Análisis de características clínicas y ecográficas de nódulos tiroideos con citología Bethesda III y su evolución / Analysis of Clinical and Ultrasound Features of Thyroid Nodules With Bethesda III Cytology and their Evolution

Introducción: Desde la implementación de la clasificación citológica de los nódulos tiroideos por el sistema Bethesda en 6 categorías, el grupo Bethesda III (BIII) es el que genera más controversias en cuanto a la conducta de seguimiento. Según la literatura corresponden a esta categoría entre el 4 y 20 % de los nódulos punzados y conllevan un riesgo de malignidad del 5-15 %. Objetivo: Determinar características clínicas y ecográficas de los nódulos tiroideos clasificados como BIII en nuestra población y analizar su evolución en el tiempo. Materiales y Métodos: Estudio descriptivo de todos los pacientes enviados a PAAF bajo guía ecográfica que resultaron BIII, entre febrero 2011 y diciembre 2013. Se describieron las características clínicas y ecográficas de dichos nódulos y su evolución. La mediana de seguimiento fue 24 meses (rango: 2 a 35 meses). Resultados: Fueron punzados 945 nódulos de 784 pacientes. Se clasificaron como BIII 85 nódulos (8,99 %) de 72 pacientes (69 mujeres y 3 varones), con una media de edad de 71,1 ±7,1 años. La mediana del diáme­tro mayor de los nódulos fue 18 mm (9 a 54 mm). El 76,1 % de los nódulos fueron sólidos, el 22,5 % mixtos y en 1 caso espongiforme. Según el patrón ecográfico: 36,7 % eran hipoecoicos, 54,4 % isoecoicos y 8,9 % hiperecoicos. El 8,33 % presentó microcalcificaciones y el 9,9 % márgenes irregulares. El 39,43 % presentó vascularización periférica, 4,23 % central y 56,34 % mixta. Evolución: De los 72 pacientes, 9 (12,1 %) se perdieron en el seguimiento, a 56 (77,8 %) se los siguió clínica y ecográficamente, y en 7 pacientes (9,7 %) se tomó conducta quirúrgica basándose en criterios clínicos y ecográficos sospechosos de malignidad, o por antecedentes familiares positivos, resultando 3 con carcinoma papilar (CP), y 4 con patología benigna. Durante el seguimiento, Fueron repunzados 40 nódulos de 35 pacientes (48,6 %) que resultaron: 2 BI, 23 BII, 14 BIII y 1 BV. De los 14 nódulos con segunda punción BIII, se operaron 7, 1 CP y 6 patología benigna. El nódulo BV resultó un CP a su cirugía. En total, fueron operados 16 pacientes con BIII (22,2 %) (7 de inicio y 8 luego de la segunda PAAF y 1 en el seguimiento clínico ecográfico), de los cuales 5 (31,25 %) resultaron CP y 11 (68,75 %) patología tiroidea benigna. Conclusión: Si bien para los nódulos tiroideos con categoría BIII se recomienda generalmente una repunción, en nuestra experiencia el hallazgo de características clínicas y ecográficas sospechosas de malignidad y/o antecedentes familiares de cáncer de tiroides permitiría en algunos pacientes optar por la cirugía tiroidea desde el inicio. Rev Argent Endocrinol Metab 52:14-21, 2015 Los autores declaran no poseer conflictos de interés.

Background: Since the implementation of the Bethesda System for cytology classification of thyroid nodules into 6 categories, the Bethesda III group (B III) has been the most controversial as regards follow-up management. Reported data shows that about 4 to 20 % of all biopsied nodules belong to this category, with the risk of malignancy being 5 to 15 %. Objective: To determine clinical and sonographic features of thyroid nodules classified as BIII in our population and analyze their evolution over time. Methods: We determined the clinical and ultrasonographic (US) features of all patients who had undergone fine needle aspiration biopsy (FNAB) in 2011-2013 at our Institution for Retirees and Pensioners. Descriptive study of all patients with nodules classified as BIII with a median follow-up time of 24 months (2 to 35 months). Results: Out of 945 nodules from 784 patients biopsied (age, mean ± SD:71.1±7.1 years), 85 (8.99 %) were classified as BIII. Six patients had received neck radiation, and 5 reported family history of thyroid cancer. The median (range) largest diameter of nodules was 18 mm (9-54 mm). Fifty-four nodules (76.1 %) were solid, 16 (22.5 %) mixed, and 1 spongiform. Based on echogenicity, 36.7 % were hypoechoic, 54.4 % isoechoic and 8.9 % hyperechoic. Twenty-two nodules (25.88 %) were taller than wider, 8.33 % had microcalcifications and 9.9 % had irregular margins. At Doppler evaluation, 39.43 % of nodules had peripheral vascularity, 4.23 % showed central vascularity and 56.34 % had mixed vascularity. In 7 out of 72 patients with BIII classification, surgery was indicated at the start based on suspicious clinical and US findings for malignancy, or family history of thyroid cancer. Out of these 7 patients, 3 were found to have papillary carcinoma (PTC), 1 follicular adenoma (FA), 1 colloid goiter (CG), 1 adenomatous nodule (AN) and 1 chronic lymphocytic thyroiditis (CLT). As regards the follow-up and evolution of the rest of the group, 9 were lost, 21 remained in observation and 35 (48.6 %) with 40 nodules underwent a second FNAB, with the following results: 2 BI, 23 BII, 14 BIII and 1 BV. Out of 14 nodules confirmed as BIII on repeat FNAB, 7 were operated on, resulting in: 2 CLT, 3 CG, 1 FA and 1 PTC. The BV nodule proved to be PTC. A total of 16 patients with BIII nodules underwent surgery (7 initially, 8 after a second FNAB, and 1 during clinical and US follow-up) and 5 (31.25 %) were PTC while 11 (68.75 %) were benign. Conclusion: Even though BIII thyroid nodules generally require a second FNAB, in our experience clinical and US findings suspicious for malignancy, or family history of thyroid cancer could allow some patients to be offered surgery at initial presentation. Rev Argent Endocrinol Metab 52:14-21, 2015 No financial conflicts of interest exist.

Ginecomastia: aspectos clínicos y etiológicos. Estudio retrospectivo y multicéntrico / Gynecomastia: Clinical and Ethiological Aspects. Retrospective, Multicenter Study

La ginecomastia es el agrandamiento benigno del tejido mamario en el varón. Es una causa frecuente de consulta que produce ansiedad e incomodidad y puede ser la expresión clínica de una enfermedad relevante. Objetivos: 1) Evaluar las características de presentación de la ginecomastia y el perfil bioquímico; 2) Evaluar la etiología de la ginecomastia en la población estudiada. Material y Métodos: Estudio retrospectivo, multicéntrico. Se evaluaron las historias clínicas de 220 varones (18-85 años) con diagnóstico clínico y por imágenes de ginecomastia, con evaluación bioquímica completa. Resultados: Se observó mayor prevalencia entre 21-30 años de edad (n = 66; 30 %). La mayoría consultó en forma espontánea (77,7 %); el resto fue derivado por otras especialidades. Principales motivos de consulta: razones estéticas (70,4 %) y dolor (27,3 %). El 23,2 % tenía antecedente de ginecomastia puberal. El tiempo de evolución previo a la consulta fue muy variable: 1 mes a 40 años. Examen físico: 122 pacientes (55,4 %) presentaron ginecomastia bilateral y 98 (44,6 %) unilateral (54,1 % izquierda y 45,9 % derecha). El 44,8 % presentó sobrepeso y 22,4 % obesidad. En 29,1 % se constató dolor mamario al examen. Un paciente (con macroprolactinoma) presentó secreción mamaria espontánea y 3 pacientes secreción mamaria provocada. Etiología: la ginecomastia idiopática fue la más frecuente (49,1 %) y de las causas secundarias, el consumo de anabólicos. Se constató un 10 % de pacientes con hipoandrogenismo, 16,4 % con hiperprolactinemia y 10,5 % con hiperestrogenemia. En 6 casos coexistieron 2 causas (total 226 causas). No se hallaron marcadores oncológicos elevados. En los < 40 años las causas más frecuentes fueron uso de anabólicos y ginecomastia puberal persistente; y en los > 40 años fueron hipogonadismo y consumo de fármacos. Los pacientes con ginecomastia bilateral tuvieron mayor tiempo de evolución, mayor IMC y menores niveles de TT versus ginecomastia ...

Gynecomastia is a benign enlargement of breast tissue in men. It occurs physiologically in three stages of life: newborns, pubescent boys and older adults. It is a frequent reason for consulting and -though generally benign- it produces anxiety and discomfort. It is important to differentiate between the asymptomatic presence of palpable breast tissue, which is of little clinical relevance, and a recent onset breast enlargement usually associated with pain and swelling, which can be a sign of illness or pharmacological impact. Aims: To evaluate the presenting features (symptoms, duration, laterality, etc.) and biochemical profile of gynecomastia; to assess the etiology of gynecomastia in the study population. Methods: Retrospective, multicenter study. We evaluated the medical records of 220 men aged 18-85 years (average age 33 years: median 39.5 ± 19.6 years) with imaging and clinical diagnosis of gynecomastia who had undergone biochemical assessment. The consultation period was from May 2002 to June 2013. The following data was assessed: breast pain, duration of gynecomastia, sexual function, galactorrhea, weight change, habits (alcohol, drug addiction, anabolic steroids), history of pubertal gynecomastia, use of medication and family history of gynecomastia. Physical examination: weight, height, body mass index (BMI), breast and gonadal examination. Laboratory: total testosterone (TT), bioavailable testosterone (Bio-T), estradiol (E2), luteinizing hormone, follicle stimulating hormone, prolactin, thyrotropin, alpha fetoprotein, β subunit of human chorionic gonadotropin and carcinoembryonic antigen. For hormonal abnormalities, each site’s reference values were considered. In all patients, gynecomastia was confirmed by ultrasound and / or mammography. Results: A higher prevalence of gynecomastia is observed in the age range between 21 and 30 years (n = 66; 30 %). Most patients presented spontaneously (77.7 %); the rest were referred from other specialties. The most frequent reasons for consultation were aesthetic reasons (70.4 %) and breast pain (27.3 %). Twenty-three point two percent of subjects had a history of pubertal gynecomastia. Evolution time prior to consultation was highly variable (1 month to 40 years). On physical examination, 122 patients (55.4 %) had bilateral and 98 patients (44.6 %) had unilateral gynecomastia (54.1 % left and 45.9 % right); 44.8 % were overweight and 22.4 % were obese. BMI: 27.2 ± 4.3 kg/m2. In 29.1 % of patients breast pain was identified on medical examination. One patient (with macroprolactinoma) had spontaneous galactorrhea and in 3 patients mammary secretion was found on physical examination. Gonadal examination was performed in 147 patients, 126 had normal testicular volume, 10 had bilateral hypotrophy, 7 had unilateral hypotrophy and 4 unilateral absence of the testis. Idiopathic gynecomastia was the most common etiology (47.8 %). The most relevant secondary cause of gynecomastia was anabolic steroids consumption (14.1 %). In 6 cases two causes coexisted (total: 226 causes). Elevated cancer markers were not found in any of the cases. If we divide the population into patients younger and older than 40, in the former the most common second­ary causes were the use of anabolic steroids and persistent pubertal gynecomastia, while in patients older than 40, they were hypogonadism and medical drug use. Patients with bilateral gynecomastia had a longer history of gynecomastia: 3.4 ± 5.7 versus 1.4 ± 1.9 years (p = 0.0004); higher BMI: 28.4 ± 4.4 versus 25.5 ± 3.5 kg/m2 (p < 0.0001) and lower TT levels: 4.7 ± 2.0 versus 5.4 ± 1.9 ng/ml (p=0.019) than patients with unilateral gynecomastia, respectively. A negative correlation between BMI and TT was found (r= -0.38, p< 0.0001). No correlation between BMI and E2 and between BMI and bio-T was found. Ultrasound was used in 83.2 % of patients and mammography in 43.6 % (both 28.2 %). Conclusions: Patients with gynecomastia consulted more often for aesthetic reasons and secondarily for breast pain. Detection of galactorrhea was rare. Gonadal examination was normal in most patients and 66.7 % were overweight or obese. Just over half of the patients presented with bilateral gynecomastia and compared with cases of unilateral gynecomastia, they had a longer history of disease, higher BMI and lower TT levels. The most common cause of gynecomastia was idiopathic in all age groups. Persistent pubertal gynecomastia and anabolic steroids consumption were frequent in patients younger than 40 years, and medical drug use and hypogonadism in patients over 40. The presence of gynecomastia may be the expression of an underlying and clinically relevant disease. This highlights the need for an adequate and complete clinical, biochemical and imaging assessment in these patients. Rev Argent Endocrinol Metab 52:22-28, 2015 No financial conflicts of interest exist.

Asociación de carcinoma papilar de tiroides y enfermedad de Graves: Inesperada evolución y eficacia de la dosis ablativa con tirotrofina recombinante humana (rhTSH) / Association of Papillary Thyroid Carcinoma and Graves' Disease: Unexpected Development and Efficiency of Ablative Dose with Recombinant Human Thyrotropin (rhTSH)

El carcinoma diferenciado de tiroides (CDT) asociado a enfermedad de Graves (EG) es una asociación relativamente rara, ocurriendo en el 0,3 % al 9,8 % de los pacientes operados por EG. Se presenta el caso de un paciente con EG y CDT de tiroides con características evolutivas y terapéuticas peculiares. Varón de 22 años que consultó por obesidad. Peso: 116,4 kg, Talla: 1,73 m, BMI: 38,9, clínicamente eutiroideo, con palpación tiroidea dificultosa por grosor de cuello. Análisis iniciales: T3, T4 y TSH dentro de rango normal y ecografía tiroidea con nódulo hipoecoico en lóbulo derecho (LD) de 11 x 10 mm. Se le solicitó punción aspirativa con aguja fina (PAAF) bajo guía ecográfica. Vuelve a los 4 meses con cuadro clínico de hipertiroidismo. Análisis: T3: 557 ng/dL, T4: 18,8 mcg/dL, T4 L: 3,73 ng/dL, TSH: < 0,01 μUI/mL, ATPO: 186 UI/mL, ATG: 965 UI/mL. La citología mostró: "Hallazgos citológicos vinculables con carcinoma papilar (CP) tiroideo". Centellograma tiroideo: "Nódulo integrado en LD". Es tratado con metimazol y se opera a los 2 meses: "Tiroidectomía total"; cuya anatomía patológica (AP) reveló un "CP variante folicular en lóbulo derecho y zona de CP variante clásica en lóbulo izquierdo". A los 35 y 60 días de operado (sin instaurar levotiroxina): presenta TSH <0,1 μUI/ml con T3 y T4 normales. Clínicamente eutiroideo, con palpación de cuello normal. Tomografía axial computada (TAC) de tórax: "Normal". Ecografía de cuello: "Lodge tiroidea bilateral libre". TRab 29 % (V.N. hasta 15 %). Centellograma tiroideo con Tc99m: "Captación patológica en región cervical media e inferior derecha y cervical inferior izquierda". Se reopera a los 4 meses de la primera cirugía (Cx). Se resecó proliferación epitelial en región de mediastino superior". AP: "Ganglio con infiltración de CP variante folicular". Análisis a los 40 días de la 2° Cx: TSH: 2,3 μUL/ml, T4 L: 0,82 ng/dL, tiroglobulina (Tg): 4,7 ng/mL. TAC de cuello y de tórax normales. Captación de I131: 1 h: 8 %, 24 h: 12 % y centellograma con 7,4 MBq de I131 "Múltiples áreas de fijación del trazador en cuello". Resonancia magnética nuclear (RMN) de cuello sin contraste: "Imagen redondeada de 10 mm a nivel paratraqueal derecha". Se logra hacer dosis ablativa con 0,9 mg de rhTSH con 200 mCi de I131, alcanzando una TSH >100 μUI/ml. A los 6 meses de la DT (sin levotiroxina): TSH >100 μUI/ml, Tg: 13,81 ng/mL, ATG: 431 UI/mL. Rastreo con 2 mCi: "Aumento patológico del radioyodo solo a nivel de la articulación esternoclavicular derecha". RMN de cuello: "Imagen en región pretraqueal derecha de menor tamaño que la anterior". Se le indicó DT de 150 mCi de I131. Posteriormente requirió 2 DT de I131 más. En la actualidad, a 4 años de la primera operación, el paciente se halla en buen estado general, con Tg negativa, con ATG en disminución franca y rastreo corporal de I131 negativo y sin signos de persistencia o recidiva de la enfermedad. Conclusiones: Varón obeso de 22 años portador de un CP de tiroides concomitante con la instalación de un hipertiroidismo por EG, con ATG positiva. Se resalta: 1) La importancia de la evaluación ecográfica inicial de un paciente con EG, 2) Tejido neoplásico residual ganglionar después de 2 Cx, efectuada por cirujano experimentado, suficientemente funcionante como para impedir elevación significativa de TSH y permitir dosis ablativa de I131; 3) Agresividad local del tumor demostrado por infiltración ganglionar y tejidos adyacentes; 4) TAC y ecografía de cuello que no pudieron identificar restos en cuello y efectividad, en cambio, de la RMNde cuello sin contraste y del centellograma tiroideo con Tc99m; 5) Eficaz utilización de la dosis ablativa con rhTSH.

Introduction: Differentiated thyroid cancer (DTC) associated with Graves' disease (GD) is a relatively rare disease, occurring in 0.3 % to 9.8 % of GD patients. Some studies suggest an increased aggressiveness of DTC in GD patients, apparently related to thyroid stimulating antibodies. We report the case of a patient with DTC and GD, describing his peculiar evolution. Case report: 22-year-old male who presented with obesity. History of a cousin with DTC and grandmother and mother with goiter. Physical examination: Weight: 116.4 kg, height: 1.73 m, BMI: 38.9. Clinically euthyroid. Thyroid palpation was difficult due to his thick neck. Initial analysis: T3, T4 and TSH within normal range. Thyroid ultrasound (US) showing 11 x 10 mm hypoechoic nodule in right lobe (RL). US-guided fine-needle aspiration (FNA) was requested. Four months later, the patient returned with clinical symptoms of hyperthyroidism (diarrhea, palpitations, insomnia, tremors, cramps and difficulty walking). Laboratory: T3: 557 ng/dl, T4: 18.8 mcg/dl, FT4: 3.73 ng/dl, TSH <0.01 μIU/mL, TPOA: 186 IU/mL, TGA: 965 IU/mL. US-guided FNA: "Cytological findings are related to papillary thyroid cancer". Thyroid Scan: "Diffuse enlargement of the gland, "warm" nodule in RL". 131I uptake was: 1st hour: 12 %, 24 hours: 58 %. He received methimazole 20 mg daily. He was operated on 2 months later ("total thyroidectomy"). Pathology: "Follicular variant of papillary thyroid carcinoma in right lobe and classical variant of papillary carcinoma in area of the left lobe". Thirty-five days after surgery (S) (without levothyroxine): TSH <0.01 μIU/mL, Tyroglobulin (Tg) 32.1 ng/mL. Sixty days after S: TSH <0.1 μIU/mL, FT4 1.2 ng/dL, T3 1.3 ng/dL. Clinically euthyroid with normal neck palpation. Chest Computed axial tomography (CT): "Normal". US of the neck: "Bilateral thyroid lodge is free". Ninety days later: TSH 0.32 μIU/mL, TRAb 29 % (normal: until 15 %). Thyroid Scan with 99mTc pertechnetate: "Pathological uptake in middle and lower cervical region right and left lower neck." He was reoperated on 4 months after his initial S: "Resection of epithelial proliferation with thyroid aspect in superior mediastinum region". Pathology: "Node with extensive infiltration of neoplastic proliferation of follicular variant of papillary carcinoma with areas of connective tissue infiltrated periganglionar of papillary thyroid cancer". Lab 40 days after the second surgery: TSH 2.3 μIU/mL, FT4 0.82 ng/dL, Tg 4.7 ng/mL. Neck and chest CT showed neither pathological lesions nor lymphadenopathy. 131I uptake with 7.4 MBq was: 1st hour: 8 % and 24 hours: 12 %. Neck Scan: "Multiple areas of tracer fixation in the neck". No pathological signs on neck palpation. Ablative dose of 7.4 GBq of 131I was performed to the patient, previously using rhTSH (two doses of 0.9 mg), reaching TSH >100 μIU/mL. Scan post ablative dose: "Important focus on right paratracheal region." Neck MRI showed: "Absence of thyroid gland. Rounded image of about 10 mm at right paratracheal level". The patient initiates suppressive therapy with levothyroxine (LT4). Six months after ablation therapy (without LT4): TSH >100 μIU/mL, Tg: 13.8 ng/mL, TGA: 431 IU/mL. Body Scan with 2 mCi: "Pathological focus of radioiodine behind the right sternoclavicular joint". New neck MRI: "Image in right pretracheal region smaller than the previous study". The patient received 5.55 GBq of 131I. The same radioiodine treatment was repeated 8 months later. At present, 4 years after the patient's initial surgery, he is in good general health, performing his normal activities, with TGA in sharp decline, negative 131I body scan and without signs of persistent or recurrent disease. Conclusions: We report a case of follicular variant papillary TC associated with GD with concomitant development of hyperthyroidism, with positive TGA, in a 22-year-old obese man. Highlights: 1) The importance of initial US exploration in a patient with GD, 2) Residual neoplastic lymph node tissue after 2 S, performed by an experienced surgeon, with enough functioning tissue to prevent a significant elevation of TSH and allow 131I ablative therapy, 3) Tumor local aggressiveness shown by adjacent tissues and lymph node infiltration, 4) Failure to identify residues in the neck by CT and US; instead, effectiveness of the neck MRI without contrast and 99mTc thyroid scan, 5) Effective use of ablative radioiodine therapy with rhTSH.