Assessment of The Bethesda System for Reporting Thyroid Cytopathology.

OBJECTIVES: Long-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA). METHODS: Histologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated. RESULTS: Follow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM). CONCLUSIONS: Appropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.

Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors.

OBJECTIVE: To characterize large adrenal tumors (≥4 cm in diameter) and to identify features associated with malignancy. PATIENTS AND METHODS: We investigated the clinical, biochemical, and imaging characteristics in a large retrospective single-center cohort of patients with adrenal tumors of 4 cm or more in diameter during the period of January 1, 2000, through December 31, 2014. RESULTS: Of 4085 patients with adrenal tumors, 705 (17%) had adrenal masses measuring 4 cm or more in diameter; of these, 373 (53%) were women, with a median age of 59 years (range, 18-91 years) and median tumor size of 5.2 cm (range, 4.0-24.4 cm). Underlying diagnoses were adrenocortical adenomas (n=216 [31%]), pheochromocytomas (n=158 [22%]), other benign adrenal tumors (n=116 [16%]), adrenocortical carcinomas (n=88 [13%]), and other malignant tumors (n=127 [18%]). Compared with benign tumors, malignant tumors were less frequently diagnosed incidentally (45.5% vs 86.7%), were larger (7 cm [range, 4-24.4 cm] vs 5 cm [range, 4-20 cm]), and had higher unenhanced computed tomographic (CT) attenuation (34.5 Hounsfield units [HU] [range, 14.1-75.5 HU] vs 11.5 HU [range, -110 to 71.3 HU]; P<.001). On multivariate analysis, older age at diagnosis, male sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT attenuation were all found to be statistically significant predictors of malignancy. CONCLUSION: The prevalence of malignancy in patients with adrenal tumors of 4 cm or more in diameter was 31%. Older age, male sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT attenuation were associated with an increased risk for malignancy. Clinical context should guide management in patients with adrenal tumors of 4 cm or more in diameter.

Patients' knowledge about the outcomes of thyroid biopsy: a patient survey.

PURPOSE: Fine-needle aspiration biopsy of the thyroid is an increasingly common outpatient procedure. Patients are counseled about the indications and risks of this procedure and informed consent is obtained. We aimed to assess the extent to which patients acquired necessary knowledge during this process. METHODS: Survey study conducted in a thyroid nodule clinic at a referral center. Adult patients who had just undergone a thyroid biopsy were asked to complete a survey, including eight questions regarding the indications and potential outcomes of thyroid biopsy. The main outcome of the study was to assess the patients' knowledge based on the response to each individual survey question. RESULTS: Two-hundred and ninety-seven patients were eligible, of which 196 (66%) completed the survey: most were women (76%), had adequate reading health literacy (95%) and a mean age of 58 years. Although 86% of patients correctly identified evaluation for thyroid cancer as the main indication for their biopsy, 56% were not aware of the likelihood of this diagnosis. Almost all (>90%) of respondents knew that results could be benign or malignant; fewer were aware of non-diagnostic (71%) or indeterminate (68%) outcomes, or of the need for additional diagnostic testing after the biopsy (33%). CONCLUSIONS: After undergoing thyroid biopsy, a high proportion of well-educated patients remained unaware of their risk for thyroid cancer, potential outcomes, and downstream consequences of their biopsy. This quality gap raises the possibility that informed consent procedures that meet legal standards may leave patients undergoing thyroid biopsy paradoxically uninformed.

Risk of Malignancy in Thyroid Nodules with Non-Diagnostic Fine-Needle Aspiration: A Retrospective Cohort Study.

BACKGROUND: Fine-needle aspiration (FNA) of thyroid nodules is commonly performed, and despite the use of ultrasound (US) guidance, the rate of non-diagnostic FNAs is still significant. The risk of malignancy of thyroid nodules with a non-diagnostic FNA is not clearly defined. However, most studies exclude the majority of patients without a repeat biopsy or surgery, thus increasing the likelihood of selection bias. The aims of this study were to determine the malignancy risk in nodules with an initial non-diagnostic FNA, and to identify the factors associated with malignancy. METHODS: This was a retrospective cohort study of patients with thyroid nodules who underwent US-guided FNA between 2004 and 2010 and had a non-diagnostic result. Patients were followed until confirmatory diagnosis of the nature of the nodule was made. The outcome of malignant or benign disease was based on one of the following: (i) final surgical pathology following thyroidectomy; (ii) repeat biopsy; (iii) clinically, based on repeat ultrasound performed at least three years following biopsy; or (iv) report of thyroid status for patients without follow-up visits contacted by mail. RESULTS: There were 699 nodules from 665 patients included. The mean age was 59 ± 15 years, and 71.7% were women. There was complete follow-up of 495 nodules. After a median follow-up of 2.7 years, thyroid cancer was found in 15 nodules. The prevalence of malignancy was 3% (15/495). The presence of nodular calcifications was the strongest predictor of thyroid malignancy (odds ratio 5.03 [confidence interval 1.8-14.7]). Initial nodule size was inversely associated with malignancy (odds ratio 0.55 [confidence interval 0.28-0.93]). However, the 193 patients without follow-up had smaller nodules compared with those included in the analysis. None of the patients with repeatedly non-diagnostic results were diagnosed with thyroid cancer at follow-up. CONCLUSION: The prevalence of thyroid cancer in nodules with non-diagnostic results is lower than the malignancy rate in thyroid nodules in general, but not negligible. They should be followed as per guidelines with heightened suspicion for nodules containing calcifications. Nodules with repeatedly non-diagnostic FNA results especially in the absence of calcifications have a low risk of malignancy and may be observed.

Survey of current approaches to non-diagnostic fine-needle aspiration from solid thyroid nodules.

The exact frequency of non-diagnostic ultrasound-guided fine-needle aspiration (USFNA) is unknown. Clinical guidelines suggest repeating USFNA of these nodules. However, there is no specific recommendation or evidence on how and when this re-aspiration should be done. We aim to describe the approaches considered by endocrinologists to yield the highest likelihood of a satisfactory sample in solid thyroid nodules. A cross-sectional survey of The Endocrine Society (TES) and the American Thyroid Association members was conducted between October and December 2012. A total of 694 surveys were returned, 648 (93.4 %) from TES. The responders were equally divided between private and academic settings and had a high degree of expertise. Thirty-nine percent of respondents estimated the frequency of non-diagnostic USFNA to be above 10 %. For its management, 311 (46 %) recommended repeating USFNA in 1-3 months. For a second non-diagnostic USFNA, 216 (31 %) recommend surgery. The most common approaches to increase the diagnostic yield were (1) use of suction with USFNA, 18 % and (2) changing the targeted area of biopsy within the nodule, 18 %. Few considered the patients' preferences as an important driver for the management of non-diagnostic USFNA. Finally, a molecular test for bypassing non-diagnostic USFNA was regarded as the most needed strategy for future research. Variability exists in the management of non-diagnostic USFNA and strategies to increase the diagnostic yield. Testing the suggested strategies in clinical trials and understanding patient's preferences should be supported by guideline panels and funding agencies.

Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules in patients taking novel oral anticoagulants.

BACKGROUND: Ultrasound-guided fine-needle aspiration biopsy (USGFNAB) is the most accurate form of evaluation for thyroid nodules. Many patients with thyroid nodules who present for USGFNAB are on anticoagulant agents, including the novel oral anticoagulants (NOACs), for stroke prevention in atrial fibrillation or venous thrombosis prophylaxis. SUMMARY: There has been at least one retrospective study describing neck USGFNAB bleeding risks in patients on antithrombotic and/or anticoagulant agents. This study concluded that there was no major bleeding risk or increase in hematoma formation in patients on antithrombotic or anticoagulant agents while undergoing USGFNAB, and there was no need to discontinue these agents prior to the procedure. With the emergence of NOACs, further recommendations should be made for patients on these agents who will be undergoing USGFNAB for thyroid nodules. Currently, there are no published studies regarding patients on NOACs who undergo USGFNAB. CONCLUSIONS: It has previously been established that patients on historical anticoagulant agents do not need to discontinue therapy prior to minor procedures such as needle aspirations or dental procedures. Therefore, in patients currently taking dabigatran, rivaroxaban, or apixaban, it is concluded that it is reasonable and safe to continue the novel oral anticoagulant agents prior to USGFNAB of thyroid nodules without major risk of bleeding. This conclusion is based not only on the fact that minor procedures are considered safe in patients on NOACs, but also because patients on historical anticoagulant agents do not need to discontinue therapy prior to minor procedures.

Symptomatic amyloid goiters: report of five cases.

BACKGROUND: Massive amyloid deposition in the thyroid to the point of goiter formation is rare. Here we describe the clinical presentation and outcomes of five patients with amyloid goiter (radiographically confirmed goiter in the context of tissue-proven thyroid amyloidosis) encountered in the past 23 years at our institution. METHODS: Mayo Clinic archives were searched between 1987 and 2010 for a diagnosis of "thyroid amyloidosis," "amyloid deposits," "amyloid deposition," or "liquid chromatography consistent with amyloid." Inclusion criteria were symptomatic thyromegaly; tissue confirmation of thyroid enlarged by amyloid deposits; and radiologic confirmation of thyroid enlargement. RESULTS: Five patients were identified who met all inclusion criteria. Amyloid goiter etiology included both primary and secondary amyloidosis, and the goiters ranged in weight from 50 to 130 g each. Diagnosis was made by fine-needle aspiration biopsy with Congo red staining and, if needed, spectrophotometry. All five patients had histories of persistent hoarseness for several years before presentation with compressive symptoms referable to their enlarging thyroids, and all had some degree of thyroid dysfunction (both hypothyroidism and hyperthyroidism) by the end of our follow-up period, which ranged from 5 months to 13 years. Two patients underwent surgical interventions, two were managed conservatively, and in one, the goiter shrank after systemic therapy for amyloidosis. CONCLUSIONS: Our clinical observations suggest slower goiter progression and a higher prevalence of thyroid dysfunction than previously thought.

Risks and benefits of parathyroid fine-needle aspiration with parathyroid hormone washout.

OBJECTIVE: To describe the experience with parathyroid fine-needle aspiration (FNA) and parathyroid hormone (PTH) washout at Mayo Clinic Rochester, Rochester, Minnesota. METHODS: We retrospectively reviewed all parathyroid FNA procedures performed at Mayo Clinic Rochester between January 2000 and December 2007. Clinical, biochemical, and imaging information, parathyroid FNA procedure, and cytology, surgical, and pathology reports were reviewed, and descriptive statistics, sensitivity, specificity, and positive predictive values are presented. RESULTS: During the study period, 75 parathyroid FNAs were performed on 74 patients. Cytology results were available for 74 of 75 procedures, with only 31% interpreted as parathyroid cells. PTH washout was performed in 67 patients (91%). Parathyroid FNA with PTH washout had a sensitivity of 84%, specificity of 100%, positive predictive value of 100%, and accuracy of 84%. At the time of surgical treatment, 2 patients were noted to have an inflammatory response from the parathyroid FNA biopsy, 1 had a parathyroid abscess, and 2 had a hematoma. In 3 of these 5 patients, the necessary conversion of a minimally invasive surgical procedure to the standard surgical approach prolonged the surgical time. CONCLUSION: Parathyroid FNA with PTH washout had a superior performance in comparison with parathyroid scanning or ultrasonography alone. The main limitations of parathyroid FNA with PTH washout are (1) the need for initial identification of a potential parathyroid adenoma by ultrasonography and (2) the number of false-negative results. Parathyroid FNA resulted in complications affecting the surgical procedure in 3 patients.

Parathyroidectomy-induced thyroiditis.

OBJECTIVE: To highlight the possibility of development of thyroiditis after parathyroidectomy. METHODS: Clinical and laboratory findings in 2 cases are presented, and the relevant literature is reviewed. RESULTS: In 2 women (84 years old and 55 years old) with no history of thyroid disease in one of them and a remote history of excision of a follicular adenoma in the other, thyrotoxicosis developed a few days to a week after parathyroidectomy for primary hyperparathyroidism. The first patient underwent bilateral cervical exploration with removal of a right inferior parathyroid adenoma, whereas the second patient had excision of 3 1/2 parathyroid glands for 4-gland hyperplasia and 2 benign nodules from the left thyroid lobe. Both surgical procedures were uncomplicated. Neither patient had received any iodinated contrast agents or medications such as lithium or amiodarone before presentation. Laboratory results showed elevated levels of free thyroxine, suppressed thyroid-stimulating hormone levels, very low radioiodine uptake (in the second patient), and an elevated thyroglobulin level (in the first patient). Both patients were treated symptomatically with beta-adrenergic antagonists. Thyroid function normalized and symptoms diminished after 1 to 2 months. CONCLUSION: Parathyroidectomy-induced thyroiditis is underrecognized. The majority of patients are asymptomatic, although clinically significant thyrotoxicosis can also occur. Candidates for parathyroidectomy should be informed of this potential complication, and thyroid function should be assessed if clinically indicated.

Development and application of magnetic resonance elastography of the normal and pathological thyroid gland in vivo.

PURPOSE: To noninvasively assess the shear stiffness of the thyroid gland in vivo in order to determine whether magnetic resonance elastography (MRE) might hold clinical utility in the diagnosis of thyroid disease. MATERIALS AND METHODS: Quantitative parametric images of thyroid stiffness in normal volunteers and patients were produced and quantitative stiffness values measured. Average gland stiffness was determined by region of interest analysis of the parametric images. This technique was used to assess stiffness of the thyroid in normal individuals (n = 12), patients with Hashimoto's thyroiditis (HT; n = 5), and patients with a solitary benign (n = 8) or malignant (n = 2) thyroid nodule. RESULTS: Mean shear modulus of normal thyroid glands was 1.9 +/- 0.6 kPa at 100 Hz and 1.3 +/- 0.5 kPa at 80 Hz, while that of HT glands was 2.8 +/- 0.6 kPa and 1.8 +/- 0.6 kPa at 80 Hz, respectively (P = 0.004 at 100 Hz). Elastographic parameters could not differentiate benign from malignant thyroid nodules in these small sample sizes. CONCLUSION: We developed a method for the application of MRE to the study of thyroid gland pathology. The results show that the HT gland can be differentiated from normal thyroid. The clinical utility of this imaging modality in the diagnosis and management of thyroid disease awaits further study.

Reliability of benign fine needle aspiration cytology of large thyroid nodules.

BACKGROUND: With increasing use of thyroid ultrasonography, thyroid nodules have been found to be extremely common. For over 25 years, fine needle aspiration (FNA) has been the pivotal diagnostic test to discriminate benign from potentially malignant thyroid nodules. Recently, false negative rates exceeding 10% have led to recommendations that thyroid nodules >/=4 cm should be resected regardless of cytology results. Our aim was to determine the false negative rate of FNA cytology on thyroid nodules >/=3 cm interpreted as benign at our institution. METHODS: A retrospective review was performed at Mayo Clinic from January 2002 through December 2006. RESULTS: From 6,921 ultrasonographic-guided thyroid FNAs, 742 were interpreted as benign and >/=3 cm. A definitive histologic diagnosis was available for 145 (20%) patients who underwent thyroidectomy: 1 (0.7%) was false negative. No additional thyroid malignancies were identified in 550 index nodules with average follow-up of 3 years. CONCLUSION: With precise ultrasonographic-guided aspiration, strict adherence to guidelines for adequacy of the sample, proper cytologic preparation, and most importantly, expert cytologic analysis, a diagnosis of benign is extremely reliable for thyroid nodules, regardless of size. Resection for diagnosis is not necessary, and a size >/=3 cm should not be an independent indication for resection.

Epidemiology of thyroid nodules.

Thyroid nodules are common and are commonly benign. The reported prevalence of nodular thyroid disease depends on the population studied and the methods used to detect nodules. Nodule incidence increases with age, and is increased in women, in people with iodine deficiency, and after radiation exposure. Numerous studies suggest a prevalence of 2-6% with palpation, 19-35% with ultrasound, and 8-65% in autopsy data. With widespread use of sensitive imaging in clinical practice, incidental thyroid nodules are being discovered with increasing frequency. Ultrasonography is the most accurate and cost-effective method for evaluating and observing thyroid nodules. Current ultrasonography machines are relatively inexpensive, sensitive, and easy to operate. Most endocrinologists are now using ultrasound examination in the initial evaluation of a patient with known or suspected thyroid nodule. The management of thyroid incidentalomas is a matter of controversy.

Hyperthyroidism and atrial myxoma--an intriguing cardio-endocrine association.

A 65-year-old woman presented with dyspnea and bilateral leg edema for 1 week, worsening fatigue for 1 month, and a 7-lb weight loss over the last summer. She was clinically and biochemically hyperthyroid. Echocardiography revealed a left atrial myxoma measuring 6.2 x 3.3 cm protruding into the mitral orifice and left ventricle during diastole. She was treated for Graves' disease with Iodine-131. Six weeks later, her left atrial myxoma measuring 10.1 x 6.2 x 2.4 cm was resected. She became euthyroid before surgery and then biochemically hypothyroid 6 weeks after radioiodine treatment, for which she subsequently required thyroxine replacement. Atrial myxomas are the most common primary cardiac neoplasms. At least 5% to 10% can be attributed to Carney's complex. More than two-thirds of patients with Carney's complex develop one or more cardiac myxomas. Although atrial myxomas in Carney's complex are histologically indistinguishable from the sporadic form, their clinical presentation and course is distinct. This is the first case of newly diagnosed Graves' disease that has been reported in association with an atrial myxoma. The features discussed in this article help differentiate between syndromic and sporadic atrial myxomas.