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The assessment of regional bone mineral density (BMD) has proved to be useful for illustrating the impact of focal bone demineralization diseases on bone mass. In these scenario, a common practice is to compare the affected limb with the contralateral limb. However, there are no studies comparing BMD differences between dominant vs nondominant limbs at these sites. In addition, most studies have assessed BMD in specific ROIs (regions of interests) instead of in the whole limb. The purpose of our study was to compare the BMD of dominant vs nondominant hands and feet in healthy individuals, using both the whole limb software and specific ROIs. We performed a cross-sectional analysis on untrained women and men over 18 years of age who volunteered to participate. BMD (g/cmsup2/sup), bone area (cmsup2/sup) and BMC (bone mineral content) (g) were measured by Lunar Prodigy DXA (GE Healthcare, Madison, WI, USA), using 2 different approaches: whole limb/region software and specific ROIs. A total of 42 subjects (11 men and 31 women) were included. Mean age was 44.19 ± 10.49 years. BMD was greater in the dominant in comparison with the nondominant hand. The difference was 0.014 (95% CI, 0.009-0.018) for the whole hand BMD, 0.023 (95% CI, 0.003-0.044) for ROI 1, and 0.016 (95% CI, 0.003-0.029) for ROI 2. No significant differences were found between dominant and nondominant foot BMD, using the whole limb software and specific ROIs. To our knowledge, this is the first study to explore the differences in BMD, bone area and BMC in terms of limb dominance, supporting the usefulness of DXA as an accurate and objective complementary diagnostic or follow-up tool in focal bone demineralization diseases.

The epidemiology of Paget's disease of bone (PDB) has changed in the last years but there is no update data on its clinical presentation, diagnosis and management in Latin America. Our aim was to describe its clinical features, diagnostic evaluation and responses to treatment in a group of PDB patients treated between June 2012 and December 2019 in an institution specialized in bone diseases, in Buenos Aires, Argentina. The frequency of PDB (180/10 714) was 1.68%. Median age was 67 (range 39-97) years and 59.5% were women. Most patients were asymptomatic (58.6%) and had monostotic disease (54.3%). Favorable responses were obtained in all patients who were treated with zoledronate (n = 36), in 10 out of 14 treated with pamidronate, in 9 out of 10 who received intravenous ibandronate and in 12 out of 13 who received oral bisphosphonates. The response rates were not significantly different when we compared monostotic vs. polyostotic disease. Among the biochemical parameters, mean values of bone specific and total alkaline phosphatase, and C-terminal crosslinked telopeptide of type I collagen decreased significantly after treatment with bisphosphonates. It seems that our results reflect the change in PDB epidemiology towards a more indolent disease. In the future, this would probably allow physicians to use lower doses of bisphosphonates than the ones historically recommended for these patients.La epidemiología de la enfermedad de Paget ósea (EPO) ha cambiado en los últimos años. Son necesarios datos actualizados sobre su forma de presentación clínica, diagnóstico y tratamiento en nuestra región. Nuestro objetivo fue describir las características clínicas, evaluación diagnóstica y respuestas al tratamiento de un grupo de pacientes con EPO en un centro especializado en salud ósea de Buenos Aires, Argentina. Se evaluaron todos los pacientes que fueron atendidos en nuestra institución por enfermedades óseas entre junio de 2012 y diciembre de 2019. La frecuencia de EPO (180/10 714) fue de 1.68%. La mediana de edad fue de 67 (rango 39-97) años. El 59.5% eran mujeres. La mayoría se encontraba asintomático (58.6%) y tenían enfermedad monostótica (54.3%). Se objetivaron respuestas favorables en todos los que recibieron zoledronato (n = 36), en 10 de 14 pacientes que recibieron pamidronato, en 9 de 10 que utilizaron ibandronato endovenoso y en 12 de 13 con bifosfonatos orales. Los porcentajes de respuesta no variaron significativamente entre pacientes con formas monostóticas y poliostóticas. Entre los parámetros bioquímicos, los valores de fosfatasa alcalina total y ósea y de Β cross-laps disminuyeron significativamente luego del tratamiento con bifosfonatos. Nuestros resultados reflejarían un cambio en la epidemiología de la EPO hacia una forma de presentación más indolente. Esto permitiría probablemente el uso de dosis más bajas de bifosfonatos que las históricamente recomendadas para estos pacientes.

The stratification of patients with differentiated thyroid cancer based on their initial risk of recurrence, according to specific clinical, histopathological and perioperative data, is an important starting point for tailoring the follow-up during the first 1–2 years after initial therapy (surgery with or without radioiodine ablation). However, risk of recurrence re-stratification based on new clinical data that becomes available after considering the response to treatment (dynamic risk assessment) provides a more accurate prediction of the status at final follow-up and a more individualized approach. In this review, we summarized the available data regarding dynamic risk of recurrence and the suggested management of differentiated thyroid cancer patients according to the response to treatment. The use of this strategy is crucial to avoid overtreatment and intensive follow-up of the vast majority of patients who will have a very good prognosis and, on the other hand, focus therapeutic efforts on those patients who will have a worse prognosis. In the future, molecular biology analysis of the tumors and well-designed prospective studies will probably refine the risk of recurrence prediction.

Some studies based on bone biopsy have demonstrated that in patients with tumor-induced osteomalacia (TIO) the mineralization process of the bone matrix is profoundly disturbed. However, the interrelationship between clinical and biochemical features and bone microarchitecture in this disease needs further analysis. With this purpose in mind, we set out three objectives: (i) to determine bone microarchitecture and estimated bone strength in a group of patients with tumor-induced osteomalacia using high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA), (ii) to investigate correlations between duration of disease, biochemical features, bone density, HR-pQCT and FEA parameters, and (iii) to compare HR-pQCT and FEA parameters with a healthy control group. Ten patients with TIO were included. All patients had non-resolved disease. At the distal radius, all bone microarchitecture parameters were significantly affected in patients with TIO in comparison with healthy controls. At the distal tibia, all parameters were significantly impaired, except for trabecular thickness. All the parameters were more affected in the distal tibia than in the distal radius. Women with TIO (n = 7) had significantly lower bone strength parameters than healthy controls. In men (n = 3), bone strength parameters were significantly lower than in the control group at the distal tibia. Alkaline phosphatase levels exhibited a negative correlation with microarchitecture parameters, failure load, and stiffness. Higher levels of parathyroid hormone correlated with poorer microarchitecture parameters. We believe that in TIO, hormonal disturbances and the lack of mechanical stimulus specially converge to generate an extremely harmful combination for bone health. © 2021 American Society for Bone and Mineral Research (ASBMR).

There are numerous reports of incidental findings of thyroglossal duct remnants (TGDR) after total thyroidectomy, but its implication on the outcome of patients with differentiated thyroid cancer (DTC) is unknown. The aim of this study was to determine the frequency of TGDR detected by ultrasonography after total thyroidectomy in patients with DTC and to evaluate the impact of this finding on the response to treatment. A total of 377 records of patients with DTC who received total thyroidectomy between January 1994 and January 2017 were reviewed. Patients with less than one year of follow-up after surgery were excluded. TGDR was diagnosed in 16 out of 377 (4.2%). Fifteen had a low risk of recurrence DTC and 13 of them were treated with radioactive iodine. All low risk patients had an excellent response to treatment. Only one with an intermediate risk of recurrence DTC had an initial structural incomplete response which changed to an indeterminate response after a modified central lymph node dissection. The median time of TGDR diagnosis after thyroidectomy was 5 years (1-16). Two patients underwent TGDR surgery due to the presence of a rapidly growing neck mass, 2.4 and 4 cm in size, detected 9 and 16 years after thyroidectomy, respectively. The prevalence of this condition seems to be rare. However, the appearance of a cystic mass during the follow-up of a patient with DTC cancer could be confused with metastatic disease. The diagnosis of TGDR seems not to have an impact on the response to treatment.Existen numerosas comunicaciones de hallazgo incidental de remanentes del conducto tirogloso (CTG) posteriores a una tiroidectomía total, pero se desconoce su implicancia en pacientes con cáncer diferenciado de tiroides (CDT). Nuestro objetivo fue determinar frecuencia de detección ecográfica de remanentes del CTG posterior a la tiroidectomía total en pacientes con CDT y evaluar el impacto del hallazgo en la respuesta al tratamiento. Se incluyeron 377 pacientes con CDT tratados con tiroidectomía total entre enero 1994 y enero 2017, con seguimiento de al menos un año posterior a la cirugía. Se detectó la presencia de remanente del CTG en 16/377 (4.2%): 15 de bajo riesgo de recurrencia y uno de riesgo intermedio. Trece recibieron radioyodo. Todos tuvieron un estado sin evidencia de enfermedad al final del seguimiento, excepto uno con riesgo intermedio que presentó una respuesta inicial estructural incompleta e indeterminada posterior al vaciamiento ganglionar. La mediana del tiempo de diagnóstico del remanente del CTG luego de la tiroidectomía fue de 5 años (rango 1-16). Dos pacientes con remanentes del CTG fueron intervenidos quirúrgicamente, ambos presentaron tumoraciones de aparición súbita en región suprahioidea, 2.4 y 4 cm, detectados a los 9 y 16 años luego de la tiroidectomía, respectivamente. La prevalencia de esta condición parece ser poco frecuente. Sin embargo, la aparición de una masa quística en el seguimiento de un paciente con CDT puede ser confundido con enfermedad metastásica y generar ansiedad. El hallazgo de remanentes del CTG parecería no tener ningún impacto en la respuesta al tratamiento.

To describe the experience of our Division of Endocrinology with multikinase inhibitor (MKI) treatment in radioiodine-resistant differentiated thyroid cancer (DTC) patients. Adults patients with a diagnosis of DTC treated with an MKI drug from March 2011 to October 2018 were registered into a retrospective database. Primary objectives were: the assessment of progression-free survival (PFS) and radiographic response evaluated according to RECIST v. 1.1. Adverse events (AEs) were evaluated by using Common Terminology Criteria for Adverse Events v. 5.0. Twenty-two patients were treated with MKIs (21 with sorafenib, one with lenvatinib as first-line treatment). Seven patients required a second-line therapy with lenvatinib and one patient required a third-line treatment with pazopanib. Median duration of treatment was 11.2 (4.8–79.6) months. Best responses with sorafenib were partial response (PR) in two patients (11%), stable disease (SD) >6 months in 13 patients (72%), and progressive disease (PD) in three patients (17%). Best responses with second-line lenvatinib were PR in one patient (33%) and SD in two patients (66%). Median PFS was 31.5 months. AEs were present in 19 (90%) patients under sorafenib. The most common AEs were hand–foot syndrome (HFS) (67%), diarrhea (52%), and hypertension (52%). Definitive withdrawal was necessary in only one patient (4.7%). Our study reflects the real-world clinical experience of an Endocrinology Division on the management of radioiodine-resistant DTC patients with sorafenib and lenvatinib, showing a beneficial therapeutic effect with acceptable tolerability.

CONTEXT: Clinical applications of genomic assessment of thyroid cancers are rapidly evolving. OBJECTIVES, DESIGN, AND SETTING: We studied tumor samples from patients with imminently threatening and rare thyroid cancers to identify genomic alterations that might correlate with outcomes and/or be productively therapeutically targetable. PATIENT CONTEXT: Progressive and metastatic, and/or rare, thyroid cancers were studied, 2012 to 2016, at Mayo Clinic sites. INTERVENTION: The intervention was Foundation One tumor interrogation. MAIN OUTCOME MEASURES: Main outcome measures included genomic alterations, patient characteristics, and overall survival. RESULTS: Samples from 55 patients were evaluated: 20 anaplastic thyroid cancers (ATCs) (36%), 25 radioactive iodine–refractory differentiated thyroid cancers (DTCs)/poorly differentiated thyroid cancers (PDTCs) (45%; 14 papillary thyroid cancer [PTCs], 6 PDTCs, 5 Hürthle cell cancers), 8 medullary thyroid cancers (MTCs) (15%), and 2 others (a spindle epithelial tumor with thymus-like differentiation, and a primary thyroid sarcoma). Overall, 72% of DTCs, 79% of ATCs, and 75% of MTCs were deemed to have potentially productively targetable alterations. The most commonly encountered mutation was of TERT promoter (56% of DTCs, 68% of ATCs)—but this is not presently targetable. Targetable BRAFV600E mutations were found in 40% of DTCs/PDTCs (83% of PTCs) and 32% of ATCs; of MTCs, 75% had targetable RET mutations, and 25% HRAS mutations. Of patient tumors with nonmutated BRAFV600E, 53% of DTC/PDTCs and 69% of ATCs had other potentially productively targetable mutations. Genomic alterations in our series of poor prognosis metastatic DTC/PDTCs also closely resembled those seen in ATC. CONCLUSIONS: Whereas genomic interrogation of favorable prognosis thyroid cancer seems ill advised, potentially productively targetable mutations were demonstrated in the majority of tumors from patients with metastatic thyroid cancers requiring systemic therapy, suggesting a rationale for the selective application of this technology.

To describe the experience with radioiodine-resistant differentiated thyroid cancer (RR-DTC) patients treated with lenvatinib in two university hospitals from Argentina. Adult patients with a diagnosis of RR-DTC treated with lenvatinib from April 2017 to February 2020 were registered into a retrospective database. Primary objectives were assessment of progression-free survival (PFS) and tumor response evaluated according to RECIST v 1.1. Adverse events (AEs) were evaluated by using Common Terminology Criteria for Adverse Events v5.0. Twenty-two patients were treated with lenvatinib, 13 of whom had previously received one or more multikinase inhibitors. Median duration of treatment was 7.1 months (2.2–24). Best overall response was complete response in one patient (4.5%), partial response in seven (31.8%), stable disease in seven (31.8%), and progressive disease in six (27.3%). Median PFS was 13.7 months (95% CI 3.2–24.2). All patients experienced at least one AE. Grade ≥3 AEs were observed in eight (36.4%) patients. Hypertension was the most frequent AE (63.6%) and the most common grade ≥3 AE (22.7%). Definitive withdrawal was necessary in two patients due to recurrent proteinuria (9%). Tumor responses and PFS in our study were in line with other real-life clinical data and they seem to be inferior to the reported in the SELECT trial, probably related to the higher number of patients with prior MKI therapy, comorbidities, and poor performance status. Although virtually all patients experienced AEs, most of them were manageable and rarely a definitive withdrawal was necessary.

Resumen El advenimiento de la terapia con inhibidores multicinasas (IMK) represento un cambio radical en el tratamiento de pacientes con carcinoma avanzado de tiroides. Hasta la fecha, 2 farmacos se encuentran aprobados por la Asociacion Nacional de Medicamentos, Alimentos y Tecnologia Medica (ANMAT) en Argentina: sorafenib, para pacientes con carcinoma diferenciado de tiroides radiorresistente, y vandetanib, para aquellos con carcinoma medular de tiroides (enfermedad progresiva y/o sintomatica). Los estudios de fase iii han demostrado que estos farmacos aumentan significativamente la supervivencia libre de progresion en este grupo de pacientes. Si bien tienen una indicacion precisa, su manejo requiere de un equipo multidisciplinario en contacto estrecho con un paciente involucrado en su tratamiento. Los efectos adversos de sorafenib y vandetanib son frecuentes, sin embargo, muchos de ellos disminuyen con el tiempo y la mayoria puede manejarse a menudo sin disminuir la dosis ni suspender el farmaco. El conocimiento del correcto manejo de los efectos adversos por parte del equipo tratante constituye una herramienta fundamental para poder educar al paciente y, consecuentemente, poder prevenirlos o minimizarlos, y de esta manera evitar complicaciones severas. El objetivo de esta publicacion es brindar una guia para el diagnostico y tratamiento de los efectos adversos de estos IMK y, por otro lado, presentar la iniciativa del Hospital de Clinicas de la Universidad de Buenos Aires en cuanto a la implementacion de la misma.

To evaluate the influence of age at diagnosis on the frequency of structural incomplete response (SIR) according to the modified risk of recurrence (RR) staging system from the American Thyroid Association guidelines.We performed a retrospective analysis of 268 patients with differentiated thyroid cancer (DTC) followed up for at least 3 years after initial treatment (total thyroidectomy and remnant ablation). The median follow-up in the whole cohort was 74.3 months (range: 36.1-317.9) and the median age at diagnosis was 45.9 years (range: 18-87). The association between age at diagnosis and the initial and final response to treatment was assessed with analysis of variance (ANOVA). Patients were also divided into several groups considering age younger and older than 40, 50, and 60 years.Age at diagnosis was not associated with either an initial or final statistically significant different SIR to treatment (When patients are correctly risk stratified, it seems that age at diagnosis is not involved in the frequency of having a SIR at the initial evaluation or at the final follow-up, so it should not be included as an additional variable to be considered in the RR classifications.

Objective To compare the historic risk of recurrence (RR) and response to therapy to risk stratification estimated with historical pathology reports (HPRs) and contemporary re-review of the pathological slides in patients with differentiated thyroid cancer (DTC). Subjects and methods Out of 210 DTC patients with low and intermediate RR who underwent total thyroidectomy and remnant ablation in our hospital, 63 available historic pathologic samples (HPS) were reviewed. The RR and the response to therapy were evaluated considering historical histological features (histological type, tumor size, capsular invasion, number of lymph node metastases) and then, reassessed after observing additional histological features (vascular invasion, extrathyroidal extension, size of lymph node metastases, presence of extranodal extension, and/or status of the resection margins). Results A change in the RR category was observed in 16 of 63 cases (25.4%). Out of 46 patients initially classified as low RR, 2 patients were reclassified as intermediate RR, 4 as high RR, and 1 as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Out of 17 patients initially classified as intermediate RR, 3 were reassigned to the low RR group, 5 as high RR, and 1 as NIFTP. The percentages of structural incomplete response at final follow-up changed from 2.2 to 0% (p = 1) in patients with low RR and from 6.3 to 20% (p = 0.53) in patients with intermediate RR. Conclusion A detailed report of specific features in the HPR of patients with DTC might give a more accurate RR classification and a better estimation of the response to treatment.

The primary purpose of this study was to validate the proposed modified 2009 American Thyroid Association Risk Stratification System (M-2009-RSS) in patients with thyroid cancer and to compare the findings with those of the 2009 ATA Risk of Recurrence (2009 ATA-RR) and the Ongoing Risk of recurrence system. The secondary purpose was to assess which risk stratification system had the best predictive value to foresee the probability of structural incomplete response or the no evidence of disease (NED) status at the end of follow-up.This retrospective review included 149 patients with differentiated thyroid cancer who had low and intermediate 2009 ATA-RR and were treated at a single experienced center and followed-up for a median of 6 years (range 3-12 years). Each patient was risk stratified using both the 2009 ATA-RR and the M-2009-RSS. The primary endpoints were 1) the best response to initial therapy defined as either excellent response, biochemical or structural incomplete response, or indeterminate response; 2) clinical status at final follow-up defined as either NED, biochemical incomplete response, structural incomplete response, indeterminate response, or recurrence (biochemical or structural disease identified after a period of NED), and 3) ongoing RR defined as low or high risk according several outcomes after initial treatment.Mean age of included patients was 45.3±13 years. Both the ATA 2009-RR and the M-2009-RSS provided clinically meaningful graded estimates with regard to the status of NED at the end of follow-up in low-risk patients (84% for 2009 ATA-RR and 74% for M-2009-RSS) or the likelihood of having persistent structural disease (0% for 2009 ATA RR and 3.6% for the M-2009-RSS). When patients were classified as low risk, the positive predictive value (PPV) and negative predictive value (NPV) to predict structural disease was 0% and 88.7% for the 2009 ATA-RR, 3.6% and 86.5% for the M-2009-RSS, and 1.6% and 68.2% for the ongoing RR (p=0.022 and 0.055 of chi-square test for PPV and NPV, respectively).Despite expanding the definition of low risk to include small-volume lymph node metastases, minor extrathyroidal extension, and minimally invasive follicular thyroid cancer, the M-2009-RSS predicts clinical outcomes (structural incomplete response and NED at the end of follow-up) that are very similar to the previously validated 2009 ATA RR classification system.

La osteomalacia oncogénica es una enfermedad rara. Existen descriptos alrededor de 337 casos. Es ocasionada por un tumor productor del factor de crecimiento fibroblástico 23 (FGF-23), hormona que disminuye la reabsorción tubular de fosfatos y altera la hidroxilación renal de la vitamina D, con hipofosfatemia, hiperfosfaturia y niveles bajos de calcitriol. Se presentan dos pacientes de 44 y 70 años, que consultaron por dolores óseos generalizados de aproximadamente un año de evolución en los que se hallaron alteraciones bioquímicas compatibles con osteomalacia hipofosfatémica. En el primer caso se realizó la resección de una tumoración en tejido celular subcutáneo del pie derecho, un año después del diagnóstico clínico. Luego de la exéresis, se disminuyó el aporte de fosfatos que recibía el paciente, pero reaparecieron los dolores al intentar suspenderlos. Ocho años más tarde, hubo recidiva local de la tumoración por lo que se efectuó resección completa. Después de la misma, se logró suspender el aporte de fosfatos. En el segundo caso, el paciente se estudió con tomografía por emisión de positrones con 18F-fluorodesoxiglucosa, hallando formación nodular hipermetabólica en partes blandas de antepie derecho, de 2.26 cm de diámetro. Luego de su escisión se pudo suspender el aporte de fosfatos. Ambos pacientes se encuentran asintomáticos con indicadores de metabolismo fosfocálcico normales. El diagnóstico anatomopatológico en ambos fue un tumor mesenquimático fosfatúrico, variante mixta del tejido conectivo, la entidad más frecuentemente asociada a la osteomalacia oncogénica.

Oncogenic osteomalacia is a rare disease. It is caused by a tumor that produces fibroblast growth factor 23, a hormone that decreases the tubular phosphate reabsorption and impairs renal hydroxylation of vitamin D. This leads to hyperphosphaturia with hypophosphatemia and low calcitriol levels. About 337 cases have been reported and we studied two cases; 44 and 70 year-old men who sought medical attention complaining of suffering diffuse bone pain over a period of approximately one year. In both cases, a laboratory test showed biochemical alterations compatible with a hypophosphatemic osteomalacia. In the first case, a soft tissue tumor of the right foot was removed, one year after the diagnosis. The patient was allowed to diminish the phosphate intake, but symptoms reappeared at this time. Eight years later, a local recurrence of the tumor was noted. A complete excision was now performed. The patient was able to finally interrupt the phosphate intake. In the second case, an F-18 fluorodeoxyglucose positron emission tomography, with computed tomography revealed a 2.26 cm diameter hypermetabolic nodule in the soft tissue of the right forefoot. After its removal, the patient discontinued the phosphate intake. Both patients are asymptomatic and show a regular phosphocalcic laboratory evaluation. The histopathological diagnosis was, in both cases, a phosphaturic mesenchymal tumor, a mixed connective tissue variant. This is the prototypical variant of these tumors.

Hypertriglyceridemia is reported as cause of 1 to 4% of the episodes of acute pancreatitis. We report the case of a 42-year-old woman with a history of obesity, type 2 diabetes mellitus, hypertriglyceridemia and hypercholesterolemia, with triglycerides of 9365 mg/dl, total cholesterol of 1822 mg/dl, one month prior to the consultation. She presented at the emergency unit with a 5 day history of abdominal pain, which progressed in intensity in the last 48 hours. Abdominal computed tomography revealed pancreatic and peripancreatic inflammation. Thirty-six hours after admission, a first session of plasmapheresis was conducted with a plasma triglyceride and cholesterol reduction of 25 and 30%, respectively. A second session was performed the next day, with a further reduction of triglycerides to 996 mg/dl and cholesterol to 238 mg/dl. During hospitalization the patient presented fever and Klebsiella pneumoniae bacteremia with no pancreatic collection or necrosis in tomography and, later on, nosocomial pneumonia, both infections with adequate response to antibiotic therapy. At the time of discharge, triglycerides and cholesterol levels were 652 mg/dl and 167 mg/dl respectively, no abdominal pain was present and the patient resumed oral nutrition. We observed a 90% reduction of triglycerides and 87% of cholesterol after 2 sessions of plasmapheresis, compared to 70% in average of reduction in most of the studies reviewed. We did not find the presence of bacteremia or nosocomial pneumonia as complications in the reported cases.

La hipertrigliceridemia es causa de 1-4% de las pancreatitis agudas. Presentamos el caso de una mujer de 42 años con antecedentes de obesidad, diabetes mellitus tipo 2, hipertrigliceridemia e hipercolesterolemia (9365 mg/dl y 1822 mg/dl, respectivamente, 1 mes previo a la consulta). Concurrió a nuestro hospital por cuadro de dolor abdominal de 5 días de evolución de tipo cólico con progresión continua en las últimas 48 horas. Se realizó tomografía de abdomen que informó imágenes compatibles con pancreatitis. A las 36 horas de su ingreso se inició la primera sesión de plasmaféresis con una reducción de triglicéridos y colesterol del 25 y 30% respectivamente y una segunda sesión al día siguiente con descenso de triglicéridos a 996 mg/dl y colesterol a 238 mg/dl. Durante su internación presentó bacteriemia por Klebsiella pneumoniae, sin colección ni necrosis pancreática detectables por tomografía de abdomen, y luego neumonía intrahospitalaria, ambas infecciones con buena respuesta a antibioticoterapia. Al alta, los triglicéridos habían descendido a 652 mg/dl, el colesterol a 167 mg/dl, el dolor abdominal había cedido y la paciente presentaba buena tolerancia por vía oral. Observamos una reducción del 90% de triglicéridos y 87% de colesterol luego de dos sesiones de plasmaféresis, comparado con 70% de reducción en promedio en la mayoría de los estudios consultados. En los mismos, no hemos encontrado la presencia de bacteriemia ni neumonía hospitalaria como complicaciones.

Objective: The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital. Subjects and methods: Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment. Results: During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment. Conclusions: About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.