A Data-Driven Approach to Refine Predictions of Differentiated Thyroid Cancer Outcomes: A Prospective Multicenter Study.

CONTEXT: The risk stratification of patients with differentiated thyroid cancer (DTC) is crucial in clinical decision making. The most widely accepted method to assess risk of recurrent/persistent disease is described in the 2015 American Thyroid Association (ATA) guidelines. However, recent research has focused on the inclusion of novel features or questioned the relevance of currently included features. OBJECTIVE: To develop a comprehensive data-driven model to predict persistent/recurrent disease that can capture all available features and determine the weight of predictors. METHODS: In a prospective cohort study, using the Italian Thyroid Cancer Observatory (ITCO) database (NCT04031339), we selected consecutive cases with DTC and at least early follow-up data (n = 4773; median follow-up 26 months; interquartile range, 12-46 months) at 40 Italian clinical centers. A decision tree was built to assign a risk index to each patient. The model allowed us to investigate the impact of different variables in risk prediction. RESULTS: By ATA risk estimation, 2492 patients (52.2%) were classified as low, 1873 (39.2%) as intermediate, and 408 as high risk. The decision tree model outperformed the ATA risk stratification system: the sensitivity of high-risk classification for structural disease increased from 37% to 49%, and the negative predictive value for low-risk patients increased by 3%. Feature importance was estimated. Several variables not included in the ATA system significantly impacted the prediction of disease persistence/recurrence: age, body mass index, tumor size, sex, family history of thyroid cancer, surgical approach, presurgical cytology, and circumstances of the diagnosis. CONCLUSION: Current risk stratification systems may be complemented by the inclusion of other variables in order to improve the prediction of treatment response. A complete dataset allows for more precise patient clustering.

Italian Guidelines for the Management of Non-Functioning Benign and Locally Symptomatic Thyroid Nodules.

AIM: This guideline (GL) is aimed at providing a reference for the management of non-functioning, benign thyroid nodules causing local symptoms in adults outside of pregnancy. METHODS: This GL has been developed following the methods described in the Manual of the National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence and only those classified as "critical" were considered in the formulation of recommendations. RESULTS: The present GL contains recommendations about the respective roles of surgery and minimally invasive treatments for the management of benign symptomatic thyroid nodules. We suggest hemithyroidectomy plus isthmectomy as the first-choice surgical treatment, provided that clinically significant disease is not present in the contralateral thyroid lobe. Total thyroidectomy should be considered for patients with clinically significant disease in the contralateral thyroid lobe. We suggest considering thermo-ablation as an alternative option to surgery for patients with a symptomatic, solid, benign, single, or dominant thyroid nodule. These recommendations apply to outpatients, either in primary care or when referred to specialists. CONCLUSION: The present GL is directed to endocrinologists, surgeons, and interventional radiologists working in hospitals, in territorial services, or private practice, general practitioners, and patients. The available data suggest that the implementation of this GL recommendations will result in the progressive reduction of surgical procedures for benign thyroid nodular disease, with a decreased number of admissions to surgical departments for non-malignant conditions and more rapid access to patients with thyroid cancer. Importantly, a reduction of indirect costs due to long-term replacement therapy and the management of surgical complications may also be speculated.

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

BACKGROUND: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING: None.

Misdiagnosed giant parathyroid cyst: differential diagnosis of a neck mass of the central region.

Parathyroid cysts (PCs) are rare benign lesions representing between the 0.08% and the 0.34% of the neck masses going on surgery. They should be considered in the differential diagnosis of neck masses, especially in the differential diagnosis of the cystic anterior neck masses.Approximately 300 cases of PC are reported within the international literature.The gold standard for diagnosis is the evidence of high-level intact parathyroid hormone in cystic fluid. It is important to diagnose PCs before surgery, not intraoperatively, in order to avoid unnecessary surgeries or superfluous excision of part of the thyroid gland and prevent the patient from iatrogenic hypothyroidism.A surgical approach is required in those patients with large-sized cysts, relapses despite needle aspirations or if it causes hyperparathyroidism.We describe a case report of a patient, initially misdiagnosed with a thyroid cyst swelling, who instead had a giant non-functioning PC, which produced dyspnoea or dysphagia.

Long-Term Adherence to Levothyroxine Replacement Therapy in Thyroidectomized Patients.

(1) Background: We evaluated the long term adherence to two distinct formulations of levothyroxine (L-T4), liquid or solid, which are differently influenced by concomitant food ingestion. (2) Methods: A total of 106 thyroidectomized patients (82 female, mean age 58.2 ± 13.3 years) on L-T4 replacement therapy in either liquid (n = 52) or solid formulation (n = 54) were administered the four-item Medication Adherence Questionnaire (MAQ). (3) Results: The study population had 59.4% adherers and 40.6% non-adherers. The global MAQ score was significantly better in patients under liquid L-T4 in comparison to those under solid L-T4 (0.42 ± 0.82 vs. 0.83 ± 0.95, respectively, p = 0.0085). The patients on tablet L-T4 forgot to take their medication more frequently than those on liquid LT4 treatment (p = 0.0159) and were more often careless at times about taking their medication (p = 0.007), whilst about one in two thyroidectomized patients preferred tablets for lifetime medication therapy. The global MAQ score was directly correlated with the circulating TSH levels in the whole study population (0.700, p < 0.0001) and inversely correlated with both the FT3 (−0.220, p = 0.0232) and FT4 (−0.327, p = 0.0006) serum concentrations. (4) Conclusions: Long-term adherence to L-T4 treatment was globally satisfactory although it was better for the liquid formulation, which appears to represent an easier-to-manage L-T4 replacement therapy for most thyroidectomized patients, particularly for those with difficulties in taking L-T4 while fasting.

Thyroid Cancer: Toward Surgical Evolution.

It has been more than five years since the American Thyroid Association (ATA) and the Italian consensus on thyroid cancer was published [...].

Neck complaints before and after uncomplicated thyroidectomy: prevalence, postoperative outcome and relationships with thyroid weight and reflux like symptoms.

PURPOSE: The surgical thyroid disease includes upper aerodigestive complaints with not homogenous prevalence and specific features. The purpose was to analyze before and after total thyroidectomy (TT) the prevalence and severity of voice, swallowing, respiratory, and reflux airway symptoms in relation with thyroid weight. METHODS: A total of 98 consenting patients undergoing TT were enrolled. Preoperatively, 1 and 3 months after TT, patients underwent videolaryngoscopy, subjective evaluation of voice (VIS), swallowing (SIS and EAT-10), respiratory (mMRC), and reflux symptoms (RSI, Gerd-Q). The scores were analyzed based on thyroid weight (<25 gr, 26-50 gr, 51-75 gr, >75 gr) and post-operative score gain was calculated from the score before TT and the follow-up examination. RESULTS: In total, 40/98 selected cases of uncomplicated TT completed the postoperative evaluation. Endoscopic signs suggestive of reflux disease were observed in 1/40 (2.5%) and 0/19 cases before and after TT respectively. The prevalence of cases with abnormal reflux symptom index decreased significantly after surgery (8/40 vs 1/40) (p < 0.05), similarly occurred for the Gerd-Q (4/40 vs 1/40) (p < 0.05). Three months after TT the voice, swallowing and respiratory scores were significantly lower than the preoperative ones (p < 0.05). The SIS correlated positively with EAT-10 and RSI. After 3 months the postoperative score gain of voice, swallowing, respiratory, and reflux symptoms (Gerd-Q) was statistically higher (p < 0.05) in the cases with heaviest gland. CONCLUSIONS: The surgical thyroid disease is associated to mild aerodigestive preoperative compressive symptoms, that include respiratory abnormalities and reflux like symptoms, regardless of the gland weight. In absence of endoscopic signs of airway reflux the presence of reflux symptoms suggests an overlapping with thyroid neck complaints. The patients undergoing uncomplicated TT had improvement in compressive symptoms and the greatest improvement is seen in larger goiters.

Endocrine surgery during COVID-19 pandemic: do we need an update of indications in Italy?

The ongoing spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a significant threat to global health. As the coronavirus outbreak began spreading, hospitals were forced to relocate resources to treat the growing number of COVID-19 patients. As a consequence, doctors across the country canceled tens of thousands of nonurgent surgeries. However, recognizing that the COVID-19 situation may be highly variable and fluid in different communities across the country, elective surgery could be still allowed in some centers for patients included in the high-priority class. The majority of endocrine disorders requiring surgical treatment in patients identifiable as first-priority class, or needing hospitalization within 30 days, are generally represented by malignant thyroid tumors, hyperthyroidism, hyperparathyroidism, and some adrenal disorders. The need for urgent intervention is evaluated on a case-by-case basis according to the severity of the symptoms, the likelihood of progression, and global clinical judgment. On the basis of the above indications, during the last 4 weeks, we performed 18 planned surgical treatments in patients with thyroid cancer (total thyroidectomies, plus lymph node dissection if needed) or multinodular toxic goiter. In no case, postoperative ventilatory support was needed, and the average hospital stay was 3 days. The negative COVID-19 status for all the treated patients was appropriately evaluated beforehand. Nobody knows how long the current COVID-19 pandemic will be lasting. Certainly, we will be requested in the next future to incrementally offer surgical services for endocrine disorders that have been deferred for the COVID-19 pandemic.

Efficacy of continuous neuromonitoring in thyroid surgery: preliminary report of a single-center experience.

BACKGROUND: The continuous intraoperative nerve monitoring (CIONM) technique seems to be acknowledged as a useful tool to prevent impending nerve injury, because it constantly provides valuable real-time information. Aim of the study is to evaluate the impact of the CIONM technique on functional outcome i.e., recurrent laryngeal nerve (RLN) palsy, compared to the traditional surgical procedure. METHODS: From January to December 2016, 197 patients who underwent thyroid surgery were included in this retrospective study: 94 patients had CIONM procedure and 103 traditional technique, according to the order of the operating room list. RESULTS: A total of 8 patients showed a damage to left or right vocal cord: 3 patients after CIONM procedure, and 5 patients after traditional surgical procedure. After matching for propensity score, 188 patients were eventually considered and 7 RLN palsy were identified: 3 in CIONM and 4 in traditional surgical procedure. The analysis performed on the matched propensity score sample showed a non-significant difference between the two procedures. CONCLUSIONS: In our experience no significant differences in functional outcomes were found between the use of CIONM and the standard technique.

Morbidity from minimally invasive video-assisted thyroidectomy: a general review.

Minimally invasive video-assisted thyroidectomy (MIVAT) is known and used worldwide, it combines the advantages associated with endoscopic magnification with those due with traditional surgery. In selected patients, it should be considered a safe and valid alternative. Indeed, a lot of comparative studies have demonstrated the advantages of MIVAT in terms of low rate of complications, reduced postoperative pain, improved cosmetic results and higher patient satisfaction over traditional surgery. Anyway, for obtaining the best results, with similar or even less complication rate than traditional surgery, surgeons should be well trained, acquired confidence with a smaller surgical incision and with the use of endoscopic instruments.

Comparative study between the effects of replacement therapy with liquid and tablet formulations of levothyroxine on mood states, self-perceived psychological well-being and thyroid hormone profile in recently thyroidectomized patients.

Following thyroid surgery, levothyroxine therapy is used to replace deficient thyroid hormones and prevent postoperative thyroid hypofunction. We compared the effects of replacement therapy with either liquid or tablet formulation of levothyroxine on mood states, self-perceived mental well-being and thyroid hormone profile in recently thyroidectomized patients. Profile of mood states, General Heath Questionnaire 12-items and thyroid hormone profile were assessed in recently (5-7 days) thyroidectomized patients at baseline and 2 months after randomization to replacement therapy with either liquid (n = 77) or tablet (n = 78) formulation of levothyroxine. After 2 months under levothyroxine replacement treatment, significant improvements of Positive Affect Scale (p < 0.001) and Negative Affect Scale (p < 0.001) of Profile of mood states, as well as of General Heath Questionnaire 12-items (p < 0.001) were observed in the study population. However, there were greater variations observed in patients assigned to liquid levothyroxine formulation in comparison to those who were assigned to levothyroxine in the form of tablet (time × treatment interaction: Positive Affect Scale of Profile of mood states, p = 0.030; Negative Affect Scale of Profile of mood states, p < 0.0001; General Heath Questionnaire 12-items, p = 0.003). As expected, circulating TSH levels significantly decreased (p <0.001) while FT3 and FT4 levels significantly increased (p < 0.0001 for both) under levothyroxine replacement therapy. These changes were significantly greater in patients treated with liquid levothyroxine formulation (time × treatment interaction: TSH, p = 0.011; FT3, p = 0.016; FT4, p = 0.028). Our data indicate a greater efficacy of liquid formulation of levothyroxine in ameliorating mood states and self-perception of mental well-being and thyroid hormone profile after 2 months of replacement therapy in recently thyroidectomized patients.

Parathyroid hormone levels 4 hours after surgery do not accurately predict post-thyroidectomy hypocalcemia.

BACKGROUND: We evaluated the reliability of intact parathyroid hormone (iPTH) levels 4 hours after thyroidectomy (4h-iPTH) as a predictor of hypocalcemia in a large series of patients. METHODS: A prospective experimental design involving 523 consecutive patients between September 1, 2004, and June 30, 2005, was employed. The specificity, sensitivity, and overall accuracy of 4h-iPTH in predicting post-thyroidectomy hypocalcemia and symptoms were determined. RESULTS: A total of 199 patients developed hypocalcemia (serum calcium concentrations <8.0 mg/dl). Five patients still were receiving vitamin D/oral calcium at 6 months after the operation. Seventy-three patients experienced mild symptoms. The 4h-iPTH levels were reduced in hypocalcemic patients (28.8 +/- 15.3 vs 11.2 +/- 11.6 pg/ml) (P < .001). The 4h-iPTH levels were within the normal range (10 to 65 pg/ml) in 360 patients (290 normocalcemic) and subnormal in 163 patients (129 hypocalcemic, of whom 62 were symptomatic). The accuracy of 4h-iPTH levels <10 pg/ml in predicting post-thyroidectomy hypocalcemia and symptoms was 80.1% and 78.6%, respectively. False-negative results were observed in 70 hypocalcemic patients (13.4%), 11 of whom were symptomatic (2.1%). CONCLUSIONS: Subnormal 4h-iPTH levels alone did not accurately predict clinically relevant postoperative hypocalcemia. The optimal cut-off level and its integration with preoperative and postoperative serum calcium concentrations should be reconsidered.

Video-assisted thyroidectomy for papillary thyroid carcinoma.

Background. The results of video-assisted thyroidectomy (VAT) were evaluated in a large series of patients with papillary thyroid carcinoma (PTC), especially in terms of completeness of the surgical resection and short-to-medium term recurrence. Methods. The medical records of all patients who underwent video-assisted thyroidectomy for PTC between June 1998 and May 2009 were reviewed. Results. Three hundred fifty-nine patients were included. One hundred twenty-six patients underwent concomitant central neck node removal. Final histology showed 285 pT1, 26 pT2, and 48 pT3 PTC. Lymph node metastases were found in 27 cases. Follow-up was completed in 315 patients. Mean postoperative serum thyroglobulin level off levothyroxine was 5.4 ng/mL. Post operative ultrasonography showed no residual thyroid tissue in all the patients. Mean post-operative (131)I uptake was 1.7%. One patient developed lateral neck recurrence. No other recurrence was observed.