Evaluation of a large set of patients with Autoimmune Polyglandular Syndrome from a single reference centre in context of different classifications.

PURPOSE: To characterize patients with APS and to propose a new approach for their follow-up. Query ID="Q1" Text="Please check the given names and familynames." METHODS: Monocentric observational retrospective study enrolling patients referred to the Outpatients clinic of the Units of Endocrinology, Diabetology, Gastroenterology, Rheumatology and Clinical Immunology of our Hospital for Autoimmune diseases. RESULTS: Among 9852 patients, 1174 (11.9%) [869 (73.9%) female] were diagnosed with APS. In 254 subjects, the diagnosis was made at first clinical evaluation (Group 1), all the other patients were diagnosed with a mean latency of 11.3 ± 10.6 years (Group 2). Group 1 and 2 were comparable for age at diagnosis (35.7 ± 16.3 vs. 40.4 ± 16.6 yrs, p = .698), but different in male/female ratio (81/173 vs 226/696, p = .019). In Group 2, 50% of patients developed the syndrome within 8 years of follow-up. A significant difference was found after subdividing the first clinical manifestation into the different outpatient clinic to which they referred (8.7 ± 8.0 vs. 13.4 ± 11.6 vs. 19.8 ± 8.7 vs. 7.4 ± 8.1 for endocrine, diabetic, rheumatologic, and gastroenterological diseases, respectively, p < .001). CONCLUSIONS: We described a large series of patients affected by APS according to splitters and lumpers. We propose a flowchart tailored for each specialist outpatient clinic taking care of the patients. Finally, we recommend regular reproductive system assessment due to the non-negligible risk of developing premature ovarian failure.

Radiofrequency ablation of functioning and non-functioning thyroid nodules: a single institution 12-month survey.

PURPOSE: Radiofrequency (RF) treatment has played an increasing role in the management of benign thyroid nodules in recent years. The aim of this retrospective study was to evaluate the efficacy of RF treatment on volume reduction in functioning and non-functioning thyroid nodules. PATIENTS AND METHODS: We reviewed the medical records of patients who had thyroid nodule RF ablation at our department between August 2017 and May 2018. Patients underwent a periodical follow-up with ultrasound examinations and thyroid function tests at 1, 3, 6 and 12 months from RF. Complications were assessed using the reporting standards of Interventional societies. RESULTS: 43 patients were submitted to thyroid nodule RF ablation treatment. Patients were subdivided into two groups, those with functioning (17 patients) or non-functioning nodules. At baseline (i.e. pre-RF treatment), the two groups of patients were superimposable for gender, age, BMI, nodule volume and maximum nodule diameter. The volume reduction of all 43 nodules was 69.1 ± 17.3% (range 26.0-94.5%) with no difference between functioning and non-functioning lesions (72.9 ± 18.1% vs 66.7 ± 16.7%, p = 0.254). A total energy delivered per nodule was 16.5 ± 6.8 kJ, with no difference between functioning and non-functioning lesions (14.5 ± 7.2 kJ vs. 18.2 ± 6.3 kJ, p = 0.083, respectively). No major complications were observed. CONCLUSIONS: Radiofrequency ablation is a clinically effective and safe outpatient treatment in patients with benign nodules. In particular, we showed that a single treatment is effective in restoring euthyroidism in patients with autonomously functioning thyroid nodules.

TSH evaluation in hypothyroid patients assuming liquid levothyroxine at breakfast or 30 min before breakfast.

PURPOSE: To compare TSH levels of hypothyroid patients treated with liquid LT4 at breakfast or 30 min before breakfast. PATIENTS AND METHODS: Subjects, aged 18-75 years old, were eligible if they presented hypothyroidism, due to Hashimoto's thyroiditis or after thyroidectomy for proven benign goiter. Seven hundred ninety-eight patients were recruited and enrolled in the study. Thirty-seven subjects withdrew from the trial. A total of 761 patients (mean age 46.2 ± 10.8 years) completed the study. The starting dose of LT4 was determined through clinical judgment, taking into account TSH levels, estimated residual thyroid function, age, body weight and comorbidities. All patients underwent TSH, fT4, and fT3 evaluation to verify achievement of euthyroidism with their initial fasting state assumption of LT4 after 8 weeks of therapy. If euthyroidism was not achieved, an appropriately adjusted LT4 dose was administered for 8 weeks, after which thyroid function parameters were checked again. If euthyroidism was achieved, the patients were asked to take LT4 at breakfast and hormone levels were checked again after 6 months. RESULTS: At the end of the study period, no significant differences in serum TSH level were observed whether LT4 was ingested at breakfast or 30 min prior in a fasting state: 2.61 ± 1.79 vs. 2.54 ± 1.86 mIU/L, respectively (p = 0.455). CONCLUSIONS: This study confirms in a large set of patients that a liquid LT4 formulation can be taken directly at breakfast and potentially improve therapeutic compliance.

Complications after fine-needle aspiration cytology: a retrospective study of 7449 consecutive thyroid nodules.

Although fine-needle aspiration (FNA) cytology of thyroid nodules is invasive, it is simple, reliable, safe, and well-accepted by patients. Local pain and minor haematomas are the most common complications, and serious ones are rare. We report the complications associated with ultrasound-guided FNA of 7449 thyroid nodules in a series of 6323 patients (5121 women and 1202 men) treated between January 2007 and March 2016 at our institution. We reviewed their medical and imaging records, and recorded the number and type of complications, time of detection, time to recovery, management, and permanent consequences. Ten patients (0.15%) had complications, which included a focal carotid intramural haematoma that spread along the carotid wall for 7cm in a young patient, and one case of tumour seeding. No complications caused permanent problems. This series shows that ultrasound-guided FNA of thyroid lesions is safe and has few complications. However, physicians should always consider the risks and benefits for each patient before the procedure.

Comparison between liquid and tablet levothyroxine formulations in patients treated through enteral feeding tube.

BACKGROUND: The majority of clinicians suggest that enteral feedings should be held 1-2 h prior to and after L-T4 administration despite lack of data for continuous enteral nutrition. AIM: The aim of this study was to: (1) compare the thyroid hormonal profile in patients submitted to L-T4 treatment in tablets or liquid formulation with an enteral feeding tube; (2) evaluate the nursing compliance with the two different formulations. SUBJECTS AND METHODS: 20 euthyroid patients submitted to total laryngectomy and thyroidectomy consecutively started L-T4 treatment in tablets (Group T) or in liquid formulation (Group L) with enteral feeding tube the day after surgery. Tablets were crushed before administration and enteral feeding was stopped for 30 min before and after L-T4 treatment, whereas liquid formulation was placed into the nasoenteric tube immediately. A questionnaire about the preparation and administration of thyroxine replacement therapy was given to the nurses. RESULTS: No difference of TSH, fT4 and fT3 before and after L-T4 treatment was observed among patients of Group L. A slightly serum TSH increase was observed in Group T, but not reaching statistical significance (2.50 ± 1.18 vs 2.94 ± 1.22 mUI/L), whereas no difference in fT4 and fT3 levels was found. Preparation and administration of liquid L-T4 was considered excellent by 12/13 nurses, whereas tablet formulation was considered poor by 10/13. CONCLUSIONS: Our data showed that liquid L-T4 formulation can be administered directly through feeding tube with no need for an empty stomach, with a significant improvement in therapy preparation and administration by nurses.

Ultrasound findings of subacute thyroiditis: a single institution retrospective review.

BACKGROUND: High resolution ultrasonography features have also been described as having a useful supporting role in the diagnosis of subacute granulomatous thyroiditis (ST), and images are generally characterized by heterogeneous hypoechoic areas of the affected tissue with lack of flow on color Doppler US. PURPOSE: To determine the sonographic features of subacute granulomatous thyroiditis. MATERIAL AND METHODS: We reviewed the medical records of patients referred at the Endocrine and Metabolic Unit of our Institution between January 2010 and December 2011. RESULTS: A total of 7520 patients were evaluated in our department between January 2010 and December 2011. Among them, 22 (0.3%) patients had a diagnosis of ST (19 women and 3 men, 45.4 ± 9.7 year; range, 33-62 years). Ultrasound examination showed bilateral ST in 64% of patients. Thyroid volume was 13.2 ± 7.7 mL, without difference if ST was unilateral (13.2 ± 7.1 mL) or bilateral (13.9 ± 8.3 mL). On grayscale US, heterogeneous diffusely or focally marked hypoechoic areas, like "lava flow", were found in all the lesions. CONCLUSION: Our data confirm the high sensitivity of US in the diagnosis of ST: diffuse hypoechoic and confluent areas with the characteristic features like "lava flow".

Usefulness of repeated recombinant human thyrotropin-stimulated thyroglobulin test in the post-surgical follow-up of very low-risk patients with differentiated thyroid carcinoma.

BACKGROUND: The European Thyroid Association (ETA) and the American Thyroid Association (ATA) guidelines identify subgroups of patients affected by thyroid carcinoma in whom, due to a low risk of recurrence, radioiodine ablation is not indicated. These patients are referred to as "very low-risk" according to the ETA consensus and "low-risk" patients according to the ATA guidelines. The recommended post-surgical follow-up of these patients is based upon periodical measurements of serum thyroglobulin (Tg) on levothyroxine therapy and neck ultrasound (US). AIM: To evaluate the usefulness of recombinant human (rh)-TSH Tg test and its repetition 2-3 yr afterwards in very low-risk patients. MATERIALS AND METHODS: We consecutively enrolled 32 patients with undetectable anti-Tg antibodies. Basal serum Tg levels was undetectable in all patients. RESULTS: Following rhTSH serum Tg remained undetectable in 23 (71.9%) patients (UP) and was >1.0 ng/ml in 9 (DP). US and whole body scan, revealed lymph node metastasis in 4/9 DP patients. A second rhTSH stimulation test (36.9±3.5 months later) was performed in all UP and in 5 DP patients without proven recurrences. All the UP and 4/5 formerly DP patients showed undetectable Tg stimulation. CONCLUSIONS: Our results suggest that rhTSH Tg test may be helpful in very low-risk patients, given its ability to differentiate those who may be considered "free of disease" from those who require further investigation and treatment. Repeated rhTSH Tg tests may be indicated only in patients with detectable serum Tg at prior stimulation testing.

Decreased number of circulating endothelial progenitor cells in patients with Graves' hyperthyroidism.

OBJECTIVE: A relevant biological role of circulating endothelial progenitor cells (EPC) was recently demonstrated. EPC are generated in the bone marrow, and interact with damaged endothelium, restoring the integrity of the monolayer. Therefore, aim of the present study was to evaluate EPC in the blood of patients with untreated Graves' hyperthyroidism (GD), in whom an increased oxidative stress was observed. DESIGN AND METHODS: Twenty-three patients with untreated active GD and 18 matched normal controls (NC) were included in the study. Circulating EPC were isolated from peripheral blood. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots, and were identified by positive double staining after 7 days in culture. Circulating levels of C reactive protein, total antioxidant power, interleukin (IL)-6, IL- 18, monocyte chemoattractant protein-1, tumor necrosis facotr- α, soluble vascular cell adhesion molecule (VCAM) and intracellular adhesion molecule were evaluated by enzymelinked immunosorbent assay kit. EPC number was also evaluated in a subgroup of GD patients after restoration of euthyroidism. RESULTS: Systolic blood pressure resulted increased in GD patients compared with control subjects whereas diastolic blood pressure was not significantly different. Patients with GD showed an increase in circulating levels of IL-18 and VCAM-1 and a reduction of total antioxidant power (p<0.05) compared to NC. Moreover, a reduced number of EPC was observed in patients with GD compared to NC (p<0.05) which turned to NC values after restoring euthyroidism. CONCLUSION: Patients with GD showed a reduction in the physiological protective mechanisms against endothelial damage, probably induced by increased inflammation and oxidative stress.

A Case of Concurrent Riedel's, Hashimoto's and Acute Suppurative Thyroiditis.

Riedel's thyroiditis (RT) is a rare form of infiltrative and inflammatory disease of the thyroid, first described by Bernard Riedel in 1896. The concurrent presence of RT and other thyroid diseases has been reported, but, the association of RT with Hashimoto's thyroiditis and acute thyroiditis has not yet been reported. We present a case of concurrent Riedel's, Hashimoto's and acute thyroiditis that occurred in a 45-year-old patient.

Modified percutaneous ethanol injection of parathyroid adenoma in primary hyperparathyroidism.

Surgery is the treatment of choice for symptomatic primary hyperparathyroidism; unlikely few patients do not meet established surgical criteria or have comorbid conditions that prohibit surgery. In these subjects, medical therapy alone offers little hope for a sustained long normocalcemic period. However percutaneous ethanol injection (PEI) may represent an alternative therapeutic procedure. It is currently in use for the treatment of secondary or tertiary hyperparathyroidism, however, few studies or case reports suggest it for the treatment of primary hyperparathyroidism. Moreover, little information is available about the long-term follow-up, where incomplete necrosis or the spreading of ethanol in the surrounding tissues is often reported. We believe that many of the side effects could be correlated to procedure itself. Taking these experiences into account, we have reasoned that in order to limit these side effects, we had to modify the standard PEI procedure. We reported this preliminary experience describing our modified PEI procedure.

Spinal needle improves diagnostic cytological specimens of thyroid nodules.

Ultrasound fine needle aspiration cytology (US-FNAC) represents the most effective test available to distinguish between benign and malignant thyroid nodules, with an accuracy approaching 95%. The major limit of this procedure it is the rate of inadequate specimens which is reported to be from 10% to 31%. Also because cost considerations have always been important and have recently become even more relevant for clinical guidelines in many countries, it is desirable to limit the number of inadequate samples. Recently, we have shown that the use of stylet needles greatly reduces inadequate cytological specimens in thyroid nodules with an intranodular vascular pattern. With the aim to improve our previous results, we have extended our procedure to all thyroid solid nodules. Between February 2004 and March 2006, 312 consecutive patients with thyroid nodule without intranodular vascular pattern at color-Doppler evaluation were enrolled in this prospective study. US-FNAC was performed by two different 25 gauge needles (Neolus [Ns] and Yale Spinal [YS]), and the two procedures were performed in alternate sequence on consecutive patients. Adequate specimens were observed in 145 (92.9%) and 153 (98%) nodules respectively investigated by Ns and in YS (p<0.005). The total cost to obtain a cytological diagnosis by Ns was of euro 12210.2 (156+12 repeated US-FNAC), whereas it was of euro 12449.7 by YS (156+3 repeated US-FNAC). Our data suggest that spinal needles are associated with a low proportion of inadequate FNAC, without increase of total direct cost, considering also the number of FNAC repetitions needed; therefore, their routine use could be taken into account.

Thyroid nodular disease: an emerging problem.

As a consequence of increasing application of ultrasound technology, the detection of asymptomatic thyroid nodules has generally increased. In fact, ultrasound epidemiological studies report that two third of subjects have at least a thyroid nodule, instead of 4-7% detected by clinicians. These evidences suggest the need of a rational approach to the thyroid nodule ''epidemia''. The question of whether clinically unapparent thyroid lesions should be assessed by cytology is still unresolved and, moreover, the clinical significance of nonpalpable (diameter <10 mm) thyroid carcinoma is still a matter of discussion. Aim of this work is to delineate a rational approach to thyroid nodules, taking in account literature data, the most recent guidelines and our clinical experience.

Fine needle cytology of complex thyroid nodules.

OBJECTIVE: To evaluate whether a preliminary aspiration (ASP) of the cystic component and/or using spinal needles in complex thyroid nodules (CTN) could improve the adequacy of cytological sampling. METHODS: Between January 2004 and December 2006, 386 consecutive patients with CTN were enrolled in this prospective investigation. Ultrasound (US) fine needle aspiration cytology (FNAC) of the solid component of the nodule (one nodule per patient) was performed using two different 25 gauge needles, with (Yale Spinal, YS) or without (Neolus, NS) a stylet, in alternate sequence on consecutive patients. In addition, a subgroup of patients presenting larger cystic component (approximately 50%) was submitted to total aspiration of the cystic component (ASP+) or not submitted (ASP-) before US-FNAC, in alternate sequence within each needle type group. All the samplings were performed by a single endocrinologist. RESULTS: Adequate specimens were observed in 163 (84.5%) and 183 (94.8%) nodules investigated by NS and YS respectively. Sampling with the stylet needle was associated with an overall significant reduction of non-diagnostic specimens (15.5% vs 5.2% by NS and YS respectively, P < 0.001). The favourable result obtained with YS was independent from preliminary aspiration of the cystic component (ASP+: 14.8% vs 5.7% by NS and YS; ASP-: 16.2% vs 4.8%, not significant). A logistic regression analysis, taking into account nodule size and presence of intranodal vascularity at eco-colour evaluation of the solid component, confirmed that needle type was the only significant predictor of successful sampling (odds ratio 3.6 (95% confidence interval 1.7-7.6), P < 0.001). CONCLUSIONS: Our data show that adopting stylet needles to perform FNAC in CTN may significantly improve the percentage of adequate sampling. On the other hand, preliminary aspiration of CTN with large cystic component does not add any advantage.

Aggressiveness and outcome of papillary thyroid carcinoma (PTC) versus microcarcinoma (PMC): a mono-institutional experience.

BACKGROUND: Papillary thyroid carcinoma (PTC) represents 70%-75% of well-differentiated thyroid cancers. Although most reports have shown that papillary thyroid microcarcinomas (PMC) follow an indolent course, a few series have demonstrated that a significant number of them are associated with extrathyroidal extension and nodal or distant metastases. METHODS: Four hundred eighty-four patients with papillary thyroid cancer (102, PMC; 382, PTC) were enrolled in this study. The median follow-up was 102 months. RESULTS: No difference between PTC and PMC patients was observed for age, gender, multifocality, extrathyroidal extension, and lymph nodes metastasis. The prevalence of nodal involvement developing during the follow-up period was significantly higher in PMC than PTC (58.8% vs. 38.5%, P = 0.002). An unfavorable clinical course occurred in 96 subjects (21.8%). Logistic analysis showed that the strongest association with the worst prognosis was found for age and TNM stage III (P < 0.001). Analysis also confirmed that the presence of intranodular vascularity is a predictor of unfavorable outcome (P = 0.044). CONCLUSIONS: We suggest always performing a total thyroidectomy followed by radiometabolic therapy in papillary carcinomas independent of their size. If the choice in PMCs should be more conservative (hemithyroidectomy), we purpose to limit this procedure to the cancers without Doppler features suggesting intranodular vascular pattern.

The predictive value of ultrasound findings in the management of thyroid nodules.

BACKGROUND: Thyroid nodules are a common medical problem, but whether fine-needle aspiration cytology (FNAC) is mandated for smaller non-palpable nodules, is controversial. AIM: To evaluate whether ultrasonographic features of thyroid nodules are associated with histological malignancy, and to identify useful criteria for clinical decision-making. DESIGN: Prospective observational study. METHODS: From January 1991 to September 2004, 5198 patients were referred to our hospital for ultrasound evaluation of thyroid nodules. Overall, 7455 nodules (diameters from 6 to 100 mm) were examined; 2865 (38.4%) were <10 mm in diameter. All patients with suspicious or malignant cytology underwent surgery. RESULTS: Of the 349 nodules undergoing surgery, 284 were malignant. The prevalence of cancer was slightly higher in nodules>or=10 mm in diameter vs. those<10 mm (5.5% vs. 3.0%, p<0.01). However, histological type and local aggressiveness were largely independent of nodule size. Microcalcifications (72.2% vs. 28.7%; p<0.001; OR 6.4, 95%CI 4.9-8.4), blurred margins (52.8% vs. 18.8%; p<0.001; OR 4.8, 95%CI 3.8-6.1), solid hypoechoic appearance (80.6% vs. 52.4%; p<0.001; OR 3.8, 95%CI 2.8-5.1), size>or=10 mm (77.4% vs. 64.9%; p<0.001; OR 1.9, 95%CI 1.4-2.5) and intranodular vascular pattern type 2 (61.6% vs. 49.7%; p<0.001; OR 1.6, 95%CI 1.2-2.0) were all significantly more frequent in malignant than in benign nodules. These associations were similar when large and small nodules were analysed separately. DISCUSSION: No single parameter, including nodule size, satisfactorily identifies a subset of patients to be electively investigated by FNAC, although several may be useful in this regard.

Ectopic lingual thyroid tissue and acquired hypothyroidism: case report.

Ectopic thyroid tissue with thyroid gland in its normal location is an extremely rare phenomenon. We present a case of a 38-year-old woman who was referred to our hospital with symptoms of hypothyroidism. Thyroid hormone measurement revealed clinical hypothyroidism with elevated anti-thyroid antibodies, neck ultrasonography showed a small tissue with the characteristic of Hashimoto thyroiditis, while the scintigraphy demonstrated only a lingual thyroid. Treatment consisted in L-thyroxine replacement to the euthyroid state. We reviewed the literature with respect to the embryological background and the clinical management of such cases.

Cost-effectiveness of fine-needle-aspiration cytology of thyroid nodules with intranodular vascular pattern using two different needle types.

OBJECTIVE: To compare the cytological findings of hypoechoic thyroid nodules with intranodular vascular pattern (pattern II) obtained by two different needles (Neolus 25 gauge, Chemil, Wenzhou, China vs Yale Spinal 25 gauge, Becton Dickinson, Madrid, Spain) in euthyroid patients and to evaluate their cost-effectiveness. METHODS: From January 2001 to December 2003, 480 euthyroid patients with a hypoechoic thyroid nodule pattern II were referred for US-FNAC. The nodules were alternatively evaluated by Neolus or by Yale Spinal with the stylet (YS+) or without the stylet (YS-), in order to evaluate if the cytological results could be due to the presence of the stylet or to the different length of the two needles. For each nodule two passes were performed and the material was obtained by capillary action. Material was smeared on slides, fixed, and stained by Papanicolaou techniques. Cytological specimens were evaluated in blind by the same experienced cytopathologist. RESULTS: Inadequate cytological specimens because of blood contamination were present in 30 (18.7%) samples by Neolus needle and in 22 (13.8%) by YS- compared to only 5 (3.1%) by YS+. In 6 (20%) cases of the 30 repeated US-FNAC by Neolus and in 4 (18%) of the 22 US-FNAC by YS-, material remained inadequate for diagnosis because of blood contamination. All the five repeated samples obtained by YS+ became adequate for diagnosis and resulted benign nodules. Direct costs of US-FNAC procedure are currently 72.30 Euro including cytological examination. The cost of Neolus and Yale needles is 0.19 Euro and 3.0 Euro, respectively. The estimated total cost to obtain a cytological diagnosis by a Neolus needle (160 + 30 repeated US-FNAC) was 13809.2 Euro vs 12919.5 Euro by Yale Spinal needle (160 + 5 repeated US-FNAC). CONCLUSION: This study demonstrates that the use of Yale Spinal needles greatly reduces inadequate cytological specimens, and therefore limits both direct and indirect costs.

[Bone density and mineral metabolism in calcitonin-deficiency patients]. / Densità ossea e metabolismo calcico in pazienti calcitonino-privi.

AIM: Calcitonin is a hormone secreted by thyroid C-cells. Its primary effect seems to be a direct inhibition of bone degradation, but the physiological function of calcitonin in humans is still uncertain. The role of this hormone in the development of osteoporosis is unknown, but few authors have shown bone mass reduction in thyroidectomy patients. METHODS: To investigate the influence of calcitonin deficiency on bone turnover, 9 males (age 31 to 66 years) submitted to total thyroidectomy in 1996 for non-toxic goitre have been studied. These patients received thyroxine treatment at individual dose but never with suppressed TSH levels. Moreover 8 sex-, age- and Body Mass Index-matched normal subjects have also been studied as control group. RESULTS: Calcitonin was undetectable in thyroidectomized patients, while the mean value was 7.1+/-3.2 pg/ml in the control group. At bone ultrasonography 50% of patients showed osteopenia, while only 1 subject showed osteopenia in the control group. The mean calcium serum level of patients was significant lower than in the control group (p<0.001). Calcium urinary level was increased in patients than controls. PTH serum levels were statistically decreased (p<0.001) in patients more than in controls. Osteocalcin showed a significantly (p<0.05) lower bone formation in patients than in controls, while the markers of resorption, deoxypyridinoline and N-terminal telopeptide of type I collagen, suggested an increased bone turnover in calcitonin-deficiency patients. CONCLUSION: The results of this study show that the chronic lack of calcitonin in total thyroidectomized patients may play a role in increased bone degradation and osteopenia with a higher risk of bone fracture.