A novel likely pathogenetic variant p.(Cys235Arg) of the MEN1 gene in multiple endocrine neoplasia type 1 with multifocal glucagonomas.

PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine syndrome caused by pathogenic variants in MEN1 tumor suppressor gene. Diagnosis is commonly based on clinical criteria and confirmed by genetic testing. The objective of the present study was to report on a MEN1 case characterized by multiple pancreatic glucagonomas, with particular concern on the possible predisposing genetic defects. METHODS: While conducting an extensive review of the most recent scientific evidence on the unusual glucagonoma familial forms, we analyzed the MEN1 gene in a 35-year-old female with MEN1, as well as her son and daughter, using Sanger and next-generation sequencing (NGS) approaches. We additionally explored the functional and structural consequences of the identified variant using in silico analyses. RESULTS: NGS did not show any known pathogenic variant in the tested regions. However, a new non-conservative variant in exon 4 of MEN1 gene was found in heterozygosity in the patient and in her daughter, resulting in an amino acid substitution from hydrophobic cysteine to hydrophilic arginine at c.703T > C, p.(Cys235Arg). This variant is absent from populations databases and was never reported in full papers: its characteristics, together with the high specificity of the patient's clinical phenotype, pointed toward a possible causative role. CONCLUSION: Our findings confirm the need for careful genetic analysis of patients with MEN1 and establish a likely pathogenic role for the new p.(Cys235Arg) variant, at least in the rare subset of MEN1 associated with glucagonomas.

Tumor enlargement in adrenal incidentaloma is related to glaucoma: a new prognostic feature?

PURPOSE: The uncertainty on the management of small adrenal incidentalomas (AIs) still represents a challenge in real clinical practice. Considering the lack of knowledge on risk factors implicated in tumour enlargement, the aim of this study was to identify risk factors for morphological changes during follow-up of adrenal incidentalomas (AIs). METHODS: We retrospectively evaluated demographic, clinical, radiological and biochemical parameters of 153 AIs (2007-2021). Patients with histological diagnosis of metastases or pheochromocytoma were excluded. To detect risk factors for tumor enlargement, diseases associated with AIs were included if their prevalence was higher than 2%. Patients were divided into two groups (A: radiological stability; B: tumor enlargement defined as > 5 mm/year in the main diameter). RESULTS: Group A: 89.5% and group B: 10.5%, mean follow-up 38.6 ± 6.9 months (range 6-240). Tumor enlargement when occurred was within 36 months of follow-up. In group B high body weight (p < 0.03), dehydroepiandrosterone sulfate (DHEAS) (p < 0.05) and direct renin concentration (DRC) (p < 0.04) were higher than group A, while aldosterone levels were lower; moreover, considering comorbidities, glaucoma and dysglycemia (p < 0.01 for both) had higher prevalence in group B. Glaucoma and dysglycemia were independent predictors of enlargement. Patients affected by glaucoma, atrial fibrillation, dysglycemia had a lower dimensional change-free survival than non-affected. CONCLUSIONS: Glaucoma might be a novel risk factor for AI enlargement. If subtle undetectable cortisol hypersecretion has a role is a topic for further research.

Transition in endocrinology: predictors of drop-out of a heterogeneous population on a long-term follow-up.

PURPOSE: To evaluate: (1) clinical and epidemiological characteristics of outpatients transitioned from Pediatrics Endocrine (PED) to Adult Endocrine Department (AED) in a tertiary center; (2) transition process features, and predictors of drop-out. METHODS: Demographic, clinical, and transition features of 170 consecutive patients with pediatric onset of chronic endocrine or metabolic disease (excluded type 1 diabetes) who transitioned from PED to AED (2007-2020) were retrospective evaluated. RESULTS: The age at transition was 18.4 ± 4 years (F:M = 1.2: 1), and mean follow-up 2.8 years. The population was heterogeneous; the most (69.4%) was affected by one, 24.1% by two or more endocrine diseases, 6.5% were followed as part of a cancer survivor's surveillance protocol. The comorbidity burden was high (37, 20.6, and 11.2% of patients had 2, 3, 4, or more diseases). The number of visits was associated with the number of endocrine diseases and the type of them. Adherent subjects had a higher number of comorbidities. Thyroid disorders and more than one comorbidity predicted the adherence to follow-up. Having performed one visit only was predictive of drop-out, regardless of the pathology at diagnosis. CONCLUSION: This is the first study that analyzed a specific transition plan for chronic endocrine diseases on long-term follow-up. The proposed "one-size-fits-all model" is inadequate in responding to the needs of patients. A structured transition plan is an emerging cornerstone.

Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients.

PURPOSE: Registered trials and real-world evidence (RWE) studies provided evidence on the efficacy of once-weekly (OW) semaglutide on hyperglycaemia and cardiovascular risk factors as add-on or de-novo treatment in type 2 diabetes (T2D). METHODS: In a retrospective analysis of electronic data files from 258 T2D patients, this RWE study aimed to explore the impact of OW semaglutide on biochemical and anthropometric outcomes after 6 and 12 months in patients receiving at least one prescription of OW semaglutide between September 2019 and May 2021. RESULTS: During the study period, 154 and 56 consecutive patients completed the 6 and 12 months of OW semaglutide treatment. HbA1c levels decreased by -1.02±0.1% after 6 months and -1.1±0.1% after 12 months of OW semaglutide (p<0.0001 for both). At these time-points, HbA1c values were <7% in 61% and 57% of cases. HbA1c reduction was greater in patients with higher baseline HbA1c levels and it occurred irrespective of gender, age, insulin therapy and complications. The residual number of cases with HbA1c ≥9% by the study end was low (5.3% vs 18.9% at baseline). Weight loss occurred in 73.5% and 78.1% of cases and, compared to baseline, it was ≥5% in 21.2- 25.4% and ≥10% in 6.8-18.2% after 6 and 12 months, respectively. Significant predictors of HbA1c reduction after 6 months of OW semaglutide treatment were baseline HbA1c (p<0.0001), bodyweight reduction (p<0.0001) and disease duration (p<0.001), while baseline HbA1c was the only predictor of HbA1c response after 12 months (p<0.0001). Reported adverse events were consistent with the known safety profile of semaglutide. CONCLUSIONS: Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients.

Clinical and radiological presentation of parasellar ectopic pituitary adenomas: case series and systematic review of the literature.

PURPOSE: Parasellar ectopic pituitary adenomas (pEPAs) are extremely rare tumors located out of the sella turcica. PEPAs are heterogeneous entities in terms of anatomical localization and secretion of anterior pituitary hormones. METHODS: Multicenter retrospective study. Clinical charts' consultation of patients diagnosed with parasellar lesions, to identify all subjects fulfilling the diagnostic criteria of parasellar EPAs. Systematic review of the literature focused on the medical management of prolactin-secreting pEPAs and on the prevalence of radiological bone invasion in pEPAs. RESULTS: We identified four cases of pEPAs: (1) 54-year-old female with a prolactin-secreting suprasellar EPA successfully treated with cabergoline; (2) 74-year-old male with a non-functioning EPA of the sphenoidal sinus treated with endoscopic transsphenoidal surgery; (3) 75-year-old female with a giant lesion of the skull base (maximum diameter 7.2 cm) diagnosed as a non-functioning EPA after biopsy; (4) 49-year-old male with a silent corticotroph EPA of the sphenoidal sinus and clivus. Three out of four cases had radiological evidence of invasion of the surrounding bone structures. A systematic review of the literature highlighted that medical therapy can be effective in prolactin-secreting pEPAs. Overall, we found mention of local invasiveness in 65/147 cases (44.2%), confirmed by radiological signs of bone invasion/erosion. CONCLUSION: Our experience confirms the heterogeneity of pEPAs in terms of clinical and radiological presentation, as well as hormone secretion. PEPAs show a high frequency of radiological bone invasion, though similar to that of sellar pituitary adenomas. Although extremely rare, pEPAs need to be considered in the differential diagnosis of parasellar lesions.

A simple and rapid approach for human herpesvirus type 8 subtype characterization using single base extension.

Sequence analysis of the ORFK1 of human herpesvirus type 8 (HHV-8) allows the identification of six major subtypes (A-F), which are related to human migrations and the clinical progression of Kaposi's sarcoma. Sequencing and subsequent phylogenetic analysis of ORFK1 is considered to be the most reliable method for HHV-8 genotyping. However, it exhibits challenges and limitations. Herein, we designed and validated a single base extension (SBE) protocol for characterization of HHV-8 ORFK1 subtypes. A nested polymerase chain reaction (PCR) protocol was carried out to amplify a small 294-bp PCR product encompassing four single nucleotide polymorphisms at positions 360, 406, 465 and 527 of the HHV-8 genome. Finally, a multiplex SBE technique was developed and validated in 20 samples previously genotyped by phylogenetic analysis. The patterns obtained in this reaction could successfully discriminate between ORFK1 subtypes. The typing results obtained completely matched with those of the 'gold standard' method in all analysed samples. This method can reliably identify HHV-8 subtypes A, B and C, which are the most prevalent ones worldwide, and the remaining subtypes (D, E and F). SBE can be useful as an efficient, rapid and low-cost screening method for viral genotyping in a single tube, particularly samples with low-quality DNA, and with easy data interpretation.

Does Maintenance of Pulmonary Blood Flow Pulsatility at the Time of the Fontan Operation Improve Hemodynamic Outcome in Functionally Univentricular Hearts?

It is unclear whether residual anterograde pulmonary blood flow (APBF) at the time of Fontan is beneficial. Pulsatile pulmonary flow may be important in maintaining a compliant and healthy vascular circuit. We, therefore, wished to ascertain whether there was hemodynamic evidence that residual pulsatile flow at time of Fontan promotes clinical benefit. 106 consecutive children with Fontan completion (1999-2018) were included. Pulmonary artery pulsatility index (PI, (systolic pressure-diastolic pressure)/mean pressure)) was calculated from preoperative cardiac catheterization. Spectral analysis charted PI as a continuum against clinical outcome. The population was subsequently divided into three pulsatility subgroups to facilitate further comparison. Median PI prior to Fontan was 0.236 (range 0-1). 39 had APBF, in whom PI was significantly greater (median: 0.364 vs. 0.177, Mann-Whitney p < 0.0001). There were four early hospital deaths (3.77%), and PI in these patients ranged from 0.214 to 0.423. There was no correlation between PI and standard cardiac surgical outcomes or systemic oxygen saturation at discharge. Median follow-up time was 4.33 years (range 0.0273-19.6), with no late deaths. Increased pulsatility was associated with higher oxygen saturations in the long term, but there was no difference in reported exercise tolerance (Ross), ventricular function, or atrioventricular valve regurgitation at follow-up. PI in those with Fontan-associated complications or the requiring pulmonary vasodilators aligned with the overall population median. Maintenance of pulmonary flow pulsatility did not alter short-term outcomes or long-term prognosis following Fontan although it tended to increase postoperative oxygen saturations, which may be beneficial in later life.

First but not second postoperative day growth hormone assessments as early predictive tests for long-term acromegaly persistence.

PURPOSE: Postoperative assessment of acromegaly activity is typically performed at least 3 months after neurosurgery (NS). Few studies have evaluated the use of early postoperative growth hormone (GH) levels as a test to predict short- and long-term remission of acromegaly. Our objective was to evaluate the diagnostic performance of serum random GH on a postoperative day one (D1-rGH) and two (D2-rGH), particularly in predicting long-term disease persistence. MATERIALS AND METHODS: Forty-one subjects with acromegaly who were undergoing NS were enrolled (mean age ± SD 47.4 ± 13.1 years at diagnosis; women 54%; macroadenomas 71%). The final assessment of disease activity was performed one year after NS. ROC curves were used to evaluate the diagnostic performance of D1-rGH and D2-rGH. RESULTS: After a 1-year follow-up, the overall remission rate was 55%. ROC analysis identified an optimal D1-rGH cut-off value of 2.1 ng/mL for diagnosing long-term disease persistence (55.6% SE; 90.9% SP). The cut-off point became 2.5 ng/mL after maximizing specificity for disease persistence (yielding a 100% positive predictive value) and 0.3 ng/mL after maximizing sensitivity for disease remission. The optimal D2-rGH cut-off value was 0.6 ng/mL (81.8% SE; 50% SP); the cut-off point became 2.9 ng/mL after maximizing specificity and 0.1 ng/mL after maximizing sensitivity, with no clinical utility. CONCLUSIONS: D1-rGH could be a highly specific test for the early diagnosis of long-term acromegaly persistence, which is predicted by a value > 2.5 ng/mL with a great degree of certainty. The diagnostic performance of D2-rGH was insufficient. Further research is required to validate these preliminary results prior to modifying the postoperative management of acromegaly.

Psychological Stress and Cancer: New Evidence of An Increasingly Strong Link.

To date stress, a highly complex process that disrupts homeostasis and involves environmental and psychosocial factors, is considered as one of the most crucial factor that affects our daily life, especially urban dweller's life. Clinical and experimental studies widely support the notion that adrenergic stimulation due to chronic stress affects inflammation and metabolism. In this work, supported by several recent scientific evidences, we show how stress plays a positive role in cancer initiation, progression and cancer metastasis, a negative role for anti-tumor immune function and therapy response. Understanding the intricacies of this interaction could provide an additional help on how act in cancer prevention and therapy.

Correction to: Transsphenoidal surgery for pituitary adenomas: early results from a single center.

Unfortunately in the original publication, the affiliation of the author Paolo Marzullo was incorrect. The author inadvertently missed out to include his second affiliation.

The cardiac proteome in patients with congenital ventricular septal defect: A comparative study between right atria and right ventricles.

Right ventricle (RV) remodelling occurs in neonatal patients born with ventricular septal defect (VSD). The presence of a defect between the two ventricles allows for shunting of blood from the left to right side. The resulting RV hypertrophy leads to molecular remodelling which has thus far been largely investigated using right atrial (RA) tissue. In this study we used proteomic and phosphoproteomic analysis in order to determine any difference between the proteomes for RA and RV. Samples were therefore taken from the RA and RV of five infants (0.34 ±â€¯0.05 years, mean ±â€¯SEM) with VSD who were undergoing cardiac surgery to repair the defect. Significant differences in protein expression between RV and RA were seen. 150 protein accession numbers were identified which were significantly lower in the atria, whereas none were significantly higher in the atria compared to the ventricle. 19 phosphorylation sites (representing 19 phosphoproteins) were also lower in RA. This work has identified differences in the proteome between RA and RV which reflect differences in contractile activity and metabolism. As such, caution should be used when drawing conclusions based on analysis of the RA and extrapolating to the hypertrophied RV. SIGNIFICANCE: RV hypertrophy occurs in neonatal patients born with VSD. Very little is known about how the atria responds to RV hypertrophy, especially at the protein level. Access to tissue from age-matched groups of patients is very rare, and we are in the unique position of being able to get tissue from both the atria and ventricle during reparative surgery of these infants. Our findings will be beneficial to future research into heart chamber malformations in congenital heart defects.

Transsphenoidal surgery for pituitary adenomas: early results from a single center.

OBJECTIVE: To evaluate early results of transsphenoidal surgery for pituitary adenomas. DESIGN: Retrospective evaluation of 90 consecutive patients undergoing endoscopic pituitary adenoma surgery (2007-2016) at "Maggiore della Carità" Hospital in Novara, Italy. Age at diagnosis, sex, symptoms at presentation, hormonal and radiological data, complications of surgery, and short-term follow-up information were collected. RESULTS: The majority of patients were male (M/F: 1.5/1, mean age at diagnosis 62.1 ± 1.5 years mean ± SEM). Most patients (91.1%) presented with a macroadenoma (27.4 mm ± 1.1 mm mean ± SEM), while 77.8% were non-functioning pituitary adenomas. Clinical presentations related to mass effect were visual impairment (74.0%) and/or hypopituitarism (55.1%). The main surgery complication was insipidus diabetes (12.2%), followed by cerebral hemorrhage (4.4%), cerebrospinal fluid (CSF) leaks (4.4%), syndrome of inappropriate antidiuresis (SIAD) (2.2%), and epistaxis (2.2%); only one patient died because of stroke. Risk of complications was not associated with tumor size (OR = 0.588, 95% CI 0.967-1.081, p = 0.443). Visual function improved in 70.6% of patients, while recovery of normal pituitary function occurred in 48.1%. Early neuroimaging studies demonstrated no residual tumor in 27.6% of patients. Invasion of cavernous sinus (OR = 3.293, 95% CI 0.897-16.738, p = 0.05) and maximum tumor diameter (OR = 6.857, 95% CI 1.039-1.309, p < 0.01) were associated with an unfavorable surgical outcome. CONCLUSIONS: Transsphenoidal endoscopic surgery for pituitary adenomas is safe and is frequently followed by improvement in visual symptoms, whereas recovery of pituitary function is less common. In our patients, complete surgical removal of adenomas is comparable to that of other series, but further investigations will be necessary to clarify the long-term risk of tumor recurrence.

Therapeutic Strategies and Clinical Outcome in Papillary Thyroid Microcarcinoma: A Multicenter Observational Study.

PURPOSE: Papillary thyroid microcarcinoma (MPTC) has an excellent prognosis. We aimed to evaluate the evolution of therapeutic strategies over time and the clinical outcome of MPTC. METHODS: In this retrospective multicenter observational study in a northwest Italian region, patients with intrathyroidal, unifocal tumor ≤1 cm in size, incidentally found at histology or preoperative cytology diagnosis, were included. Exclusion criteria were a previous head-and-neck irradiation and/or node metastases. RESULTS: From 1985 to 2012, 437 patients had an MPTC diagnosis, which was incidental in 85% and preoperative in 15%. Patients with a preoperative diagnosis were younger at the time of diagnosis (47.6 ± 12.7 years, p < 0.01) and had a larger tumor (7.0 ± 2.5 mm, p < 0.0001) than patients with an incidental diagnosis (age 52 ± 13.5 years, size 4.4 ± 2.8 mm), but there were no differences in clinical outcome between both groups. We observed a significant (p < 0.001) reduction in radioiodine remnant ablation during the years. TSH levels were: <0.1 mIU/l in 27.5%, 0.1-0.5 mlU/l in 33.7%, 0.5-2.5 mlU/l in 32.6%, 2.5-4.2 mlU/l in 3.9%, and >4.2 mlU/l in 2.3% of patients. Six patients (1.37%) had nodal recurrence; 5 of them were cured after therapy. MPTC-linked mortality was null. CONCLUSIONS: We confirmed the favorable clinical outcome of MPTC. Despite the reduction in radioiodine ablation, overtreatment of MPTC is still observed.

Topical hemostasis in laparoscopic surgery.

A major goal during any surgical intervention is minimization of blood loss, which reduces the need for blood transfusion. In open surgery, the possibility for the surgeon to use the hands directly in contact with the bleeding tissues for hemostasis, makes mechanical methods, such as compression, ligatures or sutures, important to achieve proper hemostasis. In laparoscopic surgery, where the intervention is performed by means of small incisions through which the surgeon's hand cannot directly achieve the tissues, the problem of hemostasis is critical and needs more attention. Either in open or in laparoscopic surgery, significant bleeding during surgery is controlled through vessel ligation, suturing, and electrocautery. Topical hemostatic agents are useful adjuncts to surgical hemostasis for controlling non-specific bleeding. The introduction of different devices and topical agents has made possible to perform more complex interventions also in laparoscopy. The Authors discuss about the type, the field of application, the side effects of the hemostatic devices and of the topical hemostatic agents.

Salvage image-guided intensity modulated or stereotactic body reirradiation of local recurrence of prostate cancer.

OBJECTIVE: To retrospectively evaluate external beam reirradiation (re-EBRT) delivered to the prostate/prostatic bed for local recurrence, after radical or adjuvant/salvage radiotherapy (RT). METHODS: 32 patients received re-EBRT between February 2008 and October 2013. All patients had clinical/radiological local relapse in the prostate or prostatic bed and no distant metastasis. re-EBRT was delivered with selective RT technologies [stereotactic RT including CyberKnife(TM) (Accuray, Sunnyvale, CA); image-guidance and intensity-modulated RT etc.]. Toxicity was evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Biochemical control was assessed according to the Phoenix definition (NADIR + 2 ng ml(-1)). RESULTS: Acute urinary toxicity: G0, 24 patients; G1, 6 patients; G2, 2 patients. Acute rectal toxicity: G0, 28 patients; G1, 2 patients; and G2, 1 patient. Late urinary toxicity (evaluated in 30 cases): G0, 23 patients; G1, 6 patients; G2, 1 patient. Late renal toxicity: G0, 25 patients; G1, 5 patients. A mean follow-up of 21.3 months after re-EBRT showed that 13 patients were free of cancer, 3 were alive with biochemical relapse and 12 patients were alive with clinically evident disease. Four patients had died: two of disease progression and two of other causes. CONCLUSION: re-EBRT using modern technology is a feasible approach for local prostate cancer recurrence offering 2-year tumour control in about half of the patients. Toxicity of re-EBRT is low. Future studies are needed to identify the patients who would benefit most from this treatment. ADVANCES IN KNOWLEDGE: Our series, based on experience in one hospital alone, shows that re-EBRT for local relapse of prostate cancer is feasible and offers a 2-year cure in about half of the patients.

Hormone replacement therapy, renal function and heart ultrasonographic parameters in postmenopausal women: an observational study.

BACKGROUND AND AIM: A certain degree of impaired kidney function is related to an increased cardiovascular risk. The cardiovascular protection exerted in the postmenopausal state by the hormone replacement therapy (HRT) is debated. No studies have so far explored the relationship between menopause, renal function and cardiovascular risk profile in healthy menopausal women in relation with HRT. SUBJECTS AND METHODS: A total of 362 postmenopausal healthy women with normal albumin excretion rate were recruited and divided into two groups (HRT+ and HRT-) according to the presence or absence of HRT. All participants underwent a complete routine biochemical analyses and an echocardiogram. RESULTS: Clinical characteristics of the two groups were similar, but HRT+ showed a significantly higher estimated glomerular filtration rate (GFR; by CKD-EPI formula). Regarding the heart ultrasonography, HRT+ had a significantly lower size of the aortic root and left atrium diameter (p = 0.038 and p = 0.012, respectively); no differences were found in the ejection fraction and Left Ventricular Mass Index (LVMI). In the whole study group, eGFR correlated inversely with LVMI and with the size of the aortic root (both p < 0.0001), being GFR the only determinant of the former by a stepwise regression. Dividing the study population according to an eGFR cut-off (> 80 and < 80 ml/min/1.73 m(2)); > 80 women, in comparison with < 80, showed a significantly lower LVMI and lower size of aortic bulb, further reduced in the HRT+. CONCLUSION: In a cohort of healthy, drug-naïve, postmenopausal women, HRT seems to positively affect glomerular filtration and is associated with lower values of left ventricular mass and aortic root size, thus offering a further mechanism through female hormones exert cardioprotection.

Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism.

OBJECTIVE: Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients. DESIGN: Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated. RESULTS: The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (p<0.01) and altered glucose metabolism (p<0.005) with respect to non hypopituitaric patients. In particular, triglycerides (p<0.05) and HOMA-IR (p<0.02) were higher in hypopituitaric TBI patients. CONCLUSIONS: We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle.

Incidental cancer in patients surgically treated for benign thyroid disease. Our experience at a single institution.

Increased incidence of incidental cancer in patients operated for benign thyroid disease has been reported. We report our experience about incidental thyroid cancer (ITC) in order to better characterize this nosologic entity. Between 2001 and 2009 a total of 568 patients underwent surgery for benign thyroid disease. Patients with preoperative cytology undetermined or positive for malignancy were excluded. The most frequent indication for surgery was multinodular or diffuse nontoxic goiter. We performed total thyroidectomy in 499 cases and emithyroidectomy in 69 cases. Final histology revealed ITC in 53 patients (9.3%): 44 had papillary carcinoma (20 classic variant and 24 follicular variant), 4 follicular carcinoma, 4 medullary carcinoma and 1 primitive thyroid paraganglioma. The preoperative diagnosis was multinodular or diffuse goiter in 45 cases of ITC and uninodular goiter in 8 cases. We performed total thyroidectomy in 46 case, emithyroidectomy in 4 patients with past history of lobectomy, emithyroidectomy in 3 patients with following radicalization and central neck dissection. In 14 patients the tumor was multifocal and in 12 of these patients the tumor foci were bilateral. The lesion was a microcarcinoma in 34 cases. Mean diameter of the ITC was 1.14 cm. We retrospectively reconsidered the results of preoperative ultrasound examinations in relation to the exact position of the tumor in the specimens and we found a statistically significant association between echogenicity and papillary histotype. Twenty-six patients were followed up at our Hospital. The mean follow-up period was 38.2 months. A relapse was observed in 3/26 patients. Incidental thyroid cancer in patients operated for benign disease has its own surgical and oncological relevance. A correct preoperative assessment, with a careful selection of nodules for fine-needle aspiration cytology on the basis of ultrasound pattern, could better address the choice of surgical procedure. The non irrelevant incidence of incidental thyroid cancer, the eventuality of multifocality and bilaterality and the possible occurrence of relapse, support that total thyroidectomy without residuum is a valuable option for treating benign thyroid conditions such as multinodular goitre. When an incidental cancer is diagnosed after emithyroidectomy, a radicalization with central neck dissection could be considered. We suggest that natural history of papillary microtumors and the correct surgical approach for these lesions could be better defined with a more extensive use of "Porto proposal" criteria.

Radioiodine therapy of hyperfunctioning thyroid nodules: usefulness of an implemented dose calculation algorithm allowing reduction of radioiodine amount.

AIM: Radioiodine is a common option for treatment of hyperfunctioning thyroid nodules. Due to the expected selective radioiodine uptake by adenoma, relatively high "fixed" activities are often used. Alternatively, the activity is individually calculated upon the prescription of a fixed value of target absorbed dose. We evaluated the use of an algorithm for personalized radioiodine activity calculation, which allows as a rule the administration of lower radioiodine activities. METHODS: Seventy-five patients with single hyperfunctioning thyroid nodule eligible for 131I treatment were studied. The activities of 131I to be administered were estimated by the method described by Traino et al. and developed for Graves'disease, assuming selective and homogeneous 131I uptake by adenoma. The method takes into account 131I uptake and its effective half-life, target (adenoma) volume and its expected volume reduction during treatment. A comparison with the activities calculated by other dosimetric protocols, and the "fixed" activity method was performed. 131I uptake was measured by external counting, thyroid nodule volume by ultrasonography, thyroid hormones and TSH by ELISA. RESULTS: Remission of hyperthyroidism was observed in all but one patient; volume reduction of adenoma was closely similar to that assumed by our model. Effective half-life was highly variable in different patients, and critically affected dose calculation. The administered activities were clearly lower with respect to "fixed" activities and other protocols' prescription. CONCLUSION: The proposed algorithm proved to be effective also for single hyperfunctioning thyroid nodule treatment and allowed a significant reduction of administered 131I activities, without loss of clinical efficacy.