Frequent neck US in papillary thyroid cancer likely detects non-actionable findings.

BACKGROUND: American Thyroid Association (ATA) low-intermediate-risk papillary thyroid cancer (PTC) patients without structural and biochemical evidence of disease on initial post-treatment evaluation have a low risk of recurrence. Studies have shown that with current ultrasound scans (US) and thyroglobulin assays, recurrences mostly occurred 2-8 years after initial therapy. The ATA recommends that neck US be done 6-12 months after surgery to establish patient's response to therapy, then periodically depending on risk of recurrence. The lack of clarity in recommendations on timing of follow-up US and fear of recurrence leads to frequent tests. OBJECTIVES: To evaluate the utility of routine neck US in ATA low-intermediate-risk PTC patients with no structural disease on neck US and non-stimulated thyroglobulin <1.0 ng/mL after initial therapy. METHODS: A retrospective study of 93 patients from Singapore, Saudi Arabia and Argentina with ATA low (n = 49) to intermediate (n = 44) risk PTC was conducted between 1998 and 2017. The outcome was to measure the frequency of identifying structural disease recurrence and non-actionable US abnormalities. RESULTS: Over a median follow-up of 5 years, five of the 93 patients (5.4%) developed structural neck recurrence on US at a median of 2.5 years after initial treatment. Indeterminate US abnormalities were detected in 19 of the 93 patients (20.4%) leading to additional tests, which did not detect significant disease. CONCLUSION: In ATA low-intermediate-risk PTC with no suspicious findings on neck US and a non-stimulated thyroglobulin of <1.0 ng/mL after initial therapy, frequent US is more likely to identify non-actionable abnormalities than clinically significant disease.

Comparison of different systems of ultrasound (US) risk stratification for malignancy in elderly patients with thyroid nodules. Real world experience.

PURPOSE: To comparatively assess the performance of three sonographic classification systems, American Thyroid Association (ATA), the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS), and American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE)/Associazione Medici Endocrinologi (AME) in identifying malignant nodules in an elderly population. METHODS: Cross-sectional study of patients referred for fine needle aspiration biopsy in an academic center for the elderly. One nodule/patient was considered. Nodules classified Bethesda V/VI were considered malignant. Receiver operating characteristics (ROC) curves were established and compared to evaluate diagnostic performance. Malignancy among biopsies below the size cutoff for each ultrasound classification was also compared. RESULTS: One thousand, eight hundred sixty-seven patients (92% females); median (Q1-Q3), age 71 (67-76) years, were studied showing 82.8% benign (Bethesda II) and 2.6% malignant cytology. The three classifications correctly identified malignancy (P < 0.01). Nonetheless, in the ATA and AACE/ACE/AME 16 and 2 malignant nodules, respectively, were unclassifiable. Including unclassified malignant nodules (n = 1234, malignant = 50), comparison of the ROC curves showed lower performance of ATA [area under the curve (AUC) = ATA (0.49) vs. ACR TI-RADS (0.62), p = 0.008 and ATA vs. AACE/ACE/AME (0.59), p = 0.022]. Proportion of below size cutoff biopsies for ATA, ACR TI-RADS, and AACE/ACE/AME was different [16, 42, and 29% (all p < 0.001)], but no differences in malignancy rate were observed in these nodules. CONCLUSION: The present study is the first to validate in elderly patients these classifications showing that AACE/ACE/AME and ACR TI-RADS can predict thyroid malignancy more accurately than the ATA when unclassifiable malignant nodules are considered. Moreover, in this aged segment of the population, the use of ACR TI-RADS avoided more invasive procedures.

Dynamic prediction of the risk of recurrence in patients over 60 years of age with differentiated thyroid carcinoma

ABSTRACT Objective The reclassification of the risk according to the response to the initial treatment makes the treatment of differentiated thyroid cancer (DTC) vary in each individual. As the influence of age on this diagnostic strategy is unknown, we have decided to assess it in adults who are over 60 years of age. Subjects and methods Ninety patients with DTC above 60 years old were enrolled, with total thyroidectomy plus radioiodine ablation, negative anti-thyroglobulin antibodies, follow-up ≥ 2 years and with clinical and pathological information to classify the risk of recurrence according to ATA (American Thyroid Association) and reclassify based on the response to initial therapy according to MSKCC (Memorial Sloan Kettering Cancer Center). The structural persistence at the end of the follow-up was the gold standard of our analysis. Results The structural persistence in ATA low, intermediate and high risk categories was 0, 38, and 100%, respectively. In the intermediate group, none of those with an excellent response to the initial treatment showed structural persistence, whereas 39% of those with an incomplete/indeterminate response showed structural persistence (p < 0.01). Conclusions The re-stratification according to the response to the initial treatment in patients over 60 years of age with an ATA intermediate risk of recurrence allowed for the distinction of disease-free patients at the end of the follow-up from those with structural persistence and a worse clinical progression.

Dynamic prediction of the risk of recurrence in patients over 60 years of age with differentiated thyroid carcinoma.

OBJECTIVE: The reclassification of the risk according to the response to the initial treatment makes the treatment of differentiated thyroid cancer (DTC) vary in each individual. As the influence of age on this diagnostic strategy is unknown, we have decided to assess it in adults who are over 60 years of age. SUBJECTS AND METHODS: Ninety patients with DTC above 60 years old were enrolled, with total thyroidectomy plus radioiodine ablation, negative anti-thyroglobulin antibodies, follow-up ≥ 2 years and with clinical and pathological information to classify the risk of recurrence according to ATA (American Thyroid Association) and reclassify based on the response to initial therapy according to MSKCC (Memorial Sloan Kettering Cancer Center). The structural persistence at the end of the follow-up was the gold standard of our analysis. RESULTS: The structural persistence in ATA low, intermediate and high risk categories was 0, 38, and 100%, respectively. In the intermediate group, none of those with an excellent response to the initial treatment showed structural persistence, whereas 39% of those with an incomplete/indeterminate response showed structural persistence (p < 0.01). CONCLUSIONS: The re-stratification according to the response to the initial treatment in patients over 60 years of age with an ATA intermediate risk of recurrence allowed for the distinction of disease-free patients at the end of the follow-up from those with structural persistence and a worse clinical progression.

Myxedema madness complicating postoperative follow-up of thyroid cancer.

Although hypothyroidism is associated with an increased prevalence of psychiatric manifestations, myxedema madness is rarely observed. We report the case of a 62-year-old woman with no prior history of psychiatric disorders, who presented to the emergency department with psychomotor agitation 6 weeks after total thyroidectomy for papillary thyroid cancer. Serum thyroid stimulating hormone (TSH) on admission was 62.9 mIU/L and free T4 was < 0.35 ng/dL, indicating severe hypothyroidism. After ruling out other possible causes, the diagnosis of myxedema madness was considered; hence, antipsychotic drug treatment and intravenous levothyroxine were prescribed. Behavioral symptoms returned to normal within 4 days of presentation, while levels of thyroid hormones attained normal values 1 week after admission. Recombinant TSH (Thyrogen®) was used successfully to prevent new episodes of mania due to thyroid hormone withdrawal in further controls for her thyroid cancer. This case illustrates that myxedema madness can occur in the setting of acute hypothyroidism, completely reverting with levothyroxine and antipsychotic treatment. Recombinant TSH may be a useful tool to prevent myxedema madness or any severe manifestation of levothyroxine withdrawal for the follow-up of thyroid cancer.

Myxedema madness complicating postoperative follow-up of thyroid cancer

Although hypothyroidism is associated with an increased prevalence of psychiatric manifestations, myxedema madness is rarely observed. We report the case of a 62-year-old woman with no prior history of psychiatric disorders, who presented to the emergency department with psychomotor agitation 6 weeks after total thyroidectomy for papillary thyroid cancer. Serum thyroid stimulating hormone (TSH) on admission was 62.9 mIU/L and free T4 was < 0.35 ng/dL, indicating severe hypothyroidism. After ruling out other possible causes, the diagnosis of myxedema madness was considered; hence, antipsychotic drug treatment and intravenous levothyroxine were prescribed. Behavioral symptoms returned to normal within 4 days of presentation, while levels of thyroid hormones attained normal values 1 week after admission. Recombinant TSH (Thyrogen®) was used successfully to prevent new episodes of mania due to thyroid hormone withdrawal in further controls for her thyroid cancer. This case illustrates that myxedema madness can occur in the setting of acute hypothyroidism, completely reverting with levothyroxine and antipsychotic treatment. Recombinant TSH may be a useful tool to prevent myxedema madness or any severe manifestation of levothyroxine withdrawal for the follow-up of thyroid cancer.

Differential profile of ultrasound findings associated with malignancy in mixed and solid thyroid nodules in an elderly female population.

Objective. Ultrasonographic characteristics are associated with thyroid malignancy. Our aim was to compare the diagnostic value of ultrasound features in the detection of thyroid malignancy in both solid and mixed nodules. Methods. We prospectively studied female patients (≥50 years) referred to ultrasound-guided fine needle aspiration biopsy. Ultrasound features considered suspicious were hypoechogenicity, microcalcifications, irregular margins, high anteroposterior (AP)/axial-ratio, and absent halo. Associations were separately assessed in mixed and solid nodules. Results. In a group of 504 elderly female patients (age = 69 ± 8 years), the frequency of malignant cytology was 6%. Thirty-one percent of nodules were mixed and 60% were solid. The rate of malignant cytology was similar for mixed and solid nodules (7.4 versus 5.8%, P: 0.56). While in mixed nodules none of the ultrasound characteristics were associated with malignant cytology, in solid nodules irregular margins and microcalcifications were significant (all P < 0.05). The combination of irregular margins and/or microcalcifications significantly increased the association with malignant cytology only in solid nodules (OR: 2.76 (95% CI: 1.25-6.10), P: 0.012). Conclusions. Ultrasound features were of poor diagnostic value in mixed nodules, which harbored malignant lesions as often as solid nodules. Our findings challenge the recommended minimal size for ultrasound-guided fine needle aspiration biopsy in mixed nodules.