Regional Brain Perfusion Is Associated with Endothelial Dysfunction Markers in Major Depressive Disorder.

BACKGROUND: Major depressive disorder (MDD) is an important independent risk factor for cardiovascular disease. Cumulative data suggest that depressive patients exhibit derangement in regional cerebral blood flow (rCBF), although underlying mechanisms remain mostly unknown. Endothelial dysfunction (ED), defined as different forms of abnormal endothelial activity, plays a key role in the pathogenesis of vascular disease. ED is associated with several clinical conditions characterized by high cardiovascular risk. Diverse ED markers have been found in mood disorders. PURPOSE: To evaluate the association between rCBF and peripheral ED markers in MDD patients, at baseline and after selective serotonin receptor inhibitors (SSRIs) therapy. PATIENTS AND METHODS: Twenty-seven untreated unipolar MDD patients in their first episode were evaluated with the Hamilton Depression Rating Scale (HAM-D) and brain perfusion SPECT at baseline and after 2 months of SSRIs. Statistical Parametric Mapping (SPM) was employed to evaluate rCBF; circulating endothelial cells (CECs), plasma soluble intercellular adhesion molecule (sICAM), and high-sensitivity C-reactive protein (hsCRP) were used as independent covariates. RESULTS: Baseline CECs and sICAM were increased in MDD patients compared with matching controls (p = 0.0001) and hsCRP (p = 0.03). HAM-D scores (21 items) and CECs diminished after SSRI therapy in MDD patients (p < 0.0001). There was a significant rCBF decrease, mainly in deep central structures. HAM-D change was associated with rCBF decrease at the left amygdala, right striatum levels, and Brodmann area 25. CEC change was associated with rCBF at deep brain level and sICAM with large rCBF areas at the left caudate and tectum; hsCRP was associated, to a lesser extent, with the left dorsal striatum and mesencephalic tectum. CONCLUSION: ED markers in patients with MDD are associated with significant changes in rCBF which are features of depression. These findings suggest that systemic damage/activation of the endothelium may contribute to the abnormal rCBF observed in MDD patients.

[Successful oral desensitization to levothyroxine. Report of one case]. / Desensibilización a levotiroxina. Caso clínico.

We report a 39-year-old female who underwent a total thyroidectomy as treatment for a thyroid papillary cancer. She suffered several episodes of mild angioedema in lips and tongue, after using different commercial Levothyroxine formulations, with and without excipients. Given the need to use this drug, the patient was admitted in our hospital and we proceeded to desensitize her with oral Levothyroxine. The patient fasted throughout the whole procedure, was properly monitored and had an adequate peripheral venous access. On the first day of the procedure, a 15-step protocol was performed, first administering placebo and then, compounded formulations of Levothyroxine starting from 0.01 ug, followed by doubling doses every 15 minutes until the cumulative dose of 111.95 ug was completed, corresponding to the daily dose of Levothyroxine her endocrinologist prescribed (112 ug). The patient was monitored at baseline, between each dose and up to 3 hours after the procedure was completed. There were no incidents such as urticaria, angioedema, or others. On the second day, the patient received a single-full dose of 112 ug on an empty stomach. The medication was successfully tolerated and she was discharged. Thereafter, she tolerates daily Levothyroxine.

Desensibilización a levotiroxina: caso clínico / Successful oral desensitization to levothyroxine: report of one case

We report a 39-year-old female who underwent a total thyroidectomy as treatment for a thyroid papillary cancer. She suffered several episodes of mild angioedema in lips and tongue, after using different commercial Levothyroxine formulations, with and without excipients. Given the need to use this drug, the patient was admitted in our hospital and we proceeded to desensitize her with oral Levothyroxine. The patient fasted throughout the whole procedure, was properly monitored and had an adequate peripheral venous access. On the first day of the procedure, a 15-step protocol was performed, first administering placebo and then, compounded formulations of Levothyroxine starting from 0.01 ug, followed by doubling doses every 15 minutes until the cumulative dose of 111.95 ug was completed, corresponding to the daily dose of Levothyroxine her endocrinologist prescribed (112 ug). The patient was monitored at baseline, between each dose and up to 3 hours after the procedure was completed. There were no incidents such as urticaria, angioedema, or others. On the second day, the patient received a single-full dose of 112 ug on an empty stomach. The medication was successfully tolerated and she was discharged. Thereafter, she tolerates daily Levothyroxine.

[Study and management of thyroid nodes by non specialist physicians: SOCHED consensus]. / Estudio y manejo de nódulos tiroideos por médicos no especialistas. Consenso SOCHED.

The thyroid nodule is a frequent cause of primary care consultation. The prevalence of a palpable thyroid nodule is approximately 4-7%, increasing up to 67% by the incidental detection of nodules on ultrasound. The vast majority are benign and asymptomatic, staying stable over time. The clinical importance of studying a thyroid nodule is to exclude thyroid cancer, which occurs in 5 to 10% of the nodules. The Board of SOCHED (Chilean Society of Endocrinology and Diabetes) asked the Thyroid Study Group to develop a consensus regarding the diagnostic management of the thyroid nodule in Chile, aimed at non-specialist physicians and adapted to the national reality. To this end, a multidisciplinary group of 31 experts was established among university academics, active researchers with publications on the subject and prominent members of scientific societies of endocrinology, head and neck surgery, pathology and radiology. A total of 14 questions were developed with key aspects for the diagnosis and subsequent referral of patients with thyroid nodules, which were addressed by the participants. In those areas where the evidence was insufficient or the national reality had to be considered, the consensus opinion of the experts was used through the Delphi methodology. The consensus was approved by the SOCHED board for publication.

Estudio y manejo de nódulos tiroideos por médicos no especialistas. Consenso SOCHED / Study and management of thyroid nodes by non specialist physicians: SOCHED consensus

The thyroid nodule is a frequent cause of primary care consultation. The prevalence of a palpable thyroid nodule is approximately 4-7%, increasing up to 67% by the incidental detection of nodules on ultrasound. The vast majority are benign and asymptomatic, staying stable over time. The clinical importance of studying a thyroid nodule is to exclude thyroid cancer, which occurs in 5 to 10% of the nodules. The Board of SOCHED (Chilean Society of Endocrinology and Diabetes) asked the Thyroid Study Group to develop a consensus regarding the diagnostic management of the thyroid nodule in Chile, aimed at non-specialist physicians and adapted to the national reality. To this end, a multidisciplinary group of 31 experts was established among university academics, active researchers with publications on the subject and prominent members of scientific societies of endocrinology, head and neck surgery, pathology and radiology. A total of 14 questions were developed with key aspects for the diagnosis and subsequent referral of patients with thyroid nodules, which were addressed by the participants. In those areas where the evidence was insufficient or the national reality had to be considered, the consensus opinion of the experts was used through the Delphi methodology. The consensus was approved by the SOCHED board for publication.

[Clinical features of patients with Basedow Graves disease seen at a university hospital]. / Caracterización de pacientes controlados por enfermedad de Basedow Graves en un hospital universitario.

BACKGROUND: Basedow Graves disease (BGD) is the leading cause of hyperthyroidism. The characteristics of patients seen at a university hospital may differ from those described in the general population. AIM: To describe the clinical features of patients with BGD seen at a university hospital. MATERIAL AND METHODS: Review of medical records of all patients seen at our hospital between 2009 and 2014 with the diagnosis of thyrotoxicosis, hyperthyroidism or BGD. Clinical features, laboratory results and treatments were recorded. RESULTS: We reviewed clinical records of 272 patients; 15 had to be excluded due to incomplete data. BGD was present in 77.9% (n = 212). The mean age of the latter was 42 years (range 10-81) and 76% were women. Ninety six percent were hyperthyroid at diagnosis and thyroid stimulating hormone was below 0.1 mIU/L in all patients. Median free thyroxin and triiodothyronine levels were 3.26 ng/dl and 3.16 ng/ml, respectively. Thyrotropin-receptor antibodies were positive in 98.5% and 85.7% had positive thyroid peroxidase antibodies. Graves orbitopathy (GO) was clinically present in 55% of patients. Of this group, 47% had an active GO, 26% had a moderate to severe disease and 7.8% had sight-threatening GO. As treatment, 26% received radioiodine, 44% anti-thyroid drugs exclusively, 28% underwent thyroidectomy and 2% did not require therapy. CONCLUSIONS: In this group of patients, we observed a greater frequency of severe eye disease and a high rate of surgical management. This finding could be explained by referral to highly qualified surgical and ophthalmological teams.

Association between non-melanoma and melanoma skin cancer rates, vitamin D and latitude.

Vitamin D synthesis takes place in the skin due to solar ultraviolet-B (UVB) radiation. Several studies have shown the association between low sun exposure, non-melanoma skin cancer (NMSC) and a lack of vitamin D synthesis. Since such synthesis in the body depends on the exposure of the skin to solar UVB radiation (290-320 nm), experimental measurements of this type of solar radiation are important. Tarapaca University in Arica, Chile, established a solar UV radiation laboratory in 2006 and since then this laboratory has performed systematic experimental solar UVB measurements using a calibrated biometer instrument. The results, which are presented in the current study, showed the association between NMSC and MSC rates, and the time required to produce 1,000 IU vitamin D with latitudinal variation. Solar UV index (UVI) levels reported in 6 cities from the north to the south of Chile indicated that the UVI ratio of monthly mean values was 1.8 times higher in Arica than in Punta Arenas in January (summer in Chile), whereas it was 14 times higher in June (winter). This factor is an important consideration, since vitamin D synthesis is directly associated with the exposure of individuals to solar UVB radiation. A similar trend was observed in Antofagasta, Santiago, Concepcion, Valdivia and Punta Arenas. It can be concluded from these data that there is a direct association between NMSC rates and mortality, and UVB radiation, meaning that this type of cancer would not depend on vitamin D synthesis and therefore on calcium uptake. By contrast, MSC rates increased with decreased levels of vitamin D, and thus calcium uptake, in all cities, with the only exception being Punta Arenas.

Caracterización de pacientes controlados por enfermedad de Basedow Graves en un hospital universitario / Clinical features of patients with Basedow Graves disease seen at a university hospital

Background: Basedow Graves disease (BGD) is the leading cause of hyperthyroidism. The characteristics of patients seen at a university hospital may differ from those described in the general population. Aim: To describe the clinical features of patients with BGD seen at a university hospital. Material and Methods: Review of medical records of all patients seen at our hospital between 2009 and 2014 with the diagnosis of thyrotoxicosis, hyperthyroidism or BGD. Clinical features, laboratory results and treatments were recorded. Results: We reviewed clinical records of 272 patients; 15 had to be excluded due to incomplete data. BGD was present in 77.9% (n = 212). The mean age of the latter was 42 years (range 10-81) and 76% were women. Ninety six percent were hyperthyroid at diagnosis and thyroid stimulating hormone was below 0.1 mIU/L in all patients. Median free thyroxin and triiodothyronine levels were 3.26 ng/dl and 3.16 ng/ml, respectively. Thyrotropin-receptor antibodies were positive in 98.5% and 85.7% had positive thyroid peroxidase antibodies. Graves orbitopathy (GO) was clinically present in 55% of patients. Of this group, 47% had an active GO, 26% had a moderate to severe disease and 7.8% had sight-threatening GO. As treatment, 26% received radioiodine, 44% anti-thyroid drugs exclusively, 28% underwent thyroidectomy and 2% did not require therapy. Conclusions: In this group of patients, we observed a greater frequency of severe eye disease and a high rate of surgical management. This finding could be explained by referral to highly qualified surgical and ophthalmological teams.

[Second Consensus of the Chilean Society of Endocrinology and Diabetes about insulin resistance]. / II Consenso de la Sociedad Chilena de Endocrinología y Diabetes sobre resistencia a la insulina.

Insulin resistance is a prevalent condition commonly associated with unhealthy lifestyles. It affects several metabolic pathways, increasing risk of abnormalities at different organ levels. Thus, diverse medical specialties should be involved in its diagnosis and treatment. With the purpose of unifying criteria about this condition, a scientific-based consensus was elaborated. A questionnaire including the most important topics such as cardio-metabolic risk, non-alcoholic fatty liver disease and polycystic ovary syndrome, was designed and sent to national experts. When no agreement among them was achieved, the Delphi methodology was applied. The main conclusions reached are that clinical findings are critical for the diagnosis of insulin resistance, not being necessary blood testing. Acquisition of a healthy lifestyle is the most important therapeutic tool. Insulin-sensitizing drugs should be prescribed to individuals at high risk of disease according to clinically validated outcomes. There are specific recommendations for pregnant women, children, adolescents and older people.

II Consenso de la Sociedad Chilena de Endocrinología y Diabetes sobre resistencia a la insulina

Insulin resistance is a prevalent condition commonly associated with unhealthy lifestyles. It affects several metabolic pathways, increasing risk of abnormalities at different organ levels. Thus, diverse medical specialties should be involved in its diagnosis and treatment. With the purpose of unifying criteria about this condition, a scientific-based consensus was elaborated. A questionnaire including the most important topics such as cardio-metabolic risk, non-alcoholic fatty liver disease and polycystic ovary syndrome, was designed and sent to national experts. When no agreement among them was achieved, the Delphi methodology was applied. The main conclusions reached are that clinical findings are critical for the diagnosis of insulin resistance, not being necessary blood testing. Acquisition of a healthy lifestyle is the most important therapeutic tool. Insulin-sensitizing drugs should be prescribed to individuals at high risk of disease according to clinically validated outcomes. There are specific recommendations for pregnant women, children, adolescents and older people.

Increase in C-reactive protein and lipids in adolescents with psychiatric disease.

Eighteen adolescent patients with severe psychiatric disorders were compared with healthy, eutrophics adolescents for the presence of inflammation and cardiovascular risk factors. We found significant differences in high-sensitivity C-reactive protein, total cholesterol, and triglycerides. Our results show, evidence of an inflammatory status and a deleterious lipid profile, in a very early state of psychiatric disease.

[Statement about diagnosis assessment ano non pharmacological treatment of obesity]. / Diagnóstico, evaluación y tratamiento no farmacológico del paciente con sobrepeso u obesidad.

The risk of complications of obesity is proportional to body mass index and is higher in severe or morbid obesities and when abdominal or visceral fat is predominant. In Chile the prevalence of obesity is increasing. According to the World Health Organization, obese subjects must reduce at least a 5% of their weight to reduce the risk of complications. Although this amount of reduction is seldom achieved with non pharmacological treatments, better results are obtained with multidisciplinary/ approaches that include a medical, psychosocial and laboratory assessment, to determine obesity level and different factors involved and the associated complications. In a second stage, goals of treatment are set and a personalized treatment is designed including dietary changes and physical activity. The aim is to obtain perdurable lifestyles modifications.

[Statement about the medical and surgical treatment of overweight and obesity]. / Tratamiento farmacológico o quirúrgico del paciente con sobrepeso u obesidad.

This is an updated review of the available treatments for obesity, which can be used when lifestyles modifications fail. Using the available information and the experience of the members of this advisory group, a recommendation is given about the most useful treatments, according to the severity of obesity and its complications. With regards to pharmacological treatments, only sibutramine and orlistat are approved on a worldwide basis for the treatment of obesity. These medications achieve a 10% higher weight reduction than lifestyles modification. A third medication, rimonobant, is also more effective than lifestyles modifications, but it was withdrawn due to psychological safety issues. The indications for surgical treatment and a brief description of the available techniques, success rates and complications are outlined. Finally, the need to have followed up protocols for patients and the formation of multidisciplinary treatment teams is underscored.

Diagnóstico, evaluación y tratamiento no farmacológico del paciente con sobrepeso u obesidad / Statement about diagnosis assessment ano non pharmacological treatment of obesity

The risk of complications of obesity is proportional to body mass index and is higher in severe or morbid obesities and when abdominal or visceral fat is predominant. In Chile the prevalence of obesity is increasing. According to the World Health Organization, obese subjects must reduce at least a 5 percent of their weight to reduce the risk of complications. Although this amount of reduction is seldom achieved with non pharmacological treatments, better results are obtained with multidisciplinary/ approaches that include a medical, psychosocial and laboratory assessment, to determine obesity level and different factors involved and the associated complications. In a second stage, goals of treatment are set and a personalized treatment is designed including dietary changes and physical activity. The aim is to obtain perdurable lifestyles modifications.

Tratamiento farmacológico o quirúrgico del paciente con sobrepeso u obesidad / Statement about the medical and surgical treatment of overweight and obesity

This is an updated review of the available treatments for obesity, which can be used when lifestyles modifications fail. Using the available information and the experience of the members of this advisory group, a recommendation is given about the most useful treatments, according to the severity of obesity and its complications. With regards to pharmacological treatments, only sibutramine and orlistat are approved on a worldwide basis for the treatment of obesity. These medications achieve a 10 percent higher weight reduction than lifestyles modification. A third medication, rimonobant, is also more effective than lifestyles modifications, but it was withdrawn due to psychological safety issues. The indications for surgical treatment and a brief description of the available techniques, success rates and complications are outlined. Finally, the need to have followed up protocols for patients and the formation of multidisciplinary treatment teams is underscored.

[Immunohistochemistry for pituitary hormones and Ki-67 in growth hormone producing pituitary adenomas]. / Evaluación por inmunohistoquímica de la expresión de hormonas hipofisiarias y del marcador de proliferación celular Ki-67 en tejido de adenomas causantes de acromegalia.

BACKGROUND: Growth hormone (GH) producing adenomas, frequently express several hormones. This condition could confer them a higher proliferative capacity. Ki-67 is a nuclear protein antigen that is a marker for proliferative activity. AIM: To measure the immunohistochemical hormone expression in pituitary adenomas, excised from patients with acromegaly. To determine if the plurihormonal condition of these adenomas is associated with a higher proliferative capacity, assessed through the expression of Ki-67. MATERIAL AND METHODS: Forty one paraffin embedded surgical samples of pituitary adenomas from patients with acromegalia were studied. Immunohistochemistry for GH, prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), adrenocorticotropin (ACTH) and for the expression of Ki-67 was carried out. RESULTS: All samples were positive for GH. Twenty seven had positive staining for PRL, 12 had positive staining for glycoproteic hormones and 11 for PRL and one or more glycoproteic hormones. Mean staining for Ki-67 was Z.6+/-3.3%. There were no differences in the expression of this marker between mono or plurihormonal tumors. The expression was neither associated with extrasellar extension. CONCLUSIONS: Half of GH producing pituitary adenomas are plurihormonal. There are no differences in the expression of Ki-67 between mono and plurihormonal adenomas.

Evaluación por inmunohistoquímica de la expresión de hormonas hipofisiarias y del marcador de proliferación celular Ki-67 en tejido de adenomas causantes de acromegalia / Immunohistochemistry for pituitary hormones and Ki-67 in growth hormone producing pituitary adenomas

Background: Growth hormone (GH) producing adenomas, frequently express several hormones. This condition could confer them a higher proliferative capacity. Ki-67 is a nuclear protein antigen that is a marker for proliferative activity. Aim: To measure the immunohistochemical hormone expression in pituitary adenomas, excised from patients with acromegaly. To determine if the pluríhormonal condition of these adenomas is associated with a higher proliferative capacity, assessed through the expression of Ki-67. Material and methods: Forty one paraffin embedded surgical samples of pituitary adenomas from patients with acromegalia were studied. Immunohistochemistry for GH, prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), adrenocorticotropin (ACTH) and for the expression of Ki-67 was carried out. Results: All samples were positive for GH. Twenty seven had positive staining for PRL, 12 had positive staining for glycoproteic hormones and 11 for PRL and one or more glycoproteic hormones. Mean staining for Ki-67 was Z.6±3.3 percent. There were no differences in the expression of this marker between mono or pluríhormonal tumors. The expression was neither associated with extrasellar extensión. Conclusions: Half of GH producing pituitary adenomas are pluríhormonal. There are no differences in the expression of Ki-67 between mono and plurihormonal adenomas.

Infliximab can induce a prolonged clinical remission and a decrease in thyroid hormonal requirements in a patient with SAPHO syndrome and hypothyroidism.

SAPHO syndrome is a rare entity that compromises the skeletal system (arthritis-osteitis) and is associated with various dermatological conditions such as palmoplantaris pustulosis (PPP) and acne. We present the case of a 39-year-old man with invalidating arthritis derived from a SAPHO syndrome and hypothyroidism (after radioiodine treatment for a Graves' disease). Due to the severity and refractoriness of his disease, we decided to use infliximab. He showed a prompt and prolonged response of his joint and cutaneous manifestations after three doses of a tumor necrosis factor alpha (TNF-alpha) blocker. Interestingly, he also decreased his levothyroxine requirements after TNF-alpha blockade therapy.

FABP2 Ala54Thr polymorphism and diabetes in Chilean elders.

OBJECTIVE: The FABP2 Ala54Thr polymorphism has been associated with insulin resistance and diabetes in several populations. The aim of this study was to estimate the prevalence of FABP2 genotypes in 223 Chilean subjects (136 women and 87 men aged 65-79 years) and its association with type 2 diabetes in a 4 years follow-up. METHODS: Glucose, Insulin and lipids were measured in fasting plasma samples. Insulin resistance was estimated through the homeostasis model assessment. Diabetes was diagnosed according ADA criteria. The Ala54Thr allelic variant was determined by polymerase chain reaction and restriction fragment-length polymorphism analysis. Logistic regression techniques were used to assess gene-disease associations. RESULTS: Genotype frequencies were estimated as 30.5, 49.3 and 20.2% for the Ala/Ala, Ala/Thr and Thr/Thr, respectively. The crude OR for the association between Thr54 carriers and diabetes was estimated as 2.18 (1.12-4.24). The corresponding OR for the association between Thr54 carriers with Metabolic Syndrome was 1.06 (0.59-1.88). After adjustment by BMI and age, a significant association persists for Thr54Thr carriers and diabetes (OR 2.70; 95% CI 1.113-6.527). The 4-year cumulative incidence of diabetes was higher in Thr carriers than in non-carriers (20.1% versus 8.5%; p<0.04). The adjusted association between Thr54Thr polymorphism and diabetes incidence was OR 3.84 (95% CI: 1.140-12.910) CONCLUSION: Our results strongly suggest an association between the Ala54Thr polymorphism of FABP2 with diabetes, revealing a genetic dosage effect regarding its association with diabetes in Chilean elders.

Intestinal FABP2 A54T polymorphism: association with insulin resistance and obesity in women.

OBJECTIVE: To assess the association between the Ala54Thr genetic polymorphism of the fatty acid-binding protein 2 (FABP2) gene with insulin resistance and obesity. RESEARCH METHODS AND PROCEDURES: According to a sampling scheme based on BMI, 33 adult obese women (BMI > or = 30) and 30 adult normal-weight women (BMI > 18.5 and < 25 kg/m(2)) were recruited for this study. Women with chronic inflammatory diseases or acute pathology were excluded. Glucose, insulin, leptin, lipids, and tumor necrosis factor alpha (TNF alpha) were measured in fasting plasma samples. Insulin resistance was estimated through the homeostasis model assessment for insulin resistance method. The Ala54Thr allelic variant was determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis. RESULTS: The Thr54 allele was more frequent in obese than in nonobese women (47.0% vs. 31.7; p = 0.08). Among obese women, higher TNF alpha concentrations were found when comparing the Thr54/Thr54 genotype (30.0 +/- 7.1 pg/mL) with either the Ala54/Thr54 genotype (21.2 +/- 8.4 pg/mL) or the Ala54/Ala44 genotype (20.1 +/- 7.0 pg/mL) (p < 0.05). In addition, higher fasting plasma insulin and leptin levels were found among Thr54/Thr54 homozygotes compared with the other genotypes (p < 0.05). DISCUSSION: Our results suggest that the Ala54Thr polymorphism of the FABP2 gene is associated with obesity and insulin resistance. The effect of this polymorphism might be mediated by elevated production of TNF alpha.