Prognostic factors on outcomes of follicular thyroid cancer.

PURPOSES: We investigated the influences of prognostic factors on long-term survival of patients with follicular thyroid cancer (FTC) based on all-cause mortality and two exclusive causes of death, FTC and non-FTC. METHODS: In this retrospective cohort study, we collected data of 204 patients with FTC diagnosed between 1985 and 2007 at National Taiwan University Hospital. For all-cause mortality, Cox proportional hazards models were used to estimate hazard ratios for prognostic factors. Cause-specific hazard and cumulative incidence function models were used to determine the influences of prognostic factors on FTC and non-FTC death, respectively. The dynamic processes of distant metastases and locoregional recurrences were included as time-varying factors in all models. RESULTS: The cumulative incidence of all-cause death was 24% and 45% at 10 and 20-years, respectively. Multivariate analyses identified that distant metastases, locoregional recurrences, and positive surgical margins were significant independent risk factors for overall survival, hazard, and cumulative incidence of FTC death. Age at diagnosis >60 years increased the risks of all-cause and non-FTC death as well as cumulative incidence of non-FTC death. Tumor size >4 cm had a harmful effect on overall survival. Female patients had higher risk and cumulative incidence of FTC death, but male patients had a higher cumulative incidence of non-FTC death. Lymph node metastases significantly increased the cumulative incidence of FTC death. CONCLUSION: Dynamic distant metastases and locoregional recurrences were the most dominant risk factors influencing FTC-specific hazard and cumulative incidence for FTC death by accounting for non-FTC death as a competing risk for FTC patients.

A registry of acromegaly patients and one year following up in Taiwan.

BACKGROUND/PURPOSE: The objectives of this study were to describe epidemiological data, treatment outcomes, and quality of life (QOL) of patients with acromegaly in Taiwan. METHODS: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. After enrollment, each patient was kept on observation for 1 year. RESULTS: The analyzed cohort included 272 acromegalic subjects (117 males, 155 females) with a mean age of 51.4 ± 12.9 years. Their mean age at diagnosis was 41.8 ± 12.1 years. About 83.8% patients presented symptoms of facial changes. Galactorrhea was noted at the earliest age of 32.7 ± 9.1 years. The duration between the onset of symptoms/signs and diagnosis was 6.9 ± 8.1 years. Around 70.3% patients harbored a macroadenoma. At enrollment, percentages of patients ever received surgical intervention, radiotherapy, somatostatin analogs, and dopamine agonists were 94.8%, 27.9%, 64%, and 30%, respectively. At the final following-up visit, the random growth hormone (GH), nadir GH after oral glucose tolerance test, and the insulin-like growth factor 1 levels were 2.7 ± 4.9 µg/L, 2.4 ± 6.1 µg/L, and 291.5 ± 162.4 ng/mL, respectively. The remission rate assessed by random GH level (≦2 µg/L) was 63.8%. The mean AcroQoL scores for the total 22 items were 64.0 ± 19.7. About 42.8% patients never sensed or felt discomfort about their changes in appearance. CONCLUSION: This study described the profiles of acromegaly in Taiwan. It is important to enhance early diagnosis and timely commencement of treatment to prevent serious complications of acromegaly.

Correlations of clinical parameters with quality of life in patients with acromegaly: Taiwan Acromegaly Registry.

BACKGROUND/PURPOSE: The objectives of this study were to evaluate the associations between clinical parameters and quality of life (QOL) of patients with acromegaly in Taiwan and to identify the impacts of hormone control, regimens, or co-morbidities on acromegalic patients' daily life. METHODS: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. Clinical data were recorded. The QOL of enrolled patients were assessed by using Acromegaly Quality of Life Questionnaire (AcroQoL). RESULTS: This study enrolled 272 acromegalic subjects (117 males, 155 females). Remission, defined by normalization of IGF-1, had significant positive association with QOL scores in psychological/appearance (PSY/APP) dimension (ß = 6.760, p = 0.023). Somatostatin analogues therapy had negative associations with total score and score in psychological (PSY) dimension (ß = -4.720, p = 0.046 and ß = -5.388, p = 0.035, respectively). Diabetes mellitus had negative associations with score in PSY dimension and psychological/personal relations (PSY/PER) dimensions (ß = -5.839, p = 0.034 and ß = -7.516, p = 0.013, respectively). Cerebral vascular accident (CVA) had significant negative associations with total score and scores in physical (PHY), PSY, and PSY/PER dimensions (ß = -26.632, p = 0.013; ß = -28.353, p = 0.024; ß = -25.648, p = 0.026; and ß = -34.586, p = 0.006, respectively). All these associations remained significant even after adjusted with sex and age. CONCLUSION: Our analysis suggested that not only hormone control but also therapeutic regimens and presence of co-morbidities might affect QOL of patients with acromegaly in some dimensions.

Extramedullary hematopoiesis involving the thyroid: A rare cytologic finding in otherwise healthy patients and review of literature.

BACKGROUND/PURPOSE: The thyroid gland is an uncommon site for the presence of extramedullary hematopoiesis (EMH). We report the cases of four Taiwanese women with hematopoietic elements on the smears of thyroid fine needle aspiration (FNA) samples and compare the findings with those of previously reported cases. METHODS: We retrieved the data of cases in which thyroid FNA performed between January 2000 and December 2016. The clinical manifestations, laboratory data, and image findings of cases with thyroid EMH were reported. A review of English literature was performed, and the reported cases were compared with our series. RESULTS: During the study period, 63,361 specimens of thyroid FNAs were identified. Four specimens contained hematopoietic elements from four women. Ultrasound study revealed calcifications in three patients. A review of English literature yielded 18 reports of thyroid EMH involving 29 patients. Twenty-six patients were women, and three were men. Nodule calcifications were found in 13 patients. Four patients had primary myelofibrosis, and one had chronic anemia. None had a thyroid malignancy. CONCLUSION: Four patients were noted to have bone marrow elements on the smears among 63,361 thyroid FNA samples. These four Taiwanese women presented with nodular goiter and foci of hematopoietic elements by thyroid FNA without any chronic disease of hematopoietic tissue or any evidence of a thyroid malignancy.

Adrenocorticotropic hormone levels before treatment predict recurrence of Cushing's disease.

BACKGROUND/PURPOSE: Cushing's disease (CD) is the most common cause of endogenous Cushing's syndrome. Transsphenoidal surgery (TSS) is the first choice of treatment. Predicting prognosis after treatment can benefit further strategies of management, but currently there is no convenient predictor. This study aims to investigate characteristic changes after treatment and to identify potential prognostic predictors. METHODS: We retrospectively studied the records of CD patients presenting to the National Taiwan University Hospital, Taipei, Taiwan between 1992 and 2011. They were categorized according to treatment response. Clinical features and examination findings were compared between groups. RESULTS: Forty-one patients with CD were included. The follow-up time was 0.26-19.3 years. The time interval between the onset of symptoms and diagnosis was 2.1-120.0 months. The initial remission rate of CD after the first treatment was 82.9%. Mean body mass index (BMI) was 27.4 kg/m2 before treatment and 26.0 kg/m2 3 months after treatment. The patients in remission had a greater decrease in BMI after treatment and lower dehydroepiandrosterone sulfate (DHEAS) levels before treatment, compared with the recurrent group (both p < 0.05). Adrenocorticotropic hormone (ACTH) levels before treatment showed a significant positive correlation with recurrent diseases (p < 0.05). CONCLUSION: A larger decrease in BMI after treatment and lower DHEAS levels before treatment were noted for the patients who stayed in CD remission. Higher ACTH levels before treatment predicted a recurrence of CD. These are potentially simple and practical predictors of prognosis.

Serial follow-up of presurgical treatment using pasireotide long-acting release with or without octreotide long-acting release for naïve active acromegaly.

The aim of the present study was to evaluate the serial changes of GH and IGF-1 in seven patients with naïve, active acromegaly following presurgical treatment of the somatostatin analog pasireotide long-acting release (LAR) and octreotide LAR. The patients were treated with pasireotide LAR with or without octreotide LAR for two years and underwent transsphenoidal adenomectomy. After treatment with the somatostatin analogs, the surgical cure rate was similar to that in patients who underwent transsphenoidal surgery alone. Diabetes insipidus was not identified in any patients after the operation. Pasireotide LAR was effective on GH as well as IGF-1 suppression and tumor size decreasing when used as the primary therapy. Future large-population studies to investigate the surgical curative rate after presurgical treatment with somatostatin analogs in patients with acromegaly and macroadenomas close to the cavernous sinus are warranted. However, that hyperglycemia developed following pre-surgical treatment with pasireotide should take into consideration.

The impact of locoregional recurrences and distant metastases on the survival of patients with papillary thyroid carcinoma.

OBJECTIVE: Some patients with papillary thyroid carcinoma (PTC) would suffer from locoregional recurrences or distant metastases. This study was aimed to elucidate the impacts of locoregional recurrences and distant metastases on these patients' survival. DESIGN: Retrospective hospital-based cohort study. POPULATION: Data were collected from 1636 subjects with PTC at National Taiwan University Hospital between 1985 and 2007. MEASUREMENTS: Overall and disease-specific survival curves were estimated by the Kaplan-Meier method. Time-independent and time-dependent prognostic factors were included simultaneously in multivariate analyses using Cox models. RESULTS: Overall survival (OS) rates at 10- and 20-years were 90% and 76%, respectively. The 10- and 20-year disease-specific survival (DSS) rates were 95% and 90%, respectively. Our multivariate analyses identified that older age, distant metastases (hazard ratio, HR: 6·69, 95% CI: 4·40-10·18), locoregional recurrences (HR: 1·88, 95% CI: 1·22-2·89), lymph node metastases, massive extrathyroid extension, male gender and larger tumour size (>4 cm) were significantly associated with poorer OS. Older age, distant metastases (HR: 15·03, 95% CI: 8·31-27·21), locoregional recurrences (HR: 3·63, 95% CI: 2·03-6·51), massive extrathyroid extension, male gender and larger tumour size (>4 cm) were independently related to worse DSS. The performance of high-dose (131) I ablation had a protective effect on OS and DSS. CONCLUSION: The locoregional recurrences had a moderately harmful impact on OS and DSS, but age and distant metastases were the major decisive factors for OS and DSS. High-dose (131) I ablation had a protective role. However, lymph node dissection did not alter the prognosis whenever lymph node metastases only influenced OS.

Predicting HLA genotypes using unphased and flanking single-nucleotide polymorphisms in Han Chinese population.

BACKGROUND: Genetic variation associated with human leukocyte antigen (HLA) genes has immunological functions and is associated with autoimmune diseases. To date, large-scale studies involving classical HLA genes have been limited by time-consuming and expensive HLA-typing technologies. To reduce these costs, single-nucleotide polymorphisms (SNPs) have been used to predict HLA-allele types. Although HLA allelic distributions differ among populations, most prediction model of HLA genes are based on Caucasian samples, with few reported studies involving non-Caucasians. RESULTS: Our sample consisted of 437 Han Chinese with Affymetrix 5.0 and Illumina 550 K SNPs, of whom 214 also had data on Affymetrix 6.0 SNPs. All individuals had HLA typings at a 4-digit resolution. Using these data, we have built prediction model of HLA genes that are specific for a Han Chinese population. To optimize our prediction model of HLA genes, we analyzed a number of critical parameters, including flanking-region size, genotyping platform, and imputation. Predictive accuracies generally increased both with sample size and SNP density. CONCLUSIONS: SNP data from the HapMap Project are about five times more dense than commercially available genotype chip data. Using chips to genotype our samples, however, only reduced the accuracy of our HLA predictions by only ~3%, while saving a great deal of time and expense. We demonstrated that classical HLA alleles can be predicted from SNP genotype data with a high level of accuracy (80.37% (HLA-B) ~95.79% (HLA-DQB1)) in a Han Chinese population. This finding offers new opportunities for researchers in obtaining HLA genotypes via prediction using their already existing chip datasets. Since the genetic variation structure (e.g. SNP, HLA, Linkage disequilibrium) is different between Han Chinese and Caucasians, and has strong impact in building prediction models for HLA genes, our findings emphasize the importance of building ethnic-specific models when analyzing human populations.

Hashimoto's encephalopathy: report of three cases.

Both severe thyrotoxicosis and hypothyroidism may affect brain function and cause a change in consciousness, as seen with a thyroid storm or myxedema coma. However, encephalopathy may also develop in patients with autoimmune thyroid diseases independent of actual thyroid function level, and this is known as Hashimoto's encephalopathy. Although most patients are found to have Hashimoto's thyroiditis, less frequently they have Graves' disease. Clinical manifestations include epilepsy, disturbance of consciousness, cognitive impairment, memory loss, myoclonus, hallucinations, stroke-like episodes, tremor, involuntary movements, language impairment, and gait impairment. Hashimoto's encephalopathy is a relatively rare disease. As a good response can be obtained with corticosteroid therapy, early diagnosis and treatment is very beneficial for patients. Here we report three patients with Hashimoto's encephalopathy with typical manifestations of hallucinations that were associated with hypothyroidism, hyperthyroidism, and euthyroid status, respectively. They all showed a dramatic response to methylprednisolone pulse therapy.

Reversine, a 2,6-disubstituted purine, as an anti-cancer agent in differentiated and undifferentiated thyroid cancer cells.

PURPOSE: A novel and effective treatment is urgently needed to deal with the current treatment dilemma in incurable differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC). Reversine, a small synthetic purine analogue (2,6-disubstituted purine), has been shown to be effective in tumor suppression. METHODS: We performed in vitro evaluation of anti-tumor effects of reversine on proliferation, cell cycle, and apoptosis in human PDTC, ATC, and follicular thyroid cancer cell lines, respectively. RESULTS: Treatment of these three lines with reversine inhibited proliferation in a time- and dose-dependent manner. G2/M accumulation was demonstrated in cell cycle analysis. Reversine induced apoptosis in PDTC cells with caspase-3 and caspase-8 activation, but not caspase-9. Use of a pan-caspase inhibitor before treatment with reversine attenuated cell death. Reversine also showed in vivo growth inhibitory effects on ATC cells in a xenograft nude mice model. CONCLUSIONS: Data demonstrated that reversine is effective in inhibiting the growth of thyroid cancer cells by cell cycle arrest or apoptosis, especially with the more aggressive ATC and PDTC. Apoptosis was induced by the mitochondria-independent pathway. Reversine is therefore worthy of further investigation in clinical therapeutics.

Associations between subclinical thyroid disease and metabolic syndrome.

Thyrotropin levels are outside normal reference range in subclinical thyroid disease. Metabolic syndrome (MetS) involves clustered cardiovascular risk factors, including abnormal lipids, insulin resistance, and hypertension. This study aimed to investigate associations between subclinical thyroid disease, thyrotropin levels, and metabolic syndrome in healthy subjects and identify associated biochemical markers. This cross-sectional study evaluated 9,055 healthy subjects examined at the Health Management Center, National Taiwan University Hospital from January 1, 2009 to December 31, 2009. Data collected included age, sex, height, weight, body mass index, waist circumference, pulse rate, and systolic/diastolic blood pressure. History of pregnancy, smoking/drinking status, family/personal thyroid disease, diabetes, dyslipidemia, and hypertension was obtained. Laboratory data included thyroid function tests, fasting glucose level, lipid profile, and C-reactive protein level. Participants were classified into subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroid groups according to thyrotropin levels. In euglycemic subjects, thyroid-stimulating hormone (TSH) levels correlated positively with waist circumference, triglycerides (TG), non-high density lipoprotein (HDL) cholesterol, diastolic blood pressure. In subclinical hyperthyroid subjects, TSH levels correlated positively with low density lipoprotein cholesterol (LDL-C), non-HDL cholesterol. No significant correlations were found between TSH levels and variables in the subclinical hypothyroid group. In the entire study population, TSH levels correlated positively with TG, non-HDL cholesterol, and systolic blood pressure (SBP)/diastolic blood pressure (DBP), but no correlation was shown with HDL-C. No significant associations were seen between MetS prevalence and thyrotropin levels. No clinically relevant biochemical markers, differences in thyrotropin levels, or statistical correlations are shown between subclinical thyroid disease and metabolic syndrome in healthy individuals.

The relationship of cytomorphology of medullary thyroid carcinomas between family members with the same RET proto-oncogene mutation.

OBJECTIVE: To evaluate the relationship of the cytomorphology of medullary thyroid carcinomas (MTC) between family members with the same RET proto-oncogene mutation. STUDY DESIGN: Review of the fine-needle aspiration slides of 13 cases with MTC proven by surgery and pathology from 5 unrelated families with either multiple endocrine neoplasia (MEN) type 2A or familial MTC (FMTC). RESULTS: Small, round, and abundant large oval-to-polygonal cells were major cytomorphologic findings in 66.7% of family members with exon 11, codon 634 TGC → CGC germline mutation. Small, round cells and only a few or no polygonal cells were found in 66.7% of family members with exon 11, codon 634 TGC → TTC germline mutation and in 100% of family members with codon 634 TGC → TGG germline mutations, as well as in 100% of family members with exon 10, codon 620 TGC → GGC germline mutation. CONCLUSIONS: The high rate of similarity of cytomorphology (66.7-100%) in the family members with MEN type 2A or FMTC might be related to the same etiology in the production of MTC in the same family. The relationship of the respective cytomorphology with the long-term prognosis is worth elucidating further.

In vivo evidence of duality effects for lovastatin in a nude mouse cancer model.

Statins, hydroxy-methyl-glutaryl coenzyme A reductase inhibitors, are the most effective medication for lowering cholesterol, cardiovascular morbidity and mortality. On the basis of our previous in vitro experimental results on an anaplastic thyroid cancer cell line, we designed a nude mouse model in which cancer cells were seeded subcutaneously to examine the potential anticancer effects of lovastatin in vivo. As expected, tumor growth was significantly reduced in the mice treated with 5 or 10 mg/kg/day of lovastatin compared with the positive control group. However, the tumor grew much faster in the mice treated with 1 mg/kg/day of lovastatin than in the positive control group. We suspect this result might be related to vascular endothelial growth factor. In this model, we found that lovastatin inhibits tumor growth at a high dosage (5 or 10 mg/kg/day), suggesting it could be used as an effectively adjuvant chemotherapy for cancer. However, it also promotes tumor growth at a low dosage (1 mg/kg/day). This duality effect should be further studied for patients treated with various dosages of statins.

The effects of growth inhibitory peptide on follicular thyroid cancer cell growth, migration, and invasion.

AIMS AND BACKGROUND: Thyroid cancer is the most common endocrine neoplasm worldwide. Although differentiated thyroid cancers are associated with a favorable survival, the prognosis worsens dramatically for patients with distant metastasis. Metastases from follicular thyroid carcinoma (FTC) occur earlier and are more aggressive than those from papillary thyroid carcinoma. For FTC that is resistant to radioactive iodine, new treatments are urgently needed. Human alpha-fetoprotein (HAFP) is a tumor-associated fetal protein that has been demonstrated to regulate tumorigenesis. Growth inhibitory peptide (GIP), a synthetic 34-mer peptide isolated from the third domain of HAFP, has been shown to have antitumor growth ability in various human cancers. However, the effects of GIP in FTC have not yet been studied. The aim of this study was to investigate the antitumor ability of GIP in FTC. METHODS AND STUDY DESIGN: Using both PBS and GIP control peptide as a negative control, the antiproliferative activity of GIP in the WRO human FTC cell line was determined using a tetrazolium-based colorimetric assay. In addition, cell migration and invasion assays were used to measure tumor metastasis inhibition effects in vitro. RESULTS: GIP did not inhibit WRO cell proliferation in a time- or dose-dependent manner. However, in WRO cells treated with GIP for 4 days, migration was significantly inhibited at concentrations of 50 and 100 microM (33.3% and 19.5%, respectively; both P <0.05). Cell invasion was also significantly inhibited at 50 and 100 microM (67.1% and 39.0%, respectively; both P<0.05). CONCLUSIONS: Although GIP failed to suppress FTC cell growth, it effectively interrupted both FTC cell migration and invasion abilities in vitro. Further validation in an animal model and elucidation of the underlying mechanisms will be required. GIP may potentially serve as an anti-FTC metastasis agent aiding current chemotherapy regimens.

Mutational spectrum of multiple endocrine neoplasia type 2 and sporadic medullary thyroid carcinoma in taiwan.

BACKGROUND/PURPOSE: Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant cancer predisposition syndrome, and > 95% of MEN 2 patients carry rearranged during transfection (RET) protooncogene mutants. We aimed to elucidate the genotype and phenotype relationship of RET proto-oncogene mutations in Taiwanese subjects with medullary thyroid cancer (MTC). METHODS: We genotyped the MEN-2-associated germ-line mutations by PCR-based sequencing of the RET gene. DNA was extracted from a total of 69 members from eight unrelated families with individuals affected by MTC, and from seven sporadic cases of MTC. RESULTS: RET mutations were found in four MEN 2A families, all at codon 634 (one with C>R, two with C>F, and one with C>W). One MEN 2A patient carried a de novo mutation at codon 634 (C>R). In two families of MEN 2B, all carried the mutation at codon 918 (M>T). These two cases of MEN 2B were all de novo mutations. One family of familial MTC or unclassified MEN 2 carried the codon 620 (C>F) mutation. Among the seven sporadic cases of MTC, none was found to carry any mutation in hotspot exons. Only two non-synonymous variants (T278N/exon 4 and D489N/exon 7) were found in two cases. However, these two variants were not uncommon in our elderly population. CONCLUSION: We found that all eight MTC patients with a family history or with the other phenotypes of MEN 2 had RET mutations, whereas no significant RET mutation was found in seven patients with isolated MTC without family history and other endocrine diseases. Molecular scanning of the RET gene in MEN 2 and MTC in Taiwanese patients probably should be limited to exons 10, 11 and 16, initially to be cost-effective.

The surgery and repeat aspiration outcomes of the atypia of undetermined significance/follicular lesion of undetermined significance category in The Bethesda System for Reporting Thyroid Cytopathology.

BACKGROUND/OBJECTIVE: The atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category is one of six diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). In this study, we report the diagnostic distribution of thyroid fine needle aspiration (FNA) cytology and analyze the outcome of AUS/FLUS cases. METHODS: A total of 29,937 thyroid FNA results, reported between April 2012 and December 2016, were retrieved from the database of a medical center. We reviewed the electronic medical records and analyzed the management of these patients. RESULTS: Overall frequency of AUS/FLUS is 3.1% in our laboratory, which is at the lower limit of the recommended range. Of these, 891 reports of AUS/FLUS from 770 patients were identified. Out of the 770 patients, 367 had surgical intervention. In these 367 patients, final surgical pathology yielded 204 (55.6%) malignancies, 12 indeterminateness (3.3%), and 151 (41.1%) benignity. Among these surgical patients, 113 (30.8%) had received a repeat FNA of the thyroid before thyroid resection. The difference between the malignancy rates among patients who directly received surgery after the first AUS/FLUS diagnosis (132 of 254, 52.0%) and patients having a repeat FNA before surgery (72 of 113, 63.7%) was not statistically significant. CONCLUSION: Our results are in agreement with AUS/FLUS diagnoses in less than 7% of specimens, and confirm that it is appropriate to perform either a repeat thyroid FNA or thyroid lobectomy, with the clinical decision being subject to the standardized management protocols of the second edition of TBSRTC in the AUS/FLUS category.

Computerized Cytological Features for Papillary Thyroid Cancer Diagnosis-Preliminary Report.

Fine needle aspiration cytology (FNAC) is the final diagnosis of thyroid nodules before surgery. It is important to further improve the indeterminate FNAC diagnosis results using computerized cytological features. This retrospective cross-sectional study included 240 cases, of whom 110 had histologic diagnosis of papillary thyroid cancers (PTC), 100 had nodular/adenomatous goiters/hyperplasia (benign goiters), 10 had follicular/Hurthle cell carcinomas, and 20 had follicular adenomas. Morphological and chromatic features of FNAC were quantified and analyzed. The result showed that six quantified cytological features were found significantly different between patients with a histologic diagnosis of PTC and patients with histologic diagnosis of benign goiters in multivariate analysis. These cytological features were used to estimate the malignancy risk in nodules with indeterminate FNAC results. The Area Under the Receiver Operating Characteristics (AUROC) of the diagnostic accuracy with a benign or malignant nature was 81.3% (p < 0.001), 78.7% (p = 0.014), and 56.8% (p = 0.52) for nodules with FNAC results of atypia, which is suspicious for malignancy and follicular neoplasm, respectively. In conclusion, quantification of cytological features could be used to develop a computer-aided tool for diagnosing PTC in thyroid nodules with indeterminate FNAC results.