Plasma insulin-like growth factor-II (IGF-II) and IGF-II/IGF-I ratio in a chilean case of Doege-Potter Syndrome

Introduction: Doege-Potter syndrome is a rare clinical entity characterized by recurrent hypoglycemic events caused by non-pancreatic tumors secreting an incompletely processed high-molecular-weight form of Insulin-like Growth factor-II (IGF-II). Aim: To report IGF-II and IGF-I circulating levels in a Chilean case of Doege-Potter syndrome and control individuals, and to identify the high-molecular-weight form of IGF-II. Methods: We measured IGF-II and IGF-I plasma levels using enzyme-linked immunoassays (ELISA) in the patient and ten controls. We identified the high-molecular-weight form of IGF-II performed by Western blot. Results: The plasma concentration of IGF-II in the patient was 868.9 ng/mL, which is only slightly > 80th percentile of controls (681,4 ± 212,8 ng/mL; mean ± standard deviation). In contrast, IGF-I plasma concentration in the patient was 17.6 ng/mL, which is notoriously lower than the corresponding levels in controls (109.1 ± 19.1 ng/mL). The IGF-II/IGF-I ratio in the patient was 49.4 (normal value < 10), which is 7.8 times higher compared to the average ratio of controls (6.3 ± 1.5). The high-molecular form of IGF-II presence in samples was confirmed through Western blot. Conclusions: The plasma IGF-II/IGF-I ratio better indicates the Doege-Potter syndrome's metabolic impairment than isolated measurements of circulating IGF-II or IGF-I levels.

Introducción: El síndrome de Doege-Potter es una rara entidad clínica caracterizada por eventos hipoglicémicos recurrentes causados por tumores no-pancreáticos que secretan una forma incompletamente procesada con alto peso molecular del factor de crecimiento similar a la insulina-II (IGF-II). Objetivo: Reportar los niveles circulantes de IGF-II e IGF-I en un caso chileno de síndrome de Doege-Potter y en controles, así como identificar la forma de alto peso molecular de IGF-II. Métodos: Los niveles plasmáticos de IGF-II e IGF-I se determinaron mediante inmunoensayos de tipo ELISA en el caso índice y en 10 controles. La forma de alto peso molecular de IGF-II se identificó mediante western-blot. Resultados: La concentración plasmática de IGF-II en el paciente fue de 868,9 ng/mL, que es sólo ligeramente superior al percentil 80 del grupo control (681,4 ± 212,8 ng/mL; media ± desviación estándar). Sin embargo, la concentración plasmática de IGF-I en el paciente fue de 17,6 ng/ mL, que es notoriamente inferior a la de los controles (109,1 ± 19,1 ng/mL). La razón IGF-II/IGF-I en el paciente fue de 49,4 (valor normal < 10), que es 7,8 veces superior a la media de los controles (6,3 ± 1,5). La presencia de la forma de alto peso molecular de IGF-II se confirmó mediante western-blot. Conclusiones: La razón IGF-II/IGF-I en plasma es un mejor indicador de las alteraciones metabólicas del síndrome de Doege-Potter que las mediciones aisladas de IGF-II o IGF-I circulantes.

Plasma insulin-like growth factor-II (IGF-II) and IGF-II/IGF-I ratio in a chilean case of Doege-Potter Syndrome.

INTRODUCTION: Doege-Potter syndrome is a rare clinical entity characterized by recurrent hypoglycemic events caused by non-pancreatic tumors secreting an incompletely processed high-molecular-weight form of Insulin-like Growth factor-II (IGF-II). AIM: To report IGF-II and IGF-I circulating levels in a Chilean case of Doege-Potter syndrome and control individuals, and to identify the high-molecular-weight form of IGF-II. METHODS: We measured IGF-II and IGF-I plasma levels using enzyme-linked immunoassays (ELISA) in the patient and ten controls. We identified the high-molecular-weight form of IGF-II performed by Western blot. RESULTS: The plasma concentration of IGF-II in the patient was 868.9 ng/mL, which is only slightly > 80th percentile of controls (681,4 ± 212,8 ng/mL; mean ± standard deviation). In contrast, IGF-I plasma concentration in the patient was 17.6 ng/mL, which is notoriously lower than the corresponding levels in controls (109.1 ± 19.1 ng/mL). The IGF-II/IGF-I ratio in the patient was 49.4 (normal value < 10), which is 7.8 times higher compared to the average ratio of controls (6.3 ± 1.5). The high-molecular form of IGF-II presence in samples was confirmed through Western blot. CONCLUSIONS: The plasma IGF-II/IGF-I ratio better indicates the Doege-Potter syndrome's metabolic impairment than isolated measurements of circulating IGF-II or IGF-I levels.

[An update on parathyroid carcinoma]. / Puesta al día: carcinoma paratiroideo.

Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.

Resumen ejecutivo: Enfermedad por hígado graso no alcohólico en sujetos con diabetes mellitus tipo 2: Postura conjunta de la Asociación Chilena de Hepatología (ACHHEP) y la Sociedad Chilena de Diabetología (SOCHIDIAB) / Non-alcoholic fatty liver disease in type 2 diabetes: a joint statement of the Chilean Hepatology and Diabetology Societies

Non-alcoholic fatty liver disease (NAFLD) has a high prevalence and risk of progression to cirrhosis and other complications in patients with type 2 diabetes mellitus (T2DM). Likewise, the presence of NAFLD implies a high risk of developing T2DM, determining a bidirectional relationship between them. The diabetology and hepatology societies, developed a joint initiative aiming to unify criteria, reviewing the definitions, diagnostic criteria, risk stratification, treatment, and follow-up of patients with NAFLD and T2DM. The key questions to be discussed were defined by a panel of specialists in diabetology and hepatology. The Delphi methodology was used to reach consensus on the respective recommendations. Based on the discussion generated among the experts, diagnostic and treatment algorithms were proposed, as well as an indication for referral and the role of the different specialists involved in the management of these patients. Strengthening multidisciplinary work with patients with NAFLD and T2DM will allow the early recognition of the disease, the prevention of the progression to cirrhosis, and reducing the associated complications.

Puesta al día: carcinoma paratiroideo / An update on parathyroid carcinoma

Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.

Recomendaciones para el uso correcto de densitometría ósea en la práctica clínica. Consenso de la Sociedad Chilena de Endocrinología y Diabetes / Guidelines of the Chilean Endocrinology Society for the correct clinical use of bone densitometry

Osteoporosis is a silent and frequent disease, which increases fracture risk. Approximately half of women and one of five men over 50 years old will suffer an osteoporotic fracture throughout their lives. Dual-energy x-ray absorptiometry (DXA) allows a real bone mineral density (BMD) measurement in different parts of the skeleton and is considered the "gold standard" for quantifying osteoporosis with high accuracy and precision. The Board of the Chilean Society of Endocrinology and Diabetes (SOCHED) required from the Bone Disease Study Group to develop a consensus about the "Correct use of bone densitometry in clinical practice in Chilean population". Therefore, we elaborated 25 questions which addressed key aspects about the indications for a DXA scan, and the details of how to perform and report this test. Since some of the evidence obtained was of low quality or inconclusive, we decided to create a multidisciplinary group of national experts in osteoporosis to develop a consensus in this subject. The group consisted of 22 physicians including endocrinologists, gynecologists, geriatricians, radiologists, rheumatologists and nuclear medicine specialists. Using the Delphi methodology to analyze previously agreed questions, we elaborated statements that were evaluated by the experts who expressed their degree of agreement. The final report of this consensus was approved by the SOCHED board.

Rol de la cirugía bariátrica/metabólica en el manejo de la diabetes mellitus 2. Consenso SOCHED/SCCBM / Consensus statement of the Chilean endocrinological society on the role of bariatric surgery in type 2 diabetes

Diabetes Mellitus (DM) and obesity are a public health problem in Chile. Bariatric surgery is the most effective treatment alternative to achieve a significant and sustained weight reduction in patients with morbid obesity. The results of controlled clinical trials indicate that, compared to medical treatment, surgery for obese patients with DM2 allows a better control of blood glucose and cardiovascular risk factors, reduces the need for medications and increases the likelihood for remission. Consensus conferences and clinical practice guidelines support bariatric surgery as an option to treat DM2 in Class III Obesity (Body Mass Index (BMI) > 40) regardless of the glycemic control and the complexity of pharmacological treatment and in Class II Obesity (BMI 35-39,9) with inadequate glycemic control despite optimal pharmacological treatment and lifestyle. However, surgical indication for patients with DM2 and BMI between 30-34.9, the most prevalent sub-group, is only suggested. The Chilean Societies of Endocrinology and Diabetes and of Bariatric and Metabolic Surgery decided to generate a consensus regarding the importance of other factors related to DM2 that would allow a better selection of candidates for surgery, particularly when weight does not constitute an indication. Considering the national reality, we also need a statement regarding the selection and characteristics of the surgical procedure as well as the role of the diabetologist in the multidisciplinary team.

[Guidelines of the Chilean Endocrinology Society for the correct clinical use of bone densitometry]. / Recomendaciones para el uso correcto de densitometría ósea en la práctica clínica. Consenso de la Sociedad Chilena de Endocrinología y Diabetes.

Osteoporosis is a silent and frequent disease, which increases fracture risk. Approximately half of women and one of five men over 50 years old will suffer an osteoporotic fracture throughout their lives. Dual-energy x-ray absorptiometry (DXA) allows a real bone mineral density (BMD) measurement in different parts of the skeleton and is considered the "gold standard" for quantifying osteoporosis with high accuracy and precision. The Board of the Chilean Society of Endocrinology and Diabetes (SOCHED) required from the Bone Disease Study Group to develop a consensus about the "Correct use of bone densitometry in clinical practice in Chilean population". Therefore, we elaborated 25 questions which addressed key aspects about the indications for a DXA scan, and the details of how to perform and report this test. Since some of the evidence obtained was of low quality or inconclusive, we decided to create a multidisciplinary group of national experts in osteoporosis to develop a consensus in this subject. The group consisted of 22 physicians including endocrinologists, gynecologists, geriatricians, radiologists, rheumatologists and nuclear medicine specialists. Using the Delphi methodology to analyze previously agreed questions, we elaborated statements that were evaluated by the experts who expressed their degree of agreement. The final report of this consensus was approved by the SOCHED board.

[Consensus statement of the Chilean endocrinological society on the role of bariatric surgery in type 2 diabetes]. / Rol de la cirugía bariátrica/metabólica en el manejo de la diabetes mellitus 2. Consenso SOCHED/SCCBM.

Diabetes Mellitus (DM) and obesity are a public health problem in Chile. Bariatric surgery is the most effective treatment alternative to achieve a significant and sustained weight reduction in patients with morbid obesity. The results of controlled clinical trials indicate that, compared to medical treatment, surgery for obese patients with DM2 allows a better control of blood glucose and cardiovascular risk factors, reduces the need for medications and increases the likelihood for remission. Consensus conferences and clinical practice guidelines support bariatric surgery as an option to treat DM2 in Class III Obesity (Body Mass Index (BMI) > 40) regardless of the glycemic control and the complexity of pharmacological treatment and in Class II Obesity (BMI 35-39,9) with inadequate glycemic control despite optimal pharmacological treatment and lifestyle. However, surgical indication for patients with DM2 and BMI between 30-34.9, the most prevalent sub-group, is only suggested. The Chilean Societies of Endocrinology and Diabetes and of Bariatric and Metabolic Surgery decided to generate a consensus regarding the importance of other factors related to DM2 that would allow a better selection of candidates for surgery, particularly when weight does not constitute an indication. Considering the national reality, we also need a statement regarding the selection and characteristics of the surgical procedure as well as the role of the diabetologist in the multidisciplinary team.

[From macro to micro thyroid carcinoma: records of a clinical hospital from 1991 to 2010]. / Del macro al microcarcinoma tiroideo: cambios en las características de presentación del cáncer de tiroides en un centro universitario chileno en 20 años.

BACKGROUND: The prevalence of thyroid cancer has increased, particularly in nodules smaller than 10 mm, probably due to the growing use of routine thyroid ultrasound. There is controversy about the biological behavior of micro carcinomas and the relevance of their early detection. AIM: To characterize the clinical presentation of thyroid cancer over 20 years in an University medical center and to evaluate the differences between macro and micro carcinomas. PATIENTS AND METHODS: We reviewed 1547 surgical biopsy records of thyroid cancer in our institution obtained between 1991 and 2010. RESULTS: We observed a sustained increase in the rate of thyroidectomies for thyroid cancer (per 1000 surgical procedures) in the study period. Papillary, follicular, mixed, medullary and anaplastic carcinomas were observed in 95, 3, 2, 0.5 and 0.1% of biopsies, respectively. The incidence of tumors of less than 10 mm (micro carcinoma) also increased. Those findings were associated with a significant decrease in tumor aggressiveness, determined by a low frequency of surgical margin involvement of thyroid capsule, perithyroid tissue invasion, vascular permeation and lymph node metastases. CONCLUSIONS: The increased prevalence of thyroid cancer, especially of micro carcinomas, may reflect the greater use of diagnostic ultrasound or represent a real change in the biological behavior of this disease and our data suggest that further studies are needed to know the impact of early treatment in the outcome of those patients because of the real less histologic agressiveness of micro carcinomas.

Del macro al microcarcinoma tiroideo: cambios en las características de presentación del cáncer de tiroides en un centro universitario chileno en 20 años / From macro to micro thyroid carcinoma: records of a clinical hospital from 1991 to 2010

Background: The prevalence of thyroid cancer has increased, particularly in nodules smaller than 10 mm, probably due to the growing use of routine thyroid ultrasound. There is controversy about the biological behavior of micro carcinomas and the relevance of their early detection. Aim: To characterize the clinical presentation of thyroid cancer over 20 years in an University medical center and to evaluate the differences between macro and micro carcinomas. Patients and Methods: We reviewed 1547 surgical biopsy records of thyroid cancer in our institution obtained between 1991 and 2010. Results: We observed a sustained increase in the rate of thyroidectomies for thyroid cancer (per 1000 surgical procedures) in the study period. Papillary, follicular, mixed, medullary and anaplastic carcinomas were observed in 95, 3, 2, 0.5 and 0.1% of biopsies, respectively. The incidence of tumors of less than 10 mm (micro carcinoma) also increased. Those findings were associated with a significant decrease in tumor aggressiveness, determined by a low frequency of surgical margin involvement of thyroid capsule, perithyroid tissue invasion, vascular permeation and lymph node metastases. Conclusions: The increased prevalence of thyroid cancer, especially of micro carcinomas, may reflect the greater use of diagnostic ultrasound or represent a real change in the biological behavior of this disease and our data suggest that further studies are needed to know the impact of early treatment in the outcome of those patients because of the real less histologic agressiveness of micro carcinomas.