Direct-acting antivirals used in HCV-related liver disease do not affect thyroid function and autoimmunity.

PURPOSE: It is well known that interferon-α (IFN-α), used for long time as the main therapy for HCV-related disease, induces thyroid alterations, but the impact of the new direct-acting antivirals (DAAs) on thyroid is not established. Aim of this prospective study was to evaluate if DAAs therapy may induce thyroid alterations. METHODS: A total of 113 HCV patients, subdivided at the time of the enrollment in naïve group (n = 64) and in IFN-α group (n = 49) previously treated with pegylated interferon-α and ribavirin, were evaluated for thyroid function and autoimmunity before and after 20-32 weeks of DAAs. RESULTS: Before starting DAAs, a total of 8/113 (7.1%) patients showed Hashimoto's thyroiditis (HT) all belonging to IFN-α group (8/49, 16.3%), while no HT cases were found in the naïve group. Overall, 7/113 (6.2%) patients were hypothyroid: 3/64 (4.7%) belonging to naïve group and 4/49 (8.2%) to IFN-α group. Furthermore, a total of 8/113 patients (7.1%) showed subclinical hyperthyroidism: 2/64 (3.1%) were from naïve group and 6/49 (12.2%) from IFN-α group. Interestingly, after DAAs therapy, no new cases of HT, hypothyroidism and hyperthyroidism was found in all series, while 6/11 (54.5%) patients with non-autoimmune subclinical thyroid dysfunction became euthyroid. Finally, the only association between viral genotypes and thyroid alterations was genotype 1 and hypothyroidism. CONCLUSIONS: This study supports evidence that DAAs have a limited or missing influence on thyroid in patients with HCV-related diseases. Moreover, it provides preliminary evidence that subclinical non-autoimmune thyroid dysfunction may improve after HCV infection resolution obtained by DAAs.

Role of the mononuclear cell infiltrate in Graves' orbitopathy (GO): results of a large cohort study.

OBJECTIVE: The extent to which mononuclear cells and TSH-receptor autoantibodies (TRAb) contribute to Graves' orbitopathy (GO) is not completely defined. Here we investigated the relationship between the immunohistochemical phenotype of orbital infiltrating cells and GO features in a large number of patients. METHODS: We conducted an observational cohort study in 76 consecutive patients with GO (16 men and 60 women) who underwent orbital decompression over a period of 18 consecutive months. An ophthalmological evaluation was performed in all patients, as well as immunohistochemistry for CD3, CD4, CD8, CD56 (T-cell markers), CD25 (T and B-cell marker), CD20, CD19 (B-cell markers), and CD138 (plasmacell marker) in specimens collected at decompressive surgery. RESULTS: Having established cutoff values for each marker, cell infiltrates were found in 60 patients (78.9%; CD3: 39.4%, CD4 55.2%, CD8 50%, CD56: 0%, CD25: 28.9%, CD20: 51.3%, CD19: 25%, CD138: 26.3%). Eleven (14.4%) stained exclusively for CD138 (plasmacells). Patients with CD4-positive mononuclear cells had a significantly greater GO clinical activity score (CAS) (mean difference 1.07, 95% CI - 0.33 to - 1.82, P = 0.004 by univariate, P = 0.05 by multivariate analysis). CAS as well as the remaining GO features were not affected significantly by the mononuclear cell subpopulations in multivariate analyses. CONCLUSIONS: Mononuclear cell infiltrates are present in the majority of GO patients, with a small percentage represented exclusively by plasmacells. CD4 cells exert a major role on GO activity. These findings may represent a further advancement in the comprehension of GO pathogenesis.

Thyroid autoimmunity and hypothyroidism are associated with deep molecular response in patients with chronic myeloid leukemia on tyrosine kinase inhibitors.

PURPOSE: Thyroid alterations including de novo appearance of thyroid autoimmunity are adverse effects of tyrosine kinase inhibitors, used in solid and hematologic cancer therapy, but the relationship between thyroid alterations during this treatment and the outcome of chronic myeloid leukemia remains unclear. Aim of this study was to investigate whether the presence of thyroid alterations may affect the clinical outcome of chronic myeloid leukemia on tyrosine kinase inhibitors. METHODS: We evaluated thyroid function and autoimmunity in 69 chronic myeloid leukemia patients on long-term therapy looking at the association between thyroid abnormalities and disease molecular response. RESULTS: Overall, 24 of 69 (34.8%) had one or more thyroid abnormalities during therapy. A high percentage of patients (21/69, 30.4%) showed thyroid autoimmunity (positive thyroid autoantibodies with ultrasound hypoechogenicity), while clinical and subclinical hypothyroidism and subclinical hyperthyroidism were, respectively, found in 4 of 69 (5.8%) and 3 of 69 (4.3%) of cases. Second-generation tyrosine kinase inhibitors resulted significantly associated (14/32, 43.7%) with Hashimoto's thyroiditis, compared to first generation (7/37, 18.9%; p = 0.03). Interestingly, we also found a significant association between euthyroid (14/26, 53.8%) and hypothyroid Hashimoto's thyroiditis (4/26, 15.4%) in patients with deep molecular response, as compared to euthyroid (3/43, 7%; p = 0.0001) and hypothyroid (0/43, 0%; p = 0.02) Hashimoto's thyroiditis patients with major molecular response. CONCLUSIONS: Our study confirms and extends our knowledge on the tyrosine kinase inhibitors effects on thyroid, showing that thyroid autoimmunity is frequently observed in chronic myeloid leukemia patients on long-term therapy and is associated with a better oncological response.

Analysis of metabolomics profile in hypothyroid patients before and after thyroid hormone replacement.

PURPOSE: The serum metabolic changes occurring during the transition from hypothyroidism to euthyroidism are not known. This study aimed to determine the metabolomic profile in hypothyroid patients before (HypoT0) and after (HypoT1) euthyroidism achieved through levothyroxine (L-T4) treatment. METHODS: Eighteen patients with overt primary hypothyroidism were recruited for the study. All patients were treated with L-T4 to achieve euthyroidism. Thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and metabolomics profiles were measured before and after 3 months of treatment. The euthyroid control group consisted of 28 healthy volunteers. Metabolomics analysis was performed using Nuclear Magnetic Resonance (NMR) spectroscopy. RESULTS: 1H NMR-based metabolomics profiling of patients with newly diagnosed hypothyroidism (HypoT0) showed significantly higher levels of citrate, creatinine, glycerol, myo-inositol and serine, and lower levels of proline and taurine compared to controls. Interestingly, some metabolic changes were persistent three months after pharmacological treatments, despite normal serum TSH and thyroid hormone concentrations (HypoT1). When an Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) model was built to evaluate possible differences in the metabolic profile between HypoT0 and HypoT1, the data obtained were not significantly different. CONCLUSION: These results suggest that metabolic changes in the patients with hypothyroidism may persist after normalization of serum levels of FT3, FT4, and TSH, which currently represent the gold standard in laboratory testing for diagnosis and evaluation of thyroid pathology. So, the metabolomics approach may contribute to integrate classical hormone assays and to determine the euthyroid status achievement with greater efficacy.

Features and outcome of differentiated thyroid carcinoma associated with Graves' disease: results of a large, retrospective, multicenter study.

BACKGROUND: Whether differentiated thyroid cancer (DTC) occurring concomitantly with Graves' disease (GD) is more aggressive and bound to a less favorable outcome is controversial. OBJECTIVE: Aim of this multicenter retrospective study was to compare baseline features and outcome of DTC patients with GD (DTC/GD+) or without GD (DTC/GD-). PATIENTS: Enrolled in this study were 579 patients referred to five endocrine units (Cagliari, Pavia, Pisa, Siena, and Varese) between 2005 and 2014: 193 patients had DTC/GD+ , 386 DTC/GD-. Patients were matched for age, gender and tumor size. They underwent surgery because of malignancy, large goiter size, or relapse of hyperthyroidism in GD. RESULTS: Baseline DTC features (histology, lymph node metastases, extrathyroidal extension) did not differ in the two groups, except for multifocality which was significantly more frequent in DTC/GD+ (27.5% vs. 7.5%, p < 0.0001). At the end of follow-up (median 7.5 years), 86% of DTC/GD+ and 89.6% DTC/GD- patients were free of disease. Patients with persistent or recurrent disease (PRD) had "biochemical disease" in the majority of cases. Microcarcinomas were more frequent in the DTC/GD+ group (60% vs. 37%, p < 0.0001) and had an excellent outcome, with no difference in PRD between groups. However, in carcinomas ≥ 1 cm, PRD was significantly more common in DTC/GD+ (24.4% vs. 11.5%; p = 0.005). In the whole group, univariate and multivariate analyses showed that GD+ , lymph node involvement, extrathyroidal invasion, multifocality and tall cell histotype were associated with a worse outcome. Female gender and microcarcinomas were favorable features. No association was found between baseline TSH-receptor antibody levels and outcome. Graves' orbitopathy (GO) seemed to be associated with a better outcome of DTC, possibly because patients with GO may early undergo surgery for hyperthyroidism. CONCLUSIONS: GD may be associated with a worse outcome of coexisting DTC only if cancer is ≥ 1 cm, whereas clinical outcome of microcarcinomas is not related to the presence/absence of GD.

Immunogenicity of meningococcal polysaccharide ACWY vaccine in primary immunized or revaccinated adults.

Meningococcal polysaccharide (Men-Ps) vaccine immunogenicity following either primary immunization or revaccination in adults was evaluated. The study population consisted of subjects who have received tetravalent Men-Ps vaccine once (group 1) or at least twice, with a 2-6 dose range (group 2). Human leucocyte antigen (HLA)-typing was performed by polymerase chain reaction and specific immunoglobulin (Ig)G was measured by enzyme-linked immunosorbent assay. Nine months post-immunization, the percentages of individuals with levels of anti-Men-Ps IgG ≥ 2 µg/ml were comparable in both groups, with the exception of anti-Men-PsW135 IgG, which were significantly higher in group 2. The percentage of subjects doubling IgG levels at 9 months was significantly higher in group 1. The high baseline anti-Men-Ps antibody levels negatively influenced the response to revaccination, suggesting a feedback control of specific IgG. The calculated durability of anti-Men-Ps IgG was 2·5-4·5 years, depending on the Men-Ps, following a single vaccine dose. No interference by other vaccinations nor HLA alleles association with immune response were observed. This study confirms that Men-Ps vaccine in adults is immunogenic, even when administered repeatedly, and underlines the vaccine suitability for large-scale adult immunization programmes that the higher costs of conjugate vaccines may limit in developing countries.

Primary thyroid leiomyosarcoma: a case report and review of the literature.

Primary thyroid leiomyosarcoma (LMS) is an extremely rare tumor. We report a case of a 47-year-old male with a rapidly growing neck mass and disfagia. Preoperative investigations were diagnostic of anaplastic carcinoma. Total thyroidectomy with partial esophagectomy and dissection of right infrahyoid muscles was performed. Through histolological and immunohistochemical evaluations a primary thyroid high-grade LMS was diagnosed. At 2 months of follow-up a local recurrence was detected and consequently the patient was submitted to chemotherapy with partial response. He is still alive 9 months after surgery. Diagnosis of primary thyroid LMS is difficult due to its similarity to other more common thyroid tumors. To date, there is no standard therapy and prognosis is poor.

A genetic epidemiology study of congenital adrenal hyperplasia in Italy.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD-CAH) is an autosomal recessive disorder affecting steroidogenesis, due to mutations in CYP21A2 (6p21.3). 21OHD-CAH neonatal screening is based on 17-hydroxyprogesterone (17OHP) serum levels, showing high type I error rate and low sensitivity to mild CAH forms. Here, we used an epidemiological approach, which estimates the allelic frequency (q) of an autosomal recessive disorder using the proportion of homozygous patients, the mutational spectrum and the inbreeding coefficient in a sample of affected individuals. We applied this approach to 2 independent Italian cohorts of patients with both clinical and molecular diagnosis of 21OHD-CAH from mainland Italy (N = 240) and Sardinia (N = 53). We inferred q estimates of 2.87% and 1.83%, corresponding to a prevalence of 1/1214 and 1/2986, respectively. CYP21A2 mutational spectra were quite discrepant between the 2 cohorts, with V281L representing 74% of all the mutations detected in Sardinia vs 37% in mainland Italy. These findings provide an updated fine-grained picture of 21OHD-CAH genetic epidemiology in Italy and suggest the need for a screening approach suitable to the detection of the largest number of clinically significant forms of CAH.

High prevalence of papillary thyroid carcinoma in nodular Hashimoto's thyroiditis at the first diagnosis and during the follow-up.

BACKGROUND: The association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) remains to be elucidated. MATERIALS AND METHODS: A total of 484 HT patients were retrospectively subdivided into two groups: 243 without thyroid nodules, TNs (HTN-) and 241 with TNs (HTN+). Fine-needle aspiration cytology was available in 152 HTN+ patients. This group was compared to a group of 161 patients with nodular goiter (NG) without HT. Finally, 70 HTN+ and 37 NG patients underwent surgery. RESULTS: A very high prevalence of suspicious/malignant cytology (Thy 4-5) at the first diagnosis (38/124; 31%) and during the follow-up (6/28; 22%) was found in HTN+ group. In HTN- group, 22/130 (17%) patients developed TN, but none showed malignant features during the follow-up. HTN+ patients had higher prevalence of Thy 4-5 (44/152 = 28.9%) compared to NG patients (12/161 = 7.4%, p < 0.0001). Increased independent odds ratio (OR) for malignancy was conferred by serum TSH > 1.0 µUI/ml, [OR 1.93, 95% confidence interval (CI) 1.41-2.64, p < 0.0001], male sex (OR 3.44, CI 1.48-8.02, p = 0.004) and HT (OR 3.14; CI 1.08-9.31, p < 0.05). Malignant histology (mostly PTC) was confirmed higher in HTN+ (48/70, 68.6%) compared to NG (15/37, 40.5%; p < 0.05). Higher prevalence of extrathyroidal infiltration (24/48, 50%) and vascular invasion (25/48, 52%) was found in HTN+ vs NG (2/15, 1.3% p < 0.01), (3/16, 1.8% p < 0.05), respectively. CONCLUSIONS: This study confirms higher prevalence of suspicious/malignant cytology and PTC at histology in nodular HT compared to NG, without evidence of malignancy in non-nodular HT patients during the follow-up.

Recommendations for treatment of hypothyroidism with levothyroxine and levotriiodothyronine: a 2016 position statement of the Italian Society of Endocrinology and the Italian Thyroid Association.

Levothyroxine (L-T4) is recommended as lifelong replacement therapy for hypothyroidism. Recent clinical and experimental data support the addition of levotriiodothyronine (L-T3) treatment in some selected hypothyroid patients when their symptoms persist and their quality of life remains impaired despite adequate L-T4 monotherapy. An increase in L-T3 prescriptions has been recently observed in Italy due to availability of different L-T3 formulations, making it possible to clinicians to prescribe L-T3 alone or in combination with L-T4. The aim of the present position statement was to define the correct clinical indications, schedule, duration of treatment and contraindications of combined treatment with L-T4 and L-T3 in hypothyroid patients in an attempt to guide clinicians and to avoid potential adverse effects of overtreatment.

Recommendations for post-surgical thyroid ablation in differentiated thyroid cancer: a 2015 position statement of the Italian Society of Endocrinology.

UNLABELLED: Post-surgical ablation of thyroid remnant with radioactive iodine (RAI) in differentiated thyroid cancer (DTC) is aimed to destroy any thyroid remnant in the thyroid bed (remnant ablation) and any microscopic foci of cancer cells eventually present within the thyroid remnant (adjuvant therapy). The present text is an attempt to offer practice guidelines for the indication of thyroid ablation and the preparation of DTC patients considering the latest achievement in the field and the changing epidemiology of DTC observed in the last 10 years. METHODOLOGY: The executive committee of the Italian Society of Endocrinology appointed a task force of thyroid cancer expert including Nuclear Medicine Physicians and Endocrinologists to provide a consensus on the post-surgical ablation in thyroid cancer patients. The task force had no conflict of interest and had no commercial support. A number of specific topics were selected and the members selected relevant papers by searching in the Pubmed for articles published from 2000 to January 2015. Selected studies were categorized by level of evidence, and the recommendations were graded according to the level of evidence as high (A), moderate (B), or low (C).

Anterior pituitary autoantibodies in patients with type 1 diabetes mellitus: methodological problems and clinical correlations.

BACKGROUND: Anti-pituitary antibodies (APA) were described in patients with Type 1 Diabetes (T1D) but their prevalence and relevance remain controversial. MATERIALS AND METHODS: We evaluated the APA prevalence in Sardinian sera from 100 T1D patients, 70 Type 2 Diabetes (T2D) patients and 62 healthy controls, using indirect immunofluorescence on bovine pituitary sections. To compare two different substrates, we tested using bovine sections, further T1D patient sera (n = 11, from Pisa) previously analysed for APA on monkey sections, while some T1D Sardinian patient sera (n = 22) were tested on monkey sections. According to preliminary experiments, positivity were considered ≥1:200 and ≥1:20 for bovine and monkey substrates, respectively. RESULTS AND DISCUSSION: Using bovine sections, APA were detected in 7/100 Sardinian T1D patients (at 1:200 titer) and in none of the other Sardinian sera tested. When the T1D sera from Pisa were tested on bovine and the T1D Sardinian sera were tested on monkey, none of these sera showed corresponding positivity for APA. Pituitary hormone dysfunctions were not found in the 7 APA-positive Sardinian T1D patients. The present study shows that the presence of APA at low-titer is highly related to T1D but not associated with any pituitary dysfunction while the animal species used as substrate appears crucial. CONCLUSION: Further studies are needed to ascertain whether APA detected by different animal species may have different pathological relevance in T1D and/or whether APA in the long run may predict future anterior pituitary dysfunction.

Clinical models and biochemical predictors of VTE in lung cancer.

Venous thromboembolism (VTE) is a frequent complication of lung cancer and its treatment, especially in the advanced stages of disease. The risk of a pro-thrombotic state might increase through the activation of hemostasis, occurring both via the induction of a pro-coagulant activity and with platelet involvement, ultimately leading to the development of metastases. Despite the acknowledgement of an increased thrombophilic condition in cancer patients, and the experimental evidence that heparin compounds may have direct anticancer benefits, there is no univocal consent regarding VTE prevention in cancer outpatients receiving therapy. Thus, many authors highlighted the need for the development of stratification techniques to identify at-risk patients who might benefit from thromboprophylaxis. Clinical risk models were developed and validated, in order to assign high-risk patients to a proper thromboprophylaxis regimen that, however, might not be justified in all clusters. Besides, efforts have been devoted to identify candidate biomarkers that may be used in VTE risk assessment, although none has been recognized, so far, as a predictor for VTE in lung cancer patients. In this review, we will summarize the latest information concerning this very controversial topic, with focus on some of the proposed strategies to select the appropriate patients for prophylaxis.

Pituitary autoimmunity in patients with diabetes mellitus and other endocrine disorders.

OBJECTIVE: Pituitary autoimmunity is often found in association with other endocrine autoimmune or non-autoimmune diseases. Aim of the study was to assess the prevalence of serum pituitary antibodies (PitAb) in patients with Type 1 diabetes mellitus (T1DM) or Type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: In this casecontrol study 111 patients with T1DM, 110 patients with T2DM, and 214 healthy controls were enrolled in a tertiary referral center. Pituitary, thyroperoxidase, thyroglobulin, 21-hydroxylase, and parietal cell antibodies were assessed in all cases. Endocrine function was further assessed by basal hormone measurement and by dynamic tests, as well as a pituitary magnetic resonance imaging (MRI) was performed in those patients found positive for PitAb. RESULTS: PitAb prevalence was higher in T1DM (4 out of 111, 3.6%) than in T2DM (0 out of 110, p=0.045) and in healthy subjects (1 out of 214, 0.5% p=0.029). Prevalence of other autoimmune diseases was significantly higher in patients with T1DM (45 out of 111, 40.5%) when compared with patients with T2DM (18 out of 110 T2DM, 16.3%, p<0.001). Patients with T1DM and PitAb positivity were found with a pituitary lesion at MRI in 2 cases and pituitary dysfunction in one case. CONCLUSIONS: A significant association between pituitary autoimmunity and T1DM was found, in particular in subjects with one or more other endocrine autoimmune diseases.

Telomere/telomerase system impairment in circulating angiogenic cells of geriatric patients with heart failure.

BACKGROUND: The functional characteristics of circulating angiogenic cells (CACs) are impaired in congestive heart failure (CHF) patients, suggesting that CAC dysfunction could contribute to CHF pathogenesis. However, the underlying mechanisms are only partly unraveled. No data are currently available regarding telomere/telomerase system in CACs of CHF patients. METHODS: CACs were obtained from 80 subjects: 40 healthy control subjects (CTR) [median age (IQR), 80 (76-85 yrs)] and 40 patients affected by post-ischemic cardiomyopathy CHF [median age (IQR), 82 (77-89)]. CAC and leukocyte telomere length, assessed as T/S ratio, and telomerase (TERT) activity were determined in all the enrolled subjects. Specificity and sensitivity of CAC and leukocyte T/S in discriminating between CHF and CTR were evaluated using Receiver Operator Characteristic (ROC) curve analysis and reported as AUC values. CD34+/VEGFR2+ number and pro-inflammatory cytokines plasma levels, such as IL-6 and TNF-α, were also measured. RESULTS: CAC T/S and TERT activity were significantly reduced in CHF patients compared to CTR subjects. In leukocytes, only a significant T/S reduction was observed. AUC values were higher for CAC T/S with respect to leukocyte T/S (AUC=0.89, and AUC=0.73, P<0.01, respectively). In multivariate analysis, leukocyte T/S, CAC T/S, CAC TERT activity and NT-proBNP levels were confirmed as parameters significantly associated with CHF. CD34+/VEGFR2+ number, IL-6 and TNF-α plasma levels were significantly increased in CHF patients. CONCLUSIONS: CACs from CHF patients are characterized by telomere/telomerase system impairment, providing new insight into the clinical relevance of CACs in CHF pathogenesis.

Both thyroid autoimmunity and increased serum TSH are independent risk factors for malignancy in patients with thyroid nodules.

AIM: To assess the relevance of thyroid autoimmunity and TSH as risk factors for malignancy in thyroid nodules (TN). SUBJECTS AND METHODS: Retrospective analysis on 2053 patients with single/prevalent TN submitted to fine needle aspiration cytology (FNAC). Anti-thyroid autoantibodies (ATA) [anti-thyroperoxidase (TPOAb), anti-thyroglobulin (TgAb)] and TSH were measured. Cytology was classified as benign (class II), indeterminate (class III), and suspicious or malignant (class IV). Histology was available in 301 patients. Associations of malignancy with independent variables were determined by multivariate logistic regression analysis. RESULTS: Higher prevalence of class IV (14.2% vs 6.8%: p<0.001) and class III (23.5% vs 17.1%: p<0.001) were found in ATA+ vs ATA- TN. Histology confirmed increased prevalence of cancer in ATA+ (p<0.05) TN and in those with diffuse lymphocytic thyroid infiltration (p<0.05). Interestingly, the prevalence of malignancies observed in operated class III nodules was strikingly lower in ATA+ (1/20, 5%), than in ATA- patients (34/67, 50.7%; p<0.001). Increased independent odds ratio (OR) for malignancy was conferred by any ATA [OR 2.21; 95% confidence interval (CI)=1.49-3.29, p<0.0001]; TPOAb (OR 2.15; CI=1.42-3.25, p<0.0001) and TgAb (OR 1.67; CI=1.05-2.67, p<0.05), by serum TSH>1.0 µUI/ml (OR 1.95; CI=1.01-3.76, p<0.05), and by young age (10-29 yr: OR 2.09; CI=1.02-4.26, p<0.05). A formula was calculated to assess the relative contribution of ATA, TSH, and age to the risk of TN malignancy. CONCLUSIONS: Both thyroid autoimmunity and increased TSH represent independent risk factors for TN malignancy.

Intraoperative parathyroid hormone assay during focused parathyroidectomy for primary hyperparathyroidism: is it really mandatory?

AIM: Intraoperative parathyroid hormone (PTH) assay has become an essential tool in focused parathyroid surgery. The aim of this study was to evaluate the present role of intraoperative PTH monitoring during focused parathyroidectomy for primary hyperparathyroidism in our experience. METHODS: One hundred sixty-one patients were submitted to focused parathyroidectomy with rapid intraoperative Parathyroid hormone assay monitoring. RESULTS: A >50% decrease of PTH occurred in 147 patients (91.3%); in this group persistent hypercalcemia was found in 1; in the remaining 14 (8.7%) values of PTH decreased less than 50% and bilateral neck exploration was performed. An additional pathologic parathyroid was removed in 8 cases, a third in one; in the other five further neck exploration was negative and in four of these persistent postoperative hypercalcemia was demonstrated. In 136 patients >50% decrease of PTH was obtained after 10 minutes, in the other 11 after 20. The overall operative success of the patients was 96.9% with a 5.6% incidence of multiglandular disease. Intraoperative parathormone monitoring changed the operative management in 8.7% of cases. Intraoperative parathormone monitoring was accurate in predicting operative success or failure in 98.7% of patients, with a sensitivity of 99.3%, a specificity of 92.8%, a positive predictive value of 99.3% and a negative predictive value of 92.8%. DISCUSSION AND CONCLUSION: The measurement of intraoperative PTH represents a useful tool to assist the surgeon during parathyroid surgery and its routine use significantly improves cure rates of focused parathyroidectomy. We believe that the use intraoperative PTH is still mandatory in focused parathyroidectomy avoiding relapses and consequent reintervention.