Endocrine complications after hematopoietic stem cell transplantation during childhood-Results from a close follow-up in a cohort of 152 patients.

CONTEXT: Haematopoietic stem cell transplantation (HSCT) is a therapeutic option for numerous haematologic diseases and solid tumours. Increasing indications for HSCT and reduction in associated mortality have been raising the number of paediatric HSCT survivors and their long-term toxicities. OBJECTIVE: To characterize the endocrine disorders developed after HSCT. DESIGN AND PATIENTS: Retrospective analysis of 152 patients submitted to HSCT in paediatric age with at least 24 months of follow-up at our endocrine late-effects clinics. RESULTS: Patients were followed up for 9.9 (interquartile range [IQR]: 12.2) years. The median age at HSCT was 7.5 (IQR: 9) years. At least one endocrine complication was observed in 65.1% of the patients. Primary hypogonadism was detected in 34.2%. Female gender (p < .001), HSCT > 10 years old (p = .01) and chemotherapy before HSCT (p < .001) were identified as risk factors for developing gonadal dysfunction. Growth hormone deficiency (GHD) occurred in 23.0% with a mean stature Z-score at diagnosis of -1.8 ± 1.4. GHD was associated with cranial (p < .001) and HSCT < 10 years old (p ≤ 0.001). Patients who were exposed to total body irradiation (TBI) were at higher risk for primary hypothyroidism (22.3%) (p = .01), thyroid nodules (17.1%) (p < .001), thyroid carcinoma (5.3%) (p < .001), dyslipidaemia (19.1%) (p < .001) and disturbance of carbohydrate metabolism (19.1%) (p < .001). CONCLUSION: At least one endocrine complication was diagnosed in 65.1% of patients, with gonadal dysfunction being the most prevalent. The conditioning regimen with TBI was a risk factor for the development of several endocrine disorders. This study is one of the largest series evaluating the endocrine disorders among survivors of paediatric HSCT and intends to reinforce the importance of routine follow-up of these patients.

Clinical outcomes of a cohort of 271 patients with lung metastases from differentiated thyroid carcinoma.

CONTEXT: Lung is the most common site of distant metastases from differentiated thyroid carcinoma (DTC). OBJECTIVE: To investigate the outcomes of a cohort of patients with DTC and lung metastases (LM). METHODS: A retrospective analysis of a cohort of 271 patients with LM was performed. RESULTS: The female-to-male ratio was 1:1 and the median follow-up time was 5.9 (1.1-38.4) years. Papillary thyroid carcinoma (PTC) was the most frequent type (83.4%), mainly the classic variant, followed by follicular thyroid carcinoma (FTC, 10.3%) and Hürthle cell carcinoma (HTC, 6.3%). The prevalence of PTC, FTC and HCC was different between the micronodular and macronodular LM groups [87.4%, 6.3% and 6.3% vs. 74.6%, 19.0% and 6.3%, respectively (p = .013)]. Only 5.0% of the patients had LM diagnosed after a period of remission. LM were submitted to radioactive iodine treatment (RAIT) in 84.5% (52.8% showed 131 iodine avid metastases). Complete remission was only achieved in 12.2%. Micronodular disease and age <55 years at LM diagnosis were associated with a better prognosis (p < .05). We found no difference in survival between patients with LM treated or not with RAIT. However, in patients submitted to RAIT, there was a tendency for longer survival in the group of patients with 131 I avid lesions. CONCLUSION: The classic variant of PTC was the most frequent histology found in LM of DTC. LM are rarely diagnosed in the follow-up when complete remission is achieved after surgery and 131 I. Younger age at LM diagnosis and a micronodular pattern are associated with a better prognosis.

Predictive factors for thyroid complications after radiation therapy-data from a cohort of cancer patients closely followed since they were irradiated.

INTRODUCTION: Cancer survivors are at an increased risk of adverse outcomes, including thyroid neoplasms, given the high radiosensitivity of this gland. The aim of this study is to assess the incidence and timeframe of thyroid complications in cancer patients, followed systematically since their radiation therapy, and to identify risk factors for the development of hypothyroidism and thyroid cancer. METHODS: We performed a retrospective study, including 282 subjects, who received neck, craniospinal, or total body irradiation (TBI). Patients were grouped into four primary diagnostic clusters: leukaemia, Hodgkin's disease, central nervous system, and head and neck tumours. RESULTS: Hypothyroidism was observed in 56.7% of patients, on average 6.8 ± 5.9 years after the treatment. Neck and craniospinal irradiation presented a 3.5-fold increased risk for the development of hypothyroidism compared to TBI. Papillary thyroid cancer was diagnosed in 8.5% of the patients, on average, 18.5 ± 4.9 years after radiotherapy (RT). Female gender, younger age, and lower irradiation doses were independently associated with thyroid cancer development. CONCLUSION: Our study provides useful information about the risk of hypothyroidism and thyroid cancer after RT, as it was performed in a cohort of patients closely followed since the oncological therapies, and, thus, may give new insights into the follow-up management of these patients.

Clinical outcomes of a conservative approach in cervical lymph node metastases of thyroid cancer.

CONTEXT: Lymph node metastases (LNM) can be present in 35% of patients with differentiated thyroid cancer (DTC), and the management of persistent/recurrent nodal disease has been controversial. Watchful waiting may be a reasonable approach in selected patients, but uncertainty about clinical outcomes remains a concern. OBJECTIVE: To investigate the outcomes of patients with DTC with recurrent/persistent confirmed LNM under surveillance. METHODS: Patients with LNM from DTC were selected from databases of needle washout thyroglobulin measurements and fine-needle aspiration biopsies performed in our institution. Patients with confirmed metastases, in whom active surveillance was initially proposed, were selected. Main clinical outcomes were analysed. RESULTS: We found 89 patients with LNM under surveillance. Classic papillary was the most frequent variant (44%). During a median follow-up of 3 (0.5-17.2) years, different treatments were needed in 35 (39.3%) patients: radioactive iodine (RAI) in 23 (25.8%), surgery in 9 (10.1%) and radiotherapy (RT) in 3 (3.4%). From those submitted initially to RAI, progression of disease was observed in 8 patients, 4 requiring other treatment modalities: surgery (n = 2), RT (n = 1) and RAI (n = 1). The remaining 54 (60.7%) patients maintained surveillance. In this group, progression of disease was observed in 26 (48.1%), due to increase in the number and/or volume of metastases, but further treatments were not required. CONCLUSION: In a group of patients with cervical LNM under active surveillance, only 16.9% (n = 15) required invasive intervention (surgery or RT).

A Case Report of Sheehan Syndrome: A Rare Cause of Hypopituitarism.

Sheehan syndrome is a rare cause of hypopituitarism characterized by pituitary gland necrosis after postpartum hemorrhage. It is a pertinent cause of maternal morbidity and mortality in developing countries with deficient obstetrical care but is frequently overlooked in developed countries where its occurrence is uncommon. We present the case of a 66-year-old female diagnosed with Sheehan syndrome more than 30 years after her last delivery complicated by postpartum hemorrhage. Although the patient presented several symptoms and signs of pituitary hormonal deficiencies, a diagnosis had never been established before. The complete laboratory analysis revealed a deficiency in the pituitary axis, and the cranial imaging showed an empty sella turcica. Hormonal replacement therapy resolved several impairments in terms of general energy, physical capacity, temperature regulation, skin characteristics, and sexual function. It also improved her cardiovascular and osteoporosis risk, and, most importantly, prevented a potential life-threatening adrenal crisis. This report highlights the subtle manifestations of Sheehan syndrome to help clinicians establish a prompt diagnosis. Even in developed countries such as Portugal, this condition should be regarded as a potential cause of hypopituitarism.

Effectiveness and safety of lenvatinib in a series of advanced well-differentiated thyroid carcinomas from a single tertiary cancer center and literature review.

BACKGROUND: Treatment of advanced differentiated thyroid carcinoma (DTC) remains a challenge as 25-50% of patients with locally invasive or distant metastatic disease become refractory to radioiodine (RAI) therapy. Tyrosine kinase inhibitors (TKI) are increasingly used in this setting. The SELECT trial demonstrated that lenvatinib, a multikinase inhibitor, significantly improved progression free survival (PFS) compared to placebo. Our aim was to report the effectiveness and safety of lenvatinib in our series of patients with advanced DTC. METHODS: A total of 25 patients with advanced DTC followed at a single tertiary center from January of 2016 to January of 2022 were retrospectively reviewed. RESULTS: Patients were treated with a mean daily dose of lenvatinib of 16.9 mg for a mean of 9.1 months. Median estimated PFS was 31.3 months. One patient achieved complete response. The objective response rate (ORR) was 40% and the disease control rate was 84%. The mean change in summed longest diameter of target lesions from baseline to nadir was -36.9%. Lenvatinib prolonged the tumor volume doubling time in 86.7% patients. Interestingly, we found that patients treated with a lower dose of lenvatinib (<16.9 mg daily) had a significantly higher PFS and ORR than patients treated with higher dosages (>16.9 mg). Adverse events were frequently reported. CONCLUSIONS: Our results confirm the effectiveness of lenvatinib in the management of patients with advanced DTC and support the need to adjust the dosage of lenvatinib to patient´s performance status and comorbidities.

Acute suppurative thyroiditis with Graves disease - A very rare association.

Acute suppurative thyroiditis is an uncommon disorder caused by a bacterial infection, usually presenting with normal thyroid function. It is a serious condition that requires a prompt diagnosis and treatment with antibiotics and supportive measures. A 62 years-old female presented with a painful cervical induration and odynophagia a week after a fish bone had been removed from her pharynx. She was febrile, and tachycardic and, on physical examination, a painful thyroid mass was detected. High inflammatory parameters and thyrotoxicosis were confirmed: thyroid stimulating hormone (TSH) < 0.01 mIU/L (normal range [NR] 0.27-4.2); free thyroxine (FT4) 3.86 ng/dL (NR 0.9-1.7) and anti-TSH receptor antibodies (TRABs) 5.3 U/L (NR < 1.5). Thyroid scintigraphy showed a diffuse uptake of the thyroid parenchyma suggesting Graves disease. Cervical ultrasonography revealed an abscess of the left thyroid lobe of 36 × 36 mm and fine needle aspiration biopsy (FNAB) with partial drainage was performed. Staphylococcus aureus and Streptococcus viridans were isolated, and directed antibiotic therapy was started. Clinical improvement was observed as well as a decrease of inflammatory parameters and the patient was discharged after 9 days of hospitalization. Eighteen days after discharge, thiamazole was initiated due to persistent thyrotoxicosis. Complete resolution of the abscess was documented within 6 months and the patient became euthyroid under thiamazole one year after initial presentation. To our knowledge, this is the third case reporting an association between acute thyroiditis and Graves disease. Furthermore, this is the first case detailing the simultaneous diagnosis of acute suppurative thyroiditis caused by a foreign body and Graves disease.

Adrenal findings in FDG-PET: analysis of a cohort of 1021 patients from a cancer center.

PURPOSE: The use of FDG-PET for cancer staging has led to the increasing incidence of adrenal lesions, which are usually a clinical challenge. We aimed to characterize the adrenal lesions found in FDG-PET of patients followed in a cancer center. METHODS: Retrospective analysis was conducted of all FDG-PET studies performed in our center in the last 10 years. Exams reporting adrenal lesions in the CT component and/or anomalous adrenal FDG uptake were selected. Cases were characterized by the clinical, laboratory, imaging, and pathological findings. RESULTS: We identified 27,427 FDG-PET studies. Of those, 7.6% reported adrenal findings. We included 1364 exams corresponding to 1021 patients. Only 15.6% of the patients were referred to the Endocrinology Department and 38% of the lesions were not studied. In 38.9% of the studied patients, malignant lesions were present, including metastases in 37.5%, carcinoma in 1.2%, and other malignant tumors in 0.4%. The median SUVmax of malignant lesions was significantly higher than the SUVmax of the benign findings (p < 0.05). We also observed a higher median SUVmax in adrenal metastases than in adenomas (p < 0.05). There was a tendency for higher SUVmax of adrenal carcinomas when compared with other malignant lesions (p = 0.066). The median SUVmax was not different between pheochromocytomas and other tumors (p > 0.05). CONCLUSION: Occult adrenal lesions discovered during FDG-PET/CT are common in the cancer context and are frequently benign. SUVmax may be a useful tool in the workup of adrenal lesions but with several important caveats.

Precocious and accelerated puberty in children with neurofibromatosis type 1: results from a close follow-up of a cohort of 45 patients.

PURPOSE: Central precocious puberty (CPP) in neurofibromatosis type 1 (NF1) occurs mainly in association with optic pathway glioma (OPG), but it can also develop in the absence of OPG. The aim of this study was to analyze the prevalence of puberty disorders in children with NF1 and its association with OPG and its location. METHODS: A retrospective study of 45 children with NF1 (68.9% boys) followed at our center between 2008 and 2020 was conducted. A cerebral MRI scan was performed in all children. We analyzed auxological, laboratory, and imaging data of children with CPP or accelerated puberty (AP). Treatments used for CPP/AP and their effect on height were also evaluated. RESULTS: The prevalence of puberty disorders in our cohort was 17.8% (male to female ratio of 7:1). CPP and AP were diagnosed in 8/45 (17.8%) NF1 children. Among children with puberty disorders, 5/8 (62.5%) had an OPG with chiasm involvement, 1/8 (12.5%) had an isolated optic nerve tumor, and 2/8 (25%) did not have any evidence of OPG on MRI. Fisher's exact test showed an association between CPP/AP and chiasm OPG (p = 0.025). Treatment with triptorrelin was initiated in 5/8 children, of whom four attained final predicted height. CONCLUSION: Our study confirms the higher prevalence of CPP/AP in NF1 patients, as well as an association between chiasm OPG and puberty disorders. However, CPP/AP also occurred in the absence of OPG with an incidence of 9.1%. Comprehensive evaluation of every child with NF1 regardless of the presence of OPG is therefore essential.

Isolated adrenal metastases of papillary thyroid carcinoma.

Not required for Clinical Vignette.

Is Gonadal Therapy a Promoter of Breast Cancer? Incidence of Breast Cancer in a Cohort of Survivors of Oncological Diseases Treated with Gonadal Steroids.

There is a great controversy about hormonal replacement therapy in women among the members of the scientific community. Cancer survivors have sometimes had their ovary function totally or partially destroyed, thus affecting their development and quality of life. In this study, we were looking for adverse effects caused, eventually, by estroprogestative therapy in a cohort of supplemented survivors. The occurrence of breast cancer was our main concern. Ours is a retrospective study based on the clinical records of 174 survivors of several cancer diseases. Their median ages within each of the following time frames were: diagnosis - 22 years old; start of endocrine treatment - 26 years old, and duration of treatment - 12 years old. Evaluation was composed of breast cancer assessment, osteopenia and osteoporosis incidence, and vascular events. We have found a very low incidence of breast cancer as well as of vascular events. After treatment, a high percentage of our sample displayed bone mass improvement.

ADRENAL MICROCYSTIC RETICULAR SCHWANNOMA.

OBJECTIVE: Schwannomas are usually benign tumors, originating from the Schwann cell myelin sheath around the peripheral or cranial nerves. Visceral schwannomas are rare, and less than 60 cases of adrenal schwannomas have been reported. Microcystic/reticular schwannoma (MRS) is the rarest variant of schwannoma and only 2 cases have been reported in the adrenal gland. Here we describe a third case. METHODS: We describe a case of an adrenal MRS with a comprehensive literature review. RESULTS: The patient was a 69-year-old, Caucasian female with abdominal pain. An abdominal computed tomography scan revealed a solid, lobulated, 78-mm mass of the left adrenal gland. Two inconclusive adrenal biopsies were performed and then she was referred to our tertiary center for further evaluation. No clinical or laboratorial signs of endocrine dysfunction were identified. A positron emission tomography scan with fluorodeoxyglucose showed a single left adrenal hypermetabolic mass (SUVmax = 71.7), suggestive of malignancy. In this context, an open left adrenalectomy was undertaken. The histologic evaluation showed an MRS. CONCLUSION: Adrenal MRSs are extremely rare tumors. Definitive diagnosis of schwannoma can only be made by surgical excision with histopathologic and immunohistochemical evaluation of the specimen.

Acute suppurative thyroiditis with Graves disease - A very rare association

SUMMARY Acute suppurative thyroiditis is an uncommon disorder caused by a bacterial infection, usually presenting with normal thyroid function. It is a serious condition that requires a prompt diagnosis and treatment with antibiotics and supportive measures. A 62 years-old female presented with a painful cervical induration and odynophagia a week after a fish bone had been removed from her pharynx. She was febrile, and tachycardic and, on physical examination, a painful thyroid mass was detected. High inflammatory parameters and thyrotoxicosis were confirmed: thyroid stimulating hormone (TSH) < 0.01 mIU/L (normal range [NR] 0.27-4.2); free thyroxine (FT4) 3.86 ng/dL (NR 0.9-1.7) and anti-TSH receptor antibodies (TRABs) 5.3 U/L (NR < 1.5). Thyroid scintigraphy showed a diffuse uptake of the thyroid parenchyma suggesting Graves disease. Cervical ultrasonography revealed an abscess of the left thyroid lobe of 36 × 36 mm and fine needle aspiration biopsy (FNAB) with partial drainage was performed. Staphylococcus aureus and Streptococcus viridans were isolated, and directed antibiotic therapy was started. Clinical improvement was observed as well as a decrease of inflammatory parameters and the patient was discharged after 9 days of hospitalization. Eighteen days after discharge, thiamazole was initiated due to persistent thyrotoxicosis. Complete resolution of the abscess was documented within 6 months and the patient became euthyroid under thiamazole one year after initial presentation. To our knowledge, this is the third case reporting an association between acute thyroiditis and Graves disease. Furthermore, this is the first case detailing the simultaneous diagnosis of acute suppurative thyroiditis caused by a foreign body and Graves disease.

Deception and manipulation: the arms of leishmania, a successful parasite.

Leishmania spp. are intracellular parasitic protozoa responsible for a group of neglected tropical diseases, endemic in 98 countries around the world, called leishmaniasis. These parasites have a complex digenetic life cycle requiring a susceptible vertebrate host and a permissive insect vector, which allow their transmission. The clinical manifestations associated with leishmaniasis depend on complex interactions between the parasite and the host immune system. Consequently, leishmaniasis can be manifested as a self-healing cutaneous affliction or a visceral pathology, being the last one fatal in 85-90% of untreated cases. As a result of a long host-parasite co-evolutionary process, Leishmania spp. developed different immunomodulatory strategies that are essential for the establishment of infection. Only through deception and manipulation of the immune system, Leishmania spp. can complete its life cycle and survive. The understanding of the mechanisms associated with immune evasion and disease progression is essential for the development of novel therapies and vaccine approaches. Here, we revise how the parasite manipulates cell death and immune responses to survive and thrive in the shadow of the immune system.

Adsorbed fibrinogen enhances production of bone- and angiogenic-related factors by monocytes/macrophages.

Macrophages are phagocytic cells with great importance in guiding multiple stages of inflammation and tissue repair. By producing a large number of biologically active molecules, they can affect the behavior of other cells and events, such as the foreign body response and angiogenesis. Since protein adsorption to biomaterials is crucial for the inflammatory process, we addressed the ability of the pro-inflammatory molecule fibrinogen (Fg) to modulate macrophage behavior toward tissue repair/regeneration. For this purpose, we used chitosan (Ch) as a substrate for Fg adsorption. Freshly isolated human monocytes were seeded on Ch substrates alone or previously adsorbed with Fg, and allowed to differentiate into macrophages for 10 days. Cell adhesion and morphology, formation of foreign body giant cells (FBGC), and secretion of a total of 80 cytokines and growth factors were evaluated. Both substrates showed similar numbers of adherent macrophages along differentiation as compared with RGD-coated surfaces, which were used as positive controls. Fg did not potentiate FBGC formation. In addition, actin cytoskeleton staining revealed the presence of punctuate F-actin with more elongated and interconnecting cells on Ch substrates. Antibody array screening and quantification of inflammation- and wound-healing-related factors indicated an overall reduction in Ch-based substrates versus RGD-coated surfaces. At late times, most inflammatory agents were down-regulated in the presence of Fg, in contrast to growth factor production, which was stimulated by Fg. Importantly, on Ch+Fg substrates, fully differentiated macrophages produced significant amounts of macrophage inflammatory protein-1delta (MIP-1δ), platelet-derived growth factor-BB, bone morphogenetic protein (BMP)-5, and BMP-7 compared with Ch alone. In addition, other important factors involved in bone homeostasis and wound healing, such as growth hormone, transforming growth factor-ß3, and insulin-like growth factor-binding proteins, as well as several angiogenic mediators, including endocrine gland-derived vascular endothelial factor, fibroblast growth factor-7, and placental growth factor, were significantly promoted by Fg. This work provides a new perspective on the inflammatory response in the context of bone repair/regeneration mediated by a pro-inflammatory protein (Fg) adsorbed onto a biomaterial (Ch) that does not otherwise exhibit osteogenic properties.

Análise do estado de cobertura vacinal de crianças menores de três anos no município de Fortaleza em 2017 / Analysis of the state of vaccination coverage of children under three years old in the city of Fortaleza in 2017 / Análisis del estado de cobertura de vacunación de niños menores de tres años de edad en la ciudad de Fortaleza en 2017

Objetivo: Analisar o estado atual da cobertura vacinal (CV) de crianças menores de três anos no município de Fortaleza, CE, e sua relação com a condição socioeconômica das famílias. Métodos: Pesquisa transversal de base populacional com amostragem aleatória. As informações foram obtidas por meio da aplicação de questionários e conferência de Cadernetas de Saúde quanto ao estado vacinal, bem como de dados ecológicos de desenvolvimento humano. A CV foi estimada em crianças na faixa etária de 19 a 36 meses. Resultados: Observou-se que 45,2% das crianças estudadas apresentavam-se com a CV recomendada pelo Ministério da Saúde (MS). Além disto, verificou-se fatores socioeconômicos determinantes de cobertura vacinal e que áreas descobertas de Agentes Comunitários de Saúde apresentaram pior cobertura. Conclusão: O presente estudo revela que é necessário fortalecer as ações que aumentem as cobertura vacinais no município.

Objective: To analyze the current state of the vaccination coverage (VC) of children under three years old in the city of Fortaleza, CE, and its relation with the socioeconomic status of the families. Methods: A population-based cross-sectional survey with random sampling, information was obtained through questionnaires applied and Health Booklets conferred to the vaccination status, as well as ecological human development data. VC was estimated in children between the ages of 19 and 36 months. Results: It was observed that 45.2% of studied children presented a VC recommended by the Ministry of Health. In addition, socioeconomic factors which are determinants of vaccine coverage were identified and that areas not covered by community health agents have worse coverage. Conclusion: The present study reveals that it is necessary to strengthen actions that increase VC in the municipality.

Objetivo: Analizar el estado actual de la cobertura vacunal (CV) de niños menores de tres años en el municipio de Fortaleza y su relación con la condición socioeconómica de las familias. Métodos: Investigación transversal de base poblacional con muestreo aleatorio, se obtuvo información a través de cuestionarios aplicados y Cuadernos de Salud conferidos al estado vacunal, así como datos ecológicos de desarrollo humano. La CV fue estimada en niños en el grupo de edad de 19 a 36 meses. Resultados: Se observó que el 45,2% de los niños estudiados se presentaban con la CV recomendada por el Ministerio de Salud. Además, que factores socioeconómicos son determinantes de cobertura vacunal y que áreas descubiertas de agentes comunitarios de salud presentan peor cobertura. Conclusión: El presente estudio revela que es necesario fortalecer las acciones que aumenten las CV en el municipio.

The stability of self-assembled monolayers with time and under biological conditions.

The stability of self-assembled monolayers (SAMs) of different functionalities (CH(3)-, OH-, and EG4-) over time under appropriate storage conditions and when immersed in cell culture media was evaluated. X-ray photoelectron spectroscopy (XPS) was used to detect the oxidized sulfur species (S(2p) binding energy from 167 to 168 eV) resulting from oxidation of the surfaces. CH(3)-terminated SAMs stored for a period of 9 weeks in a nitrogen chamber were not altered. The same did not happen with OH- and EG4-SAMs, for which the XPS spectra evidenced oxidized peaks after 2 weeks. Regarding the stability of these surfaces under biological conditions, 30 min of immersion at 37 degrees C in serum-free or 10% fetal bovine serum (FBS) supplemented medium did not induce detectable oxidation. However, a small percentage of oxidized sulfur could have been washed out by the media, as confirmed in studies using SAMs immersed in water. Despite the possible rinsing out of oxidized thiols, high amounts of oxidation can still be detected by XPS. SAMs degradation during ethanol sterilization was not detectable by XPS, although a small increase on the wettability of OH-SAMs was observed. The data suggest that SAMs must be used freshly prepared, being recommended for short-term biological studies.

Immune response regulation by leishmania secreted and nonsecreted antigens.

Leishmania infection consists in two sequential events, the host cell colonization followed by the proliferation/dissemination of the parasite. In this review, we discuss the importance of two distinct sets of molecules, the secreted and/or surface and the nonsecreted antigens. The importance of the immune response against secreted and surface antigens is noted in the establishment of the infection and we dissect the contribution of the nonsecreted antigens in the immunopathology associated with leishmaniasis, showing the importance of these panantigens during the course of the infection. As a further example of proteins belonging to these two different groups, we include several laboratorial observations on Leishmania Sir2 and LicTXNPx as excreted/secreted proteins and LmS3arp and LimTXNPx as nonsecreted/panantigens. The role of these two groups of antigens in the immune response observed during the infection is discussed.