Ahmet Dirikoc

The Association Between Thyroid Carcinoma and Hashimoto's Thyroiditis: The Ultrasonographic and Histopathologic Characteristics of Malignant Nodules

BACKGROUND Some but not all reports, particularly those of a retrospective nature, have noted an increased risk of carcinoma in thyroid nodules in patients with Hashimotos thyroiditis (HT). Thyroid cancer (TC) in patients with HT, however, have been reported to have a better prognosis. In the presence of HT, the ultrasonography (US) appearance of the thyroid gland might vary greatly, making it more difficult to differentiate between benign and malignant nodules. The aim of this study was to determine if there is an association between TC and HT and to determine if the US and histopathologic characteristics of malignant nodules in patients with and without HT are similar. METHODS Six hundred thirteen patients who underwent total thyroidectomy between 2005 and 2008 for nodular goiter were included in this study. The preoperative US characteristics and postoperative histopathologic features in patients with and without HT were compared. The diagnosis of HT was based on histopathologic features. RESULTS Ninety-two patients had HT. The prevalence of TC in the HT patients was 45.7%. In contrast, it was 29% in patients without HT (p = 0.001). The prevalence of HT in the patients with TC was 21.8% and in patients without TC was 11.9% (p = 0.001). The rate of incidental TC, defined as TC identified during surgery or following histopathologic examination of permanent sections despite preoperative benign cytology results, was higher in patients with HT (33.3%) than in those without (13.0%) HT (p = 0.004). The US characteristics of papillary thyroid carcinoma, which included number of nodules, echogenity, echoic texture, microcalcifications, macrocalcifications, halo sign, and regularity of margins, were similar in the group with HT compared with the group without HT. When the histopathologic characteristics of papillary thyroid carcinoma in patients with and without HT were compared, again there was no significant difference. CONCLUSIONS We suggest that there is an association between HT and TC, and HT may predispose to the development of TC. This indicates the need for close observation of neoplastic changes in patients with HT. Nevertheless, the presence of HT seems to have no effect on the US and histopathologic characteristics of malignant nodules in TC patients. This finding may indicate that evaluation of nodules and initial treatment of TC in these patients does not require different management.

Percutaneous laser ablation of an autonomous thyroid nodule: effects on nodule size and histopathology of the nodule 2 years after the procedure.

Ultrasound (US)–guided percutaneous laser ablation (PLA) is a new procedure for decreasing the size of thyroid nodules (1–5). It has been used to treat compressive symptoms in benign solitary cold thyroid nodules (1–5) and to reduce thyroid hormone production in autonomous functioning thyroid nodules (6–9). In two cases of anaplastic thyroid carcinoma, it was used for palliative purposes (7,10). Pacella et al. (11) first described thermal injury of thyroid tissue by PLA. We previously studied the effects of PLA on the cytology of hypofunctioning thyroid nodules, nodule volume, and thyroid function, but did not report data on histopathologic changes produced by US-guided PLA in thyroid nodules (4). We now describe the histopathology of an autonomously functioning thyroid nodule 2 years after PLA. A 25-year-old woman presented with swelling of the neck and difficulty breathing. On physical examination, a nontender, mobile, moderately firm nodule of about 3 cm was noted in the right lobe of the thyroid. Serum thyrotropin (thyroid-stimulating hormone, TSH) was 0.55 mIU=mL (normal range: 0.4–4 mIU=mL), serum free thyroxine level was 1.21 ng=dL (normal range: 0.85–1.78 ng=dL), and serum free triiodothyronine level was 3.85 pg=mL (normal range: 1.57– 4.71 pg=mL), all within normal limits. Serum antithyroid peroxidase antibody was 5 IU=mL (normal range: 0–35 IU=mL), anti-thyroglobulin antibody (anti-TgAb) was 10 IU=mL (normal range: 0–40 IU=mL), serum Tg level was 10 ng=mL (normal range: 0–55 ng=mL), and serum calcitonin level was 1 pg=mL (normal range: 5.0–11.5 pg=mL). US was performed using a Pro 200 Scanner (GE Medical Systems Kyunggido, Korea), and a 13.50 mL solid nodule was detected in the right lobe of the thyroid. Echogenity was normal in the remaining thyroid tissue. Technetium-99m (Tc) scintigraphy showed a hot nodule in the right lobe, with slight suppression of 99m Tc uptake in the remainder of the thyroid (Fig. 1). US-guided fine-needle aspiration biopsy of the nodule showed benignappearing thyrocytes, which formed occasional follicles. The patient refused surgery or radioiodine treatment. PLA of the thyroid nodule was advised, and she accepted and gave informed consent to the procedure. The approval of the local ethics committee was obtained (Ataturk Education and Research Hospital, Ankara; date: 09.11.2004; record no.: 2004=10=009). A 16-mm-long, 21-gauge (0.8 mm) needle was custommanufactured for the nodule. Sedation was obtained with 7.5 mg diazepam (SABA Pharmaceuticals, Istanbul, Turkey) 1 hour prior to the procedure. The skin above the nodule was sterilized with 95% ethanol, and 2 mL of 2% Lidocaine was injected subcutaneously. The custom-produced needle was inserted under US guidance into the proper position within the nodule along its long axis. Then, a bare flat-end fiber, 400mm in diameter, was inserted through needle lumen. The fiber tip was aligned with the needle tip, and then advanced 5 mm to provide direct contact with thyroid tissue. Two-plane US imaging was used to confirm that the fiber tip was at least 2 cm from surrounding vital organs. A total of 3000 J of energy was transferred through the fiber tip within 600 seconds with 5 W power by an electronic infrared diode laser at 810 nm wavelength using a gallium-aluminumarsenide power source (model 15 plus; Diomed, Cambridge, UK) (1,2,4,6,9,10). The patient experienced neck discomfort and pain extending toward the chin. The pain ceased after power transfer was stopped, and no complications were encountered after the procedure. Indirect laryngoscopic examinations before and after the procedure were normal. The thyroid nodule volume, which was 13.50 mL before the procedure, decreased to 8.40 mL 3 months later and to 4.20 mL 6 months after PLA. The patient’s compression symptoms (difficulty in breathing and difficulty in swallowing) decreased from 7 points to 2 points when evaluated by visual analog scale (min, 0; max, 10) (1,2,4). Nine months after PLA, however, the volume of the nodule had increased to 5.5 mL; at 1 year it was 6.6 mL; at 2 years it was 10 mL. Serum TSH, triiodothyronine, and thyroxine remained normal, but serum anti-TgAb level, which was 10 IU=mL before the procedure, increased to 150 IU=mL at the 6th month and regressed to 60 IU=mL at the 24th month. US-guided fine-needle aspiration biopsy was performed 1 year after PLA and showed no evidence of malignancy. Scintigraphies performed at 12th and 24th months by Tc showed that the hot nodule was still present, but serum TSH was normal (0.72mIU=mL) at 24 months. The patient felt that the size of the nodule was increasing, and the visual analog scale was increased to 7 points. Therefore, thyroidectomy was advised, and the patient agreed to this. The patient underwent complete resection of the right lobe, which contained the nodule, isthmusectomy, and near-total resection of the left lobe. Macroscopic examination showed a white-gray lesion in the region of the nodule, surrounded by hemorrhagic areas (Fig. 2). Rare old and new hemorrhagic regions, minimal fibrosis, and multiple microfollicles with colloid in their lumen were observed (Fig. 3) on histopathological examination. In the thyroid tissue surrounding the nodule, lymphoid cells with occasional germinal centers were observed (Fig. 4). Also, lymphocytic infiltration was observed in the opposite lobe. PLA-induced thermal injury in human thyroid tissue was first described by Pacella et al. (11). They reported the histopathology of single nodules in two patients whose THYROID Volume 18, Number 7, 2008 a Mary Ann Liebert, Inc. DOI: 10.1089=thy.2007.0316

Correlation of normal thyroid ultrasonography with thyroid tests

BACKGROUND Thyroid disorders are frequently seen in the community. Thyroid ultrasonography (US) is commonly used in the diagnosis of thyroid diseases. The relationship between heterogeneous echogenicity of thyroid gland and thyroid tests are well known. METHODS The aim of this study is to evaluate the correlation of normal US with the thyroid tests. A total of 681 individuals were enrolled in the study. Individuals were separated into two groups as normal (group 1) and hypoechoic (group 2) according to the echogenicity in US. Subjects with nodular thyroid lesions were excluded from the study. Thyroid stimulating hormone (TSH), free T4 (fT4), thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb) values were recorded in both groups and thyroid stimulating hormone receptor antibody (TRAb) was recorded in individuals with low TSH. RESULTS 86.1% of individuals in group 1 had normal TSH, 93.7% had normal thyroid antibodies and in 77.6% of individuals, all thyroid tests performed were normal. In the 6.9% of the group 2, all reviewed thyroid tests were normal (P<0.001). CONCLUSIONS Our study shows that US is correlated with normal thyroid function tests and is a valuable tool in the prediction of normal thyroid function.

Evaluation of cytopathological findings in thyroid nodules with macrocalcification: macrocalcification is not innocent as it seems

OBJECTIVE Microcalcification is strongly correlated with papillary thyroid cancer. It is not clear whether macrocalcification is associated with malignancy. In this study, we aimed to assess the result of fine needle aspiration biopsies (FNAB) of thyroid nodules with macrocalcifications. SUBJECTS AND METHODS We retrospectively evaluated 269 patients (907 nodules). Macrocalcifications were classified as eggshell and parenchymal macrocalcification. FNAB results were divided into four groups: benign, malignant, suspicious for malignancy, and non-diagnostic. RESULTS There were 79.9% female and 20.1% male and mean age was 56.9 years. Macrocalcification was detected in 46.3% nodules and 53.7% nodules had no macrocalcification. Parenchymal and eggshell macrocalcification were observed in 40.5% and 5.8% nodules, respectively. Cytologically, malignant and suspicious for malignancy rates were higher in nodules with macrocalcification compared to nodules without macrocalcification (p = 0.004 and p = 0.003, respectively). Benign and non-diagnostic cytology results were similar in two groups (p > 0.05). Nodules with eggshell calcification had higher rate of suspicious for malignancy and nodules with parenchymal macrocalcification had higher rates of malignant and suspicious for malignancy compared to those without macrocalcification (p = 0.01, p = 0.003 and p = 0.007, respectively). CONCLUSIONS Our findings suggest that macrocalcifications are not always benign and are not associated with increased nondiagnostic FNAB results. Macrocalcification, particularly the parenchymal type should be taken into consideration.

The relationship between diurnal variation of TSH and thyroid blood flow with Doppler ultrasonography in healthy adults

Abstract Aim. To determine the presence of a correlation between the Doppler parameters of thyroid blood flow and diurnal variation of TSH. Method. Thirty healthy adults were included. FT3, FT4, and TSH measurements were made at 08.00, 16.00, and 24.00. Thyroid volumes were calculated followed by peak systolic velocity (PSV) and resistance index (RI) from the inferior thyroid artery by Doppler ultrasonography. Results. The difference between diurnal measurements of TSH was found to be significant (1.29 ± 0.55 vs 3.09 ± 1.52; p < 0.001). PSV was detected to be higher at 24.00 compared to values measured at 08.00 and 16.00 (27.75 ± 9.54 vs 24.9 ± 8.51; p < 0.01 and 27.75 ± 9.54 vs 25.88 ± 9.82; p < 0.05). Mean RI values were lower at 24.00 compared to those at 08.00 and 16.00 (0.53 ± 0.07 vs 0.57 ± 0.07; p < 0.001 and 0.53 ± 0.08 vs 0.56 ± 0.05; p < 0.05). Conclusion. Thyroid blood flow should be evaluated diurnally by Doppler ultrasonography in thyroid pathologies.

Hypocalcemia development in patients operated for primary hyperparathyroidism: Can it be predicted preoperatively?

Objective Primary hyperparathyroidism (PHP) is a common endocrine disease, and its most effective treatment is surgery. Postoperative hypocalcemia is a morbidity of parathyroid surgeries, and it may extend hospitalization durations. The purpose of this study is to determine the predictive factors related to the development of hypocalcemia and hungry bone syndrome (HBS) in patients who underwent parathyroidectomy for PHP. Materials and methods Laboratory data comprising parathyroid hormone (PTH), calcium, phosphate, 25-OHD, albumin, magnesium, alkaline phosphatase (ALP), blood urea nitrogen (BUN), and thyroid stimulating hormone (TSH) of the patients were recorded preoperatively, on the 1st and 4th days postoperatively, and in the 6th postoperative month, and their neck ultrasound (US) and bone densitometry data were also recorded. Results Hypocalcemia was seen in 63 patients (38.4%) on the 1st day after parathyroidectomy. Ten patients (6.1%) had permanent hypocalcemia in the 6th month after surgery. Out of the patients who underwent parathyroidectomy for PHP, 22 (13.4%) had HBS. The incidence of postoperative hypocalcemia was higher in patients who underwent parathyroidectomy for PHP, who had parathyroid hyperplasia, and who had osteoporosis. Preoperative PTH, ALP, and BUN values were higher in those patients who developed HBS. Furthermore, HBS was more common in patients who had osteoporosis, who had parathyroid hyperplasia, and who underwent thyroidectomy simultaneously with parathyroidectomy. Conclusions As a result, patients who have the risk factors for development of hypocalcemia and HBS should be monitored more attentively during the perioperative period.

Evaluation of Postural Parathyroid Hormone Change in Patients with Primary Hyperparathyroidism

Purpose. In the present study, we aimed to investigate postural change of PTH in normal individuals and in patients with primary hyperparathyroidism (PHPT). Methods. Twenty-two patients with PHPT and nine healthy controls were enrolled. Following 12 h of fast, patients stayed in recumbent position for an hour and PTH and total Ca measurements were performed at the 45th and 60th minutes of resting. Afterwards, the patients resumed an upright posture for an hour and again blood samples were taken at the 45th and 60th minutes of standing. Results. In the PHPT group, mean PTH was calculated as 153.9 pg/mL in the recumbent position while it was 206.3 during upright position (Δ change was 47.7) (P < 0.001). In the control group mean serum PTH was measured as 41.2 pg/mL in the recumbent position while it was 44.8 pg/mL in the upright position (Δ change was 1.7) (P = 0.11). In both groups, serum Ca was higher in the upright position compared to the recumbent position (P < 0.001). Conclusion. Postural change of serum PTH is significant only in PHPT group. Postural PTH test may give a clue to the clinician when the diagnosis of PHPT is equivocal.

Thyroid malignancy risk in different clinical thyroid diseases

Background/aim: To evaluate the malignancy risk of thyroid nodules in different clinical thyroid diseases. Materials and methods: Patients who underwent thyroidectomy between 2007 and 2014 were grouped as euthyroid, hypothyroid, and hyperthyroid. Further classification was made depending on the presence of solitary/multiple thyroid nodules. Results: Among 2870 patients, 1719 (59.9%) were euthyroid, 962 (33.5%) were hyperthyroid, and 189 (6.6%) were hypothyroid. Overall malignancy was detected in 980 (34.1%) patients. Malignancy rates were 42.1%, 42.9%, and 18.3% in the euthyroid, hypothyroid, and hyperthyroid groups, respectively (P < 0.001). A total 41.4% of patients with euthyroid nodular goiter (ENG) and 46.3% of patients with euthyroid multinodular goiter (EMNG) had thyroid malignancy (P = 0.169). Mean tumor size and capsular and vascular invasion were significantly lower in EMNG than in ENG. Among hypothyroid patients, 45.7% with solitary and 42.2% with multiple nodules were malignant (P = 0.705). When toxic nodular goiter and toxic multinodular goiter were analyzed together, malignancy rate was 24.7% (104/421), and when Graves with nodule/nodules was considered, it was 19.7% (59/299). Conclusion: In hypothyroid or euthyroid patients who underwent thyroidectomy, malignancy rate was higher than 40%, and was lower in hyperthyroid patients. Patients with multiple nodules carry a similar risk of malignancy as patients with solitary nodules, independent of the functional status.

Can ratio of the biggest tumor diameter to total tumor diameter be a new parameter in the differential diagnosis of agressive and favorable multifocal papillary thyroid microcarcinoma

OBJECTIVES In this study, we aimed to evaluate the usefulness of a new parameter -ratio of the biggest tumor diameter to total tumor diameter- for the differentiation of agressive and favorable papillary thyroid microcarcinomas (PTMC). MATERIALS AND METHODS The diameter of the biggest tumor focus was taken as the primary tumor diameter. Total tumor diameter was calculated as the sum of the maximal diameter of each lesion. Ratio of primary tumor diameter to total tumor diameter was defined as tumor diameter ratio (TDR). Positive and negative predictive value, sensitivity and specificity of TDR to predict capsular invasion, extrathyroidal extension (ETE) and lymph node metastasis (LNM) were determined. RESULTS Mean TDR was significantly lower in multifocal PTMC patients with capsular invasion, ETE, lymphovascular invasion and LNM compared to patients without these features. The sensitivities of TDR for the detection of LNM, ETE and capsular invasion were 100%, 100% and 94.2%, respectively. Specificity of TDR was 86.2% for LNM, 88% for ETE and 94.7% for capsular invasion. Best cut off values of TDR that can predict capsular invasion, ETE and LNM in multifocal PTMC were 0.62, 0.57 and 0.56, respectively. Multifocal papillary thyroid carcinoma patients with capsular invasion, ETE and LNM had significantly lower mean TDR when compared to ones without these features. CONCLUSION Decreased TDR was associated with capsular invasion, ETE and LNM in patients with multifocal PTMC and PTC. This new parameter might be particularly helpful for the detection of aggressive behavior in multifocal PTMCs.