure. Endoscopic techniques that do not rely on CO2 insufflation have still to be set. We have developed a new procedure that was offered to 20 selected patients with a localized parathyroid adenoma. A 3-minute CO2 insufflation (12 mm Hg) through a conventional trocar inserted under the strap muscles is used just to anatomically dissect the virtual thyrotracheal groove. Actually, the working space is maintained by means of skin retractors so as to allow needlescopic instruments to perform a parathyroid adenomectomy with the gasless procedure. In all cases the parathyroid adenoma was removed through a 1.5-cm skin incision. Quick parathyroid hormone assays always confirmed the removal of all pathologic glands and permitted unilateral cervical exploration. Mean operative time was 71.7 +/- 35.5 minutes. No complication was registered. At follow-up, all patients were normocalcemic. This new endoscopic approach to the neck seems to be safe, effective, and cosmetically satisfactory.

Adenoma↗

Preoperative localization of suspicious parathyroid adenomas by assay of parathyroid hormone in needle aspirates.

OBJECTIVE: To determine the usefulness of parathyroid hormone (PTH) measurement in needle aspirates of a suspicious neck mass to confirm its parathyroid nature in patients with primary hyperparathyroidism. METHODS: Thirty-three patients with surgically proved primary hyperparathyroidism were submitted to neck ultrasound (US), parathyroid scintigraphy, and assay of PTH in the aspirate (PTHa) of the suspicious cervical mass. RESULTS: Based on the results of neck US and parathyroid scintigraphy, patients were divided into two groups. Group 1: 16 patients (seven with nodular goiter) with concordant positive US and scintigraphic results. In all but one patient, PTHa was detectable and often markedly elevated (> 1000 pg in 12 patients, between 292 pg and 803 pg in three patients and 53 pg in one patient). The patient with undetectable PTHa had a small lower left parathyroid adenoma (8x8x10 mm). Group 2: 17 patients (12 with nodular goiter) with discordant US and scintigraphic results. PTHa established the parathyroid nature of the mass in 13 cases (> 1000 pg in 8 patients, between 501 pg and 953 pg in three patients and 90 and 79 pg in two patients): 11 of these had a suspected lesion by US examination but the scintigraphy results were negative; two had a mass that gave positive scintigraphy results but was of uncertain origin according to US: in both cases an intrathyroidal parathyroid adenoma was found. PTHa was undetectable in four cases (three with nodular goiter): all of these had equivocal US results, and three had positive scans and one a negative scan. CONCLUSIONS: Assay of PTHa is a simple method and should be useful for confirming the parathyroid nature of a cervical mass in patients with discordant or non-diagnostic US and scintigraphic results.

Adenoma↗

Usefulness of echo-color Doppler in differentiating parathyroid lesions from other cervical masses.

The aim of our study was to clarify possible differential color Doppler US features between parathyroid lesions and other cervical masses. A total of 56 parathyroid lesions in 54 patients with primary hyperparathyroidism were preoperatively examined with color Doppler sonography. Color Doppler flow patterns were compared with those of 72 thyroid nodules and 20 cervical lymph nodes. In 38 parathyroid lesions a correlation between color Doppler patterns and size, location, and pathological findings was performed. Color Doppler sonography showed five vascular distribution patterns: pattern I, absence of flow; pattern II, focal peripheral flow ("vascular pole") with arterial Doppler spectrum; pattern III, peripheral flow; pattern IV, internal flow ("parenchymal pattern"); pattern V, peripheral and intranodular flow. Pattern I was not specific for any cervical lesion considered. Conversely, pattern IV was observed solely in parathyroid lesions, and pattern II was observed in only one nonparathyroid lesion (thyroid nodule). Mixed pattern (pattern V) was observed solely in thyroid nodules. In addition, pattern III was a characteristic finding of thyroid nodules and was observed in only one parathyroid lesion. Color Doppler patterns of the parathyroid masses did not correlate with the size of the lesion or pathological findings, but only with the location of the gland. Our study showed that color Doppler assessment of parathyroid lesions is a useful integration of gray-scale US and may be helpful in distinguishing parathyroid lesions from other cervical masses.

Adenoma↗

Treating severe Graves' ophthalmopathy.

Most patients with Graves' disease have some evidence of ocular involvement, but this is commonly mild, requiring only local measures. A minority of patients (3-5%) have severe Graves' ophthalmopathy, for which the three main treatment procedures are represented by high-dose glucocorticoids, orbital radiotherapy and orbital decompression. Favourable results with medical treatment have been reported in approximately 60% of patients, with particular regard to inflammatory changes, newly developed eye muscle dysfunction and optic neuropathy. Orbital decompression is indicated in severe eye disease not responsive to glucocorticoids and/or irradiation, particularly in the presence of marked proptosis and optic neuropathy. Not conclusive or unsatisfactory results have been obtained with other medical treatment procedures, including immunosuppressive drugs, intravenous immunoglobulins and plasmapheresis. Recently favourable responses have been reported with somatostatin analogues. Rehabilitative surgery involving either the eye muscles or the eyelids is not infrequently required after medical treatment or decompression. Permanent control of thyroid hyperfunction by radioiodine or thyroidectomy is advisable when severe ophthalmopathy is present. Exacerbation of ophthalmopathy following radioiodine may occur but can be prevented by concomitant administration of glucocorticoids. Smoking deleteriously influences the course of ophthalmopathy and its response to treatment.

Glucocorticoids↗

Characterization of monoclonal thyroid-stimulating and thyrotropin binding-inhibiting autoantibodies from a Hashimoto's patient whose children had intrauterine and neonatal thyroid disease.

A multiplicity of TSH receptor autoantibodies (TSHRAbs) have been characterized after subcloning heterohybridomas produced from the lymphocytes of a patient who has Hashimoto's thyroiditis and had three children with intrauterine or neonatal hyperthyroidism. Twelve clones produced stimulating TSHRAbs that increased cAMP levels and iodide uptake in rat FRTL-5 thyroid cells and increased cAMP levels in Chinese hamster ovary (CHO) cells transfected with the human TSHR; like 95% of Graves' stimulating TSHRAbs, all 12 have their functional epitope on the N-terminus of the TSHR extracellular domain, requiring residues 90-165 for activity. All 12 bind to human thyroid membranes in the absence, but not the presence, of TSH, but are only weak inhibitors of TSH binding in assays measuring TSH binding-inhibiting Igs (TBIIs). In contrast, 8 different clones produced TSHRAbs that did not increase cAMP levels, but, instead, exhibited significant TBII activity. Four inhibited the ability of TSH or a stimulating TSHRAb to increase cAMP levels and had their functional epitope on the C-terminal portion of the TSHR external domain, residues 261-370, mimicking the properties of blocking TSHRAbs that cause hypothyroidism in patients with idiopathic myxedema. The 4 other TBIIs inhibited the ability of TSH, but not that of a stimulating TSHRAb, to increase cAMP levels, like TBIIs in Graves' patients. The functional epitope for 3 of these Graves'-like TBIIs was residues 90-165; the functional epitope for the fourth was residues 24-89. The fourth also increased arachidonic acid release and inositol phosphate levels in FRTL-5 thyroid cells and exhibited conversion activity, i.e. the ability to increase cAMP levels in the presence of an anti-human IgG. Thus, this TBII exhibited signal transduction activity, unlike the other 3 Graves'-like TBIIs. The patient, therefore, has stimulating TSHRAbs and 3 different types of TBIIs, each with different functional properties and different epitopes on the TSHR.

Adult↗

Skeletal integrity in men chronically treated with suppressive doses of L-thyroxine.

We measured bone mineral density (BMD) (lumbar spine, femoral neck, Ward's triangle, and trochanter) in 34 men given suppressive doses of levothyroxine (L-T4) for a mean of 10.2 years. Indications for treatment were nontoxic goiter (n = 5) or thyroidectomy for differentiated thyroid cancer (n = 6) or nontoxic goiter (n = 3). Patients were followed at our institution and treated with the minimal amount of L-T4 able to suppress thyroid-stimulating hormone (TSH). At the time of evaluation, free T3 was normal in all cases, whereas free T4 was increased in 14 men (41.2%). The mean daily dose of L-T4 was 172 +/- 6 microg, and the cumulative dose of L-T4 was 673 +/- 71 mg. We found no significant difference between patients and age- and weight-matched controls in BMD (g/cm2) at any site of measurement (lumbar spine 1.144 +/- 0.12 vs. 1.168 +/- 0.15; femoral neck 0.979 +/- 0.13 vs. 1.001 +/- 0.13; Ward's triangle 0.854 +/- 0.17 vs. 0.887 +/- 0.15; and trocanther 0.852 +/- 0.13 vs. 0.861 +/- 0.13). BMD was not correlated with the duration of therapy, cumulative or mean daily dose of L-T4, serum levels of free T4, free T3, osteocalcin, and bone alkaline phosphatase. Serum calcium and osteocalcin were slightly but significantly elevated in patients compared with controls, whereas there was no difference in intact parathyroid hormone, bone alkaline phosphatase, and sex hormone-binding globulin (marker of thyroid hormone action). Our data suggest that L-T4 suppressive therapy, if carefully carried out and monitored, using the smallest dose necessary to suppress TSH secretion, has no significant effects on bone metabolism and bone mass in men.

Absorptiometry, Photon↗

Identification and characterization of a novel de novo mutation (L346V) in the thyroid hormone receptor beta gene in a family with generalized thyroid hormone resistance.

We have investigated an Italian family with generalized resistance to thyroid hormone (RTH), consisting of two individuals with elevated serum thyroid hormones (TH) and a non-suppressed TSH, together with unaffected family members, for a mutation in the thyroid hormone receptor beta gene (hTR beta). We have identified a single nucleotide substitution (1321 CTT to GTT) corresponding to a leucine to valine substitution at codon 346 (L346V) in the predicted protein. The index case and her affected child are heterozygous for the receptor defect, with normal sequence in unaffected family members. Furthermore, both parents of the index case were unaffected, suggesting that the mutation had arisen de novo. When expressed in vitro, the L346V mutant receptor showed a marked reduction in its affinity for tri-iodothyronine (T3), impaired ligand-dependent transactivation and potent dominant negative activity. Its functional impairment could not be alleviated, even at supraphysiological concentrations of T3, suggesting that the mutation might interfere with the intrinsic ligand-dependent transactivation function (AF-2) located in the hormone binding domain of hTR beta. Finally, the presence of the L346V mutation in the son of the propositus, who died from complications associated with congenital heart disease, raises the possibility that RTH might have contributed to the pathogenesis or severity of the latter.

Adult↗

Comparison among sonography, double-tracer subtraction scintigraphy, and double-phase scintigraphy in the detection of parathyroid lesions.

OBJECTIVE: This study prospectively evaluated the sensitivity of high-resolution sonography compared with double-tracer 201Tl-99mTc scintigraphy (Tl-Tc) subtractive scintigraphy and double-phase 99mTc-sestamibi (Tc-MIBI) scintigraphy prior to surgery in the assessment of patients with primary hyperparathyroidism in a geographic region where areas of endemic thyroid goiter are present. SUBJECTS AND METHODS: Sonography and scintigraphy were used as first-step imaging procedures in 73 patients with primary hyperparathyroidism. In 30 (41%) of 73 cases, we found an association with a thyroid abnormality. We compared sonography with double-tracer Tl-Tc scintigraphy in 41 cases, with Tc-MIBI scintigraphy in 22 other cases, and with both scintigraphic studies in 10 other cases. RESULTS: Surgery demonstrated 68 solitary parathyroid lesions (66 adenomas, one hyperplasia, and one carcinoma), two adenomas in two patients, and multiple hyperplastic glands in two patients for a total of seven lesions. In one case no abnormal parathyroid gland was found. Overall sensitivity of sonography, Tl-Tc, and Tc-MIBI scintigraphy was 85%, 62%, and 82%, respectively. In patients with concomitant thyroid disease, the sensitivity of sonography, dual-tracer Tl-Tc, and Tc-MIBI was 77%, 67%, and 80%, respectively. CONCLUSION: Our study proves that sonography and scintigraphy are equally able to detect parathyroid lesions before surgery in patients with concomitant thyroid diseases. In patients without thyroid abnormalities, detection rates of sonography and Tc-MIBI do not show any statistical difference, and the detection rate of Tl-Tc is significantly inferior to that of sonography. Sonography alone should be used as the first step for localization of abnormal parathyroid glands prior to surgery, and Tc-MIBI scintigraphy should be used as the second step when sonography is negative.

Adolescent↗

Do clinical manifestations of resistance to thyroid hormone correlate with the functional alteration of the corresponding mutant thyroid hormone-beta receptors?

Resistance to thyroid hormone (RTH), a syndrome characterized by variable tissue hyposensitivity to thyroid hormone, is linked to mutations in the thyroid hormone receptor-beta (TR beta) gene. The purpose of this study was to determine whether the clinical phenotypes of RTH can be translated in terms of functional impairment of the corresponding mutant TR beta. Data from 124 subjects with RTH representing 18 different mutant TR beta s, showed that serum free T4 levels correlated with the degree of T3-binding impairment of the corresponding TR beta in 12 of these mutant TR beta s (group I), but not in the remaining 6 (group II). In subjects from both groups studied in detail by the administration of incremental doses of T3, the degree of thyrotroph resistance to T3 correlated with the magnitude of endogenous free T4 elevation at baseline, but did not parallel the resistance of peripheral tissues. In transfection studies, all group I mutant TR beta s inhibited positive transactivation by the wild type TR beta s to a similar degree in the presence of 1 nmol/L T3, whereas group II mutant TR beta s exerted a weaker inhibition that was not related to their T3-dependent trans-activation when tested alone. Similar results were obtained with negatively regulated reporter genes. It is concluded that the clinical severity of RTH, determined by thyrotroph resistance, can be predicted from the degree of T3 binding impairment and dominant negative potency of mutant TR beta s, but the degree of peripheral tissue resistance and related clinical manifestations is limited by putative genetic or environmental factors that modulate the effect of thyroid hormone.

Adolescent↗