Oya Topaloglu

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.

Subcapsular Hematoma Complication During Percutaneous Laser Ablation to a Hypoactive Benign Solitary Thyroid Nodule

Ultrasound (US)–guided percutaneous laser ablation (PLA) is a new procedure for reducing the size of large nonfunctioning thyroid nodules (1–5). It has also been used to treat autonomously functioning thyroid nodules (6–9), and was employed for palliative purposes in two cases with anaplastic thyroid carcinoma (7,10). Although fine-needle aspiration biopsy (FNAB) may be complicated by hematoma formation, there are few, if any, reports of this occurrence after PLA treatment of thyroid nodules. We would like to report this complication. A 42-year-old man with an apparently otherwise unremarkable past medical history presented with swelling of the neck and difficulty in breathing and swallowing. Physical examination revealed a 4 cm, mobile, nontender nodule of medium consistency in the right lobe of the thyroid. Serum TSH, free T4, free T3, thyroglobulin, and calcitonin were normal, and tests for antibodies to thyroid peroxidase and thyroglobulin were negative. Ultrasonography was performed by Pro 200 Scanner (GE Medical Systems, Kyunggido, Korea), and a 16.8 mL solid nodule was observed in right lobe of the thyroid. Scintigraphy performed by Technetium-99m (99mTc) showed a cold nodule in the right lobe of the thyroid. FNAB of the nodule was read as benign. The patient refused surgery but agreed to undergo PLA. Informed consent for this procedure was given by the patient, and the hospital’s ethics committee approved it. Because of the large size of the nodule, the procedure was planned in two stages, first the inferior half of the nodule and then the superior half. A 32mm, 21-gauge (0.8 mm) needle was custom manufactured for the first procedure. Sedation was obtained with 7.5 mg diazepam (SABA Pharmaceuticals, Istanbul, Turkey) 1 hour prior to the procedure. After subcutaneous injection of 2 mL 2% lidocaine, the custom-produced needle was inserted with US guidance, into inferior part of nodule along its long axis. The proper position of needle tip within the nodule was confirmed by two-plane US images. Then, a bare flat-end fiber, 400 mm in diameter, was inserted through needle lumen. The fiber tip was aligned with the needle tip. Then, the fiber tip was advanced 5 mm to provide direct contact with the tissue. Two-plane US images were obtained to confirm that the fiber tip was at least 2 cm from surrounding vital structures like esophagus, laryngeal nerve, and trachea. Laser ablation was performed by an electronic infrared diode laser at 810 nm wavelength using a Gallium-AluminumArsenide (GaAlAs) power source (model 15 plus; Diomed, Cambridge, UK) (1,2,4,6,9,10). A total of 720 J of energy was transferred within 240 seconds with 3 W power. US after this initial procedure showed a hypoechoic region under the capsule in the inferior–anterior part of nodule. The patient, however, did not experience any unusual pain or change in breathing or swallowing. The second part of procedure was cancelled, and records of the first procedure were examined. The usual changes associated with the procedure started to appear at 70 seconds. Thirty seconds later, at 100th second, a hypoechoic area started to appear and later expanded in the inferior–anterior subcapsular region of the nodule. The patient was hospitalized and monitored closely with the surgical team. Cross-sectional diameter of the hypoechoic area was 10 mm in transverse axis, 20 mm in vertical axis, and 10 mm in longitudinal axis. Its volume was calculated to be 1.04 mL. Volume of an ellipsoid object is calculated by the formula V1⁄4 (a b c) p=6, where a, b, and c are dimensions of the object. Because the hypoechoic area was not vascular in color Doppler US, diagnosis of arterial or venous pseudoaneurysm was excluded, and the area was considered as a hematoma. Forty-eight hours after the procedure, dimensions of the hematoma had regressed to 4 mm in transverse axis, 2 mm in vertical axis, and 10 mm in longitudinal axis. By 1 month after the procedure the hematoma had completely resorbed. The history was again taken from the patient, and this time he indicated that he had taken 300 mg acetyl salicylic acid daily for 1 year. He had not given this history initially because he did not think that it was important as far as the procedure was concerned. The most common complication of PLA for thyroid nodules is pain in the neck (1–9,11–14). It is often a burning-like sensation that develops during the procedure and begins to cease immediately after the cessation of the procedure. Analgesic drugs are usually not needed for this pain. Complaint of pain during swallowing occurred in these cases for 3–7 days, and completely resorbed at 7th day by application of paracetamol 1000 mg=day (4). Neck pain developing after the procedure is usually moderate, and may be referred to the shoulder and can last for up to 8 days. In some cases acetyl THYROID Volume 18, Number 8, 2008 a Mary Ann Liebert, Inc. DOI: 10.1089=thy.2007.0338

Hyperprolactinaemia associated with increased thyroid volume and autoimmune thyroiditis in patients with prolactinoma.

The aim of this investigation was to evaluate the effects of hyperprolactinaemia on thyroid function, volume and nodularity in patients with prolactinoma.

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.

Preclinical atherosclerosis in patients with prolactinoma.

OBJECTIVE The aim of this study was to evaluate the effect of hyperprolactinemia on body fat, insulin sensitivity, inflammatory markers, and cardiovascular risk in patients with prolactinoma. METHODS The study included 35 untreated hyperprolactinemic patients with pituitary adenomas, and 36 age-, gender-, and body mass index (BMI)-matched healthy controls without any known disease. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR, lipid profile, high-sensitivity C-reactive protein (hs-CRP), and heart-type fatty acid binding protein (H-FABP) levels were measured. Waist and hip circumference (WC and HC) were measured in all the participants. The body fat percentage was measured, and the visceral fat and abdominal fat percentages were measured via bioelectrical impedance (BIA). In addition, carotid intima media thickness (CIMT) was measured using high-resolution B-mode ultrasound. RESULTS The serum glucose level, HOMA-IR, triglyceride level, and SC were significantly higher in the patient group than in the control group. The hs-CRP level and CIMT were significantly higher in the hyperprolactinemic patients. Visceral and truncal fat percentages were significantly higher in the patients with prolactinoma. H-FABP levels were similar in the 2 groups, and there was a positive correlation between the prolactin (PRL) and H-FABP protein levels. CONCLUSIONS Based on the present findings, hyperprolactinemia is associated with preclinical atherosclerosis and metabolic abnormalities. Patients with hyperprolactinemia might experience cardiovascular disease in the long term. Metabolic control should be achieved in addition to the control of hyperprolactinemia in the clinical management of patients diagnosed with prolactinoma.

Three noninvasive methods in the evaluation of subclinical cardiovascular disease in patients with acromegaly: epicardial fat thickness, aortic stiffness and serum cell adhesion molecules

Several studies have reported increased risk of cardiovascular disease due to early development of endothelial dysfunction and structural vascular changes in patients with acromegaly.

Copeptin, a surrogate marker for arginine vasopressin, is associated with cardiovascular risk in patients with polycystic ovary syndrome.

BackgroundWomen with polycystic ovary syndrome (PCOS) have higher risk for cardiovascular disease (CVD). Copeptin has been found to be predictive for myocardial ischemia. We tested whether copeptin is the predictor for CVD in PCOS patients, who have an increased risk of cardiovascular disease.MethodsThis was a cross sectional controlled study conducted in a training and research hospital. The study population consisted of 40 reproductive-age PCOS women and 43 control subjects. We evaluated anthropometric and metabolic parameters, carotid intima media thickness and copeptin levels in both PCOS patients and control group.ResultsMean fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-C), free testosterone, 17-OH progesterone, Dehydroepiandrosterone sulfate (DHEAS), carotid intima media thickness (CIMT) levels were significantly higher in PCOS patients. Mean copeptin level was in 12.61 ± 3.05 pmol/L in PCOS patients while mean copeptin level was 9.60 ± 2.80 pmol/L in healthy control women (p < 0.001). After adjustment for age and BMI, copeptin level was positive correlated with fasting insulin, free testosterone levels, CIMT, and HOM A-IR.ConclusionsCopeptin appeared to have an important role in metabolic response and subsequent development of atherosclerosis in insulin resistant, hyperandrogenemic PCOS patients.

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).

Is There Any Association Between Thrombosis and Tissue Factor Pathway Inhibitor Levels in Patients With Vitamin D Deficiency

Objective: The aim of this study was to evaluate the relationship between vitamin D levels and hemostatic factors like tissue factor pathway inhibitor (TFPI). Methods: Patients who had 25-hydroxyvitamin D3 (25(OH)D3) levels measured were included. Coagulation and hemostatic parameters were evaluated. Patients were divided into 3 groups based on 25(OH)D3 levels as group 1 (25(OH)D3 < 10 ng/mL, n = 25), group 2 (25(OH)D3 = 10-19.9 ng/mL, n = 22), and group 3 (25(OH)D3 ≥ 20 ng/mL, n = 28). Results: A total of 75 patients with a mean age of 39 (range 18-57) years were included in the study. Prothrombin time was longer in group 3 than in group 2 (P = .043). The TFPI levels were higher in group 3 than in the other groups (P < .001). There was a strong positive correlation between 25(OH)D3 and TFPI levels (r = .47, P < .001). Conclusion: Further studies are needed for evaluation of the role of TFPI in hemostasis and thrombotic process in patients with vitamin D deficiency.