Cevdet Aydin

Effects of percutaneous laser ablation treatment in benign solitary thyroid nodules on nodule volume, thyroglobulin and anti-thyroglobulin levels, and cytopathology of nodule in 1 yr follow-up

Objective: To investigate the effects of ultrasound (US)-guided percutaneous laser ablation (PLA) in the treatment of benign solid hypoactive thyroid nodules on nodule volume, thyroid functions, nodule cytology and patients’ complaints. Material and method: Criteria for enrollment in the study were as follows: patients with euthyroid, benign, hypofunctional nodule who had compressive symptoms or cosmetic complaints, but considered inoperable, or who rejected surgical treatment. PLA procedure at 3–5 watts (W) was applied to 15 thyroid nodules of 12 patients (4 male and 8 female; age range 20–78 yr, mean age 47.42±17.05 yr), and patients were followed up for 12 months. Thyroid functions and nodule volumes (ultrasonographically) were evaluated. US-guided fine needle aspiration biopsy (FNAB) was performed before and after the procedure, and biopsy specimens were cytologically evaluated. Results: The mean nodule volume before the procedure was 11.97 ml (min-max 0.95–26.30 ml). However, 12 months after the procedure the mean nodule volume was 2.21±2.32 ml (min–max 0.10–7.65 ml). The mean reduction in nodule volumes was 82%. Thyroglobulin levels reached peak values at 1 month after the procedure, and anti-thyroglobulin levels at 3 months after the procedure. FNAB performed at 12th month showed neutrophil polymorphs, macrophages, abundant cell debris, colloid, multinucleated giant cells, and small fragments of fibrous stroma which indicated that PLA procedure led to degenerative changes in nodules. Conclusion: US-guided PLA is a new, successful treatment method which is reliable in the long term in benign solid thyroid nodules for selected patients who are inoperable or do not prefer surgery.

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

Assessment of left ventricular functions by tissue Doppler echocardiography in patients with Cushing's disease

Objective: To verify whether tissue Doppler imaging (TDI) could contribute to a better understanding of the natural history of cardiomyopathy in active Cushing’s disease (CD), through its enhanced sensitivity to diastolic dysfunction, and identifying preliminary regional signs of systolic dysfunction before the appearance of clinical symptoms of cardiac pathologies. Methods: Eleven women with newly diagnosed CD and 32 control cases, purposely matched for gender, age, body mass index and co-incidental diseases were enrolled in this study. Echocardiographic examinations were assessed by conventional echocardiography and tissue Doppler imaging. The peak systolic velocity (S’m), early diastolic myocardial peak velocity (E’m), late diastolic myocardial peak velocity (A’m), isovolumic acceleration (IVA), myocardial pre-contraction time (PCT’m), myocardial contraction time (CT’m) and myocardial relaxation time (RT’m) were measured at septal and lateral mitral anulus. Results: In TDI, E’m and, E’m/A’m ratio were significantly lower, and PCT’m/CT’m ratio was higher, S’m, A’m, peak early diastole/E’m ratio, PCT’m, and isovolumetric myocardial relaxation time values were similar at lateral and septal anulus in patients with CD than controls (p>0.05). Lateral and septal anulus IVA were significantly lower in patients with CD than the control group (p<0.05). Correlation analysis showed that IVA time at lateral anulus correlated positively with S’m at lateral anulus (r=0.58; p=0.002) and IVA time at septal anulus correlated positively with S’m at septal anulus (r=0.51; p=0.008). Conclusion: Our study confirms that patients with CD have impaired diastolic function. More importantly, we also demonstrated an impairment of myocardial systolic function in patients with CD by TDI. We recommend using TDI in addition to conventional echocardiography parameters for the cardiovascular risk assessment of patients with Cushing’ syndrome.

Diagnostic accuracy of Thyroid Imaging Reporting and Data System in the prediction of malignancy in nodules with atypia and follicular lesion of undetermined significance cytologies

Thyroid Imaging Reporting and Data System (TIRADS) is a simple and reliable reporting system for the prediction of malignancy. We aimed to determine the role of TIRADS in the prediction of malignancy in subcategories of Bethesda Category III, atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS).

Effective treatment of severe pregnancy and lactation-related osteoporosis with teriparatide: case report and review of the literature

Abstract Pregnancy or lactation-related osteoporosis (PLO) is a very rare and debilitating condition which is usually diagnosed during the last trimester of the pregnancy or early postpartum period. Herein, we report a case with severe PLO and multiple vertebral compression fractures that were successfully treated with teriparatide. Twenty-three-year-old female patient was admitted to our clinic two months after her first spontaneous vaginal delivery with the complaint of severe back pain. Bone mineral density was measured using dual energy X-ray absorptiometry (DEXA), and low T- and Z-scores were observed in lumbar vertebras. In vertebral MRI, severe height loss was detected in thoracic (T) 5,7,10,11,12 vertebras. After exclusion of the other possible causes of OP, she was diagnosed to have PLO and the lactation was stopped. She was treated with calcium 1000 mg/day, cholecalciferol 800 mg/day and teriparatide 20 µg/day. At the 12th and 18th month of therapy, BMD was increased by 8% and 27%, respectively, at the lumbar spine and pain was completely relieved in few months. There are pharmacological therapy modalities that can be used in PLO. Bisphosphonates are effective, but there are some concerns that they accumulate in bone and may expose fetus in subsequent pregnancies. Teriparatide is a strong candidate to be the optimal medical therapy in severe cases since it is effective and safe.

The role of postoperative Tc-99m pertechnetate scintigraphy in estimation of remnant mass and prediction of successful ablation in patients with differentiated thyroid cancer.

ObjectiveSurgery and radioactive iodine (RAI) ablation constitute the mainstay of the treatment of differentiated thyroid carcinoma (DTC). In this study, we aimed to evaluate the diagnostic value of postoperative early Tc-99m pertechnetate scanning to detect remnant thyroid tissue and predict ablation success. MethodsDTC patients evaluated with postoperative Tc-99m pertechnetate scintigraphy and treated with RAI between January 2007 and December 2014 were recruited. The results of Tc-99m pertechnetate scanning were compared with therapeutic I-131 whole-body scanning (TxWBS) and diagnostic I-131 whole-body scanning (DxWBS) performed 6–9 months after RAI. ResultsThere were 154 (21.5%) male and 563 (78.5%) female patients, with a mean age of 49.11±12.35 years. Postoperative Tc-99m pertechnetate scanning was positive in 499 patients (69.6%) and negative in 218 (30.4%) patients. There were 673 (93.9%) patients with a positive TxWBS scan and 44 (6.1%) patients with negative TxWBS scan. Considering TxWBS as the standard test, sensitivity, specificity, positive predictive value, and negative predictive value of Tc-99m pertechnetate scanning were 72.2, 70.5, 97.4, and 14.2%, respectively. DxWBS was positive in 57 (9.0%) and negative in 564 (91%) patients. Ablation dose was higher and preablation thyroglobulin was lower in patients with negative DxWBS (P=0.001 and 0.04, respectively). Overall, 171 (92.9%) of 184 patients with negative Tc-99m pertechnetate had negative DxWBS. ConclusionPostoperative Tc-99m pertechnetate scintigraphy has a high positive predictive value to detect remnant tissue in patients with DTC. Although negative Tc-99m pertechnetate scanning does not indicate removal of all thyroid tissue, it is related to successful ablation in more than 90% of patients.

Gigantomastia and Macroprolactinemia Responding to Cabergoline Treatment: A Case Report and Minireview of the Literature

Background. Macroprolactinemia is defined as predominance of high molecular weight prolactin forms in the circulation. Although macroprolactin is considered as a biologically inactive molecule, some authorities suggest treatment in symptomatic cases. Gigantomastia is defined as excess breast tissue and most cases in the literature were treated by surgical intervention. Case. A 44-year-old woman was admitted to our clinic with gigantomastia and galactorrhea. The patient had a demand for surgical therapy. In laboratory examination, she had hyperprolactinemia and macroprolactinemia. Pituitary imaging revealed 6 mm microadenoma in right side of the hypophysis. Since she was symptomatic, cabergolin treatment was started. Macroprolactin became negative, breast circumference decreased significantly, and galactorrhea resolved after treatment. Conclusion. Gigantomastia might be the presenting symptom in patients with macroprolactinemia. In these patients medical treatment with cabergoline may be used initially as an alternative to surgical approach.

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.

A new approach for standardization and increased accuracy of lymph node washout thyroglobulin in patients with differentiated thyroid carcinoma.

High values of fine needle aspiration washout thyroglobulin (FNAB‐Tg) are diagnostic for metastatic lesions of thyroid cancer. However, there is not a consensus on cutoff for high FNAB‐Tg level. In this study, we aimed to determine a more accurate and standardized parameter for FNAB‐Tg.

The correlation of sodium iodide symporter and BRAFV600E mutation in classical variant papillary thyroid carcinoma

BRAF(V600E) mutation was analyzed by real-time polymerase chain reaction in 96 consecutive cases with classical variant papillary thyroid cancer, and immunohistochemical staining of Na+/I- symporter (NIS) protein was evaluated. Localization (intracellular or membranous), density, and the intensity of cytoplasmic staining were characterized semiquantitatively. Extrathyroidal invasion, surgical margin positivity, and lymph node metastasis were compared with BRAF(V600E) mutation and NIS expression. Eighty-eight patients who had at least 24-month follow-up were also included in survival analysis. BRAF(V600E) mutation was determined in 78.1% (75/96) and functional NIS activity in 74% (71/96) of the cases. There were statistically significant differences in mean ages between BRAF(V600E) mutation-positive (48.6) and BRAF(V600E) mutation-negative cases (37.3; Levene test, P=.419; Student t test, P=.001). The surgical margin positivity (46.7%) and extrathyroidal extension percentage (54.7%) in the BRAF(V600E) mutation-positive group were higher than the negative (28.6% and 33.3%, respectively) group, without statistical significance (P=.138 and P=.084, respectively). Functional NIS activity was higher in BRAF(V600E) mutation-positive cases (78.1%) than mutation-negative ones (57.1%; P=.047). The possibility of moderate and intense cytoplasmic staining in BRAF(V600E) mutation-positive cases (72%) was 6.3 times higher than the possibility of weak staining (28%) in the mutation-positive cases (95% confidence interval, 2.2-18.8; P=.001). Functional NIS expression is higher in patients with classical variant papillary thyroid cancer with BRAF(V600E) mutation. However, the clinical features were not found to be associated with NIS expression. There may be different mechanisms determining the outcome of therapy.