Giorgio Grani

Background: Permanent postoperative hypoparathyroidism (p-HypoPT) is a major long-term complication of thyroid surgery; however, its incidence remains uncertain because reported rates are influenced by heterogeneous case mix and variable follow-up. We assessed the burden and determinants of p-HypoPT in patients undergoing surgery for differentiated thyroid cancer (DTC) with long-term endocrine follow-up. Methods: We retrospectively analysed prospectively collected data from 518 consecutive adults with DTC enrolled in a dedicated longitudinal endocrine follow-up programme between 2013 and 2022. p-HypoPT was operationally defined as the persistent requirement for oral calcium and/or active vitamin D supplementation at ≥12 months after surgery. Independent associations were assessed by means of multivariable logistic regression. Rates were also explored across the 2015 and 2025 American Thyroid Association (ATA) risk categories. Results: p-HypoPT occurred in 60/518 patients (11.6%). Median follow-up was 10.8 years (IQR 8.0–12.8), and all patients with p-HypoPT remained on calcium and/or active vitamin D supplementation at their latest available follow-up. Central neck dissection was associated with p-HypoPT in multivariable analysis (adjusted OR 2.94, 95% CI 1.55–5.57; p < 0.001). Under the 2025 ATA classification, p-HypoPT frequencies differed across categories in unadjusted analysis (p = 0.005), with the highest frequency in the high-intermediate-risk group (23.9%). This association was attenuated after adjustment for central and lateral neck dissection and was no longer statistically significant (global p = 0.566). Conclusions: Permanent hypoparathyroidism represents a relevant long-term burden after DTC surgery. Its assessment should account for both the duration of postoperative surveillance and the extent of surgery, moving beyond aggregate rates derived from heterogeneous thyroidectomy cohorts. More granular, procedure-specific and risk-adjusted estimates may ultimately support meaningful quality comparisons and provide a more individualised assessment of long-term functional risk.

Background: Permanent postoperative hypoparathyroidism (p-HypoPT) is a major long-term complication of thyroid surgery; however, its incidence remains uncertain because reported rates are influenced by heterogeneous case mix and variable follow-up. We assessed the burden and determinants of p-HypoPT in patients undergoing surgery for differentiated thyroid cancer (DTC) with long-term endocrine follow-up. Methods: We retrospectively analysed prospectively collected data from 518 consecutive adults with DTC enrolled in a dedicated longitudinal endocrine follow-up programme between 2013 and 2022. p-HypoPT was operationally defined as the persistent requirement for oral calcium and/or active vitamin D supplementation at ≥12 months after surgery. Independent associations were assessed by means of multivariable logistic regression. Rates were also explored across the 2015 and 2025 American Thyroid Association (ATA) risk categories. Results: p-HypoPT occurred in 60/518 patients (11.6%). Median follow-up was 10.8 years (IQR 8.0–12.8), and all patients with p-HypoPT remained on calcium and/or active vitamin D supplementation at their latest available follow-up. Central neck dissection was associated with p-HypoPT in multivariable analysis (adjusted OR 2.94, 95% CI 1.55–5.57; PConclusions: Permanent hypoparathyroidism represents a relevant long-term burden after DTC surgery. Its assessment should account for both the duration of postoperative surveillance and the extent of surgery, moving beyond aggregate rates derived from heterogeneous thyroidectomy cohorts. More granular, procedure-specific and risk-adjusted estimates may ultimately support meaningful quality comparisons and provide a more individualised assessment of long-term functional risk.

Objective: Anaplastic thyroid carcinoma (ATC) is an extremely aggressive cancer, traditionally refractory to conventional treatments. The combined therapy with lenvatinib and pembrolizumab (L + P) is supported by a preclinical rationale based on the distinctive immunological profile of ATC. We propose a real-life study to evaluate relevant clinical outcomes and identify survival predictors in a cohort of ATC patients treated with the combined therapy in two Italian referral centers. Methods: Sixteen ATC patients treated with the combination of L + P were retrospectively included. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed according to RECIST 1.1 criteria. Baseline patient characteristics, including immuno-nutritional status (calculated using the CONUT score), were analyzed to identify potential predictors of response. Results: A median OS of 10 months (95% CI: 4.2–15.9 months) and a median PFS of 6.0 months (95% CI: 0–12.7 months) were observed after L + P therapy. Complete response was observed in 6.2% and partial response in 31.3% of patients, resulting in an ORR of 37.5%; the DCR was 68.8%. Progressive disease occurred in 25% of patients. Furthermore, a baseline CONUT score ≤ 2 resulted in a significantly longer OS (log-rank, P = 0.001) and PFS (P = 0.05) compared to CONUT score ≥ 3, while a non-significantly longer OS was observed between patients with a baseline ECOG PS of 0–2 and those with a baseline ECOG PS ≥ 3. Conclusion: Our study confirms the efficacy and safety of L + P therapy, identifying the CONUT score as a prognostic factor.

Thyroid nodules are common incidental findings, but only a small proportion of cases are malignant (4–6.5%) or symptomatic. Numerous follow-up examinations and invasive diagnostic procedures, such as fine-needle aspiration, fine-needle biopsies, and thyroidectomies, are performed, leading to potentially costly and time-consuming diagnostic procedures and overtreatment. Most experts and scientific societies (EFSUMB, WFUMB, etc.) encourage the use of multiparametric ultrasound evaluation (MPUS) to improve thyroid nodule characterization due to the continuous technological developments including new ultrasound software (microvascular flow imaging, elastosonography, etc.), contrast media (CEUS), and artificial intelligence (AI). Therefore, the recognition and proper use of new multiparametric ultrasound features of thyroid nodules are essential for minimizing unnecessary interventions and guiding appropriate treatment. The goal of these guidelines is to help initiate use of these features in routine clinical practice. In addition, we analyze the use of MPUS in some emblematic thyroid scenarios, such as cytologically indeterminate nodules, multinodular goiters, and extrathyroidal extension of the malignant nodule, and the usefulness of MPUS as a guide for thyroid biopsy/aspiration and in the staging of cervical lymph nodes. Recommendations based on the level of evidence of the published literature and on the EFSUMB expert group’s consensus are given for each question.

Thyroid nodules are common incidental findings but only a small proportion of cases are malignant (4–6.5%) or symptomatic. Numerous follow-up examinations and invasive diagnostic procedures, such as fine-needle aspiration, fine-needle biopsies, and thyroidectomies, are performed, leading to potentially costly and time-consuming diagnostic procedures and overtreatment. Most experts and scientific societies (EFSUMB, WFUMB, etc.) encourage the use of multiparametric ultrasound (MPUS) evaluation to improve thyroid nodule characterization due to the continuous technological developments including new ultrasound software (microvascular flow imaging, elastosonography, etc.), contrast media (CEUS), and artificial intelligence (AI). Therefore, the recognition and proper use of new multiparametric ultrasound features of thyroid nodules are essential for minimizing unnecessary interventions and guiding appropriate treatment. The goal of these guidelines is to help initiate use of these features in routine clinical practice. In addition, we analyze the use of MPUS in some emblematic thyroid scenarios, such as cytologically indeterminate nodules, multinodular goiters, and extrathyroidal extension of the malignant nodule, and the usefulness of MPUS as a guide for thyroid biopsy/aspiration and in the staging of cervical lymph nodes. Recommendations based on the level of evidence of the published literature and on the EFSUMB expert group’s consensus are given for each question.

Indeterminate thyroid cytology presents a significant diagnostic challenge, often leading to difficult treatment decisions for both physicians and patients. Effective communication of these uncertainties is crucial, especially in a surgical setting, where decisions can have long-lasting impacts. This is particularly important for younger surgeons who may lack extensive clinical experience. This study aimed to plan, develop, implement, and pilot a communication protocol designed for surgeons, particularly those in training, to navigate uncertainty and build trust with their patients. Additionally, it documented the reactions of patients managed using this approach. Fifty-two patients diagnosed with indeterminate thyroid cytology were enrolled between March 2023 and January 2024 at the Endocrine Surgery Unit of "Azienda Ospedialiera Universitaria Policlinico Umberto I" in Rome, Italy. A communication protocol based on the SPIKES model (Setting, Perception, Invitation, Knowledge, Emotion, Strategy), a six-step protocol for guiding difficult conversations, was designed to structure discussions around uncertain diagnoses. Patient consultations were conducted in three phases: the initial outpatient visit, pre-surgery admission, and a follow-up one week after surgery. During each encounter, patients' emotional responses were recorded using open-ended questions. To ensure clarity, a Decision Aid (DA) tool was introduced during the K-Knowledge phase of SPIKES, to better explain the risks and treatment options. A mixed-methods approach was used to analyze both qualitative and quantitative data from patient feedback. The adapted protocol was found to be effective in enhancing patient comprehension and emotional response. Approximately 80% of patients reported emotional relief after the first consultation, and by the third encounter, 91% expressed a sense of well-being or trust. The most frequently reported emotional states across all three encounters were serenity, reassurance, and trust. A small subset of patients continued to experience concern or fatigue. Additionally, 96% of participants rated the communication as clear, and 88.5% considered the final therapeutic decision as the correct one. This pilot study suggests that a structured SPIKES-based communication protocol can help address gaps in patient understanding, trust, and satisfaction when managing indeterminate thyroid cytology. Implementing such protocols may streamline communication in surgical settings, improve patient-centered care, and support physicians, particularly trainees, in managing complex patient interactions.

Background: Ultrasound (US) examination is the pivotal test to assess the risk of cancer and the indication for fine needle aspiration cytology (FNAC) in thyroid nodules (TNs). The subcapsular location of a TN may strengthen the indication for FNAC as, in TN resulting malignant at cytology may favor surgery rather than active surveillance. However, the definition of a subcapsular TN remains unclear. This study aimed to evaluate the interobserver agreement (IOA) among thyroid US experts in classifying TNs as subcapsular or not. Methods: Twelve raters received an electronic link to a file containing static US images and were asked to assess 60 TNs for subcapsular location, blinded to all other TN characteristics. The overall IOA was calculated, and the TN US features were subsequently analyzed to evaluate their potential influence on interobserver variability. The raters had high or very high thyroid US experience. Two experienced operators preliminarily selected the case series and analyzed the findings. All cases were derived from patients undergoing surgery and histological diagnosis. The IOA was calculated according to Fleiss’ kappa, ranging from 0.0 (no agreement) to 1.0 (perfect agreement). Results: The overall IOA was fair (κ = 0.34), with a slightly better result in the subgroup of raters with higher experience (κ = 0.39). A higher IOA value (κ = 0.38) was observed in TNs of medium size. Following multiple sub-analyses, the highest κ value (0.46) was observed in the subgroup of TNs that were categorized as EU-TIRADS 5 and were smaller than 2 cm. Conclusions: The overall IOA among US experts when assessing TNs as subcapsular was unsatisfactory. A clear and standardized definition of subcapsular position is needed to improve clinical decision-making. Future guidelines should address this issue to ensure consistent assessment and management of subcapsular TNs.

Introduction: Little is known about sex differences in lenvatinib treatment safety and efficacy. Methods: Real-word retrospective Italian multicenter study enrolling patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib. Results: A total of 138 patients (64 females) were included, with a median follow-up of 26 months (2–72). More men performed physical activities (34% vs 17%, P = 0.024). The frequency of smoking and alcohol consumption was higher in men (58% vs 33%, P = 0.003; 45% vs 17%, P = 0.001). We did not find sex differences in lenvatinib dose reduction due to adverse events (AEs) (78% females vs 85% males). Ninety-nine percent of patients developed at least one adverse event (AE), with no sex difference in their number and the time to first AE. Severe AEs occurred in 74% of males and 66% of females (P = 0.398), with a mean dose of 18.2 mg (±5.7), and a median time to the first serious AE of 9 weeks (1–154). Stomatitis/mucositis and hematological disorders were more frequent in females (48% vs 30%, P = 0.016; 17% vs 4%, P = 0.011). Gastrointestinal disorders were higher in males (15% vs 2%, P = 0.010). Eighty-seven patients interrupted lenvatinib due to AEs (median time: 3 months (0–48), mean dose: 17 mg ±5.5). Discontinuation occurred in 21 patients, five for severe AEs. No sex differences were found in progression-free survival, overall survival or disease control rate. Liver metastases were associated with disease progression (HR: 3.73, 95% CI: 1.06–13.12, P = 0.040) or death (HR: 4.82, 95% CI: 1.75–13.25, P = 0.002) only in females. Conclusion: Lenvatinib is effective in both sexes and exhibits a good safety profile, with a sex difference in the frequencies of some adverse events.