Fabio Monzani

COAGULATION AND FIBRINOLYTIC SYSTEM IMPAIRMENT IN INSULIN DEPENDENT DIABETES MELLITUS

Selected coagulation and fibrinolytic parameters were assessed in 40 insulin dependent diabetes mellitus patients with varying degrees of metabolic control; 30 healthy subjects matched for age and sex formed the control group. Activated Partial Thromboplastin Time, Prothrombin Time, Fibrinogen, Factor VII, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, Plasminogen Activator Inhibitor-1, tissue-Plasminogen Activator were functionally evaluated. Antigenic levels of tissue-Plasminogen Activator, Thrombin-Antithrombin complexes and fibrinolytic specific product B beta 15-42 were also determined. Compared to the control group diabetic patients displayed significantly higher levels of Fibrinogen (p < 0.01), Factor VII (p < 0.01), Thrombin-Antithrombin complexes (p < 0.01) and Plasminogen Activator Inhibitor-1 activity (p < 0.01). Regardless of the normal level of the tissue-Plasminogen Activator-related antigen, diabetic patients had tissue-Plasminogen Activator activity lower than the control group (p < 0.05). Coagulation Factor VII and Thrombin-Antithrombin complexes were increased only in the patients with poor metabolic control (p < 0.01). Activated Partial Thromboplastin Time, Prothrombin Time, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, B beta 15-42 fibrin peptide were found to be in the normal range. Fibrinogen correlated positively with fasting blood glucose (p < 0.05) and Thrombin-Antithrombin complexes with glycosylated haemoglobin (p < 0.05), whereas Factor VII was positively correlated with glycemia (p < 0.01) and glycosylated haemoglobin (p < 0.05). Higher levels of Fibrinogen were found in patients affected by nephropathy (p < 0.005) or neuropathy (p < 0.05). These results demonstrate an impairment of the haemostatic balance in diabetic patients, that is a possible hypercoagulable state, which represents an important factor in the pathogenesis of atherosclerotic complications.

Papillary Thyroid Cancer: Time Course of Recurrences During Postsurgery Surveillance

CONTEXT The current use of life-long follow-up in patients with papillary thyroid cancer (PTC) is based largely on the study of individuals diagnosed and treated in the latter half of the 20th century when recurrence rates were approximately 20% and relapses detected up to 20-30 years after surgery. Since then, however, diagnosis, treatment, and postoperative monitoring of PTC patients have evolved significantly. OBJECTIVES The objective of the study was to identify times to PTC recurrence and rates by which these relapses occurred in a more recent patient cohort. PATIENTS AND DESIGN We retrospectively analyzed follow-up data for 1020 PTC patients consecutively diagnosed in 1990-2008 in 8 Italian hospital centers for thyroid disease. Patients underwent thyroidectomy, with or without radioiodine ablation of residual thyroid tissue and were followed up with periodic serum thyroglobulin assays and neck sonography. RESULTS At the initial posttreatment (≤ 12 months) examination, 948 patients had no structural/functional evidence of disease. During follow-up (5.1-20.4 years; median 10.4 years), recurrence (cervical lymph nodes, thyroid bed) was diagnosed in 13 (1.4%) of these patients. All relapses occurred 8 or fewer years after treatment (10 within the first 5 years, 6 within the first 3 years). Recurrence was unrelated to the use/omission of postoperative radioiodine ablation. CONCLUSION In PTC patients whose initial treatment produces disease remission (no structural evidence of disease), recurrent disease is rare, and it usually occurs during the early postoperative period. The picture of recurrence timing during the follow-up provides a foundation for the design of more cost-effective surveillance protocols for PTC patients.

Is Elastography Actually Useful in the Presurgical Selection of Thyroid Nodules with Indeterminate Cytology

BACKGROUND Although fine-needle aspiration cytology remains the mainstay of the preoperative workup of thyroid nodules, those with follicular proliferation still represent a diagnostic challenge. Real-time elastography (RTE) estimates the stiffness/elasticity of lesions and is regarded as a promising technique for the presurgical selection of thyroid nodules (including those with indeterminate cytology). AIM Our aim was to verify the potential role of RTE in the presurgical diagnosis of cancer in a large cohort of consecutive patients with follicular thyroid nodules. PATIENTS AND METHODS One hundred two patients were submitted to conventional ultrasonography and RTE evaluation before being operated on for thyroid nodule with indeterminate cytology (54% single nodules). Tissue stiffness on RTE was scored from 1 (greatest elasticity) to 4 (no elasticity). RESULTS At conventional ultrasonography examination, the nodules (median diameter 2.2 cm) were solid (cystic areas < 10%); microcalcifications were detected in 56% of them and a hypoechoic pattern in 64%. Elasticity was high in eight cases only (score 1-2) although low in 94 (score 3-4). Cancer was diagnosed in 36 nodules (35%), being associated with microcalcifications (P < 0.0001) and inversely related to nodule diameter (P < 0.01). Malignancy was detected in 50% of the nodules with RTE score 1-2 and in 34% of those with score 3-4. Therefore, either the positive (34%) or the negative predictive value (50%) was clinically negligible. CONCLUSIONS The current study does not confirm the recently reported usefulness of RTE in presurgical selection of nodules with indeterminate cytology and suggest the need for quantitative analytical assessment of nodule stiffness to improve RTE efficacy.

Five‐year follow‐up of percutaneous ethanol injection for the treatment of hyperfunctioning thyroid nodules: a study of 117 patients

Percutaneous ethanol injection (PEI) has been suggested as an alternative to radioiodine and surgery for the treatment of autonomous thyroid nodules (ATN).

Identification and optimal postsurgical follow-up of patients with very low-risk papillary thyroid microcarcinomas

CONTEXT Most papillary thyroid microcarcinomas (PTMCs; ≤ 1 cm diameter) are indolent low-risk tumors, but some cases behave more aggressively. Controversies have thus arisen over the optimum postoperative surveillance of PTMC patients. OBJECTIVES We tested the hypothesis that clinical criteria could be used to identify PTMC patients with very low mortality/recurrence risks and attempted to define the best strategy for their management and long-term surveillance. DESIGN We retrospectively analyzed data from 312 consecutively diagnosed PTMC patients with T1N0M0 stage disease, no family history of thyroid cancer, no history of head-neck irradiation, unifocal PTMC, no extracapsular involvement, and classic papillary histotypes. Additional inclusion criteria were complete follow-up data from surgery to at least 5 yr after diagnosis. All 312 had undergone (near) total thyroidectomy [with radioactive iodine (RAI) remnant ablation in 137 (44%) - RAI group] and were followed up yearly with cervical ultrasonography and serum thyroglobulin, TSH, and thyroglobulin antibody assays. RESULTS During follow-up (5-23 yr, median 6.7 yr), there were no deaths due to thyroid cancer or reoperations. The first (6-12 months after surgery) and last postoperative cervical sonograms were negative in all cases. Final serum thyroglobulin levels were undetectable (<1 ng/ml) in all RAI patients and almost all (93%) of non-RAI patients. CONCLUSION Accurate risk stratification can allow safe follow-up of most PTMC patients with a less intensive, more cost-effective protocol. Cervical ultrasonography is the mainstay of this protocol, and negative findings at the first postoperative examination are highly predictive of positive outcomes.

Neuromuscular symptoms and dysfunction in subclinical hypothyroid patients: beneficial effect of L‐T4 replacement therapy

The presence of neuromuscular symptoms was ascertained by questionnaire in 33 consecutive patients with subclinical hypothyroidism (sHT) as compared to 44 age‐ and sex‐matched controls. Blood was sampled for PTH, magnesium, phosphate, and total and ionized calcium determination. Patients reporting three or more symptoms were also studied by surface electromyography (sEMG). The study was repeated following a six‐month L‐T4 course.

Thyroid autoimmunity and dysfunction associated with type I interferon therapy

Abstract.Type I interferons are currently used for the treatment of chronic viral hepatitis, multiple sclerosis and several hematological and solid tumors. Side effects are not uncommon, and include multiple alterations in thyroid function, some of which are unrelated to autoimmunity. Review of the literature revealed an overall mean prevalence of incident thyroid dysfunction of 6.2%, hypothyroidism occurring more frequently (3.9%) than hyperthyroidism (2.3%). Destructive thyroiditis characterized by early transient thyrotoxicosis followed by hypothyroidism has also been described. Thyroid dysfunction was mainly subclinical, and spontaneous resolution occurred in almost 60% of patients with or without withdrawal of interferon. Risk factors for developing thyroid abnormalities were female sex and the presence of pre-existing autoimmune thyroiditis. Whether prolonged interferon therapy will increase the likelihood of experiencing thyroid dysfunction, as well as the relationship between incident thyroid autoimmunity and the efficacy of interferon therapy, are still open questions. Although the most-likely explanation for thyroid disease occurring with type I interferon therapy remains an autoimmune reaction or immune system dysregulation, a direct inhibitory effect on thyrocytes may be presumed in patients who developed hypothyroidism without autoimmunity. However, the mechanisms of thyroid damage induced by type I interferons have not yet been clarified in detail. We recommend routine evaluation of serum thyroid-stimulating hormone during interferon therapy. A systematic thyroid assessment is useful only for those patients with pre-existing thyroiditis or incident dysfunction. Although discontinuation of interferon therapy is seldom required, it may be necessary in patients who develop Graves’ disease and overt hyperthyroidism.

RECIPROCAL CHANGES OF SERUM THYROGLOBULIN AND TSH IN RESIDENTS OF A MODERATE ENDEMIC GOITRE AREA

Subjects living in iodine deficient areas were reported to have elevated serum thyroglobulin (Tg) concentrations. This finding was interpreted as related to thyroid stimulation. Discrepant results, however, were found when serum Tg concentrations were correlated either with serum TSH or with goitre size. In this study we investigated the relationships between goitre size, serum Tg and serum TSH in 488 unselected adult subjects living in an endemic area of North‐Western Tuscany (Garfagnana district). The control group comprised 352 subjects residing in a non‐endemic area. In the endemic area a high prevalence of goitre was found (80·1%), thyroid enlargement being slight to moderate in the majority of cases and very large only in six subjects. Serum Tg concentrations increased and serum TSH levels decreased with the size of goitre. Statistical analysis by the chi‐square cross correlation test showed that the converse changes of serum Tg and serum TSH in relation to goitre size were highly significant. These findings indicate that the increase of serum Tg occurring in endemic goitrous subjects may be related to factors other than TSH stimulation. Functional autonomy of the thyroid may account for the finding of low serum TSH and elevated serum Tg values in patients with large goitres. The present data do not exclude the possibility that the release of Tg is influenced by TSH stimulation, but indicate that other factors may be responsible for the increased levels of Tg found in endemic goitre.

Percutaneous ethanol injection treatment of autonomous thyroid adenoma: hormonal and clinical evaluation

OBJECTIVE We have evaluated the efficacy of percutaneous ethanol Injection as an alternative to surgery and iodlne‐131 treatment in solitary autonomous thyroid adenoma.

Folate, homocysteine, vitamin B12, and polymorphisms of genes participating in one-carbon metabolism in late-onset Alzheimer's disease patients and healthy controls.

AIMS We screened 378 late-onset Alzheimers disease (LOAD) patients and 308 matched controls for the presence of the common MTHFR 677C>T, MTRR 66A>G, MTR 2756 A>G, and TYMS 28 bp repeat polymorphisms, searching for association with disease risk and age at onset. Moreover, we searched for correlation between each of the studied polymorphisms and available data on plasma homocysteine (Hcy), serum folate, and vitamin B12 values. RESULTS We observed a significant increased frequency of the MTHFR 677T allele (0.48 vs. 0.42; p=0.019) and of MTHFR 677CT (OR=1.46; 95%CI=1.03-2.06) and TT genotypes (OR=1.62; 95%CI=1.05-2.49) in LOAD subjects with respect to controls. We also observed a significant increased frequency of the MTRR 66G allele (0.49 vs. 0.43; p=0.044) and of the MTRR 66GG genotype (OR=1.57; 95%CI=1.01-2.46) in the LOAD group. Significantly increased mean plasma Hcy levels (22.7±1.7 vs 14.5±1.7 μmol/L; p=0.037) and decreased serum folate values (5.7±0.5 vs. 7.8±0.8 ng/mL; p=0.005) were observed in LOAD subjects with respect to controls, whilst the difference in serum vitamin B12 values did not reach statistical significance. Several interactions between the studied polymorphisms and biochemical biomarkers were observed. None of the studied polymorphisms was associated with disease age at onset. INNOVATION The present study suggests that the MTRR 66G allele might contribute to LOAD risk and confirms an increased frequency of the MTHFR 677T allele in LOAD. CONCLUSION Overall, present results support a contribution for one-carbon metabolism to LOAD pathogenesis.