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Objective: Outcomes of patients with cytologically indeterminate thyroid nodules not referred for thyroidectomy have hardly been investigated. We previously reported outcomes of 322 patients with thyroid nodules classified according to the Bethesda System of Reporting Thyroid Cytology (BSRTC) as indeterminate (B3/B4), of whom 123 (38.2%) underwent thyroidectomy. In the present extension study, we investigated adherence and outcomes in the remaining unoperated 199 patients. Methods: We conducted a file review of 189/199 patients with thyroid nodules cytologically diagnosed as B3 (n = 174) or B4 (n = 15) in 2011–2012 who were conservatively followed at our institution until 2019. Results: Among 174 patients with B3 nodules, 140 (80.4%) underwent repeated ultrasound. Nodular growth was detected in 23 (16.4%), and findings remained stable in 105 (75%). Fine-needle aspiration was repeated in 88/174 patients (50.6%), with B2 results in 62 (70.4%) and B3/B4/B5 in 20 (22.7%). Thyroidectomy was performed in 14/174 patients (8%) in the B3 and 5/15 patients (33%) in the B4 group at a median of 5 years’ follow-up; thyroid cancer was diagnosed in 4/14 patients (28.5%) and 3/5 patients (60%), respectively. For B3 patients who remained unoperated, none had evidence of thyroid cancer at last follow-up. A reason for avoiding surgery was documented in 6/10 unoperated B4 patients (1 thyroid lymphoma, 3 died of unrelated causes, 2 were considered inoperable due to advanced age). Conclusions: Most patients with initially unoperated B3/B4 nodules adhere, at least partially, to active surveillance. For B3 nodules, subsequent thyroidectomy and thyroid cancer detection are rare events, and patients may be safely managed without using molecular markers. Thyroid cancer is diagnosed in most B4 patients who undergo thyroidectomy in our institution.

With the current aging of the world's population, primary hyperparathyroidism (PHPT) is increasingly detected in the elderly. Yet data on the presentation and outcome of PHPT in this group are scarce. The objective was to describe a cohort of patients aged 75 years or more with PHPT observed in our endocrine clinic.A retrospective analysis of medical records in an endocrine clinic at a tertiary hospital. We evaluated 182 patients with PHPT, aged 75 years or more at their last follow-up, all diagnosed at age 65 or more. Laboratory data were compared at diagnosis and last follow-up.Mean age at diagnosis was 73 ± 4 years, last follow-up was at 83 ± 4 years, and mean follow-up was 11.3 ± 5.5 years. Osteoporosis, fractures, and nephrolithiasis were diagnosed in 114(63 %), 84(46 %), and 43(24 %) patients, respectively. Overall, 150 patients had an indication for surgery; of them, the 29 who underwent parathyroidectomy were younger than the non-operated patients and had higher rates of hypercalciuria. During the follow-up of the 141 patients who did not undergo operation, serum and urinary calcium levels significantly had decreased, and vitamin D level had increased at last visit (10.4 ± 0.5 mg/dl, 161 ± 70 mg/24 h, 69 ± 17 nmol/l, p0.01 respectively) compared with levels at diagnosis (10.6 ± 0.2 mg/dl, 223 ± 95 mg/24 h, 53 ± 15 nmol/l, respectively, p = 0.001). Overall, 38 of the 182 patients (20 %) died during follow-up; these patients were significantly older at diagnosis (76 ± 5 vs. 72 ± 4 years) but there were no differences in laboratory variables.While most patients had a formal indication for surgery, few underwent parathyroidectomy. Serum and urinary calcium significantly decreased during follow-up in patients who did not undergo surgery. Our data are reassuring and support at least the consideration of conservative treatment for these patients.

To investigate gender-associated differences in the presentation, course, and outcomes of primary hyperparathyroidism (PHPT).A retrospective institutional cohort.The database of a tertiary endocrine institute was retrospectively screened for patients treated for PHPT in 2010-2018. Clinical, biochemical, and imaging data were collected. Presentation, management, and outcome variables were compared by gender and by age at diagnosis (50/≥50 years).The cohort included 182 women and 161 men diagnosed with PHPT at age 57.6 ± 12.8 and followed for 6.3 ± 5.5 years. There were no gender differences in age at detection of hypercalcemia and basal levels of serum and urinary calcium, serum PTH, and serum 25-hydroxyvitamin D. Men had a higher prevalence of nephrolithiasis (33 % vs 21 %, p = 0.01). Women had a higher frequency of osteoporosis (65 % vs 45 %, p 0.001), and a lower mean lumbar spine T-score at PHPT diagnosis. At last follow-up, women had worse bone mineral density (BMD) results in all measured sites (lumbar spine, femoral neck, distal radius) and more fractures (34 % vs 20 %, p = 0.004), despite more frequent and longer pharmacological treatment of osteoporosis. On analysis by age, all these gender-associated differences were statistically significant only in patients diagnosed at age ≥50 years. Parathyroidectomy was performed in 52 % of women and 42 % of men (p = 0.06).The main differences between male and female patients with PHPT are the higher prevalence, more intensive pharmacological treatment, and worse outcomes of osteoporosis in women. Tailoring the optimal medical and/or surgical treatment for fracture prevention in patients with PHPT remains a major challenge, especially in older women.

Distant metastatic spread is the most frequent cause of thyroid cancer-related death. The objective of this study was to evaluate overall and disease-related survival of patients with differentiated thyroid cancer (DTC) and distant metastases (DM) attending a single medical center and to investigate variables predictive of better long-term outcomes.The Rabin Medical Center Thyroid Cancer Registry was searched for patients with DM from DTC.The cohort included 138 patients (58.7% female) diagnosed at age 54.7 ± 19.5 years. Mean primary tumor size was 33.9 ± 26 mm. Most patients (57.7%) were stage T3/T4; 48.7% had extrathyroidal extension; 53.5% had lymph node metastases. Histopathology yielded papillary and follicular thyroid carcinoma in 66.7% and 13.8%, respectively, and intermediate/poorly differentiated carcinoma in 19.6%. All but 2 patients underwent total thyroidectomy, and 133/138 (96.4%) received radioactive iodine (RAI) therapy. DM were synchronous in 55.1%. The mean follow-up was 8.2 years from detection of metastases. The common sites of metastases were the lungs (85.6% of patients), bones (39.9%), brain (5.8%) and liver (3.6%). At last follow-up, resolution was documented in 24.6% of patients, improvement/stable disease in 31.6%, and structurally progressive disease in 43.4%. By the end of the study, 40.6% of patients died, 23.2% of DTC. Improved overall survival and disease progression were associated with younger age, lung-only DM, and metastatic RAI avidity.Patients with DTC and DM treated by standard-of-care approaches frequently achieve favorable long-term outcomes. Novel therapies might be necessary in only a minority of these patients, and the reported prognostic factors can aid in their identification.CR = complete response; DM = distant metastases; DTC = differentiated thyroid cancer; ETE = extra-thyroidal extension; M0 = detected during follow-up; M1 = detected at diagnosis; MSKCC = Memorial Sloan Kettering Cancer Center; NED = no evidence of disease; OS = overall survival; PFS = progression free survival; PTC = papillary thyroid cancer; RAI = radioactive iodine; Tg = thyroglobulin.

Objective: This institutional study sought to retrospectively evaluate disease progression and survival of patients with differentiated thyroid cancer (DTC) and bone metastases (BM) and to investigate variables predictive of better long-term outcomes. Methods: The Rabin Medical Center Thyroid Cancer Registry was searched for patients with bone-metastatic DTC. Variables including a patient's gender and age, pathology of the thyroid tumor, and characteristics of BM were retrieved and analyzed in association with disease progression and mortality. Results: The cohort included 64 patients (48.4% female). Mean age at diagnosis was 62.1 ± 14.3 years; mean primary tumor size was 41 ± 30 mm. Overall, 60.4% had stage T3/T4 disease; 46.3% had extrathyroidal extension; 40% had lymph-node metastases. Histopathology yielded papillary and follicular DTC in 40.6% and 32.8% of patients, respectively, and poorly/intermediately differentiated carcinoma in 26.6%. BM were synchronous in 50%. Mean follow-up was 11 ± 9.6 years from DTC detection. The common first sites of BM detection were spine (46.9% of patients), pelvis (37.5%) and ribs (21.9%). Nineteen patients (29.7%) presented with multiple-site BM, of whom 15 (78.9%) had spinal metastases. After initial treatment, 62/64 patients had structural persistence, and at last follow-up, 57.8% had progressive disease. Overall, 54.7% of patients died, 71.4% of DTC. Improved long-term outcomes were associated with younger age, lower tumor stage, no extrathyroidal extension, bone-only metastases, and non-spinal BM. Younger age and non-spinal BM were the only independent predictors for improved survival. Conclusions: Selected patients with bone-metastatic DTC may achieve fair long-term outcomes. Spinal metastases are associated with disseminated skeletal spread and increased mortality. Abbreviations: BM = bone metastases; COX = multivariate analyses; DM = distant metastases; DSM = disease-specific mortality; DSS = disease-specific survival; DTC = differentiated thyroid carcinoma; ETE = extrathyroidal extension; LNM = lymph node metastases; OM = overall mortality; OS = overall survival; PTCFV = papillary thyroid carcinoma; RAI = radioactive iodine; SM = spinal metastases; SRE = skeletal-related event; txWBS = whole-body scan after RAI therapy.

Brain metastases from non-medullary thyroid carcinoma (NMTC) are rare, with a reported frequency of ~1%, and patient survival time is 2 years, supporting an aggressive treatment approach.